Friday, April 19, 2024
4/19/2024
Effects of Cortical Stimulation on Motor Recovery Cortical stimulation (CS) techniques, such as epidural cortical stimulation (ECS) and repeated transcranial magnetic stimulation (rTMS), are emerging as potential therapeutic tools to enhance the efficacy of post-stroke rehabilitation. Excitatory electrical cortical stimulation (eCS) or repeated Transcranial Magnetic Stimulation (rTMS) over the infarcted motor cortex, or disruptive low-frequency rTMS over the contralateral non-infarcted motor cortex, can lead to motor improvements of the paretic limb. Current theories suggest that cortical stimulation following ischemic damage “re- balances” interhemispheric activity between the non-infarcted and infarcted hemispheres interconnected via reciprocal excitatory circuits. In humans, facilitatory stimulation (high- frequency) ECS or rTMS over the infarcted motor cortex or disruptive stimulation (low- frequency) rTMS has been shown to improve performance of the paretic side; however, several studies also fail to support these findings. In rats, we and others have found that high-frequency (50Hz – 100Hz) ECS over the peri-lesion motor cortex following a focal, moderate stroke concurrent with motor rehabilitative training (RT), robustly improves functional motor recovery. Peri-infarct ECS+RT also results in functional and structural neural plasticity in the remaining motor cortex compared to RT alone. However, following severe strokes or controlled cortical impacts, a model of moderate to severe TBI, ipsi- injury high-frequency ECS+RT sub-optimally improves recovery compared to RT alone. We hypothesize that following moderate to severe damage to the motor cortex, low- frequency stimulation over the non-infarcted motor cortex concurrent with RT will be more effective at improving impaired motor function compared to high-frequency ipsi- injury ECS+RT or RT alone. BDNF binding to TrkB is necessary and sufficient to improve motor function and drive neural plasticity after stroke. CS+Rt also provides motor recovery through CS's ability to increase BDNF/TrkB signaling. We also hypothesize that this facilitation may be sensitive to endogenous BDNF/TrkB activity altered by age, and that pharmacological enhancement of TrkB signaling will maximize CS effects in aged animals.These studies will lay the foundation to better understand the lack of consensus across studies and to begin investigating the mechanisms underlying CS effects in stroke recovery.
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