Strategic infarct locations for post-stroke depressive symptoms: a lesion- and disconnection-symptom mapping study

Weaver, Nick A, Lim, Jae-Sung, Schilderinck, Janniek, Biessels, Geert Jan, Kang, Yeonwook, Kim, Beom Joon, Kuijf, Hugo J, Lee, Byung-Chul, Lee, Keon-Joo, Yu, Kyung-Ho, Bae, Hee-Joon, Biesbroek, J Matthijs


Biological Psychiatry: Cognitive Neuroscience and Neuroimaging


BACKGROUND: Depression is the most common neuropsychiatric complication after stroke. Infarct location is associated with poststroke depressive symptoms (PSDS), but it remains debated which brain structures are critically involved. We performed a large-scale lesion-symptom mapping study to identify infarct locations and white matter disconnections associated with PSDS.

METHODS: We included 553 patients (mean [SD] age = 69 [11] years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale. Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (voxel-based lesion-symptom mapping) and at predefined regions of interest to relate infarct location to PSDS. We externally validated our findings in an independent stroke cohort (N = 459). Finally, disconnectome-based analyses were performed using SVR voxel-based lesion-symptom mapping, in which white matter fibers disconnected by the infarct were analyzed instead of the infarct itself.

RESULTS: Infarcts in the right amygdala, right hippocampus, and right pallidum were consistently associated with PSDS (permutation-based p < .05) in SVR voxel-based lesion-symptom mapping and SVR region-of-interest analyses. External validation confirmed the association between infarcts in the right amygdala and pallidum, but not the right hippocampus, and PSDS. Disconnectome-based analyses revealed that disconnections in the right parahippocampal white matter, right thalamus and pallidum, and right anterior thalamic radiation were significantly associated (permutation-based p < .05) with PSDS.

CONCLUSIONS: Infarcts in the right amygdala and pallidum and disconnections of right limbic and frontal cortico-basal ganglia-thalamic circuits are associated with PSDS. Our findings provide a comprehensive and integrative picture of strategic infarct locations for PSDS and shed new light on pathophysiological mechanisms of depression after stroke.