• Wenjun Hong, Zaixing Liu, Xin Zhang, Ming Li, Zhixuan Yu, Yuxin Wang, Minmin Wang, Yanan Wu, Shengjie Fang, Bo Yang, Rong Xu, and Zhiyong Zhao.
• Department of Rehabilitation Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
• Bmc Med. 2024 Jun 18; 22 (1): 247247.

BackgroundAnalyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments.MethodsIn 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.ResultsOur findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, 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 supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset.ConclusionsThe FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute 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 non-acute stroke.Trial RegistrationAll data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).© 2024. The Author(s).

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