Prefrontal Cortex as a Central Hub of Structural Diaschisis Following Subcortical Stroke

BACKGROUND: After a subcortical stroke, structural and functional alterations have often been observed in brain regions far from the lesion, a phenomenon suspected but not yet confirmed as diaschisis. This study investigated the existence and patterns of diaschisis following subcortical stroke. METHODS: This observational, single-center, cross-sectional study was conducted in China from August 2014 to September 2023. We recruited patients with subcortical stroke with hemiplegia and unilateral lesions in the basal ganglia or corona radiata. Healthy controls were recruited from the community using an age- and sex-matching strategy with the patients. Patients were categorized by the National Institutes of Health Stroke Scale scores: mild (<5) and moderate (5-15) deficits. Using magnetic resonance imaging techniques, we analyzed gray matter volume alterations with voxel-based morphometry and causal structural networks with the causal structural covariance network method. RESULTS: Of the 566 patients initially screened, 102 were enrolled. Due to recruitment constraints, only 46 healthy controls were recruited, limiting successful matching. The final analysis included 90 patients and 44 controls. The patient group (62 men and 28 women) had a mean age of 60.64±9.93 years, while the healthy group (23 men and 21 women) had a mean age of 59.43±5.01 years. We found significant gray matter volume loss in the medial superior frontal gyrus and identified both positive and negative directional connectivity patterns between this region and other areas in the prefrontal cortex (inferior frontal gyrus), temporal regions (superior and middle temporal gyri), limbic structures (insula, cingulate gyrus, and parahippocampus), and precentral. Notably, the causal network in patients with mild deficits was more complex. CONCLUSIONS: These findings support the existence of structural diaschisis following subcortical stroke, centered in the prefrontal cortex. This study underscores the importance of brain-wide imaging markers and may contribute to developing brain stimulation targets.