Resting-State Activity and Connectivity of Dopaminergic Key Areas and Outcome After a Severe Stroke

Brain reserve capacity has recently gained an increasing interest in stroke recovery research to provide a deeper understanding of outcome variability. For instance, global and focal parameters of brain health, such as white matter hyperintensity burden or the structural reserve of the cerebellum, have been linked to recovery. Recently, it was shown that the pre-stroke structural state of key areas of the dopaminergic network might influence outcomes after stroke. We reanalyzed resting-state functional MRI data of 19 severely impaired acute stroke patients and 19 healthy controls and computed amplitudes of low-frequency fluctuations (ALFF) and functional connectivity (FC) in and between eight subcortical and cortical areas of the nigrostriatal and mesocorticolimbic dopaminergic network of the contralesional hemisphere. Linear regression modeling was used to compare patients and controls and combine patients' ALFF and FC data with clinical follow-up data obtained after 3-6 months. The group comparison revealed a significant upregulation of ALFF in the prefrontal cortices, the ventral tegmental area, the nucleus accumbens, and the caudate nucleus. Additionally, for some regions and connections within the nigrostriatal and mesocorticolimbic network, ALFF and FC estimates were significantly linked to global disability and symptom burden at follow-up. These data indicate a link between the pre-stroke functional state of key areas and pathways of the contralesional dopaminergic system and recovery from a severe stroke, thereby adding novel functional insights to recent structural data and promoting the emerging concepts of brain reserve capacity after stroke.