Influence of Brain Oscillation-Dependent TMS on Motor Function

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Study Description: We will study if corticospinal excitability (primary outcome measure) varies across different sensorimotor alpha EEG waveform oscillation phases in healthy older adults and chronic stroke patients. Sensorimotor cortical neuronal spiking is highest at sensorimotor alpha oscillation...

Study Description: We will study if corticospinal excitability (primary outcome measure) varies across different sensorimotor alpha EEG waveform oscillation phases in healthy older adults and chronic stroke patients. Sensorimotor cortical neuronal spiking is highest at sensorimotor alpha oscillation troughs and lowest at sensorimotor alpha oscillation peaks, suggesting that cortical excitability is higher at sensorimotor alpha oscillation troughs relative to peaks. We will address these questions using closed-loop TMS. Based on this previous work, we hypothesize that corticospinal excitability (primary outcome measure) will be increased at sensorimotor alpha oscillation troughs compared to peaks in healthy older adults (Experiment 1), and chronic stroke patients (Experiment 2). Objectives: Transcranial magnetic stimulation (TMS) is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been customarily applied uncoupled from brain oscillatory activity (as measured using EEG waveforms), resulting in variability in the biological response to each stimulus, small effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e., EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical inhibition, motor function and cognitive processing, and therefore influences brain function. For example, corticospinal excitability (as measured with TMS) in healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity). We recently replicated this result in young healthy adults. We therefore aim to extend these findings to two new populations: healthy older adults (Experiment 1) and patients with chronic stroke (Experiment 2). Previous studies have demonstrated that older adults exhibit significant differences in motor cortical physiology compared to young adults, so Experiment 1 will be performed to determine whether an association between sensorimotor alpha oscillatory phase and corticospinal excitability is present in healthy aging. Additionally, Experiment 2 will be performed to determine if the expected association between sensorimotor alpha oscillatory phase and corticospinal excitability is also present after chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing more effective TMS-based (i.e., closed-loop) interventions. In both experiments, TMS delivery will be timed to specific sensorimotor alpha oscillation phases. We expect the results of this work to provide new insights into how corticospinal excitability is affected by sensorimotor alpha oscillation phase in the aged and post-stroke brain, which could lead to more effective use of sensorimotor alpha oscillation-dependent neuromodulatory TMS protocols in the future. Transcranial magnetic stimulation (TMS) is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been customarily applied uncoupled from brain oscillatory activity (as measured using EEG waveforms), resulting in variability in the biological response to each stimulus, small effect sizes and significant inter-individual variability. Brain oscillatory activity (i.e., EEG waveform oscillatory activity) in the alpha band (8-12 Hz) is linked to cortical inhibition, motor function and cognitive processing, and therefore influences brain function. For example, corticospinal excitability (as measured with TMS) in healthy humans varies depending on the sensorimotor alpha oscillatory phase during which TMS is delivered: corticospinal excitability is higher when TMS is delivered during sensorimotor alpha oscillation troughs (i.e., maximum surface negativity) and lower when TMS is delivered during sensorimotor alpha oscillation peaks (i.e., maximum surface positivity); We recently replicated this result in young healthy adults. We therefore aim to extend these findings to two new populations: healthy older adults (Experiment 1) and patients with chronic stroke (Experiment 2). Previous studies have demonstrated that older adults exhibit significant differences in motor cortical physiology compared to young adults, so Experiment 1 will be performed to determine whether an association between sensorimotor alpha oscillatory phase and corticospinal excitability is present in healthy aging. Additionally, Experiment 2 will be performed to determine if the expected association between sensorimotor alpha oscillatory phase and corticospinal excitability is also present after chronic stroke. Importantly, acquiring information regarding how the aged and damaged brain respond to EEG waveform oscillation-dependent closed-loop TMS will be critical for developing more effective TMS-based (i.e., closed-loop) interventions. In both experiments, TMS delivery will be timed to specific sensorimotor alpha oscillation phases. We expect the results of this work to provide new insights into how corticospinal excitability is affected by sensorimotor alpha oscillation phase, which could lead to more effective use of sensorimotor alpha oscillation-dependent neuro-modulatory TMS protocols in the future. Endpoints: For both experiments, the primary outcome measure is corticospinal excitability. Exploratory outcome measures include MEP amplitude variability, and TMS-induced oscillations. Study Population: Up to 24 older healthy volunteers (ages 50 and older) and up to 28 stroke patients (age 18 and older). Phase: N/A Description of Sites /Facilities Enrolling Participants: This is a single-center study, being performed at the NIH Clinical Center Description of Study Intervention: N/A Study Duration: 6 years Participant Duration: Up to 1 year

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