Model-Based Analyses for the Causal Relationship Between Post-stroke Impairments and Functional Brain Connectivity Regarding the Effects of Kinesthetic Illusion Therapy Combined With Conventional Exercise

Aims: Therapy with kinesthetic illusion of segmental body part induced by visual stimulation (KINVIS) may allow the treatment of severe upper limb motor deficits in post-stroke patients. Herein, we investigated: (1) whether the effects of KINVIS therapy with therapeutic exercise (TherEx) on motor functions were induced through improved spasticity, (2) the relationship between resting-state functional connectivity (rs-FC) and motor functions before therapy, and (3) the baseline characteristics of rs-FC in patients with the possibility of improving their motor functions. Methods: Using data from a previous clinical trial, three path analyses in structural equation modeling were performed: (1) a mediation model in which the indirect effects of the KINVIS therapy with TherEx on motor functions through spasticity were drawn, (2) a multiple regression model with pre-test data in which spurious correlations between rs-FC and motor functions were controlled, and (3) a multiple regression model with motor function score improvements between pre- and post-test in which the pre-test rs-FC associated with motor function improvements was explored. Results: The mediation model illustrated that although KINVIS therapy with TherEx did not directly improve motor function, it improved spasticity, which led to ameliorated motor functions. The multiple regression model with pre-test data suggested that rs-FC of bilateral parietal regions is associated with finger motor functions, and that rs-FC of unaffected parietal and premotor areas is involved in shoulder/elbow motor functions. Moreover, the multiple regression model with motor function score improvements suggested that the weaker the rs-FC of bilateral parietal regions or that of the supramarginal gyrus in an affected hemisphere and the cerebellar vermis, the greater the improvement in finger motor function. Conclusion: The effects of KINVIS therapy with TherEx on upper limb motor function may be mediated by spasticity. The rs-FC, especially that of bilateral parietal regions, might reflect potentials to improve post-stroke impairments in using KINVIS therapy with TherEx.