Figure 2:

Lesion locations associated with depression intersect a connected brain circuit, not an individual brain region. (A) A sample lesion from a depressed subject and a non-depressed subject are depicted in green. Standard voxel-based lesion-symptom mapping identified no lesioned voxels significantly associated with depression. (B) Functional connectivity of each lesion location to the rest of the brain was computed using resting state functional connectivity data from 1000 healthy controls. A focal region in the left dorsolateral prefrontal cortex showed greater functional connectivity to lesions of depressed subjects than to lesions of non-depressed subjects (depicted in red; voxel-level family-wise error [FWE] corrected p < 0.05). (C) Using normative connectome data, we examined the whole-brain functional connectivity of this region, generating a depression circuit. By definition, lesions from depressed subjects will intersect positive nodes of this network (sample lesion shown in violet) while lesions from non-depressed subjects will not (sample lesion shown in cyan). In panels B and C, the red-yellow coloration indicates regions positively connected to the region, while the blue-green coloration indicates regions negatively connected (anti-correlated) to the region. Network maps are thresholded at T = ±5 for ease of visualization (actual network maps were unthresholded). Z coordinates of slices in panel C: −25, −5, 15, 35, 55.