Cortical motor network flexibility during lower limb motor activity and deficiencies after stroke

Abstract Background and Purpose Motor network flexibility, the ability to switch between different neural network connectivity configurations, is a key feature of normal motor behavior and motor learning. Limited flexibility of the motor system to adapt to environmental stimuli is a pervasive feature of mobility impairment in chronic stroke survivors. The reduced capacity to modulate cortical motor network connectivity during motor behavior has been implicated as a key neural mechanism for constrained flexibility of the motor system. However, whether the theory of reduced cortical motor network flexibility prevails in the lower limb corticomotor system and in the context of functional lower limb motor behaviors remains unknown. In this study, we tested the capacity of the lower limb motor cortex to react to external stimuli using transcranial magnetic stimulation (TMS) and the ability of the cortex to modulate motor network connectivity during lower limb motor activity in a group of chronic stroke survivors and age-matched older adult controls. We evaluated the relationship between activity-dependent modulation of TMS-evoked motor cortical connectivity and post-stroke clinical and biomechanical walking function as well as corticospinal excitability of the paretic leg. Methods Chronic stroke survivors (n=14) and older adults (n=9) completed concurrent TMS-electroencephalography (EEG) testing, clinical evaluation, and biomechanical walking assessment. EEG was recorded during TMS delivered over the contralesional (c)M1 and ipsilesional (i)M1 during rest and active ipsilateral plantarflexion. Interhemispheric connectivity was calculated as the post-TMS (0-300ms) imaginary part of coherence value between electrodes overlying cM1 and iM1 within the beta frequency range (15-30Hz). We compared cM1 and iM1 TMS-evoked beta coherence between groups during rest and active conditions and tested associations with walking impairment and paretic leg corticospinal excitability in stroke survivors. Results In older adult controls, TMS-evoked beta coherence was greater compared to stroke survivors and showed a reduction from rest during active motor conditions regardless of hemisphere. Stroke survivors showed lower TMS-evoked beta coherence during cM1 TMS and a lack of modulation between rest and active conditions. Higher cM1 TMS-evoked beta coherence at rest and reduction of beta coherence during paretic plantarflexion was associated with greater paretic ankle moment during walking and lower levels of clinical lower limb motor impairment. Increased beta coherence during iM1 TMS at rest was associated with the presence of a MEP in the paretic lower limb. Conclusions We found that, like findings in animal models and the upper limb, the lower limb corticomotor system showed reduced cortical network reactivity to external stimuli (TMS), and impaired modulation of cortical network connectivity during lower limb motor activity after stroke. Impaired cortical reactivity and modulation were associated with post-stroke clinical and biomechanical walking function and corticomotor excitability of the paretic leg, supporting the link between cortical network connectivity, motor network flexibility and lower limb motor behavior. These findings have important implications for the development of targeted and individualized treatments to improve lower limb disability in stroke survivors.