A Human Depression Circuit Derived From Focal Brain Lesions.
Depression
Functional MRI
Functional connectivity
Imaging
Lesion
Network
Stroke
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
15 11 2019
15 11 2019
Historique:
received:
15
02
2019
revised:
24
07
2019
accepted:
25
07
2019
pubmed:
29
9
2019
medline:
7
10
2020
entrez:
29
9
2019
Statut:
ppublish
Résumé
Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results. Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression. Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression. Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.
Sections du résumé
BACKGROUND
Focal brain lesions can lend insight into the causal neuroanatomical substrate of depression in the human brain. However, studies of lesion location have led to inconsistent results.
METHODS
Five independent datasets with different lesion etiologies and measures of postlesion depression were collated (N = 461). Each 3-dimensional lesion location was mapped to a common brain atlas. We used voxel lesion symptom mapping to test for associations between depression and lesion locations. Next, we computed the network of regions functionally connected to each lesion location using a large normative connectome dataset (N = 1000). We used these lesion network maps to test for associations between depression and connected brain circuits. Reproducibility was assessed using a rigorous leave-one-dataset-out validation. Finally, we tested whether lesion locations associated with depression fell within the same circuit as brain stimulation sites that were effective for improving poststroke depression.
RESULTS
Lesion locations associated with depression were highly heterogeneous, and no single brain region was consistently implicated. However, these same lesion locations mapped to a connected brain circuit, centered on the left dorsolateral prefrontal cortex. Results were robust to leave-one-dataset-out cross-validation. Finally, our depression circuit derived from brain lesions aligned with brain stimulation sites that were effective for improving poststroke depression.
CONCLUSIONS
Lesion locations associated with depression fail to map to a specific brain region but do map to a specific brain circuit. This circuit may have prognostic utility in identifying patients at risk for poststroke depression and therapeutic utility in refining brain stimulation targets.
Identifiants
pubmed: 31561861
pii: S0006-3223(19)31557-4
doi: 10.1016/j.biopsych.2019.07.023
pmc: PMC7531583
mid: NIHMS1543275
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
749-758Subventions
Organisme : NINDS NIH HHS
ID : K23 NS083741
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113929
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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