Plasticity of neural networks: Diagnostic and therapeutic transcranial magnetic stimulation of healthy and infarcted brains

Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment, making stroke the leading cause of adult disability. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for the promotion of upper limb recovery after stroke. rTMS is a non-invasive brain stimulation method that can modulate brain activity through electromagnetic induction. Before rTMS treatment can be applied in clinical rehabilitation programs, its long-term clinical efficacy needs to be evaluated, its working mechanism needs to be better understood, and patient selection criteria need to be defined.
The first chapters of this thesis describe fundamental research on how TMS can be used to modulate brain networks to target them therapeutically. The second part of this thesis focuses on the development of rTMS therapy for upper limb recovery after stroke. We show that rTMS treatment promotes upper limb recovery after stroke, reduces disability and dependence, and shortens the length of stay in a phase 2 randomized controlled trial in sixty stroke patients. We identified two potential treatment mechanisms that operate independently: normalization of motor cortex physiology and reorganization of the motor area in the affected brain hemisphere. Finally, we found that treatment efficacy is associated with residual motor function and intact corticospinal tract integrity. Therefore, selecting patients for rTMS treatment based on residual motor function or CST integrity may improve upper limb outcome. These results form the basis for a phase-3 multi-center clinical trial on the efficacy of rTMS treatment for the promotion of upper limb recovery after stroke.