Contribution Of Interhemispheric Functional Connectivity To Motor Recovery After Subcortical Stroke

Background: After focal damage, cerebral networks reorganize their structural and functional properties to compensate for both local and remote impairment. Resting-state functional connectivity(rs FC) analyses have identified stroke-induced disturbances of the functional network architecture in both animals and patients. Functional reorganization accounts for spontaneous restoration of motor function after stroke.(1) The exact functional role of the contralesional M1 in motor recovery is a topic of debate. Here we investigated longitudinal changes in the rs FC of the contralesional primary sensorimotor cortex(CL_PSMC) and their association with motor recovery after stroke.(2) Most of previous studies have focused on functional reorganization of the sensorimotor network; however, the functional reorganization in other networks after stroke and their associations with motor recovery remain unclear. We examined interhemispheric rs FC in stroke patients using a recently proposed approach, voxel-mirrored homotopic connectivity(VMHC) which can quantify directly functional interactions between the cerebral hemispheres.(3) Previous rs FC analyses in stroke patients were performed at a group level and revealed that motor recovery might be associated with the increase of rs FC, particularly between interhemispheric sensorimotor areas. However, it remain unknown on the longitudinal changes of the inter-hemispheric rs FC at an individual level after stroke. We aimed to identify dynamic change of interhemispheric rs FC after stroke at the individual level.Methods: Nineteen subcortical stroke patients with motor deficits were studied longitudinally. Five resting-state f MRI sessions and clinical assessments were performed over a period of 1 year at 5 consecutive time points, i.e., within the first week, at 2 weeks, 1 month, 3 months, and 1 year after stroke onset. Nineteen age- and gender-matched healthy subjects were recruited as normal controls.(1) The CL_PSMC was defined as a region centered at the voxel that had greatest activation during hand motion task. The dynamic changes in the rs FCs of the CL_PSMC within the whole brain were evaluated and correlated with the Motricity Index(MI) scores.(2) We compared interhemispheric rs FC between patients and healthy controls using a one-way ANOVA, and a mixed model was used to evaluatethe dynamic changes of homotopic connectivity during recovery. Associations between these altered functional properties and clinical variables were finally explored.(3) Six male patients(age range: 49.2±3.9 years) who completed all 5 sessions and six age-matched male controls were enrolled in this part of study. The patients were assessed by neurological examinations and scanned with resting-state f MRI and diffusion tensor imaging(DTI) across five consecutive time points in a single year. Using a region of interest method,we analyzed the ratios of the fractional anisotropy(r FA) between the affected and unaffected sides of the corticospinal tract(CST). The resting-state f MRI images were preprocessed and analyzed to obtain the VMHC values. The dynamic changes of VMHC and the brain area with acute reduce of VMHC within a sensorimotor network were evaluated. Then we traced out the change curve of VMHC in these brain areas following stroke. Results:(1) Compared with healthy controls, the rs FCs of the CL_PSMC with the bilateral PSMC were initially decreased, then gradually increased, and finally restored to the normal level 1 year later. Moreover, the dynamic change in the interhemispheric rs FC between the bilateral PSMC in these patients was positively correlated with the MI scores. However, the intra-hemispheric rs FC of the CL_PSMC was not correlated with the MI scores.(2) We observed reduced interhemispheric rs FC in stroke patients relative to healthy controls, including the basal ganglia nucleus, the primary motor cortex, the inferior parietal lobule, the superior parietal lobule, the angular gyrus, the prefrontal lobe and the middle temporal gyrus. And there was also a significantly increased VMHC in the inferior temporal gyrus. Further analyses demonstrated the bilateral primary motor cortex, the inferior parietal lobule, the precuneus, the cerebellum, the amygdala exhibited linearly increased VMHC. And initially increased VMHC of the inferior temporal gyrus was gradually decreased. The dynamic changes of homotopicconnectivity were correlated with motor recovery. Conclusions:(1) This study shows dynamic changes in the rs FCs of the CL_PSMC after stroke and suggests that the increased inter-hemispheric rs FC between the bilateral PSMC may facilitate motor recovery in stroke patients.(2) Our ?ndings provide further evidence of an association between motor recovery and interhemispheric rs FC. We suggest that subcortical stroke may induce homotopic connectivity changes in extensive areas, affecting not only the sensorimotor area connect to the lesion but also cognitive processing regions after stroke.(3) Individual analyses of the longitudinal changes in the inter-hemispheric rs FC and CST impairments shed light on the relationship between inter-hemispheric rs FC changes and motor recovery, suggesting a potential application of interhemispheric rs FC in predicting motor outcome after subcortical stroke.