Investigating manual dexterity in healthy people and patients after stroke using multi-locus transcranial magnetic stimulation

ended

Upper limb dexterity is a unique human ability commonly compromised by stroke. I suggest that the upper limb dexterity after stroke may be compromised as a result of dysfunctional inhibition of the nearby muscles. In patients with mild motor impairment, this results in a lack of independent finger movements. In moderately-to-severely affected patients, the pathological synergies pose a major problem, affecting both proximal and distal joint movements. I will develop methods for evaluating the neural origins of the upper limb dexterity and its recovery after stroke, and for improving compromised motor control by transcranial magnetic stimulation (TMS) combined with electroencephalography, electromyography, and structural magnetic resonance imaging. I will perform multi-muscle cortical mapping using a novel neuromodulation technology, namely multi-locus TMS (mTMS), which allows stimulation of the nearby cortical targets with millisecond-scale delays between the pulses without moving the stimulator. This unique feature of mTMS will enable us to determine local excitation/inhibition (E/I) interactions among the cortical representations of different upper limb muscles. I will evaluate whether abnormal control of independent finger movements can be structurally and functionally explained in terms of the local E/I balance at the motor cortex. Then, I will utilize this information to develop unprecedented mTMS protocols that take into account the individual organization of the motor cortex and the possibility of its selective neuromodulation. In summary, I aim to demonstrate that (1) the intricate patterns of local E/I balance at the motor cortex are involved in the orchestration of muscle synergies, (2) the malfunctioning of this complex circuitry after stroke can lead to abnormal muscle-specific corticospinal excitability and impaired upper limb motor function, and (3) the local E/I balance can be manipulated with physiologically tuned multi-site mTMS protocols.