The distribution, number, and certain neurochemical identities of infracortical white matter neurons in the brains of a southern lesser galago, a black-capped squirrel monkey, and a crested macaque.

In the current study, we examined the number, distribution, and aspects of the neurochemical identities of infracortical white matter neurons, also termed white matter interstitial cells (WMICs), in the brains of a southern lesser galago (Galago moholi), a black-capped squirrel monkey (Saimiri boliviensis boliviensis), and a crested macaque (Macaca nigra). Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most dense close to inner cortical border, decreasing in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed estimates of approximately 1.1, 10.8, and 37.7 million WMICs within the infracortical white matter of the galago, squirrel monkey, and crested macaque, respectively. The total numbers of WMICs form a distinct negative allometric relationship with brain mass and white matter volume when examined in a larger sample of primates where similar measures have been obtained. In all three primates studied, the highest densities of WMICs were in the white matter of the frontal lobe, with the occipital lobe having the lowest. Immunostaining revealed significant subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS) and calretinin, with very few WMICs containing parvalbumin, and none containing calbindin. The nNOS and calretinin immunopositive WMICs represent approximately 21% of the total WMIC population; however, variances in the proportions of these neurochemical phenotypes were noted. Our results indicate that both the squirrel monkey and crested macaque might be informative animal models for the study of WMICs in neurodegenerative and psychiatric disorders in humans.

The Topography of the Frontal Terminations of the Uncinate Fasciculus Revisited Through Focused Fiber Dissections: Shedding Light on a Current Controversy and Introducing the Insular Apex as a Key Anatomoclinical Area.

BACKGROUND: Recent studies advocate a connectivity pattern wider than previously believed of the uncinate fasciculus that extends to the ventrolateral and dorsolateral prefrontal cortices. These new percepts on the connectivity of the tract suggest a more expansive role for the uncinate fasciculus. Our aim was to shed light on this controversy through fiber dissections. METHODS: Twenty normal adult human formalin-fixed cerebral hemispheres were used. Focused dissections on the insular, orbitofrontal, ventromedial, ventrolateral, and dorsolateral prefrontal areas were performed to record the topography of the frontal terminations of the uncinate fasciculus. RESULTS: Three discrete fiber layers were consistently disclosed: the first layer was recorded to terminate at the posterior orbital gyrus and pars orbitalis, the second layer at the posterior two thirds of the gyrus rectus, and the last layer at the posterior one third of the paraolfactory gyrus. The insular apex was documented as a crucial landmark regarding the topographic differentiation of the uncinate and occipitofrontal fasciculi (i.e., fibers that travel ventrally belong to the uncinate fasciculus whereas those traveling dorsally are occipitofrontal fibers). CONCLUSIONS: The frontal terminations of the uncinate fasciculus were consistently documented to project to the posterior orbitofrontal area. The area of the insular apex is introduced for the first time as a crucial surface landmark to effectively distinguish the stems of the uncinate and occipitofrontal fasciculi. This finding could refine the spatial resolution of awake subcortical mapping, especially for insular lesions, and improve the accuracy of in vivo diffusion tensor imaging protocols.

Anatomy and White Matter Connections of the Lingual Gyrus and Cuneus.

BACKGROUND: The medial occipital lobe, composed of the lingual gyrus and cuneus, is necessary for both basic and higher level visual processing. It is also known to facilitate cross-modal, nonvisual functions, such as linguistic processing and verbal memory, after the loss of the visual senses. A detailed cortical model elucidating the white matter connectivity associated with this area could improve our understanding of the interacting brain networks that underlie complex human processes and postoperative outcomes related to vision and language. METHODS: Generalized q-sampling imaging tractography, validated by gross anatomic dissection for qualitative visual agreement, was performed on 10 healthy adult controls obtained from the Human Connectome Project. RESULTS: Major white matter connections were identified by tractography and validated by gross dissection, which connected the medial occipital lobe with itself and the adjacent cortices, especially the temporal lobe. The short- and long-range connections identified consisted mainly of U-shaped association fibers, intracuneal fibers, and inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, middle longitudinal fasciculus, and lingual-fusiform connections. CONCLUSIONS: The medial occipital lobe is an extremely interconnected system, supporting its ability to perform coordinated basic visual processing, but also serves as a center for many long-range association fibers, supporting its importance in nonvisual functions, such as language and memory. The presented data represent clinically actionable anatomic information that can be used in multimodal navigation of white matter lesions in the medial occipital lobe to prevent neurologic deficits and improve patients' quality of life after cerebral surgery.

TMS of the occipital face area modulates cross-domain identity priming.

Accumulating evidence suggests that besides its function in early facial feature processing, the role of the right occipital face area (rOFA) extends to higher level, image-independent processing. Recent studies hint at the possibility that the activity of this region can be modulated by semantic information as well. To test whether the OFA is sensitive to semantic information in a functionally relevant way, we implemented a cross-domain, name-face priming paradigm combined with state-dependent transcranial magnetic stimulation, whereby stimulation preferentially facilitates the processing of attributes encoded by less active neural populations. Our volunteers performed a familiarity decision task for target face images preceded by primes that were either the name of the same identity (congruent), a name of a different person (incongruent), or the character string 'XXXXX' (no prime). Stimulating the rOFA at target stimulus onset, we observed the disappearance of the behavioral disadvantage of incongruent primes, compared to the vertex control condition. Performance in the congruent and no prime conditions remained intact. This result suggests the existence of neural populations in the rOFA that take part in the semantic processing of identity, probably in interplay with other nodes in the extended face network.

Cytoarchitectonic segregation of human posterior intraparietal and adjacent parieto-occipital sulcus and its relation to visuomotor and cognitive functions.

Human posterior intraparietal sulcus (pIPS) and adjacent posterior wall of parieto-occipital sulcus (POS) are functionally diverse, serving higher motor, visual and cognitive functions. Its microstructural basis, though, is still largely unknown. A similar or even more pronounced architectonical complexity, as described in monkeys, could be assumed. We cytoarchitectonically mapped the pIPS/POS in 10 human postmortem brains using an observer-independent, quantitative parcellation. 3D-probability maps were generated within MNI reference space and used for functional decoding and meta-analytic coactivation modeling based on the BrainMap database to decode the general structural-functional organization of the areas. Seven cytoarchitectonically distinct areas were identified: five within human pIPS, three on its lateral (hIP4-6) and two on its medial wall (hIP7-8); and two (hPO1, hOc6) in POS. Mediocaudal areas (hIP7, hPO1) were predominantly involved in visual processing, whereas laterorostral areas (hIP4-6, 8) were associated with higher cognitive functions, e.g. counting. This shift was mirrored by systematic changes in connectivity, from temporo-occipital to premotor and prefrontal cortex, and in cytoarchitecture, from prominent Layer IIIc pyramidal cells to homogeneous neuronal distribution. This architectonical mosaic within human pIPS/POS represents a structural basis of its functional and connectional heterogeneity. The new 3D-maps of the areas enable dedicated assessments of structure-function relationships.

Neuropil Distribution in the Anterior Cingulate and Occipital Cortex of Artiodactyls.

Relatively little neuroscience research has been focused on artiodactyls. Recent observations of complex social interactions in domestic and wild species suggest that analyses of artiodactyl brain anatomy would be of comparative value. In this study, we examined how the distribution of cortical neuropil space (a proxy for connectivity) varies across representative members of this diverse clade. Using image analysis techniques, we quantified the neuropil space in the anterior cingulate cortex (ACC) and the occipital (putative primary visual) cortex (OC) of 12 artiodactyl species from adult specimens. Additionally, we conducted a preliminary investigation of variation in ACC neuropil space in a developmental series of five white-tailed deer (Odocoileus virginianus). Results indicate a consistent pattern of greater neuropil space in the ACC in comparison to the OC among all species, and a gradual increase in ACC neuropil space toward maturity in the white-tailed deer. Given the taxa that have the greatest cortical neuropil space, we hypothesize that such enhanced connectivity might be needed to support behaviors such as group foraging and attentiveness to conspecifics. These results help advance a broader understanding of diversity in neural circuitry in artiodactyls and point to the need for more in-depth comparisons of cortical neuron morphology and organization in this relatively understudied taxonomic group. Anat Rec, 301:1871-1881, 2018. © 2018 Wiley Periodicals, Inc.

Area TEO and "Area ?": cytoarchitectonic confusion corrected by connectivity and cortical ablation.

Throughout history, researchers who examine the structure and function of the brain debate one another about how cortical areas are defined, as well as how these areas should be named. Different pieces of empirical evidence are used to define brain areas and it is important to preserve the accurate history of this evidence and the timeline of studies that lead to areal definitions that are either still used today or have been modified. As such, this paper traces the early history of a brain area located at the junction between the occipital and temporal lobes of the macaque known as TEO. This historical analysis leads to four main findings. First, even though Bonin and Bailey are credited with the definition of area TEO in 1947, they did not have the cytoarchitectonic evidence to support the distinction of TEO from adjacent areas. Second, the first evidence definitively separating area TEO from TE was actually based on connectivity as identified with strychnine neuronography by Petr et al. in 1949. Third, causal evidence from ablation studies conducted by Iwai and Mishkin (Experimental Neurology 25(4):585-594, 1969) supported this distinction by showing that TEO and TE were functionally distinct from one another. Fourth, researchers in the 1970s began referring to TEO as posterior inferotemporal (PIT) and TE as anterior inferotemporal (AIT), which is an important historical clarification as the PIT/AIT nomenclature is presently attributed to studies conducted more than a decade later. Altogether, this paper aims to preserve the historical origin of area TEO, as well as the empirical evidence that was used to originally differentiate this cortical expanse from surrounding areas.

The Dynamical Regime of Sensory Cortex: Stable Dynamics around a Single Stimulus-Tuned Attractor Account for Patterns of Noise Variability.

Correlated variability in cortical activity is ubiquitously quenched following stimulus onset, in a stimulus-dependent manner. These modulations have been attributed to circuit dynamics involving either multiple stable states ("attractors") or chaotic activity. Here we show that a qualitatively different dynamical regime, involving fluctuations about a single, stimulus-driven attractor in a loosely balanced excitatory-inhibitory network (the stochastic "stabilized supralinear network"), best explains these modulations. Given the supralinear input/output functions of cortical neurons, increased stimulus drive strengthens effective network connectivity. This shifts the balance from interactions that amplify variability to suppressive inhibitory feedback, quenching correlated variability around more strongly driven steady states. Comparing to previously published and original data analyses, we show that this mechanism, unlike previous proposals, uniquely accounts for the spatial patterns and fast temporal dynamics of variability suppression. Specifying the cortical operating regime is key to understanding the computations underlying perception.

A cross-validated cytoarchitectonic atlas of the human ventral visual stream.

The human ventral visual stream consists of several areas that are considered processing stages essential for perception and recognition. A fundamental microanatomical feature differentiating areas is cytoarchitecture, which refers to the distribution, size, and density of cells across cortical layers. Because cytoarchitectonic structure is measured in 20-micron-thick histological slices of postmortem tissue, it is difficult to assess (a) how anatomically consistent these areas are across brains and (b) how they relate to brain parcellations obtained with prevalent neuroimaging methods, acquired at the millimeter and centimeter scale. Therefore, the goal of this study was to (a) generate a cross-validated cytoarchitectonic atlas of the human ventral visual stream on a whole brain template that is commonly used in neuroimaging studies and (b) to compare this atlas to a recently published retinotopic parcellation of visual cortex (Wang et al., 2014). To achieve this goal, we generated an atlas of eight cytoarchitectonic areas: four areas in the occipital lobe (hOc1-hOc4v) and four in the fusiform gyrus (FG1-FG4), then we tested how the different alignment techniques affect the accuracy of the resulting atlas. Results show that both cortex-based alignment (CBA) and nonlinear volumetric alignment (NVA) generate an atlas with better cross-validation performance than affine volumetric alignment (AVA). Additionally, CBA outperformed NVA in 6/8 of the cytoarchitectonic areas. Finally, the comparison of the cytoarchitectonic atlas to a retinotopic atlas shows a clear correspondence between cytoarchitectonic and retinotopic areas in the ventral visual stream. The successful performance of CBA suggests a coupling between cytoarchitectonic areas and macroanatomical landmarks in the human ventral visual stream, and furthermore, that this coupling can be utilized for generating an accurate group atlas. In addition, the coupling between cytoarchitecture and retinotopy highlights the potential use of this atlas in understanding how anatomical features contribute to brain function. We make this cytoarchitectonic atlas freely available in both BrainVoyager and FreeSurfer formats (http://vpnl.stanford.edu/vcAtlas). The availability of this atlas will enable future studies to link cytoarchitectonic organization to other parcellations of the human ventral visual stream with potential to advance the understanding of this pathway in typical and atypical populations.

Lines of Baillarger in vivo and ex vivo: Myelin contrast across lamina at 7T MRI and histology.

The human cerebral cortex is characterized by a number of features that are not uniformly distributed, such as the presence of multiple cytoarchitectonic elements and of myelinated layers running tangentially to the cortex surface. The presence and absence of these features are the basis of the parcellation of the cerebral cortex in several areas. A number of areas show myelin increases localized within the cortex, e.g., the stria of Gennari located in layer IV of the primary visual cortex. Sub-millimeter MRI can resolve myelin variations across the human cortex and may allow in vivo parcellation of these brain areas. Here, we image within-area myelination. We modified a T1-weighted (T1-w) MPRAGE sequence to enhance myelin visualization within the cortex. First, we acquired images from an ex vivo sample, and compared MRI laminar profiles from calcarine (corresponding to primary visual cortex) and extra-calcarine areas with histology sections from the same locations. Laminar profiles between myelin stained sections and the T1-w images were similar both in calcarine as well as extra-calcarine cortex. In calcarine cortex, the profile reveals the stria of Gennari. In extra-calcarine cortex, a similar profile exists which we suggest corresponds to the lines of Baillarger. Next, we adapted the same sequence to image within-area myelination in vivo. Also in in vivo data, we discriminated similar laminar profiles in calcarine and extra-calcarine cortex, extending into parietal and frontal lobes. We argue that this myelin pattern outside the calcarine cortex represents the lines of Baillarger.

Cytoarchitecture of the human lateral occipital cortex: mapping of two extrastriate areas hOc4la and hOc4lp.

The microstructural correlates of the functional segregation of the human lateral occipital cortex are largely unknown. Therefore, we analyzed the cytoarchitecture of this region in ten human post-mortem brains using an observer-independent and statistically testable parcellation method to define the position and extent of areas in the lateral occipital cortex. Two new cytoarchitectonic areas were found: an anterior area hOc4la and a posterior area hOc4lp. hOc4la was located behind the anterior occipital sulcus in rostral and ventral portions of this region where it occupies the anterior third of the middle and inferior lateral occipital gyri. hOc4lp was found in caudal and dorsal portions of this region where it extends along the superior and middle lateral occipital gyri. The cytoarchitectonic areas were registered to 3D reconstructions of the corresponding brains, which were subsequently spatially normalized to the Montreal Neurological Institute reference space. Continuous probabilistic maps of both areas based on the analysis of ten brains were generated to characterize their inter-subject variability in location and size. The maps of hOc4la and hOc4lp were then used as seeds for meta-analytic connectivity modeling and quantitative functional decoding to identify their co-activation patterns and assignment to functional domains. Convergent evidence from their location, topography, size, functional domains and connectivity indicates that hOc4la and hOc4lp are the potential anatomical correlates of the functionally defined lateral occipital areas LO-1 and LO-2.

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo.

A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca(2+)-imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca(2+) channels and fails to induce action potential firing. Blocking GABA(A) receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA(A) receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.

RIG-1 receptor expression in the pathology of Alzheimer's disease.

BACKGROUND: Neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease (AD) and involves activation of the innate immune response via recognition of diverse stimuli by pattern recognition receptors (PRRs). The inflammatory inducers and precise innate signaling pathway contributing to AD pathology remain largely undefined. RESULTS: In the present study we analyzed expression levels of innate immune proteins in temporal and occipital cortices from preclinical (no cognitive impairment, NCI, N = 22) to mild cognitive impairment (MCI, N = 20) associated with AD pathology (N = 20) and AD patients (N = 23). We found that retinoic acid-inducible gene-I (RIG-1) is significantly elevated in the temporal cortex and plasma in patients with MCI. In addition, primary human astrocytes stimulated with the RIG-1 ligand 5'ppp RNA showed increased expression of amyloid precursor protein (APP) and amyloid-ß (Aß), supporting the idea that RIG-1 is involved in the pathology of MCI associated with early progression to AD. CONCLUSION: These findings suggest that RIG-1 may play a critical role in incipient AD.

Overnight changes in the slope of sleep slow waves during infancy.

STUDY OBJECTIVES: Slow wave activity (SWA, 0.5-4.5 Hz) is a well-established marker for sleep pressure in adults. Recent studies have shown that increasing sleep pressure is reflected by an increased synchronized firing pattern of cortical neurons, which can be measured by the slope of sleep slow waves. Thus we aimed at investigating whether the slope of sleep slow waves might provide an alternative marker to study the homeostatic regulation of sleep during early human development. DESIGN: All-night sleep electroencephalography (EEG) was recorded longitudinally at 2, 4, 6, and 9 months after birth. SETTING: Home recording. PATIENTS OR PARTICIPANTS: 11 healthy full-term infants (5 male, 6 female). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The slope of sleep slow waves increased with age. At all ages the slope decreased from the first to the last hour of non rapid-eye-movement (NREM) sleep, even when controlling for amplitude differences (P < 0.002). The decrease of the slope was also present in the cycle-by-cycle time course across the night (P < 0.001) at the age of 6 months when the alternating pattern of low-delta activity (0.75-1.75 Hz) is most prominent. Moreover, we found distinct topographical differences exhibiting the steepest slope over the occipital cortex. CONCLUSIONS: The results suggest an age-dependent increase in synchronization of cortical activity during infancy, which might be due to increasing synaptogenesis. Previous studies have shown that during early postnatal development synaptogenesis is most pronounced over the occipital cortex, which could explain why the steepest slope was found in the occipital derivation. Our results provide evidence that the homeostatic regulation of sleep develops early in human infants.

Neural circuitry of masked emotional face processing in youth with bipolar disorder, severe mood dysregulation, and healthy volunteers.

Youth with bipolar disorder (BD) and those with severe, non-episodic irritability (severe mood dysregulation, SMD) show face-emotion labeling deficits. These groups differ from healthy volunteers (HV) in neural responses to emotional faces. It is unknown whether awareness is required to elicit these differences. We compared activation in BD (N=20), SMD (N=18), and HV (N=22) during "Aware" and "Non-aware" priming of shapes by emotional faces. Subjects rated how much they liked the shape. In aware, a face (angry, fearful, happy, neutral, blank oval) appeared (187 ms) before the shape. In non-aware, a face appeared (17 ms), followed by a mask (170 ms), and shape. A Diagnosis-by-Awareness-by-Emotion ANOVA was not significant. There were significant Diagnosis-by-Awareness interactions in occipital regions. BD and SMD showed increased activity for non-aware vs. aware; HV showed the reverse pattern. When subjects viewed angry or neutral faces, there were Emotion-by-Diagnosis interactions in face-emotion processing regions, including the L precentral gyrus, R posterior cingulate, R superior temporal gyrus, R middle occipital gyrus, and L medial frontal gyrus. Regardless of awareness, BD and SMD differ in activation patterns from HV and each other in multiple brain regions, suggesting that BD and SMD are distinct developmental mood disorders.

Separate parts of occipito-temporal white matter fibers are associated with recognition of faces and places.

A central finding of functional MRI studies is the highly selective response of distinct brain areas in the occipital temporal cortex to faces and places. However, little is known about the association of white matter fibers with the processing of these object categories. In the current study we used DTI-based tractography to reconstruct two main fibers that connect the occipital lobe with the anterior temporal lobe (inferior longitudinal fasciculus-ILF) and with the frontal lobe (inferior fronto-occipital fasciculus-IFOF) in normal individuals. In addition to MRI scans subjects performed face, scene and body recognition tasks outside the scanner. Results show that recognition of faces and scenes were selectively associated with separate parts of the ILF. In particular, face recognition was highly associated with the fractional anisotropy (FA) of the anterior part of the ILF in the right hemisphere. In contrast, scene recognition was strongly correlated with the FA of the posterior and middle but not the anterior part of the ILF bilaterally. Our findings provide the first demonstration that faces and places are not only associated with distinct brain areas but also with separate parts of white matter fibers.

Faster metabolite (1)H transverse relaxation in the elder human brain.

(1)H magnetic resonance spectroscopy (MRS) is unique among imaging modalities because signals from several metabolites are measured during a single examination period. Each metabolite reflects a distinct intracellular process. Furthermore transverse (T2 ) relaxation times probe the viability of the cell microenvironment, e.g., the viscosity of the cellular fluids, the microscopic susceptibility distribution within the cells, and the iron content. In this study, T2s of brain metabolites were measured in the occipital lobe of eighteen young and fourteen elderly subjects at a field strength of 4 tesla. The T2s of N-acetylaspartate, total creatine, and total choline were 23%, 16% and 10% shorter in elderly than in young subjects. The findings of this study suggest that noninvasive detection of T2 provides useful biological information on changes in the cellular microenvironment that take place during aging.

MHCI requires MEF2 transcription factors to negatively regulate synapse density during development and in disease.

Major histocompatibility complex class I (MHCI) molecules negatively regulate cortical connections and are implicated in neurodevelopmental disorders, including autism spectrum disorders and schizophrenia. However, the mechanisms that mediate these effects are unknown. Here, we report a novel MHCI signaling pathway that requires the myocyte enhancer factor 2 (MEF2) transcription factors. In young rat cortical neurons, MHCI regulates MEF2 in an activity-dependent manner and requires calcineurin-mediated activation of MEF2 to limit synapse density. Manipulating MEF2 alone alters synaptic strength and GluA1 content, but not synapse density, implicating activity-dependent MEF2 activation as critical for MHCI signaling. The MHCI-MEF2 pathway identified here also mediates the effects of a mouse model of maternal immune activation (MIA) on connectivity in offspring. MHCI and MEF2 levels are higher, and synapse density is lower, on neurons from MIA offspring. Most important, dysregulation of MHCI and MEF2 is required for the MIA-induced reduction in neural connectivity. These results identify a previously unknown MHCI-calcineurin-MEF2 signaling pathway that regulates the establishment of cortical connections and mediates synaptic defects caused by MIA, a risk factor for autism spectrum disorders and schizophrenia.

Cytoarchitectonic mapping of the human dorsal extrastriate cortex.

The dorsal visual stream consists of several functionally specialized areas, but most of their cytoarchitectonic correlates have not yet been identified in the human brain. The cortex adjacent to Brodmann area 18/V2 was therefore analyzed in serial sections of ten human post-mortem brains using morphometrical and multivariate statistical analyses for the definition of areal borders. Two previously unknown cytoarchitectonic areas (hOc3d, hOc4d) were detected. They occupy the medial and, to a smaller extent, lateral surface of the occipital lobe. The larger area, hOc3d, is located dorso-lateral to area V2 in the region of superior and transverse occipital, as well as parieto-occipital sulci. Area hOc4d was identified rostral to hOc3d; it differed from the latter by larger pyramidal cells in lower layer III, thinner layers V and VI, and a sharp cortex-white-matter borderline. The delineated areas were superimposed in the anatomical MNI space, and probabilistic maps were calculated. They show a relatively high intersubject variability in volume and position. Based on their location and neighborhood relationship, areas hOc3d and hOc4d are putative anatomical substrates of functionally defined areas V3d and V3a, a hypothesis that can now be tested by comparing probabilistic cytoarchitectonic maps and activation studies of the living human brain.

Hemispheric asymmetry in the fusiform gyrus distinguishes Homo sapiens from chimpanzees.

While the neural basis for linguistic communication has been linked to brain structural asymmetries found only in humans (wider connective spacing is found between the minicolumns of neurons in the left hemisphere language areas), it is unknown if the opposite microanatomical asymmetry exists in the fusiform gyrus which typically supports a right hemisphere bias for face processing. Unlike language, face processing is an ability shared with chimpanzees and, as Darwin observed, the widespread use of facial expressions in animal communication suggests a biological basis. We tested the principle that minicolumn asymmetry follows typical functional dominance in humans, and tested its evolutionary continuity, by measuring minicolumn width, neuronal size and density in the mid-fusiform cortex in 14 humans and 14 chimpanzees. We found that microanatomical asymmetry distinguishes humans from chimpanzees although the direction of asymmetry is the same as in language areas-the right hemisphere contained narrower minicolumns and smaller pyramidal neurons, as in auditory language areas. Uniformly narrow minicolumns in chimpanzees and in the human right hemisphere are consistent with mechanistic predictions supporting the apparent bias towards holistic face processing. Wider minicolumns and larger neurons in the human left hemisphere may be consistent with a language function such as word-form processing. Microanatomical asymmetry in the neocortex therefore provides a correlate of hemispheric specialisation.