Cerebral Cortex - recent issues

Information Processing Streams in Rodent Barrel Cortex: The Differential Functions of Barrel and Septal Circuits

Alloway, K. D. — 2008-04-10

Rodent somatosensory cortex contains an isomorphic map of the mystacial whiskers in which each whisker is represented by neuronal populations, or barrels, that are separated from each other by intervening septa. Separate afferent pathways convey somatosensory information to the barrels and septa that represent the input stages for 2 partially segregated circuits that extend throughout the other layers of barrel cortex. Whereas the barrel-related circuits process spatiotemporal information generated by whisker contact with external objects, the septa-related circuits encode the frequency and other kinetic features of active whisker movements. The projection patterns from barrel cortex indicate that information processed by the septa-related circuits is used both separately and in combination with information from the barrel-related circuits to mediate specific functions. According to this theory, outputs from the septal processing stream modulate the brain regions that regulate whisking behavior, whereas both processing streams cooperate with each other to identify external stimuli encountered by passive or active whisker movements. This theoretical view prompts several testable hypotheses about the coordination of neuronal activity during whisking behavior. Foremost among these, motor brain regions that control whisker movements are more strongly coordinated with the septa-related circuits than with the barrel-related circuits.

Evidence for Impaired Long-Term Potentiation in Schizophrenia and Its Relationship to Motor Skill Leaning

2008-04-10

Several lines of evidence suggest that schizophrenia (SCZ) is associated with disrupted plasticity in the cortex. However, there is little direct neurophysiological evidence of aberrant long-term potentiation (LTP)–like plasticity in SCZ and little human evidence to establish a link between LTP to learning and memory. LTP was evaluated using a neurophysiological paradigm referred to as paired associative stimulation (PAS). PAS involves pairing of median nerve electric stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (for abductor pollicis brevis muscle activation) delivered at 25-ms interstimulus interval. This pairing was delivered at a frequency of 0.1 Hz for 30 min. LTP was reflected by the change in motor evoked potentials (MEPs) before and after PAS. In addition, motor skill learning was assessed using the rotary pursuit task. Compared with healthy subjects, patients with SCZ demonstrated significant MEP facilitation deficits following PAS and impaired rotary-pursuit motor learning. Across all subjects there was a significant association between LTP and motor skill learning. These data provide evidence for disrupted LTP in SCZ, whereas the association between LTP with motor skill learning suggests that the deficits in learning and memory in SCZ may be mediated through disordered LTP.

Spatio temporal Dynamics of Face Recognition

2008-04-10

To better understand face recognition, it is necessary to identify not only which brain structures are implicated but also the dynamics of the neuronal activity in these structures. Latencies can then be compared to unravel the temporal dynamics of information processing at the distributed network level. To achieve high spatial and temporal resolution, we used intracerebral recordings in epileptic subjects while they performed a famous/unfamiliar face recognition task. The first components peaked at 110 ms in the fusiform gyrus (FG) and simultaneously in the inferior frontal gyrus, suggesting the early establishment of a large-scale network. This was followed by components peaking at 160 ms in 2 areas along the FG. Important stages of distributed parallel processes ensued at 240 and 360 ms involving up to 6 regions along the ventral visual pathway. The final components peaked at 480 ms in the hippocampus. These stages largely overlapped. Importantly, event-related potentials to famous faces differed from unfamiliar faces and control stimuli in all medial temporal lobe structures. The network was bilateral but more right sided. Thus, recognition of famous faces takes place through the establishment of a complex set of local and distributed processes that interact dynamically and may be an emergent property of these interactions.

Cognitive Control, Goal Maintenance, and Prefrontal Function in Healthy Aging

Paxton, J. L., Barch, D. M., Racine, C. A., Braver, T. S. — 2008-04-10

Cognitive control impairments in healthy older adults may partly reflect disturbances in the ability to actively maintain goal-relevant information, a function that depends on the engagement of lateral prefrontal cortex (PFC). In 2 functional magnetic resonance imaging studies, healthy young and older adults performed versions of a task in which contextual cues provide goal-relevant information used to bias processing of subsequent ambiguous probes. In Study 1, a blocked design and manipulation of the cue–probe delay interval revealed a generalized pattern of enhanced task-related brain activity in older adults but combined with a specific delay-related reduction of activity in lateral PFC regions. In Study 2, a combined blocked/event-related design revealed enhanced sustained (i.e., across-trial) activity but a reduction in transient trial-related activation in lateral PFC among older adults. Further analyses of within-trial activity dynamics indicated that, within these and other lateral PFC regions, older adults showed reduced activation during the cue and delay period but increased activation at the time of the probe, particularly on high-interference trials. These results are consistent with the hypothesis that age-related impairments in goal maintenance abilities cause a compensatory shift in older adults from a proactive (seen in young adults) to a reactive cognitive control strategy.

Critical Spatial Frequencies for Illusory Contour Processing in Early Visual Cortex

Zhan, C. A., Baker, C. L. — 2008-04-10

Single neurons in primate V2 and cat A18 exhibit identical orientation tuning for sinewave grating and illusory contour stimuli. This cue invariance is also manifested in similar orientation maps to these stimuli, but in V1/A17 the illusory contour maps appear reversed. We hypothesized that this map reversal depends upon the spatial frequencies of the inducers in the illusory contours, relative to the spatial selectivities of these brain areas. We employed intrinsic signal optical imaging to measure orientation maps in cat A17/18 to illusory contours with inducers at spatial frequencies from 0.15 to 1.6 cpd. A17 illusory contour maps were indeed reversed compared with grating-driven maps for inducer spatial frequencies <1.3 cpd, whereas A18 maps were invariant. Simulations based on known neurophysiology demonstrated that map reversal can arise from linear filtering, and map invariance can be explained by a nonlinear (filter-rectify-filter) mechanism. The simulation also correctly predicted that A17 could show invariant maps when the inducer spatial frequency is sufficiently high (1.6 cpd), and that A18 maps could reverse at lower inducer frequencies (0.18 cpd). Thus, the map reversal or invariance to illusory contours depends critically on the relationship of the inducer spatial frequencies to the spatial filtering properties of neurons in each brain area.

Involvement of the Cerebellar Dorsal Vermis in Vergence Eye Movements in Monkeys

Nitta, T., Akao, T., Kurkin, S., Fukushima, K. — 2008-04-10

Frontal-eyed primates use both smooth pursuit in frontoparallel planes (frontal pursuit) and pursuit-in-depth (vergence pursuit) to track objects moving slowly in 3-dimensional (3D) space. To understand how 3D-pursuit signals represented in frontal eye fields are processed further by downstream pathways, monkeys were trained to pursue a spot moving in 3D virtual space. We characterized pursuit signals in Purkinje (P) cells in the cerebellar dorsal vermis and their discharge during vergence pursuit. In 41% of pursuit P-cells, 3D-pursuit signals were observed. However, the majority of vermal-pursuit P-cells (59%) discharged either for vergence pursuit (43%) or for frontal pursuit (16%). Moreover, the majority (74%) of vergence-related P-cells carried convergence signals, displaying both vergence eye position and velocity sensitivity during sinusoidal and step vergence eye movements. Preferred frontal-pursuit directions of vergence + frontal-pursuit P-cells were distributed in all directions. Most pursuit P-cells (73%) discharged before the onset of vergence eye movements; the median lead time was 16 ms. Muscimol infusion into the sites where convergence P-cells were recorded resulted in a reduction of peak convergence eye velocity, of initial convergence eye acceleration, and of frontal-pursuit eye velocity. These results suggest involvement of the dorsal vermis in conversion of 3D-pursuit signals and in convergence eye movements.

Lack of Orientation and Direction Selectivity in a Subgroup of Fast-Spiking Inhibitory Interneurons: Cellular and Synaptic Mechanisms and Comparison with Other Electrophysiological Cell Types

Nowak, L. G., Sanchez-Vives, M. V., McCormick, D. A. — 2008-04-10

Neurons in cat area 17 can be grouped in 4 different electrophysiological cell classes (regular spiking, intrinsically bursting, chattering, and fast spiking [FS]). However, little is known of the functional properties of these different cell classes. Here we compared orientation and direction selectivity between these cell classes in cat area 17 and found that a subset of FS inhibitory neurons, usually with complex receptive fields, exhibited little selectivity in comparison with other cell types. Differences in occurrence and amplitude of gamma-range membrane fluctuations, as well as in numbers of action potentials in response to optimal visual stimuli, did not parallel differences observed for orientation and direction selectivity. Instead, differences in selectivity resulted mostly from differences in tuning of the membrane potential responses, although variations in spike threshold also contributed: weakly selective FS neurons exhibited both a lower spike threshold and more broadly tuned membrane potential responses in comparison with the other cell classes. Our results are consistent with the hypothesis that a subgroup of FS neurons receives connections and possesses intrinsic properties allowing the generation of weakly selective responses. The existence of weakly selective inhibitory neurons is consistent with orientation selectivity models that rely on broadly tuned inhibition.

Rhesus Monkey and Human Share a Similar Topography of the Corpus Callosum as Revealed by Diffusion Tensor MRI In Vivo

Hofer, S., Merboldt, K.-D., Tammer, R., Frahm, J. — 2008-04-10

A recent study of the corpus callosum (CC) in humans revealed a new topographical arrangement of the cortical connectivity pattern. To explore the CC topography in nonhuman primates, we applied magnetic resonance diffusion tensor imaging and tract tracing techniques in individual rhesus monkeys in vivo. The results demonstrate that the CC topography of primates and humans is surprisingly similar. In particular, the relatively large representation and caudal extension of commissural frontal fibers in the CC is observed in both the monkey and human brain. If evolutionary changes in relative brain volumes are reflected in the arrangement of related fibers crossing the CC, the current study is in line with the fact that the relative volume of the frontal lobe did not significantly increase after the split of the hominid line from other primates.

Enhanced Response of Neurons in Rat Somatosensory Cortex to Stimuli Containing Temporal Noise

Lak, A., Arabzadeh, E., Diamond, M. E. — 2008-04-10

Sensory stimuli under natural conditions often consist of a temporally irregular sequence of events, contrasting with the periodic sequences commonly used as stimuli in the laboratory. These experiments compared the responses of neurons in rat barrel cortex with trains of whisker movements with different frequencies; each train possessed either a periodic or an irregular, "noisy" temporal structure. Periodic stimulus trains were composed of a sequence of 21 whisker deflections separated by 20 equal interdeflection intervals (IDIs). Noisy trains were matched for mean IDI but included intervals shorter and longer than the mean IDI. Cortical responses were equivalent for periodic and noisy stimuli for frequencies up to 10 Hz. Above 10 Hz, temporal noise led to a larger response magnitude, and this effect was amplified as deflection frequency increased. Noise also caused a sharpening of the temporal precision of response to the individual deflections of the stimulus train. Cortical neurons thus appear to be "tuned" to respond in a different way to stimuli characterized by temporal unpredictability. As a consequence, perceptual judgments that depend on somatosensory cortical firing rate may be affected by the presence of temporal noise.

Cortical Connections of the Macaque Anterior Intraparietal (AIP) Area

2008-04-10

We traced the cortical connections of the anterior intraparietal (AIP) area, which is known to play a crucial role in visuomotor transformations for grasping. AIP displayed major connections with 1) areas of the inferior parietal lobule convexity, the rostral part of the lateral intraparietal area and the SII region; 2) ventral visual stream areas of the lower bank of the superior temporal sulcus and the middle temporal gyrus; and 3) the premotor area F5 and prefrontal areas 46 and 12. Additional connections were observed with the caudal intraparietal area and the ventral part of the frontal eye field. This study suggests that visuomotor transformations for object-oriented actions, processed in AIP, rely not only on dorsal visual stream information related to the object's physical properties but also on ventral visual stream information related to object identity. The identification of direct anatomical connections with the inferotemporal cortex suggests that AIP also has a unique role in linking the parietofrontal network of areas involved in sensorimotor transformations for grasping with areas involved in object recognition. Thus, AIP could represent a crucial node in a cortical circuit in which hand-related sensory and motor signals gain access to representations of object identity for tactile object recognition.

Tracking the Temporal Dynamics of Updating Cognitive Control: An Examination of Error Processing

West, R., Travers, S. — 2008-04-10

In 2 experiments, we used event-related brain potentials (ERPs) to examine the temporal dynamics of neural processes related to adjustments of cognitive control following errors in the counting Stroop task. The ERPs elicited by errors revealed the error-related negativity (ERN) and error positivity consistent with a large body of literature. In addition, errors were associated with a frontal slow wave between 200 and 2000 ms after the response that was consistent with the activity of neural generators in the lateral frontal cortex. The ERN and frontal slow wave were correlated with posterror slowing of response time and positive affect (i.e., happiness and calmness) during task performance. These data are consistent with the idea that interactions between anterior cingulate cortex and lateral frontal cortex support adjustments of cognitive control and that this neural network is sensitive to the influence of affect experienced during task performance.

Unusual Patch-Matrix Organization in the Retrosplenial Cortex of the reeler Mouse and Shaking Rat Kawasaki

2008-04-10

The rat granular retrosplenial cortex (GRS) is a simplified cortex, with distinct stratification and, in the uppermost layers, distinct modularity. Thalamic and cortical inputs are segregated by layers and in layer 1 colocalize, respectively, with apical dendritic bundles originating from neurons in layers 2 or 5. To further investigate this organization, we turned to reelin-deficient reeler mouse and Shaking rat Kawasaki. We found that the disrupted lamination, evident in Nissl stains in these rodents, is in fact a patch–matrix mosaic of segregated afferents and dendrites. Patches consist of thalamocortical connections, visualized by vesicular glutamate transporter 2 (VGluT2) or AChE. The surrounding matrix consists of corticocortical terminations, visualized by VGluT1 or zinc. Dendrites concentrate in the matrix or patches, depending on whether they are OCAM positive (matrix) or negative (patches). In wild-type rodents and, presumably, mutants, OCAM⁺ structures originate from layer 5 neurons. By double labeling for dendrites (filled by Lucifer yellow in fixed slice) and OCAM immunofluorescence, we ascertained 2 populations in reeler: dendritic branches either preferred (putative layer 5 neurons) or avoided (putative supragranular neurons) the OCAM⁺ matrix. We conclude that input–target relationships are largely preserved in the mutant GRS and that dendrite–dendrite interactions involving OCAM influence the formation of the mosaic configuration.

A Frontoparietal Network for Spatial Attention Reorienting in the Auditory Domain: A Human fMRI/MEG Study of Functional and Temporal Dynamics

2008-04-10

Several studies have identified a supramodal network critical to the reorienting of attention toward stimuli at novel locations and which involves the right temporoparietal junction and the inferior frontal areas. The present functional magnetic resonance imaging (fMRI)\magnetoencephalography (MEG) study investigates: 1) the cerebral circuit underlying attentional reorienting to spatially varying sound locations; 2) the circuit related to the regular change of sound location in the same hemifield, the change of sound location across hemifields, or sounds presented randomly at different locations on the azimuth plane; 3) functional temporal dynamics of the observed cortical areas exploiting the complementary characteristics of the fMRI and MEG paradigms. fMRI results suggest 3 distinct roles: the supratemporal plane appears modulated by variations of sound location; the inferior parietal lobule is modulated by the cross-meridian effect; and the inferior frontal cortex is engaged by the inhibition of a motor response. MEG data help to elucidate the temporal dynamics of this network by providing high-resolution time series with which to measure latency of neural activation manipulated by the reorienting of attention.

Decomposing the Neural Correlates of Antisaccade Eye Movements Using Event-Related fMRI

2008-04-10

The antisaccade task is a model of the conflict between an unwanted reflexive response (which must be inhibited) and a complex volitional response (which must be generated). The present experiment aimed to investigate separately the neural correlates of these cognitive components using a delayed saccade paradigm to dissociate saccade inhibition from generation. Seventeen healthy volunteers completed event-related functional magnetic resonance imaging at 1.5 T during saccades to and away from a peripheral visual target (prosaccades and antisaccades, respectively). Saccades were requested in response to an auditory go signal on average 12 s after peripheral target appearance. It was found that the right supramarginal gyrus showed significantly greater activation during the inhibition phase than the generation phase of the paradigm for both antisaccade and prosaccade trials, suggesting a role in saccade inhibition or stimulus detection. On the other hand, the right lateral frontal eye field and bilateral intraparietal sulcus showed evidence of selective involvement in antisaccade generation. Ventrolateral and dorsolateral prefrontal cortices showed comparable levels of activation in both phases of the task. These areas likely fulfill a more general supervisory role in the volitional control of eye movements, such as stimulus appraisal, task set, and decision making.

Action Outcomes Are Represented in Human Inferior Frontoparietal Cortex

de C. Hamilton, A. F., Grafton, S. T. — 2008-04-10

The simple action of pressing a switch has many possible interpretations—the actor could be turning on a light, deleting critical files from a computer, or even turning off a life-support system. In each of these cases, the motor parameters of the action are the same but the physical outcome differs. We report evidence of suppressed responses in right inferior parietal and right inferior frontal cortex when participants saw repeated movies showing the same action outcome, but these regions did not distinguish the kinematic parameters by which the action was accomplished. Thus, these brain areas encode the physical outcomes of human actions in the world. These results are compatible with a hierarchical model of human action understanding in which a cascade of specialized processes from occipital to parietal and frontal regions allow humans to understand the physical consequences of actions in the world and the intentions underlying those actions.

Shared Neural Resources between Music and Language Indicate Semantic Processing of Musical Tension-Resolution Patterns

Steinbeis, N., Koelsch, S. — 2008-04-10

Harmonic tension-resolution patterns have long been hypothesized to be meaningful to listeners familiar with Western music. Even though it has been shown that specifically chosen musical pieces can prime meaningful concepts, the empirical evidence in favor of such a highly specific semantic pathway has been lacking. Here we show that 2 event-related potentials in response to harmonic expectancy violations, the early right anterior negativity (ERAN) and the N500, could be systematically modulated by simultaneously presented language material containing either a syntactic or a semantic violation. Whereas the ERAN was reduced only when presented concurrently with a syntactic language violation and not with a semantic language violation, this pattern was reversed for the N500. This is the first piece of evidence showing that tension- resolution patterns represent a route to meaning in music.

Rhythmic Spontaneous Activity in the Piriform Cortex

2008-04-10

Slow spontaneous rhythmic activity is generated and propagates in neocortical slices when bathed in an artificial cerebrospinal fluid with ionic concentrations similar to the ones in vivo. This activity is extraordinarily similar to the activation of the cortex in physiological conditions (e.g., slow-wave sleep), thus representing a unique in vitro model to understand how cortical networks maintain and control ongoing activity. Here we have characterized the activity generated in the olfactory or piriform cortex and endopiriform nucleus (piriform network). Because these structures are prone to generate epileptic discharges, it seems critical to understand how they generate and regulate their physiological rhythmic activity. The piriform network gave rise to rhythmic spontaneous activity consisting of a succession of up and down states at an average frequency of 1.8 Hz, qualitatively similar to the corresponding neocortical activity. This activity originated in the deep layers of the piriform network, which displayed higher excitability and denser connectivity. A remarkable difference with neocortical activity was the speed of horizontal propagation (114 mm/s), one order of magnitude faster in the piriform network. Properties of the piriform cortex subserving fast horizontal propagation may underlie the higher vulnerability of this area to epileptic seizures.

Cortical Steady-State Responses to Central and Peripheral Auditory Beats

Draganova, R., Ross, B., Wollbrink, A., Pantev, C. — 2008-04-10

Different types of generation mechanisms of 40-Hz auditory steady-state response (ASSR) were investigated using diotic and dichotic stimulation with 500- and 540-Hz pure tones of 1.0-s duration and 2.0-s stimulus onset asynchrony. When the sum of both tones was presented to both ears simultaneously, they interacted at cochlear level and resulted in perception of a 40-Hz beat termed "peripheral beat." Dichotic presentation of the 500-Hz tone to one ear and the 540-Hz tone to the other one resulted in beat perception as the effect of central interaction, most likely in the superior olivary nuclei and was termed "central beat." ASSR and transient N1m responses were found in the averaged 151-channel whole-head magnetoencephalographic recordings under both stimulus conditions and were modeled with single spatiotemporal equivalent current dipoles in both hemispheres. The ASSR sources in both conditions were more anterior, more inferior, and more medial compared with N1m sources. Right hemispheric lateralization of the magnetic field strength was found for the ASSR in both stimulus conditions. Although the central and peripheral beat interacted at different levels of the auditory system, the initial responses were projected along the afferent auditory pathway and activated common cortical sources.

Que PASA? The Posterior-Anterior Shift in Aging

Davis, S. W., Dennis, N. A., Daselaar, S. M., Fleck, M. S., Cabeza, R. — 2008-04-10

A consistent finding from functional neuroimaging studies of cognitive aging is an age-related reduction in occipital activity coupled with increased frontal activity. This posterior–anterior shift in aging (PASA) has been typically attributed to functional compensation. The present functional magnetic resonance imaging sought to 1) confirm that PASA reflects the effects of aging rather than differences in task difficulty; 2) test the compensation hypothesis; and 3) investigate whether PASA generalizes to deactivations. Young and older participants were scanned during episodic retrieval and visual perceptual tasks, and age-related changes in brain activity common to both tasks were identified. The study yielded 3 main findings. First, inconsistent with a difficulty account, the PASA pattern was found across task and confidence levels when matching performance among groups. Second, supporting the compensatory hypothesis, age-related increases in frontal activity were positively correlated with performance and negatively correlated with the age-related occipital decreases. Age-related increases and correlations with parietal activity were also found. Finally, supporting the generalizability of the PASA pattern to deactivations, aging reduced deactivations in posterior midline cortex but increased deactivations in medial frontal cortex. Taken together, these findings demonstrate the validity, function, and generalizability of PASA, as well as its importance for the cognitive neuroscience of aging.

Attention and Executive Systems Abnormalities in Adults with Childhood ADHD: A DT-MRI Study of Connections

2008-04-10

Attention-deficit/hyperactivity disorder (ADHD) is hypothesized to be due, in part, to structural defects in brain networks influencing cognitive, affective, and motor behaviors. Although the current literature on fiber tracts is limited in ADHD, gray matter abnormalities suggest that white matter (WM) connections may be altered selectively in neural systems. A prior study (Ashtari et al. 2005), using diffusion tensor magnetic resonance imaging (DT-MRI), showed alterations within the frontal and cerebellar WM in children and adolescents with ADHD. In this study of adults with childhood ADHD, we hypothesized that fiber pathways subserving attention and executive functions (EFs) would be altered. To this end, the cingulum bundle (CB) and superior longitudinal fascicle II (SLF II) were investigated in vivo in 12 adults with childhood ADHD and 17 demographically comparable unaffected controls using DT-MRI. Relative to controls, the fractional anisotropy (FA) values were significantly smaller in both regions of interest in the right hemisphere, in contrast to a control region (the fornix), indicating an alteration of anatomical connections within the attention and EF cerebral systems in adults with childhood ADHD. The demonstration of FA abnormalities in the CB and SLF II in adults with childhood ADHD provides further support for persistent structural abnormalities into adulthood.

Influence of Binocular Competition on the Expression Profiles of CRMP2, CRMP4, Dyn I, and Syt I in Developing Cat Visual Cortex

Cnops, L., Hu, T.-T., Burnat, K., Arckens, L. — 2008-04-10

The visual cortex is vulnerable to changes in visual input, especially during the critical period when numerous molecules drive the refinement of the circuitry. From a list of potential actors identified in a recent proteomics study, we selected 2 collapsin response mediator proteins (CRMP2/CRMP4) and 2 synaptic proteins, Dynamin I (Dyn I) and Synaptotagmin I (Syt I), for in-depth analysis of their developmental expression profile in cat visual cortex. CRMP2 and CRMP4 levels were high early in life and clearly declined toward adulthood. In contrast, Dyn I expression levels progressively augmented during maturation. Syt I showed low levels at eye opening and in adults, high levels around the peak of the critical period, and maximal levels at juvenile age. We further determined a role for each molecule in ocular dominance plasticity. CRMP2 and Syt I levels decreased in area 17 upon monocular deprivation, whereas CRMP4 and Dyn I levels remained unaffected. In contrast, binocular removal of pattern vision had no influence on CRMP2 and Syt I expression in kitten area 17. This study illustrates that not the loss of quality of vision through visual deprivation, but disruption of normal binocular visual experience is crucial to induce the observed molecular changes.

Cortical Neuronal Responses to Optic Flow Are Shaped by Visual Strategies for Steering

Page, W. K., Duffy, C. J. — 2008-03-11

We hypothesized that neuronal responses to virtual self-movement would be enhanced during steering tasks. We recorded the activity of medial superior temporal (MSTd) neurons in monkeys trained to steer a straight-ahead course, using optic flow. We found smaller optic flow responses during active steering than during the passive viewing of the same stimuli. Behavioral analysis showed that the monkeys had learned to steer using local motion cues. Retraining the monkeys to use the global pattern of optic flow reversed the effects of the active-steering task: active steering then evoked larger responses than passive viewing.

We then compared the responses of neurons during active steering by local motion and by global patterns: Local motion trials promoted the use of local dot movement near the center of the stimulus by occluding the peripheral visual field midway through the trial. Global pattern trials promoted the use of radial pattern movement by occluding the central visual field midway through the trial. In this study, identical full-field optic-flow stimuli evoked larger responses in global-pattern trials than in local motion trials. We conclude that the selection of specific visual cues reflects strategies for active steering and alters MSTd neuronal responses to optic flow.

The Different Neural Correlates of Action and Functional Knowledge in Semantic Memory: An fMRI Study

2008-03-11

Previous reports suggest that the internal organization of semantic memory is in terms of different "types of knowledge," including "sensory" (information about perceptual features), "action" (motor-based knowledge of object utilization), and "functional" (abstract properties, as function and context of use). Consistent with this view, a specific loss of action knowledge, with preserved functional knowledge, has been recently observed in patients with left frontoparietal lesions. The opposite pattern (impaired functional knowledge with preserved action knowledge) was reported in association with anterior inferotemporal lesions. In the present study, the cerebral representation of action and functional knowledge was investigated using event-related analysis of functional magnetic resonance imaging data. Fifteen subjects were presented with pictures showing pairs of manipulable objects and asked whether the objects within each pair were used with the same manipulation pattern ("action knowledge" condition) or in the same context ("functional knowledge" condition). Direct comparisons showed action knowledge, relative to functional knowledge, to activate a left frontoparietal network, comprising the intraparietal sulcus, the inferior parietal lobule, and the dorsal premotor cortex. The reverse comparison yielded activations in the retrosplenial and the lateral anterior inferotemporal cortex. These results confirm and extend previous neuropsychological data and support the hypothesis of the existence of different types of information processing in the internal organization of semantic memory.

Pax6-/- Mice Have a Cell Nonautonomous Defect in Nonradial Interneuron Migration

Gopal, P. P., Golden, J. A. — 2008-03-11

The mammalian neocortex comprises two major neuronal subtypes; interneurons derived from the ganglionic eminence (GE) and projection neurons from the cortical ventricular zone (VZ). These separate origins necessitate distinct pathways of migration. Using mouse genetics and embryonic forebrain slice culture assays, we sought to identify substrates and/or guidance molecules for nonradial cell migration (NRCM). Mice carrying a mutation in Pax6 (Sey^–/–), a paired domain transcription factor, are reported to have increased numbers of cortical inhibitory interneurons, suggesting that Pax6 could induce inhibitors of interneuron development or alternatively play a repressive role in guiding NRCM and/or specifying interneurons. Unexpectedly, we found a cell nonautonomous reduction in the distance Sey^–/– neurons migrated, reflecting a disorganized migration, with frequent changes in direction. In contrast, no difference in the number of nonradially migrating GE cells was observed in Sey^–/– mice. Our data indicate that the increased numbers of interneurons observed in Sey^–/– do not result from an increased rate or number of nonradially migrating cells; instead, loss of Pax6 results in the ectopic specification of interneurons in the cortical VZ. Further, our data indicate that the known axonal disorganization in Sey^–/– mice contributes to the observed reduced distance of NRCM.

Hyperconnectivity of Local Neocortical Microcircuitry Induced by Prenatal Exposure to Valproic Acid

Rinaldi, T., Silberberg, G., Markram, H. — 2008-03-11

Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render cortical modules more sensitive to stimulation and once activated, more autonomous, isolated, and more difficult to command. This could underlie some of the core symptoms observed in humans prenatally exposed to valproic acid.

Asymmetric Synaptic Depression in Cortical Networks

Chelaru, M. I., Dragoi, V. — 2008-03-11

Synaptic depression is essential for controlling the balance between excitation and inhibition in cortical networks. Several studies have shown that the depression of intracortical synapses is asymmetric, that is, inhibitory synapses depress less than excitatory ones. Whether this asymmetry has any impact on cortical function is unknown. Here we show that the differential depression of intracortical synapses provides a mechanism through which the gain and sensitivity of cortical circuits shifts over time to improve stimulus coding. We examined the functional consequences of asymmetric synaptic depression by modeling recurrent interactions between orientation-selective neurons in primary visual cortex (V1) that adapt to feedforward inputs. We demonstrate analytically that despite the fact that excitatory synapses depress more than inhibitory synapses, excitatory responses are reduced less than inhibitory ones to increase the overall response gain. These changes play an active role in generating selective gain control in visual cortical circuits. Specifically, asymmetric synaptic depression regulates network selectivity by amplifying responses and sensitivity of V1 neurons to infrequent stimuli and attenuating responses and sensitivity to frequent stimuli, as is indeed observed experimentally.

Visual Scenes Trigger Immediate Syntactic Reanalysis: Evidence from ERPs during Situated Spoken Comprehension

Knoeferle, P., Habets, B., Crocker, M. W., Munte, T. F. — 2008-03-11

A central topic in sentence comprehension research is the kinds of information and mechanisms involved in resolving temporary ambiguity regarding the syntactic structure of a sentence. Gaze patterns in scenes during spoken sentence comprehension have provided strong evidence that visual scenes trigger rapid syntactic reanalysis. However, they have also been interpreted as reflecting nonlinguistic, visual processes. Furthermore, little is known as to whether similar processes of syntactic revision are triggered by linguistic versus scene cues. To better understand how scenes influence comprehension and its time course, we recorded event-related potentials (ERPs) during the comprehension of spoken sentences that relate to depicted events. Prior electrophysiological research has observed a P600 when structural disambiguation toward a noncanonical structure occurred during reading and in the absence of scenes. We observed an ERP component with a similar latency, polarity, and distribution when depicted events disambiguated toward a noncanonical structure. The distributional similarities further suggest that scenes are on a par with linguistic contexts in triggering syntactic revision. Our findings confirm the interpretation of previous eye movement studies and highlight the benefits of combining ERP and eye-tracking measures to ascertain the neuronal processes enabled by, and the locus of attention in, visual contexts.

The Functional Integration of the Anterior Cingulate Cortex during Conflict Processing

Fan, J., Hof, P. R., Guise, K. G., Fossella, J. A., Posner, M. I. — 2008-03-11

Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.

Visual, Somatosensory, and Bimodal Activities in the Macaque Parietal Area PEc

Breveglieri, R., Galletti, C., Monaco, S., Fattori, P. — 2008-03-11

Caudal area PE (PEc) of the macaque posterior parietal cortex has been shown to be a crucial node in visuomotor coordination during reaching. The present study was aimed at studying visual and somatosensory organization of this cortical area. Visual stimulations activated 53% of PEc neurons. The overwhelming majority (89%) of these visual cells were best activated by a dark stimulus on a lighter background. Somatosensory stimulations activated 56% of PEc neurons: most were joint neurons (73%); a minority (24%) showed tactile receptive fields, most of them located on the arms. Area PEc has not a clear retinotopy or somatotopy. Among the cells tested for both somatosensory and visual sensitivity, 22% were bimodal, 25% unimodal somatosensory, 34% unimodal visual, and 19% were insensitive to either stimulation. No clear clustering of the different classes of sensory neurons was observed. Visual and somatosensory receptive fields of bimodal cells were not in register. The damage in the human brain of the likely homologous of macaque PEc produces deficits in locomotion and in whole-body interaction with the visual environment. Present data show that macaque PEc has sensory properties and a functional organization in line with the view of an involvement of this area in those processes.

Distinct Causal Influences of Parietal Versus Frontal Areas on Human Visual Cortex: Evidence from Concurrent TMS-fMRI

2008-03-11

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level–dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1–V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1–V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex.

Volume of Left Heschl's Gyrus and Linguistic Pitch Learning

2008-03-11

Research on the contributions of the human nervous system to language processing and learning has generally been focused on the association regions of the brain without considering the possible contribution of primary and adjacent sensory areas. We report a study examining the relationship between the anatomy of Heschl's Gyrus (HG), which includes predominately primary auditory areas and is often found to be associated with nonlinguistic pitch processing and language learning. Unlike English, most languages of the world use pitch patterns to signal word meaning. In the present study, native English-speaking adult subjects learned to incorporate foreign pitch patterns in word identification. Subjects who were less successful in learning showed a smaller HG volume on the left (especially gray matter volume), but not on the right, relative to learners who were successful. These results suggest that HG, typically shown to be associated with the processing of acoustic cues in nonspeech processing, is also involved in speech learning. These results also suggest that primary auditory regions may be important for encoding basic acoustic cues during the course of spoken language learning.

A Larynx Area in the Human Motor Cortex

Brown, S., Ngan, E., Liotti, M. — 2008-03-11

The map of the human motor cortex has lacked a representation for the intrinsic musculature of the larynx ever since the electrical stimulation studies of Penfield. In addition, there has been no attempt to localize this area using neuroimaging techniques. Because of the central importance of laryngeal function to vocalization, we sought to localize an area controlling the intrinsic muscles of the larynx by using functional magnetic resonance imaging and to place this area in a somatotopic context. We had subjects perform a series of oral tasks designed to isolate elementary components of phonation and articulation, including vocalization of a vowel, lip movement, and tongue movement. In addition, and for the first time in a neuroimaging study, we had subjects perform "glottal stops," in other words forced closure of the glottis in the absence of vocalizing. The results demonstrated a larynx-specific area in the motor cortex that is activated comparably by vocal and nonvocal laryngeal tasks. Converging evidence suggests that this area is the principal vocal center of the human motor cortex. Finally, the location of this larynx area is strikingly different from that reported in the monkey. We discuss the implications of this observation for the evolution of vocal communication in humans.

Observer-Independent Cytoarchitectonic Mapping of the Human Superior Parietal Cortex

2008-03-11

The human superior parietal cortex (SPC; Brodmann areas [BA] 5 and 7) comprises the superior parietal lobule and medial wall of the intraparietal sulcus (mIPS) laterally and the posterior paracentral lobule and precuneus medially. Receptor autoradiographic and functional studies indicate more complex segregations in the SPC than suggested by Brodmann (1909). Differences to other historical maps may be due to anatomical variability between brains and different definition criteria for areas. To provide a reliable anatomical reference of the SPC, we performed an observer-independent cytoarchitectonic mapping of this region in 10 human postmortem brains. Cytoarchitecture was analyzed in cell-body–stained brain sections using gray-level index profiles. Multivariate statistical analysis of profile shape allowed the exact localization of cytoarchitectonic borders and quantification of interareal differences. We identified 3 areas in BA 5 (5L, 5M, and 5Ci), 4 in BA 7 (7PC, 7A, 7P, and 7M), and 1 in the anterior mIPS (hIP3). Locations of their borders relative to macroanatomical landmarks varied considerably between brains and hemispheres. Cytoarchitectonic profiles of areas 5Ci and hIP3 differed most from those of the remaining areas, and differences between subareas were stronger in BA 5 than in BA 7. These areas are possible structural correlates of functional segregations within the SPC.

The Relationship between Study Processing and the Effects of Cue Congruency at Retrieval: fMRI Support for Transfer Appropriate Processing

Park, H., Rugg, M. D. — 2008-03-11

Using functional magnetic resonance imaging, the present study investigated whether the enhanced memory performance associated with congruent relative to incongruent retrieval cues is modulated by how items are encoded. Subjects studied a list of visually presented words and pictures and attempted to recognize these items in a later memory test. Half of the studied items were tested with a congruent cue (word–word and picture–picture), whereas the remainders were tested with an incongruent cue (word–picture and picture–word). For both words and pictures, regions where study activity was greater for congruently than incongruently cued items overlapped regions where activity differentiated the 2 classes of study material. Thus, word congruency effects overlapped regions where activity elicited by study words exceeded the activity elicited by pictures. Similarly, picture congruency effects overlapped regions demonstrating enhanced activity for pictures relative to words. In addition, several regions, including dorsolateral prefrontal cortex and intraparietal sulcus, demonstrated material-nonspecific congruency effects. The findings suggest that items benefit from a congruent retrieval cue when their study processing resembles the processing later engaged by the retrieval cue. Consistent with the principle of transfer appropriate processing, the benefit of a congruent retrieval cue derives from the interaction between study and retrieval processing.

Subcolumnar Dendritic and Axonal Organization of Spiny Stellate and Star Pyramid Neurons within a Barrel in Rat Somatosensory Cortex

Egger, V., Nevian, T., Bruno, R. M. — 2008-03-11

Excitatory neurons at the level of cortical layer 4 in the rodent somatosensory barrel field often display a strong eccentricity in comparison with layer 4 neurons in other cortical regions. In rat, dendritic symmetry of the 2 main excitatory neuronal classes, spiny stellate and star pyramid neurons (SSNs and SPNs), was quantified by an asymmetry index, the dendrite-free angle. We carefully measured shrinkage and analyzed its influence on morphological parameters. SSNs had mostly eccentric morphology, whereas SPNs were nearly radially symmetric. Most asymmetric neurons were located near the barrel border. The axonal projections, analyzed at the level of layer 4, were mostly restricted to a single barrel except for those of 3 interbarrel projection neurons. Comparing voxel representations of dendrites and axon collaterals of the same neuron revealed a close overlap of dendritic and axonal fields, more pronounced in SSNs versus SPNs and considerably stronger in spiny L4 neurons versus extragranular pyramidal cells. These observations suggest that within a barrel dendrites and axons of individual excitatory cells are organized in subcolumns that may confer receptive field properties such as directional selectivity to higher layers, whereas the interbarrel projections challenge our view of barrels as completely independent processors of thalamic input.

Morphological and Metabolic Changes in the Cortex of Mice Lacking the Functional Presynaptic Active Zone Protein Bassoon: A Combined 1H-NMR Spectroscopy and Histochemical Study

2008-03-11

Mice lacking functional presynaptic active zone protein Bassoon are characterized by an enlarged cerebral cortex and an altered cortical activation pattern. This morphological and functional phenotype is associated with defined metabolic distortions as detected by a metabonomic approach using high-field (14.1 T) high-resolution ¹H-nuclear magnetic resonance spectroscopy (MRS) in conjunction with statistical pattern recognition. Within the cortex but not in the cerebellum, concentrations of N-acetyl aspartate, glutamine, and glutamate are significantly reduced, whereas the majority of all other detectable low molecular metabolites are unchanged. The reduction of the neuron-specific metabolite N-acetyl aspartate in the cortex coincides with a significant decrease in neuronal density in cortical layer V. Comparing the neuron with glia cell densities across the cortex reveals cortex layer–dependent alterations in the ratio between both cell types. Whereas the ratio shifts significantly toward neurons in the cortical input layers IV, the ratio is reversed in cortical layer V. Consequently, the previously observed altered neuronal activation pattern in the cortex is reflected not only in defined cytoarchitectural anomalies but also in metabolic disturbances in the glutamine–glutamate and N-acetyl aspartate metabolism.

Brain Activations during Judgments of Positive Self-conscious Emotion and Positive Basic Emotion: Pride and Joy

2008-03-11

We aimed to investigate the neural correlates associated with judgments of a positive self-conscious emotion, pride, and elucidate the difference between pride and a basic positive emotion, joy, at the neural basis level using functional magnetic resonance imaging. Study of the neural basis associated with pride might contribute to a better understanding of the pride-related behaviors observed in neuropsychiatric disorders. Sixteen healthy volunteers were studied. The participants read sentences expressing joy or pride contents during the scans. Pride conditions activated the right posterior superior temporal sulcus and left temporal pole, the regions implicated in the neural substrate of social cognition or theory of mind. However, against our prediction, we did not find brain activation in the medial prefrontal cortex, a region responsible for inferring others' intention or self-reflection. Joy condition produced activations in the ventral striatum and insula/operculum, the key nodes of processing of hedonic or appetitive stimuli. Our results support the idea that pride is a self-conscious emotion, requiring the ability to detect the intention of others. At the same time, judgment of pride might require less self-reflection compared with those of negative self-conscious emotions such as guilt or embarrassment.

Role of Prefrontal and Parietal Cortices in Associative Learning

Anderson, J. R., Byrne, D., Fincham, J. M., Gunn, P. — 2008-03-11

Two studies were performed that compared a "Paired" condition in which participants studied paired associates with a "Generated" condition in which participants completed word fragments to produce paired associates. In both tasks, participants were responsible for memory of the material either studied or generated. The experiments revealed significant differences between the responses of a predefined prefrontal region and a predefined parietal region. The parietal region responded more in the Generated condition than the Paired condition, whereas there was no difference in the prefrontal region. On the other hand, the prefrontal region responded to the delay between study and test in both the Paired and Generated conditions, whereas the parietal region only responded to delay in the Generated condition. This pattern of results is consistent with the hypothesis that the parietal region is responsive to changes in problem representation and the prefrontal region to retrieval operations. An information-processing model embodying these assumptions was fit to the blood oxygen level–dependent responses in these regions.

Lifespan Alterations of Basal Dendritic Trees of Pyramidal Neurons in the Human Prefrontal Cortex: A Layer-Specific Pattern

Petanjek, Z., Judas, M., Kostovic, I., Uylings, H. B.M. — 2008-03-11

The postnatal development and lifespan alterations in basal dendrites of large layer IIIC and layer V pyramidal neurons were quantitatively studied. Both classes of neurons were characterized by rapid dendritic growth during the first postnatal months. At birth, layer V pyramidal neurons had larger and more complex dendritic trees than those of layer IIIC; however, at 1 postnatal month both classes of neurons displayed a similar extent of dendritic outgrowth. In addition, after a more than year-long "dormant" period of only fine dendritic rearrangement, layer IIIC pyramidal neurons displayed a second period of dendritic growth, starting at the end of the second year and continuing in the third year. During that period, the dendritic tree of layer IIIC pyramidal neurons became more extensive than that of layer V pyramidal neurons. Thus, layer IIIC pyramidal neurons appear to show a biphasic pattern of postnatal dendritic development. Furthermore, the childhood period was characterized by transient increase in size of pyramidal cell somata, which was more pronounced for neurons in layer IIIC. These structural changes occurred during both the period of rapid cognitive development in preschool children and the period of protracted cognitive maturation during the childhood, puberty, and adolescence.

The Representation of Blinking Movement in Cingulate Motor Areas: A Functional Magnetic Resonance Imaging Study

Hanakawa, T., Dimyan, M. A., Hallett, M. — 2008-03-11

Recent anatomical evidence from nonhuman primates indicates that cingulate motor areas (CMAs) play a substantial role in the cortical control of upper facial movement. Using event-related functional magnetic resonance imaging in 10 healthy subjects, we examined brain activity associated with volitional eye closure involving primarily the bilateral orbicularis oculi. The findings were compared with those from bimanual tapping, which should identify medial frontal areas nonsomatotopically or somatotopically related to bilateral movements. In a group-level analysis, the blinking task was associated with rostral cingulate activity more strongly than the bimanual tapping task. By contrast, the bimanual task activated the caudal cingulate zone plus supplementary motor areas. An individual-level analysis indicated that 2 foci of blinking-specific activity were situated in the cingulate or paracingulate sulcus: one close to the genu of the corpus callosum (anterior part of rostral cingulate zone) and the posterior part of rostral cingulate zone. The present data support the notion that direct cortical innervation of the facial subnuclei from the CMAs might control upper face movement in humans, as previously implied in nonhuman primates. The CMAs may contribute to the sparing of upper facial muscles after a stroke involving the lateral precentral motor regions.

Absence of LPA1 Signaling Results in Defective Cortical Development

2008-03-11

Lysophosphatidic acid (LPA) is a simple phospholipid with extracellular signaling properties mediated by specific G protein–coupled receptors. At least 2 LPA receptors, LPA₁ and LPA₂, are expressed in the developing brain, the former enriched in the neurogenic ventricular zone (VZ), suggesting a normal role in neurogenesis. Despite numerous studies reporting the effects of exogenous LPA using in vitro neural models, the first LPA₁ loss-of-function mutants reported did not show gross cerebral cortical defects in the 50% that survived perinatal demise. Here, we report a role for LPA₁ in cortical neural precursors resulting from analysis of a variant of a previously characterized LPA₁-null mutant that arose spontaneously during colony expansion. These LPA₁-null mice, termed maLPA₁, exhibit almost complete perinatal viability and show a reduced VZ, altered neuronal markers, and increased cortical cell death that results in a loss of cortical layer cellularity in adults. These data support LPA₁ function in normal cortical development and suggest that the presence of genetic modifiers of LPA₁ influences cerebral cortical development.

Dopamine Modulation of Prefrontal Cortex Interneurons Occurs Independently of DARPP-32

Trantham-Davidson, H., Kroner, S., Seamans, J. K. — 2008-03-11

Dopamine (DA) exerts a strong influence on inhibition in prefrontal cortex. The main cortical interneuron subtype targeted by DA are fast-spiking -aminobutyric acidergic (GABAergic) cells that express the calcium-binding protein parvalbumin. D1 stimulation depolarizes these interneurons and increases excitability evoked by current injection. The present study examined whether this direct DA-dependent modulation of fast-spiking interneurons involves DARPP-32. Whole-cell patch-clamp recordings were made from fast-spiking interneurons in brain slices from DARPP-32 knockout (KO) mice, wild-type mice, and rats. Low concentrations of DA (100 nM) increased interneuron excitability via D1 receptors, protein kinase A, and cyclic adenosine 3',5'-monophosphate in slices from both normal and DARPP-32 KO mice. Immunohistochemical staining of slices from normal animals revealed a lack of colocalization of DARPP-32 with calcium-binding proteins selective for fast-spiking interneurons, indicating that these interneurons do not express DARPP-32. Therefore, although DARPP-32 impacts cortical inhibition through a previously demonstrated D2-dependent regulation of GABAergic currents in pyramidal cells, it is not involved in the direct D1-mediated regulation of fast-spiking interneurons.

A Common Neural Network for Cognitive Reserve in Verbal and Object Working Memory in Young but not Old

2008-03-11

Epidemiologic evidence suggests that cognitive reserve (CR) mitigates the effects of aging on cognitive function. The goal of this study was to see whether a common neural mechanism for CR could be demonstrated in brain imaging data acquired during the performance of 2 tasks with differing cognitive processing demands. Young and elder subjects were scanned with functional magnetic resonance imaging (fMRI) while performing a delayed item response task that used either letters (40 young, 18 old) or shapes (24 young, 21 old). Difficulty or load was manipulated by varying the number of stimuli that were presented for encoding. Load-dependent fMRI signal corresponding to each trial component (stimulus presentation, retention delay, and probe) and task (letter or shape) was regressed onto 2 putative CR variables. Canonical variates analysis was applied to the resulting maps of regression coefficients, separately for each trial component, to summarize the imaging data—CR relationships. There was a latent brain pattern noted in the stimulus presentation phase that manifested similar relationships between load-related encoding activation and CR variables across the letter and shape tasks in the young but not the elder age group. This spatial pattern could represent a general neural instantiation of CR that is affected by the aging process.

The Hippocampal CA1 Region and Dentate Gyrus Differentiate between Environmental and Spatial Feature Encoding through Long-Term Depression

Kemp, A., Manahan-Vaughan, D. — 2008-03-11

Novel spatial information is encoded in the hippocampus by plastic changes of synaptic properties. Novel space consists of several types of information that may evoke differential synaptic responses in individual hippocampal subregions. To examine this possibility, we recorded field potentials from the dentate gyrus (DG) and CA1 region in freely moving adult rats. Stimulation protocols that were marginally subthreshold for the induction of persistent long-term potentiation (LTP) or long-term depression (LTD) were implemented, concurrent with exposure to novel spatial information. We found that in both hippocampal subregions, exploration of a novel empty hole board facilitated LTP. However, LTD facilitation was subregion specific and dependent on the nature of the cues. In the CA1 region, partially concealed cues had a facilitatory effect on LTD. LTD in the DG was facilitated by large directional cues. Thus, although LTP was facilitated uniformly in both areas by the same novel environment, LTD was facilitated in a region-specific manner, based on the nature of the cue. This implies that spatial changes within an environment elicit local changes of synaptic weights dependent on the type of information and, hence, generate a complete cognitive map as a consequence of cooperation of synaptic plasticity in all participating subregions.

Cortical Connections of Area V4 in the Macaque

Ungerleider, L. G., Galkin, T. W., Desimone, R., Gattass, R. — 2008-02-14

To determine the locus, full extent, and topographic organization of cortical connections of area V4 (visual area 4), we injected anterograde and retrograde tracers under electrophysiological guidance into 21 sites in 9 macaques. Injection sites included representations ranging from central to far peripheral eccentricities in the upper and lower fields. Our results indicated that all parts of V4 are connected with occipital areas V2 (visual area 2), V3 (visual area 3), and V3A (visual complex V3, part A), superior temporal areas V4t (V4 transition zone), MT (medial temporal area), and FST (fundus of the superior temporal sulcus [STS] area), inferior temporal areas TEO (cytoarchitectonic area TEO in posterior inferior temporal cortex) and TE (cytoarchitectonic area TE in anterior temporal cortex), and the frontal eye field (FEF). By contrast, mainly peripheral field representations of V4 are connected with occipitoparietal areas DP (dorsal prelunate area), VIP (ventral intraparietal area), LIP (lateral intraparietal area), PIP (posterior intraparietal area), parieto-occipital area, and MST (medial STS area), and parahippocampal area TF (cytoarchitectonic area TF on the parahippocampal gyrus). Based on the distribution of labeled cells and terminals, projections from V4 to V2 and V3 are feedback, those to V3A, V4t, MT, DP, VIP, PIP, and FEF are the intermediate type, and those to FST, MST, LIP, TEO, TE, and TF are feedforward. Peripheral field projections from V4 to parietal areas could provide a direct route for rapid activation of circuits serving spatial vision and spatial attention. By contrast, the predominance of central field projections from V4 to inferior temporal areas is consistent with the need for detailed form analysis for object vision.

The Role of Sleep in Declarative Memory Consolidation--Direct Evidence by Intracranial EEG

Axmacher, N., Haupt, S., Fernandez, G., Elger, C. E., Fell, J. — 2008-02-14

Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking state but may become saturated after some time awake. Sleep, in this model, specifically favors restoration of synaptic plasticity and accelerated memory consolidation while asleep and briefly afterwards. To distinguish between these different views, we recorded intracranial electroencephalograms from the hippocampus and rhinal cortex of human subjects while they retrieved information acquired either before or after a "nap" in the afternoon or on a control day without nap. Reaction times, hippocampal event-related potentials, and oscillatory gamma activity indicated a temporal gradient of hippocampal involvement in information retrieval on the control day, suggesting hippocampal–neocortical information transfer during waking state. On the day with nap, retrieval of recent items that were encoded briefly after the nap did not involve the hippocampus to a higher degree than retrieval of items encoded before the nap. These results suggest that sleep facilitates rapid processing through the hippocampus but is not necessary for information transfer into the neocortex per se.

Lateralized Anterior Cingulate Function during Error Processing and Conflict Monitoring as Revealed by High-Resolution fMRI

Lutcke, H., Frahm, J. — 2008-02-14

Recent studies have reported that functional subdivisions of anterior cingulate cortex (ACC) may be selectively responsible for conflict and error-related processing. We examined this claim by imaging ACC activation to correct and erroneous response inhibitions in a GoNogo task. After localizing the ACC cluster in individual subjects using functional magnetic resonance imaging (fMRI) at standard resolution (2 x 2 x 4 mm³), high-resolution fMRI (1.5 x 1.5 x 1.5 mm³) of the ACC was performed in a second session to investigate its precise functional anatomy. At standard resolution, and in agreement with previous studies, ACC was activated for correct and incorrect responses, albeit more so for errors. High-resolution maps of activated ACC clusters revealed localized and reproducible foci in 9 out of 10 volunteers. Multisubject analysis suggested a bilateral distribution of error-related processes in ACC, whereas correct inhibitions only seemed to activate ACC in the right hemisphere. Subsequent region of interest analysis largely confirmed the activation maps. Our results contribute toward a better understanding of the microanatomy of ACC and demonstrate the potential of fMRI for mapping the functional architecture of brain regions involved in cognitive tasks at a previously unaccomplished spatial scale.

Functional Organization of Color Domains in V1 and V2 of Macaque Monkey Revealed by Optical Imaging

Lu, H. D., Roe, A. W. — 2008-02-14

Areas V1 and V2 of Macaque monkey visual cortex are characterized by unique cytochrome-oxidase (CO)–staining patterns. Initial electrophysiological studies associated CO blobs in V1 with processing of surface properties such as color and brightness and the interblobs with contour information processing. However, many subsequent studies showed controversial results, some supporting this proposal and others failing to find significant functional differences between blobs and interblobs. In this study, we have used optical imaging to map color-selective responses in V1 and V2. In V1, we find striking "blob-like" patterns of color response. Fine alignment of optical maps and CO-stained tissue revealed that color domains in V1 strongly associate with CO blobs. We also find color domains in V1 align along centers of ocular dominance columns. Furthermore, color blobs in V1 have low orientation selectivity and do not overlap with centers of orientation domains. In V2, color domains coincide with thin stripes; orientation-selective domains coincide with thick and pale stripes. We conclude that color and orientation-selective responses are preferentially located in distinct CO compartments in V1 and V2. We propose that the term "blob" encompasses both the concept of "CO blob" and "color domain" in V1.

Morphology of the Ventral Frontal Cortex: Relationship to Femininity and Social Cognition

Wood, J. L., Heitmiller, D., Andreasen, N. C., Nopoulos, P. — 2008-02-14

Females have been shown in a number of studies to be more adept in social perception compared with males. In addition, studies have reported that brain regions important in interpretation of nonverbal social cues, such as the ventral frontal cortex (VFC), are morphologically different between genders. To investigate the relationship between the structure of the VFC and social cognition, gray matter volume and surface area of the VFC were measured on magnetic resonance imaging (MRI) scans from 30 men and 30 women matched for age and IQ. The VFC was subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). The SG, but not the OFC, was proportionately larger in women. A subset of subjects was administered the Interpersonal Perception Task (IPT), a test of social perceptiveness, and the Personal Attributes Questionnaire (PAQ), a scale of femininity and masculinity. Identification with more feminine traits on the PAQ correlated with greater SG gray matter volume and surface area. In addition, higher degrees of femininity correlated with better performance on the IPT. Taken together, these data suggest a complex relationship between femininity, social cognition, and the structure of the SG.

Processing Prosodic Boundaries in Natural and Hummed Speech: An fMRI Study

Ischebeck, A. K., Friederici, A. D., Alter, K. — 2008-02-14

Speech contains prosodic cues such as pauses between different phrases of a sentence. These intonational phrase boundaries (IPBs) elicit a specific component in event-related brain potential studies, the so-called closure positive shift. The aim of the present functional magnetic resonance imaging study is to identify the neural correlates of this prosody-related component in sentences containing segmental and prosodic information (natural speech) and hummed sentences only containing prosodic information. Sentences with 2 IPBs both in normal and hummed speech activated the middle superior temporal gyrus, the rolandic operculum, and the gyrus of Heschl more strongly than sentences with 1 IPB. The results from a region of interest analysis of auditory cortex and auditory association areas suggest that the posterior rolandic operculum, in particular, supports the processing of prosodic information. A comparison of natural speech and hummed sentences revealed a number of left-hemispheric areas within the temporal lobe as well as in the frontal and parietal lobe that were activated more strongly for natural speech than for hummed sentences. These areas constitute the neural network for the processing of natural speech. The finding that no area was activated more strongly for hummed sentences compared with natural speech suggests that prosody is an integrated part of natural speech.

Six3 Controls the Neural Progenitor Status in the Murine CNS

Appolloni, I., Calzolari, F., Corte, G., Perris, R., Malatesta, P. — 2008-02-14

Six3, a homeodomain-containing transcriptional regulator belonging to the Six/so family, shows a defined spatiotemporal expression pattern in the developing murine telencephalon, suggesting that it may control the development of specific subsets of neural progenitors. We find that retrovirus-mediated misexpression of Six3 causes clonal expansion of isolated cortical progenitor cells by shortening their cell cycle and by prolonging their amplification period, while maintaining them in an immature precursor state. Our results show that the observed effects exerted by Six3 overexpression in mammalian brain depend strictly on the integrity of its DNA-binding domain, suggesting that Six3 action likely relies exclusively on its transcriptional activity. In vivo upregulation of Six3 expression in single progenitor cells of the embryonic telencephalon keeps them in an undifferentiated state. Our observations point to a role of Six3 in the control of the subtle equilibrium between proliferation and differentiation of defined precursor populations during mammalian neurogenesis.

Effect of Physiological Activity on an NMDA-Dependent Form of Cortical Plasticity in Human

Huang, Y.-Z., Rothwell, J. C., Edwards, M. J., Chen, R.-S. — 2008-02-14

Retention of motor learning can be enhanced or degraded by subsequent performance of a different task. Neurophysiologically this may reflect interference in synaptic plasticity by ongoing neural activity in the brain. Here we demonstrate that N-methyl-D-aspartate (NMDA) dependent aftereffects of repetitive transcranial magnetic stimulation (rTMS) also are subject to interference effects, suggesting that it may be possible to investigate these basic mechanisms in the intact human brain. We measured the motor-evoked potential (MEP) amplitude and short-interval intracortical inhibition (SICI) in the first dorsal interosseous (FDI) muscle after continuous or intermittent theta burst (cTBS/iTBS) forms of rTMS. In resting subjects, cTBS depressed MEPs and reduced SICI for about 20 min, whereas iTBS had the opposite effect. However, if subjects contracted the FDI during TBS, then effects on the MEP were abolished, although effects of cTBS on SICI remained. Contraction immediately after TBS enhanced the facilitatory effect of iTBS and reversed the usual inhibitory effect of cTBS into facilitation. Contraction 10 min after cTBS (iTBS not tested) had only a transient (3–4 min) effect on MEPs. These interactions with behavior may relate to mechanisms of interference between learning paradigms in human and be similar to effects on synaptic long-term potentiation/depression described in animal experiments.

Perisylvian Sulcal Morphology and Cerebral Asymmetry Patterns in Adults Who Stutter

2008-02-14

Previous investigations of cerebral anatomy in persistent developmental stutterers have reported bilateral anomalies in the perisylvian region and atypical patterns of cerebral asymmetry. In this study, perisylvian sulcal patterns were analyzed to compare subjects with persistent developmental stuttering (PDS) and an age-, hand-, and gender-matched control group. This analysis was accomplished using software designed for 3-dimensional sulcal identification and extraction. Patterns of cerebral asymmetry were also investigated with standard planimetric measurements. PDS subjects showed a small but significant increase in both the number of sulci connecting with the second segment of the right Sylvian fissure and in the number of suprasylvian gyral banks (of sulci) along this segment. No differences were seen in the left perisylvian region for either sulcal number or gyral bank number. Measurements of asymmetry revealed typical patterns of cerebral asymmetry in both groups with no significant differences in frontal and occipital width asymmetry, frontal and occipital pole asymmetry, or planum temporale and Sylvian fissure asymmetries. The subtle difference in cortical folding of the right perisylvian region observed in PDS subjects may correlate with functional imaging studies that have reported increased right-hemisphere activity during stuttered speech.