Enhanced Inter-hemispheric Functional Connectivity Compensates For Anatomical Connection Damages In Chronic Subcortical Ischemic Stroke

Objective:Motor recovery after stroke has been shown to be correlated with both the fractional anisotropy(FA) of the affected corticospinal tract(CST) and the inter-hemispheric resting-state functional connectivity(rs FC) of the primary motor cortex(M1). However, the role of the restoration or enhancement of the M1-M1 rs FC in motor recovery remains largely unknown. We aimed to clarify this issue by investigating correlations between the M1-M1 rs FC and the integrity of the M1-M1 anatomical connection and the affected CST in chronic subcortical stroke patients with good motor outcomes.Subjects and Methods:A total of 20 well-recovered stroke patients(13 males and 7 females) with a unilateral chronic ischemic infarct, involving of the internal capsule and neighboring regions were included. 16 age-matched healthy subjects(7males and 9 females) were also recruited as controls. Structural images, resting-state f MRI and diffusion tensor imaging(DTI) were acquired using a 3.0 T scanner(GE Signa HD-X).DTI was used to reconstruct the M1-M1 anatomical connection and bilateral CSTs. White matter integrity of these tracts was assessed using FA. Resting-state functional MRI was used to calculate M1-M1 rs FC. Group differences in these measures were compared. Then, correlations between M1-M1 rs FC and FA of the M1-M1 anatomical connection and the affected CST were analyzed in stroke patients. Ischemic stroke patients were divided into the left brain damage(LBD) and right brain damage(RBD) subgroups, the effect of lesion sides was analyzed. At last, these findings were confirmed using the voxel-based analysis(VBA).Results:1. Compared to healthy controls, chronic ischemic stroke patients exhibited significantly reduced FA in the affected CST and the M1-M1 anatomical connection and a significantly increased M1-M1 rs FC.2. The FA values of the affected CST were positively correlated with theM1-M1 anatomical connection, and these FA values were negatively correlated with the M1-M1 rs FC in these patients.3. Compared to the total chronic ischemic stroke patient group, the RBD and LBD subgroup displayed similar trends of significant differences and correlations.4. The whole brain voxel-wise analyses demonstrated that chronic ischemic stroke patients also exhibited significantly reduced FA in the affected CST and the M1-M1 anatomical connection and a significantly increased M1-M1 rs FC.Conclusion:1. The M1-M1 anatomical connectivity impairment is related to CST damage in chronic subcortical ischemic stroke patients.2. The enhanced M1-M1 rs FC may reflect a compensatory mechanism for motor deficits resulting from the impairment of the CST and the M1-M1 anatomical connection, which may account for similar motor recovery in subcortical stroke patients with varying degrees of CST impairments.3. The whole brain voxel-wise analyses confirmed that the correlations between the affected CST, the M1-M1 anatomical connection and the M1-M1 rs FC changes examined in this study are the main characteristic changes in chronic subcortical stroke patients.