Year: 2021
Type: article
Abstract: The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped, and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 µm ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.
Source: NeuroImage
Institutions: Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Brigham and Women's Hospital, Stiftung Charité, Charité – Universitätsmedizin Berlin
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,300
Funders: U.S. Department of Defense, James S. McDonnell Foundation, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, NIH Office of the Director, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources, NIH Blueprint for Neuroscience Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G106490469, G187944815, G2058387751, G2227408383, Brainstem Connectome Mapping to Guide Targeted Stimulant Therapy in Patients with Traumatic Coma, G2998073318, G3070797169, G323562261, Segmenting Brain Structures for Neurological Disorders, G393103480, Inferring in Vivo Cytoarchitectural Borders in the Medial Temporal Lobe, G4143200577, Algorithms for MR and OCT-based Architectonic and Laminar Segmentation, The Human Connectome Project (HCP), OCTology: histology using optical coherence tomography, G4621073790, A Connectome-Based Clinical Trial Platform to Promote Early Recovery of Consciousness after Traumatic Coma, Deep Learning Algorithms for FreeSurfer, G5096156415, Accelerated Software Tools for Neuroimaging Analysis, Nobrainer: A robust and validated neural network tool suite for imagers, Computeserver Structural &Functional Image Analysis, Neuropathology of CTE and Delayed Effects of TBI: Toward In-Vivo Diagnostics, MRI, Genetics & Cognitive Precursors of AD and Dementia, Open-source software for multi-scale mapping of the human brain, Clinical & biological signatures of post-traumatic neurodegeneration: Toward in vivo diagnosis of the late effects of TBI., G7000385371, Deep Learning Algorithms for FreeSurfer, Software Tools for Automated Modeling of White Matter Fascicles from Diffusion MR, Methods for mapping cell adhesion receptors, Center for Functional Imaging Technologies, G7881056414, Tools for Analyzing Cortical Structure and Connectivity, Epidemiology of Dementia in the Framingham Study, A Storage Area Network for Structural and Functional Image Analysis, Imaging and Analysis Techniques to Construct a Cell Census Atlas of the Human Brain, A Longitudinal Analysis Stream for FreeSurfer, VCID Biomarkers Coordinating Center, FreeSurfer Development, Maintenance, and Hardening, Center for Mesoscale Mapping, Diagnosing the undiagnosable: studies of Alzheimer disease mimics and confounders via "neuropathometry" of dissection photos with 3D scanning, South Texas Alzheimer's Disease Center, Silicon Graphics Prism Extreme 128P/1TB
OpenAlex ID: W3214890427