Structure-Function Changes In Fine-grained Sensorimotor Pathways And Their Effects On Motor Outcome In Stroke

Stroke is the leading cause of adult disability worldwide.Motor impairment is the most common domain of functional deficit after stroke,which is attribute to a high prevalence of subcortical motor pathway damage.Previous studies have shown that nerve cells in the brain area are been directly damaged would undergo degeneration and necrosis,and other areas that are not directly damaged would also undergo secondary degeneration or reorganization,resulting in extensive changes in the structure and function of the whole brain.In recent years,advanced magnetic resonance imaging(MRI)technology provides a new way to explore brain structure and function.Many imaging studies have reported the pair wise correlation between the changes of brain structure and function and the degree of injury or recovery of motor function following stroke,but few studies have revealed the potential causal relationship between structure damage,functional reorganization and behavioral dysfunction.The sensorimotor cortex(SMC)is the most vulnerable cortical area after subcortical stroke,and its injury is closely related to motor dysfunction,so it has been considered as the core brain region for clinical intervention to promote motor recovery.However,the structure-function changes of SMC fine pathways in subcortical stroke and their effects on motor impairment remain unclear.Considering the above problems in stroke studies,here,we collected diffusion tensor imaging(DTI)and resting-state magnetic resonance imaging(f MRI)data of 35 patients with unilateral subcortical moderate to severe chronic stroke and 43 age matched healthy controls,and have conducted in-depth research as follows:Part I.The Structural damage of fine sensorimotor pathways after subcortical strokeThe corticospinal tract(CST)descending from SMC is often direct injured by stroke lesions.Secondary degeneration occurs in callosal sensorimotor fibers(CSMF),which connects the interhemispheric SMC.SMC includes the primary motor cortex(M1),dorsal premotor cortex(PMd),ventral premotor cortex(PMv),primary somatosensory cortex(S1),supplementary motor area(SMA)and supplementary premotor area(pre SMA).At present,the damage of fine structural pathway of CST and CSMF originating from these 6 subareas of SMC and the relationship with motor dysfunction are not clear.We used high-resolution map of sensorimotor pathways to analyze the damage of fine structural pathways of CST and CSMF after stroke from multiple perspectives:(1)the involvement severity degree of fine structural pathways of CST(direct damage)caused by stroke lesions;(2)the global microstructure damage of each fine fiber tract in the pathways of CST and CSMF;(3)the slice-level microstructure damage of each fine fiber tract in the pathways of CST and CSMF.Further,correlation analysis with Fugl-Meyer assessment of upper extremity(FM-UE)were performed.The results showed that:(1)All the fine sub-pathway structures of CST and CSMF were damaged by focal stroke lesion.In the fine CST pathways;(2)The CST originating from M1 made the greatest contribution to the prediction of motor dysfunction;(3)The slice-level microstructure damage analysis further revealed the specific damaged locations of the fine structure pathway.(4)The cerebral peduncle-internal capsular posterior limb region of CST,the radial crown region of CST originating from M1 and S1,the cortical region near M1 and the body of corpus callosum in CSMF all showed positive correlations with the severity of motor function injury of the upper limb.Part II.Functional changes of fine pathways in the SMC mediate the relationship between structural injury and motor dysfunctionPart I study have found the extensive damage to the fine pathways of CST and CSMF,and these damages were associated with motor dysfunction.We further speculate that the damage of these fine-structural pathways may indirectly affect motor behavior by affecting the functional connectivity(FC)of the corresponding pathways.We identified functional pathways associated with specific structural pathway damage,namely covaried structural-functional pathways,and further analyzed the mediating role of FC by establishing a simple mediation model.The results showed that:(1)The FC originating from subregions of SMC corresponding to fine CST and CSMF pathways were extensively reorganized;(2)Nine structurally and functionally covaried pathways were identified that were related to the damage of CST originating from M1,PMd,and S1.Bilateral FC of M1,PMd,and PMv covaried with secondary degeneration of corresponding CSMF.These covarying structures and functions were significantly correlated with FM-UE.(3)FC between the ipsilesional PMd and contralesional cerebellum(β =-0.141,P < 0.05,CI = [-0.319 to-0.015])and interhemispheric FC of the PMd(β = 0.169,P < 0.05,CI = [0.015–0.391])showed significant mediation effects in the prediction of motor impairment with structural damage of the CST and CSMF,suggesting that the structural injury may indirectly affect the motor injury by affecting the functional reorganization.Part III.Dynamic changes of sensorimotor structural-functional covaried pathways and the relationship with recovery of upper limb motor functionThis part of the study further explored the dynamic changes of sensorimotor fine structure-functional pathways,especially whether the covaried structural-functional pathways with mediating effects play a more critical role in motor recovery.We conducted a longitudinal follow-up study on the same group of stroke patients before and after rehabilitation intervention.The results showed that:(1)After rehabilitation intervention,the structural and functional changes in the covaried pathways were not obvious,however,the structure-function coupling decreased significantly;(2)The mediating functional pathways(FC between the ipsilesional PMd and contralesional cerebellum,FC between bilateral PMd)can predict the improvement of the upper limb motor function;(3)In the PMd-cerebellum functional pathway affected by CST structural damage,patients with severe FC deficit were the first to have functional recovery of the pathway;in the bilateral PMd functional pathway affected by CSMF structural damage,the corpus callosum structure of patients with severe functional connectivity injury were the first to recovery.The FC of these two pathways decreased after intervention in patients with no obvious FC damage before the intervention.In conclusion,this dissertation used MRI technology(DTI and f MRI)combined with high-resolution fine maps of SMC to analyze the structural damage and functional reorganization of sensorimotor fine pathways in unilateral subcortical stroke with a large sample size,providing a new idea for the study of the structure-function coupling of specific brain pathways.In particular,the mediating role of the FC between PMd-cerebellum and bilateral PMd was found,which possibly provided objective evidence for using PMd as a target for neuroregulation in clinical rehabilitation.The findings of dynamic changes in the sensorimotor structuralfunctional covaried pathways further suggest that the mediating pathways may promote motor recovery through adaptive balance and slight tuning.Thus,neural regulation of PMd or cerebellum should consider the FC level of patients at baseline;that is,it would be effective to promote recovery of pathway function in patients with more severe injury at baseline,but not in patients with less severe impairment at baseline.