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A Human Depression Circuit Derived From Focal Brain Lesions.

ABSTRACT: 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.

SUBMITTER: Padmanabhan JL

PROVIDER: S-EPMC7531583 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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A Human Depression Circuit Derived From Focal Brain Lesions.

Padmanabhan Jaya L JL Cooke Danielle D Joutsa Juho J Siddiqi Shan H SH Ferguson Michael M Darby R Ryan RR Soussand Louis L Horn Andreas A Kim Na Young NY Voss Joel L JL Naidech Andrew M AM Brodtmann Amy A Egorova Natalia N Gozzi Sophia S Phan Thanh G TG Corbetta Maurizio M Grafman Jordan J Fox Michael D MD

Biological psychiatry 20190802 10

<h4>Background</h4>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.<h4>Methods</h4>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 lesio ...[more]

PMID: 31561861

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Project description:A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions.

Dataset Information

A Human Depression Circuit Derived From Focal Brain Lesions.

Publications

A Human Depression Circuit Derived From Focal Brain Lesions.

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