A Human Depression Circuit Derived From Focal Brain Lesions

Jaya L. Padmanabhan*, Danielle Cooke, Juho Joutsa, Shan H. Siddiqi, Michael Ferguson, R. Ryan Darby, Louis Soussand, Andreas Horn, Na Young Kim, Joel L. Voss, Andrew M. Naidech, Amy Brodtmann, Natalia Egorova, Sophia Gozzi, Thanh G. Phan, Maurizio Corbetta, Jordan Grafman, Michael D. Fox

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)749-758
Number of pages10
JournalBiological psychiatry
Volume86
Issue number10
DOIs
StatePublished - Nov 15 2019

Keywords

  • Depression
  • Functional MRI
  • Functional connectivity
  • Imaging
  • Lesion
  • Network
  • Stroke

ASJC Scopus subject areas

  • Biological Psychiatry

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