Influence of Brain Oscillation-Dependent TMS on Motor Function
| Status: | Recruiting |
|---|---|
| Conditions: | Healthy Studies, Healthy Studies, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/8/2019 |
| Start Date: | September 11, 2018 |
| End Date: | July 3, 2021 |
| Contact: | Margaret K Hayward, C.R.N.P. |
| Email: | mimi.hayward@nih.gov |
| Phone: | (301) 451-1335 |
Background:
When people have a stroke, they often have difficulty moving their arms and hands.
Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke
can move their arms and hands. But the effects of TMS are minor, and it doesn t work for
everyone. Researchers want to study how to time brain stimulation so that the effects are
more consistent.
Objective:
To understand how the brain responds to transcranial magnetic stimulation so that treatments
for people with stroke can be improved.
Eligibility:
Adults ages 18 and older who had a stroke at least 6 months ago
Healthy volunteers ages 60 and older
Design:
Participants will have up to 5 visits.
At visit 1, participants will be screened with medical history and physical exam.
Participants with stroke will also have TMS and surface electromyography (sEMG).
For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants
may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple
movements during TMS.
For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded.
At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table
that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the
loud noise.
At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG,
small electrodes on the scalp will record brainwaves. Participants will sit still, watch a
movie, or do TMS.
Participants may be asked to have 2 extra visits to redo procedures.
When people have a stroke, they often have difficulty moving their arms and hands.
Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke
can move their arms and hands. But the effects of TMS are minor, and it doesn t work for
everyone. Researchers want to study how to time brain stimulation so that the effects are
more consistent.
Objective:
To understand how the brain responds to transcranial magnetic stimulation so that treatments
for people with stroke can be improved.
Eligibility:
Adults ages 18 and older who had a stroke at least 6 months ago
Healthy volunteers ages 60 and older
Design:
Participants will have up to 5 visits.
At visit 1, participants will be screened with medical history and physical exam.
Participants with stroke will also have TMS and surface electromyography (sEMG).
For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants
may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple
movements during TMS.
For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded.
At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table
that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the
loud noise.
At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG,
small electrodes on the scalp will record brainwaves. Participants will sit still, watch a
movie, or do TMS.
Participants may be asked to have 2 extra visits to redo procedures.
OBJECTIVE: 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). 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 neuromodulatory TMS protocols in the future.
STUDY POPULATION: Up to 24 older healthy volunteers (ages 60 and older) and up to 28 stroke
patients (age 18 and older).
DESIGN: Each experiment will begin with MRI to allow for co-registration with a frameless
stereotactic device for the precise targeting of TMS. In Experiment 1, healthy older adults
will receive single-pulse, closed-loop TMS to the motor cortex upper extremity (UE) area
(M1-UE) during sensorimotor alpha oscillation (a) troughs (i.e., maximum surface negativity),
(b) peaks (i.e., maximum surface positivity), and (c) uncoupled from sensorimotor alpha
oscillation phase (as measured with EEG) using a within-subject design. In Experiment 2,
chronic stroke patients will also complete the same procedures described for Experiment 1,
except that TMS will be delivered to the ipsilesional M1-UE. For each experiment, up to 700
single-pulse TMS pulses will be delivered (excluding pulses used to identify scalp hotspot
and resting motor threshold), and all subjects will be given rest breaks as needed.
OUTCOME MEASURES: For both experiments, the primary outcome measure is corticospinal
excitability. The secondary outcome measure is effective intracortical connectivity between
M1 and the rest of the brain. Exploratory outcome measures include MEP amplitude variability,
TMS-induced oscillations, and resting state EEG brain connectivity.
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). 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 neuromodulatory TMS protocols in the future.
STUDY POPULATION: Up to 24 older healthy volunteers (ages 60 and older) and up to 28 stroke
patients (age 18 and older).
DESIGN: Each experiment will begin with MRI to allow for co-registration with a frameless
stereotactic device for the precise targeting of TMS. In Experiment 1, healthy older adults
will receive single-pulse, closed-loop TMS to the motor cortex upper extremity (UE) area
(M1-UE) during sensorimotor alpha oscillation (a) troughs (i.e., maximum surface negativity),
(b) peaks (i.e., maximum surface positivity), and (c) uncoupled from sensorimotor alpha
oscillation phase (as measured with EEG) using a within-subject design. In Experiment 2,
chronic stroke patients will also complete the same procedures described for Experiment 1,
except that TMS will be delivered to the ipsilesional M1-UE. For each experiment, up to 700
single-pulse TMS pulses will be delivered (excluding pulses used to identify scalp hotspot
and resting motor threshold), and all subjects will be given rest breaks as needed.
OUTCOME MEASURES: For both experiments, the primary outcome measure is corticospinal
excitability. The secondary outcome measure is effective intracortical connectivity between
M1 and the rest of the brain. Exploratory outcome measures include MEP amplitude variability,
TMS-induced oscillations, and resting state EEG brain connectivity.
- INCLUSION CRITERIA:
- Healthy older adults:
- Age 60 and over
- Willingness/ability to provide informed consent
Stroke patients:
- Age 18 and over
- Unilateral or bilateral upper limb hemiparesis 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 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
- MRI contraindications, as per NMR Center MRI Safety Screening Questionnaire, such
as metal implants and pregnancy. Pregnancy for women of childbearing potential
will be assessed using pregnancy test within 24 hours preceding MRI procedures.
- TMS contraindications, such as:
- Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects
inside the eye or skull
- Diagnosed severe hearing loss
- 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
- MRI contraindications, as per NMR Center MRI Safety Screening Questionnaire, such
as metal implants and pregnancy. Pregnancy for women of childbearing potential
will be assessed using pregnancy test within 24 hours preceding MRI procedures.
- TMS contraindications, such as:
- Pacemaker, implanted pump, stimulator, cochlear implant, or metal objects
inside the eye or skull
- Diagnosed severe hearing loss
- Staff from our section
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 800-411-1222
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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