Dataset Information

Hierarchical organization of cortical and thalamic connectivity.

ABSTRACT: The mammalian cortex is a laminar structure containing many areas and cell types that are densely interconnected in complex ways, and for which generalizable principles of organization remain mostly unknown. Here we describe a major expansion of the Allen Mouse Brain Connectivity Atlas resource¹, involving around a thousand new tracer experiments in the cortex and its main satellite structure, the thalamus. We used Cre driver lines (mice expressing Cre recombinase) to comprehensively and selectively label brain-wide connections by layer and class of projection neuron. Through observations of axon termination patterns, we have derived a set of generalized anatomical rules to describe corticocortical, thalamocortical and corticothalamic projections. We have built a model to assign connection patterns between areas as either feedforward or feedback, and generated testable predictions of hierarchical positions for individual cortical and thalamic areas and for cortical network modules. Our results show that cell-class-specific connections are organized in a shallow hierarchy within the mouse corticothalamic network.

SUBMITTER: Harris JA

PROVIDER: S-EPMC8433044 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Hierarchical organization of cortical and thalamic connectivity.

Harris Julie A JA Mihalas Stefan S Hirokawa Karla E KE Whitesell Jennifer D JD Choi Hannah H Bernard Amy A Bohn Phillip P Caldejon Shiella S Casal Linzy L Cho Andrew A Feiner Aaron A Feng David D Gaudreault Nathalie N Gerfen Charles R CR Graddis Nile N Groblewski Peter A PA Henry Alex M AM Ho Anh A Howard Robert R Knox Joseph E JE Kuan Leonard L Kuang Xiuli X Lecoq Jerome J Lesnar Phil P Li Yaoyao Y Luviano Jennifer J McConoughey Stephen S Mortrud Marty T MT Naeemi Maitham M Ng Lydia L Oh Seung Wook SW Ouellette Benjamin B Shen Elise E Sorensen Staci A SA Wakeman Wayne W Wang Quanxin Q Wang Yun Y Williford Ali A Phillips John W JW Jones Allan R AR Koch Christof C Zeng Hongkui H

Nature 20191030 7781

The mammalian cortex is a laminar structure containing many areas and cell types that are densely interconnected in complex ways, and for which generalizable principles of organization remain mostly unknown. Here we describe a major expansion of the Allen Mouse Brain Connectivity Atlas resource<sup>1</sup>, involving around a thousand new tracer experiments in the cortex and its main satellite structure, the thalamus. We used Cre driver lines (mice expressing Cre recombinase) to comprehensively ...[more]

PMID: 31666704

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Project description:Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

Dataset Information

Hierarchical organization of cortical and thalamic connectivity.

Publications

Hierarchical organization of cortical and thalamic connectivity.

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