Cerebral Cortex - Advance Access

Neuronal Encoding of Human Kinematic Invariants during Action Observation

Casile, A., Dayan, E., Caggiano, V., Hendler, T., Flash, T., Giese, M. A. — Fri, 20 Nov 2009 05:47:26 PST

Human movements, besides entailing the presence of a body shape, comply with characteristic kinematic laws of motion. Psychophysical studies show that low-level motion perception is biased toward stimuli complying with these laws. However, the neuronal structures that are sensitive to the kinematic laws of observed bodily movements are still largely unknown. We investigated this issue by dissociating, by means of computer-generated characters, form and motion information during the observation of human movements. In a functional imaging experiment, we compared the levels of blood oxygen level–dependent activity elicited by human actions complying with or violating the kinematic laws of human movements. Actions complying with normal kinematic laws of motion differentially activated the left dorsal premotor and dorsolateral prefrontal cortex as well as the medial frontal cortex. These findings suggest that the kinematic laws of human movements specifically modulate the responses of neuronal circuits also involved in action recognition and that are predominantly located in the left frontal lobe.

Cholinergic Modulation Differs between Basal and Apical Dendritic Excitation of Hippocampal CA1 Pyramidal Cells

Leung, L. S., Peloquin, P. — Thu, 19 Nov 2009 06:37:33 PST

We hypothesize that endogenous cholinergic modulation of dendritic processing of hippocampal CA1 is layer specific, and it specifically enhances spike output resulting from basal as compared with the apical dendritic excitation. Laminar profiles of evoked field potentials were recorded in the CA1 area of urethane-anesthetized rats using multichannel silicon probes and analyzed as current source density. High-frequency stimulation of the pontis oralis (PnO) attenuated the midapical more than the basal or distal apical dendritic excitatory sink. Population spike (PS) and excitatory sink–PS potentiation resulting from basal dendritic excitation were facilitated, while the PS evoked by apical dendritic stimulation was attenuated by PnO stimulation. Perfusion of cholinergic agonist carbachol onto hippocampal slices in vitro also attenuated the apical more than the basal dendritic excitatory postsynaptic potentials. Excitatory sink attenuation and PS changes after PnO stimulation were blocked by systemic or local scopolamine and by intracerebroventricular (icv) M1 receptor antagonist pirenzepine but not by icv M2 receptor antagonist AFDX–116 or nicotinic antagonists. However, a hippocampal theta rhythm activated by PnO stimulation was blocked by systemic but not by local scopolamine. We conclude that endogenous acetylcholine mediates a stronger presynaptic inhibition of the midapical than basal and distal apical excitation mainly through M1 receptors.

Superadditive Responses in Superior Temporal Sulcus Predict Audiovisual Benefits in Object Categorization

Werner, S., Noppeney, U. — Wed, 18 Nov 2009 06:46:53 PST

Merging information from multiple senses provides a more reliable percept of our environment. Yet, little is known about where and how various sensory features are combined within the cortical hierarchy. Combining functional magnetic resonance imaging and psychophysics, we investigated the neural mechanisms underlying integration of audiovisual object features. Subjects categorized or passively perceived audiovisual object stimuli with the informativeness (i.e., degradation) of the auditory and visual modalities being manipulated factorially. Controlling for low-level integration processes, we show higher level audiovisual integration selectively in the superior temporal sulci (STS) bilaterally. The multisensory interactions were primarily subadditive and even suppressive for intact stimuli but turned into additive effects for degraded stimuli. Consistent with the inverse effectiveness principle, auditory and visual informativeness determine the profile of audiovisual integration in STS similarly to the influence of physical stimulus intensity in the superior colliculus. Importantly, when holding stimulus degradation constant, subjects’ audiovisual behavioral benefit predicts their multisensory integration profile in STS: only subjects that benefit from multisensory integration exhibit superadditive interactions, while those that do not benefit show suppressive interactions. In conclusion, superadditive and subadditive integration profiles in STS are functionally relevant and related to behavioral indices of multisensory integration with superadditive interactions mediating successful audiovisual object categorization.

Differential Expression of LIM-Homeodomain Factors in Cajal-Retzius Cells of Primates, Rodents, and Birds

Abellan, A., Menuet, A., Dehay, C., Medina, L., Retaux, S. — Wed, 18 Nov 2009 06:46:44 PST

Reelin-expressing Cajal-Retzius (CR) cells are among the earliest generated cells in the mammalian cerebral cortex and are believed to be crucial for both the development and the evolution of a laminated pattern in the pallial wall of the telencephalon. LIM-homeodomain (LIM-hd) transcription factors are expressed during brain development in a highly restricted and combinatorial manner, and they specify regional and cellular identity. We have investigated the expression of the LIM-hd members Lhx1/Lhx2/Lhx5/Lhx6/Lhx9 in the reelin-expressing cells, the pallium, and the regions of origin of CR cells including the cortical hem of 3 amniote species: the mouse, the chick, and the macaque monkey. We found major differences in the combinatorial LIM-hd expression in the marginal zone as well as in the hem. 1) Lhx5 is a "preferential LIM-hd" for CR cells in mammals but not expressed by these cells in chicks. 2) Lhx2 is expressed in the hem of the chick, whereas it is excluded from this region in mouse. 3) Whereas mouse CR cells express Lhx5/Lhx1, their monkey counterparts express 4 of these factors: Lhx1/Lhx2/Lhx5/Lhx9. We discuss our findings in evolutionary terms for the specification of the midline hem and CR cell type and the emergence of the cortical lamination pattern.

Neural Aspects of Sentence Comprehension: Syntactic Complexity, Reversibility, and Reanalysis

Meltzer, J. A., McArdle, J. J., Schafer, R. J., Braun, A. R. — Tue, 17 Nov 2009 05:29:49 PST

Broca's area is preferentially activated by reversible sentences with complex syntax, but various linguistic factors may be responsible for this finding, including syntactic movement, working-memory demands, and post hoc reanalysis. To distinguish between these, we tested the interaction of syntactic complexity and semantic reversibility in a functional magnetic resonance imaging study of sentence–picture matching. During auditory comprehension, semantic reversibility induced selective activation throughout the left perisylvian language network. In contrast, syntactic complexity (object-embedded vs. subject-embedded relative clauses) within reversible sentences engaged only the left inferior frontal gyrus (LIFG) and left precentral gyrus. Within irreversible sentences, only the LIFG was sensitive to syntactic complexity, confirming a unique role for this region in syntactic processing. Nonetheless, larger effects of reversibility itself occurred in the same regions, suggesting that full syntactic parsing may be a nonautomatic process applied as needed. Complex reversible sentences also induced enhanced signals in LIFG and left precentral regions on subsequent picture selection, but with additional recruitment of the right hemisphere homolog area (right inferior frontal gyrus) as well, suggesting that post hoc reanalysis of sentence structure, compared with initial comprehension, engages an overlapping but larger network of brain regions. These dissociable effects may offer a basis for studying the reorganization of receptive language function after brain damage.

Neural Systems for Reading Aloud: A Multiparametric Approach

Graves, W. W., Desai, R., Humphries, C., Seidenberg, M. S., Binder, J. R. — Tue, 17 Nov 2009 05:29:48 PST

Reading aloud involves computing the sound of a word from its visual form. This may be accomplished 1) by direct associations between spellings and phonology and 2) by computation from orthography to meaning to phonology. These components have been studied in behavioral experiments examining lexical properties such as word frequency; length in letters or phonemes; spelling–sound consistency; semantic factors such as imageability, measures of orthographic, or phonological complexity; and others. Effects of these lexical properties on specific neural systems, however, are poorly understood, partially because high intercorrelations among lexical factors make it difficult to determine if they have independent effects. We addressed this problem by decorrelating several important lexical properties through careful stimulus selection. Functional magnetic resonance imaging data revealed distributed neural systems for mapping orthography directly to phonology, involving left supramarginal, posterior middle temporal, and fusiform gyri. Distinct from these were areas reflecting semantic processing, including left middle temporal gyrus/inferior-temporal sulcus, bilateral angular gyrus, and precuneus/posterior cingulate. Left inferior frontal regions generally showed increased activation with greater task load, suggesting a more general role in attention, working memory, and executive processes. These data offer the first clear evidence, in a single study, for the separate neural correlates of orthography–phonology mapping and semantic access during reading aloud.

Neural Components Underlying Behavioral Flexibility in Human Reversal Learning

Fri, 13 Nov 2009 09:45:47 PST

The ability to flexibly respond to changes in the environment is critical for adaptive behavior. Reversal learning (RL) procedures test adaptive response updating when contingencies are altered. We used functional magnetic resonance imaging to examine brain areas that support specific RL components. We compared neural responses to RL and initial learning (acquisition) to isolate reversal-related brain activation independent of cognitive control processes invoked during initial feedback-based learning. Lateral orbitofrontal cortex (OFC) was more activated during reversal than acquisition, suggesting its relevance for reformation of established stimulus–response associations. In addition, the dorsal anterior cingulate (dACC) and right inferior frontal gyrus (rIFG) correlated with change in postreversal accuracy. Because optimal RL likely requires suppression of a prior learned response, we hypothesized that similar regions serve both response inhibition (RI) and inhibition of learned associations during reversal. However, reversal-specific responding and stopping (requiring RI and assessed via the stop-signal task) revealed distinct frontal regions. Although RI-related regions do not appear to support inhibition of prepotent learned associations, a subset of these regions, dACC and rIFG, guide actions consistent with current reward contingencies. These regions and lateral OFC represent distinct neural components that support behavioral flexibility important for adaptive learning.

Diminished Parietal Cortex Activity Associated with Poor Motion Direction Discrimination Performance in Schizophrenia

Wang, J., Brown, R., Dobkins, K. R., McDowell, J. E., Clementz, B. A. — Fri, 13 Nov 2009 09:45:46 PST

The results of multiple investigations indicate visual motion–processing abnormalities in schizophrenia. There is little information, however, about the time course and neural correlates of motion-processing abnormalities among these subjects. For the present study, 13 schizophrenia and 13 healthy subjects performed a simple motion direction discrimination task with peripherally presented moving grating stimuli (5 or 10 deg/s). Dense-array electroencephalography data were collected simultaneously. The goal was to discern whether neural deviations associated with motion-processing abnormalities among schizophrenia patients occur early or late in the visual-processing stream. Schizophrenia patients were worse at judging the direction of motion gratings, had enhanced early neural activity (about 90 ms after stimulus onset), and deficient target detection–related late neural activity over parietal cortex (about 400 ms after stimulus onset). In addition, there was a strong association (accounting for 36% of performance variance) between poor behavioral performance and lower target detection–related brain activity among schizophrenia patients. These findings suggest that abnormalities in later stages of motion-processing mechanisms, perhaps beyond extrastriate cortex, may account for behavioral deviations among schizophrenia subjects.

The Modulation of Orexin A on HCN Currents of Pyramidal Neurons in Mouse Prelimbic Cortex

Fri, 13 Nov 2009 09:45:45 PST

The hyperpolarization-activated/cyclic nucleotide (HCN)–gated channels make important contributions to neural excitability. In prefrontal cortex, HCN channels are localized on the distal dendrites of layer V pyramidal neurons and decrease neural excitability when they are open. In the present study, using whole-cell voltage clamp recordings, the effect of an arousal peptide, orexin A, on HCN currents in layer V pyramidal neurons from mouse prelimbic cortex (PL), the homolog of the prefrontal cortex was investigated. The results demonstrated that orexin A suppressed HCN currents and shifted their activation curve to a more negative direction. This action of orexin A was blocked by SB334867, an orexin receptor 1 (OXR1) blocker and bisindolylmaleimide, a protein kinase C (PKC) inhibitor, indicating the involvement of OXR1 and PKC. The excitatory effect of orexin A on PL pyramidal neurons was enhanced when HCN currents were diminished, while attenuated when HCN currents were enlarged. In summary, orexin A inhibits HCN currents and enhances excitability of pyramidal neurons in PL, which may contribute to arousal and cognition.

Microtomographic Analysis of Neuronal Circuits of Human Brain

Fri, 13 Nov 2009 09:45:44 PST

We report a 3D analysis of the neuronal circuits of human cerebral cortex. Neuronal circuits, which are essential for brain functions, are built up by neurons as a 3D network, so tracing the 3D neuronal network of human cerebral cortex is the first step to understanding the mechanism of human brain functions. The cortical microstructures were visualized by X-ray microtomographic imaging of adult frontal cortex tissue stained with metal impregnation. Skeletonized wire models were built by tracing the 3D distribution of X-ray absorption coefficients. The obtained neuronal models were composed of 240 pyramidal neurons and 131 interneurons. Capillary vessel structures along with blood cells in the capillary lumen were also visualized and traced to build capillary network models. Possible neuronal circuits were analytically resolved from the skeletonized wire models. The operating mechanism of the resolved circuits is discussed on the basis of neurotransmission in the circuits. The results also indicate that X-ray microtomography is a potential method of visualizing the neuronal circuits of the brain.

Multiple Forms of Learning Yield Temporally Distinct Electrophysiological Repetition Effects

Race, E. A., Badre, D., Wagner, A. D. — Fri, 13 Nov 2009 09:45:43 PST

Prior experience with a stimulus leads to multiple forms of learning that facilitate subsequent behavior (repetition priming) and neural processing (repetition suppression). Learning can occur at the level of stimulus-specific features (stimulus learning), associations between stimuli and selected decisions (stimulus–decision learning), and associations between stimuli and selected responses (stimulus–response learning). Although recent functional magnetic resonance imaging results suggest that these distinct forms of learning are associated with repetition suppression (neural priming) in dissociable regions of frontal and temporal cortex, a critical question is how these different forms of learning influence cortical response dynamics. Here, electroencephalography (EEG) measured the temporal structure of neural responses when participants classified novel and repeated stimuli, using a design that isolated the effects of distinct levels of learning. Event-related potential and spectral EEG analyses revealed electrophysiological effects due to stimulus, stimulus–decision, and stimulus–response learning, demonstrating experience-dependent cortical modulation at multiple levels of representation. Stimulus-level learning modulated cortical dynamics earlier in the temporal-processing stream relative to stimulus–decision and stimulus–response learning. These findings indicate that repeated stimulus processing, including the mapping of stimuli to decisions and actions, is influenced by stimulus-level and associative learning mechanisms that yield multiple forms of experience-dependent cortical plasticity.

Postsynaptic Deregulation in GAP-43 Heterozygous Mouse Barrel Cortex

Kelly, E. A., Tremblay, M.-E., McCasland, J. S., Majewska, A. K. — Fri, 13 Nov 2009 09:45:42 PST

Formation of whisker-related barrels in primary somatosensory cortex (S1) requires communication between presynaptic thalamocortical afferents (TCAs) and postsynaptic cortical neurons. GAP-43 is crucially involved in targeting TCAs to postsynaptic S1 neurons but its influence on the interactions between these 2 elements has not been explored. Here, we tested the hypothesis that reduced early expression of presynaptic GAP-43 (GAP-43 heterozygous [HZ] mice) alters postsynaptic differentiation of barrel cells. We found a transient increase in cytochrome oxidase staining between P6 and P14 in HZ animals, indicative of increased metabolic activity in barrel cortex during this time. Golgi impregnation and microtubule-associated protein 2 immunohistochemistry showed anomalous dendritic patterning in GAP-43 HZ cortex at P5, with altered dendritic length and branching and abnormal retention of dendrites that extend into developing septa. This deficiency was no longer apparent at P7, suggesting partial recovery of dendritic pruning processes. Finally, we showed early defects in synaptogenesis from P4 to P5 with increased colocalization of NR1 and GluR1 staining in HZ mice. By P7, this colocalization had normalized to wild type levels. Taken together, our findings suggest abnormal postsynaptic differentiation in GAP-43 HZ cortex during early barrel development, followed by adaptive compensation and partial phenotypic rescue.

Perceptual and Semantic Contributions to Repetition Priming of Environmental Sounds

De Lucia, M., Cocchi, L., Martuzzi, R., Meuli, R. A., Clarke, S., Murray, M. M. — Wed, 11 Nov 2009 06:21:50 PST

Repetition of environmental sounds, like their visual counterparts, can facilitate behavior and modulate neural responses, exemplifying plasticity in how auditory objects are represented or accessed. It remains controversial whether such repetition priming/suppression involves solely plasticity based on acoustic features and/or also access to semantic features. To evaluate contributions of physical and semantic features in eliciting repetition-induced plasticity, the present functional magnetic resonance imaging (fMRI) study repeated either identical or different exemplars of the initially presented object; reasoning that identical exemplars share both physical and semantic features, whereas different exemplars share only semantic features. Participants performed a living/man-made categorization task while being scanned at 3T. Repeated stimuli of both types significantly facilitated reaction times versus initial presentations, demonstrating perceptual and semantic repetition priming. There was also repetition suppression of fMRI activity within overlapping temporal, premotor, and prefrontal regions of the auditory "what" pathway. Importantly, the magnitude of suppression effects was equivalent for both physically identical and semantically related exemplars. That the degree of repetition suppression was irrespective of whether or not both perceptual and semantic information was repeated is suggestive of a degree of acoustically independent semantic analysis in how object representations are maintained and retrieved.

Cortical Representation of Interaural Time Difference in Congenital Deafness

Tillein, J., Hubka, P., Syed, E., Hartmann, R., Engel, A.K., Kral, A. — Wed, 11 Nov 2009 06:21:49 PST

Binaural cues are required for localization of sound sources. In the present paper, representation of binaural cues has been investigated in the adult auditory cortex. Hearing and congenitally deaf cats were stimulated through binaural cochlear implants and unit responses were collected in the subregion of field A1 showing the largest amplitudes of evoked local field potentials. Sensitivity to interaural time difference (ITD) in the range from –600 to 600 µs was tested at intensities of 0–10 dB above hearing threshold. Template ITD functions were fitted to the data and parameters of ITD functions were compared between deaf and hearing animals. In deaf animals, fewer units responded to binaural stimulation, and those that responded had smaller maximal evoked firing rate. The fit to the template ITD functions was significantly worse in deaf animals, and the modulation depth in ITD functions was smaller, demonstrating a decrease in ITD sensitivity. With increasing binaural levels, hearing controls demonstrated systematic changes in ITD functions not found in deaf animals. Bimodal responses, likely related to precedence effect, were rare in deaf animals. The data demonstrate that despite some rudimentary sensitivity to interaural timing, cortical representation of ITDs is substantially altered by congenital auditory deprivation.

Distinct Temporospatial Interhemispheric Interactions in the Human Primary and Premotor Cortex during Movement Preparation

Wed, 11 Nov 2009 06:21:47 PST

The preparation of a voluntary unimanual action requires sequential processing in bihemispheric motor areas. In both animals and humans, activity in the dorsal premotor cortex (PMd) ipsilateral to the moving hand has been demonstrated to precede ipsilateral primary motor cortex (M1) activity. We investigated with double-pulse transcranial magnetic stimulation how right-hemispheric motor areas (rM1, rPMd) modulate left M1 (lM1) during the preparatory period of a finger movement with the dominant right hand. We tested the hypothesis that the influence of higher order motor areas such as rPMd on lM1 (rPMd-lM1) precedes interhemispheric interactions between homologue primary motor areas (rM1-lM1). rPMd-lM1 showed modulation in the early and late phase of movement preparation, whereas the intrinsic state of inhibition between rM1-lM1 was only modulated in the late phase. The present results complement existing hierarchical models of cortical movement control by demonstrating temporospatially distinct involvement of interhemispheric interactions from PMd and M1 during movement preparation.

Opposing Effects of 5,7-DHT Infusions into the Orbitofrontal Cortex and Amygdala on Flexible Responding

Man, M.S., Dalley, J.W., Roberts, A.C. — Tue, 10 Nov 2009 07:09:02 PST

Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.

Frequency Facilitation at Mossy Fiber-CA3 Synapses of Freely Behaving Rats Contributes to the Induction of Persistent LTD via an Adenosine-A1 Receptor-Regulated Mechanism

Hagena, H., Manahan-Vaughan, D. — Tue, 10 Nov 2009 07:09:01 PST

Frequency facilitation (FF), comprising a rapid and multiple-fold increase in the magnitude of evoked field potentials, is elicited by low-frequency stimulation (LFS) at mossy fiber–CA3 synapses. Here, we show that in freely behaving rats, FF reliably occurs in response to 1 and 2Hz but not in response to 0.25-, 0.3-, or 0.5-Hz LFS. Strikingly, prolonged (~600 s) FF was tightly correlated to the induction of long-term depression (LTD) in freely moving animals. Although LFS at 2 Hz elicited unstable FF and unstable LTD, application of LFS at 1 Hz elicited pronounced FF, as well as robust LTD that persisted for over 24 h. This correlation of prolonged FF with LTD was absent at stimulation frequencies that did not induce FF. The adenosine-A1 receptor appears to participate in these effects: Application of adenosine-A1, but not adenosine-A3, receptor antagonists enhanced mossy fiber synaptic transmission and occluded FF. Furthermore, adenosine-A1 receptor antagonism resulted in more stable FF at 1 or 2 Hz and elicited more potent LTD. These data support the fact that FF contributes to the enablement of long-term information storage at mossy fiber–CA3 synapses and that the adenosine-A1 receptor may regulate the thresholds for this process.

Prefrontal Cortical Contribution to Risk-Based Decision Making

St. Onge, J. R., Floresco, S. B. — Thu, 05 Nov 2009 05:23:36 PST

Damage to various regions of the prefrontal cortex (PFC) impairs decision making involving evaluations about risks and rewards. However, the specific contributions that different PFC subregions make to risk-based decision making are unclear. We investigated the effects of reversible inactivation of 4 subregions of the rat PFC (prelimbic medial PFC, orbitofrontal cortex [OFC], anterior cingulate, and insular cortex) on probabilistic (or risk) discounting. Rats were well trained to choose between either a "Small/Certain" lever that always delivered 1 food pellet, or another, "Large/Risky" lever, which delivered 4 pellets, but the probability of receiving reward decreased across 4 trial blocks (100%, 50%, 25%, and 12.5%). Infusions of gama-aminobutyric acid agonists muscimol/baclofen into the medial PFC increased risky choice. However, similar medial PFC inactivations decreased risky choice when the Large/Risky reward probability increased over a session. OFC inactivation increased response latencies in the latter trial blocks without affecting choice. Anterior cingulate or insular inactivations were without effect. The effects of prelimbic inactivations were not attributable to disruptions in response flexibility or judgments about the relative value of probabilistic rewards. Thus, the prelimbic, but not other PFC regions, plays a critical role in risk discounting, integrating information about changing reward probabilities to update value representations that facilitate efficient decision making.

Developmental Expression of the Oligodendrocyte Myelin Glycoprotein in the Mouse Telencephalon

Thu, 05 Nov 2009 05:23:35 PST

The oligodendrocyte myelin glycoprotein is a glycosylphosphatidylinositol-anchored protein expressed by neurons and oligodendrocytes in the central nervous system. Attempts have been made to identify the functions of the myelin-associated inhibitory proteins (MAIPs) after axonal lesion or in neurodegeneration. However, the developmental roles of some of these proteins and their receptors remain elusive. Recent studies indicate that NgR1 and the recently discovered receptor PirB restrict cortical synaptic plasticity. However, the putative factors that trigger these effects are unknown. Because Nogo-A is mostly associated with the endoplasmic reticulum and myelin associated glycoprotein appears late during development, the putative participation of OMgp should be considered. Here, we examine the pattern of development of OMgp immunoreactive elements during mouse telencephalic development. OMgp immunoreactivity in the developing cortex follows the establishment of the thalamo-cortical barrel field. At the cellular level, we located OMgp neuronal membranes in dendrites and axons as well as in brain synaptosome fractions and axon varicosities. Lastly, the analysis of the barrel field in OMgp-deficient mice revealed that although thalamo-cortical connections were formed, their targeting in layer IV was altered, and numerous axons ectopically invaded layers II–III. Our data support the idea that early expressed MAIPs play an active role during development and point to OMgp participating in thalamo-cortical connections.

Responses of MSTd and MT Neurons during Smooth Pursuit Exhibit Similar Temporal Frequency Dependence on Retinal Image Motion

Inaba, N., Kawano, K. — Thu, 05 Nov 2009 05:23:33 PST

When our eyes are in constant motion, the world around us remains perceptually stable; although eye movements produce slips of the visual scene on our retinae. In our previous study, we suggested that visual motion in space is served by neurons, which compensate retinal-image motion due to pursuit eye movements, in the dorsal part of the medial superior temporal (MSTd) area. Additionally, neurons in the middle temporal (MT) area respond to retinal-image motion. In the present study, to further elucidate the visual properties of MSTd/MT neurons, we investigated the neuronal response to the motion of checkerboard patterns (CBPs) in addition to the random-dot pattern used in the previous study. We found that neuronal responses in both areas decreased regardless of fixation or pursuit when the temporal frequency of the CBPs exceeded 20 Hz on the retina. Our results support the idea that pursuit-speed compensation observed in area MSTd might be formed by the reception of retina-based visual information from MT neurons because both areas MT and MSTd were dependent on retina-based information during pursuit eye movements.

Secretogranin III Is an Astrocyte Granin That Is Overexpressed in Reactive Glia

Paco, S., Pozas, E., Aguado, F. — Thu, 05 Nov 2009 05:23:32 PST

Astrocytes release peptide and nonpeptide transmitters that influence neuronal development, function, and plasticity. However, the molecular components of the astroglial secretory pathways in vivo are largely unknown. Here, we analyze in astrocytes the production, expression regulation, trafficking, and release of secretogranin III (SgIII), a member of the multifunctional granin family. We show that astroglial cells in culture synthesize and release a nonprocessed form of SgIII. In vivo studies show that many neuronal populations produce and transport SgIII. In particular, the highest SgIII expression in the cerebral cortex in vivo is present in astroglial cells. Both SgIII protein and mRNA are abundantly detected in cortical astrocytes and in Bergmann glial cells. Moreover, the levels of SgIII mRNA and protein in reactive astrocytes, induced by perforating injury increase dramatically. These results implicate SgIII in the astrocyte secretory pathway in vivo and show that its expression is finely regulated during glial activation. The robust expression of SgIII in astrocytes and its regulation in the injured brain suggest both intracellular and extracellular roles for this glial granin in the physiology and repair/damage of neuronal circuits.

Cerebral Lateralization of Face-Selective and Body-Selective Visual Areas Depends on Handedness

Willems, R. M., Peelen, M. V., Hagoort, P. — Wed, 04 Nov 2009 02:47:36 PST

The left-hemisphere dominance for language is a core example of the functional specialization of the cerebral hemispheres. The degree of left-hemisphere dominance for language depends on hand preference: Whereas the majority of right-handers show left-hemispheric language lateralization, this number is reduced in left-handers. Here, we assessed whether handedness analogously has an influence upon lateralization in the visual system. Using functional magnetic resonance imaging, we localized 4 more or less specialized extrastriate areas in left- and right-handers, namely fusiform face area (FFA), extrastriate body area (EBA), fusiform body area (FBA), and human motion area (human middle temporal [hMT]). We found that lateralization of FFA and EBA depends on handedness: These areas were right lateralized in right-handers but not in left-handers. A similar tendency was observed in FBA but not in hMT. We conclude that the relationship between handedness and hemispheric lateralization extends to functionally lateralized parts of visual cortex, indicating a general coupling between cerebral lateralization and handedness. Our findings indicate that hemispheric specialization is not fixed but can vary considerably across individuals even in areas engaged relatively early in the visual system.

Reduction of Basal Forebrain Cholinergic System Parallels Cognitive Impairment in Patients at High Risk of Developing Alzheimer's Disease

Wed, 04 Nov 2009 02:47:35 PST

Neuropathological studies suggest that the basal forebrain cholinergic system (BFCS) is affected in Alzheimer's disease (AD), but there is no in vivo evidence of early damage to this system in subjects at high risk of developing AD. Here, we found that mild cognitive impairment (MCI) patients exhibited significant volume reduction of the nucleus basalis of Meynert (NbM) using recently developed probabilistic maps of the BFCS space. In addition, volumes of different magnocellular compartments varied significantly with regional gray matter atrophy in regions known to be affected by AD and were found to correlate with cognitive decline in MCI patients. Bilateral reductions of the horizontal nucleus of the diagonal band of Broca (Ch3) and frontal lobe (medial frontal, orbital, subcallosal gyrus, anterior cingulate, and middle frontal gyrus) were significantly associated with a global decline in cognitive status, whereas volume reduction of the posterior compartment of Ch4 (NbM) and temporal lobe (including hippocampus, entorhinal cortex, and amygdala) were associated with impaired delayed recall in MCI patients. These findings establish, for the first time, a link between degeneration of specific cholinergic compartments of the BFCS and cognitive-related deficits in subjects at high risk of developing AD.

Rapid Formation of Pragmatic Rule Representations in the Human Brain during Instruction-Based Learning

Ruge, H., Wolfensteller, U. — Wed, 04 Nov 2009 02:47:33 PST

The present functional magnetic resonance imaging study investigated the instruction-based learning of novel arbitrary stimulus–response mappings in order to understand the brain mechanisms that enable successful behavioral rule implementation in the absence of trial-and-error learning. We developed a novel task design that allowed the examination of rapidly evolving brain activation dynamics starting from an explicit instruction phase and further across a short behavioral practice phase. As a first key result, the study revealed that different sets of brain regions displayed either decreasing or increasing activation profiles already across the first few practice trials, suggesting an impressively rapid redistribution of labor throughout the brain. Furthermore, behavioral performance improvement across practice was tightly coupled with brain activation during the practice phase (caudate nucleus), the instruction phase (lateral midprefrontal cortex), or both (lateral premotor cortex bordering prefrontal cortex). Together, the present results provide first important insights into the brain systems involved in the rapid transfer of control from initially abstract rule representations induced by explicit instructions toward pragmatic representations enabling the fluent behavioral implementation.

Color Selectivity of Neurons in the Posterior Inferior Temporal Cortex of the Macaque Monkey

Yasuda, M., Banno, T., Komatsu, H. — Fri, 30 Oct 2009 08:23:07 PDT

We recorded the activities of neurons in the lateral surface of the posterior inferior temporal cortex (PIT) of 3 hemispheres of 3 monkeys performing a visual fixation task. We characterized the color and shape selectivities of each neuron, mapped its receptive field (RF), and studied the distributions of these response properties. Using a set of color stimuli that were systematically distributed in Commission Internationale de l'Eclairage-xy chromaticity diagram, we found numerous color-selective neurons distributed throughout the area examined. Neurons in the ventral region tended to have sharper color tuning than those in the dorsal region. We also found a crude retinotopic organization in the ventral region. Within the ventral region of PIT, neurons in the dorsal part had RFs that overlapped the foveal center; the eccentricity of RFs increased in the more ventral part, and neurons in the anterior and posterior parts had RFs that represented the lower and upper visual fields, respectively. In all 3 hemispheres, the region where sharply tuned color-selective neurons were concentrated was confined within this retinotopic map. These findings suggest that PIT is a heterogeneous area and that there is a circumscribed region within it that has crude retinotopic organization and is involved in the processing of color.

Integrated Cannabinoid CB1 Receptor Transmission within the Amygdala-Prefrontal Cortical Pathway Modulates Neuronal Plasticity and Emotional Memory Encoding

Tan, H., Lauzon, N. M., Bishop, S. F., Bechard, M. A., Laviolette, S. R. — Fri, 30 Oct 2009 08:23:01 PDT

The cannabinoid CB1 receptor system is functionally involved in the processing and encoding of emotionally salient sensory information, learning and memory. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC). In addition, synaptic plasticity in the form of long-term potentiation (LTP) within the BLA > mPFC pathway is an established correlate of exposure to emotionally salient events. We performed a series of in vivo LTP studies by applying tetanic stimulation to the BLA combined with recordings of local field potentials within prelimbic cortical (PLC) region of the rat mPFC. Systemic pretreatment with AM-251 dose dependently blocked LTP along the BLA–PLC pathway and also the behavioral acquisition of conditioned fear memories. We next performed a series of microinfusion experiments wherein CB1 receptor transmission within the BLA > PLC circuit was pharmacologically blocked. Asymmetrical, interhemispheric blockade of CB1 receptor transmission along the BLA > PLC pathway prevented the acquisition of emotionally salient associative memory. Our results indicate that coordinated CB1 receptor transmission within the BLA > PLC pathway is critically involved in the encoding of emotional fear memories and modulates neural plasticity related to the encoding of emotionally salient associative learning.

Immaturities in Reward Processing and Its Influence on Inhibitory Control in Adolescence

Geier, C.F., Terwilliger, R., Teslovich, T., Velanova, K., Luna, B. — Thu, 29 Oct 2009 12:01:17 PDT

The nature of immature reward processing and the influence of rewards on basic elements of cognitive control during adolescence are currently not well understood. Here, during functional magnetic resonance imaging, healthy adolescents and adults performed a modified antisaccade task in which trial-by-trial reward contingencies were manipulated. The use of a novel fast, event-related design enabled developmental differences in brain function underlying temporally distinct stages of reward processing and response inhibition to be assessed. Reward trials compared with neutral trials resulted in faster correct inhibitory responses across ages and in fewer inhibitory errors in adolescents. During reward trials, the blood oxygen level–dependent signal was attenuated in the ventral striatum in adolescents during cue assessment, then overactive during response preparation, suggesting limitations during adolescence in reward assessment and heightened reactivity in anticipation of reward compared with adults. Importantly, heightened activity in the frontal cortex along the precentral sulcus was also observed in adolescents during reward-trial response preparation, suggesting reward modulation of oculomotor control regions supporting correct inhibitory responding. Collectively, this work characterizes specific immaturities in adolescent brain systems that support reward processing and describes the influence of reward on inhibitory control. In sum, our findings suggest mechanisms that may underlie adolescents’ vulnerability to poor decision-making and risk-taking behavior.

The Temporal Dynamics of the Muller-Lyer Illusion

Weidner, R., Boers, F., Mathiak, K., Dammers, J., Fink, G. R. — Thu, 29 Oct 2009 12:01:15 PDT

By attaching arrows to a line's ends, the Müller-Lyer illusion can be used to modulate perceived line length. In the present study, we investigated the dynamics of the brain processes underlying this illusion using magnetoencephalography. Subjects were presented with a horizontal line with arrows attached to its ends. Across trials, the angles formed by the arrows were repeatedly changed such that 2 variants of the Müller-Lyer length illusion were either induced or not. The onset of both variants of the illusion revealed consistent activations in visual areas between 85 and 130 ms after stimulus onset, as well as strong and longer lasting activations along the ventral visual processing stream including inferior occipital, inferior temporal, and fusiform gyrus within the range of 195–220 ms. Subsequent neural activation was observed in the right superior temporal cortex, as well as in the right inferior parietal and the right inferior frontal cortex. The time course and the location of the activations suggest that the mechanisms involved in generating the Müller-Lyer illusion are closely linked to the ones associated with object perception, consistent with theories considering a relevant contribution of higher visual areas to the generation of the Müller-Lyer illusion.

Projection from Visual Areas V2 and Prostriata to Caudal Auditory Cortex in the Monkey

Thu, 29 Oct 2009 12:01:14 PDT

Studies in humans and monkeys report widespread multisensory interactions at or near primary visual and auditory areas of neocortex. The range and scale of these effects has prompted increased interest in interconnectivity between the putatively "unisensory" cortices at lower hierarchical levels. Recent anatomical tract-tracing studies have revealed direct projections from auditory cortex to primary visual area (V1) and secondary visual area (V2) that could serve as a substrate for auditory influences over low-level visual processing. To better understand the significance of these connections, we looked for reciprocal projections from visual cortex to caudal auditory cortical areas in macaque monkeys. We found direct projections from area prostriata and the peripheral visual representations of area V2. Projections were more abundant after injections of temporoparietal area and caudal parabelt than after injections of caudal medial belt and the contiguous areas near the fundus of the lateral sulcus. Only one injection was confined to primary auditory cortex (area A1) and did not demonstrate visual connections. The projections from visual areas originated mainly from infragranular layers, suggestive of a "feedback"-type projection. The selective localization of these connections to peripheral visual areas and caudal auditory cortex suggests that they are involved in spatial localization.

Role of Late Maternal Thyroid Hormones in Cerebral Cortex Development: An Experimental Model for Human Prematurity

Wed, 28 Oct 2009 10:58:16 PDT

Hypothyroxinemia affects 35–50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers’ organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.

Theta Oscillations Mediate Interaction between Prefrontal Cortex and Medial Temporal Lobe in Human Memory

Anderson, K. L., Rajagovindan, R., Ghacibeh, G. A., Meador, K. J., Ding, M. — Tue, 27 Oct 2009 12:03:57 PDT

The medial temporal lobe (MTL) and the prefrontal cortex (PFC) are known to be critical structures for human memory processes. Furthermore, it has been suggested that they are part of a memory network. Although memory-modulated interaction between PFC and MTL has been observed at the hemodynamic level, it remains unclear what the neuronal process is that mediates the communication between these 2 areas. Experiments in rodents suggest that field oscillations in the theta band (4–8 Hz) facilitate PFC–MTL interaction. No such evidence has been reported in humans. To address this problem, cortical electrical activity from MTL, PFC, and lateral temporal lobe was recorded from implanted electrode grids in 3 epilepsy patients performing a verbal free recall task. The data were analyzed using a parametric spectral method to obtain estimates of power, coherence, and Granger causality. A task-modulated increase in coherence values between PFC and MTL was seen during free recall as opposed to a baseline condition. Concurrently, the number of coherent PFC–MTL site pairs was significantly increased during recall. Granger causality analysis further revealed that the increased coherence is a consequence of higher bidirectional information flow between the 2 regions, with a generally greater driving from MTL to PFC, namely, (MTL->PFC) > (PFC->MTL).

Leading Process Branch Instability in Lis1+/- Nonradially Migrating Interneurons

Gopal, P. P., Simonet, J. C., Shapiro, W., Golden, J. A. — Tue, 27 Oct 2009 12:03:54 PDT

Mammalian forebrain development requires extensive migration, yet the mechanisms through which migrating neurons sense and respond to guidance cues are not well understood. Similar to the axon growth cone, the leading process and branches of neurons may guide migration, but the cytoskeletal events that regulate branching are unknown. We have previously shown that loss of microtubule-associated protein Lis1 reduces branching during migration compared with wild-type neurons. Using time-lapse imaging of Lis1^+/– and Lis1^+/+ cells migrating from medial ganglionic eminence explant cultures, we show that the branching defect is not due to a failure to initiate branches but a defect in the stabilization of new branches. The leading processes of Lis1^+/– neurons have reduced expression of stabilized, acetylated microtubules compared with Lis1^+/+ neurons. To determine whether Lis1 modulates branch stability through its role as the noncatalytic β regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b, exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type neurons phenocopies the branch instability observed in Lis1^+/– neurons, and a PAF antagonist rescues leading process branching in Lis1^+/– neurons. These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization.

Neural Correlates of the Spatial and Expectancy Components of Endogenous and Stimulus-Driven Orienting of Attention in the Posner Task

Doricchi, F., Macci, E., Silvetti, M., Macaluso, E. — Wed, 21 Oct 2009 02:38:42 PDT

Voluntary orienting of visual attention is conventionally measured in tasks with predictive central cues followed by frequent valid targets at the cued location and by infrequent invalid targets at the uncued location. This implies that invalid targets entail both spatial reorienting of attention and breaching of the expected spatial congruency between cues and targets. Here, we used event-related functional magnetic resonance imaging (fMRI) to separate the neural correlates of the spatial and expectancy components of both endogenous orienting and stimulus-driven reorienting of attention. We found that during endogenous orienting with predictive cues, there was a significant deactivation of the right Temporal–Parietal Junction (TPJ). We also discovered that the lack of an equivalent deactivation with nonpredictive cues was matched to drop in attentional costs and preservation of attentional benefits. The right TPJ showed equivalent responses to invalid targets following predictive and nonpredictive cues. On the contrary, infrequent-unexpected invalid targets following predictive cues specifically activated the right Middle and Inferior Frontal Gyrus (MFG–IFG). Additional comparisons with spatially neutral trials demonstrated that, independently of cue predictiveness, valid targets activate the left TPJ, whereas invalid targets activate both the left and right TPJs. These findings show that the selective right TPJ activation that is found in the comparison between invalid and valid trials results from the reciprocal canceling of the different activations that in the left TPJ are related to the processing of valid and invalid targets. We propose that left and right TPJs provide "matching and mismatching to attentional template" signals. These signals enable reorienting of attention and play a crucial role in the updating of the statistical contingency between cues and targets.

Effect of Familial Sinistrality on Planum Temporale Surface and Brain Tissue Asymmetries

Wed, 21 Oct 2009 02:38:41 PDT

The impact of having left-handers (LHs) among one's close relatives, called familial sinistrality (FS), on neuroanatomical markers of left-hemisphere language specialization was studied in 274 normal adults, including 199 men and 75 women, among whom 77 men and 27 women were positive for FS. Measurements of the surface of a phonological cortical area, the "planum temporale" (PT), and gray and white matter hemispheric volumes and asymmetries were made using brain magnetic resonance images. The size of the left PT of subjects with left-handed close relatives (FS+) was reduced by 10%, decreasing with the number of left-handed relatives, and lowest when the subject's mother was left-handed. Such findings had no counterparts in the right hemisphere, and the subject's handedness and sex were found to have no significant effect or interaction with FS on the left PT size. The FS+ subjects also exhibited increased gray matter volume, reduced hemispheric gray matter leftward asymmetry, and, in LHs, reduced strength of hand preference. These results add to the increasing body of evidence suggesting multiple and somewhat independent mechanisms for the inheritance of hand and language lateralization.

Spinogenesis and Pruning from Early Visual Onset to Adulthood: An Intracellular Injection Study of Layer III Pyramidal Cells in the Ventral Visual Cortical Pathway of the Macaque Monkey

Elston, G. N., Oga, T., Okamoto, T., Fujita, I. — Wed, 21 Oct 2009 02:38:43 PDT

Neocortical pyramidal cells are characterized by markedly different structure among cortical areas in the mature brain. In the ventral visual pathway of adult primates, pyramidal cells become increasingly more branched and more spinous with anterior progression through the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. It is not known how these regional specializations in neuron structure develop. Here, we report that the basal dendritic trees of layer III pyramidal cells in V1, V2, V4, TEO, and TE were characterized by unique growth profiles. Different numbers of spines were grown in the dendritic trees of cells among these cortical areas and then subsequently pruned. In V1, V2, and V4, more spines were pruned than grew resulting in a net decrease in the number of spines in the dendritic trees following the onset of visual experience. In TEO and TE, neurons grew more spines than they pruned from visual onset to adulthood. These data suggest that visual experience may influence neuronal maturation in different ways in different cortical areas.

The Importance of Failure: Feedback-Related Negativity Predicts Motor Learning Efficiency

van der Helden, J., Boksem, M. A. S., Blom, J. H. G. — Mon, 19 Oct 2009 01:11:19 PDT

Learning from past mistakes is of prominent importance for successful future behavior. In the present study, we tested whether reinforcement learning signals in the brain are predictive of adequate learning of a sequence of motor actions. We recorded event-related potentials (ERPs) while subjects engaged in a sequence learning task. The results showed that brain responses to feedback (the feedback-related negativity [FRN]) predicted whether subjects learned to avoid an erroneous response the next time this action had to be performed. Our findings add to a growing literature on feedback-based performance adjustment, by showing that FRN amplitudes may reflect the acquisition of motor skill and the consolidation of contingencies between stimuli or cues and their associated responses, providing evidence that learning efficiency and future performance can be predicted by the neural response to current feedback: FRN amplitude associated with a mistake is predictive of whether this mistake will be repeated, or learned from.

Profiles of Precentral and Postcentral Cortical Mean Thicknesses in Individual Subjects over Acute and Subacute Time-Scales

Tue, 13 Oct 2009 02:44:08 PDT

Human precentral and postcentral cortical areas interact to generate sensorimotor functions. Recent imaging work suggests that pre- and postcentral cortical thicknesses of an individual vary over time-scales of years and decades due to aging, disease, and other factors. In contrast, there is little understanding of how thicknesses of these areas vary in an individual over time-scales of minutes and weeks. This study used longitudinal magnetic resonance imaging (MRI) and computational morphometry approaches in 5 healthy subjects to assess how mean thicknesses, and intra- and interhemispheric relationships in mean thicknesses, of these areas vary in an individual subject over minutes and weeks. Within each individual, absolute differences in thicknesses over these times were small and similar in the precentral (mean = 0.02–0.04 mm) and postcentral (mean = 0.03–0.05 mm) areas. Each individual also had a consistent intrahemispheric disparity and interhemispheric asymmetrical or symmetrical relationship in thicknesses of these areas over these times. The results provide new understanding of within-individual cortical thickness variability in these areas and raise the possibility that longitudinal thickness profiling can provide a baseline definition of short time-scale thickness variability that can be used to detect acute and subacute changes in pre- and postcentral thicknesses at an individual subject level.

Cytoarchitecture and Probabilistic Maps of the Human Posterior Insular Cortex

Kurth, F., Eickhoff, S. B., Schleicher, A., Hoemke, L., Zilles, K., Amunts, K. — Mon, 12 Oct 2009 00:44:06 PDT

The human posterior insula was shown to respond to a wide variety of stimulation paradigms (e.g. pain, somatosensory, or auditory processing) in functional imaging experiments. Although various anatomical maps of this region have been published over the last century, these schemes show variable results. Moreover, none can directly be integrated with functional imaging data. Hence, our current knowledge about the structure–function relationships in this region remains limited. We therefore remapped the posterior part of the human insular cortex in 10 postmortem brains using an observer-independent approach. This analysis revealed the existence of 3 cytoarchitectonically distinct areas in the posterior insula. The examined brains were then 3D reconstructed and spatially normalized to the Montreal Neurological Institute single-subject template. Probabilistic maps for each area were calculated by superimposing the individual delineations, and a cytoarchitectonic summary map was computed to chart the regional architectonic organization. These maps can be used to identify the anatomical correlates of functional activations observed in neuroimaging studies and to understand the microstructural correlates of the functional segregation of the human posterior insula.

Cortical Anatomy in Autism Spectrum Disorder: An In Vivo MRI Study on the Effect of Age

Fri, 09 Oct 2009 04:41:23 PDT

There is increasing evidence that children with autism spectrum disorder (ASD) have age-related differences from controls in cortical volume (CV). It is less clear, however, if these persist in adulthood and whether these reflect alterations in cortical thickness (CT) or cortical surface area (SA). Hence, we used magnetic resonance imaging to investigate the relationship between age and CV, CT, and SA in 127 males aged 10 through 60 years (76 with ASD and 51 healthy controls). "Regional" analyses (using cortical parcellation) identified significant age-by-group interactions in both CV and CT (but not SA) in the temporal lobes and within these the fusiform and middle temporal gyri. Spatially nonbiased "vertex-based" analysis replicated these results and identified additional "age-by-group" interactions for CT within superior temporal, inferior and medial frontal, and inferior parietal cortices. Here, CV and CT were 1) significantly negatively correlated with age in controls, but not in ASD, and 2) smaller in ASD than controls in childhood but vice versa in adulthood. Our findings suggest that CV dysmaturation in ASD extends beyond childhood, affects brain regions crucial to social cognition and language, and is driven by CT dysmaturation. This may reflect primary abnormalities in cortical plasticity and/or be secondary to disturbed interactions between individuals with ASD and their environment.

Brain Anatomy Changes Associated with Persistent Neuropathic Pain Following Spinal Cord Injury

Gustin, S. M., Wrigley, P. J., Siddall, P. J., Henderson, L. A. — Thu, 08 Oct 2009 07:07:53 PDT

Persistent neuropathic pain commonly occurs following spinal cord injury (SCI). It remains one of the most challenging management problems in this condition. In order to develop more effective treatments, a better understanding of the neural changes associated with neuropathic SCI pain is required. The aim of this investigation was to use diffusion tensor imaging (DTI) to determine if persistent neuropathic pain following SCI is associated with changes in regional brain anatomy and connectivity. In 23 subjects with complete thoracic SCI, 12 with below-level neuropathic pain and 11 without pain, and 45 healthy control subjects, a series of whole-brain DTI scans were performed. The mean diffusivity (MD) of each voxel was calculated and values compared between groups. This analysis revealed that neuropathic pain following SCI is associated with significant differences in regional brain anatomy. These anatomical changes were located in pain-related regions as well as regions of the classic reward circuitry, that is, the nucleus accumbens and orbitofrontal, dorsolateral prefrontal, and posterior parietal cortices. The right posterior parietal cortex projected to most regions that displayed an anatomical change. Analysis of the fiber tracts connecting areas of MD differences revealed no significance differences in MD values between the SCI pain, SCI no pain, and control groups.

Synchronization Dynamics in Response to Plaid Stimuli in Monkey V1

Lima, B., Singer, W., Chen, N.-H., Neuenschwander, S. — Wed, 07 Oct 2009 08:34:39 PDT

Gamma synchronization has generally been associated with grouping processes in the visual system. Here, we examine in monkey V1 whether gamma oscillations play a functional role in segmenting surfaces of plaid stimuli. Local field potentials (LFPs) and spiking activity were recorded simultaneously from multiple sites in the opercular and calcarine regions while the monkeys were presented with sequences of single and superimposed components of plaid stimuli. In accord with the previous studies, responses to the single components (gratings) exhibited strong and sustained gamma-band oscillations (30–65 Hz). The superposition of the second component, however, led to profound changes in the temporal structure of the responses, characterized by a drastic reduction of gamma oscillations in the spiking activity and systematic shifts to higher frequencies in the LFP (~10% increase). Comparisons between cerebral hemispheres and across monkeys revealed robust subject-specific spectral signatures. A possible interpretation of our results may be that single gratings induce strong cooperative interactions among populations of cells that share similar response properties, whereas plaids lead to competition. Overall, our results suggest that the functional architecture of the cortex is a major determinant of the neuronal synchronization dynamics in V1.

Tonic Modulation of GABA Release by Nicotinic Acetylcholine Receptors in Layer V of the Murine Prefrontal Cortex

Wed, 07 Oct 2009 08:34:31 PDT

By regulating the neocortical excitability, nicotinic acetylcholine receptors (nAChRs) control vigilance and cognition and are implicated in epileptogenesis. Modulation of -aminobutyric acid (GABA) release often accompanies these processes. We studied how nAChRs regulate GABAergic transmission in the murine neocortex with immunocytochemical and patch-clamp methods. The cholinergic fibers densely innervated the somatosensory, visual, motor, and prefrontal cortices (PFC). Laminar distribution was broadly homogeneous, especially in the PFC. The cholinergic terminals were often adjacent to the soma and dendrites of GABAergic interneurons, but well-differentiated synapses were rare. Tonically applied nicotine (1–100 µM) increased the frequency of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) on pyramidal neurons in PFC layer V. The contribution of nAChR types was assessed by using 1 µM dihydro-β-erythroidine (DHβE), to block heteromeric nAChRs, and 10 nM methyllycaconitine (MLA), to block homomeric nAChRs. Both inhibitors antagonized the effect of nicotine on IPSCs, suggesting that mixed nAChR types control pyramidal neuron inhibition in layer V. To determine whether nAChRs are expressed on basket cells’ terminals, we studied miniature IPSCs (mIPSCs). These were revealed using 0.5 µM tetrodotoxin and 50 µM Cd²⁺ to isolate the GABAergic terminals from the action potential drive. The nicotinic stimulation of mIPSCs was antagonized by DHβE, but not MLA, indicating that heteromeric nAChRs prevail in GABAergic terminals. Immunocytochemistry confirmed the expression of nAChRs on basket cells’ somata and terminals. Finally, when the ionotropic glutamatergic transmission was blocked, nicotine partially inhibited the IPSCs, an effect counteracted by both DHβE and MLA. Therefore, a fraction of nAChRs are capable of activating GABAergic interneurons that in turn inhibit other GABAergic interneurons, thereby reducing the IPSCs. We conclude that heteromeric nAChRs control GABA release presynaptically, whereas mixed nAChRs regulate both excitation and inhibition of interneurons, the balance depending on the overall glutamatergic drive.

Motor Cortex Plasticity Predicts Recovery in Acute Stroke

Mon, 05 Oct 2009 00:14:58 PDT

Repetitive transcranial magnetic stimulation of the brain given as intermittent theta burst stimulation (iTBS) can induce long-term potentiation (LTP)–like changes in the stimulated hemisphere and long-term depression (LTD)–like changes in the opposite hemisphere. We evaluated whether LTP- and LTD-like changes produced by iTBS in acute stroke correlate with outcome at 6 months. We evaluated the excitability of affected hemisphere (AH) and unaffected hemisphere (UH) by measuring motor threshold and motor-evoked potential (MEP) amplitude under baseline conditions and after iTBS of AH in 17 patients with acute ischemic stroke. Baseline amplitude of MEPs elicited from AH was significantly smaller than that of MEPs elicited from UH, and baseline motor threshold was higher for the AH. Higher baseline MEP values in UH correlated with poor prognosis. iTBS produced a significant increase in MEP amplitude for AH that was significantly correlated with recovery. A nonsignificant decrease in MEP amplitude was observed for the UH. When the decrease in the amplitude of UH MEPs was added to the regression model, the correlation was even higher. Functional recovery is directly correlated with LTP-like changes in AH and LTD-like changes in UH and inversely correlated with the baseline excitability of UH.

Age-Related Shifts in Brain Activity Dynamics during Task Switching

Jimura, K., Braver, T. S. — Mon, 05 Oct 2009 00:14:57 PDT

Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes.

Ventral Premotor and Inferior Parietal Cortices Make Distinct Contribution to Action Organization and Intention Understanding

Bonini, L., Rozzi, S., Serventi, F. U., Simone, L., Ferrari, P. F., Fogassi, L. — Mon, 05 Oct 2009 00:14:56 PDT

It is well known that ventral premotor area F5 codes the goal of executed and observed motor acts. This area is anatomically connected with part of the inferior parietal cortex (area PFG), which has been recently shown to play a role in action organization and intention understanding. The aims of the present study were 1) to assess whether the discharge of F5 motor neurons and mirror neurons (MNs) codes action goals and 2) to clarify the relative contribution of F5 and PFG in action organization and intention understanding. To this purpose, we first recorded from F5 motor neurons and MNs of 2 monkeys while performing a motor task constituted by 2 actions ("grasp-to-eat" and "grasp-to-place") or observing the same task done by an experimenter. Results showed that some F5 neurons code grasping according to the goal of the action in which it is embedded. Subsequently, we recorded from PFG motor neurons and MNs of the same monkeys, using the same tasks. The comparison between the neuronal properties of F5 and PFG motor neurons suggests that PFG plays a major role in organizing natural actions. Furthermore, the similarities between MNs properties of the 2 areas indicate that they constitute a functional circuit underlying others’ intention understanding.

Does Brain Activity at Rest Reflect Adaptive Strategies? Evidence from Speech Processing after Cochlear Implantation

Mon, 05 Oct 2009 00:14:55 PDT

In functional neuroimaging studies, task-related activity refers to the signal difference between the stimulation and rest conditions. We asked whether long-term changes in the sensory environment may affect brain activity at rest. To answer this question, we compared regional cerebral blood flow between a group of normally hearing controls and a group of cochlear-implanted (CI) deaf patients. Here we present evidence that long-term alteration of auditory experience, such as profound deafness followed by partial auditory recuperation through cochlear implantation, leads to functional cortical reorganizations at rest. Without any visual or auditory stimulation, CI subjects showed changes of cerebral blood flow in the visual, auditory cortex, Broca area, and in the posterior temporal cortex with an increment of activity in these areas from the time of activation of the implant to less than a year after the implantation.

Synaptic Organization of Connections between the Temporal Cortex and Pulvinar Nucleus of the Tree Shrew

Chomsung, R. D., Wei, H., Day-Brown, J. D., Petry, H. M., Bickford, M. E. — Thu, 01 Oct 2009 03:41:27 PDT

We examined the synaptic organization of reciprocal connections between the temporal cortex and the dorsal (Pd) and central (Pc) subdivisions of the tree shrew pulvinar nucleus, regions innervated by the medial and lateral superior colliculus, respectively. Both Pd and Pc subdivisions project topographically to 2 separate regions of the temporal cortex; small injections of anterograde tracers placed in either Pd or Pc labeled 2 foci of terminals in the temporal cortex. Pulvinocortical pathways innervated layers I–IV, with beaded axons oriented perpendicular to the cortical surface, where they synapsed with spines that did not contain gamma amino butyric acid (GABA), likely located on the apical dendrites of pyramidal cells. Projections from the temporal cortex to the Pd and Pc originate from layer VI cells, and form small terminals that contact small caliber non-GABAergic dendrites. These results suggest that cortical terminals are located distal to tectopulvinar terminals on the dendritic arbors of Pd and Pc projection cells, which subsequently contact pyramidal cells in the temporal cortex. This circuitry could provide a mechanism for the pulvinar nucleus to activate subcortical visuomotor circuits and modulate the activity of other visual cortical areas. The potential relation to primate tecto-pulvino-cortical pathways is discussed.

A Multivariate Analysis of Age-Related Differences in Default Mode and Task-Positive Networks across Multiple Cognitive Domains

Tue, 29 Sep 2009 05:38:12 PDT

We explored the effects of aging on 2 large-scale brain networks, the default mode network (DMN) and the task-positive network (TPN). During functional magnetic resonance imaging scanning, young and older participants carried out 4 visual tasks: detection, perceptual matching, attentional cueing, and working memory. Accuracy of performance was roughly matched at 80% across tasks and groups. Modulations of activity across conditions were assessed, as well as functional connectivity of both networks. Younger adults showed a broader engagement of the DMN and older adults a more extensive engagement of the TPN. Functional connectivity in the DMN was reduced in older adults, whereas the main pattern of TPN connectivity was equivalent in the 2 groups. Age-specific connectivity also was seen in TPN regions. Increased activity in TPN areas predicted worse accuracy on the tasks, but greater expression of a connectivity pattern associated with a right dorsolateral prefrontal TPN region, seen only in older adults, predicted better performance. These results provide further evidence for age-related differences in the DMN and new evidence of age differences in the TPN. Increased use of the TPN may reflect greater demand on cognitive control processes in older individuals that may be partially offset by alterations in prefrontal functional connectivity.

Temporal Dynamics of Selective Attention during Dichotic Listening

Ross, B., Hillyard, S. A, Picton, T. W — Tue, 29 Sep 2009 05:38:10 PDT

The ability to selectively attend to one sound and ignore other competing sounds is essential for auditory communication. Subjects in our study detected occasional changes in the frequency of amplitude modulation in sounds presented to one ear while ignoring sounds in the other ear. Neuromagnetic source analysis revealed attention-related activity in a cortical network including primary auditory cortices, posterior superior temporal gyri, inferior parietal lobules (IPLs), inferior frontal gyri (IFG), and medial frontal gyri. Time courses of event-related magnetoencephalography responses were analyzed during the interval between stimulus presentation and behavioral response. Enhanced neural responses to targets and standards in the attended ear indicated early modulation of sensitivity in the attended sensory channel. A subsequent process of discriminative stimulus selection was indexed by a response increase over time for targets and decreasing activity for standards. Enhanced responses to deviants in the unattended ear indicated discriminative processing of unattended inputs as well, though to a lesser extent than for attended stimuli. Superior temporal gyrus, planum temporale, and the IPL were prominently involved in stimulus selection, whereas medial frontal regions were linked to initiation of behavioral responses and sustained activity in IFG suggested a role in attentional control.

A Role for the Intraparietal Sulcus in Transforming Musical Pitch Information

Foster, N. E. V., Zatorre, R. J. — Tue, 29 Sep 2009 05:38:09 PDT

The present functional magnetic resonance imaging study investigates the neural substrates of relative pitch. Musicians and nonmusicians performed 2 same/different discrimination tasks (simple and transposed melody) that differed in whether they required precise encoding and comparison of relative pitch structure, along with 2 control tasks (rhythm and phoneme). The transposed melody task involved a musical transposition of 4 semitones between the target and comparison patterns, requiring listeners to use interval information rather than the absolute value of the individual pitches. Contrasting the transposed melody to the simple melody condition revealed greater activation in the cortex within the intraparietal sulcus (IPS) bilaterally; control tasks did not elicit significant activity in the IPS. Moreover, a whole-brain voxel-wise regression analysis of brain oxygenation level–dependent signal showed that activity within the right IPS predicted task performance for both musicians and nonmusicians specifically in the transposed melody condition. Successful performance of the transposed melody task requires encoding and comparison of auditory patterns having different tonal reference points—thus simple tonal memory is not sufficient. Our results point to a role for the IPS in transforming high-level auditory information. We suggest that this area may support a general capacity for transformation and comparison of systematically related stimulus attributes.

P2Y12 Receptor Protein in Cortical Gray Matter Lesions in Multiple Sclerosis

Amadio, S., Montilli, C., Magliozzi, R., Bernardi, G., Reynolds, R., Volonte, C. — Sat, 26 Sep 2009 04:13:42 PDT

Although Multiple Sclerosis (MS) is regarded as a white matter disease, the incidence of demyelination and axonal injury is prominent also in gray matter. In MS, extracellular adenosine triphosphate (ATP) is an important mediator of central nervous system pathology via its ability to cause oligodendrocyte excitotoxicity. We have analyzed the distribution pattern of all ionotropic P2X and metabotropic P2Y receptors for ATP in postmortem samples of the cerebral cortex from healthy human subjects as well as MS patients. We focus particularly on the P2Y₁₂ subtype that is highly enriched in oligodendrocytes. We correlate the expression of this receptor to the extent of gray matter demyelination and pathological alterations occurring during secondary progressive MS. Using triple immunofluorescence and confocal analysis, we show that in sections of cerebral cortex from postmortem MS brains, the P2Y₁₂ protein is present in myelin and interlaminar astrocytes but absent from protoplasmic astrocytes residing in the deeper cortical layers, from microglia/macrophages, and from intact demyelinated axons. We report that a decreased P2Y₁₂ receptor immunoreactivity in proximity to the lesions is directly correlated with the extent of demyelination found in all types of gray matter cortical plaques (I–III) and subcortical white matter. Our study provides further insights into the pathogenetic features of MS and suggests that the loss of purinergic P2Y₁₂ receptors might be detrimental to tissue integrity.

The Number of Attentional Foci and Their Precision Are Dissociated in the Posterior Parietal Cortex

Shim, W. M., Alvarez, G. A., Vickery, T. J., Jiang, Y. V. — Fri, 25 Sep 2009 05:20:57 PDT

Many everyday tasks require us to track moving objects with attention. The demand for attention increases both when more targets are tracked and when the targets move faster. These 2 aspects of attention—assigning multiple attentional foci (or indices) to targets and monitoring each focus with precision—may tap into different cognitive and brain mechanisms. In this study, we used functional magnetic resonance imaging to quantify the response profile of dorsal attentional areas to variations in the number of attentional foci and their spatiotemporal precision. Subjects were asked to track a specific spoke of either 1 or 2 pinwheels that rotated at various speeds. Their tracking performance declined both when more pinwheels were tracked and when the tracked pinwheels rotated faster. However, posterior parietal activity increased only when subjects tracked more pinwheels but remained flat when they tracked faster moving pinwheels. The frontal eye fields and early visual areas increased activity when there were more targets and when the targets rotated faster. These results suggest that the posterior parietal cortex is specifically involved in indexing independently moving targets with attention but not in monitoring each focus with precision.

Setting the Frame: The Human Brain Activates a Basic Low-Frequency Network for Language Processing

Fri, 25 Sep 2009 05:20:57 PDT

Low-frequency fluctuations (LFFs) are a major source of variation in fMRI data. This has been established in numerous experiments—particularly in the resting state. Here we investigate LFFs in a task-dependent setting. We hypothesized that LFFs may contain information about cognitive networks that are specific to the overall task domain without being time locked to stimulus onsets. We analyzed data of 6 fMRI experiments, 4 of which belonged to the language domain. After regressing out specifics of the experimental design and low-pass filtering (<0.1 Hz), we found that the 4 language experiments produced a correlational pattern that was not present in the 2 nonlanguage studies. Specifically, a region in the posterior part of the left superior temporal sulcus/gyrus was consistently correlated with both the left Brodmann's area 44 and the left frontal operculum in all 4 language studies, whereas this correlation was not found in the 2 other experiments. This finding indicates the existence of a basic network that acts as a general framework for language processing. In contrast to networks obtained by a conventional conjunction analysis of activation maps, this network is independent of experimental specifics such as stimulus onsets and exists in the low-frequency range.

Neural Modulation of Temporal Encoding, Maintenance, and Decision Processes

Harrington, D. L., Zimbelman, J. L., Hinton, S. C., Rao, S. M. — Thu, 24 Sep 2009 04:44:20 PDT

Time perception emerges from an interaction among multiple processes that are normally intertwined. Therefore, a challenge has been to disentangle timekeeping from other processes. Though the striatum has been implicated in interval timing, it also modulates nontemporal processes such as working memory. To distinguish these processes, we separated neural activation associated with encoding, working-memory maintenance, and decision phases of a time-perception task. We also asked whether neuronal processing of duration (i.e., pure tone) was distinct from the processing of identity (i.e., pitch perception) or sensorimotor features (i.e., control task). Striatal activation was greater when encoding the duration than the pitch or basic sensory features, which did not differentially engage the striatum. During the maintenance phase, striatal activation was similar for duration and pitch but at baseline in the control task. In the decision phase, a stepwise reduction in striatal activation was found across the 3 tasks, with activation greatest in the timing task and weakest in the control task. Task-related striatal activations in different cognitive phases were distinguished from those of the supplementary motor area, inferior frontal gyrus, thalamus, frontoparietal cortices, and the cerebellum. Our results were consistent with a model in which timing emerges from context-dependent corticostriatal interactions.

Level of Executive Function Influences Verbal Memory in Amnestic Mild Cognitive Impairment and Predicts Prefrontal and Posterior Cingulate Thickness

Wed, 23 Sep 2009 11:58:11 PDT

This study aims to investigate the relationship between executive function and verbal memory and to explore the underlying neuroanatomical correlates in 358 individuals with amnestic mild cognitive impairment (MCI) and 222 healthy controls (HCs). The MCI participants were divided into 2 groups (high vs. low) based on executive function task performance. Results demonstrated that although both MCI groups were impaired on all memory measures relative to HCs, MCI individuals with higher executive function (HEF) demonstrated better verbal memory performance than those with lower executive function (LEF), particularly on measures of learning. The 2 MCI groups did not differ in mesial temporal morphometric measures, but the MCI LEF group showed significant thinning in dorsolateral prefrontal and posterior cingulate cortices bilaterally compared with the MCI HEF and HCs. Further, thickness in numerous regions of frontal cortex, and bilateral posterior cingulate, was significantly associated with memory performance in all MCI participants above and beyond the contribution of the mesial temporal regions known to be associated with episodic memory. Overall, these results demonstrate the importance of evaluating executive function in individuals with MCI to predict involvement of brain areas beyond the mesial temporal lobe.

Comparative Cytoarchitectural Analyses of Striate and Extrastriate Areas in Hominoids

Wed, 23 Sep 2009 11:58:10 PDT

The visual cortex is the largest sensory modality representation in the neocortex of humans and closely related species, and its size and organization has a central role in discussions of brain evolution. Yet little is known about the organization of visual brain structures in the species closest to humans—the apes—thus, making it difficult to evaluate hypotheses about recent evolutionary changes. The primate visual cortex is comprised of numerous cytoarchitectonically distinct areas, each of which has a specific role in the processing of visual stimuli. We examined the histological organization of striate (V1) and 2 extrastriate (V2 and ventral posterior) cortical areas in humans, 5 ape species, and a macaque. The cytoarchitectural patterns of visual areas were compared across species using quantitative descriptions of cell volume densities and laminar patterns. We also investigated potential scaling relationships between cell volume density and several brain, body, and visual system variables. The results suggest that interspecific variability in the cytoarchitectural organization of visual system structures can arise independently of global brain and body size scaling relationships. In particular, species-specific differences in cell volume density seem to be most closely linked to the size of structures in the visual system.

Cultural Constraints on Brain Development: Evidence from a Developmental Study of Visual Word Processing in Mandarin Chinese

Cao, F., Lee, R., Shu, H., Yang, Y., Xu, G., Li, K., Booth, J. R. — Tue, 22 Sep 2009 12:14:40 PDT

Developmental differences in phonological and orthographic processing in Chinese were examined in 9 year olds, 11 year olds, and adults using functional magnetic resonance imaging. Rhyming and spelling judgments were made to 2-character words presented sequentially in the visual modality. The spelling task showed greater activation than the rhyming task in right superior parietal lobule and right inferior temporal gyrus, and there were developmental increases across tasks bilaterally in these regions in addition to bilateral occipital cortex, suggesting increased involvement over age on visuo-orthographic analysis. The rhyming task showed greater activation than the spelling task in left superior temporal gyrus and there were developmental decreases across tasks in this region, suggesting reduced involvement over age on phonological representations. The rhyming and spelling tasks included words with conflicting orthographic and phonological information (i.e., rhyming words spelled differently or nonrhyming words spelled similarly) or nonconflicting information. There was a developmental increase in the difference between conflicting and nonconflicting words in left inferior parietal lobule, suggesting greater engagement of systems for mapping between orthographic and phonological representations. Finally, there were developmental increases across tasks in an anterior (Broadman area [BA] 45, 46) and posterior (BA 9) left inferior frontal gyrus, suggesting greater reliance on controlled retrieval and selection of posterior lexical representations.

The Neural Basis of Categorical Face Perception: Graded Representations of Face Gender in Fusiform and Orbitofrontal Cortices

Freeman, J. B., Rule, N. O., Adams, R. B., Ambady, N. — Fri, 18 Sep 2009 01:01:39 PDT

Face gender, like many other things, is perceived categorically: Subjective perceptions are distorted toward the categories, male or female, and the objective gradiency inherent across faces is partially lost. The neural basis of such categorical face perception remains virtually unknown. Participants passively viewed faces whose sexually dimorphic content was morphed monotonically from male to female while neural activity was measured using functional magnetic resonance imaging. Subjective perceptions revealed strong nonlinearity despite monotonic linear changes in face gender, consistent with categorical perception. Neuroimaging results indicated that the lateral fusiform gyrus, bilaterally, and the fusiform face area linearly encoded graded parameters of objective face gender, but these regions correlated substantially less with subjective perceptions (which were nonlinear and affected by categorical perception effects). Such subjective perceptions, however, were represented in the orbitofrontal cortex, but this region correlated substantially less with objective parameters. The attention-independent graded representations of face gender in fusiform and orbitofrontal cortices reveal how objective face parameters are encoded and transformed into subjective categorically warped perceptions in the human brain.

GABAergic Differentiation Induced by Mash1 Is Compromised by the bHLH Proteins Neurogenin2, NeuroD1, and NeuroD2

Roybon, L., Mastracci, T. L., Ribeiro, D., Sussel, L., Brundin, P., Li, J.-Y. — Fri, 18 Sep 2009 01:01:37 PDT

During forebrain development, Mash1 directs -aminobutyric acid (GABA)ergic neuron differentiation ventrally in the ganglionic eminences. Repression of Mash1 in the cortex is necessary to prevent the formation of GABAergic interneurons. Negative regulation of Mash1 has been attributed to members of the Neurogenin family; the genetic ablation of Neurogenin2 (Ngn2) leads to the derepression of Mash1 and the formation of ectopic GABAergic neurons in the cortex. We have developed an in vitro system to clarify the importance of NeuroD proteins in the Mash1 regulatory pathway. Using a neurosphere culture system, we show that the downstream effectors of the Ngn2 pathway NeuroD1 and NeuroD2 can abrogate GABAergic differentiation directed by Mash1. The ectopic expression of either of these genes in Mash1-expressing cells derived from the lateral ganglionic eminence, independently downregulate Mash1 expression without affecting expression of distal less homeodomain genes. This results in a complete loss of the GABAergic phenotype. Moreover, we demonstrate that ectopic expression of Mash1 in cortical progenitors is sufficient to phenocopy the loss of Ngn2 and strongly enhances ectopic GABAergic differentiation. Collectively, our results define the compensatory and cross-regulatory mechanisms that exist among basic helix-loop-helix transcription factors during neuronal fate specification.

Population Response to Contextual Influences in the Primary Visual Cortex

Wed, 16 Sep 2009 06:45:49 PDT

Collinear proximal flankers can facilitate the detection of a low-contrast target or generate false-alarm target detection in the absence of a target. Although these effects are known to involve subthreshold neuronal interactions beyond the classical receptive field, the underlying neuronal mechanisms are not fully understood. Here, we used voltage-sensitive dye imaging that emphasizes subthreshold population activity, at high spatial and temporal resolution and imaged the visual cortex of fixating monkeys while they were presented with a low-contrast Gabor target, embedded within collinear or orthogonal flankers. We found that neuronal activity at the target site in area primary visual cortex increased and response latency decreased due to spatial spread of activation from the flankers’ site. This increased activity was smaller than expected by a linear summation. The presentation of flankers alone induced strong spatial filling-in at the target site. Importantly, the increased neuronal activity at the target site was synchronized over time, both locally and with neuronal population at the flanker's site. This onset synchronization was higher for collinear than for orthogonal flankers. We further show that synchrony is a superior code over amplitude, for discriminating collinear from orthogonal pattern. These results suggest that population synchrony can serve as a code to discriminate contextual effects.

Perceptual Expectation Evokes Category-Selective Cortical Activity

Esterman, M., Yantis, S. — Wed, 16 Sep 2009 06:45:44 PDT

Selective visual attention directed to a location (even in the absence of a stimulus) increases activity in the corresponding regions of visual cortex and enhances the speed and accuracy of target perception. We further explored top-down influences on perceptual representations by manipulating observers’ expectations about the category of an upcoming target. Observers viewed a display in which an object (either a face or a house) gradually emerged from a state of phase-scrambled noise; a cue established expectation about the object category. Observers were faster to categorize faces (gender discrimination) or houses (structural discrimination) when the category of the partially scrambled object matched their expectation. Functional magnetic resonance imaging revealed that this expectation was associated with anticipatory increases in category-specific visual cortical activity, even in the absence of object- or category-specific visual information. Expecting a face evoked increased activity in face-selective cortical regions in the fusiform gyrus and superior temporal sulcus. Conversely, expecting a house increased activity in parahippocampal gyrus. These results suggest that visual anticipation facilitates subsequent perception by recruiting, in advance, the same cortical mechanisms as those involved in perception.

Dual Effect of Glutamate on GABAergic Interneuron Survival during Cerebral Cortex Development in Mice Neonates

Wed, 16 Sep 2009 06:45:41 PDT

In term and preterm neonates, massive glutamate release can lead to excitotoxic white-matter and cortical lesions. Because of its high permeability toward calcium, the N-methyl-D-aspartic acid (NMDA) receptor is thought to play an important role in excitotoxic lesions and NMDA antagonists therefore hold promise for neuroprotection. We found that, in neonatal mouse cortex, a given NMDA concentration exerted either excitotoxic or antiapoptotic effects depending on the cortical layers. In layer VI, NMDA led to excitotoxicity, sustained calcium mobilization, and necrosis of Gad67GFP neurons. In the immature layers II–IV, NMDA decreased apoptosis and induced transient calcium mobilization. The NMDA antagonist MK801 acted as a potent caspase-3 activator in immature layers II–IV and affected gamma aminobutyric acid (GABA)ergic interneurons. The apoptotic effect of MK801-induced BAX expression, mitochondrial potential collapse and caspase-9 activation. In vivo Bax small interfering ribonucleic acid and a caspase-9 inhibitor abrogated MK801-induced apoptosis and pyknotic nucleus formation. Ketamine, an anesthetic with NMDA antagonist properties, mimicked the apoptotic effects of MK801. These data indicate a dual effect of glutamate on survival of immature and mature GABAergic neurons and suggest that ketamine may induce apoptosis of immature GABAergic neurons.

BDNF Val66Met Polymorphism Influences Motor System Function in the Human Brain

Thu, 10 Sep 2009 06:31:43 PDT

Brain-derived neurotrophic factor (BDNF) is important to brain functions such as plasticity and repair. A single nucleotide polymorphism for this growth factor, val⁶⁶met, is common and associated with decreased activity-dependent BDNF release. The current study evaluated the effects of this polymorphism in relation to human brain motor system function, short-term plasticity, and learning. Functional magnetic resonance imaging (fMRI) scanning during right index finger movement (n = 24) identified activation in a broad sensorimotor network. However, subjects with the polymorphism showed smaller activation volume within several brain regions as compared with subjects without the polymorphism. Repeat fMRI after 25 min of right index finger training found that the 2 genotype groups modulated brain activation differently. In several brain regions, subjects with the polymorphism showed greater activation volume reduction, whereas subjects without the polymorphism showed greater activation volume expansion. On a driving-based motor learning task (independent cohort, n = 29), subjects with the polymorphism showed greater error during short-term learning and poorer retention over 4 days, relative to subjects without the polymorphism. The presence of this BDNF polymorphism is associated with differences in brain motor system function, altered short-term plasticity, and greater error in short-term motor learning. The broader implications of these findings are considered.

Effects of Aging on Paired-Pulse Behavior of Rat Somatosensory Cortical Neurons

David-Jurgens, M., Dinse, H. R. — Thu, 10 Sep 2009 06:31:41 PDT

Aging affects all levels of neural processing including changes of intracortical inhibition and cortical excitability. The paired-pulse stimulation protocol, the application of 2 stimuli in close succession, is used to investigate cortical excitability. The paired-pulse behavior is characterized by the fact that the second response is significantly suppressed at short interstimulus intervals (ISIs) but approaches the first response with increasing ISIs. However, there are controversial reports about the influence of age on paired-pulse behavior. We therefore used pairs of tactile stimuli (ISIs from tens to hundreds of milliseconds) to record extracellular responses of somatosensory cortical neurons of young and aged rats. Paired-pulse behavior was quantified as the ratio of the amplitude of the second response divided by the first. For all ISIs, we found significantly higher ratios in the old animals indicating reduced paired-pulse suppression (PPS). Evaluation of the single response components revealed a significant reduction of the response to the first stimulus for old animals but no age-dependent decrement to the second. Changes in PPS are usually mediated by modulating the second response characteristics. Thus, our data demonstrate reduced PPS due to an overall reduction of the first response as a form of modified PPS developing at old age.

A Selective Interplay between Aberrant EPSPKA and INaP Reduces Spike Timing Precision in Dentate Granule Cells of Epileptic Rats

Epsztein, J., Sola, E., Represa, A., Ben-Ari, Y., Crepel, V. — Wed, 09 Sep 2009 08:27:30 PDT

Spike timing precision is a fundamental aspect of neuronal information processing in the brain. Here we examined the temporal precision of input–output operation of dentate granule cells (DGCs) in an animal model of temporal lobe epilepsy (TLE). In TLE, mossy fibers sprout and establish recurrent synapses on DGCs that generate aberrant slow kainate receptor–mediated excitatory postsynaptic potentials (EPSP_KA) not observed in controls. We report that, in contrast to time-locked spikes generated by EPSP_AMPA in control DGCs, aberrant EPSP_KA are associated with long-lasting plateaus and jittered spikes during single-spike mode firing. This is mediated by a selective voltage-dependent amplification of EPSP_KA through persistent sodium current (I_NaP) activation. In control DGCs, a current injection of a waveform mimicking the slow shape of EPSP_KA activates I_NaP and generates jittered spikes. Conversely in epileptic rats, blockade of EPSP_KA or I_NaP restores the temporal precision of EPSP–spike coupling. Importantly, EPSP_KA not only decrease spike timing precision at recurrent mossy fiber synapses but also at perforant path synapses during synaptic integration through I_NaP activation. We conclude that a selective interplay between aberrant EPSP_KA and I_NaP severely alters the temporal precision of EPSP–spike coupling in DGCs of chronic epileptic rats.

Circuit-based Localization of Ferret Prefrontal Cortex

Duque, A., McCormick, D. A. — Mon, 07 Sep 2009 22:14:49 PDT

We examined the extent of the ferret prefrontal cortex (PFC) and its reciprocal connections with the mediodorsal nucleus of the thalamus (MD) by anterograde and retrograde labeling in 6- to 14-week-old male ferrets. Our results indicate that in the ferret, as in other species, MD projects heavily to the PFC although it also projects to other cortical and subcortical structures. The MD projection to PFC terminates largely in layer IV with lighter innervation of layers II, III, V, and VI. The cells projecting back to MD are mostly in layer VI. The parvocellular component of MD projects to and receives projections from the more caudal and dorsomedial component of the PFC, whereas the magnocellular portion of MD projects to and receives projections from the more rostral and lateral component of the PFC. With these results we have localized the ferret PFC, defined as a frontal cortical region with heavy reciprocal connections with the MD.

Noninvasive Functional and Structural Connectivity Mapping of the Human Thalamocortical System

Zhang, D., Snyder, A. Z., Shimony, J. S., Fox, M. D., Raichle, M. E. — Thu, 03 Sep 2009 03:38:55 PDT

Relating structural connectivity with functional activity is fundamentally important to understanding the brain's physiology. The thalamocortical system serves as a good model system for exploring structure/function relationships because of its well-documented anatomical connectivity. Here we performed functional and structural magnetic resonance mapping of the human thalamocortical system using intrinsic brain activity and diffusion-weighted imaging. The accuracy of these imaging techniques is tested by comparison with human histology registered to common anatomical space and connectional anatomy derived from nonhuman primates. In general, there is good overall concordance among structural, functional, and histological results which suggests that a simple model of direct anatomical connectivity between the cerebral cortex and the thalamus is capable of explaining much of the observed correlations in neuronal activity. However, important differences between structural and functional mapping results are also manifest which suggests a more complex interpretation and emphasizes the unique contributions from structural and functional mapping.

The Subventricular Zone Is the Developmental Milestone of a 6-Layered Neocortex: Comparisons in Metatherian and Eutherian Mammals

Wed, 02 Sep 2009 05:51:10 PDT

The major lineages of mammals (Eutheria, Metatheria, and Monotremata) diverged more than 100 million years ago and have undergone independent changes in the neocortex. We found that adult South American gray short-tailed opossum (Monodelphis domestica) and tammar wallaby (Macropus eugenii) possess a significantly lower number of cerebral cortical neurons compared with the mouse (Mus musculus). To determine whether the difference is reflected in the development of the cortical germinal zones, the location of progenitor cell divisions was examined in opossum, tammar wallaby, and rat. The basic pattern of the cell divisions was conserved, but the emergence of a distinctive band of dividing cells in the subventricular zone (SVZ) occurred relatively later in the opossum (postnatal day [P14]) and the tammar wallaby (P40) than in rodents. The planes of cell divisions in the ventricular zone (VZ) were similar in all species, with comparable mRNA expression patterns of Brn2, Cux2, NeuroD6, Tbr2, and Pax6 in opossum (P12 and P20) and mouse (embryonic day 15 and P0). In conclusion, the marsupial neurodevelopmental program utilizes an organized SVZ, as indicated by the presence of intermediate (or basal) progenitor cell divisions and gene expression patterns, suggesting that the SVZ emerged prior to the Eutherian–Metatherian split.

Representation of Neck Velocity and Neck-Vestibular Interactions in Pursuit Neurons in the Simian Frontal Eye Fields

Wed, 26 Aug 2009 10:24:31 PDT

The smooth pursuit system must interact with the vestibular system to maintain the accuracy of eye movements in space (i.e., gaze-movement) during head movement. Normally, the head moves on the stationary trunk. Vestibular signals cannot distinguish whether the head or whole body is moving. Neck proprioceptive inputs provide information about head movements relative to the trunk. Previous studies have shown that the majority of pursuit neurons in the frontal eye fields (FEF) carry visual information about target velocity, vestibular information about whole-body movements, and signal eye- or gaze-velocity. However, it is unknown whether FEF neurons carry neck proprioceptive signals. By passive trunk-on-head rotation, we tested neck inputs to FEF pursuit neurons in 2 monkeys. The majority of FEF pursuit neurons tested that had horizontal preferred directions (87%) responded to horizontal trunk-on-head rotation. The modulation consisted predominantly of velocity components. Discharge modulation during pursuit and trunk-on-head rotation added linearly. During passive head-on-trunk rotation, modulation to vestibular and neck inputs also added linearly in most neurons, although in half of gaze-velocity neurons neck responses were strongly influenced by the context of neck rotation. Our results suggest that neck inputs could contribute to representing eye- and gaze-velocity FEF signals in trunk coordinates.

Spatial Remapping of Cortico-striatal Connectivity in Parkinson's Disease

Wed, 26 Aug 2009 10:24:29 PDT

Parkinson's disease (PD) is characterized by striatal dopamine depletion, especially in the posterior putamen. The dense connectivity profile of the striatum suggests that these local impairments may propagate throughout the whole cortico-striatal network. Here we test the effect of striatal dopamine depletion on cortico-striatal network properties by comparing the functional connectivity profile of the posterior putamen, the anterior putamen, and the caudate nucleus between 41 PD patients and 36 matched controls. We used multiple regression analyses of resting-state functional magnetic resonance imaging data to quantify functional connectivity across different networks. Each region had a distinct connectivity profile that was similarly expressed in patients and controls: the posterior putamen was uniquely coupled to cortical motor areas, the anterior putamen to the pre–supplementary motor area and anterior cingulate cortex, and the caudate nucleus to the dorsal prefrontal cortex. Differences between groups were specific to the putamen: although PD patients showed decreased coupling between the posterior putamen and the inferior parietal cortex, this region showed increased functional connectivity with the anterior putamen. We conclude that dopamine depletion in PD leads to a remapping of cerebral connectivity that reduces the spatial segregation between different cortico-striatal loops. These alterations of network properties may underlie abnormal sensorimotor integration in PD.

Enlarged Brain Ventricles and Impaired Neurogenesis in the Ts1Cje and Ts2Cje Mouse Models of Down Syndrome

Wed, 26 Aug 2009 10:24:28 PDT

Down syndrome (DS) is the most common cause of mental retardation. Although structural and neurogenic abnormalities have been shown in the brains of DS patients, the molecular etiology is still unknown. To define it, we have performed structural and histological examinations of the brains of Ts1Cje and Ts2Cje, 2 mouse models for DS. These mice carry different length of trisomic segments of mouse chromosome 16 that are orthologous to human chromosome 21. At 3 months of age, ventricular enlargements were observed in both Ts1Cje and Ts2Cje brains at a similar degree. Both mice also showed decreases of the number of doublecortin-positive neuroblasts and thymidine-analog BrdU-labeled proliferating cells in the subventricular zone of the lateral ventricles (LVs) and in the hippocampal dentate gyrus at a similar degree, suggesting impaired adult neurogenesis. Additionally, at embryonic day 14.5, both strains of mice, when compared with diploid littermates, had smaller brains and decreased cortical neurogenesis that could possibly contribute to the ventricular enlargements observed in adulthood. Our findings suggest that the trisomic segment of the Ts1Cje mouse, which is shared with Ts2Cje, contains the genes that are responsible for these abnormal phenotypes and could be relevant to the mental retardation associated with DS.

Development of Cannabinoid 1 Receptor Protein and Messenger RNA in Monkey Dorsolateral Prefrontal Cortex

Eggan, S. M., Mizoguchi, Y., Stoyak, S. R., Lewis, D. A. — Mon, 24 Aug 2009 07:11:28 PDT

Adolescent cannabis use is associated with an increased risk of schizophrenia and with impairments in cognitive processes reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC). Additionally, maternal cannabis use is associated with cognitive dysfunction in offspring. The effects of cannabis are mediated by the cannabinoid 1 receptor (CB1R), which is present in high density in the primate DLPFC. In order to determine how developmental changes in CB1Rs might render DLPFC circuitry vulnerable to cannabis exposure, we examined the density and innervation patterns of CB1R-immunoreactive (IR) axons and the expression of CB1R mRNA in the DLPFC from 81 macaque monkeys, ranging in age from embryonic 82 days to 18 years. Overall CB1R immunoreactivity in the gray matter robustly increased during the perinatal period and achieved adult levels by 1 week postnatal. However, laminar analyses revealed that CB1R-IR axon density significantly decreased with age in layers 1–2 but significantly increased in layer 4, especially during adolescence. In contrast, CB1R mRNA levels were highest 1 week postnatal, declined over the next 2 months, and then remained unchanged into adulthood. These findings provide a potential substrate for discrete, age-dependent effects of cannabis exposure on the maturation of primate DLPFC circuitry.

Maturational Trajectories of Cortical Brain Development through the Pubertal Transition: Unique Species and Sex Differences in the Monkey Revealed through Structural Magnetic Resonance Imaging

Mon, 24 Aug 2009 07:11:27 PDT

Characterizing normal brain development in the rhesus macaque is a necessary prerequisite for establishing better nonhuman primate models of neuropathology. Structural magnetic resonance imaging scans were obtained on 37 rhesus monkeys (20 Male, 17 Female) between 10 and 64 months of age. Effects of age and sex were analyzed with a cross-sectional design. Gray matter (GM) and white matter (WM) volumes were determined for total brain and major cortical regions using an automatic segmentation and parcellation pipeline. Volumes of major subcortical structures were evaluated. Unlike neural maturation in humans, GM volumes did not show a postpubertal decline in most cortical regions, with the notable exception of the prefrontal cortex. Similar to humans, WM volumes increased through puberty with less change thereafter. Caudate, putamen, amygdala, and hippocampus increased linearly as did the corpus callosum. Males and females showed similar maturational patterns, although males had significantly larger brain volumes. Females had a proportionately larger caudate, putamen, and hippocampus, whereas males had both an absolute and relatively larger corpus callosum. The authors discuss the possible implications of these findings for research using the rhesus macaque as a model for neurodevelopmental disorders.

Munc13-2 Differentially Affects Hippocampal Synaptic Transmission and Plasticity

Breustedt, J., Gundlfinger, A., Varoqueaux, F., Reim, K., Brose, N., Schmitz, D. — Fri, 21 Aug 2009 05:56:47 PDT

The short-term dynamics of synaptic communication between neurons provides neural networks with specific frequency-filter characteristics for information transfer. The direction of short-term synaptic plasticity, that is, facilitation versus depression, is highly dependent on and inversely correlated to the basal release probability of a synapse. Amongst the processes implicated in shaping the release probability, proteins that regulate the docking and priming of synaptic vesicles at the active zone are of special importance. Here, we found that a member of the Munc13 protein family of priming proteins, namely Munc13-2, is essential for normal release probability at hippocampal mossy fiber synapses. Paired pulse and frequency facilitation were strongly increased, whereas mossy fiber long-term potentiation was unaffected in the absence of Munc13-2. In contrast, transmission at 3 other types of hippocampal synapses, Schaffer-collateral, associational-commissural, as well as inhibitory synapses onto CA3 pyramidal neurons was unaffected by the loss of Munc13-2.

The Brain of Opera Singers: Experience-Dependent Changes in Functional Activation

Kleber, B., Veit, R., Birbaumer, N., Gruzelier, J., Lotze, M. — Wed, 19 Aug 2009 10:54:08 PDT

Several studies have shown that motor-skill training over extended time periods results in reorganization of neural networks and changes in brain morphology. Yet, little is known about training-induced adaptive changes in the vocal system, which is largely subserved by intrinsic reflex mechanisms. We investigated highly accomplished opera singers, conservatory level vocal students, and laymen during overt singing of an Italian aria in a neuroimaging experiment. We provide the first evidence that the training of vocal skills is accompanied by increased functional activation of bilateral primary somatosensory cortex representing articulators and larynx. Opera singers showed additional activation in right primary sensorimotor cortex. Further training-related activation comprised the inferior parietal lobe and bilateral dorsolateral prefrontal cortex. At the subcortical level, expert singers showed increased activation in the basal ganglia, the thalamus, and the cerebellum. A regression analysis of functional activation with accumulated singing practice confirmed that vocal skills training correlates with increased activity of a cortical network for enhanced kinesthetic motor control and sensorimotor guidance together with increased involvement of implicit motor memory areas at the subcortical and cerebellar level. Our findings may have ramifications for both voice rehabilitation and deliberate practice of other implicit motor skills that require interoception.

Dopamine Receptor D1/D5 Gene Expression in the Medial Prefrontal Cortex Predicts Impulsive Choice in Rats

Tue, 18 Aug 2009 12:20:28 PDT

A neuropsychological hallmark of attention deficit/hyperactivity disorder (ADHD) is the reduced ability to tolerate delay of reinforcement, leading to impulsive choice. Genetic association studies have implicated several genes involved in dopaminergic neurotransmission in ADHD. In this study, we investigated whether differences in the expression level of these dopamine-related genes of rats predict the individual level of impulsive choice. Among all frontostriatal brain regions tested, only in the medial prefrontal cortex (mPFC), we observed significant positive correlations between impulsive choice and transcript levels of the dopamine receptor D₁, the dopamine receptor D₅ and calcyon. Local mPFC infusions of the D₁/D₅ receptor antagonist SCH 23390 and agonist SKF 38393 resulted in increased impulsive choice, in agreement with the idea that endogenous receptor D₁/D₅ stimulation in the mPFC promotes the choice of large delayed rewards. Together, these data indicate that this class of dopamine receptors in the mPFC plays a pivotal role in impulsive choice, and aberrancies thereof might contribute to ADHD symptomatology.

Activity in Preserved Left Hemisphere Regions Predicts Anomia Severity in Aphasia

Fridriksson, J., Bonilha, L., Baker, J. M., Moser, D., Rorden, C. — Mon, 17 Aug 2009 11:49:16 PDT

Understanding the neural mechanism that supports preserved language processing in aphasia has implications for both basic and applied science. This study examined brain activation associated with correct picture naming in 15 patients with aphasia. We contrasted each patient's activation to the activation observed in a neurologically healthy control group, allowing us to identify regions with unusual activity patterns. The results revealed that increased activation in preserved left hemisphere areas is associated with better naming performance in aphasia. This relationship was linear in nature; progressively less cortical activation was associated with greater severity of anomia. These findings are consistent with others who suggests that residual language function following stroke relies on preserved cortical areas in the left hemisphere.

Noradrenergic Modulation of Cortical Networks Engaged in Visuomotor Processing

Grefkes, C., Wang, L. E., Eickhoff, S. B., Fink, G. R. — Mon, 17 Aug 2009 11:49:14 PDT

Both animal and human data suggest that stimulation of the noradrenergic system may influence neuronal excitability in regions engaged in sensory processing and visuospatial attention. We tested the hypothesis that the neural mechanisms subserving motor performance in tasks relying on the visuomotor control of goal-directed hand movements might be modulated by noradrenergic influences. Healthy subjects were stimulated using the selective noradrenaline reuptake inhibitor reboxetine (RBX) in a placebo-controlled crossover design. Functional magnetic resonance imaging and dynamic causal modeling (DCM) were used to assess drug-related changes in blood oxygen level–dependent activity and interregional connectivity while subjects performed a joystick task requiring goal-directed movements. Improved task performance under RBX was associated with increased activity in right visual, intraparietal and superior frontal cortex (premotor/frontal eye field). DCM revealed that the neuronal coupling among these regions was significantly enhanced when subjects were stimulated with RBX. Concurrently, right intraparietal cortex and right superior frontal cortex exerted a stronger driving influence on visuomotor areas of the left hemisphere, including SMA and M1. These effects were independent from task difficulty. The data suggest that stimulating noradrenergic mechanisms may rearrange the functional network architecture within and across the hemispheres, for example, by synaptic gating, thereby optimizing motor behavior.

The Left Ventral Occipito-Temporal Response to Words Depends on Language Lateralization but Not on Visual Familiarity

Cai, Q., Paulignan, Y., Brysbaert, M., Ibarrola, D., Nazir, T. A. — Fri, 14 Aug 2009 11:21:56 PDT

The sensitivity of the left ventral occipito-temporal (vOT) cortex to visual word processing has triggered a considerable debate about the role of this region in reading. One popular view is that the left vOT underlies the perceptual expertise needed for rapid skilled reading. Because skilled reading breaks down when words are presented in a visually unfamiliar format, we tested this hypothesis by analyzing vOT responses to horizontally presented words (familiar format) and vertically presented words (unfamiliar format). In addition, we compared the activity in participants with left and right cerebral dominance for language generation. Our results revealed 1) that the vOT activity during reading is lateralized to the same side as the inferior frontal activity during word generation, 2) that vertically and horizontally presented words triggered the same amount of activity in the vOT of the dominant hemisphere, but 3) that there was significantly more activity for vertically presented words in the vOT of the nondominant hemisphere. We suggest that the reading-related activity in vOT reflects the integration of general perceptual processes with language processing in the anterior brain regions and is not limited to skilled reading in the familiar horizontal format.

How the Brain Represents the Reward Value of Fat in the Mouth

Grabenhorst, F., Rolls, E. T., Parris, B. A., d'Souza, A. A. — Fri, 14 Aug 2009 11:21:55 PDT

The palatability and pleasantness of the sensory properties of foods drive food selection and intake and may contribute to overeating and obesity. Oral fat texture can make food palatable and pleasant. To analyze its neural basis, we correlated humans’ subjective reports of the pleasantness of the texture and flavor of a high- and low-fat food with a vanilla or strawberry flavor, with neural activations measured with functional magnetic resonance imaging. Activity in the midorbitofrontal and anterior cingulate cortex was correlated with the pleasantness of oral fat texture and in nearby locations with the pleasantness of flavor. The pregenual cingulate cortex showed a supralinear response to the combination of high fat and pleasant, sweet flavor, implicating it in the convergence of fat texture and flavor to produce a representation of highly pleasant stimuli. The subjective reports of oral fattiness were correlated with activations in the midorbitofrontal cortex and ventral striatum. The lateral hypothalamus and amygdala were more strongly activated by high- versus low-fat stimuli. This discovery of which brain regions track the subjective hedonic experience of fat texture will help to unravel possible differences in the neural responses in obese versus lean people to oral fat, a driver of food intake.

Ontogeny of Progesterone Receptor Expression in the Subplate of Fetal and Neonatal Rat Cortex

Jahagirdar, V., Wagner, C. K. — Fri, 14 Aug 2009 11:21:54 PDT

The progesterone receptor (PR) is transiently expressed in the rat cortex during development and its expression is initiated in the developmentally critical layer, the subplate. As subplate neurons pioneer thalamocortical and corticofugal connectivity, the expression of PR in this layer suggests an important function for PR in cortical development. Using immunocytochemistry for PR, the present study determined the precise ontogeny of PR expression in subplate neurons. The number of cells containing PR immunoreactivity (PRir) within the subplate was quantified from embryonic day (E) 17 through postnatal day (P) 14. The subplate was positively identified by the marker calretinin and by BrDU birthdating. The results demonstrate that PRir is undetectable in fetal cortex on E17, but is first observed in the subplate on E18. The number of PRir cells peaks on P2 and then steadily declines, until PRir is once again not detectable in subplate by P14. This developmental window of PR expression within the subplate coincides with establishment of early cortical circuitry and the gradual demise of subplate cells, suggesting that PR may play a critical role in mediating these fundamental developmental processes.

Transcranial Magnetic Stimulation of the Parietal Cortex Facilitates Spatial Working Memory: Near-Infrared Spectroscopy Study

Yamanaka, K., Yamagata, B., Tomioka, H., Kawasaki, S., Mimura, M. — Fri, 14 Aug 2009 11:21:53 PDT

The present study investigated whether transcranial magnetic stimulation (TMS) to the parietal cortex improves the performance of healthy persons in a spatial working memory (WM) task. The effect of TMS on the frontal cortex was examined by measuring oxygenated hemoglobin (oxy-Hb) with near-infrared spectroscopy. Fifty-two healthy persons received either 100% resting motor threshold TMS at 5 Hz (real TMS) or sham TMS while engaged in a spatial WM task or a control visuospatial attention task. TMS was applied to either the left or the right parietal cortex during the delay period of the task. Reaction times improved in the spatial WM task, but not in the control task, with real TMS, whereas sham TMS had no effect. This improvement was only observed when TMS was applied to the right parietal cortex. Application of real TMS to the right parietal cortex also significantly increased frontal oxy-Hb levels during the WM task, but reduced oxy-Hb during the control task. These results suggest that TMS to the right parietal cortex may selectively facilitate spatial WM. Hemispheric asymmetry and the frontoparietal network theory may explain the observed effect of right parietal TMS on spatial WM.

Distinct and Overlapping Functional Zones in the Cerebellum Defined by Resting State Functional Connectivity

O'Reilly, J. X., Beckmann, C. F., Tomassini, V., Ramnani, N., Johansen-Berg, H. — Fri, 14 Aug 2009 11:21:49 PDT

The cerebellum processes information from functionally diverse regions of the cerebral cortex. Cerebellar input and output nuclei have connections with prefrontal, parietal, and sensory cortex as well as motor and premotor cortex. However, the topography of the connections between the cerebellar and cerebral cortices remains largely unmapped, as it is relatively unamenable to anatomical methods. We used resting-state functional magnetic resonance imaging to define subregions within the cerebellar cortex based on their functional connectivity with the cerebral cortex. We mapped resting-state functional connectivity voxel-wise across the cerebellar cortex, for cerebral–cortical masks covering prefrontal, motor, somatosensory, posterior parietal, visual, and auditory cortices. We found that the cerebellum can be divided into at least 2 zones: 1) a primary sensorimotor zone (Lobules V, VI, and VIII), which contains overlapping functional connectivity maps for domain-specific motor, somatosensory, visual, and auditory cortices; and 2) a supramodal zone (Lobules VIIa, Crus I, and II), which contains overlapping functional connectivity maps for prefrontal and posterior-parietal cortex. The cortical connectivity of the supramodal zone was driven by regions of frontal and parietal cortex which are not directly involved in sensory or motor processing, including dorsolateral prefrontal cortex and the frontal pole, and the inferior parietal lobule.

Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala

Thu, 13 Aug 2009 12:24:57 PDT

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

The Effect of Variation in Expression of the Candidate Dyslexia Susceptibility Gene Homolog Kiaa0319 on Neuronal Migration and Dendritic Morphology in the Rat

Thu, 13 Aug 2009 12:24:56 PDT

We investigated the postnatal effects of embryonic knockdown and overexpression of the candidate dyslexia gene homolog Kiaa0319. We used in utero electroporation to transfect cells in E15/16 rat neocortical ventricular zone with either 1) small hairpin RNA (shRNA) vectors targeting Kiaa0319, 2) a KIAA0319 expression construct, 3) Kiaa0319 shRNA along with KIAA0319 expression construct ("rescue"), or 4) a scrambled version of Kiaa0319 shRNA. Knockdown, but not overexpression, of Kiaa0319 resulted in periventricular heterotopias that contained large numbers of both transfected and non–transfected neurons. This suggested that Kiaa0319 shRNA disrupts neuronal migration by cell autonomous as well as non–cell autonomous mechanisms. Of the Kiaa0319 shRNA–transfected neurons that migrated into the cortical plate, most migrated to their appropriate lamina. In contrast, neurons transfected with the KIAA0319 expression vector attained laminar positions subjacent to their expected positions. Neurons transfected with Kiaa0319 shRNA exhibited apical, but not basal, dendrite hypertrophy, which was rescued by overexpression of KIAA0319. The results provide additional supportive evidence linking candidate dyslexia susceptibility genes to migrational disturbances during brain development, and extends the role of Kiaa0319 to include growth and differentiation of dendrites.

Tracking Lexical Access in Speech Production: Electrophysiological Correlates of Word Frequency and Cognate Effects

Strijkers, K., Costa, A., Thierry, G. — Thu, 13 Aug 2009 12:24:55 PDT

The present study establishes an electrophysiological index of lexical access in speech production by exploring the locus of the frequency and cognate effects during overt naming. We conducted 2 event-related potential (ERP) studies with 16 Spanish–Catalan bilinguals performing a picture naming task in Spanish (L1) and 16 Catalan–Spanish bilinguals performing a picture naming task in Spanish (L2). Behavioral results showed a clear frequency effect and an interaction between frequency and cognate status. The ERP elicited during the production of high-frequency words diverged from the low-frequency ERP between 150 and 200 ms post-target presentation and kept diverging until voice onset. The same results were obtained when comparing cognate and noncognate conditions. Positive correlations were observed between naming latencies and mean amplitude of the P2 component following the divergence, for both the lexical frequency and the cognate effects. We conclude that lexical access during picture naming begins approximately 180 ms after picture presentation. Furthermore, these results offer direct electrophysiological evidence for an early influence of frequency and cognate status in speech production. The theoretical implications of these findings for models of speech production are discussed.

The Role of Dopamine in the Prelimbic Cortex and the Dorsomedial Striatum in Instrumental Conditioning

Lex, B., Hauber, W. — Wed, 12 Aug 2009 20:43:11 PDT

The prelimbic (PL) region of the prefrontal cortex and the posterior subregion of the dorsomedial striatum (pDMS) are components of a corticostriatal circuit subserving instrumental learning. Here, we examined whether dopamine (DA) signals conveyed to the PL and pDMS are critical for instrumental learning. Rats with 6-hydroxydopamine or vehicle infusion into the PL and pDMS were trained to press 2 levers, either for food pellets or a sucrose solution. Thereafter, we tested whether the animals were sensitive 1) to a selective degradation of 1 of 2 outcomes using a specific satiety procedure and 2) to a selective degradation of 1 of 2 contingencies controlling instrumental behavior. Rats with PL DA depletion displayed a reduced rate of lever presses but appeared to be sensitive to outcome devaluation and contingency degradation. Thus, PL DA seems to modulate lever pressing but does not support instrumental conditioning. In contrast, rats with pDMS DA depletion had intact response rates and were sensitive to selective outcome devaluation; however, they showed a reduced sensitivity to contingency degradation. Therefore, pDMS DA signaling seems not to be involved in maintaining lever pressing but instead contributes to instrumental conditioning by supporting the detection of causal relationships between an action and its consequences.

Activation of Muscarinic Acetylcholine Receptors Induces a Nitric Oxide-Dependent Long-Term Depression in Rat Medial Prefrontal Cortex

Huang, C.-C., Hsu, K.-S. — Fri, 07 Aug 2009 11:51:11 PDT

Cholinergic neurotransmission in the medial prefrontal cortex (mPFC) is critical for normal processing of cue detection and cognitive performance. However, the mechanism by which cholinergic system modifies mPFC synaptic function remains unclear. Here we show that activation of muscarinic acetylcholine receptors (mAChRs) by carbamoylcholine (CCh) induces long-term depression (CCh-LTD) of excitatory synaptic transmission on mPFC layer V pyramidal neurons. The induction of CCh-LTD is dependent on M₁ mAChR activation but does not require N-methyl-D-aspartate receptor activation or coincident synaptic stimulation. Activation of phospholipase C (PLC), protein kinase C (PKC), and postsynaptic Ca²⁺ release from inositol 1,4,5-triphosphate (IP₃) receptor–sensitive internal stores are required for CCh-LTD induction. The expression of CCh-LTD is likely to be presynaptic because it is accompanied by a decrease in 1/(coefficient of variance)² and an increase in synaptic failure and paired-pulse ratio of synaptic responses. CCh-LTD is blocked by nitric oxide (NO) synthase inhibitors, soluble guanylyl cyclase (sGC) inhibitor, and protein kinase G (PKG) inhibitor. Synaptic stimulation of M₁ mAChRs with prolonged paired-pulse low-frequency stimulation also triggers LTD. These results suggest that activation of M₁ mAChRs can induce LTD on mPFC layer V pyramidal neurons through the activation of postsynaptic PLC/PKC/IP₃ receptor- and subsequently presynaptic NO/sGC/PKG-dependent signaling processes.

Deletion of CREB1 from the Dorsal Telencephalon Reduces Motivational Properties of Cocaine

McPherson, C. S., Mantamadiotis, T., Tan, S.-S., Lawrence, A. J. — Fri, 07 Aug 2009 11:51:09 PDT

Transcriptional changes in neurons underpin the long-lived cellular response to environmental stimuli, and cAMP-responsive element-binding protein (CREB1) has been implicated in this process. Exposure to psychostimulants such as cocaine results in persistent neuronal plasticity in cortical circuitry that likely modulates the motivation to use the drug again. To examine whether CREB1 in cortical glutamatergic neurons was implicated in cocaine use, we developed conditional CREB1 mutants that exhibit ablation of functional CREB1 in the cortex and hippocampus. Here we report that CREB1 mutants show normal locomotor responses to acute and chronic cocaine and develop a place preference for cocaine. However, CREB1 mutants demonstrate a diminished drive to self-administer cocaine under operant conditions. We conclude that there is a specific role for CREB1 in telencephalic glutamatergic neurons regulating the motivational properties of cocaine.

Neural Processing during Older Adults' Comprehension of Spoken Sentences: Age Differences in Resource Allocation and Connectivity

Peelle, J. E., Troiani, V., Wingfield, A., Grossman, M. — Fri, 07 Aug 2009 11:51:08 PDT

Speech comprehension remains largely preserved in older adults despite significant age-related neurophysiological change. However, older adults’ performance declines more rapidly than that of young adults when listening conditions are challenging. We investigated the cortical network underlying speech comprehension in healthy aging using short sentences differing in syntactic complexity, with processing demands further manipulated through speech rate. Neural activity was monitored using blood oxygen level–dependent functional magnetic resonance imaging. Comprehension of syntactically complex sentences activated components of a core sentence-processing network in both young and older adults, including the left inferior and middle frontal gyri, left inferior parietal cortex, and left middle temporal gyrus. However, older adults showed reduced recruitment of inferior frontal regions relative to young adults; the individual degree of recruitment predicted accuracy at the more difficult fast speech rate. Older adults also showed increased activity in frontal regions outside the core sentence-processing network, which may have played a compensatory role. Finally, a functional connectivity analysis demonstrated reduced coherence between activated regions in older adults. We conclude that decreased activation of specialized processing regions, and limited ability to coordinate activity between regions, contribute to older adults’ difficulty with sentence comprehension under difficult listening conditions.

Mechanisms of Working Memory Disruption by External Interference

Clapp, W. C., Rubens, M. T., Gazzaley, A. — Fri, 31 Jul 2009 03:03:26 PDT

The negative impact of external interference on working memory (WM) performance is well documented; yet, the mechanisms underlying this disruption are not sufficiently understood. In this study, electroencephalogram and functional magnetic resonance imaging (fMRI) data were recorded in separate experiments that each introduced different types of visual interference during a period of WM maintenance: distraction (irrelevant stimuli) and interruption (stimuli that required attention). The data converged to reveal that regardless of the type of interference, the magnitude of processing interfering stimuli in the visual cortex (as rapidly as 100 ms) predicted subsequent WM recognition accuracy for stored items. fMRI connectivity analyses suggested that in the presence of distraction, encoded items were maintained throughout the delay period via connectivity between the middle frontal gyrus and visual association cortex, whereas memoranda were not maintained when subjects were interrupted but rather reactivated in the postinterruption period. These results elucidate the mechanisms of external interference on WM performance and highlight similarities and differences of distraction and multitasking.

Cell-Type Specific Properties of Pyramidal Neurons in Neocortex Underlying a Layout that Is Modifiable Depending on the Cortical Area

Groh, A., Meyer, H. S., Schmidt, E. F., Heintz, N., Sakmann, B., Krieger, P. — Thu, 30 Jul 2009 02:16:12 PDT

To understand sensory representation in cortex, it is crucial to identify its constituent cellular components based on cell-type–specific criteria. With the identification of cell types, an important question can be addressed: to what degree does the cellular properties of neurons depend on cortical location? We tested this question using pyramidal neurons in layer 5 (L5) because of their role in providing major cortical output to subcortical targets. Recently developed transgenic mice with cell-type–specific enhanced green fluorescent protein labeling of neuronal subtypes allow reliable identification of 2 cortical cell types in L5 throughout the entire neocortex. A comprehensive investigation of anatomical and functional properties of these 2 cell types in visual and somatosensory cortex demonstrates that, with important exceptions, most properties appear to be cell-type–specific rather than dependent on cortical area. This result suggests that although cortical output neurons share a basic layout throughout the sensory cortex, fine differences in properties are tuned to the cortical area in which neurons reside.

TMS Over Human Frontal Eye Fields Disrupts Trans-saccadic Memory of Multiple Objects

Prime, S. L., Vesia, M., Crawford, J. D. — Wed, 29 Jul 2009 06:23:30 PDT

We recently showed that transcranial magnetic stimulation (TMS) over the right parietal eye fields disrupts memory of object features and locations across saccades. We applied TMS over the frontal eye fields (FEF) as subjects compared the feature details of visual targets presented either within a single eye fixation (Fixation Task) or across a saccade (Saccade Task). TMS pulses were randomly delivered at one of 3 time intervals around the time of the saccade, or at equivalent times in the Fixation Task. A No-TMS control confirmed that subjects could normally retain ~3 visual features. TMS in the Fixation Task had no effect compared with No-TMS, but differences among TMS times were found during right FEF stimulation. TMS over either the right or left FEF disrupted memory performance in the Saccade Task when stimulation coincided most closely with the saccade. The capacity to compare pre-and postsaccadic features was reduced to 1–2 objects, as expected if the spatial aspect of memory was disrupted. These findings suggest that the FEF plays a role in the spatial processing involved in trans-saccadic memory of visual features. We propose that this process employs saccade-related feedback signals similar to those observed in spatial updating.

COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

Wed, 29 Jul 2009 06:23:29 PDT

The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496–1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output.

Nonlinear Response of the Anterior Cingulate and Prefrontal Cortex in Schizophrenia as a Function of Variable Attentional Control

Fri, 24 Jul 2009 10:40:39 PDT

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level–dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Forelimb Muscle Representations and Output Properties of Motor Areas in the Mesial Wall of Rhesus Macaques

Boudrias, M.-H., Lee, S.-P., Svojanovsky, S., Cheney, P. D. — Fri, 24 Jul 2009 10:40:38 PDT

In this study, forelimb organizations and output properties of the supplementary motor area (SMA) and the dorsal cingulate motor area (CMAd) were assessed and compared with primary motor cortex (M1). Stimulus-triggered averages of electromyographic activity from 24 muscles of the forelimb were computed from layer V sites of 2 rhesus monkeys performing a reach-to-grasp task. No clear segregation of the forelimb representation of proximal and distal muscles was found in SMA. In CMAd, sites producing poststimulus effects in proximal muscles tended to be located caudal to distal muscle sites, although the number of effects was limited. For both SMA and CMAd, facilitation effects were more prevalent in distal than in proximal muscles. At an intensity of 60 µA, the mean latencies of M1 facilitation effects were 8 and 12.1 ms shorter and the magnitudes ~10 times greater than those from SMA and CMAd. Our results show that corticospinal neurons in SMA and CMAd provide relatively weak input to spinal motoneurons compared with the robust effects from M1. However, a small number of facilitation effects from SMA and CMAd had latencies as short as the shortest ones from M1 suggesting a minimum linkage to motoneurons as direct as that from M1.

Memory Encoding and Dopamine in the Aging Brain: A Psychopharmacological Neuroimaging Study

Wed, 22 Jul 2009 06:51:10 PDT

Normal aging brings with it changes in dopaminergic and memory functions. However, little is known about how these 2 changes are related. In this study, we identify a link between dopamine, episodic memory networks, and aging, using pharmacological functional magnetic resonance imaging. Young and older adults received a D2-like agonist (Bromocriptine, 1.25 mg), a D2-like antagonist (Sulpiride, 400 mg), and Placebo, in a double-blind crossover procedure. We observed group differences, during memory encoding, in medial temporal, frontal, and striatal regions and moreover, these regions were differentially sensitive across groups to dopaminergic perturbation. These findings suggest that brain systems underlying memory show age-related changes and that dopaminergic function may be key in understanding these changes. That these changes have behavioral consequences was suggested by the observation that drug modulations were most pronounced in older subjects with poorer recognition memory. Our findings provide direct evidence linking ageing, memory, and dopaminergic change.

The Selectivity and Functional Connectivity of the Anterior Temporal Lobes

Simmons, W. K., Reddish, M., Bellgowan, P. S. F., Martin, A. — Mon, 20 Jul 2009 13:30:32 PDT

One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by "resting-state" functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others.

Context-Dependent Place-Selective Responses of the Neurons in the Medial Parietal Region of Macaque Monkeys

Sato, N., Sakata, H., Tanaka, Y. L., Taira, M. — Mon, 20 Jul 2009 13:30:30 PDT

To investigate the role of the medial parietal region (MPR), comprising area 7m and the retrosplenial and posterior cingulate cortices, in spatial navigation, we analyzed the spatial aspect of the responses of the MPR neurons in monkeys while they actively performed a navigation task in a virtual environment. One-third of the analyzed MPR neurons were activated depending on the location of the monkeys in the environment, that is, showed place-selective responses. Some neurons showed varying responses based on the starting point (SP) or destination. We further investigated the responses of the place-selective neurons when the monkeys were shown animations of the entire navigation route, including the preferred field, and a segment of the route, including an area around the preferred field, and a still image of the preferred field. We observed that the responses of some place-selective neurons reduced when the monkeys viewed the preferred field in the segmented animation or in the still image compared with when they viewed the entire animation. These results suggested that the knowledge about the SP or destination, that is, context, is necessary to activate place-selective neurons. The effect of such contextual information suggests that the MPR plays decisive roles in spatial processing such as navigation.

Early Continuous White Noise Exposure Alters Auditory Spatial Sensitivity and Expression of GAD65 and GABAA Receptor Subunits in Rat Auditory Cortex

Xu, J., Yu, L., Cai, R., Zhang, J., Sun, X. — Mon, 20 Jul 2009 13:30:27 PDT

Sensory experiences have important roles in the functional development of the mammalian auditory cortex. Here, we show how early continuous noise rearing influences spatial sensitivity in the rat primary auditory cortex (A1) and its underlying mechanisms. By rearing infant rat pups under conditions of continuous, moderate level white noise, we found that noise rearing markedly attenuated the spatial sensitivity of A1 neurons. Compared with rats reared under normal conditions, spike counts of A1 neurons were more poorly modulated by changes in stimulus location, and their preferred locations were distributed over a larger area. We further show that early continuous noise rearing induced significant decreases in glutamic acid decarboxylase 65 and -aminobutyric acid (GABA)_A receptor 1 subunit expression, and an increase in GABA_A receptor 3 expression, which indicates a returned to the juvenile form of GABA_A receptor, with no effect on the expression of N-methyl-D-aspartate receptors. These observations indicate that noise rearing has powerful adverse effects on the maturation of cortical GABAergic inhibition, which might be responsible for the reduced spatial sensitivity.

Broca's Area Homologue in Chimpanzees (Pan troglodytes): Probabilistic Mapping, Asymmetry, and Comparison to Humans

Mon, 20 Jul 2009 13:30:24 PDT

Neural changes that occurred during human evolution to support language are poorly understood. As a basis of comparison to humans, we used design-based stereological methods to estimate volumes, total neuron numbers, and neuron densities in Brodmann's areas 44 and 45 in both cerebral hemispheres of 12 chimpanzees (Pan troglodytes), one of our species’ closest living relatives. We found that the degree of interindividual variation in the topographic location and quantitative cytoarchitecture of areas 44 and 45 in chimpanzees was comparable to that seen in humans from previous studies. However, in contrast to the documented asymmetries in humans, we did not find significant population-level hemispheric asymmetry for any measures of areas 44 and 45 in chimpanzees. Furthermore, there was no relationship between asymmetries of stereological data and magnetic resonance imaging–based measures of inferior frontal gyrus morphology or hand preference on 2 different behavioral tasks. These findings suggest that Broca's area in the left hemisphere expanded in relative size during human evolution, possibly as an adaptation for our species’ language abilities.

Neurotrophin-3 Is Involved in the Formation of Apical Dendritic Bundles in Cortical Layer 2 of the Rat

Mon, 20 Jul 2009 13:30:22 PDT

Apical dendritic bundles from pyramidal neurons are a prominent feature of cortical neuropil but with significant area specializations. Here, we investigate mechanisms of bundle formation, focusing on layer (L) 2 bundles in rat granular retrosplenial cortex (GRS), a limbic area implicated in spatial memory. By using microarrays, we first searched for genes highly and specifically expressed in GRS L2 at postnatal day (P) 3 versus GRS L2 at P12 (respectively, before and after bundle formation), versus GRS L5 (at P3), and versus L2 in barrel field cortex (BF) (at P3). Several genes, including neurotrophin-3 (NT-3), were identified as transiently and specifically expressed in GRS L2. Three of these were cloned and confirmed by in situ hybridization. To test that NT-3–mediated events are causally involved in bundle formation, we used in utero electroporation to overexpress NT-3 in other cortical areas. This produced prominent bundles of dendrites originating from L2 neurons in BF, where L2 bundles are normally absent. Intracellular biocytin fills, after physiological recording in vitro, revealed increased dendritic branching in L1 of BF. The controlled ectopic induction of dendritic bundles identifies a new role for NT-3 and a new in vivo model for investigating dendritic bundles and their formation.

Modulation of Perception and Brain Activity by Predictable Trajectories of Facial Expressions

Fri, 17 Jul 2009 06:03:16 PDT

People track facial expression dynamics with ease to accurately perceive distinct emotions. Although the superior temporal sulcus (STS) appears to possess mechanisms for perceiving changeable facial attributes such as expressions, the nature of the underlying neural computations is not known. Motivated by novel theoretical accounts, we hypothesized that visual and motor areas represent expressions as anticipated motion trajectories. Using magnetoencephalography, we show predictable transitions between fearful and neutral expressions (compared with scrambled and static presentations) heighten activity in visual cortex as quickly as 165 ms poststimulus onset and later (237 ms) engage fusiform gyrus, STS and premotor areas. Consistent with proposed models of biological motion representation, we suggest that visual areas predictively represent coherent facial trajectories. We show that such representations bias emotion perception of subsequent static faces, suggesting that facial movements elicit predictions that bias perception. Our findings reveal critical processes evoked in the perception of dynamic stimuli such as facial expressions, which can endow perception with temporal continuity.

A DTI Investigation of Neural Substrates Supporting Tool Use

Ramayya, A. G., Glasser, M. F., Rilling, J. K. — Thu, 16 Jul 2009 10:16:52 PDT

Recent functional neuroimaging and brain lesion studies have implicated a network of left hemisphere regions in human tool use: 1) posterior middle temporal cortex involved in conceptual knowledge of tools, 2) posterior inferior parietal cortex for representations of learned tool use gestures, and 3) anterior inferior parietal cortex, along with posterior inferior frontal and ventral premotor cortices, involved in grasping and manipulating objects. Here, we use diffusion tensor imaging (DTI) to investigate the anatomical connections that support this putative network. DTI scans were acquired from nineteen right-handed males and a deterministic tractography algorithm was used to identify connections between these regions implicated in tool use. Three of the resulting pathways were larger in the left than the right hemisphere. One connected posterior middle temporal cortex and the anterior inferior parietal cortex, a second connected posterior middle temporal cortex and the posterior inferior parietal cortex, and a third connected anterior inferior parietal cortex and the frontal lobe. In contrast, the connection between the posterior inferior parietal cortex and the frontal lobe was highly rightwardly asymmetric. Although further study is necessary to establish the functions of these pathways, we integrate our findings with previous evidence from functional neuroimaging and apraxia studies to suggest some possible functions.

A 1H-MR Spectroscopy Study of Changes in Glutamate and Glutamine (Glx) Concentrations in Frontal Spectra after Administration of Memantine

van Wageningen, H., Jorgensen, H. A., Specht, K., Hugdahl, K. — Wed, 15 Jul 2009 06:27:33 PDT

Glutamate is the major excitatory neurotransmitter in the brain and therefore important for cognitive functions. The aim of the study was to investigate if administration of the N-methyl-D-aspartate receptor antagonist memantine to healthy individuals would affect brain activation when performing an auditory attention task. The task was a variant of a dichotic listening task with different instructions that tap demands for attention and cognitive control. We asked the question if memantine administration would lead to reduction in glutamatergic neurotransmission in areas related to attention and cognitive control. Left and right frontal glutamate and glutamine (Glx) concentrations were measured, using ¹H-MR spectroscopy. Twenty-five healthy adults were scanned twice in a counterbalanced design, either drug naive or after administration of memantine for 21 days. The results showed that memantine significantly reduced Glx concentrations, and this reduction was associated with a reduction in brain activation in prefrontal cortex, which could have implications for understanding the neuronal mechanisms underlying higher cognitive functions such as cognitive control.

Overlapping and Distinct Neural Representations of Numbers and Verbal Transitive Series

Prado, J., Noveck, I. A., Van Der Henst, J.-B. — Wed, 15 Jul 2009 06:27:32 PDT

It is a familiar and intuitive notion that human numerical and logical reasoning skills are tightly related. However, very little is known about the interaction between numerical knowledge and logical reasoning in the brain. Using functional magnetic resonance imaging in healthy subjects, we investigated ordered relations as they are expressed in number (4 is greater than 2) and in transitive reasoning (A is to the left of C after receiving; A is to the left of B; B is to the left of C) in order to determine the extent to which the same neural substrates support both. We found that representing an ordered series verbally learned by transitive reasoning draws on the representations of numbers in the anterior intraparietal sulcus. We further observed that, unlike numbers, transitive series are additionally encoded in the basal ganglia–dopamine system. Intraparietal and basal ganglia mechanisms are not active to the same extent at the same time. Although the intraparietal representations of number preferentially supports a verbal transitive series soon after learning, the basal ganglia are engaged when the series is well practiced. This finding suggests that the transient activation of number representations supports the representation of verbal transitive series until their late encoding in the basal ganglia–dopamine system by associative reinforcement mechanisms.

Duration of Coherence Intervals in Electrical Brain Activity in Perceptual Organization

Nikolaev, A. R., Gepshtein, S., Gong, P., van Leeuwen, C. — Mon, 13 Jul 2009 03:10:33 PDT

We investigated the relationship between visual experience and temporal intervals of synchronized brain activity. Using high-density scalp electroencephalography, we examined how synchronized activity depends on visual stimulus information and on individual observer sensitivity. In a perceptual grouping task, we varied the ambiguity of visual stimuli and estimated observer sensitivity to this variation. We found that durations of synchronized activity in the beta frequency band were associated with both stimulus ambiguity and sensitivity: the lower the stimulus ambiguity and the higher individual observer sensitivity the longer were the episodes of synchronized activity. Durations of synchronized activity intervals followed an extreme value distribution, indicating that they were limited by the slowest mechanism among the multiple neural mechanisms engaged in the perceptual task. Because the degree of stimulus ambiguity is (inversely) related to the amount of stimulus information, the durations of synchronous episodes reflect the amount of stimulus information processed in the task. We therefore interpreted our results as evidence that the alternating episodes of desynchronized and synchronized electrical brain activity reflect, respectively, the processing of information within local regions and the transfer of information across regions.

Absolute Pitch--Functional Evidence of Speech-Relevant Auditory Acuity

Oechslin, M. S., Meyer, M., Jancke, L. — Fri, 10 Jul 2009 10:20:09 PDT

Absolute pitch (AP) has been shown to be associated with morphological changes and neurophysiological adaptations in the planum temporale, a cortical area involved in higher-order auditory and speech perception processes. The direct link between speech processing and AP has hitherto not been addressed. We provide first evidence that AP compared with relative pitch (RP) ability is associated with significantly different hemodynamic responses to complex speech sounds. By systematically varying the lexical and/or prosodic information of speech stimuli, we demonstrated consistent activation differences in AP musicians compared with RP musicians and nonmusicians. These differences relate to stronger activations in the posterior part of the middle temporal gyrus and weaker activations in the anterior mid-part of the superior temporal gyrus. Furthermore, this pattern is considerably modulated by the auditory acuity of AP. Our results suggest that the neural underpinnings of pitch processing expertise exercise a strong influence on propositional speech perception (sentence meaning).

Transforming Growth Factor {beta} Promotes Neuronal Cell Fate of Mouse Cortical and Hippocampal Progenitors In Vitro and In Vivo: Identification of Nedd9 as an Essential Signaling Component

Vogel, T., Ahrens, S., Buttner, N., Krieglstein, K. — Wed, 08 Jul 2009 05:00:27 PDT

Transforming Growth Factor β (Tgfβ) and associated signaling effectors are expressed in the forebrain, but little is known about the role of this multifunctional cytokine during forebrain development. Using hippocampal and cortical primary cell cultures of developing mouse brains, this study identified Tgfβ-regulated genes not only associated with cell cycle exit of progenitors but also with adoption of neuronal cell fate. Accordingly, we observed not only an antimitotic effect of Tgfβ on progenitors but also an increased expression of neuronal markers in Tgfβ treated cultures. This effect was dependent upon Smad4. Furthermore, in vivo loss-of-function analyses using Tgfβ2^–^/–/Tgfβ3^–^/– double mutant mice showed the opposite effect of increased cell proliferation and fewer neurons in the cerebral cortex and hippocampus. Gata2, Runx1, and Nedd9 were candidate genes regulated by Tgfβ and known to be involved in developmental processes of neuronal progenitors. Using siRNA-mediated knockdown, we identified Nedd9 as an essential signaling component for the Tgfβ-dependent increase in neuronal cell fate. Expression of this scaffolding protein, which is mainly described as a signaling molecule of the β1-integrin pathway, was not only induced after Tgfβ treatment but was also associated with morphological changes of the Nestin-positive progenitor pool observed upon exposure to Tgfβ.

Serotoninergic Fine-Tuning of the Excitation-Inhibition Balance in Rat Visual Cortical Networks

Moreau, A. W., Amar, M., Le Roux, N., Morel, N., Fossier, P. — Wed, 08 Jul 2009 07:09:23 PDT

Fundamental brain functions depend on a balance between excitation (E) and inhibition (I) that is highly adjusted to a 20–80% set point in layer 5 pyramidal neurons (L5PNs) of rat visual cortex. Dysregulations of both the E–I balance and the serotonergic system in neocortical networks lead to serious neuronal diseases including depression, schizophrenia, and epilepsy. However, no link between the activation of neuronal 5-hydroxytryptamine receptors (5-HTRs) and the cortical E–I balance has yet been reported. Here we used a combination of patch-clamp recordings of composite stimulus-locked responses in L5PN following local electrical stimulations in either layer 2/3 or 6, simultaneous measurement of excitatory and inhibitory conductance dynamics, together with selective pharmacological targeting and single-cell reverse transcriptase-polymerase chain reaction. We show that cortical serotonin shifts the E–I balance in favor of more E and we reveal fine and differential modulations of the E–I balance between 5-HTR subtypes, in relation to whether layer 2/3 or 6 was stimulated and in concordance with the specific expression pattern of these subtypes in pyramidal cells and deep interneurons. This first evidence for the functional segregation of 5-HTR subtypes sheds new light on their coherent functioning in polysynaptic sensory circuits.

Vesicular Glutamate Transporter VGLUT1 Has a Role in Hippocampal Long-Term Potentiation and Spatial Reversal Learning

Thu, 02 Jul 2009 06:50:42 PDT

Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely complementary distribution in the mature rodent brain and tend to segregate to synapses with different physiological properties. In the hippocampus, VGLUT1 is the dominate subtype in adult animals, whereas VGLUT2 is transiently expressed during early postnatal development. We generated and characterized VGLUT1 knockout mice in order to examine the functional contribution of this transporter to hippocampal synaptic plasticity and hippocampus-dependent spatial learning. Because complete deletion of VGLUT1 resulted in postnatal lethality, we used heterozygous animals for analysis. Here, we report that deletion of VGLUT1 resulted in impaired hippocampal long-term potentiation (LTP) in the CA1 region in vitro. In contrast, heterozygous VGLUT2 mice that were investigated for comparison did not show any changes in LTP. The reduced ability of VGLUT1-deficient mice to express LTP was accompanied by a specific deficit in spatial reversal learning in the water maze. Our data suggest a functional role of VGLUT1 in forms of hippocampal synaptic plasticity that are required to adapt and modify acquired spatial maps to external stimuli and changes.

Auditory Attentional Control and Selection during Cocktail Party Listening

Hill, K. T., Miller, L. M. — Thu, 02 Jul 2009 06:50:41 PDT

In realistic auditory environments, people rely on both attentional control and attentional selection to extract intelligible signals from a cluttered background. We used functional magnetic resonance imaging to examine auditory attention to natural speech under such high processing-load conditions. Participants attended to a single talker in a group of 3, identified by the target talker's pitch or spatial location. A catch-trial design allowed us to distinguish activity due to top-down control of attention versus attentional selection of bottom-up information in both the spatial and spectral (pitch) feature domains. For attentional control, we found a left-dominant fronto-parietal network with a bias toward spatial processing in dorsal precentral sulcus and superior parietal lobule, and a bias toward pitch in inferior frontal gyrus. During selection of the talker, attention modulated activity in left intraparietal sulcus when using talker location and in bilateral but right-dominant superior temporal sulcus when using talker pitch. We argue that these networks represent the sources and targets of selective attention in rich auditory environments.

Experience-Dependent Gene Expression in Adult Visual Cortex

Chen, J., Yamahachi, H., Gilbert, C. D. — Wed, 01 Jul 2009 13:54:41 PDT

Experience-dependent plasticity of the adult visual cortex underlies perceptual learning and recovery of function following central nervous system lesions. To reveal the signal transduction cascades involved in adult cortical plasticity, we utilized a model of remapping of cortical topography following binocular retinal lesions. In this model, the lesion projection zone (LPZ) of primary visual cortex (V1) recovers visually driven activity by the sprouting of horizontal axonal connections originating from the cells in the surrounding region. To explore the molecular mechanism underlying this process, we used gene microarrays from an expression library prepared from Macaque V1. By microarray analysis of gene expression levels in the LPZ and the surrounding region, and subsequent confirmation with Quantitative Real-Time polymerase chain reaction and in situ hybridization, the participation of a number of genes was observed, including the Rho GTPase family. Its role in regulation of cytoskeleton assembly provides a possible link between the alteration of neural activity and cortical functional reorganization.

IQ-Related fMRI Differences during Cognitive Set Shifting

Wed, 01 Jul 2009 13:54:40 PDT

This event-related functional magnetic resonance imaging study compared neural correlates of executive function (cognitive set-shifting) in 28 healthy participants with either high (HIQ) or average (AIQ) intelligence. Despite comparable behavioral performance (except for slower reactions), the AIQ participants showed greater (especially prefrontal) activation during response selection; the HIQ participants showed greater activation (especially parietal) during feedback evaluation. HIQ participants appeared to engage cognitive resources to support more efficient strategies (planning during feedback in preparation for the upcoming response) which resulted in faster responses and less need for response inhibition and conflict resolution. Whether greater intelligence is associated with more or less brain activity (the "neural efficiency" debate) depends therefore on the specific component of the task being examined as well as the brain region recruited. One implication is that caution must be exercised when drawing conclusions from differences in activation between groups of individuals in whom IQ may differ (e.g., psychiatric vs. control samples).

Auditory Selective Attention to Speech Modulates Activity in the Visual Word Form Area

Yoncheva, Y. N., Zevin, J. D., Maurer, U., McCandliss, B. D. — Wed, 01 Jul 2009 13:54:39 PDT

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level–dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers.

Synapses of Horizontal Connections in Adult Rat Somatosensory Cortex Have Different Properties Depending on the Source of their Axons

Hickmott, P. W. — Wed, 01 Jul 2009 13:54:38 PDT

In somatosensory cortex (S1) tactile stimulation activates specific regions. The borders between representations of different body parts constrain the spread of excitation and inhibition: connections that cross from one representation to another (cross-border, CB) are weaker than those remaining within the representation (noncross border, NCB). Thus, physiological properties of CB and NCB synapses onto layer 2/3 pyramidal neurons were compared using whole-cell recordings in layer 2/3 neurons close to the border between the forepaw and lower jaw representations. Electrical stimulation of CB and NCB connections was used to activate synaptic potentials. Properties of excitatory (EPSPs) and inhibitory (IPSPs) postsynaptic potentials (PSP) were determined using 3 methods: 1) minimal stimulation to elicit single-fiber responses; 2) stimulation in the presence of extracellular Sr²⁺ to elicit asynchronous quantal responses; 3) short trains of stimulation at various frequencies to examine postsynaptic potential (PSP) dynamics. Both minimal and asynchronous quantal EPSPs were smaller when evoked by CB than NCB stimulation. However, the dynamics of EPSP and IPSP trains were not different between CB and NCB stimulation. These data suggest that individual excitatory synapses from connections that cross a border (CB) have smaller amplitudes than those that come from within a representation (NCB), and suggest a postsynaptic locus for the difference.

Expectancy Constraints in Degraded Speech Modulate the Language Comprehension Network

Obleser, J., Kotz, S. A. — Fri, 26 Jun 2009 04:54:18 PDT

In speech comprehension, the processing of auditory information and linguistic context are mutually dependent. This functional magnetic resonance imaging study examines how semantic expectancy ("cloze probability") in variably intelligible sentences ("noise vocoding") modulates the brain bases of comprehension. First, intelligibility-modulated activation along the superior temporal sulci (STS) was extended anteriorly and posteriorly in low-cloze sentences (e.g., "she weighs the flour") but restricted to a mid-superior temporal gyrus/STS area in more predictable high-cloze sentences (e.g., "she sifts the flour"). Second, the degree of left inferior frontal gyrus (IFG) (Brodmann's area 44) involvement in processing low-cloze constructions was proportional to increasing intelligibility. Left inferior parietal cortex (IPC; angular gyrus) activation accompanied successful speech comprehension that derived either from increased signal quality or from semantic facilitation. The results show that successful decoding of speech in auditory cortex areas regulates language-specific computation (left IFG and IPC). In return, semantic expectancy can constrain these speech-decoding processes, with fewer neural resources being allocated to highly predictable sentences. These findings offer an important contribution toward the understanding of the functional neuroanatomy in speech comprehension.

Spatial Distribution of Deep Sulcal Landmarks and Hemispherical Asymmetry on the Cortical Surface

Im, K., Jo, H. J., Mangin, J.-F., Evans, A. C., Kim, S. I., Lee, J.-M. — Fri, 26 Jun 2009 04:54:17 PDT

The locally deepest regions of major sulci, the sulcal pits, are thought to be the first cortical folds to develop and are closely related to functional areas. We examined the spatial distribution of sulcal pits across the entire cortical region, and assessed the hemispheric asymmetry in their frequency and distribution in a large group of normal adult brains. We automatically extracted sulcal pits from magnetic resonance imaging data using surface-based methods and constructed a group map from 148 subjects. The spatial distribution of the sulcal pits was relatively invariant between individuals, showing high frequency and density in specific focal areas. The left and right sulcal pits were spatially covariant in the regions of the earliest developed sulci. The sulcal pits with great spatial invariance appear to be useful as stable anatomical landmarks. We showed the most significant asymmetry in the frequency and spatial variance of sulcal pits in the superior temporal sulcus, which might be related to the lateralization of language function to the left hemisphere, developing more consistently and strongly than for the right. Our analyses support previous empirical and theoretical studies, and provide additional insights concerning the anatomical and functional development of the brain.

Reading Aloud Boosts Connectivity through the Putamen

Seghier, M. L., Price, C. J. — Fri, 26 Jun 2009 04:54:16 PDT

Functional neuroimaging and lesion studies have frequently reported thalamic and putamen activation during reading and speech production. However, it is currently unknown how activity in these structures interacts with that in other reading and speech production areas. This study investigates how reading aloud modulates the neuronal interactions between visual recognition and articulatory areas, when both the putamen and thalamus are explicitly included. Using dynamic causal modeling in skilled readers who were reading regularly spelled English words, we compared 27 possible pathways that might connect the ventral anterior occipito-temporal sulcus (aOT) to articulatory areas in the precentral cortex (PrC). We focused on whether the neuronal interactions within these pathways were increased by reading relative to picture naming and other visual and articulatory control conditions. The results provide strong evidence that reading boosts the aOT–PrC pathway via the putamen but not the thalamus. However, the putamen pathway was not exclusive because there was also evidence for another reading pathway that did not involve either the putamen or the thalamus. We conclude that the putamen plays a special role in reading but this is likely to vary with individual reading preferences and strategies.

Output Properties and Organization of the Forelimb Representation of Motor Areas on the Lateral Aspect of the Hemisphere in Rhesus Macaques

Boudrias, M.-H., McPherson, R. L., Frost, S. B., Cheney, P. D. — Fri, 26 Jun 2009 04:54:15 PDT

Motor output capabilities of the forelimb representation of dorsal motor area (PMd) and ventral motor area (PMv) were compared with primary motor cortex (M1) in terms of latency, strength, sign, and distribution of effects. Stimulus-triggered averages (60 µA) of electromyographic activity collected from 24 forelimb muscles were computed at 314 tracks in 2 monkeys trained to perform a reach-to-grasp task. The onset latency and magnitude of facilitation effects from PMd and PMv were significantly longer and 7- to 9-fold weaker than those from M1. Proximal muscles were predominantly represented in PMd and PMv. A joint-dependent flexor or extensor preference was also present. Distal and proximal muscle representations were intermingled in PMd and PMv. A gradual increase in latency and decrease in magnitude of effects were observed in moving from M1 surface sites toward more anterior sites in PMd. For many muscles, segregated areas producing suppression effects were found along the medial portion of PMd and adjacent M1. Although some facilitation effects from PMd and PMv had onset latencies as short as those from M1 in the same muscle, suggesting equal direct linkage, the vast majority had properties consistent with a more indirect linkage to motoneurons either through corticocortical connections with M1 and/or interneuronal linkages in the spinal cord.

Regional Response Differences Across the Human Amygdaloid Complex during Social Conditioning

Davis, F. C., Johnstone, T., Mazzulla, E. C., Oler, J. A., Whalen, P. J. — Thu, 25 Jun 2009 06:46:20 PDT

The amygdala is consistently implicated in biologically relevant learning tasks such as Pavlovian conditioning. In humans, the ability to identify individual faces based on the social outcomes they have predicted in the past constitutes a critical form of associative learning that can be likened to "social conditioning." To capture such learning in a laboratory setting, participants learned about faces that predicted negative, positive, or neutral social outcomes. Participants reported liking or disliking the faces in accordance with their learned social value. During acquisition, we observed differential functional magnetic resonance imaging activation across the human amygdaloid complex consistent with previous lesion, electrophysiological, and functional neuroimaging data. A region of the medial ventral amygdala and a region of the dorsal amygdala/substantia innominata showed signal increases to both Negative and Positive faces, whereas a lateral ventral region displayed a linear representation of the valence of faces such that Negative > Positive > Neutral. This lateral ventral locus also differed from the dorsal and medial loci in that the magnitude of these responses was more resistant to habituation. These findings document a role for the human amygdala in social learning and reveal coarse regional dissociations in amygdala activity that are consistent with previous human and nonhuman animal data.

Common and Dissociable Prefrontal Loci Associated with Component Mechanisms of Analogical Reasoning

Tue, 23 Jun 2009 00:10:44 PDT

The ability to draw analogies requires 2 key cognitive processes, relational integration and resolution of interference. The present study aimed to identify the neural correlates of both component processes of analogical reasoning within a single, nonverbal analogy task using event-related functional magnetic resonance imaging. Participants verified whether a visual analogy was true by considering either 1 or 3 relational dimensions. On half of the trials, there was an additional need to resolve interference in order to make a correct judgment. Increase in the number of dimensions to integrate was associated with increased activation in the lateral prefrontal cortex as well as lateral frontal pole in both hemispheres. When there was a need to resolve interference during reasoning, activation increased in the lateral prefrontal cortex but not in the frontal pole. We identified regions in the middle and inferior frontal gyri which were exclusively sensitive to demands on each component process, in addition to a partial overlap between these neural correlates of each component process. These results indicate that analogical reasoning is mediated by the coordination of multiple regions of the prefrontal cortex, of which some are sensitive to demands on only one of these 2 component processes, whereas others are sensitive to both.

Altered Water Diffusivity in Cortical Association Tracts in Children with Early Deprivation Identified with Tract-Based Spatial Statistics (TBSS)

Govindan, R. M., Behen, M. E., Helder, E., Makki, M. I., Chugani, H. T. — Mon, 22 Jun 2009 05:15:43 PDT

Institutional rearing is associated with neurocognitive and behavioral difficulties. Although such difficulties are thought to reflect abnormal neurologic development resulting from early social deprivation (ED) and there is evidence for functional abnormality in children with histories of ED, the impact of early deprivation on brain anatomy has received little study in humans. The present study utilized an objective and sensitive neuroimaging analysis technique (Tract-Based Spatial Statistics) to evaluate white matter fractional anisotropy (FA) and diffusivity in a group of right-handed children with histories of ED (n = 17; mean age = 10.9 + 2.6 years) as compared with age-matched healthy controls (n = 15; mean age = 11.7 ± 2.8 years). Participants underwent magnetic resonance imaging diffusion tensor imaging sequences and comprehensive neuropsychological evaluations. Results revealed reduced FA in frontal, temporal, and parietal white matter including components of uncinate and superior longitudinal fasciculi, in children with histories of ED, providing further support for limbic and paralimbic abnormalities in children with such histories. Furthermore, white matter abnormalities were associated with duration of time in the orphanage and with inattention and hyperactivity scores. It is suspected that the observed white matter abnormalities are associated with multiple depriving factors (e.g., poor prenatal care, postnatal stress) associated with institutional caregiving.

Topographical Functional Connectivity Pattern in the Perisylvian Language Networks

Xiang, H.-D., Fonteijn, H. M., Norris, D. G., Hagoort, P. — Mon, 22 Jun 2009 05:15:42 PDT

We performed a resting-state functional connectivity study to investigate directly the functional correlations within the perisylvian language networks by seeding from 3 subregions of Broca's complex (pars opercularis, pars triangularis, and pars orbitalis) and their right hemisphere homologues. A clear topographical functional connectivity pattern in the left middle frontal, parietal, and temporal areas was revealed for the 3 left seeds. This is the first demonstration that a functional connectivity topology can be observed in the perisylvian language networks. The results support the assumption of the functional division for phonology, syntax, and semantics of Broca's complex as proposed by the memory, unification, and control (MUC) model and indicated a topographical functional organization in the perisylvian language networks, which suggests a possible division of labor for phonological, syntactic, and semantic function in the left frontal, parietal, and temporal areas.

Cerebellar Engagement in an Action Observation Network

Sokolov, A. A., Gharabaghi, A., Tatagiba, M. S., Pavlova, M. — Mon, 22 Jun 2009 05:15:42 PDT

The cerebellum has traditionally been viewed as a brain structure subserving skilled motor behaviors. However, the cerebellum might be involved not only in movement coordination, but also in action observation and understanding of others’ actions. Veridical visual perception of human body motion is of immense importance for a variety of daily-life situations and for successful social interactions. Here, by combining visual psychophysics with a lesion analysis, we assessed visual sensitivity to human walking in patients with lesions to the left cerebellum. Patients with left lateral cerebellar lesions exhibit deficits in visual sensitivity to body motion, whereas medial lesions do not substantially affect visual perception of human locomotion. The findings point to left lateral cerebellar involvement in an action observation network. We discuss possible mechanisms of cerebellar engagement in visual social perception revealed by body motion.

Activation of Sensory-Motor Areas in Sentence Comprehension

Desai, R. H., Binder, J. R., Conant, L. L., Seidenberg, M. S. — Mon, 22 Jun 2009 05:15:41 PDT

The sensory–motor account of conceptual processing suggests that modality-specific attributes play a central role in the organization of object and action knowledge in the brain. An opposing view emphasizes the abstract, amodal, and symbolic character of concepts, which are thought to be represented outside the brain's sensory–motor systems. We conducted a functional magnetic resonance imaging study in which the participants listened to sentences describing hand/arm action events, visual events, or abstract behaviors. In comparison to visual and abstract sentences, areas associated with planning and control of hand movements, motion perception, and vision were activated when understanding sentences describing actions. Sensory–motor areas were activated to a greater extent also for sentences with actions that relied mostly on hands, as opposed to arms. Visual sentences activated a small area in the secondary visual cortex, whereas abstract sentences activated superior temporal and inferior frontal regions. The results support the view that linguistic understanding of actions partly involves imagery or simulation of actions, and relies on some of the same neural substrate used for planning, performing, and perceiving actions.

Dissociation Between Memory Accuracy and Memory Confidence Following Bilateral Parietal Lesions

Simons, J. S., Peers, P. V., Mazuz, Y. S., Berryhill, M. E., Olson, I. R. — Fri, 19 Jun 2009 11:35:03 PDT

Numerous functional neuroimaging studies have observed lateral parietal lobe activation during memory tasks: a surprise to clinicians who have traditionally associated the parietal lobe with spatial attention rather than memory. Recent neuropsychological studies examining episodic recollection after parietal lobe lesions have reported differing results. Performance was preserved in unilateral lesion patients on source memory tasks involving recollecting the context in which stimuli were encountered, and impaired in patients with bilateral parietal lesions on tasks assessing free recall of autobiographical memories. Here, we investigated a number of possible accounts for these differing results. In 3 experiments, patients with bilateral parietal lesions performed as well as controls at source recollection, confirming the previous unilateral lesion results and arguing against an explanation for those results in terms of contralesional compensation. Reducing the behavioral relevance of mnemonic information critical to the source recollection task did not affect performance of the bilateral lesion patients, indicating that the previously observed reduced autobiographical free recall might not be due to impaired bottom-up attention. The bilateral patients did, however, exhibit reduced confidence in their source recollection abilities across the 3 experiments, consistent with a suggestion that parietal lobe lesions might lead to impaired subjective experience of rich episodic recollection.

The Contribution of the Parietal Lobes to Speaking and Writing

Brownsett, S. L. E., Wise, R. J. S. — Tue, 16 Jun 2009 01:39:51 PDT

The left parietal lobe has been proposed as a major language area. However, parietal cortical function is more usually considered in terms of the control of actions, contributing both to attention and cross-modal integration of external and reafferent sensory cues. We used positron emission tomography to study normal subjects while they overtly generated narratives, both spoken and written. The purpose was to identify the parietal contribution to the modality-specific sensorimotor control of communication, separate from amodal linguistic and memory processes involved in generating a narrative. The majority of left and right parietal activity was associated with the execution of writing under visual and somatosensory control irrespective of whether the output was a narrative or repetitive reproduction of a single grapheme. In contrast, action-related parietal activity during speech production was confined to primary somatosensory cortex. The only parietal area with a pattern of activity compatible with an amodal central role in communication was the ventral part of the left angular gyrus (AG). The results of this study indicate that the cognitive processing of language within the parietal lobe is confined to the AG and that the major contribution of parietal cortex to communication is in the sensorimotor control of writing.

How Reliable Are Visual Context Effects in the Parahippocampal Place Area?

Epstein, R. A., Ward, E. J. — Tue, 16 Jun 2009 01:39:50 PDT

The parahippocampal place area (PPA) is a region of human cortex that responds more strongly to visual scenes (e.g., landscapes or cityscapes) than to other visual stimuli. It has been proposed that the primary function of the PPA is encoding of contextual information about object co-occurrence. Supporting this context hypothesis are reports that the PPA responds more strongly to strong-context than to weak-context objects and more strongly to famous faces (for which contextual associations are available) than to nonfamous faces. We reexamined the reliability of these 2 effects by scanning subjects with functional magnetic resonance imaging while they viewed strong- and weak-context objects, scrambled versions of these objects, and famous and nonfamous faces. "Contextual" effects for objects were observed to be reliable in the PPA at slow presentation rates but not at faster presentation rates intended to discourage scene imagery. We were unable to replicate the earlier finding of preferential PPA response to famous versus nonfamous faces. These results are difficult to reconcile with the hypothesis that the PPA encodes contextual associations but are consistent with a competing hypothesis that the PPA encodes scenic layout.

Brain Maturation in Adolescence and Young Adulthood: Regional Age-Related Changes in Cortical Thickness and White Matter Volume and Microstructure

Thu, 11 Jun 2009 07:44:25 PDT

The development of cortical gray matter, white matter (WM) volume, and WM microstructure in adolescence is beginning to be fairly well characterized by structural magnetic resonance imaging (sMRI) and diffusion tensor imaging (DTI) studies. However, these aspects of brain development have rarely been investigated concurrently in the same sample and hence the relations between them are not understood. We delineated the age-related changes in cortical thickness, regional WM volume, and diffusion characteristics and investigated the relationships between these properties of brain development. One hundred and sixty-eight healthy participants aged 8–30 years underwent sMRI and DTI. The results showed regional age-related cortical thinning, WM volume increases, and changes in diffusion parameters. Cortical thickness was the most strongly age-related parameter. All classes of measures showed unique associations with age. The results indicate that cortical thinning in adolescence cannot be explained by WM maturation in underlying regions as measured by volumetry or DTI. Moderate associations between cortical thickness and both volume and diffusion parameters in underlying WM regions were also found, although the relationships were not strong. It is concluded that none of the measures are redundant and that the integration of the 3 will yield a more complete understanding of brain maturation.

Identification of the Hippocampal Input to Medial Prefrontal Cortex In Vitro

Parent, M. A., Wang, L., Su, J., Netoff, T., Yuan, L.-L. — Wed, 10 Jun 2009 06:27:42 PDT

To delineate the cellular mechanisms underlying the function of medial prefrontal cortex (mPFC) networks, it is critical to understand how synaptic inputs from various afferents are integrated and drive neuronal activity in this region. Using a newly developed slice preparation, we were able to identify a bundle of axons that contain extraneocortical fibers projecting to neurons in the prelimbic cortex. The anatomical origin and functional connectivity of the identified fiber bundle were probed by in vivo track tracing in combination with optic and whole-cell recordings of neurons in layers 2/3 and 5/6. We demonstrate that the identified bundle contains afferent fibers primarily from the ventral hippocampus but does not include contributions from the mediodorsal nucleus of the thalamus, amygdala, or lateral hypothalamus/medial forebrain bundle. Further, we provide evidence that activation of this fiber bundle results in patterned activity of neurons in the mPFC, which is distinct from that of laminar stimulation of either the deep layers 5/6 or the superficial layer 1. Evoked excitatory postsynaptic potentials are monosynaptic and glutamatergic and exhibit bidirectional changes in synaptic efficacy in response to physiologically relevant induction protocols. These data provide the necessary groundwork for the characterization of the hippocampal pathway projecting to the mPFC.

Attenuation of Somatosensory Responses to Self-Produced Tactile Stimulation

Hesse, M. D., Nishitani, N., Fink, G. R., Jousmaki, V., Hari, R. — Mon, 08 Jun 2009 08:06:05 PDT

Sensory stimulation resulting from one's own behavior or the outside world is easily differentiated by healthy persons who are able to predict the sensory consequences of their own actions. This ability has been related to cortical attenuation of activation elicited by self-produced stimulation. To date, however, the neural processes underlying this modulation remain to be elucidated. We therefore recorded whole-scalp magnetoencephalographic (MEG) signals from 10 young adults either when they were touched by another person with a brush or when they touched themselves with the same device. The main MEG responses peaked at the primary somatosensory cortex at 54 ± 2 ms. Signals and source strengths were about a fifth weaker to self-produced than external touch. Importantly, attenuation was present in each subject. Control recordings indicated that the suppression was neither caused by hand movements as such nor by visual cues. The very early start of the attenuation already about 30 ms after stimulation onset is in line with the hypothesis of forward mechanisms, based on motor commands, as the basis of differentiation between self-produced and externally produced tactile sensations.

On Emotional Conflict: Interference Resolution of Happy and Angry Prosody Reveals Valence-Specific Effects

Mon, 08 Jun 2009 08:06:04 PDT

To comprehend emotional prosodic cues in speech is a critical function of human social life. However, it is common in everyday communication that conflicting information in emotional prosody and semantic content co-occur. Here, we sought to specify brain regions involved in conflict monitoring of these interfering communication channels. By means of functional magnetic resonance imaging, we obtained signal increases in the right dorsal anterior cingulate cortex and right superior temporal gyrus (STG) and superior temporal sulcus when participants listened to incongruous compared with congruous sentences. Moreover, valence-specific effects were found in the left inferior frontal gyrus and left STG for happily intoned sentences expressing a negative content. The left caudate nucleus along with the thalamus was active when angrily intoned sentences were coupled with positive semantic content. Our results suggest a brain network that monitors conflict in emotional prosody and emotional semantic content comprising of medial prefrontal areas that have previously been associated with cognitive conflict processing. Furthermore, our study extends the knowledge of these processes by suggesting valence-specific differences of emotional conflict processing.

Preserving Syntactic Processing across the Adult Life Span: The Modulation of the Frontotemporal Language System in the Context of Age-Related Atrophy

Mon, 08 Jun 2009 08:06:03 PDT

Although widespread neural atrophy is an inevitable consequence of normal aging, not all cognitive abilities decline as we age. For example, spoken language comprehension tends to be preserved, despite atrophy in neural regions involved in language function. Here, we combined measures of behavior, functional activation, and gray matter (GM) change in a younger (19–34 years) and older group (49–86 years) of participants to identify the mechanisms leading to preserved language comprehension across the adult life span. We focussed primarily on syntactic functions because these are strongly left lateralized, providing the potential for contralateral recruitment. In an functional magnetic resonance imaging study, we used a word-monitoring task to minimize working memory demands, manipulating the availability of semantics and syntax to ask whether syntax is preserved in aging because of the functional recruitment of other brain regions, which successfully compensate for neural atrophy. Performance in the older group was preserved despite GM loss. This preservation was related to increased activity in right hemisphere frontotemporal regions, which was associated with age-related atrophy in the left hemisphere frontotemporal network activated in the young. We argue that preserved syntactic processing across the life span is due to the shift from a primarily left hemisphere frontotemporal system to a bilateral functional language network.

Human V6: The Medial Motion Area

Fri, 05 Jun 2009 10:15:40 PDT

Cortical-surface-based functional Magnetic Resonance Imaging mapping techniques and wide-field retinotopic stimulation were used to verify the presence of pattern motion sensitivity in human area V6. Area V6 is highly selective for coherently moving fields of dots, both at individual and group levels and even with a visual stimulus of standard size. This stimulus is a functional localizer for V6. The wide retinotopic stimuli used here also revealed a retinotopic map in the middle temporal cortex (area MT/V5) surrounded by several polar-angle maps that resemble the mosaic of small areas found around macaque MT/V5. Our results suggest that the MT complex (MT+) may be specialized for the analysis of motion signals, whereas area V6 may be more involved in distinguishing object and self-motion.

Tis21 Expression Marks Not Only Populations of Neurogenic Precursor Cells but Also New Postmitotic Neurons in Adult Hippocampal Neurogenesis

Attardo, A., Fabel, K., Krebs, J., Haubensak, W., Huttner, W. B., Kempermann, G. — Fri, 29 May 2009 04:21:05 PDT

During embryonic cortical development, expression of Tis21 is associated with cell cycle lengthening and neurogenic divisions of progenitor cells. We here investigated if the expression pattern of Tis21 also correlates with the generation of new neurons in the adult hippocampus. We used Tis21 knock-in mice expressing green fluorescent protein (GFP) and studied Tis21-GFP expression together with markers of adult hippocampal neurogenesis in newly generated cells. We found that Tis21-GFP 1) was absent from the radial glia–like putative stem cells (type-1 cells), 2) first appeared in transient amplifying progenitor cells (type-2 and 3 cells), 3) did not colocalize with markers of early postmitotic maturation stage, 4) was expressed again in maturing neurons, and 5) finally decreased in mature granule cells. Our data show that, in the course of adult neurogenesis, Tis21 is expressed in a phase additional to the one of the embryonic neurogenesis. This additional phase of expression might be associated with a new and different function of Tis21 than during embryonic brain development, where no Tis21 is expressed in mature neurons. We hypothesize that this function is related to the final functional integration of the newborn neurons. Tis21 can thus serve as new marker for key stages of adult neurogenesis.

Separate Processing of Texture and Form in the Ventral Stream: Evidence from fMRI and Visual Agnosia

Cavina-Pratesi, C., Kentridge, R. W., Heywood, C. A., Milner, A. D. — Thu, 28 May 2009 08:44:03 PDT

Real-life visual object recognition requires the processing of more than just geometric (shape, size, and orientation) properties. Surface properties such as color and texture are equally important, particularly for providing information about the material properties of objects. Recent neuroimaging research suggests that geometric and surface properties are dealt with separately within the lateral occipital cortex (LOC) and the collateral sulcus (CoS), respectively. Here we compared objects that differed either in aspect ratio or in surface texture only, keeping all other visual properties constant. Results on brain-intact participants confirmed that surface texture activates an area in the posterior CoS, quite distinct from the area activated by shape within LOC. We also tested 2 patients with visual object agnosia, one of whom (DF) performed well on the texture task but at chance on the shape task, whereas the other (MS) showed the converse pattern. This behavioral double dissociation was matched by a parallel neuroimaging dissociation, with activation in CoS but not LOC in patient DF and activation in LOC but not CoS in patient MS. These data provide presumptive evidence that the areas respectively activated by shape and texture play a causally necessary role in the perceptual discrimination of these features.

Mentalizing under Uncertainty: Dissociated Neural Responses to Ambiguous and Unambiguous Mental State Inferences

Jenkins, A. C., Mitchell, J. P. — Thu, 28 May 2009 08:44:02 PDT

The ability to read the minds of others (i.e., to mentalize) requires that perceivers understand a wide range of different kinds of mental states, including not only others’ beliefs and knowledge but also their feelings, desires, and preferences. Moreover, although such inferences may occasionally rely on observable features of a situation, perceivers more typically mentalize under conditions of "uncertainty," in which they must generate plausible hypotheses about a target's mental state from ambiguous or otherwise underspecified information. Here, we use functional neuroimaging to dissociate the neural bases of these 2 distinct social–cognitive challenges: 1) mentalizing about different types of mental states (beliefs vs. preferences) and 2) mentalizing under conditions of varying ambiguity. Although these 2 aspects of mentalizing have typically been confounded in earlier research, we observed a double dissociation between the brain regions sensitive to type of mental state and ambiguity. Whereas ventral and dorsal aspects of medial prefrontal cortex responded more during ambiguous than unambiguous inferences regardless of the type of mental state, the right temporoparietal junction was sensitive to the distinction between beliefs and preferences irrespective of certainty. These results underscore the emerging consensus that, rather than comprising a single mental operation, social cognition makes flexible use of different processes as a function of the particular demands of the social context.

The Impact of Second Language Learning on Semantic and Nonsemantic First Language Reading

Nosarti, C., Mechelli, A., Green, D. W., Price, C. J. — Thu, 28 May 2009 08:44:02 PDT

The relationship between orthography (spelling) and phonology (speech sounds) varies across alphabetic languages. Consequently, learning to read a second alphabetic language, that uses the same letters as the first, increases the phonological associations that can be linked to the same orthographic units. In subjects with English as their first language, previous functional imaging studies have reported increased left ventral prefrontal activation for reading words with spellings that are inconsistent with their orthographic neighbors (e.g., PINT) compared with words that are consistent with their orthographic neighbors (e.g., SHIP). Here, using functional magnetic resonance imaging (fMRI) in 17 Italian–English and 13 English–Italian bilinguals, we demonstrate that left ventral prefrontal activation for first language reading increases with second language vocabulary knowledge. This suggests that learning a second alphabetic language changes the way that words are read in the first alphabetic language. Specifically, first language reading is more reliant on both lexical/semantic and nonlexical processing when new orthographic to phonological mappings are introduced by second language learning. Our observations were in a context that required participants to switch between languages. They motivate future fMRI studies to test whether first language reading is also altered in contexts when the second language is not in use.

Cortical Connections to Area TE in Monkey: Hybrid Modular and Distributed Organization

Borra, E., Ichinohe, N., Sato, T., Tanifuji, M., Rockland, K. S. — Sat, 23 May 2009 01:26:21 PDT

To investigate the fine anatomical organization of cortical inputs to visual association area TE, 2–3 small injections of retrograde tracers were made in macaque monkeys. Injections were made as a terminal procedure, after optical imaging and electrophysiological recording, and targeted to patches physiologically identified as object-selective. Retrogradely labeled neurons occurred in several unimodal visual areas, the superior temporal sulcus, intraparietal sulcus (IPS), and prefrontal cortex (PFC), consistent with previous studies. Despite the small injection size (<0.5 mm wide), the projection foci in visual areas, but not in IPS or PFC, were spatially widespread (4–6 mm in extent), and predominantly consisted of neurons labeled by only one of the injections. This can be seen as a quasi-modular organization. In addition, within each projection focus, there were scattered neurons projecting to one of the other injections, together with some double-labeled (DL) neurons, in a more distributed pattern. Finally, projection foci included smaller "hotspots," consisting of intermixed neurons, single-labeled by the different injections, and DL neurons. DL neurons are likely the result of axons having extended, spatially separated terminal arbors, as demonstrated by anterograde experiments. These results suggest a complex, hybrid connectivity architecture, with both modular and distributed components.

Adaptive Changes in Firing of Primary Auditory Cortical Neurons following Illumination Shift from Light to Dark in Freely Moving Guinea Pigs

Ojima, H., Taoka, M., Iriki, A. — Fri, 22 May 2009 19:13:02 PDT

Some animals are forced to rely more on non-visual signals, such as audition or olfaction, than on vision when a bright environment becomes dark. By recording from a primary-like auditory cortex (field A) in freely moving guinea pigs, possible changes in the responsiveness of single units were explored in association with illumination changes. For a subset of units, we found that robust decreases (off-decrease) or increases (off-increase) in baseline discharge (BsD) were initiated soon after room light was silently extinguished. These neuronal changes were accompanied by the initiation of explorative locomotion, possibly reflecting a changed internal brain state. Preferred acoustic stimuli evoked salient excitatory responses against the reduced BsD level in the dark for the off-decrease units, and salient inhibitory responses against the increased BsD level for the off-increase units. Histological verification indicated that the units showing such BsD changes were located predominantly in layer V or its vicinity. These results are discussed in the context of the effects of the brainstem neuromodulatory systems that are activated during behavioral adaptation to new environments.

The Cortical Site of Visual Suppression by Transcranial Magnetic Stimulation

Thielscher, A., Reichenbach, A., Ugurbil, K., Uludag, K. — Fri, 22 May 2009 19:13:00 PDT

In visual suppression paradigms, transcranial magnetic stimulation (TMS) applied ~90 ms after visual stimulus presentation over occipital visual areas can robustly interfere with visual perception, thereby most likely affecting feedback activity from higher areas (Amassian VE, Cracco RQ, Maccabee PJ, Cracco JB, Rudell A, Eberle L. 1989. Suppression of visual perception by magnetic coil stimulation of human occipital cortex. Electroencephalogr Clin Neurophysiol 74:458–462.). It is speculated that the observed effects might stem primarily from the disruption of V1 activity. This hypothesis, although under debate, argues in favor of a special role of V1 in visual awareness. In this study, we combine TMS, functional magnetic resonance imaging, and calculation of the induced electric field to study the neural correlates of visual suppression. For parafoveal visual stimulation in the lower right half of the visual field, area V2d is shown to be the likely TMS target based on its anatomical location close to the skull surface. Furthermore, isolated stimulation of area V3 also results in robust visual suppression. Notably, V3 stimulation does not directly affect the feedback from higher visual areas that is relayed mainly via V2 to V1. These findings support the view that intact activity patterns in several early visual areas (rather than merely in V1) are likewise important for the perception of the stimulus.

Cerebellar Inputs to Intraparietal Cortex Areas LIP and MIP: Functional Frameworks for Adaptive Control of Eye Movements, Reaching, and Arm/Eye/Head Movement Coordination

Prevosto, V., Graf, W., Ugolini, G. — Fri, 22 May 2009 19:12:59 PDT

Using retrograde transneuronal transfer of rabies virus in combination with a conventional tracer (cholera toxin B), we studied simultaneously direct (thalamocortical) and polysynaptic inputs to the ventral lateral intraparietal area (LIPv) and the medial intraparietal area (MIP) in nonhuman primates. We found that these areas receive major disynaptic inputs from specific portions of the cerebellar nuclei, the ventral dentate (D), and ventrolateral interpositus posterior (IP). Area LIPv receives inputs from oculomotor domains of the caudal D and IP. Area MIP is the target of projections from the ventral D (mainly middle third), and gaze- and arm-related domains of IP involved in reaching and arm/eye/head coordination. We also showed that cerebellar cortical "output channels" to MIP predominantly stem from posterior cerebellar areas (paramedian lobe/Crus II posterior, dorsal paraflocculus) that have the required connectivity for adaptive control of visual and proprioceptive guidance of reaching, arm/eye/head coordination, and prism adaptation. These findings provide important insight about the interplay between the posterior parietal cortex and the cerebellum regarding visuospatial adaptation mechanisms and visual and proprioceptive guidance of movement. They also have potential implications for clinical approaches to optic ataxia and neglect rehabilitation.

Severe Scene Learning Impairment, but Intact Recognition Memory, after Cholinergic Depletion of Inferotemporal Cortex Followed by Fornix Transection

Browning, P. G. F., Gaffan, D., Croxson, P. L., Baxter, M. G. — Fri, 15 May 2009 05:47:00 PDT

To examine the generality of cholinergic involvement in visual memory in primates, we trained macaque monkeys either on an object-in-place scene learning task or in delayed nonmatching-to-sample (DNMS). Each monkey received either selective cholinergic depletion of inferotemporal cortex (including the entorhinal cortex and perirhinal cortex) with injections of the immunotoxin ME20.4-saporin or saline injections as a control and was postoperatively retested. Cholinergic depletion of inferotemporal cortex was without effect on either task. Each monkey then received fornix transection because previous studies have shown that multiple disconnections of temporal cortex can produce synergistic impairments in memory. Fornix transection mildly impaired scene learning in monkeys that had received saline injections but severely impaired scene learning in monkeys that had received cholinergic lesions of inferotemporal cortex. This synergistic effect was not seen in monkeys performing DNMS. These findings confirm a synergistic interaction in a macaque monkey model of episodic memory between connections carried by the fornix and cholinergic input to the inferotemporal cortex. They support the notion that the mnemonic functions tapped by scene learning and DNMS have dissociable neural substrates. Finally, cholinergic depletion of inferotemporal cortex, in this study, appears insufficient to impair memory functions dependent on an intact inferotemporal cortex.

Functional Organization of the Somatosensory Cortical Layer 6 Feedback to the Thalamus

Lam, Y.-W., Sherman, S. M. — Fri, 15 May 2009 05:46:56 PDT

The pathway from cortical layer 6 to the thalamus is a property of all thalamic relay nuclei. This pathway, as a population, directly excites relay cells and indirectly inhibits them via the thalamic reticular nucleus. To understand the circuit organization of this cortical feedback, we used laser-scanning photostimulation, which specifically activates somata or dendrites, to stimulate the primary somatosensory cortex in an in vitro thalamocortical slice preparation while recording from neurons of the ventral posterior medial nucleus. Layer 6 photostimulation evoked biphasic excitatory postsynaptic current/inhibitory postsynaptic current (EPSC/IPSC) responses in the neurons of the ventral posterior medial nucleus, indicating that such photostimulation strongly activates reticular cells. These disynaptic IPSCs were greatly suppressed or abolished by bath application of the muscarinic agonist acetyl-β-methylcholine. Our results suggest that the top-down modulation of thalamic neurons from cortical layer 6 involves an inhibitory component via the thalamic reticular nucleus, and this component can be selectively reduced by cholinergic input. Finally, we found the footprints for the excitatory corticothalamic and the inhibitory cortico-reticulo-thalamic inputs to be located in similar positions, though in some cases they are offset. Both patterns have implications for cortico-reticulo-thalamic circuitry.

Population-Based Corticospinal Interactions in Macaques Are Correlated with Visuomotor Processing

Asher, I., Zinger, N., Yanai, Y., Israel, Z., Prut, Y. — Thu, 14 May 2009 08:18:45 PDT

Visuomotor transformation is a fundamental process in executing voluntary actions. The final steps of this transformation are presumed to take place in the corticospinal (CS) system, yet the way in which the motor cortex (MC) interacts with spinal circuitry during this process is unclear. We studied neural correlates of visuomotor transformation in the MC and cervical spinal cord while monkeys performed an isometric wrist task. We recorded 2 measures of population activity: local field potential (LFP), reflecting local synaptic inputs and multi-unit activity (MUA), reflecting spiking activity emitted by nearby neurons. We found robust cortical and spinal responses locked to visual and motor events. In motor cortex, LFP responses were predominantly visually related; MUA responses were mostly motor related. Spinal LFP responses were generally weak, yet spinal MUAs showed visual and motor responses with distinctive patterns. For both structures, amplitudes of visual responses were positively correlated with amplitudes of motor responses and negatively correlated with reaction times. The temporal relations of cortical and spinal responses shifted from weak coactivation before movement to increased coupling following torque onset, with cortical leading spinal activity. Thus, ongoing CS interactions may exist at early stages of movement preparation. These interactions are dynamic and may shape the executed motor action.

The Truth about Lying: Inhibition of the Anterior Prefrontal Cortex Improves Deceptive Behavior

Thu, 14 May 2009 08:18:42 PDT

Recent neuroimaging studies have indicated a predominant role of the anterior prefrontal cortex (aPFC) in deception and moral cognition, yet the functional contribution of the aPFC to deceptive behavior remains unknown. We hypothesized that modulating the excitability of the aPFC by transcranial direct current stimulation (tDCS) could reveal its functional contribution in generating deceitful responses. Forty-four healthy volunteers participated in a thief role-play in which they were supposed to steal money and then to attend an interrogation with the Guilty Knowledge Test. During the interrogation, participants received cathodal, anodal, or sham tDCS. Remarkably, inhibition of the aPFC by cathodal tDCS did not lead to an impairment of deceptive behavior but rather to a significant improvement. This effect manifested in faster reaction times in telling lies, but not in telling the truth, a decrease in sympathetic skin-conductance response and feelings of guilt while deceiving the interrogator and a significantly higher lying quotient reflecting skillful lying. Increasing the excitability of the aPFC by anodal tDCS did not affect deceptive behavior, confirming the specificity of the stimulation polarity. These findings give causal support to recent correlative data obtained by functional magnetic resonance imaging studies indicating a pivotal role of the aPFC in deception.

Hedonic and Informational Functions of the Human Orbitofrontal Cortex

Elliott, R., Agnew, Z., Deakin, J.F.W. — Tue, 12 May 2009 15:14:09 PDT

Functional imaging studies have revealed roles for orbitofrontal cortex (OFC) in reward processing and decision making. In many situations, rewards signal that the current behavior should be maintained, whereas punishments cue a change in behavior. Thus, hedonic responses to reinforcers are conflated with their function as behavioral cues. In an attempt to disambiguate these functions, we performed a functional magnetic resonance imaging study of a 2-choice decision-making task. After each trial, subjects were rewarded or punished and independently provided with a cue to maintain or change behavior. We identified key regions of OFC involved in these processes. An anterior medial focus responded to reward, whereas bilateral lateral foci responded to punishment. The right-sided lateral region that responded to punishment also responded to cues for behavior change (shift), whereas a more ventral and anterior bilateral region responded to cues for behavioral maintenance (stay). The right-sided stay region responded specifically when stay cues were combined with punishment. These results support the view that OFC codes both hedonic responses to reinforcers and their behavioral consequences. Punishments and shift cues are associated with the same right lateral OFC focus, suggesting a fundamental connection between emotive response to negative reinforcement and use of negative information to cue behavioral change.

Functional Neuroanatomy of Mirroring during a Unimanual Force Generation Task

Sehm, B., Perez, M.A., Xu, B., Hidler, J., Cohen, L.G. — Mon, 11 May 2009 19:00:38 PDT

Performance of a unimanual motor task often induces involuntary mirror electromyographic (EMG) activity in the opposite, resting hand. In spite of the ubiquitous presence of mirroring, little is known regarding the underlying cortical contributions. Here, we used functional magnetic resonance imaging (fMRI) to study brain regions activated in association with parametric increases in right isometric wrist flexion force (10%, 20%, 30%, and 70%) in 12 healthy volunteers. During scanning, EMG activity was recorded bilaterally from flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BB), and triceps brachii (TB). Mirror EMG was observed in left FCR during 20%, 30%, and 70% of force. Left ECR, BB, and TB showed mirror EMG only at 70% of force. Increasing force was associated with a linear increase of blood-oxygen-level–dependent (BOLD) signal in bilateral primary motor cortex (M1), supplementary motor area (SMA), caudal cingulate, and cerebellum. Mirroring in the left FCR correlated with activity in bilateral M1, SMA, and the cerebellum. Overall, our results suggest that activity in these regions might reflect sensorimotor processes operating in association with mirroring and suggest caution when interpreting fMRI activity in studies that involve unilateral force generation tasks in the absence of simultaneous bilateral EMG/kinematics measurements.

Mapping Surface Variability of the Central Sulcus in Musicians

Mon, 11 May 2009 12:42:51 PDT

We employed a sulcal geometry–based approach to investigate the morphology of the central sulcus (CS) in musicians (pianists). The anterior and posterior walls of the CS were first manually outlined from high-resolution magnetic resonance (MR) images of 41 right-handed subjects (20 musicians and 21 controls), followed by a surface reconstruction and parameterization procedure to ensure the anatomical correspondence of surface locations across subjects. The intrasulcal length, surface area, and local variability of the CS were measured. There were no significant differences in either the intrasulcal length or surface area of the anterior or posterior walls between the 2 groups. However, we observed that the controls had a pronounced left-larger-than-right asymmetry that was reduced in the musicians. Importantly, we found that the musicians showed greater local variability in the middle section (i.e., somatotopic hand area) of the right CS and the lower section of the left CS as compared with the controls. Further analysis revealed significantly negative correlations between the variability of the middle section of the right CS and the age of commencement of musical training. Our findings suggest that the musicians might be associated with plastic changes in the 3D morphology of the CS in response to long-term motor skill training.

Interacting Outcome Retrieval, Anticipation, and Feedback Processes in the Human Brain

Walsh, N. D., Phillips, M. L. — Fri, 08 May 2009 13:30:23 PDT

Cognitive control is an inherently multivariate phenomenon, and its neural basis is currently unclear. Here we examined using functional magnetic resonance imaging how participants retrieve prelearnt information from memory, use this information to guide responses for an impending decision, and adjust their responses based on outcome feedback. We developed a behavioral task designed to manipulate memory outcome–retrieval load, outcome-anticipation interval, and outcome-feedback processes. This allowed us to understand the neural basis of these cognitive processes in isolation and how they interact. Extending previous work, we found a retrieval-load by outcome-feedback interaction in the left globus pallidus; an outcome-feedback by anticipation-interval interaction in the inferior prefrontal cortex; a retrieval-load by anticipation-interval interaction in the midcingulate gyrus and a load by interval by outcome interaction in the right frontal pole. These results further advance our knowledge of how fundamental cognitive processes interact physiologically to give rise to higher-level behavioral control.

Neural Signatures of Stimulus Features in Visual Working Memory--A Spatiotemporal Approach

Fri, 08 May 2009 13:30:22 PDT

We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal "what/where" segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams.

Number Processing Pathways in Human Parietal Cortex

Santens, S., Roggeman, C., Fias, W., Verguts, T. — Fri, 08 May 2009 13:30:21 PDT

Numerous studies have identified the intraparietal sulcus (IPS) as an area critically involved in numerical processing. IPS neurons in macaques are tuned to a preferred numerosity, hence neurally coding numerosity in a number-selective way. Neuroimaging studies in humans have demonstrated number-selective processing in the anterior parts of the IPS. Nevertheless, the processes that convert visual input into a number-selective neural code remain unknown. Computational studies have suggested that a neural coding stage that is sensitive, but not selective to number, precedes number-selective coding when processing nonsymbolic quantities but not when processing symbolic quantities. In Experiment 1, we used functional magnetic resonance imaging to localize number-sensitive areas in the human brain by searching for areas exhibiting increasing activation with increasing number, carefully controlling for nonnumerical parameters. An area in posterior superior parietal cortex was identified as a substrate for the intermediate number-sensitive steps required for processing nonsymbolic quantities. In Experiment 2, the interpretation of Experiment 1 was confirmed with a connectivity analysis showing that a shared number-selective representation in IPS is reached through different pathways for symbolic versus nonsymbolic quantities. The preferred pathway for processing nonsymbolic quantities included the number-sensitive area in superior parietal cortex, whereas the pathway for processing symbolic quantities did not.

Function-based Intersubject Alignment of Human Cortical Anatomy

Wed, 06 May 2009 10:13:03 PDT

Making conclusions about the functional neuroanatomical organization of the human brain requires methods for relating the functional anatomy of an individual's brain to population variability. We have developed a method for aligning the functional neuroanatomy of individual brains based on the patterns of neural activity that are elicited by viewing a movie. Instead of basing alignment on functionally defined areas, whose location is defined as the center of mass or the local maximum response, the alignment is based on patterns of response as they are distributed spatially both within and across cortical areas. The method is implemented in the two-dimensional manifold of an inflated, spherical cortical surface. The method, although developed using movie data, generalizes successfully to data obtained with another cognitive activation paradigm—viewing static images of objects and faces—and improves group statistics in that experiment as measured by a standard general linear model (GLM) analysis.

Cortical Connections of the Macaque Caudal Ventrolateral Prefrontal Areas 45A and 45B

Gerbella, M., Belmalih, A., Borra, E., Rozzi, S., Luppino, G. — Thu, 30 Apr 2009 05:35:58 PDT

We have found that the 2 architectonic subdivisions of the prefrontal area 45, 45A and 45B, display connectivity patterns that clearly distinguish them from one another and from their neighboring architectonic areas. Area 45A is primarily connected to the frontal areas 45B, 12l, caudal 12r, 12o, 10, rostrodorsal 46, 9/8B, 44, 8/FEF (frontal eye field), and the SEF (supplementary eye field), temporal area IPa, and unique among all the studied areas, to the superior temporal polysensory (STP) area and auditory parabelt areas. Area 45B displayed much stronger frontal connections with the oculomotor areas 8/FEF, 8r, and the SEF than those of area 45A, primary connections with areas 12l, caudal 12r, 12o, and 8B, and unlike area 45A, with areas ventrorostral 46, rostral 12r, 12m, and 13m. Temporal connections were all virtually confined to areas IPa, intermediate TEa/m, and TE. Additional labeling was found in lateral intraparietal area. Our data suggest that 45A and 45B are 2 distinct areas, possibly playing a differential role in nonspatial information processing: area 45A corresponds to the prefrontal sector for which a role in communication behavior and homology with the human area 45 was proposed, whereas area 45B is a distinct prearcuate area, possibly affiliated to the oculomotor frontal system.

Structural Connectivity for Visuospatial Attention: Significance of Ventral Pathways

Thu, 30 Apr 2009 05:35:56 PDT

In the present study, we identified the most probable trajectories of point-to-point segregated connections between functional attentional centers using a combination of functional magnetic resonance imaging and a novel diffusion tensor imaging–based algorithm for pathway extraction. Cortical regions activated by a visuospatial attention task were subsequently used as seeds for probabilistic fiber tracking in 26 healthy subjects. Combining probability maps of frontal and temporoparietal regions yielded a network that consisted of dorsal and ventral connections. The dorsal connections linked temporoparietal cortex with the frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling along superior longitudinal and arcuate fascicles, these fibers are well described in relation to spatial attention. However, the ventral connections, which traveled in the white matter between insula (INS) cortex and putamen parallel to the sylvian fissure, were not previously described for visuospatial attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG, these connections may provide an anatomical substrate for crossmodal cortical integration needed for stimulus perception and response in relation to current intention. The newly anatomically described integral network for visuospatial attention might improve the understanding of spatial attention deficits after white matter lesions.

What Motivates the Adolescent? Brain Regions Mediating Reward Sensitivity across Adolescence

Thu, 30 Apr 2009 05:35:56 PDT

The relation between brain development across adolescence and adolescent risky behavior has attracted increasing interest in recent years. It has been proposed that adolescents are hypersensitive to reward because of an imbalance in the developmental pattern followed by the striatum and prefrontal cortex. To date, it is unclear if adolescents engage in risky behavior because they overestimate potential rewards or respond more to received rewards and whether these effects occur in the absence of decisions. In this study, we used a functional magnetic resonance imaging paradigm that allowed us to dissociate effects of the anticipation, receipt, and omission of reward in 10- to 12-year-old, 14- to 15-year-old, and 18- to 23-year-old participants. We show that in anticipation of uncertain outcomes, the anterior insula is more active in adolescents compared with young adults and that the ventral striatum shows a reward-related peak in middle adolescence, whereas young adults show orbitofrontal cortex activation to omitted reward. These regions show distinct developmental trajectories. This study supports the hypothesis that adolescents are hypersensitive to reward and adds to the current literature in demonstrating that neural activation differs in adolescents even for small rewards in the absence of choice. These findings may have important implications for understanding adolescent risk-taking behavior.

Dual Mechanisms for the Cross-Sensory Spread of Attention: How Much Do Learned Associations Matter?

Fiebelkorn, I. C., Foxe, J. J., Molholm, S. — Fri, 24 Apr 2009 08:28:15 PDT

The spread of attention-related processing across anatomically separated cortical regions plays an important role in the binding of an object's features, both within and across sensory modalities. We presented multiple exemplars of semantically congruent multisensory objects (e.g., dogs with barks) and semantically incongruent multisensory objects (e.g., guitars with barks) while recording high-density event-related potentials and tested whether highly learned associations among the multisensory features of well-known objects modulated the spread of attention from an attended visual stimulus to its paired, task-irrelevant sound. Our findings distinguish dual mechanisms for the cross-sensory spread of attention: 1) a stimulus-driven spread of attention that occurs whenever a task-irrelevant sound is simultaneously presented with an attended visual stimulus, independent of highly learned associations, and 2) a representation-driven spread of attention that occurs in response to a task-irrelevant sound that is semantically congruent with a visual target and is therefore dependent on highly learned associations. The first mechanism is thought to reflect bottom-up feature binding, whereas the second mechanism is thought to reflect the top-down activation of a stored object representation that includes the well-known object's multisensory features. When a semantically congruent, task-irrelevant sound is simultaneously presented with a well-known visual target, the combined spread of attention through both mechanisms appears additive.

Connections of Auditory and Visual Cortex in the Prairie Vole (Microtus ochrogaster): Evidence for Multisensory Processing in Primary Sensory Areas

Campi, K. L., Bales, K. L., Grunewald, R., Krubitzer, L. — Fri, 24 Apr 2009 08:28:14 PDT

In prairie voles, primary sensory areas are dominated by neurons that respond to one sensory modality, but some neurons also respond to stimulation of other modalities. To reveal the anatomical substrate for these multimodal responses, we examined the connections of the primary auditory area + the anterior auditory field (A1 + AAF), the temporal anterior area (TA), and the primary visual area (V1). A1 + AAF had intrinsic connections and connections with TA, multimodal cortex (MM), V1, and primary somatosensory area (S1). TA had intrinsic connections and connections with A1 + AAF, MM, and V2. Callosal connections were observed in homotopic locations in auditory cortex for both fields. A1 + AAF and TA receive thalamic input primarily from divisions of the medial geniculate nucleus but also from the lateral geniculate nucleus (LGd), the lateral posterior nucleus, and the ventral posterior nucleus (VP). V1 had dense intrinsic connections and connections with V2, MM, auditory cortex, pyriform cortex (Pyr), and, in some cases, somatosensory cortex. V1 had interhemispheric connections with V1, V2, MM, S1, and Pyr and received thalamic input from LGd and VP. Our results indicate that multisensory integration occurs in primary sensory areas of the prairie vole cortex, and this may be related to behavioral specializations associated with its niche.

An fMRI Study of Functional Abnormalities in the Verbal Working Memory System and the Relationship to Clinical Symptoms in Chronic Schizophrenia

Hashimoto, R.-i., Lee, K., Preus, A., McCarley, R. W., Wible, C. G. — Fri, 24 Apr 2009 08:28:12 PDT

There has been evidence for functional abnormalities of the verbal working memory system in schizophrenia. Verbal working memory crucially involves the interplay between the anterior and posterior language systems, and previous studies have shown converging evidence for abnormalities in the posterior language system in schizophrenia. In this functional magnetic resonance imaging study, we measured cortical activity in chronic schizophrenic patients and matched healthy controls during auditory and visual verbal working memory tasks. We employed 1) regional analyses specifically targeting the posterior language system and 2) analyses of functional connectivity between anterior and posterior language regions. We performed these analyses separately for each memory stage and modality. In the regional analyses, the left sylvian–parietal–temporal (Spt) area consistently showed reduced activation during encoding and retrieval stages in schizophrenia. Magnitudes of activation in the left posterior superior temporal sulcus were correlated with the severity of delusions at every memory stage. Functional connectivity analyses revealed reduced connectivity between the left Spt and the anterior insula during the encoding of auditory words. In addition, the connectivity strength was correlated with the severity of auditory hallucinations. These findings identify abnormal components in the verbal working memory system and illustrate their possible overlap with the mechanisms of core schizophrenic symptoms.

Quantifying the Adequacy of Neural Representations for a Cross-Language Phonetic Discrimination Task: Prediction of Individual Differences

Raizada, R. D. S., Tsao, F.-M., Liu, H.-M., Kuhl, P. K. — Wed, 22 Apr 2009 12:45:32 PDT

In order for stimuli to be perceptually discriminable, their representations in the brain must be distinct. Investigating the task of discriminating the syllables /ra/ and /la/, we hypothesized that the more distinct a person's neural representations of those sounds were, the better their behavioral ability to discriminate them would be. Standard neuroimaging approaches are ill-suited to testing this hypothesis as they have problems differentiating between neural representations spatially intermingled within the same brain area. We therefore performed multi-voxel pattern-based analysis of the functional magnetic resonance imaging (fMRI) activity elicited by these syllables, in native speakers of English and Japanese. In right primary auditory cortex, the statistical separability of these fMRI patterns predicted subjects’ behavioral ability to tell the sounds apart, not only across groups but also across individuals. This opens up a new approach for identifying neural representations and for quantifying their task suitability.

Connecting Long Distance: Semantic Distance in Analogical Reasoning Modulates Frontopolar Cortex Activity

Green, A. E., Kraemer, D. J. M., Fugelsang, J. A., Gray, J. R., Dunbar, K. N. — Tue, 21 Apr 2009 12:14:57 PDT

Solving problems often requires seeing new connections between concepts or events that seemed unrelated at first. Innovative solutions of this kind depend on analogical reasoning, a relational reasoning process that involves mapping similarities between concepts. Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key characteristic of the kind of analogical mapping that can support innovation (i.e., identifying similarities across greater semantic distance reveals connections that support more innovative solutions and models). However, the neural substrates of semantically distant analogical mapping are not well understood. Here, we used functional magnetic resonance imaging (fMRI) to measure brain activity during an analogical reasoning task, in which we parametrically varied the semantic distance between the items in the analogies. Semantic distance was derived quantitatively from latent semantic analysis. Across 23 participants, activity in an a priori region of interest (ROI) in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. This ROI was centered on a functional peak that we previously associated with analogical mapping. To our knowledge, these data represent a first empirical characterization of how the brain mediates semantically distant analogical mapping.