Cerebral Cortex - recent issues

Cover

Fri, 06 Nov 2009 17:37:06 PST

Associate Editors

Fri, 06 Nov 2009 17:37:06 PST

Subscriptions

Fri, 06 Nov 2009 17:37:06 PST

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Binder, J. R., Desai, R. H., Graves, W. W., Conant, L. L. — Fri, 06 Nov 2009 17:37:06 PST

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

Sex Differences in Resting-State Neural Correlates of Openness to Experience among Older Adults

Sutin, A. R., Beason-Held, L. L., Resnick, S. M., Costa, P. T. — Fri, 06 Nov 2009 17:37:07 PST

We investigated sex differences in the resting-state neural correlates of Openness to Experience, a universal personality trait defined by cognitive flexibility, attention to feelings, creativity, and preference for novelty. Using resting-state positron-emission tomography from 100 older individuals (>55 years of age), we identified associations between Openness and resting-state regional cerebral blood flow that replicated across 2 assessments of the same sample, approximately 2 years apart. Openness correlated positively with prefrontal activity in women, anterior cingulate activity in men, and orbitofrontal activity in both sexes, which suggests that areas linked to cognitive flexibility (women), monitoring processes (men), and reward and emotional processing (both) underlie individual differences in Openness. The results challenge the implicit assumption that the same trait will rely on the same neural mechanisms across all who express it.

Not What You Expect: Experience but not Expectancy Predicts Conditioned Responses in Human Visual and Supplementary Cortex

Moratti, S., Keil, A. — Fri, 06 Nov 2009 17:37:07 PST

When paired with aversive events, visual conditioned stimuli (CS) provoke increased activations in visual cortex. It is unclear however whether these changes reflect cognitive processes such as expectancy of the aversive unconditioned stimulus (US), or implicit associative learning of the contingencies outside awareness. Here, we used the "gambler's fallacy" phenomenon to parametrically and inversely manipulate the expectancy of an US and the number of conditioning trials: Increasing the number of CS–US pairings was associated with participants expecting the US to be less likely and vice versa. Magnetocortical activity evoked by the CS in occipital and supplementary motor areas was linearly related to the associative strength (number of CS–US pairings), but decreased as a function of expectancy. These results suggest that the cortical facilitation of fear cue processing is determined by associative strength and previous exposure to learning contingencies rather than by the cognitive anticipation for the US.

Differences in Intrinsic Properties and Local Network Connectivity of Identified Layer 5 and Layer 6 Adult Mouse Auditory Corticothalamic Neurons Support a Dual Corticothalamic Projection Hypothesis

Llano, D. A., Sherman, S. M. — Fri, 06 Nov 2009 17:37:07 PST

Intrinsic properties, morphology, and local network circuitry of identified layer 5 and layer 6 auditory corticothalamic neurons were compared. We injected fluorescent microspheres into the mouse auditory thalamus to prelabel corticothalamic neurons, then recorded and filled labeled layer 5 or layer 6 auditory cortical neurons in vitro. We observed low-threshold bursting in adult, but not juvenile, layer 5 corticothalamic neurons that was voltage and time dependent with nonlinear input–output properties, whereas adult layer 6 corticothalamic neurons demonstrated a regular spiking. Layer 5 corticothalamic neurons had larger somata, thicker apical dendrites and were more likely to have a layer 1 apical dendrite than layer 6 neurons. Using laser photostimulation, identified layer 5 corticothalamic neurons received excitatory input from a wide area of layers 2/3, 4, and 5 with widespread -aminobutyric acidergic input from layer 2/3 and lower layer 5, whereas layer 6 corticothalamic neurons from the same cortical column received circumscribed excitatory input and discrete patches of inhibition derived from layer 6 of adjacent columns. These data demonstrate that layer 5 and layer 6 corticothalamic neurons receive unique sets of inputs and process them in different manners, supporting the hypothesis that layer-specific corticothalamic projections play distinct roles in information processing.

Locus Coeruleus Activation Facilitates Memory Encoding and Induces Hippocampal LTD that Depends on {beta}-Adrenergic Receptor Activation

Lemon, N., Aydin-Abidin, S., Funke, K., Manahan-Vaughan, D. — Fri, 06 Nov 2009 17:37:07 PST

Spatial memory formation is enabled through synaptic information processing, in the form of persistent strengthening and weakening of synapses, within the hippocampus. It is, however, unclear how relevant spatial information is selected for encoding, in preference to less pertinent information. As the noradrenergic locus coeruleus (LC) becomes active in response to novel experiences, we hypothesized that the LC may provide the saliency signal required to promote hippocampal encoding of relevant information through changes in synaptic strength. Test pulse stimulation evoked stable basal synaptic transmission at Schaffer collateral (SC)–CA1 stratum radiatum synapses in freely behaving adult rats. Coupling of these test pulses with electrical stimulation of the LC induced long-term depression (LTD) at SC–CA1 synapses and induced a transient suppression of theta-frequency oscillations. Effects were N-methyl-D-aspartate and β-adrenergic receptor dependent. Activation of the LC also increased CA1 noradrenalin levels and facilitated the encoding of spatial memory for a single episode via a β-adrenoceptor–dependent mechanism. Our results demonstrate that the LC plays a key role in the induction of hippocampal LTD and in promoting the encoding of spatial information. This LC–hippocampal interaction may reflect a means by which salient information is distinguished for subsequent synaptic processing.

In Vivo MRI of Altered Brain Anatomy and Fiber Connectivity in Adult Pax6 Deficient Mice

Fri, 06 Nov 2009 17:37:07 PST

The impact of developmental ablation of Pax6 function on morphology and functional connectivity of the adult cerebrum was studied in cortex-specific Pax6 knockout mice (Pax6cKO) using structural magnetic resonance imaging (MRI), manganese-enhanced MRI, and diffusion tensor MRI in conjunction with fiber tractography. Mutants presented with decreased volumes of total brain and olfactory bulb, reduced cortical thickness, and altered layering of the piriform cortex. Tracking of major neuronal fiber bundles revealed a disorganization of callosal fibers with an almost complete lack of interhemispheric connectivity. In Pax6cKO mice intrahemispheric callosal fibers as well as intracortical fibers were predominantly directed along a rostrocaudal orientation instead of a left–right and dorsoventral orientation found in controls. Fiber disorganization also involved the septohippocampal connection targeting mostly the lateral septal nucleus. The hippocampus was rostrally extended and its volume was increased relative to that of the forebrain and midbrain. Manganese-induced MRI signal enhancement in the CA3 region suggested a normal function of hippocampal pyramidal cells. Noteworthy, several morphologic disturbances in gray and white matter of Pax6cKO mice were similar to observations in human aniridia patients. The present findings indicate an important role of Pax6 in the development of both the cortex and cerebral fiber connectivity.

Cortical Mechanisms for Online Control of Hand Movement Trajectory: The Role of the Posterior Parietal Cortex

Archambault, P. S., Caminiti, R., Battaglia-Mayer, A. — Fri, 06 Nov 2009 17:37:07 PST

The parietal mechanisms for the control of hand movement trajectory were studied by recording cell activity in area 5 of monkeys making direct reaches to visual targets and online corrections of movement trajectory, after change of target location in space. The activity of hand-related cells was fitted with a linear model including hand position, movement direction, and speed. The neural activity modulation mostly led, but also followed, hand movement. When a change of hand trajectory occurred, the pattern of activity associated with the movement to the first target evolved into that typical of the movement to the second one, thus following the corresponding variations of the hand kinematics. The visual signal concerning target location in space did not influence the firing activity associated with the direction of hand movement within the first 150 ms after target presentation. This might be the time necessary for the visuo-motor transformation underlying reaching. We conclude that online control of hand trajectory not only resides in the relationships between neural activity and kinematics, but, under specific circumstances, also on the coexistence of signals about ongoing and future hand movement direction.

Paraneoplastic Antigen-Like 5 Gene (PNMA5) Is Preferentially Expressed in the Association Areas in a Primate Specific Manner

Takaji, M., Komatsu, Y., Watakabe, A., Hashikawa, T., Yamamori, T. — Fri, 06 Nov 2009 17:37:07 PST

To understand the relationship between the structure and function of primate neocortical areas at a molecular level, we have been screening for genes differentially expressed across macaque neocortical areas by restriction landmark cDNA scanning (RLCS). Here, we report enriched expression of the paraneoplastic antigen-like 5 gene (PNMA5) in association areas but not in primary sensory areas, with the lowest expression level in primary visual cortex. In situ hybridization in the primary sensory areas revealed PNMA5 mRNA expression restricted to layer II. Along the ventral visual pathway, the expression gradually increased in the excitatory neurons from the primary to higher visual areas. This differential expression pattern was very similar to that of retinol-binding protein (RBP) mRNA, another association-area-enriched gene that we reported previously. Additional expression analysis for comparison of other genes in the PNMA gene family, PNMA1, PNMA2, PNMA3, and MOAP1 (PNMA4), showed that they were widely expressed across areas and layers but without the differentiated pattern of PNMA5. In mouse brains, PNMA1 was only faintly expressed and PNMA5 was not detected. Sequence analysis showed divergence of PNMA5 sequences among mammals. These findings suggest that PNMA5 acquired a certain specialized role in the association areas of the neocortex during primate evolution.

Too Little, Too Late: Reduced Visual Span and Speed Characterize Pure Alexia

Starrfelt, R., Habekost, T., Leff, A. P. — Fri, 06 Nov 2009 17:37:07 PST

Whether normal word reading includes a stage of visual processing selectively dedicated to word or letter recognition is highly debated. Characterizing pure alexia, a seemingly selective disorder of reading, has been central to this debate. Two main theories claim either that 1) Pure alexia is caused by damage to a reading specific brain region in the left fusiform gyrus or 2) Pure alexia results from a general visual impairment that may particularly affect simultaneous processing of multiple items. We tested these competing theories in 4 patients with pure alexia using sensitive psychophysical measures and mathematical modeling. Recognition of single letters and digits in the central visual field was impaired in all patients. Visual apprehension span was also reduced for both letters and digits in all patients. The only cortical region lesioned across all 4 patients was the left fusiform gyrus, indicating that this region subserves a function broader than letter or word identification. We suggest that a seemingly pure disorder of reading can arise due to a general reduction of visual speed and span, and explain why this has a disproportionate impact on word reading while recognition of other visual stimuli are less obviously affected.

Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment

Fri, 06 Nov 2009 17:37:07 PST

Preterm birth results in significant neurodevelopmental disability. A neonatal rodent model of chronic sublethal hypoxia (CSH), which mimics effects of preterm birth, was used to characterize neurodevelopmental consequences of prolonged exposure to hypoxia using tissue anisotropy measurements from diffusion tensor imaging. Corpus callosum, cingulum, and fimbria of the hippocampus revealed subtle, yet significant, hypoxia-induced modifications during maturation (P15–P51). Anisotropy differences between control and CSH mice were greatest at older ages (>P40) in these regions. Neither somatosensory cortex nor caudate putamen revealed significant differences between control and CSH mice at any age. We assessed control and CSH mice using tests of general activity and cognition for behavioral correlates of morphological changes. Open-field task revealed greater locomotor activity in CSH mice early in maturation (P16–P18), whereas by adolescence (P40–P45) differences between control and CSH mice were insignificant. These results may be associated with lack of cortical and subcortical anisotropy differences between control and CSH mice. Spatial-delayed alternation and free-swim tasks in adulthood revealed lasting impairments for CSH mice in spatial memory and behavioral laterality. These differences may correlate with anisotropy decreases in hippocampal and callosal connectivities of CSH mice. Thus, CSH mice revealed developmental and behavioral deficits that are similar to those observed in low birth weight preterm infants.

Axon Morphologies and Convergence Patterns of Projections from Different Sensory-Specific Cortices of the Anterior Ectosylvian Sulcus onto Multisensory Neurons in the Cat Superior Colliculus

Fuentes-Santamaria, V., Alvarado, J. C., McHaffie, J. G., Stein, B. E. — Fri, 06 Nov 2009 17:37:07 PST

Corticofugal projections to the thalamus reveal 2 axonal morphologies, each associated with specific physiological attributes. These determine the functional characteristics of thalamic neurons. It is not clear, however, whether such features characterize the corticofugal projections that mediate multisensory integration in superior colliculus (SC) neurons. The cortico-collicular projections from cat anterior ectosylvian sulcus (AES) are derived from its visual, auditory, and somatosensory representations and are critical for multisensory integration. Following tracer injections into each subdivision, 2 types of cortico-collicular axons were observed. Most were categorized as type I and consisted of small-caliber axons traversing long distances without branching, bearing mainly small boutons. The less frequent type II had thicker axons, more complex branching patterns, larger boutons, and more complex terminal boutons. Following combinatorial injections of 2 different fluorescent tracers into defined AES subdivisions, fibers from each were seen converging onto individual SC neurons and indicate that such convergence, like that in the corticothalamic system, is mediated by 2 distinct morphological types of axon terminals. Nevertheless, and despite the conservation of axonal morphologies across different subcortical systems, it is not yet clear if the concomitant physiological attributes described in the thalamus are directly applicable to multisensory integration.

Regional Patterns of Cerebral Cortical Differentiation Determined by Diffusion Tensor MRI

Kroenke, C. D., Taber, E. N., Leigland, L. A., Knutsen, A. K., Bayly, P. V. — Fri, 06 Nov 2009 17:37:07 PST

The morphology of axonal and dendritic arbors in the immature cerebral cortex influences the degree of anisotropy in water diffusion. This enables cortical maturation to be monitored by the noninvasive technique of diffusion tensor magnetic resonance imaging (DTI). Herein, we utilized DTI of postmortem ferret brain to quantify regional and temporal patterns in cortical maturation. We found that diffusion anisotropy within the isocortex decreases over the first month of life, coinciding closely in time with expansion of axonal and dendritic cellular processes of pyramidal neurons. Regional patterns consist of differences between allocortex and isocortex, a regional anisotropy gradient that closely parallels the transverse neurogenetic gradient, and differences between primary and nonprimary isocortical areas. By combining the temporal and regional factors, the isocortical developmental gradient magnitude corresponds to a 5-day difference in maturity between relatively developed rostral/caudal isocortex at the gradient source and less mature isocortex at the occipital pole. Additionally, the developmental trajectory of primary areas precedes nonprimary areas by 2.7 days. These quantitative estimates coincide with previous histological studies of ferret development. Similarities in cerebral cortical diffusion anisotropy observed between ferret and other species suggest the framework developed here is of general potential relevance.

Functional Heterogeneity of Inferior Parietal Cortex during Mathematical Cognition Assessed with Cytoarchitectonic Probability Maps

Wu, S. S., Chang, T. T., Majid, A., Caspers, S., Eickhoff, S. B., Menon, V. — Fri, 06 Nov 2009 17:37:07 PST

Although the inferior parietal cortex (IPC) has been consistently implicated in mathematical cognition, the functional roles of its subdivisions are poorly understood. We address this problem using probabilistic cytoarchitectonic maps of IPC subdivisions intraparietal sulcus (IPS), angular gyrus (AG), and supramarginal gyrus. We quantified IPC responses relative to task difficulty and individual differences in task proficiency during mental arithmetic (MA) tasks performed with Arabic (MA-A) and Roman (MA-R) numerals. The 2 tasks showed similar levels of activation in 3 distinct IPS areas, hIP1, hIP2, and hIP3, suggesting their obligatory role in MA. Both AG areas, PGa and PGp, were strongly deactivated in both tasks, with stronger deactivations in posterior area PGp. Compared with the more difficult MA-R task, the MA-A task showed greater responses in both AG areas, but this effect was driven by less deactivation in the MA-A task. AG deactivations showed prominent overlap with lateral parietal nodes of the default mode network, suggesting a nonspecific role in MA. In both tasks, greater bilateral AG deactivation was associated with poorer performance. Our findings suggest a close link between IPC structure and function and they provide new evidence for behaviorally salient functional heterogeneity within the IPC during mathematical cognition.

The Brain Network Underlying Serial Visual Search: Comparing Overt and Covert Spatial Orienting, for Activations and for Effective Connectivity

Fairhall, S.L., Indovina, I., Driver, J., Macaluso, E. — Fri, 06 Nov 2009 17:37:07 PST

We used functional magnetic resonance imaging (fMRI) to investigate the brain basis of overt and covert forms of attention during search, while employing stringent control of both eye movements and attentional shifts. A factorial design compared overt and covert forms of goal-directed serial search versus stimulus-driven tracking. To match ocular changes and the number and magnitude of attention shifts across cells in the design, stimulus-driven tracking involved trial-specific "replay" of previous goal-directed eye movements. We found that, in terms of cortical activations, engagement of the dorsal fronto-parietal network by goal-directed attention did not depend on oculomotor requirements, being found similarly for covert attention, in accord with other work. However, analyses of effective connectivity (or "functional coupling") revealed that information flow within this network changed significantly as a function of both the task (goal-directed or stimulus-driven) and the overt versus covert form of attention. Additionally, we observed a distinct set of subcortical regions (pulvinar and caudate nucleus) engaged primarily during the covert form of goal-directed search. We conclude that dynamics within the dorsal fronto-parietal attentional system flexibly reorganize to integrate task demands and oculomotor requirements.

Double Dissociation of Spike Timing-Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex

Fri, 06 Nov 2009 17:37:07 PST

Spike timing–dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timing-dependent long-term potentiation (t-LTP) requires postsynaptic NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4-to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit–containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit–preferring antagonist blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead. These data demonstrate an NMDA receptor subunit-dependent double dissociation of t-LTD and t-LTP mechanisms at layer 4-to-layer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

Additive Effects of Attention and Stimulus Contrast in Primary Visual Cortex

Thiele, A., Pooresmaeili, A., Delicato, L. S., Herrero, J. L., Roelfsema, P. R. — Fri, 06 Nov 2009 17:37:07 PST

Previous studies have proposed a variety of mechanisms by which attention influences neuronal activity. Here we investigated the mechanisms of attention in the striate cortex of monkeys performing a spatial or an object-based attention task at various stimulus contrasts and compared neuronal contrast response functions with and without attention. Our data are best described by an "additive" interaction: The influence of attention on the neuronal response is relatively independent of the stimulus contrast, at least when the stimulus has enough contrast to become visible. This shows that attention adds to the neuronal responses in a largely contrast invariant manner. These data support recent functional magnetic resonance imaging studies and suggest that feedback from higher areas exerts a constant attentional drive that is mostly task not stimulus driven.

Analysis of c-fos and zif268 Expression Reveals Time-Dependent Changes in Activity Inside and Outside the Lesion Projection Zone in Adult Cat Area 17 after Retinal Lesions

Hu, T.-T., Laeremans, A., Eysel, U. T., Cnops, L., Arckens, L. — Fri, 06 Nov 2009 17:37:07 PST

Retinal lesions induce a topographic reorganization in the corresponding lesion projection zone (LPZ) in the visual cortex of adult cats. To gain a better insight into the reactivation dynamics, we investigated the alterations in cortical activity throughout area 17. We implemented in situ hybridization and real-time polymerase chain reaction to analyze the spatiotemporal expression patterns of the activity marker genes zif268 and c-fos. The immediate early gene (IEG) data confirmed a strong and permanent activity decrease in the center of the LPZ as previously described by electrophysiology. A recovery of IEG expression was clearly measured in the border of the LPZ. We were able to register reorganization over 2.5–6 mm. We also present evidence that the central retinal lesions concomitantly influence the activity in far peripheral parts of area 17. Its IEG expression levels appeared dependent of time and distance from the LPZ. We therefore propose that coupled changes in activity occur inside and outside the LPZ. In conclusion, alterations in activity reporter gene expression throughout area 17 contribute to the lesion-induced functional reorganization.

Integrating Visual and Tactile Information in the Perirhinal Cortex

Holdstock, J. S., Hocking, J., Notley, P., Devlin, J. T., Price, C. J. — Fri, 06 Nov 2009 17:37:07 PST

By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual–tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual–tactile) than unimodal (visual–visual or tactile–tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual–tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.

A Simple Rule for Axon Outgrowth and Synaptic Competition Generates Realistic Connection Lengths and Filling Fractions

Kaiser, M., Hilgetag, C. C., van Ooyen, A. — Fri, 06 Nov 2009 17:37:07 PST

Neural connectivity at the cellular and mesoscopic level appears very specific and is presumed to arise from highly specific developmental mechanisms. However, there are general shared features of connectivity in systems as different as the networks formed by individual neurons in Caenorhabditis elegans or in rat visual cortex and the mesoscopic circuitry of cortical areas in the mouse, macaque, and human brain. In all these systems, connection length distributions have very similar shapes, with an initial large peak and a long flat tail representing the admixture of long-distance connections to mostly short-distance connections. Furthermore, not all potentially possible synapses are formed, and only a fraction of axons (called filling fraction) establish synapses with spatially neighboring neurons. We explored what aspects of these connectivity patterns can be explained simply by random axonal outgrowth. We found that random axonal growth away from the soma can already reproduce the known distance distribution of connections. We also observed that experimentally observed filling fractions can be generated by competition for available space at the target neurons—a model markedly different from previous explanations. These findings may serve as a baseline model for the development of connectivity that can be further refined by more specific mechanisms.

GABAergic Inhibitory Interneurons in the Posterior Piriform Cortex of the GAD67-GFP Mouse

Young, A., Sun, Q.-Q. — Fri, 06 Nov 2009 17:37:07 PST

-Aminobutyric acid (GABA)–releasing inhibitory interneurons, a critical component of cortical circuitry, are involved in myriad known functional roles. However, information regarding the cytoarchitectural, physiological, and molecular properties of interneurons in posterior piriform cortex (PPC) is sparse. Taking advantage of the glutamic acid decarboxylase (GAD)67–enhanced green fluorescent protein (EGFP) mouse, we used in vitro whole-cell patch-clamp techniques to record from GABAergic interneurons across all 3 layers of PPC and, subsequently, to reconstruct their morphology. For the first time, 5 groups of interneurons are identified, whose firing types are defined based on those described within neocortex. Interestingly, each interneuron group with a distinct firing type also exhibits unique morphological properties, laminar distributions, and excitatory synaptic properties. The dendritic and axonal processes demonstrate subtype-specific orientations and a differential expression of spines and boutons, respectively. In addition, the active and passive electrophysiological properties of these cells show marked intergroup differences. Immunohistochemical techniques revealed a laminar-specific distribution of calcium-binding proteins and vasoactive intestinal peptide (VIP) expression. Surprisingly, excitatory synaptic properties in several groups lack target-specific differences seen in neocortical circuits, reflecting a circuit arranged with less complexity. These data aid in the identification of PPC interneurons and allow us to make well-supported postulations about their functional properties.

Erratum

Fri, 06 Nov 2009 17:37:07 PST

Medial Prefrontal Cortex 5-HT2A Density Is Correlated with Amygdala Reactivity, Response Habituation, and Functional Coupling

Wed, 07 Oct 2009 07:16:17 PDT

Feedback inhibition of the amygdala via medial prefrontal cortex (mPFC) is an important component in the regulation of complex emotional behaviors. The functional dynamics of this corticolimbic circuitry are, in part, modulated by serotonin (5-HT). Serotonin 2A (5-HT_2A) receptors within the mPFC represent a potential molecular mechanism through which 5-HT can modulate this corticolimbic circuitry. We employed a multimodal neuroimaging strategy to explore the relationship between threat-related amygdala reactivity, assessed using blood oxygen level–dependent functional magnetic resonance imaging, and mPFC 5-HT_2A density, assessed using [¹⁸F]altanserin positron emission tomography in 35 healthy adult volunteers. We observed a significant inverse relationship wherein greater mPFC 5-HT_2A density was associated with reduced threat-related right amygdala reactivity. Remarkably, 25–37% of the variability in amygdala reactivity was explained by mPFC 5-HT_2A density. We also observed a positive correlation between mPFC 5-HT_2A density and the magnitude of right amygdala habituation. Furthermore, functional coupling between the amygdala and mPFC was positively correlated with 5-HT_2A density suggesting that effective integration of emotionally salient information within this corticolimbic circuitry may be modulated, at least in part, by mPFC 5-HT_2A. Collectively, our results indicate that mPFC 5-HT_2A is strongly associated with threat-related amygdala reactivity as well as its temporal habituation and functional coupling with prefrontal regulatory regions.

Priming and Backward Influences in the Human Brain: Processing Interactions during the Stroop Interference Effect

Appelbaum, L. G., Meyerhoff, K. L., Woldorff, M. G. — Wed, 07 Oct 2009 07:16:17 PDT

This study investigated neural processing interactions during Stroop interference by varying the temporal separation of relevant and irrelevant features of congruent, neutral, and incongruent colored-bar/color-word stimulus components. High-density event-related potentials (ERPs) and behavioral performance were measured as participants reported the bar color as quickly as possible, while ignoring the color words. The task-irrelevant color words could appear at 1 of 5 stimulus onset asynchronies (SOAs) relative to the task-relevant bar-color occurrence: –200 or –100 ms before, +100 or +200 ms after, or simultaneously. Incongruent relative to congruent presentations elicited slower reaction times and higher error rates (with neutral in between), and ERP difference waves containing both an early, negative-polarity, central-parietal deflection, and a later, more left-sided, positive-polarity component. These congruency-related differences interacted with SOA, showing the greatest behavioral and electrophysiological effects when irrelevant stimulus information preceded the task-relevant target and reduced effects when the irrelevant information followed the relevant target. We interpret these data as reflecting 2 separate processes: 1) a ‘priming influence’ that enhances the magnitude of conflict-related facilitation and conflict-related interference when a task-relevant target is preceded by an irrelevant distractor; and 2) a reduced ‘backward influence’ of stimulus conflict when the irrelevant distractor information follows the task-relevant target.

Detection of Fixed and Variable Targets in the Monkey Prefrontal Cortex

Kusunoki, M., Sigala, N., Gaffan, D., Duncan, J. — Wed, 07 Oct 2009 07:16:17 PDT

Behavioral significance is commonly coded by prefrontal neurons. The significance of a stimulus can be fixed through experience; in complex behavior, however, significance commonly changes with short-term context. To compare these cases, we trained monkeys in 2 versions of visual target detection. In both tasks, animals monitored a series of pictures, making a go response (saccade) at the offset of a specified target picture. In one version, based on "consistent mapping" in human visual search, target and nontarget pictures were fixed throughout training. In the other, based on "varied mapping," a cue at trial onset defined a new target. Building up over the first 1 s following this cue, many cells coded short-term context (cue/target identity) for the current trial. Thereafter, the cell population showed similar coding of behavioral significance in the 2 tasks, with selective early response to targets, and later, sustained activity coding target or nontarget until response. This population similarity was seen despite quite different activity in the 2 tasks for many single cells. At the population level, the results suggest similar prefrontal coding of fixed and short-term behavioral significance.

Inhibition of cAMP Response Element-Binding Protein Reduces Neuronal Excitability and Plasticity, and Triggers Neurodegeneration

Jancic, D., Lopez de Armentia, M., Valor, L. M., Olivares, R., Barco, A. — Wed, 07 Oct 2009 07:16:18 PDT

The cAMP-responsive element-binding protein (CREB) pathway has been involved in 2 major cascades of gene expression regulating neuronal function. The first one presents CREB as a critical component of the molecular switch that controls long-lasting forms of neuronal plasticity and learning. The second one relates CREB to neuronal survival and protection. To investigate the role of CREB-dependent gene expression in neuronal plasticity and survival in vivo, we generated bitransgenic mice expressing A-CREB, an artificial peptide with strong and broad inhibitory effect on the CREB family, in forebrain neurons in a regulatable manner. The expression of A-CREB in hippocampal neurons impaired L-LTP, reduced intrinsic excitability and the susceptibility to induced seizures, and altered both basal and activity-driven gene expression. In the long-term, the chronic inhibition of CREB function caused severe loss of neurons in the CA1 subfield as well as in other brain regions. Our experiments confirmed previous findings in CREB-deficient mutants and revealed new aspects of CREB-dependent gene expression in the hippocampus supporting a dual role for CREB-dependent gene expression regulating intrinsic and synaptic plasticity and promoting neuronal survival.

The Influence of Multiple Primes on Bottom-Up and Top-Down Regulation during Meaning Retrieval: Evidence for 2 Distinct Neural Networks

Whitney, C., Grossman, M., Kircher, T. T. J. — Wed, 07 Oct 2009 07:16:18 PDT

Meaning retrieval of a word can proceed fast and effortlessly or can be characterized by a controlled search for candidate lexical items and a subsequent selection process. In the current study, we facilitated meaning retrieval by increasing the number of words that were related to the final target word in a triplet (e.g., lion–stripes–tiger). To induce higher search and selection demands, we presented ambiguous words as targets (i.e., homonyms like ball) in half of the trials. Hereby, the dominant (game), low-frequent (dance), or both meanings of the homonym were primed. Participants performed a relatedness judgment during functional magnetic resonance imaging. Activation in a bilateral network (angular gyrus, rostromedial prefrontal cortex) increased linearly with multiple related primes, whereas the posterior left inferior prefrontal cortex (pLIPC) showed the reverse activation pattern for unambiguous trials. When homonyms served as targets, pLIPC responded strongest when both meanings or low-frequent concepts were addressed. Additional anterior left inferior prefrontal cortex activation was observed for the latter trials only. The data support an interaction between 2 distinct cerebral networks that can be linked to automatic bottom-up support and top-down control during meaning retrieval. They further imply a functional specialization of the LIPC along an anterior–posterior dimension.

Greater Working Memory Load Results in Greater Medial Temporal Activity at Retrieval

Schon, K., Quiroz, Y. T., Hasselmo, M. E., Stern, C. E. — Wed, 07 Oct 2009 07:16:18 PDT

Most functional magnetic resonance imaging (fMRI) studies examining working memory (WM) load have focused on the prefrontal cortex (PFC) and have demonstrated increased prefrontal activity with increased load. Here we examined WM load effects in the medial temporal lobe (MTL) using an fMRI Sternberg task with novel complex visual scenes. Trials consisted of 3 sequential events: 1) sample presentation (encoding), 2) delay period (maintenance), and 3) probe period (retrieval). During sample encoding, subjects saw either 2 or 4 pictures consecutively. During retrieval, subjects indicated whether the probe picture matched one of the sample pictures. Results revealed that activity in the left anterior hippocampal formation, bilateral retrosplenial area, and left amygdala was greater at retrieval for trials with larger memory load, whereas activity in the PFC was greater at encoding for trials with larger memory load. There was no load effect during the delay. When encoding, maintenance, and retrieval periods were compared with fixation, activity was present in the hippocampal body/tail and fusiform gyrus bilaterally during encoding and retrieval, but not maintenance. Bilateral dorsolateral prefrontal activity was present during maintenance, but not during encoding or retrieval. The results support models of WM predicting that activity in the MTL should be modulated by WM load.

Experience-Dependent, Rapid Structural Changes in Hippocampal Pyramidal Cell Spines

Kitanishi, T., Ikegaya, Y., Matsuki, N., Yamada, M. K. — Wed, 07 Oct 2009 07:16:18 PDT

Morphological changes in dendritic spines may contribute to the fine tuning of neural network connectivity. The relationship between spine morphology and experience-dependent neuronal activity, however, is largely unknown. In the present study, we combined 2 histological analyses to examine this relationship: 1) Measurement of spines of neurons whose morphology was visualized in brain sections of mice expressing membrane-targeted green florescent protein (Thy1-mGFP mice) and 2) Categorization of CA1 neurons by immunohistochemical monitoring of Arc expression as a putative marker of recent neuronal activity. After mice were exposed to a novel, enriched environment for 60 min, neurons that expressed Arc had fewer small spines and more large spines than Arc-negative cells. These differences were not observed when the exploration time was shortened to 15 min. This net-balanced structural change is consistent with both synapse-specific enhancement and suppression. These results provide the first evidence of rapid morphological changes in spines that were preferential to a subset of neurons in association with an animal's experiences.

The Neural Architecture of Music-Evoked Autobiographical Memories

Janata, P. — Wed, 07 Oct 2009 07:16:18 PDT

The medial prefrontal cortex (MPFC) is regarded as a region of the brain that supports self-referential processes, including the integration of sensory information with self-knowledge and the retrieval of autobiographical information. I used functional magnetic resonance imaging and a novel procedure for eliciting autobiographical memories with excerpts of popular music dating to one's extended childhood to test the hypothesis that music and autobiographical memories are integrated in the MPFC. Dorsal regions of the MPFC (Brodmann area 8/9) were shown to respond parametrically to the degree of autobiographical salience experienced over the course of individual 30 s excerpts. Moreover, the dorsal MPFC also responded on a second, faster timescale corresponding to the signature movements of the musical excerpts through tonal space. These results suggest that the dorsal MPFC associates music and memories when we experience emotionally salient episodic memories that are triggered by familiar songs from our personal past. MPFC acted in concert with lateral prefrontal and posterior cortices both in terms of tonality tracking and overall responsiveness to familiar and autobiographically salient songs. These findings extend the results of previous autobiographical memory research by demonstrating the spontaneous activation of an autobiographical memory network in a naturalistic task with low retrieval demands.

Relationships between Brain Activation and Brain Structure in Normally Developing Children

Wed, 07 Oct 2009 07:16:18 PDT

Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region. These relationships remained even after effects of age or general cognitive ability were statistically controlled. These results localized cortical regions where mature morphology corresponds to mature patterns of activation, and may suggest a role for experience in mediating brain structure–activation relationships.

Stimulus-Response Profile during Single-Pulse Transcranial Magnetic Stimulation to the Primary Motor Cortex

Wed, 07 Oct 2009 07:16:18 PDT

We examined the stimulus–response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus–response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.

No Neglect-Specific Deficits in Reaching Tasks

Wed, 07 Oct 2009 07:16:18 PDT

It is well established that patients with hemispatial neglect present with severe visuospatial impairments, but studies that have directly investigated visuomotor control have revealed diverging results, with some studies showing that neglect patients perform relatively better on such tasks. The present study compared the visuomotor performance of patients with and without neglect after right-hemisphere stroke with those of age-matched controls. Participants were asked to point either directly towards targets or halfway between two stimuli, both with and without visual feedback during movement. Although we did not find any neglect-specific impairment, both patient groups showed increased reaction times to leftward stimuli as well as decreased accuracies for open loop leftward reaches. We argue that these findings agree with the view that neglect patients code spatial parameters for action veridically. Moreover, we suggest that lesions in the right hemisphere may cause motor deficits irrespective of the presence of neglect and we performed an initial voxel-lesion symptom analysis to assess this. Lesion-symptom analysis revealed that the reported deficits did not result from damage to neglect-associated areas alone, but were further associated with lesions to crucial nodes in the visuomotor control network (the basal ganglia as well as occipito-parietal and frontal areas).

Detecting Wrong Notes in Advance: Neuronal Correlates of Error Monitoring in Pianists

Ruiz, M. H., Jabusch, H.-C., Altenmuller, E. — Wed, 07 Oct 2009 07:16:18 PDT

Music performance is an extremely rapid process with low incidence of errors even at the fast rates of production required. This is possible only due to the fast functioning of the self-monitoring system. Surprisingly, no specific data about error monitoring have been published in the music domain. Consequently, the present study investigated the electrophysiological correlates of executive control mechanisms, in particular error detection, during piano performance. Our target was to extend the previous research efforts on understanding of the human action-monitoring system by selecting a highly skilled multimodal task. Pianists had to retrieve memorized music pieces at a fast tempo in the presence or absence of auditory feedback. Our main interest was to study the interplay between auditory and sensorimotor information in the processes triggered by an erroneous action, considering only wrong pitches as errors. We found that around 70 ms prior to errors a negative component is elicited in the event-related potentials and is generated by the anterior cingulate cortex. Interestingly, this component was independent of the auditory feedback. However, the auditory information did modulate the processing of the errors after their execution, as reflected in a larger error positivity (Pe). Our data are interpreted within the context of feedforward models and the auditory–motor coupling.

Cortical and Subcortical Mechanisms for Precisely Controlled Force Generation and Force Relaxation

Spraker, M. B., Corcos, D. M., Vaillancourt, D. E. — Wed, 07 Oct 2009 07:16:18 PDT

Gripping objects during everyday manual tasks requires the coordination of muscle contractions and muscle relaxations. The vast majority of studies have focused on muscle contractions. Although previous work has examined the motor cortex during muscle relaxation, the role of brain areas beyond motor cortex remains to be elucidated. The present study used functional magnetic resonance imaging to directly compare slow and precisely controlled force generation and force relaxation in humans. Contralateral primary motor cortex and bilateral caudate nucleus had greater activity during force generation compared with force relaxation. Conversely, right dorsolateral prefrontal cortex (DLPFC) had greater activity while relaxing force compared with generating force. Also, anterior cingulate cortex had greater deactivation while relaxing force compared with generating force. These findings were further strengthened by the fact that force output parameters such as the amplitude, rate, duration, variability, and error did not affect the brain imaging findings. These results demonstrate that the neural mechanisms underlying slow and precisely controlled force relaxation differ across prefrontal–striatal and motor cortical–striatal circuits. Moreover, this study demonstrates that the DLPFC is not only involved in slow and precisely controlled force generation, but has greater involvement in regulating slow and precisely controlled muscle relaxation.

Dopaminergic Neuromodulation of Semantic Processing: A 4-T fMRI Study with Levodopa

Copland, D. A., McMahon, K. L., Silburn, P. A., de Zubicaray, G. I. — Wed, 07 Oct 2009 07:16:18 PDT

There is emerging evidence that alterations in dopaminergic transmission can influence semantic processing, yet the neural mechanisms involved are unknown. The influence of levodopa (L-DOPA) on semantic priming was investigated in healthy individuals (n = 20) using event-related functional magnetic resonance imaging with a randomized, double-blind crossover design. Critical prime–target pairs consisted of a lexical ambiguity prime and 1) a target related to the dominant meaning of the prime (e.g., bank–money), 2) a target related to the subordinate meaning (e.g., fence–sword), or 3) an unrelated target (e.g., ball–desk). Behavioral data showed that both dominant and subordinate meanings were primed on placebo. In contrast, there was preserved priming of dominant meanings and no significant priming of subordinate meanings on L-DOPA, the latter associated with decreased anterior cingulate and dorsal prefrontal cortex activity. Dominant meaning activation on L-DOPA was associated with increased activity in the left rolandic operculum and left middle temporal gyrus. These findings suggest that L-DOPA enhances frequency-based semantic focus via prefrontal and temporal modulation of automatic semantic priming and through engagement of anterior cingulate mechanisms supporting attentional/controlled priming.

Consonants and Vowels Contribute Differently to Visual Word Recognition: ERPs of Relative Position Priming

Carreiras, M., Dunabeitia, J. A., Molinaro, N. — Wed, 07 Oct 2009 07:16:18 PDT

This paper shows that the nature of letters—consonant versus vowel—modulates the process of letter position assignment during visual word recognition. We recorded Event Related Potentials while participants read words in a masked priming semantic categorization task. Half of the words included a vowel as initial, third, and fifth letters (e.g., acero [steel]). The other half included a consonant as initial, third, and fifth (e.g., farol [lantern]). Targets could be preceded 1) by the initial, third, and fifth letters (relative position; e.g., aeo—acero and frl—farol), 2) by 3 consonants or vowels that did not appear in the target word (control; e.g., iui—acero and tsb—farol), or 3) by the same words (identity: acero–acero, farol–farol). The results showed modulation in 2 time windows (175–250 and 350–450 ms). Relative position primes composed of consonants produced similar effects to the identity condition. These 2 differed from the unrelated control condition, which showed a larger negativity. In contrast, relative position primes composed of vowels produced similar effects to the unrelated control condition, and these 2 showed larger negativities as compared with the identity condition. This finding has important consequences for cracking the orthographic code and developing computational models of visual word recognition.

Aging Influences the Neural Correlates of Lexical Decision but Not Automatic Semantic Priming

Gold, B. T., Andersen, A. H., Jicha, G. A., Smith, C. D. — Wed, 07 Oct 2009 07:16:18 PDT

Human behavioral data indicate that older adults are slower to perform lexical decisions (LDs) than young adults but show similar reaction time gains when these decisions are primed semantically. The present study explored the functional neuroanatomic bases of these frequently observed behavioral findings. Young and older groups completed unprimed and primed LD tasks while functional magnetic resonance imaging (fMRI) was recorded, using a fully randomized trial design paralleling those used in behavioral research. Results from the unprimed task found that age-related slowing of LD was associated with decreased activation in perceptual extrastriate regions and increased activation in regions associated with higher level linguistic processes, including prefrontal cortex. In contrast to these age-related changes in brain activation, the older group showed a preserved pattern of fMRI decreases in inferior temporal cortex when LD was primed semantically. These findings provide evidence that older adults’ LD abilities benefit from contexts that reduce the need for frontally mediated strategic processes and capitalize on the continued sensitivity of inferior temporal cortex to automatic semantic processes in aging.

Distracters Impair and Create Working Memory-Related Neuronal Activity in the Prefrontal Cortex

Wed, 07 Oct 2009 07:16:19 PDT

The prefrontal cortex (PFC) has a central role in working memory (WM). Resistance to distraction is considered a fundamental feature of WM and PFC neuronal activity. However, although unexpected stimuli often disrupt our work, little is known about the underlying neuronal mechanisms involved. In the present study, we investigated whether irregularly presented distracters disrupt WM task performance and underlying neuronal activity. We recorded single neuron activity in the PFC of 2 monkeys performing WM tasks and investigated effects of auditory and visual distracters on WM performance and neuronal activity. Distracters impaired memory task performance and affected PFC neuronal activity. Distraction that was of the same sensory modality as the memorandum was more likely to impair WM performance and interfere with memory-related neuronal activity than information that was of a different sensory modality. The study also shows that neurons not involved in memory processing in less demanding conditions may become engaged in WM processing in more demanding conditions. The study demonstrates that WM performance and underlying neuronal activity are vulnerable to irregular distracters and suggests that the PFC has mechanisms that help to compensate for disruptive effects of external distracters.

Structural Correlates of Semantic and Phonemic Fluency Ability in First and Second Languages

Grogan, A., Green, D. W., Ali, N., Crinion, J. T., Price, C. J. — Wed, 07 Oct 2009 07:16:19 PDT

Category and letter fluency tasks are commonly used clinically to investigate the semantic and phonological processes central to speech production, but the neural correlates of these processes are difficult to establish with functional neuroimaging because of the relatively unconstrained nature of the tasks. This study investigated whether differential performance on semantic (category) and phonemic (letter) fluency in neurologically normal participants was reflected in regional gray matter density. The participants were 59 highly proficient speakers of 2 languages. Our findings corroborate the importance of the left inferior temporal cortex in semantic relative to phonemic fluency and show this effect to be the same in a first language (L1) and second language (L2). Additionally, we show that the pre-supplementary motor area (pre-SMA) and head of caudate bilaterally are associated with phonemic more than semantic fluency, and this effect is stronger for L2 than L1 in the caudate nuclei. To further validate these structural results, we reanalyzed previously reported functional data and found that pre-SMA and left caudate activation was higher for phonemic than semantic fluency. On the basis of our findings, we also predict that lesions to the pre-SMA and caudate nuclei may have a greater impact on phonemic than semantic fluency, particularly in L2 speakers.

Reading and Subcortical Auditory Function

Banai, K., Hornickel, J., Skoe, E., Nicol, T., Zecker, S., Kraus, N. — Wed, 07 Oct 2009 07:16:19 PDT

Although it is largely agreed that phonological processing deficits are a major cause of poor reading, the neural origins of phonological processing are not well understood. We now show, for the first time, that phonological decoding, measured with a test of single-nonword reading, is significantly correlated with the timing of subcortical auditory processing and also, to a lesser extent, with the robustness of subcortical representation of the harmonic content of speech, but not with pitch encoding. The relationships we observe between reading and subcortical processing fall along a continuum, with poor readers at one end and good readers at the other. These data suggest that reading skill may depend on the integrity of subcortical auditory mechanisms and are consistent with the idea that subcortical representation of the acoustic features of speech may play a role in normal reading as well as in the development of reading disorders. These data establish a significant link between subcortical auditory function and reading, thereby contributing to the understanding of the biological bases of reading. At a more general level, these findings are among the first to establish a direct relationship between subcortical sensory function and a specific cognitive skill (reading). We argue that this relationship between cortical and subcortical function could be shaped during development by the corticofugal pathway and that this cortical–subcortical link could contribute to the phonological processing deficits experienced by poor readers.

Background Dopamine Concentration Dependently Facilitates Long-term Potentiation in Rat Prefrontal Cortex through Postsynaptic Activation of Extracellular Signal-Regulated Kinases

Kolomiets, B., Marzo, A., Caboche, J., Vanhoutte, P., Otani, S. — Wed, 07 Oct 2009 07:16:19 PDT

Altered levels of tonic/background dopamine in prefrontal cortex (PFC) may underlie modifications of executive cognitive function. We showed previously in rat PFC slices that exogenously supplied background dopamine facilitates induction of long-term potentiation (LTP), a possible cellular substrate for the long-term component of executive cognitive function. In the present study, we characterized cellular and molecular mechanisms underlying this modulatory dopamine effect. We show first that the LTP-facilitating effect of tonic/background dopamine follows an inverted-U shape concentration curve and that the effective level of background dopamine slowly activates postsynaptic extracellular signal-regulated kinases (ERKs) to facilitate LTP. Furthermore, we show the evidence that LTP-inducing high-frequency stimulation evokes endogenous release of dopamine in PFC slices. This fast dopamine serves as a trigger for LTP in the presence of the background dopamine. In its absence, the endogenous dopamine triggered, instead, long-term depression. These results indicate that appropriate levels of tonic/background dopamine serve to activate critical molecular factors in PFC neurons and thereby facilitate induction of synaptic potentiation.

Gonadal Hormones Modulate the Dendritic Spine Densities of Primary Cortical Pyramidal Neurons in Adult Female Rat

Chen, J.-R., Yan, Y.-T., Wang, T.-J., Chen, L.-J., Wang, Y.-J., Tseng, G.-F. — Wed, 07 Oct 2009 07:16:19 PDT

Adult dendritic arbors and spines can be modulated by environment and gonadal hormones that have been reported to affect also those of hippocampal and prefrontal cortical neurons. Here we investigated whether female gonadal hormones and estrous cycle alter the dendrites of primary cortical neurons. We employed intracellular dye injection in semifixed brain slices and 3-dimensional reconstruction to study the dendritic arbors and spines of the major cortical output cells, layer III and V pyramidal neurons, during different stages of the estrous cycle. Dendritic spines of both pyramidal neurons were more numerous during proestrus than estrus and diestrus, whereas dendritic arbors remained unaffected. Ovariohysterectomy (OHE) reduced dendritic spines by 24–30% in 2 weeks, whereas subcutaneous estrogen or progesterone supplement restored it to normal estrous/diestrous level in 14 days; neither treatment affected the dendritic arbors. Reduction of dendritic spines following OHE was associated with decrease of PSD-95 suggesting decrease of excitatory synapses. Thus, fluctuation of gonadal hormones during the female sex cycle is likely to modulate primary cortical functions and loss of gonadal hormones for instance following menopause might compromise cortical function, and the effect could be reversed by exogenous female sex hormones.

Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness

Wed, 07 Oct 2009 07:16:19 PDT

Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51–59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.

Movement-Specific Repetition Suppression in Ventral and Dorsal Premotor Cortex during Action Observation

Majdandzic, J., Bekkering, H., van Schie, H. T., Toni, I. — Wed, 07 Oct 2009 07:16:19 PDT

There are several models of premotor cortex contributions to sensorimotor behavior. For instance, the ventral premotor cortex (PMv) appears to be involved in processing visuospatial object properties for grasping, whereas the dorsal premotor cortex (PMd) is involved in using arbitrary rules to guide advance motor planning. These models have focused on individual movements. Here, we examine the premotor responses evoked during the processing of individual movements functionally embedded in an action. We tested whether processing hand–object interactions and action end states would differentially engage PMv and PMd. We used a repetition suppression (RS)–functional magnetic resonance imaging paradigm in which we independently manipulated the observed grip, the end position of the object (independent of its spatial location), and the hand trajectory. By comparing novel and repeated trials for each of these action components, we could isolate RS effects specific to each of them. Repeating the grasp component attenuated activity in right PMv, whereas repeating the end state of the action reduced blood oxygen level–dependent activity in the left PMd. These results suggest that PMv is involved in controlling the kinematic means of an appropriate hand–object interaction, whereas PMd is focused on specifying the desired end state of an action.

Engagement of Fusiform Cortex and Disengagement of Lateral Occipital Cortex in the Acquisition of Radiological Expertise

Wed, 07 Oct 2009 07:16:19 PDT

The human visual pathways that are specialized for object recognition stretch from lateral occipital cortex (LO) to the ventral surface of the temporal lobe, including the fusiform gyrus. Plasticity in these pathways supports the acquisition of visual expertise, but precisely how training affects the different regions remains unclear. We used functional magnetic resonance imaging to measure neural activity in both LO and the fusiform gyrus in radiologists as they detected abnormalities in chest radiographs. Activity in the right fusiform face area (FFA) correlated with visual expertise, measured as behavioral performance during scanning. In contrast, activity in left LO correlated negatively with expertise, and the amount of LO that responded to radiographs was smaller in experts than in novices. Activity in the FFA and LO correlated negatively in experts, whereas in novices, the 2 regions showed no stable relationship. Together, these results suggest that the FFA becomes more engaged and left LO less engaged in interpreting radiographic images over the course of training. Achieving expert visual performance may involve suppressing existing neural representations while simultaneously developing others.

Developmental Trajectories of Magnitude Processing and Interference Control: An fMRI Study

Wood, G., Ischebeck, A., Koppelstaetter, F., Gotwald, T., Kaufmann, L. — Wed, 07 Oct 2009 07:16:19 PDT

Neurodevelopmental changes regarding interference and magnitude processing were assessed in 3 age groups (children, n = 10; young adults, n = 11; elderly participants, n = 9) by using an functional magnetic resonance imaging version of the numerical Stroop task. Behaviorally, comparable distance and size congruity effects were found in all 3 age groups. Distance effects were most pronounced in the more difficult numerical task, whereas size congruity effects were comparable across tasks. In response to interference, an age-linear trend in the pattern of activation in left and right prefrontal and left middle temporal regions of the brain was observed. This implicates that with increasing age interference control requires increasing effort (possible explanations for children's relatively lower interference effects are provided). In contrast, the distance effect produced a negative linear trend in right prefrontal, supplementary motor area, and intraparietal cortex. This suggests that relative to old adults, children and young adults had to recruit a larger network upon processing magnitude. The latter findings are even more remarkable considering that the behavioral effects were similar across groups. In summary, the developmental trajectories of interference control and magnitude processing differ, although these cognitive functions activate partially overlapping brain regions.

Associate Editors

Fri, 11 Sep 2009 20:31:40 PDT

Subscriptions

Fri, 11 Sep 2009 20:31:40 PDT

The Resting Brain: Unconstrained yet Reliable

Fri, 11 Sep 2009 20:31:40 PDT

Recent years have witnessed an upsurge in the usage of resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity (fcMRI), both in normal and pathological populations. Despite this increasing popularity, concerns about the psychologically unconstrained nature of the "resting-state" remain. Across studies, the patterns of functional connectivity detected are remarkably consistent. However, the test–retest reliability for measures of resting state fcMRI measures has not been determined. Here, we quantify the test–retest reliability, using resting scans from 26 participants at 3 different time points. Specifically, we assessed intersession (>5 months apart), intrasession (<1 h apart), and multiscan (across all 3 scans) reliability and consistency for both region-of-interest and voxel-wise analyses. For both approaches, we observed modest to high reliability across connections, dependent upon 3 predictive factors: 1) correlation significance (significantly nonzero > nonsignificant), 2) correlation valence (positive > negative), and 3) network membership (default mode > task positive network). Short- and long-term measures of the consistency of global connectivity patterns were highly robust. Finally, hierarchical clustering solutions were highly reproducible, both across participants and sessions. Our findings provide a solid foundation for continued examination of resting state fcMRI in typical and atypical populations.

Feature Binding in the Feedback Layers of Area V2

Shipp, S., Adams, D. L., Moutoussis, K., Zeki, S. — Fri, 11 Sep 2009 20:31:40 PDT

The visual features of an object are processed by multiple, functionally specialized areas of cerebral cortex. When several objects are seen simultaneously, what mechanism preserves the association of features that belong to a single item? We address this question—known as the "binding problem"—by examining combinatorial feature selectivity of neurons in area V2. In recording from anesthetized macaques, we estimate that dual selectivity for chromatic and spatiotemporal attributes is 50% more common (27% vs. 18% sampling frequency) in superficial and deep layer neurons receiving feedback connections from higher areas, compared with layer 4-3 neurons relaying ascending signals. The operation of feedback pathways is thought to mediate attentional modulation of activity that may achieve binding through acting to select one single object for higher representation and filtering out competing objects. We propose that dual-selective neurons perform a "bridging" function, mediating the transfer of feedback-induced bias between feature dimensions. The bias can be propagated through V2 output neurons (of unitary selectivity) to higher levels of specialized processing and so promote selection of the target object's representation among multiple feature maps. The bridging function would thus act to unify the outcome of parallel, object-selective processes taking place along segregated visual pathways.

Prefrontostriatal Circuitry Regulates Effort-Related Decision Making

Hauber, W., Sommer, S. — Fri, 11 Sep 2009 20:31:40 PDT

The anterior cingulate cortex (ACC), the basolateral amygdala (BLA), and the dopamine in the nucleus accumbens (NAc) are part of a neural system that is critically involved in making decisions on how much effort to invest for rewards. In the present study, we sought to identify functional interactions between ACC and NAc regulating effort-based decision making. Rats were tested in a T-maze cost–benefit task in which they could either choose to climb a barrier to obtain a large reward (LR) in one arm or a small reward in the other arm without a barrier. Experiment 1 revealed that bilateral excitotoxic lesions of the core subregion of the NAc impaired effort-based decision making, that is, reduced the preference for the high effort–LR option when having the choice to obtain a low reward with little effort. Experiment 2 showed that disconnection of the ACC and NAc core using an asymmetrical excitotoxic lesion procedure impaired effort-based decision making. The present data provide evidence that effort-based decision making is governed by an interconnected neural system that requires serial information transfer between ACC and NAc core.

The Electrotonic Structure of Pyramidal Neurons Contributing to Prefrontal Cortical Circuits in Macaque Monkeys Is Significantly Altered in Aging

Kabaso, D., Coskren, P. J., Henry, B. I., Hof, P. R., Wearne, S. L. — Fri, 11 Sep 2009 20:31:40 PDT

Whereas neuronal numbers are largely preserved in normal aging, subtle morphological changes occur in dendrites and spines, whose electrotonic consequences remain unexplored. We examined age-related morphological alterations in 2 types of pyramidal neurons contributing to working memory circuits in the macaque prefrontal cortex (PFC): neurons in the superior temporal cortex forming "long" projections to the PFC and "local" projection neurons within the PFC. Global dendritic mass homeostasis, measured by 3-dimensional scaling analysis, was conserved with aging in both neuron types. Spine densities, dendrite diameters, lengths, and branching complexity were all significantly reduced in apical dendrites of long projection neurons with aging, but only spine parameters were altered in local projection neurons. Despite these differences, voltage attenuation due to passive electrotonic structure, assuming equivalent cable parameters, was significantly reduced with aging in the apical dendrites of both neuron classes. Confirming the electrotonic analysis, simulated passive backpropagating action potential efficacy was significantly higher in apical but not basal dendrites of old neurons. Unless compensated by changes in passive cable parameters, active membrane properties, or altered synaptic properties, these effects will increase the excitability of pyramidal neurons, compromising the precisely tuned activity required for working memory, ultimately resulting in age-related PFC dysfunction.

Different Spatial Scales of Shape Similarity Representation in Lateral and Ventral LOC

Drucker, D. M., Aguirre, G. K. — Fri, 11 Sep 2009 20:31:40 PDT

We investigated the relationship between stimulus similarity for a set of parameterized shapes and the spatial scale of neural representation within subregions of the lateral occipital complex (LOC) using a carryover functional magnetic resonance imaging design. In ventral but not lateral LOC, a linear recovery from adaptation proportional to shape dissimilarity was seen. In contrast, a strong correspondence of the distributed neural pattern and stimulus similarity was observed in lateral LOC but not ventral LOC. Further, ventral LOC voxels were found to be broadly tuned and represent all aspects of stimulus similarity, whereas lateral LOC voxels were narrowly tuned and preferentially represented the shape of small features rather than their orientation within the shape. The results, indicating a coarse spatial coding of shape features in lateral LOC and a more focused coding of the entire shape space within ventral LOC, may be related to hierarchical models of object processing.

Glutamatergic Inhibition in Sensory Neocortex

Lee, C. C., Sherman, S. M. — Fri, 11 Sep 2009 20:31:40 PDT

In the mammalian brain, glutamate and -aminobutyric acid are considered major excitatory and inhibitory neurotransmitters, respectively. However, we have found evidence that glutamate can also act as a postsynaptic inhibitory neurotransmitter in layer 4 of the neocortex. Using whole-cell recordings from layer 4 neurons in slice preparations from the mouse visual, auditory, and somatosensory cortices, we found that metabotropic glutamate receptor (mGluR) agonists (ACPD, APDC, and DCG IV) elicit a robust, long-lasting hyperpolarization that is abolished by the group II mGluR antagonist, MCCG. This response largely involves a K⁺ conductance mediated by G-protein activity and GIRK channels. Furthermore, electrical and photostimulation of the intracortical inputs to layer 4 elicits a similar hyperpolarization that is blocked by group II mGluR antagonists. This novel inhibition mediated by group II mGluRs may be an unappreciated mechanism for refining cortical receptive fields in layer 4 and may enable synaptic gain control during periods of high activity.

Hemispheric Asymmetry of Auditory Evoked Fields Elicited by Spectral versus Temporal Stimulus Change

Okamoto, H., Stracke, H., Draganova, R., Pantev, C. — Fri, 11 Sep 2009 20:31:40 PDT

The investigation of functional hemispheric asymmetries regarding auditory processing in the human brain still remains a challenge. Classical lesion and recent neuroimaging studies indicated that speech is dominantly processed in the left hemisphere, whereas music is dominantly processed in the right. However, recent studies demonstrated that the functional hemispheric asymmetries were not limited to the processing of highly cognitive sound signals like speech and music but rather originated from the basic neural processing of elementary sound features, that is, spectral and temporal acoustic features. Here, in contrast to previous studies, we used carefully composed tones and pulse trains as stimuli, balanced the overall physical sound input between spectral and temporal change conditions, and demonstrated the time course of neural activity evoked by spectral versus temporal sound input change by means of magnetoencephalography (MEG). These original findings support the hypothesis that spectral change is dominantly processed in the right hemisphere, whereas temporal change is dominantly processed in the left.

Double Dissociation between Motor and Visual Imagery in the Posterior Parietal Cortex

Pelgrims, B., Andres, M., Olivier, E. — Fri, 11 Sep 2009 20:31:40 PDT

Because motor imagery (MI) and visual imagery (VI) are influenced differently by factors such as biomechanical constraints or stimulus size, it is conceivable that they rely on separate processes, possibly involving distinct cortical networks, a view corroborated by neuroimaging and neuropsychological studies. In the posterior parietal cortex, it has been suggested that the superior parietal lobule (SPL) underlies VI, whereas MI relies on the supramarginalis gyrus (SMG). However, because several brain imaging studies have also shown an overlap of activations in SPL and SMG during VI or MI, the question arises as to which extent these 2 subregions really contribute to distinct imagery processes. To address this issue, we used repetitive transcranial magnetic stimulation to induce virtual lesions of either SMG or SPL in subjects performing a MI (hand drawing rotation) or a VI (letter rotation) task. Whatever hemisphere was stimulated, SMG lesions selectively altered MI, whereas SPL lesions only affected VI, demonstrating a double dissociation between MI and VI. Because these deficits were not influenced by the angular distance of the stimuli, we suggest that SMG and SPL are involved in the reenactment of the motor and visual representations, respectively, and not in mental rotation processes per se.

Input Specificity and Dependence of Spike Timing-Dependent Plasticity on Preceding Postsynaptic Activity at Unitary Connections between Neocortical Layer 2/3 Pyramidal Cells

Fri, 11 Sep 2009 20:31:40 PDT

Layer 2/3 (L2/3) pyramidal cells receive excitatory afferent input both from neighbouring pyramidal cells and from cortical and subcortical regions. The efficacy of these excitatory synaptic inputs is modulated by spike timing–dependent plasticity (STDP). Here we report that synaptic connections between L2/3 pyramidal cell pairs are located proximal to the soma, at sites overlapping those of excitatory inputs from other cortical layers. Nevertheless, STDP at L2/3 pyramidal to pyramidal cell connections showed fundamental differences from known STDP rules at these neighbouring contacts. Coincident low-frequency pre- and postsynaptic activation evoked only LTD, independent of the order of the pre- and postsynaptic cell firing. This symmetric anti-Hebbian STDP switched to a typical Hebbian learning rule if a postsynaptic action potential train occurred prior to the presynaptic stimulation. Receptor dependence of LTD and LTP induction and their pre- or postsynaptic loci also differed from those at other L2/3 pyramidal cell excitatory inputs. Overall, we demonstrate a novel means to switch between STDP rules dependent on the history of postsynaptic activity. We also highlight differences in STDP at excitatory synapses onto L2/3 pyramidal cells which allow for input specific modulation of synaptic gain.

TMS-Adaptation Reveals Abstract Letter Selectivity in the Left Posterior Parietal Cortex

Cattaneo, Z., Rota, F., Walsh, V., Vecchi, T., Silvanto, J. — Fri, 11 Sep 2009 20:31:40 PDT

Activation of the left posterior parietal cortex (PPC) has been associated with the encoding of letters independent of visual form. Here we used transcranial magnetic stimulation (TMS)-adaptation to investigate whether this abstract letter selectivity plays a causal role in letter processing. Visual adaptation was used to manipulate the initial activation state of neurons tuned to different letters prior to the application of TMS, after which subjects performed a detection task on letters that were presented in a different case from the adapting letter. After adaptation, TMS applied over the left PPC facilitated the detection of the adapted letter, whereas it had no impact on the detection of nonadapted letters. TMS applied over the right PPC had no significant effect on either type of letter. This interaction between adaptation and the effects of left PPC TMS demonstrates that adaptation modulated neural activity in the left PPC and thus demonstrates abstract letter selectivity in this region. Importantly, as the adapted letter and the target letters were presented in different cases, this finding demonstrates that the left PPC plays a causal role in letter processing independent of visual form.

Associative Motor Cortex Plasticity: Direct Evidence in Humans

Fri, 11 Sep 2009 20:31:40 PDT

Previous studies have shown that paired associative stimulation (PAS) protocol, in which peripheral nerve stimuli are followed by transcranial magnetic stimulation (TMS) of the motor cortex at intervals that produce an approximately synchronous activation of cortical networks, enhances the amplitude of motor evoked potentials (MEPs) evoked by cortical stimulation. Indirect data support the hypothesis that the enhancement of MEPs produced by PAS involves long-term potentiation like changes in cortical synapses. The aim of present paper was to investigate the central nervous system level at which PAS produces its effects. We recorded corticospinal descending volleys evoked by single pulse TMS of the motor cortex before and after PAS in 4 conscious subjects who had an electrode implanted in the cervical epidural space for the control of pain. The descending volleys evoked by TMS represent postsynaptic activity of corticospinal neurones that can provide indirect information about the effectiveness of synaptic inputs to these neurones. PAS significantly enhanced the amplitude of later descending waves, whereas the earliest descending wave was not significantly modified by PAS. The present results show that PAS may increase the amplitude of later corticospinal volleys, consistent with a cortical origin of the effect of PAS.

Damage to White Matter Fiber Tracts in Acute Spatial Neglect

Karnath, H.-O., Rorden, C., Ticini, L. F. — Fri, 11 Sep 2009 20:31:40 PDT

Previous statistical voxelwise lesion-behavior mapping (VLBM) studies have demonstrated that spatial neglect is associated with cortical and subcortical gray matter damage. However, it has also been suggested that the disorder may result from white matter injury. Our aim was to investigate the white matter connectivity in a large sample of 140 stroke patients. We combined a VLBM approach with the histological maps of the human white matter fiber tracts provided by the Jülich probabilistic cytoarchitectonic atlas. We found that damage of right perisylvian white matter connections—the superior longitudinal fasciculus, the inferior occipitofrontal fasciculus, and the superior occipitofrontal fasciculus—is a typical finding in patients with spatial neglect. However, the analysis also revealed that the largest portion of the lesion area, namely between 89.1% and 96.6%, affected brain structures other than the perisylvian white matter fiber tracts. Predominantly, these included gray matter structures such as the superior temporal, inferior parietal, inferior frontal, and insular cortices, as well as subcortically the putamen and the caudate nucleus. Damage of gray matter structures thus appears to be a strong predictor of spatial neglect.

The Brain's Intention to Imitate: The Neurobiology of Intentional versus Automatic Imitation

Bien, N., Roebroeck, A., Goebel, R., Sack, A. T. — Fri, 11 Sep 2009 20:31:40 PDT

Whenever we observe a movement of a conspecific, our mirror neuron system becomes activated, urging us to imitate the observed movement. However, because such automatic imitation is not always appropriate, an inhibitive component keeping us from imitating everything we see seems crucial for an effective social behavior. This becomes evident from neuropsychological conditions like echopraxia, in which this suppression is absent. Here, we unraveled the neurodynamics underlying this proposed inhibition of automatic imitation by measuring and manipulating brain activity during the execution of a stimulus–response compatibility paradigm. Within the identified connectivity network, right middle/inferior frontal cortex sends neural input concerning general response inhibition to right premotor cortex, which is involved in automatic imitation. Subsequently, the fully prepared imitative response is sent to left opercular cortex that functions as a final gating mechanism for intentional imitation. We propose an informed neurocognitive model of inhibition of automatic imitation, suggesting a functional dissociation between automatic and intentional imitation.

When the Brain Changes Its Mind: Flexibility of Action Selection in Instructed and Free Choices

Fleming, S. M., Mars, R. B., Gladwin, T. E., Haggard, P. — Fri, 11 Sep 2009 20:31:40 PDT

The neural mechanisms underlying the selection and initiation of voluntary actions in the absence of external instructions are poorly understood. These mechanisms are usually investigated using a paradigm where different movement choices are self-generated by a participant on each trial. These "free choices" are compared with "instructed choices," in which a stimulus informs subjects which action to make on each trial. Here, we introduce a novel paradigm to investigate these modes of action selection, by measuring brain processes evoked by an instruction to either reverse or maintain free and instructed choices in the period before a "go" signal. An unpredictable instruction to change a response plan had different effects on free and instructed choices. In instructed trials, change cues evoked a larger P300 than no-change cues, leading to a significant interaction of choice and change condition. Free-choice trials displayed a trend toward the opposite pattern. These results suggest a difference between updating of free and instructed action choices. We propose a theoretical framework for internally generated action in which representations of alternative actions remain available until a late stage in motor preparation. This framework emphasizes the high modifiability of voluntary action.

Overlap and Segregation in Predorsal Premotor Cortex Activations Related to Free Selection of Self-Referenced and Target-Based Finger Movements

Beudel, M., de Jong, B. M. — Fri, 11 Sep 2009 20:31:40 PDT

In reaching movements, parietal contributions can be distinguished that are based on representations of external space and body scheme. By functional magnetic resonance imaging, we examined 16 healthy subjects to see whether such segregation similarly exists in the frontal lobes when visuomotor actions are not specified but when free choices are allowed. Free selection was button based (target based) or finger based (self-referenced), with invariant instructions as control. To avoid a visual attention bias, instructions were auditory presented. Statistical parametric mapping revealed that free button selection with the same finger was associated with increased activations in the anterior cingulate cortex (ACC), right posterodorsal prefrontal cortex (PFC) including the rostral extension of the dorsal premotor cortex (pre-PMd), and the anterodorsal PFC. Prefrontal activation related to free finger selection (pressing the same button) was restricted to an anteromedial segment of the posterodorsal PFC/pre-PMd. Bilateral inferior parietal activations were present in both free-choice conditions. Pre-PMd and parietal contributions to free selection support concepts on early-stage action selection in dorsal visuomotor pathways. The rostral–caudal segregation in pre-PMd activations reflected that in anterior direction, frontal processing is gradually less involved in selection of environmental information but increasingly committed to self-referenced selection. ACC particularly contributes to free selection between external goals.

Proteomic Analysis Illuminates a Novel Structural Definition of the Claustrum and Insula

Mathur, B. N., Caprioli, R. M., Deutch, A. Y. — Fri, 11 Sep 2009 20:31:40 PDT

The claustrum is a prominent but ill-defined forebrain structure that has been suggested to integrate multisensory information and perhaps transform percepts into consciousness. The claustrum's shape and vague borders have hampered experimental assessment of its functions. We used matrix-assisted laser desorption ionization–imaging mass spectrometry to reveal a novel protein marker, G-protein gamma2 subunit (Gng2), which is enriched in the claustrum but not adjacent structures of the rat forebrain. The spatial pattern of Gng2 expression suggests key differences from commonly held views of the claustrum's structure. Using anatomical methods, we found that the rat claustrum is present only at striatal levels of the telencephalon and does not extend to frontal cortical territories. Moreover, the claustrum is surrounded on all sides by layer VI insular cortex cells in both the rat and primate. Using these defining characteristics of the claustrum, we found that the claustrum projects to cortical but not to subcortical sites. The definition of the claustrum as a cortical site is considered. The identification of a claustrum-specific protein opens the door to selective molecular lesions and the subsequent evaluation of the role of the claustrum in cognition.

Thalamic Input to Distal Apical Dendrites in Neocortical Layer 1 Is Massive and Highly Convergent

Rubio-Garrido, P., Perez-de-Manzo, F., Porrero, C., Galazo, M. J., Clasca, F. — Fri, 11 Sep 2009 20:31:40 PDT

Input to apical dendritic tufts is now deemed crucial for associative learning, attention, and similar "feedback" interactions in the cerebral cortex. Excitatory input to apical tufts in neocortical layer 1 has been traditionally assumed to be predominantly cortical, as thalamic pathways directed to this layer were regarded relatively scant and diffuse. However, the sensitive tracing methods used in the present study show that, throughout the rat neocortex, large numbers (mean ~4500/mm²) of thalamocortical neurons converge in layer 1 and that this convergence gives rise to a very high local density of thalamic terminals. Moreover, we show that the layer 1–projecting neurons are present in large numbers in most, but not all, motor, association, limbic, and sensory nuclei of the rodent thalamus. Some layer 1–projecting axons branch to innervate large swaths of the cerebral hemisphere, whereas others arborize within only a single cortical area. Present data imply that realistic modeling of cortical circuitry should factor in a dense axonal canopy carrying highly convergent thalamocortical input to pyramidal cell apical tufts. In addition, they are consistent with the notion that layer 1-projecting axons may be a robust anatomical substrate for extensive "feedback" interactions between cortical areas via the thalamus.

A Common Network in the Left Cerebral Hemisphere Represents Planning of Tool Use Pantomimes and Familiar Intransitive Gestures at the Hand-Independent Level

Kroliczak, G., Frey, S. H. — Fri, 11 Sep 2009 20:31:40 PDT

Evidence from neuropsychology and neuroimaging implicates parietal and frontal areas of the left cerebral hemisphere in the representation of skills involving the use of tools and other artifacts. On the basis of neuropsychological data, it has been claimed that 1) independent mechanisms within the left hemisphere may support the representation of these skills (transitive actions) versus meaningful gestures that do not involve manipulating objects (intransitive actions), and 2) both cerebral hemispheres may participate in the representation of intransitive gestures. Functional magnetic resonance imaging was used to test these hypotheses in 12 healthy adults while they planned and executed tool use pantomimes or intransitive gestures with their dominant right (Exp. 1) or nondominant left (Exp. 2) hands. Even when linguistic processing demands were controlled, planning either type of action was associated with asymmetrical increases in the same regions of left parietal (the intraparietal sulcus, supramarginal gyrus, and caudal superior parietal lobule) and dorsal premotor cortices. Effects were greater for tool use pantomimes, but only when the right hand was involved. Neither group nor individual analyses revealed evidence for greater bilateral activity during intransitive gesture planning. In summary, at the hand-independent level, transitive and intransitive actions are represented in a common, left-lateralized praxis network.

Involvement of Nicotinic and Muscarinic Receptors in the Endogenous Cholinergic Modulation of the Balance between Excitation and Inhibition in the Young Rat Visual Cortex

Lucas-Meunier, E., Monier, C., Amar, M., Baux, G., Fregnac, Y., Fossier, P. — Fri, 11 Sep 2009 20:31:40 PDT

This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a significant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological specificity of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation-locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and -aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of ^*β4 receptors located on glutamatergic fibers. DHβE, the selective 4β2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh amplifies the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons.

Inverse Mapping the Neuronal Substrates of Face Categorizations

Smith, M. L., Fries, P., Gosselin, F., Goebel, R., Schyns, P. G. — Fri, 11 Sep 2009 20:31:40 PDT

Face perception is a complex process involving a network of brain structures, dynamically processing information to enable judgments about a face to be made (e.g., familiarity, identity, and expression). Here we introduce an analysis methodology that makes it possible to directly study this information processing in the brain from spatially and temporally resolved magnetoencephalographic signals. We apply our methodology to the study of 2 face categorization tasks, gender and expressiveness, and track the processing of 3 key visual features that underlie behavioral performance, over time and throughout the cortex. We find information processing correlates beginning from 90 ms following stimulus onset, where features are processed in isolation in occipital extrastriate regions. Over time, processing of successively more features and feature combinations takes place in occipitotemporal regions, with maximal information processing of visual information coinciding with the well-established face-selective M170 component at 170 ms. Later still, around 250–400 ms, cortical activity responds significantly more to task-specific features and their complex combinations. These results indicate a complex process of visual information processing during face perception with face parts processed in isolation at very early stages, and task-specific processing of combinations of features taking place within 300 ms. Crucially, our approach specifically establishes which information in the visual stimulus the brain signal is responding to and how this varies with time, cortical location, and task demands to establish a more precise tracking of information processing mechanisms in the cortex during face perception.

Intermediate Neuronal Progenitors (Basal Progenitors) Produce Pyramidal-Projection Neurons for All Layers of Cerebral Cortex

Fri, 11 Sep 2009 20:31:40 PDT

The developing cerebral cortex contains apical and basal types of neurogenic progenitor cells. Here, we investigated the cellular properties and neurogenic output of basal progenitors, also called intermediate neuronal progenitors (INPs). We found that basal mitoses expressing transcription factor Tbr2 (an INP marker) were present throughout corticogenesis, from embryonic day 10.5 through birth. Postnatally, Tbr2⁺ progenitors were present in the dentate gyrus, subventricular zone (SVZ), and posterior periventricle (pPV). Two morphological subtypes of INPs were distinguished in the embryonic cortex, "short radial" in the ventricular zone (VZ) and multipolar in the SVZ, probably corresponding to molecularly defined INP subtypes. Unexpectedly, many short radial INPs appeared to contact the apical (ventricular) surface and some divided there. Time-lapse video microscopy suggested that apical INP divisions produced daughter INPs. Analysis of neurogenic divisions (Tis21-green fluorescent protein [GFP]⁺) indicated that INPs may produce the majority of projection neurons for preplate, deep, and superficial layers. Conversely, proliferative INP divisions (Tis21-GFP^–) increased from early to middle corticogenesis, concomitant with SVZ growth. Our findings support the hypothesis that regulated amplification of INPs may be an important factor controlling the balance of neurogenesis among different cortical layers.

Functional Selectivity of Interhemispheric Connections in Cat Visual Cortex

Fri, 11 Sep 2009 20:31:40 PDT

The functional specificity of callosal connections was investigated in visual areas 17 and 18 of adult cats, by combining in vivo optical imaging of intrinsic signals with labeling of callosal axons. Local injections of neuronal tracers were performed in one hemisphere and eight single callosal axons were reconstructed in the opposite hemisphere. The distributions of injection sites and callosal axon terminals were analyzed with respect to functional maps in both hemispheres. Typically, each callosal axon displayed 2 or 3 clusters of synaptic boutons in layer II/III and the upper part of layer IV. These clusters were preferentially distributed in regions representing the same orientation and the same visuotopic location as that at the corresponding injection sites in the opposite hemisphere. The spatial distribution of these clusters was elongated and its main axis correlated well with the preferred orientation at the injection site. These results demonstrate a specific organization of interhemispheric axons that link cortical regions representing the same orientation and the same location of visual stimuli. Visual callosal connections are thus likely involved in the processing of coherent information in terms of shape and position along the midline of the visual field, which may facilitate the fusion of both hemifields into the percept of a single visual scene.

Attention Reshapes Center-Surround Receptive Field Structure in Macaque Cortical Area MT

Anton-Erxleben, K., Stephan, V. M., Treue, S. — Fri, 11 Sep 2009 20:31:40 PDT

Directing spatial attention to a location inside the classical receptive field (cRF) of a neuron in macaque medial temporal area (MT) shifts the center of the cRF toward the attended location. Here we investigate the influence of spatial attention on the profile of the inhibitory surround present in many MT neurons. Two monkeys attended to the fixation point or to 1 of 2 random dot patterns (RDPs) placed inside or next to the cRF, whereas a third RDP (the probe) was briefly presented in quick succession across the cRF and surround. The probe presentation responses were used to compute a map of the excitatory receptive field and its inhibitory surround. Attention systematically reshapes the receptive field profile, independently shifting both center and surround toward the attended location. Furthermore, cRF size is changed as a function of relative distance to the attentional focus: attention inside the cRF shrinks it, whereas directing attention next to the cRF expands it. In addition, we find systematic changes in surround inhibition and cRF amplitude. This nonmultiplicative push–pull modulation of the receptive field's center-surround structure optimizes processing at and near the attentional focus to strengthen the representation of the attended stimulus while reducing influences from distractors.

Stress-Induced Dendritic Remodeling in the Prefrontal Cortex is Circuit Specific

Shansky, R. M., Hamo, C., Hof, P. R., McEwen, B. S., Morrison, J. H. — Fri, 11 Sep 2009 20:31:40 PDT

Chronic stress exposure has been reported to induce dendritic remodeling in several brain regions, but it is not known whether individual neural circuits show distinct patterns of remodeling. The current study tested the hypothesis that the projections from the infralimbic (IL) area of the medial prefrontal cortex (mPFC) to the basolateral nucleus of the amygdala (BLA), a pathway relevant to stress-related mental illnesses like depression and post-traumatic stress disorder, would have a unique pattern of remodeling in response to chronic stress. The retrograde tracer FastBlue was injected into male rats’ BLA or entorhinal cortex (EC) 1 week prior to 10 days of immobilization stress. After cessation of stress, FastBlue-labeled and unlabeled IL pyaramidal neurons were loaded with fluorescent dye Lucifer Yellow to visualize dendritic arborization and spine density. As has been previously reported, randomly selected (non-FastBlue-labeled) neurons showed stress-induced dendritic retraction in apical dendrites, an effect also seen in EC-projecting neurons. In contrast, BLA-projecting neurons showed no remodeling with stress, suggesting that this pathway may be particularly resilient against the effects of stress. No neurons showed stress-related changes in spine density, contrasting with reports that more dorsal areas of the mPFC show stress-induced decreases in spine density. Such region- and circuit-specificity in response to stress could contribute to the development of stress-related mental illnesses.

Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity

Krienen, F. M., Buckner, R. L. — Fri, 11 Sep 2009 20:31:40 PDT

Multiple, segregated fronto-cerebellar circuits have been characterized in nonhuman primates using transneuronal tracing techniques including those that target prefrontal areas. Here, we used functional connectivity MRI (fcMRI) in humans (n = 40) to identify 4 topographically distinct fronto-cerebellar circuits that target 1) motor cortex, 2) dorsolateral prefrontal cortex, 3) medial prefrontal cortex, and 4) anterior prefrontal cortex. All 4 circuits were replicated and dissociated in an independent data set (n = 40). Direct comparison of right- and left-seeded frontal regions revealed contralateral lateralization in the cerebellum for each of the segregated circuits. The presence of circuits that involve prefrontal regions confirms that the cerebellum participates in networks important to cognition including a specific fronto-cerebellar circuit that interacts with the default network. Overall, the extent of the cerebellum associated with prefrontal cortex included a large portion of the posterior hemispheres consistent with a prominent role of the cerebellum in nonmotor functions. We conclude by providing a provisional map of the topography of the cerebellum based on functional correlations with the frontal cortex.

Cerebral Cortex - recent issues

Cover

Associate Editors

Subscriptions

Table of Contents

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Sex Differences in Resting-State Neural Correlates of Openness to Experience among Older Adults

Not What You Expect: Experience but not Expectancy Predicts Conditioned Responses in Human Visual and Supplementary Cortex

Differences in Intrinsic Properties and Local Network Connectivity of Identified Layer 5 and Layer 6 Adult Mouse Auditory Corticothalamic Neurons Support a Dual Corticothalamic Projection Hypothesis

Locus Coeruleus Activation Facilitates Memory Encoding and Induces Hippocampal LTD that Depends on {beta}-Adrenergic Receptor Activation

In Vivo MRI of Altered Brain Anatomy and Fiber Connectivity in Adult Pax6 Deficient Mice

Cortical Mechanisms for Online Control of Hand Movement Trajectory: The Role of the Posterior Parietal Cortex

Paraneoplastic Antigen-Like 5 Gene (PNMA5) Is Preferentially Expressed in the Association Areas in a Primate Specific Manner

Too Little, Too Late: Reduced Visual Span and Speed Characterize Pure Alexia

Hypoxic Injury during Neonatal Development in Murine Brain: Correlation between In Vivo DTI Findings and Behavioral Assessment

Axon Morphologies and Convergence Patterns of Projections from Different Sensory-Specific Cortices of the Anterior Ectosylvian Sulcus onto Multisensory Neurons in the Cat Superior Colliculus

Regional Patterns of Cerebral Cortical Differentiation Determined by Diffusion Tensor MRI

Functional Heterogeneity of Inferior Parietal Cortex during Mathematical Cognition Assessed with Cytoarchitectonic Probability Maps

The Brain Network Underlying Serial Visual Search: Comparing Overt and Covert Spatial Orienting, for Activations and for Effective Connectivity

Double Dissociation of Spike Timing-Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex

Additive Effects of Attention and Stimulus Contrast in Primary Visual Cortex

Analysis of c-fos and zif268 Expression Reveals Time-Dependent Changes in Activity Inside and Outside the Lesion Projection Zone in Adult Cat Area 17 after Retinal Lesions

Integrating Visual and Tactile Information in the Perirhinal Cortex

A Simple Rule for Axon Outgrowth and Synaptic Competition Generates Realistic Connection Lengths and Filling Fractions

GABAergic Inhibitory Interneurons in the Posterior Piriform Cortex of the GAD67-GFP Mouse

Erratum

Medial Prefrontal Cortex 5-HT2A Density Is Correlated with Amygdala Reactivity, Response Habituation, and Functional Coupling

Priming and Backward Influences in the Human Brain: Processing Interactions during the Stroop Interference Effect

Detection of Fixed and Variable Targets in the Monkey Prefrontal Cortex

Inhibition of cAMP Response Element-Binding Protein Reduces Neuronal Excitability and Plasticity, and Triggers Neurodegeneration

The Influence of Multiple Primes on Bottom-Up and Top-Down Regulation during Meaning Retrieval: Evidence for 2 Distinct Neural Networks

Greater Working Memory Load Results in Greater Medial Temporal Activity at Retrieval

Experience-Dependent, Rapid Structural Changes in Hippocampal Pyramidal Cell Spines

The Neural Architecture of Music-Evoked Autobiographical Memories

Relationships between Brain Activation and Brain Structure in Normally Developing Children

Stimulus-Response Profile during Single-Pulse Transcranial Magnetic Stimulation to the Primary Motor Cortex

No Neglect-Specific Deficits in Reaching Tasks

Detecting Wrong Notes in Advance: Neuronal Correlates of Error Monitoring in Pianists

Cortical and Subcortical Mechanisms for Precisely Controlled Force Generation and Force Relaxation

Dopaminergic Neuromodulation of Semantic Processing: A 4-T fMRI Study with Levodopa

Consonants and Vowels Contribute Differently to Visual Word Recognition: ERPs of Relative Position Priming

Aging Influences the Neural Correlates of Lexical Decision but Not Automatic Semantic Priming

Distracters Impair and Create Working Memory-Related Neuronal Activity in the Prefrontal Cortex

Structural Correlates of Semantic and Phonemic Fluency Ability in First and Second Languages

Reading and Subcortical Auditory Function

Background Dopamine Concentration Dependently Facilitates Long-term Potentiation in Rat Prefrontal Cortex through Postsynaptic Activation of Extracellular Signal-Regulated Kinases

Gonadal Hormones Modulate the Dendritic Spine Densities of Primary Cortical Pyramidal Neurons in Adult Female Rat

Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness

Movement-Specific Repetition Suppression in Ventral and Dorsal Premotor Cortex during Action Observation

Engagement of Fusiform Cortex and Disengagement of Lateral Occipital Cortex in the Acquisition of Radiological Expertise

Developmental Trajectories of Magnitude Processing and Interference Control: An fMRI Study

Associate Editors

Subscriptions

Table of contents

The Resting Brain: Unconstrained yet Reliable

Feature Binding in the Feedback Layers of Area V2

Prefrontostriatal Circuitry Regulates Effort-Related Decision Making

The Electrotonic Structure of Pyramidal Neurons Contributing to Prefrontal Cortical Circuits in Macaque Monkeys Is Significantly Altered in Aging

Different Spatial Scales of Shape Similarity Representation in Lateral and Ventral LOC

Glutamatergic Inhibition in Sensory Neocortex

Hemispheric Asymmetry of Auditory Evoked Fields Elicited by Spectral versus Temporal Stimulus Change

Double Dissociation between Motor and Visual Imagery in the Posterior Parietal Cortex

Input Specificity and Dependence of Spike Timing-Dependent Plasticity on Preceding Postsynaptic Activity at Unitary Connections between Neocortical Layer 2/3 Pyramidal Cells

TMS-Adaptation Reveals Abstract Letter Selectivity in the Left Posterior Parietal Cortex

Associative Motor Cortex Plasticity: Direct Evidence in Humans

Damage to White Matter Fiber Tracts in Acute Spatial Neglect

The Brain's Intention to Imitate: The Neurobiology of Intentional versus Automatic Imitation

When the Brain Changes Its Mind: Flexibility of Action Selection in Instructed and Free Choices

Overlap and Segregation in Predorsal Premotor Cortex Activations Related to Free Selection of Self-Referenced and Target-Based Finger Movements

Proteomic Analysis Illuminates a Novel Structural Definition of the Claustrum and Insula

Thalamic Input to Distal Apical Dendrites in Neocortical Layer 1 Is Massive and Highly Convergent

A Common Network in the Left Cerebral Hemisphere Represents Planning of Tool Use Pantomimes and Familiar Intransitive Gestures at the Hand-Independent Level

Involvement of Nicotinic and Muscarinic Receptors in the Endogenous Cholinergic Modulation of the Balance between Excitation and Inhibition in the Young Rat Visual Cortex

Inverse Mapping the Neuronal Substrates of Face Categorizations

Intermediate Neuronal Progenitors (Basal Progenitors) Produce Pyramidal-Projection Neurons for All Layers of Cerebral Cortex

Functional Selectivity of Interhemispheric Connections in Cat Visual Cortex

Attention Reshapes Center-Surround Receptive Field Structure in Macaque Cortical Area MT

Stress-Induced Dendritic Remodeling in the Prefrontal Cortex is Circuit Specific

Segregated Fronto-Cerebellar Circuits Revealed by Intrinsic Functional Connectivity