Mapping the subcortical connectivity of the human default mode network

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 basa...

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Autores principales:	Jian Li, William H. Curley, Bastien Guerin, Darin D. Dougherty, Adrian V. Dalca, Bruce Fischl, Andreas Horn, Brian L. Edlow
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Subcortical connectivity Default mode network Consciousness Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/bfb2a68a306c42acb607a1e222f9bcd8
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spelling	oai:doaj.org-article:bfb2a68a306c42acb607a1e222f9bcd82021-12-04T04:33:18ZMapping the subcortical connectivity of the human default mode network1095-957210.1016/j.neuroimage.2021.118758https://doaj.org/article/bfb2a68a306c42acb607a1e222f9bcd82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1053811921010302https://doaj.org/toc/1095-9572The 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.Jian LiWilliam H. CurleyBastien GuerinDarin D. DoughertyAdrian V. DalcaBruce FischlAndreas HornBrian L. EdlowElsevierarticleSubcortical connectivityDefault mode networkConsciousnessNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeuroImage, Vol 245, Iss , Pp 118758- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Subcortical connectivity Default mode network Consciousness Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Subcortical connectivity Default mode network Consciousness Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Jian Li William H. Curley Bastien Guerin Darin D. Dougherty Adrian V. Dalca Bruce Fischl Andreas Horn Brian L. Edlow Mapping the subcortical connectivity of the human default mode network
description	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.
format	article
author	Jian Li William H. Curley Bastien Guerin Darin D. Dougherty Adrian V. Dalca Bruce Fischl Andreas Horn Brian L. Edlow
author_facet	Jian Li William H. Curley Bastien Guerin Darin D. Dougherty Adrian V. Dalca Bruce Fischl Andreas Horn Brian L. Edlow
author_sort	Jian Li
title	Mapping the subcortical connectivity of the human default mode network
title_short	Mapping the subcortical connectivity of the human default mode network
title_full	Mapping the subcortical connectivity of the human default mode network
title_fullStr	Mapping the subcortical connectivity of the human default mode network
title_full_unstemmed	Mapping the subcortical connectivity of the human default mode network
title_sort	mapping the subcortical connectivity of the human default mode network
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/bfb2a68a306c42acb607a1e222f9bcd8
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Mapping the subcortical connectivity of the human default mode network

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