Biology subjects

Gabrieli, J. D.

Publications and source records attributed to Gabrieli, J. D..

6 recordsLinked to original sources

bioRxiv2020

Asymmetric Functional Gradients in the Human Subcortex

A central principle in our understanding of cerebral cortical organization is that homotopic left and right areas are functionally linked to each other, and also connected with structures that share similar functions within each cerebral cortical hemisphere. Here we refer to this concept as interhemispheric functional symmetry (IHFS). While multiple studies have described the distribution and variations of IHFS in the cerebral cortex, descriptions of IHFS in the subcortex are largely absent in the neuroscientific literature. Further, the proposed anatomical basis of IHFS is centered on callosal and other commissural tracts. These commissural fibers are present in virtually all cerebral cortical areas, but almost absent in the subcortex. There is thus an important knowledge gap in our understanding of subcortical IHFS. What is the distribution and variations of subcortical IHFS, and what are the anatomical correlates and physiological implications of this important property in the subcortex? Using fMRI functional gradient analyses in a large dataset (Human Connectome Project, n=1003), here we explored IHFS in human thalamus, lenticular nucleus, cerebellar cortex, and caudate nucleus. Our detailed descriptions provide an empirical foundation upon which to build hypotheses for the anatomical and physiological basis of subcortical IHFS. Our results indicate that direct or driver cerebral cortical afferent connectivity, as opposed to indirect or modulatory cerebral cortical afferent connectivity, is associated with stronger subcortical IHFS in thalamus and lenticular nucleus. In cerebellar cortex and caudate, where there is no variability in terms of either direct vs. indirect or driver vs. modulatory cerebral cortical afferent connections, connectivity to cerebral cortical areas with stronger cerebral cortical IHFS is associated with stronger IHFS in the subcortex. These two observations support a close relationship between subcortical IHFS and connectivity between subcortex and cortex, and generate new testable hypotheses that advance our understanding of subcortical organization.

neuroscience↗

bioRxiv2019

Functional Territories of Human Dentate Nucleus

Anatomical connections link the cerebellar cortex with multiple distinct sensory, motor, association, and paralimbic areas of the cerebrum. These projections allow a topographically precise cerebellar modulation of multiple domains of neurological function, and underscore the relevance of the cerebellum for the pathophysiology of numerous disorders in neurology and psychiatry. The majority of fibers that exit the cerebellar cortex synapse in the dentate nuclei (DN) before reaching extracerebellar structures such as cerebral cortex. Although the DN have a central position in the anatomy of the cerebello-cerebral circuits, the functional neuroanatomy of human DN remains largely unmapped. Neuroimaging research has redefined broad categories of functional division in the human brain showing that primary processing, attentional (task positive) processing, and default-mode (task negative) processing are three central poles of neural macro-scale functional organization. This new macro-scale understanding of the range and poles of brain function has revealed that a broad spectrum of human neural processing categories (primary, task positive, task negative) is represented not only in the cerebral cortex, but also in the thalamus, striatum, and cerebellar cortex. Whether functional organization in DN obeys a similar set of macroscale divisions, and whether DN are yet another compartment of representation of a broad spectrum of human neural processing categories, remains unknown. Here we show for the first time that human DN is optimally divided into three functional territories as indexed by high spatio-temporal resolution resting-state MRI in 60 healthy adolescents, and that these three distinct territories contribute uniquely to default-mode, salience-motor, and visual brain networks. These conclusions are supported by novel analytical strategies in human studies of DN organization, including 64-channel MRI imaging, data-driven methods, and replication in an independent sample. Our findings provide a systems neuroscience substrate for cerebellar output to influence multiple broad categories of neural control - namely default- mode, attentional, and multiple unimodal streams of information processing including motor and visual. They also provide a validated data-driven mapping of functions in human DN, crucial for the design of methodology and interpretation of results in future neuroimaging studies of brain function and dysfunction.

neuroscience↗

bioRxiv2018

Functional specialization is independent of microstructural variation in cerebellum but not in cerebral cortex

The human brain is understood to follow fundamental principles linking form (such as microstructure and anatomical connectivity) to function (perceptual, motor, cognitive, emotional, and other processes). Most of this understanding is based on knowledge of the cerebral cortex, where functional specialization is thought to be closely linked to microstructural variation as well as anatomical connectivity. The Universal Cerebellar Transform (UCT) theory has posited that the cerebellum has a different form-function organization in which microstructure is uniform, and in which functional specialization is determined solely by anatomical connectivity with extracerebellar structures. All cerebellar functions may thus be subserved by a common microstructural - and hence computational - substrate. Here we tested this hypothesis by measuring microstructural variation and functional specialization as indexed by magnetic resonance imaging in 1003 healthy humans. Cerebral cortex exhibited the expected pattern of microstructure-function correlation, but functional specialization was independent of microstructural variation in the cerebellum. These findings support the idea that cerebellar functional specialization is not determined by microstructure, and hence that cerebellar functions may be computationally constant across domains.\n\nSIGNIFICANCE STATEMENTThe cerebellum is estimated to contain more than half the neurons in the human brain, is known to be involved in motoric, cognitive, and emotional functions, and is implicated in many neurological and neuropsychological disorders, but remains far less studied than the cerebral cortex. The Universal Cerebellar Transform (UCT) theory posits that one uniform computation underlies all cerebellar functions across multiple domains, but testing that idea has been difficult. Here we find that unlike the cerebral cortex, in which microstructural variation is associated with functional variation, the cerebellum exhibits relatively uniform microstructure across functionally distinct regions. These findings support UCT theory, and draw a sharp distinction between form-function relations in the cerebellum versus the cerebral cortex.

neuroscience↗

bioRxiv2018

LittleBrain: a gradient-based tool for the topographical interpretation of cerebellar neuroimaging findings

Gradient-based approaches to brain function have recently unmasked fundamental properties of brain organization. Diffusion map embedding analysis of resting-state fMRI data revealed a primary-to-transmodal axis of cerebral cortical macroscale functional organization. The same method was recently used to analyze resting-state data within the cerebellum, revealing for the first time a sensorimotor-fugal macroscale organization principle of cerebellar function. Cerebellar gradient 1 extended from motor to non-motor task-unfocused (default-mode network) areas, and cerebellar gradient 2 isolated task-focused processing regions. Here we present a freely available and easily accessible tool that applies this new knowledge to the topographical interpretation of cerebellar neuroimaging findings. LittleBrain generates scatterplots that illustrate the relationship between cerebellar data (e.g., volumetric patient study clusters, task activation maps, etc.) and cerebellar gradients 1 and 2. This novel method of data mapping provides alternative, gradual visualizations that complement discrete parcellation maps of cerebellar functional neuroanatomy. We present application examples to show that LittleBrain can also capture subtle, progressive aspects of cerebellar functional neuroanatomy that would be difficult to visualize using conventional mapping techniques. Download and use instructions can be found at https://xaviergp.github.io/littlebrain.

neuroscience↗

bioRxiv2018

Triple representation of language, working memory, social and emotion processing in the cerebellum: convergent evidence from task and seed-based resting-state fMRI analyses in a single large cohort

Delineation of functional topography is critical to the evolving understanding of the cerebellums role in a wide range of nervous system functions. We used data from the Human Connectome Project (n=787) to analyze cerebellar fMRI task activation (motor, working memory, language, social and emotion processing) and resting-state functional connectivity calculated from cerebral cortical seeds corresponding to the peak Cohens d of each task contrast. The combination of exceptional statistical power, activation from both motor and multiple non-motor tasks in the same participants, and convergent resting-state networks in the same participants revealed novel aspects of the functional topography of the human cerebellum. Consistent with prior studies there were two distinct representations of motor activation. Newly revealed were three distinct representations each for working memory, language, social, and emotional task processing that were largely separate for these four cognitive and affective domains. In most cases, the task-based activations and the corresponding resting-network correlations were congruent in identifying the two motor representations and the three non-motor representations that were unique to working memory, language, social cognition, and emotion. The definitive localization and characterization of distinct triple representations for cognition and emotion task processing in the cerebellum opens up new basic science questions as to why there are triple representations (what different functions are enabled by the different representations?) and new clinical questions (what are the differing consequences of lesions to the different representations?).\n\nHIGHLIGHTS- We analyzed motor and multiple nonmotor task fMRI activations in the cerebellum.\n- Resting-state seeds were placed at each task activation peak in the cerebral cortex.\n- We describe cerebellar task topography in the largest single cohort studied to date.\n- Nonmotor cerebellar task activation revealed a pattern of triple representation.\n- Resting-state analysis revealed an overlapping pattern of triple representation.

neuroscience↗

bioRxiv2018

Functional gradients of the cerebellum: a fundamental movement-to-thought principle

A central principle for understanding the cerebral cortex is that macroscale anatomy reflects a functional hierarchy from primary to transmodal processing. In contrast, the central axis of motor and nonmotor macroscale organization in the cerebellum remains unknown. Here we applied diffusion map embedding to resting-state data from the Human Connectome Project dataset (n=1003), and show for the first time that cerebellar functional regions follow a gradual organization which progresses from primary (motor) to transmodal (DMN, task-unfocused) regions. A secondary axis extends from task-unfocused to task-focused processing. Further, these two principal gradients reveal functional properties of the well-established cerebellar double motor representation, and its relationship with the recently described triple nonmotor representation. These interpretations are further supported by data-driven clustering and cerebello-cerebral functional connectivity analyses. Importantly, these descriptions remain observable at the individual subject level. These findings, from an exceptionally large and high-quality dataset, provide new and fundamental insights into the functional organization of the human cerebellum, unmask new testable hypotheses for future studies, and yield an unprecedented tool for the topographical, macroscale interpretation of cerebellar findings.

neuroscience↗