Lower cognitive control network connectivity in stroke participants with depressive features

Around one-third of people develop depression following ischaemic stroke, yet the underlying mechanisms are poorly understood. Post-stroke depression has been linked to frontal infarcts, mainly lesions in the left dorsolateral prefrontal cortex (DLPFC). But depression is a network disorder that cannot be fully characterised through lesion-symptom mapping. Researchers of depression in non-stroke populations have successfully tapped into the cognitive control network (CCN) using the bilateral DLPFC as a seed, and found that CCN resting-state connectivity is reduced in even mildly depressed subjects, compared to healthy controls. Hence, we aimed to investigate the association between post-stroke depressive features and the CCN resting-state connectivity in a stroke population. We analysed DLPFC resting-state connectivity in 64 stroke participants, 20 of whom showed depressive features assessed with the Patient Health Questionnaire (PHQ-9) at 3 months after stroke. We directly compared groups showing symptoms of depression with those who did not, and performed a regression with PHQ-9 scores in all participants, controlling for age, gender, lesion volume and stroke severity. Post-stroke depression was associated with lower connectivity between the left DLPFC and the right supramarginal gyrus (SMG) in both group and regression analyses. Neither the seed nor the results overlapped with stroke lesions. These findings confirm an important role of the left DLPFC in post-stroke depression, but now show that large-scale network disruptions following stroke associated with depressive features occur without lesions in the DLPFC.