Distance-related functional reorganization predicts motor outcome in stroke patients

Abstract

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yield valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in chronic stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in chronic stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments.Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis.Results Our findings demonstrated that the left inferior frontal gyrus (IFG) displayed distance-independent FCD changes, while the bilateral supplementary motor area (SMA), cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral SMA and the motor function of lower limbs, and a negative correlation between increased FCD in the left IFG and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset.Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in chronic stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving chronic stroke.Trial registration All data for the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022).