Gradients of neurotransmitter receptor expression in the macaque cortex.

Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions is needed. In this study, we used in vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrated the receptor data with anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of receptor expression per neuron. This aligns with the cortical hierarchy from sensory cortex to higher cognitive areas. A second gradient, driven by serotonin 5-HT1A receptors, peaks in the anterior cingulate, default mode and salience networks. We found a similar pattern of 5-HT1A expression in the human brain. Thus, the macaque may be a promising translational model of serotonergic processing and disorders. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration in higher cognitive areas.

Brain Reactions to Opening and Closing the Eyes: Salivary Cortisol and Functional Connectivity.

This study empirically assessed the strength and duration of short-term effects induced by brain reactions to closing/opening the eyes on a few well-known resting-state networks. We also examined the association between these reactions and subjects' cortisol levels. A total of 55 young adults underwent 8-min resting-state fMRI (rs-fMRI) scans under 4-min eyes-closed and 4-min eyes-open conditions. Saliva samples were collected from 25 of the 55 subjects before and after the fMRI sessions and assayed for cortisol levels. Our empirical results indicate that when the subjects were relaxed with their eyes closed, the effect of opening the eyes on conventional resting-state networks (e.g., default-mode, frontal-parietal, and saliency networks) lasted for roughly 60-s, during which we observed a short-term increase in activity in rs-fMRI time courses. Moreover, brain reactions to opening the eyes had a pronounced effect on time courses in the temporo-parietal lobes and limbic structures, both of which presented a prolonged decrease in activity. After controlling for demographic factors, we observed a significantly positive correlation between pre-scan cortisol levels and connectivity in the limbic structures under both conditions. Under the eyes-closed condition, the temporo-parietal lobes presented significant connectivity to limbic structures and a significantly positive correlation with pre-scan cortisol levels. Future research on rs-fMRI could consider the eyes-closed condition when probing resting-state connectivity and its neuroendocrine correlates, such as cortisol levels. It also appears that abrupt instructions to open the eyes while the subject is resting quietly with eyes closed could be used to probe brain reactivity to aversive stimuli in the ventral hippocampus and other limbic structures.

Receptor architecture of macaque and human early visual areas: not equal, but comparable.

Existing cytoarchitectonic maps of the human and macaque posterior occipital cortex differ in the number of areas they display, thus hampering identification of homolog structures. We applied quantitative in vitro receptor autoradiography to characterize the receptor architecture of the primary visual and early extrastriate cortex in macaque and human brains, using previously published cytoarchitectonic criteria as starting point of our analysis. We identified 8 receptor architectonically distinct areas in the macaque brain (mV1d, mV1v, mV2d, mV2v, mV3d, mV3v, mV3A, mV4v), and their respective counterpart areas in the human brain (hV1d, hV1v, hV2d, hV2v, hV3d, hV3v, hV3A, hV4v). Mean densities of 14 neurotransmitter receptors were quantified in each area, and ensuing receptor fingerprints used for multivariate analyses. The 1st principal component segregated macaque and human early visual areas differ. However, the 2nd principal component showed that within each species, area-specific differences in receptor fingerprints were associated with the hierarchical processing level of each area. Subdivisions of V2 and V3 were found to cluster together in both species and were segregated from subdivisions of V1 and from V4v. Thus, comparative studies like this provide valuable architectonic insights into how differences in underlying microstructure impact evolutionary changes in functional processing of the primate brain and, at the same time, provide strong arguments for use of macaque monkey brain as a suitable animal model for translational studies.

Personalized brain models identify neurotransmitter receptor changes in Alzheimer's disease.

Alzheimer's disease involves many neurobiological alterations from molecular to macroscopic spatial scales, but we currently lack integrative, mechanistic brain models characterizing how factors across different biological scales interact to cause clinical deterioration in a way that is subject-specific or personalized. As important signalling molecules and mediators of many neurobiological interactions, neurotransmitter receptors are promising candidates for identifying molecular mechanisms and drug targets in Alzheimer's disease. We present a neurotransmitter receptor-enriched multifactorial brain model, which integrates spatial distribution patterns of 15 neurotransmitter receptors from post-mortem autoradiography with multiple in vivo neuroimaging modalities (tau, amyloid-ß and glucose PET, and structural, functional and arterial spin labelling MRI) in a personalized, generative, whole-brain formulation. In a heterogeneous aged population (n = 423, ADNI data), models with personalized receptor-neuroimaging interactions showed a significant improvement over neuroimaging-only models, explaining about 70% (±20%) of the variance in longitudinal changes to the six neuroimaging modalities. In Alzheimer's disease patients (n = 25, ADNI data), receptor-imaging interactions explained up to 39.7% (P < 0.003, family-wise error-rate-corrected) of inter-individual variability in cognitive deterioration, via an axis primarily affecting executive function. Notably, based on their contribution to the clinical severity in Alzheimer's disease, we found significant functional alterations to glutamatergic interactions affecting tau accumulation and neural activity dysfunction and GABAergic interactions concurrently affecting neural activity dysfunction, amyloid and tau distributions, as well as significant cholinergic receptor effects on tau accumulation. Overall, GABAergic alterations had the largest effect on cognitive impairment (particularly executive function) in our Alzheimer's disease cohort (n = 25). Furthermore, we demonstrate the clinical applicability of this approach by characterizing subjects based on individualized 'fingerprints' of receptor alterations. This study introduces the first robust, data-driven framework for integrating several neurotransmitter receptors, multimodal neuroimaging and clinical data in a flexible and interpretable brain model. It enables further understanding of the mechanistic neuropathological basis of neurodegenerative progression and heterogeneity, and constitutes a promising step towards implementing personalized, neurotransmitter-based treatments.

A dopamine gradient controls access to distributed working memory in the large-scale monkey cortex.

Dopamine is required for working memory, but how it modulates the large-scale cortex is unknown. Here, we report that dopamine receptor density per neuron, measured by autoradiography, displays a macroscopic gradient along the macaque cortical hierarchy. This gradient is incorporated in a connectome-based large-scale cortex model endowed with multiple neuron types. The model captures an inverted U-shaped dependence of working memory on dopamine and spatial patterns of persistent activity observed in over 90 experimental studies. Moreover, we show that dopamine is crucial for filtering out irrelevant stimuli by enhancing inhibition from dendrite-targeting interneurons. Our model revealed that an activity-silent memory trace can be realized by facilitation of inter-areal connections and that adjusting cortical dopamine induces a switch from this internal memory state to distributed persistent activity. Our work represents a cross-level understanding from molecules and cell types to recurrent circuit dynamics underlying a core cognitive function distributed across the primate cortex.

Distribution of the Noradrenaline Innervation and Adrenoceptors in the Macaque Monkey Thalamus.

Noradrenaline (NA) in the thalamus has important roles in physiological, pharmacological, and pathological neuromodulation. In this work, a complete characterization of NA axons and Alpha adrenoceptors distributions is provided. NA axons, revealed by immunohistochemistry against the synthesizing enzyme and the NA transporter, are present in all thalamic nuclei. The most densely innervated ones are the midline nuclei, intralaminar nuclei (paracentral and parafascicular), and the medial sector of the mediodorsal nucleus (MDm). The ventral motor nuclei and most somatosensory relay nuclei receive a moderate NA innervation. The pulvinar complex receives a heterogeneous innervation. The lateral geniculate nucleus (GL) has the lowest NA innervation. Alpha adrenoceptors were analyzed by in vitro quantitative autoradiography. Alpha-1 receptor densities are higher than Alpha-2 densities. Overall, axonal densities and Alpha adrenoceptor densities coincide; although some mismatches were identified. The nuclei with the highest Alpha-1 values are MDm, the parvocellular part of the ventral posterior medial nucleus, medial pulvinar, and midline nuclei. The nucleus with the lowest Alpha-1 receptor density is GL. Alpha-2 receptor densities are highest in the lateral dorsal, centromedian, medial and inferior pulvinar, and midline nuclei. These results suggest a role for NA in modulating thalamic involvement in consciousness, limbic, cognitive, and executive functions.

Organization of the macaque monkey inferior parietal lobule based on multimodal receptor architectonics.

The macaque monkey inferior parietal lobe (IPL) is a structurally heterogeneous brain region, although the number of areas it contains and the anatomical/functional relationship of identified subdivisions remains controversial. Neurotransmitter receptor distribution patterns not only reveal the position of the cortical borders, but also segregate areas associated to different functional systems. Thus we carried out a multimodal quantitative analysis of the cyto- and receptor architecture of the macaque IPL to determine the number and extent of distinct areas it encompasses. We identified four areas on the IPL convexity arranged in a caudo-rostral sequence, as well as two areas in the parietal operculum, which we projected onto the Yerkes19 surface. We found rostral areas to have relatively smaller receptor fingerprints than the caudal ones, which is in an agreement with the functional gradient along the caudo-rostral axis described in previous studies. The hierarchical analysis segregated IPL areas into two clusters: the caudal one, contains areas involved in multisensory integration and visual-motor functions, and rostral cluster, encompasses areas active during motor planning and action-related functions. The results of the present study provide novel insights into clarifying the homologies between human and macaque IPL areas. The ensuing 3D map of the macaque IPL, and the receptor fingerprints are made publicly available to the neuroscientific community via the Human Brain Project and BALSA repositories for future cyto- and/or receptor architectonically driven analyses of functional imaging studies in non-human primates.

Multimodal 3D atlas of the macaque monkey motor and premotor cortex.

In the present study we reevaluated the parcellation scheme of the macaque frontal agranular cortex by implementing quantitative cytoarchitectonic and multireceptor analyses, with the purpose to integrate and reconcile the discrepancies between previously published maps of this region. We applied an observer-independent and statistically testable approach to determine the position of cytoarchitectonic borders. Analysis of the regional and laminar distribution patterns of 13 different transmitter receptors confirmed the position of cytoarchitectonically identified borders. Receptor densities were extracted from each area and visualized as its "receptor fingerprint". Hierarchical and principal components analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their fingerprints. Finally, functional connectivity pattern of each identified area was analyzed with areas of prefrontal, cingulate, somatosensory and lateral parietal cortex and the results were depicted as "connectivity fingerprints" and seed-to-vertex connectivity maps. We identified 16 cyto- and receptor architectonically distinct areas, including novel subdivisions of the primary motor area 4 (i.e. 4a, 4p, 4m) and of premotor areas F4 (i.e. F4s, F4d, F4v), F5 (i.e. F5s, F5d, F5v) and F7 (i.e. F7d, F7i, F7s). Multivariate analyses of receptor fingerprints revealed three clusters, which first segregated the subdivisions of area 4 with F4d and F4s from the remaining premotor areas, then separated ventrolateral from dorsolateral and medial premotor areas. The functional connectivity analysis revealed that medial and dorsolateral premotor and motor areas show stronger functional connectivity with areas involved in visual processing, whereas 4p and ventrolateral premotor areas presented a stronger functional connectivity with areas involved in somatomotor responses. For the first time, we provide a 3D atlas integrating cyto- and multi-receptor architectonic features of the macaque motor and premotor cortex. This atlas constitutes a valuable resource for the analysis of functional experiments carried out with non-human primates, for modeling approaches with realistic synaptic dynamics, as well as to provide insights into how brain functions have developed by changes in the underlying microstructure and encoding strategies during evolution.

New boundaries and dissociation of the mouse hippocampus along the dorsal-ventral axis based on glutamatergic, GABAergic and catecholaminergic receptor densities.

In rodents, gene-expression, neuronal tuning, connectivity and neurogenesis studies have postulated that the dorsal, the intermediate and the ventral hippocampal formation (HF) are distinct entities. These findings are underpinned by behavioral studies showing a dissociable role of dorsal and ventral HF in learning, memory, stress and emotional processing. However, up to now, the molecular basis of such differences in relation to discrete boundaries is largely unknown. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA, kainate and mGluR2/3 , GABAergic GABAA (including benzodiazepine binding sites), GABAB , dopaminergic D1/5 and noradrenergic α1 and α2 receptors as key modulators for signal transmission in hippocampal functions, using quantitative in vitro receptor autoradiography along the dorsal-ventral axis of the mouse HF. Beside general different receptor profiles of the dentate gyrus (DG) and Cornu Ammonis fields (CA1, CA2, CA3, CA4/hilus), we detected substantial differences between dorsal, intermediate and ventral subdivisions and individual layers for all investigated receptor types, except GABAB . For example, striking higher densities of α2 receptors were detected in the ventral DG, while the dorsal DG possesses higher numbers of kainate, NMDA, GABAA and D1/5 receptors. CA1 dorsal and intermediate subdivisions showed higher AMPA, NMDA, mGluR2/3 , GABAA , D1/5 receptors, while kainate receptors are higher expressed in ventral CA1, and noradrenergic α1 and α2 receptors in the intermediate region of CA1. CA2 dorsal was distinguished by higher kainate, α1 and α2 receptors in the intermediate region, while CA3 showed a more complex dissociation. Our findings resulted not only in a clear segmentation of the mouse hippocampus along the dorsal-ventral axis, but also provides insights into the neurochemical basis and likely associated physiological processes in hippocampal functions. Therein, the presented data has a high impact for future studies modeling and investigating dorsal, intermediate and ventral hippocampal dysfunction in relation to neurodegenerative diseases or psychiatric disorders.

Sulcal morphology of ventral temporal cortex is shared between humans and other hominoids.

Hominoid-specific brain structures are of particular importance in understanding the evolution of human brain structure and function, as they are absent in mammals that are widely studied in the extended neuroscience field. Recent research indicates that the human fusiform gyrus (FG), which is a hominoid-specific structure critical for complex object recognition, contains a tertiary, longitudinal sulcus (mid-fusiform sulcus, MFS) that bisects the FG into lateral and medial parallel gyri. The MFS is a functional and architectonic landmark in the human brain. Here, we tested if the MFS is specific to the human FG or if the MFS is also identifiable in other hominoids. Using magnetic resonance imaging and cortical surface reconstructions in 30 chimpanzees and 30 humans, we show that the MFS is also present in chimpanzees. The MFS is relatively deeper and cortically thinner in chimpanzees compared to humans. Additional histological analyses reveal that the MFS is not only present in humans and chimpanzees, but also in bonobos, gorillas, orangutans, and gibbons. Taken together, these results reveal that the MFS is a sulcal landmark that is shared between humans and other hominoids. These results require a reconsideration of the sulcal patterning in ventral temporal cortex across hominoids, as well as revise the compensation theory of cortical folding.

Anatomy of nerve fiber bundles at micrometer-resolution in the vervet monkey visual system.

Although the primate visual system has been extensively studied, detailed spatial organization of white matter fiber tracts carrying visual information between areas has not been fully established. This is mainly due to the large gap between tracer studies and diffusion-weighted MRI studies, which focus on specific axonal connections and macroscale organization of fiber tracts, respectively. Here we used 3D polarization light imaging (3D-PLI), which enables direct visualization of fiber tracts at micrometer resolution, to identify and visualize fiber tracts of the visual system, such as stratum sagittale, inferior longitudinal fascicle, vertical occipital fascicle, tapetum and dorsal occipital bundle in vervet monkey brains. Moreover, 3D-PLI data provide detailed information on cortical projections of these tracts, distinction between neighboring tracts, and novel short-range pathways. This work provides essential information for interpretation of functional and diffusion-weighted MRI data, as well as revision of wiring diagrams based upon observations in the vervet visual system.

Julich-Brain: A 3D probabilistic atlas of the human brain's cytoarchitecture.

Cytoarchitecture is a basic principle of microstructural brain parcellation. We introduce Julich-Brain, a three-dimensional atlas containing cytoarchitectonic maps of cortical areas and subcortical nuclei. The atlas is probabilistic, which enables it to account for variations between individual brains. Building such an atlas was highly data- and labor-intensive and required the development of nested, interdependent workflows for detecting borders between brain areas, data processing, provenance tracking, and flexible execution of processing chains to handle large amounts of data at different spatial scales. Full cortical coverage was achieved by the inclusion of gap maps to complement cortical maps. The atlas is dynamic and will be adapted as mapping progresses; it is openly available to support neuroimaging studies as well as modeling and simulation; and it is interoperable, enabling connection to other atlases and resources.

Receptor-driven, multimodal mapping of cortical areas in the macaque monkey intraparietal sulcus.

The intraparietal sulcus (IPS) is structurally and functionally heterogeneous. We performed a quantitative cyto-/myelo- and receptor architectonical analysis to provide a multimodal map of the macaque IPS. We identified 17 cortical areas, including novel areas PEipe, PEipi (external and internal subdivisions of PEip), and MIPd. Multivariate analyses of receptor densities resulted in a grouping of areas based on the degree of (dis)similarity of their receptor architecture: a cluster encompassing areas located in the posterior portion of the IPS and associated mainly with the processing of visual information, a cluster including areas found in the anterior portion of the IPS and involved in sensorimotor processing, and an 'intermediate' cluster of multimodal association areas. Thus, differences in cyto-/myelo- and receptor architecture segregate the cortical ribbon within the IPS, and receptor fingerprints provide novel insights into the relationship between the structural and functional segregation of this brain region in the macaque monkey.

Four new cytoarchitectonic areas surrounding the primary and early auditory cortex in human brains.

The architectonical organization of putatively higher auditory areas in the human superior temporal gyrus and sulcus is not yet well understood. To provide a coherent map of this part of the brain, which is involved in language and other functions, we examined the cytoarchitecture and cortical parcellation of this region in histological sections of ten human postmortem brains using an observer-independent mapping approach. Two new areas were identified in the temporo-insular region (areas TeI, TI). TeI is medially adjacent to the primary auditory cortex (area Te1). TI is located between TeI and the insular cortex. Laterally adjacent to previously mapped areas Te2 and Te3, two new areas (STS1, STS2) were identified in the superior temporal sulcus. All four areas were mapped over their whole extent in serial, cell-body stained sections, and their cytoarchitecture was analyzed using quantitative image analysis and multivariate statistics. Interestingly, area TeI, which is located between area Te1 and area TI at the transition to the insula, was more similar in cytoarchitecture to lateral area Te2.1 than to the directly adjacent areas TI and Te1. Such structural similarity of areas medially and laterally to Te1 would be in line with the core-belt-parabelt concept in macaques. The cytoarchitectonic probabilistic maps of all areas show the localization of the areas and their interindividual variability. The new maps are publicly available and provide a basis to further explore structural-functional relationship of the language network in the temporal cortex.

BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices.

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy.

Multimodal mapping and analysis of the cyto- and receptorarchitecture of the human hippocampus.

The human hippocampal formation is relevant for various aspects of memory and learning, and the different hippocampal regions are differentially affected by neuropsychiatric disorders. Therefore, the hippocampal formation has been subject of numerous cytoarchitectonic and other mapping studies, which resulted in divergent parcellation schemes. To understand the principles of hippocampal architecture, it is necessary to integrate different levels of hippocampal organisation, going beyond one modality. We here applied a multimodal mapping approach combining cyto- and multi-receptorarchitectonic analyses, and generated probabilistic maps in stereotaxic space of the identified regions. Cytoarchitecture in combination with the regional and laminar distribution of 15 neurotransmitter receptors visualized by in vitro receptor autoradiography were analysed in seven hemispheres from 6 unfixed shock frozen and serially sectioned brains. Cytoarchitectonic delineations for generation of probabilistic maps were carried out on histological sections from ten fixed, paraffin embedded and serially sectioned brains. Nine cyto- and receptorarchitectonically distinct regions were identified within the hippocampal formation (i.e., fascia dentata, cornu Ammonis (CA) regions 1-4, prosubiculum, subiculum proper, presubiculum and parasubiculum), as well as the hippocampal-amygdaloid transition area and the periallocortical transsubiculum. Subsequently generated probabilistic maps quantify intersubject variability in the size and extent of these cyto- and receptorarchitectonically distinct regions. The regions did not differ in their volume between the hemispheres and gender. Receptor mapping revealed additional subdivisions which could not be detected by cytoarchitectonic analysis alone. They correspond to parcellations previously found in immunohistochemical and connectivity studies. The multimodal approach enabled the definition of regions not consistently reported, e.g., CA4 region or prosubiculum. The ensuing detailed probabilistic maps of the hippocampal formation constitute the basis for future architectonically informed analyses of in vivo neuroimaging studies.

Primate hippocampus size and organization are predicted by sociality but not diet.

The hippocampus is well known for its roles in spatial navigation and memory, but it is organized into regions that have different connections and functional specializations. Notably, the region CA2 has a role in social and not spatial cognition, as is the case for the regions CA1 and CA3 that surround it. Here, we investigated the evolution of the hippocampus in terms of its size and organization in relation to the evolution of social and ecological variables in primates, namely home range, diet and different measures of group size. We found that the volumes within the whole cornu ammonis coevolve with group size, while only the volume of CA1 and subiculum can also be predicted by home range. On the other hand, diet, expressed as a shift from folivory towards frugivory, was shown to not be related to hippocampal volume. Interestingly, CA2 was shown to exhibit phylogenetic signal only against certain measures of group size, but not with ecological factors. We also found that sex differences in the hippocampus are related to body size sex dimorphism. This is in line with reports of sex differences in hippocampal volume in non-primates that are related to social structure and sex differences in behaviour. Our findings support the notion that in primates, the hippocampus is a mosaic structure evolving in line with social pressures, where certain subsections evolve in line with spatial ability too.

Listening to real-world sounds: fMRI data for analyzing connectivity networks.

There is a growing interest in functional magnetic resonance imaging (fMRI) studies on connectivity networks in the brain when subjects are under exposure to natural sensory stimulation. Because of a complicated coupling between spontaneous and evoked brain activity under real-world stimulation, there is no critical mapping between the experimental inputs and corresponding brain responses. The dataset contains auditory fMRI scans and T1-weighted anatomical scans acquired under eyes-closed and eyes-open conditions. Within each scanning condition, the subject was presented 12 different sound clips, including human voices followed by animal vocalizations. The dataset is meant to be used to assess brain dynamics and connectivity networks under natural sound stimulation; it also allows for empirical investigation of changes in fMRI responses between eyes-closed and eyes-open conditions, between animal vocalizations and human voices, as well as between the 12 different sound clips during auditory stimulation. The dataset is a supplement to the research findings in the paper "Brain dynamics and connectivity networks under natural auditory stimulation" published in NeuroImage.

Receptor density pattern confirms and enhances the anatomic-functional features of the macaque superior parietal lobule areas.

The macaque monkey superior parietal lobule (SPL) is part of a neuronal network involved in the integration of information from visual and somatosensory cortical areas for execution of reaching and grasping movements. We applied quantitative in vitro receptor autoradiography to analyse the distribution patterns of 15 different receptors for glutamate, GABA, acetylcholine, serotonin, dopamine, and adenosine in the SPL of three adult male Macaca fascicularis monkeys. For each area, mean (averaged over all cortical layers) receptor densities were visualized as a receptor fingerprint of that area. Multivariate analyses were conducted to detect clusters of areas according to the degree of (dis)similarity of their receptor organization. Differences in regional and laminar receptor distributions confirm the location and extent of areas V6, V6Av, V6Ad, PEc, PEci, and PGm as found in cytoarchitectonic and functional studies, but also enable the definition of three subdivisions within area PE. Receptor densities are higher in supra- than in infragranular layers, with the exception of kainate, M2, and adenosine receptors. Glutamate and GABAergic receptors are the most expressed in all areas analysed. Hierarchical cluster analyses demonstrate that SPL areas are organized in two groups, an organization that corresponds to the visual or sensory-motor characteristics of those areas. Finally, based on present results and in the framework of our current understanding of the structural and functional organization of the primate SPL, we propose a novel pattern of homologies between human and macaque SPL areas.

Brain dynamics and connectivity networks under natural auditory stimulation.

The analysis of functional magnetic resonance imaging (fMRI) data is challenging when subjects are under exposure to natural sensory stimulation. In this study, a two-stage approach was developed to enable the identification of connectivity networks involved in the processing of information in the brain under natural sensory stimulation. In the first stage, the degree of concordance between the results of inter-subject and intra-subject correlation analyses is assessed statistically. The microstructurally (i.e., cytoarchitectonically) defined brain areas are designated either as concordant in which the results of both correlation analyses are in agreement, or as discordant in which one analysis method shows a higher proportion of supra-threshold voxels than does the other. In the second stage, connectivity networks are identified using the time courses of supra-threshold voxels in brain areas contingent upon the classifications derived in the first stage. In an empirical study, fMRI data were collected from 40 young adults (19 males, average age 22.76 ±â€¯3.25), who underwent auditory stimulation involving sound clips of human voices and animal vocalizations under two operational conditions (i.e., eyes-closed and eyes-open). The operational conditions were designed to assess confounding effects due to auditory instructions or visual perception. The proposed two-stage analysis demonstrated that stress modulation (affective) and language networks in the limbic and cortical structures were respectively engaged during sound stimulation, and presented considerable variability among subjects. The network involved in regulating visuomotor control was sensitive to the eyes-open instruction, and presented only small variations among subjects. A high degree of concordance was observed between the two analyses in the primary auditory cortex which was highly sensitive to the pitch of sound clips. Our results have indicated that brain areas can be identified as concordant or discordant based on the two correlation analyses. This may further facilitate the search for connectivity networks involved in the processing of information under natural sensory stimulation.