A Human Depression Circuit Derived From Focal Brain Lesions

Area of Science:

• Neuroscience
• Neurology
• Psychiatry

Background:

• Focal brain lesions offer insights into the neuroanatomical basis of depression.
• Previous studies on lesion location and depression have yielded inconsistent findings.

Purpose of the Study:

• To investigate the neuroanatomical substrate of depression using voxel lesion symptom mapping.
• To identify specific brain circuits associated with depression following focal brain lesions.
• To explore the potential of identified circuits for prognostic and therapeutic applications.

Main Methods:

• Collated five independent datasets (N=461) with diverse lesion etiologies and depression measures.
• Mapped 3D lesion locations to a common brain atlas and employed voxel lesion symptom mapping.
• Computed functional brain networks connected to lesion sites using a normative connectome dataset (N=1000).
• Validated findings using leave-one-dataset-out cross-validation and compared with effective brain stimulation sites.

Main Results:

• Lesion locations associated with depression were heterogeneous, without a single consistently implicated brain region.
• These heterogeneous lesion locations consistently mapped to a specific brain circuit centered on the left dorsolateral prefrontal cortex.
• Results demonstrated robustness through cross-validation and alignment with effective brain stimulation targets for poststroke depression.

Conclusions:

• Depression following focal brain lesions is associated with a specific brain circuit, not a single region.
• This identified circuit holds potential for prognostic utility in identifying at-risk patients.
• The circuit may also offer therapeutic utility by refining targets for brain stimulation interventions.