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

Weaver, N. A.; Lim, J.-S.; Schilderinck, J.; Biessels, G. J.; Kang, Y.; Kim, B. J.; Kuijf, H. J.; Lee, B.-C.; Lee, K.-J.; Yu, K.-H.; Bae, H.-J.; Biesbroek, J. M.

doi:10.1101/2021.05.05.442398

bioRxiv · 10.1101/2021.05.05.442398

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

Weaver, N. A.·Lim, J.-S.·Schilderinck, J.·Biessels, G. J.·Kang, Y.·Kim, B. J.·Kuijf, H. J.·Lee, B.-C.·Lee, K.-J.·Yu, K.-H.·Bae, H.-J.·Biesbroek, J. M.

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Abstract

BackgroundDepression is the most common neuropsychiatric complication after stroke. Infarct location is associated with post-stroke 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. MethodsWe included 553 patients (age 69{+/-}11 years, 42% female) with acute ischemic stroke. PSDS were measured using the 30-item Geriatric Depression Scale (GDS-30). Multivariable support vector regression (SVR)-based analyses were performed both at the level of individual voxels (SVR-VLSM) and predefined regions of interest (SVR-ROI) 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-VLSM, 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<0.05) in SVR-VLSM and SVR-ROI. External validation (N=459) 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<0.05) with PSDS. ConclusionsInfarcts 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.

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Weaver, N. A., Lim, J.-S., Schilderinck, J., Biessels, G. J., Kang, Y., Kim, B. J., Kuijf, H. J., Lee, B.-C., Lee, K.-J., Yu, K.-H., Bae, H.-J., Biesbroek, J. M.. 2021-05-05. Strategic infarct locations for post-stroke depressive symptoms: a lesion- and disconnection-symptom mapping study. https://doi.org/10.1101/2021.05.05.442398

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