Project description:Structurally segregated and functionally specialized regions of the human cerebral cortex are interconnected by a dense network of cortico-cortical axonal pathways. By using diffusion spectrum imaging, we noninvasively mapped these pathways within and across cortical hemispheres in individual human participants. An analysis of the resulting large-scale structural brain networks reveals a structural core within posterior medial and parietal cerebral cortex, as well as several distinct temporal and frontal modules. Brain regions within the structural core share high degree, strength, and betweenness centrality, and they constitute connector hubs that link all major structural modules. The structural core contains brain regions that form the posterior components of the human default network. Looking both within and outside of core regions, we observed a substantial correspondence between structural connectivity and resting-state functional connectivity measured in the same participants. The spatial and topological centrality of the core within cortex suggests an important role in functional integration.
Project description:Although the structure of cortical networks provides the necessary substrate for their neuronal activity, the structure alone does not suffice to understand the activity. Leveraging the increasing availability of human data, we developed a multi-scale, spiking network model of human cortex to investigate the relationship between structure and dynamics. In this model, each area in one hemisphere of the Desikan-Killiany parcellation is represented by a $1\,\mathrm{mm^{2}}$ column with a layered structure. The model aggregates data across multiple modalities, including electron microscopy, electrophysiology, morphological reconstructions, and diffusion tensor imaging, into a coherent framework. It predicts activity on all scales from the single-neuron spiking activity to the area-level functional connectivity. We compared the model activity with human electrophysiological data and human resting-state functional magnetic resonance imaging (fMRI) data. This comparison reveals that the model can reproduce aspects of both spiking statistics and fMRI correlations if the inter-areal connections are sufficiently strong. Furthermore, we study the propagation of a single-spike perturbation and macroscopic fluctuations through the network. The open-source model serves as an integrative platform for further refinements and future in silico studies of human cortical structure, dynamics, and function.
Project description:ObjectiveThe cerebral network subserving repetition suppression (RS) of the P50 auditory evoked response as observed using paired-identical-stimulus (S1-S2) paradigms is not well-described.MethodsWe analyzed S1-S2 data from electrodes placed on the cortices of 64 epilepsy patients. We identified regions with maximal amplitude responses to S1 (i.e., stimulus registration), regions with maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions with no or minimal RS 30-80 ms post stimulation.ResultsSeveral temporal, parietal and cingulate area regions were shown to have significant initial registration activity (i.e., strong P50 response to S1). Moreover, prefrontal, cingulate, and parietal lobe regions not previously proposed to be part of the P50 habituation neural circuitry were found to exhibit significant RS.ConclusionsThe data suggest that the neural network underlying the initial phases of the RS process may include regions not previously thought to be involved like the parietal and cingulate cortexes. In addition, a significant role for the frontal lobe in mediating this function is supported.SignificanceA number of regions of interest are identified through invasive recording that will allow further probing of the RS function using less invasive technology.
Project description:Repetition suppression (RS) phenomena, such as those observed using paired-identical-stimulus (S1-S2) paradigms, likely reflect adaptive functions such as habituation and, more specifically, sensory gating.To better characterize the neural networks underlying RS, we analyzed auditory S1-S2 data from electrodes placed on the cortices of 64 epilepsy patients who were being evaluated for surgical therapy. We identified regions with maximal amplitude responses to S1 (i.e., stimulus registration regions), regions with maximal suppression of responses to S2 relative to S1 (i.e., RS), and regions with no or minimal RS.Auditory perceptual regions, such as the superior temporal gyri, were shown to have significant initial registration activity (i.e., strong response to S1). Several prefrontal, cingulate, and parietal lobe regions were found to exhibit stronger RS than those recorded from the auditory perceptual areas.The data strongly suggest that the neural network underlying repetition suppression may include regions not previously thought to be involved, such as the parietal and cingulate cortexes. In addition, the data also support the notion that the initial response to stimuli and the ability to suppress the stimuli if repeated are two separate, but likely related, functions.
Project description:The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a "small-world" architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.
Project description:Synaptic transmission constitutes the primary mode of communication between neurons. It is extensively studied in rodent but not human neocortex. We characterized synaptic transmission between pyramidal neurons in layers 2 and 3 using neurosurgically resected human middle temporal gyrus (MTG, Brodmann area 21), which is part of the distributed language circuitry. We find that local connectivity is comparable with mouse layer 2/3 connections in the anatomical homologue (temporal association area), but synaptic connections in human are 3-fold stronger and more reliable (0% vs 25% failure rates, respectively). We developed a theoretical approach to quantify properties of spinous synapses showing that synaptic conductance and voltage change in human dendritic spines are 3-4-folds larger compared with mouse, leading to significant NMDA receptor activation in human unitary connections. This model prediction was validated experimentally by showing that NMDA receptor activation increases the amplitude and prolongs decay of unitary excitatory postsynaptic potentials in human but not in mouse connections. Since NMDA-dependent recurrent excitation facilitates persistent activity (supporting working memory), our data uncovers cortical microcircuit properties in human that may contribute to language processing in MTG.
Project description:The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping. Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and CMR(O(2)). The stimuli used included (i) diffuse isoluminant chromatic displays; (ii) high spatial-frequency achromatic luminance gratings; and (iii) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled in a consistent ratio of approximately 2:1. The most potent stimulus produced CBF and CMR(O(2)) increases of 48 +/- 5% and 25 +/- 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed CMR(O(2)) increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism.
Project description:Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution.
Project description:Mapping cortical hemispheric asymmetries in infants would increase our understanding of the origins and developmental trajectories of hemispheric asymmetries. We analyze longitudinal cortical hemispheric asymmetries in 73 healthy subjects at birth, 1, and 2 years of age using surface-based morphometry of magnetic resonance images with a specific focus on the vertex position, sulcal depth, mean curvature, and local surface area. Prominent cortical asymmetries are found around the peri-Sylvian region and superior temporal sulcus (STS) at birth that evolve modestly from birth to 2 years of age. Sexual dimorphisms of cortical asymmetries are present at birth, with males having the larger magnitudes and sizes of the clusters of asymmetries than females that persist from birth to 2 years of age. The left supramarginal gyrus (SMG) is significantly posterior to the right SMG, and the maximum position difference increases from 10.2 mm for males (6.9 mm for females) at birth to 12.0 mm for males (8.4 mm for females) by 2 years of age. The right STS and parieto-occipital sulcus are significantly larger and deeper than those in the left hemisphere, and the left planum temporale is significantly larger and deeper than that in the right hemisphere at all 3 ages. Our results indicate that early hemispheric structural asymmetries are inherent and gender related.