Influence of Brain Oscillation-Dependent TMS on Motor Function

Study Description:

We will study if corticospinal excitability, intracortical inhibition and intracortical facilitation vary across different sensorimotor alpha and beta electroencephalography (EEG) waveform oscillation phases in healthy adults and chronic stroke patients. In young healthy adults, sensorimotor cortical neuronal spiking is highest at sensorimotor alpha oscillation troughs and lowest at sensorimotor alpha oscillation peaks. Short interval cortical inhibition (SICI) is unaffected by alpha phase, consistent with alpha phase representing a form of transient, pulsed excitation, unaffected by gamma-aminobutyric acid (GABA)-mediated inhibition. In contrast to sensorimotor alpha, motor evoked potential (MEP) amplitudes are not maximal at the trough phase of the sensorimotor beta rhythm.

Objectives:

TMS is a potential adjunct therapy for post-stroke neurorehabilitation. So far, it has been customarily applied uncoupled from brain oscillatory activity, resulting in variability in the biological response to each stimulus, small effect sizes and significant inter-individual variability. Alpha band oscillatory activity is linked to cortical excitation and inhibition, motor function and cognitive processing. It is possible that TMS effects could be more consistent when applied to specific phases or phase angles of ongoing brain oscillatory activity. For example, corticospinal excitability (as measured with TMS) in healthy humans varies depending on the sensorimotor alpha and beta oscillatory phase during which TMS is delivered. There is no information available on intracortical facilitation and inhibition as a function of beta phase angle in healthy humans. In Experiments 1 and 3 we have been assessing alpha phase-dependent corticospinal excitability measures. In Experiment 2, we will assess beta and secondarily alpha phase-dependent intracortical inhibitory and facilitatory circuits in young and older adults.

Endpoints:

For experiments 1 and 3, the primary outcome measure is corticospinal excitability. For Experiment 2, the primary outcome is SICI. Exploratory outcome measures may include MEP amplitude variability, SICI, short intracortical facilitation (SICF) and intracortical facilitation (ICF) and TMS-induced oscillations.

• INCLUSION CRITERIA:
• Healthy younger adults:

• Ages 18 years to less than 50 years. (18 to 49)
• Willingness/ability to provide informed consent.
• Ability to induce a motor evoked potential in the muscle target of the upper extremity, as evaluated during the TMS Screening.
• Healthy older adults:

• Age 50 and over
• Willingness/ability to provide informed consent.
• Ability to induce a motor evoked potential in the muscle target of the upper extremity, as evaluated during the TMS Screening.
• Stroke patients:

• Age 18 and over.
• Unilateral or bilateral upper limb paresis with the ability to voluntarily contract a finger, hand, wrist, or elbow muscle in the affected arm(s).
• Stroke onset > 6 months prior to participation.
• Intact M1 sufficient to induce motor evoked potentials in the affected upper extremity following ipsilesional TMS, as evaluated during the TMS Screening.
• Willingness/ability to provide informed consent.

• If the investigator feels the individual s capacity to provide informed consent is questionable, the NIH Human Subjects Protection Unit (HSPU) will be requested to determine the individual s ability to consent.

Exclusion criteria

• Healthy younger and older adults:

• Presence of severe neurological or medical disorder (e.g., Parkinson s disease or multiple sclerosis).
• History of seizures.
• Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), tri-cyclic or other anti-depressants, benzodiazepines, or prescription stimulants.
• TMS contraindications, such as:

• Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside the eye or skull.
• Diagnosed severe hearing loss.
• Current pregnancy.
• Staff from our section.
• Stroke patients:

• Presence of severe neurological or medical disorder, other than stroke (e.g., Parkinson s disease or multiple sclerosis).
• History of brainstem stroke.
• History of seizures.
• Chronic use of antipsychotic drugs (e.g., chlorpromazine or clozapine), benzodiazepines, or prescription stimulants.
• TMS contraindications, such as:

• Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects inside

the eye or skull.

---Diagnosed severe hearing loss.

• Current pregnancy.
• Staff from our section.