Neurotypical Adults
Conditions
Brief summary
Transcranial magnetic stimulation (TMS) interventions could feasibly strengthen residual corticospinal tract (CST) connections and enhance recovery of paretic hand function after stroke. To maximize the therapeutic effects of such interventions, they must be delivered during poststroke brain activity patterns during which TMS best activates the residual corticospinal tract and enhances neural transmission within it (i.e., brain state-dependent TMS). In this study, the investigators will test the feasibility of real-time, personalized brain state-dependent TMS in neurotypical adults. Participants will visit the laboratory for one day of testing. Upon arrival, participants will provide their informed consent; afterwards, they will complete eligibility screening. The investigators will then place recording electrodes on the scalp using a swim-type cap and on the left first dorsal interosseous, abductor pollicis brevis, and extensor digitorum communis muscles. After determining the location at which TMS best elicits muscle twitches in the left first dorsal interosseous, the investigators will determine the lowest possible intensity at which TMS elicits muscle twitches at least half of the time in this muscle. Then, the investigators will deliver 6 blocks of 100 single TMS pulses while the participant rests quietly with their eyes open; stimulation will be delivered at an intensity that is 20% greater than the lowest possible intensity at which TMS elicits muscle twitches at least half of the time. Afterwards, the investigators will use the muscle and brain activity recordings acquired during these 6 blocks to build a personalized mathematical model that identifies which patterns of brain activity correspond to the largest TMS-evoked muscle twitches. The investigators will then use this model to detect the occurrence of these brain activity patterns in real-time; when these patterns are detected, single TMS pulses will be delivered. Afterwards, all recording electrodes will be removed, participation will be complete, and participants will leave the laboratory. The investigators will recruit a total of 16 neurotypical adults for this study.
Interventions
Single-pulse TMS will be applied to the right hemisphere during brain activity patterns associated with strong and weak corticospinal tract activation. Single-pulse TMS will also be applied to the right hemisphere during random brain activity patterns.
Sponsors
Emory University
University of Texas at Austin
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants will receive single-pulse TMS during personalized brain activity patterns reflecting either strong or weak corticospinal tract activation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Right-hand dominance * Willingness to participate * Ability to provide informed consent
Exclusion criteria
* History of major neurological, orthopedic, psychiatric, or cardiovascular disease * Presence of contraindications to transcranial magnetic stimulation (TMS) or peripheral nerve stimulation (PNS), including: * history of adverse reactions to TMS or PNS * history of stroke or head injury * metal in head, eyes, neck, chest/trunk, or arms, including but not limited to shrapnel, * surgical clips, fragments from metalworking, fragments from welding * implanted devices * history of frequent and severe headaches or migraines * immediate family history of seizure or epilepsy * personal history of seizure or epilepsy * current, suspected, or planned pregnancy * current or recent (within the last 3 months) use of medications acting on the central nervous system, including but not limited to: antipsychotic drugs, antidepressants, benzodiazepines, prescription stimulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor-evoked Potential (MEP) Amplitudes | single session | Peak-to-peak MEP amplitudes elicited by single transcranial magnetic stimulation (TMS) pulses delivered during personalized strong and weak CST states will be measured from the left first dorsal interosseous muscle. At the individual participant level, all MEP amplitudes will be normalized to the mean MEP amplitude observed in that participant. Mean normalized MEP amplitudes will be compared across CST states. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| State-targeting Accuracy | single session | An offline version of the real-time EEG analysis algorithm will be used to determine the brain state (i.e., strong or weak CST states, or neither) immediately preceding delivery of each single TMS pulse. The proportion of trials during which the online and offline versions of the real-time EEG analysis algorithm produce the same brain state prediction will be calculated per participant and used as a state-targeting accuracy metric. State-targeting accuracy metrics will be compared to the theoretical chance level (0.5). |
Countries
United States
Participant flow
Pre-assignment details
There were no specific pre-assignment procedures or events for this study.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Adults Healthy adults received single-pulse TMS the right motor cortex during personalized brain states reflecting strong corticospinal tract (CST) activation (strong CST states), weak CST states, and random CST states. Stimulation was delivered at 120% of resting motor threshold and motor-evoked potentials (MEPs) were recorded from the left first dorsal interosseous muscle. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Healthy Adults |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 20.8 years STANDARD_DEVIATION 3.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Motor-evoked Potential (MEP) Amplitudes
Peak-to-peak MEP amplitudes elicited by single transcranial magnetic stimulation (TMS) pulses delivered during personalized strong and weak CST states will be measured from the left first dorsal interosseous muscle. At the individual participant level, all MEP amplitudes will be normalized to the mean MEP amplitude observed in that participant. Mean normalized MEP amplitudes will be compared across CST states.
Time frame: single session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Strong CST States | Motor-evoked Potential (MEP) Amplitudes | 1.13 arbitrary units (normalized microvolts) | Standard Error 0.05 |
| Weak CST States | Motor-evoked Potential (MEP) Amplitudes | 0.96 arbitrary units (normalized microvolts) | Standard Error 0.04 |
| Random CST States | Motor-evoked Potential (MEP) Amplitudes | 0.90 arbitrary units (normalized microvolts) | Standard Error 0.05 |
Secondary
State-targeting Accuracy
An offline version of the real-time EEG analysis algorithm will be used to determine the brain state (i.e., strong or weak CST states, or neither) immediately preceding delivery of each single TMS pulse. The proportion of trials during which the online and offline versions of the real-time EEG analysis algorithm produce the same brain state prediction will be calculated per participant and used as a state-targeting accuracy metric. State-targeting accuracy metrics will be compared to the theoretical chance level (0.5).
Time frame: single session
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Strong CST States | State-targeting Accuracy | 94.5 percentage of trials accurately targeted | Standard Error 1.1 |
| Weak CST States | State-targeting Accuracy | 89.5 percentage of trials accurately targeted | Standard Error 2.7 |
| Random CST States | State-targeting Accuracy | NA percentage of trials accurately targeted | — |