Distributed Feedforward and Feedback Processing across Perisylvian Cortex Supports Human Speech

Speech production is a complex human function requiring continuous feedforward commands together with reafferent feedback processing. These processes are carried out by distinct frontal and posterior cortical networks, but the degree and timing of their recruitment and dynamics remain unknown. We present a novel deep learning architecture that translates neural signals recorded directly from cortex to an interpretable representational space that can reconstruct speech. We leverage state-of-the-art learnt decoding networks to disentangle feedforward vs. feedback processing. Unlike prevailing models, we find a mixed cortical architecture in which frontal and temporal networks each process both feedforward and feedback information in tandem. We elucidate the timing of feedforward and feedback related processing by quantifying the derived receptive fields. Our approach provides evidence for a surprisingly mixed cortical architecture of speech circuitry together with decoding advances that have important implications for neural prosthetics.

H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion by activating TRNP1 expression

ABSTRACTIncrease in the size of human neocortex, acquired in evolution, accounts for the unique cognitive capacity of humans. This expansion appears to reflect the evolutionarily-enhanced proliferative ability of basal progenitors (BPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, whether or how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in BP amplification and cortical expansion. Through epigenetic profiling of sorted BPs, we show that H3K9 acetylation is low in murine BPs and high in human BPs. Elevated H3K9ac preferentially increases BP proliferation, increasing the size and folding of the normally smooth mouse neocortex. Mechanistically, H3K9ac drives BP amplification by increasing expression of the evolutionarily regulated gene, TRNP1, in the developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture.One Sentence SummaryH3K9ac promotes basal progenitor amplification, neocortex expansion and gyrification by activating TRNP1 expression in evolution.

Transient cortical circuits match spontaneous and sensory-driven activity during development

At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form the functional template for the establishment of global thalamocortical networks and cortical architecture. The earliest connections are established autonomously. However, activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex. The early-generated, largely transient neurons of the subplate play a key role in integrating spontaneous and sensory-driven activity. Early pathological conditions—such as hypoxia, inflammation, or exposure to pharmacological compounds—alter spontaneous activity patterns, which subsequently induce disturbances in cortical network activity. This cortical dysfunction may lead to local and global miswiring and, at later stages, can be associated with neurological and psychiatric conditions.

Dynamic dot displays reveal material motion network in the human brain

ABSTRACTThere is growing research interest in the neural mechanisms underlying the recognition of material categories and properties. This research field, however, is relatively more recent and limited compared to investigations of the neural mechanisms underlying object and scene category recognition. Motion is particularly important for the perception of non-rigid materials, but the neural basis of non-rigid material motion remains unexplored. Using fMRI, we investigated which brain regions respond preferentially to material motion versus other types of motion. We introduce a new database of stimuli – dynamic dot materials – that are animations of moving dots that induce vivid percepts of various materials in motion, e.g. flapping cloth, liquid waves, wobbling jelly. Control stimuli were scrambled versions of these same animations and rigid three-dimensional rotating dots. Results showed that isolating material motion properties with dynamic dots (in contrast with other kinds of motion) activates a network of cortical regions in both ventral and dorsal visual pathways, including areas normally associated with the processing of surface properties and shape, and extending to somatosensory and premotor cortices. We suggest that such a widespread preference for material motion is due to strong associations between stimulus properties. For example viewing dots moving in a specific pattern not only elicits percepts of material motion; one perceives a flexible, non-rigid shape, identifies the object as a cloth flapping in the wind, infers the object’s weight under gravity, and anticipates how it would feel to reach out and touch the material. These results are a first important step in mapping out the cortical architecture and dynamics in material-related motion processing.

Reverse-Engineering the Cortical Architecture for Controlled Semantic Cognition

We present a ‘reverse engineering’ approach to deconstruct cognition into neurocomputational mechanisms and their underlying cortical architecture, using controlled semantic cognition as a test case. By systematically varying the structure of a computational model and assessing the functional consequences, we identified architectural properties necessary for generating the core functions of the semantic system. Semantic cognition presents a challenging test case as the brain must achieve two seemingly contradictory functions: abstracting context-invariant conceptual representations across time and modalities, whilst producing specific context-sensitive behaviours appropriate for the immediate task. These functions were best achieved in models possessing a single, deep multimodal hub with sparse connections from modality-specific inputs, and control systems acting on peripheral rather than deep network layers. These architectural features correspond well with those suggested by neural data, strongly supporting the efficacy of the reverse engineering approach, and further generating novel hypotheses about the neuroanatomy of controlled semantic cognition.

Determining the association between regionalisation of cortical morphology and cognition in 10,145 children

ABSTRACTIndividuals undergo protracted changes in cortical morphology during childhood and adolescence, coinciding with cognitive development. Studies quantifying the association between brain structure and cognition do not always assess regional cortical morphology relative to global brain measures and typically rely on mass univariate statistics or ROI-based analyses. After controlling for global brain measures, it is possible to detect a residual regionalisation pattern indicating the size or thickness of different regions relative to the total cortical surface area or mean thickness. Individual variability in regionalisation may be important for understanding and predicting between subject variability in cognitive performance. Here we sought to determine whether the relative configuration of cortical architecture across the whole cortex was associated with cognition using a novel multivariate omnibus statistical test (MOSTest) in 10,145 children aged 9-10 years from the Adolescent Brain and Cognitive Development (ABCD) Study. MOSTest is better powered to detect associations that are widely distributed across the cortex compared to methods that assume sparse associations. We then quantified the magnitude of the association between vertex-wise cortical morphology and cognitive performance using a linear weighted sum across vertices, based on the estimated vertex-wise effect sizes. We show that the relative pattern of cortical architecture, after removing the effects of global brain measures, predicted unique variance associated with cognition across different imaging modalities and cognitive domains.SIGNIFICANCE STATEMENTThis paper demonstrates a significant advance in our understanding of the relationship between cortical morphology and individual variability in cognition. There is increasing evidence that brain-behaviour associations are distributed across the cortex. Using the unprecedented sample from the Adolescent Brain and Cognitive Development (ABCD) study and a novel application of a multivariate statistical approach (MOSTest), we have discovered specific distributed regionalization patterns across the cortex associated with cognition across multiple cognitive domains. This furthers our understanding of the relationship between brain structure and cognition, namely that these associations are not sparse and localized as assumed with traditional neuroimaging analyses. This multivariate method is extremely versatile and can be used in several different applications.

Disruption of Transient SERT Expression in Thalamic Glutamatergic Neurons Alters Trajectory of Postnatal Interneuron Development in the Mouse Cortex

In mice, terminal differentiation of subpopulations of interneurons occurs in late postnatal stages, paralleling the emergence of the adult cortical architecture. Here, we investigated the effects of altered initial cortical architecture on later interneuron development. We identified that a class of somatostatin (SOM)-expressing GABAergic interneurons undergoes terminal differentiation between 2nd and 3rd postnatal week in the mouse somatosensory barrel cortex and upregulates Reelin expression during neurite outgrowth. Our previous work demonstrated that transient expression (E15-P10) of serotonin uptake transporter (SERT) in thalamocortical projection neurons regulates barrel elaboration during cortical map establishment. We show here that in thalamic neuron SERT knockout mice, these SOM-expressing interneurons develop at the right time, reach correct positions and express correct neurochemical markers, but only 70% of the neurons remain in the adult barrel cortex. Moreover, those neurons that remain display altered dendritic patterning. Our data indicate that a precise architecture at the cortical destination is not essential for specifying late-developing interneuron identities, their cortical deposition, and spatial organization, but dictates their number and dendritic structure ultimately integrated into the cortex. Our study illuminates how disruption of temporal-specific SERT function and related key regulators during cortical map establishment can alter interneuron development trajectory that persists to adult central nervous system.