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The layers of the neocortex each have a unique anatomical connectivity and functional role. Their exploration in the human brain, however, has been severely restricted by the limited spatial resolution of non-invasive measurement techniques. Here, we exploit the sensitivity and specificity of ultra-high field fMRI at 7 Tesla to investigate responses to natural sounds at deep, middle, and superficial cortical depths of the human auditory cortex. Specifically, we compare the performance of computational models that represent different hypotheses on sound processing inside and outside the primary auditory cortex (PAC). We observe that while BOLD responses in deep and middle PAC layers are equally well represented by a simple frequency model and a more complex spectrotemporal modulation model, responses in superficial PAC are better represented by the more complex model. This indicates an increase in processing complexity in superficial PAC, which remains present throughout cortical depths in the non-primary auditory cortex. These results suggest that a relevant transformation in sound processing takes place between the thalamo-recipient middle PAC layers and superficial PAC. This transformation may be a first computational step towards sound abstraction and perception, serving to form an increasingly more complex representation of the physical input.

De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles., The mTOR pathway is a key regulator of normal brain development. Here, the authors identify de novo mutations in RHEB, an mTOR activator protein, in patients with intellectual disability associated with megalencephaly and find a role for RHEB in regulating neuronal soma size and migration in vitro and in vivo.

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent technical and methodological progress in neuroimaging has helped advance our understanding of this important issue, with diffusion weighted images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). However, comparing these two distinct datasets, each of which can be encoded into a different complex network, is by no means trivial as pairwise link-to-link comparisons represent a relatively restricted perspective and provide only limited information. Thus, we have adopted a more integrative systems approach, exploiting theoretical graph analyses to study both SC and rsFC datasets gathered independently from healthy human subjects. The aim is to find the main architectural traits shared by the structural and functional networks by paying special attention to their common hierarchical modular organization. This approach allows us to identify a common skeleton from which a new, optimal, brain partition can be extracted, with modules sharing both structure and function. We describe these emerging common structure-function modules (SFMs) in detail. In addition, we compare SFMs with the classical Resting State Networks derived from independent component analysis of rs-fMRI functional activity, as well as with anatomical parcellations in the Automated Anatomical Labeling atlas and with the Broadmann partition, highlighting their similitude and differences. The unveiling of SFMs brings to light the strong correspondence between brain structure and resting-state dynamics., Comment: Accepted in Nature Scientific Reports. 56 pages, 15 figures

Cataloged from PDF version of article. The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin 33 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations. © 2011 Nature America, Inc. All rights reserved.