Optimizing and Exploring TMS-EEG Techniques

Objective:

The goal of this thematic protocol is to optimize and develop the use of TMS-EEG as a method
for measuring cortical connectivity and TMS-evoked EEG potentials. This protocol will also be
used to train new members of our laboratory and pilot future hypothesis-driven studies. This
protocol includes thematic permission to use non-invasive techniques regarded as having
minimal risk in healthy individuals, such as, MRI, EEG, EMG, low-frequency stimulation (less
than or equal to 1 Hz), electrical stimulation of the skin to mimic the somatosensory
artifact of TMS, and behavioral tests.

Study Population:

We plan to recruit up to 500 healthy volunteers, aged 18 and over.

Design:

Exploratory sub-studies under this protocol will answer questions about how to optimize TMS-
EEG and TMS-fMRI to obtain imaging or physiological outcomes. These studies will generally
vary one parameter at a time in a systematic way and will use various statistical measures,
such as effect size, to compare results obtained under different conditions.

Outcome Measures:

- MRI/fMRI measures of anatomical and functional connectivity and activation

- EEG measures of the response to TMS, connectivity between areas, and background activity

- EMG measures of evoked muscle activity

- Psychophysical and behavioral measures of brain system function

- INCLUSION CRITERIA:

- Age 18 and older

- Able to provide consent

For some sub-studies, we may limit participation by handedness or eye dominance.

EXCLUSION CRITERIA:

- Any current major neurological or psychiatric disorder, such as, (but not limited to)
stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression

- Findings on neurological examination indicative of significant brain disease

- Individuals with significant and symptomatic health concerns, such as cardiovascular
disease, malignancy, or connective tissue disorder

- History of seizure, defined as a diagnosis by a health care provider of one or more
epileptic seizures or an anecdotal history which, in the opinion of the PI, is
suggestive of epileptic seizure. Any individual who answers other than negatively to
the question, Have you ever had an epileptic seizure on screening will be questioned
directly by the PI

- Current oral use of a medication that lowers the seizure threshold such as
neuroleptics, beta lactams, isoniazid, metronidazole, tricyclic or other
antidepressants, or prescription stimulants

- Individuals regularly taking medications that cause significant psychomotor activation
or depression, e.g., stimulants and CNS depressant drugs such as benzodiazepines, will
be excluded.

- For MRI studies: Any metal in the body which would make having an MRI scan unsafe,
such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses,
artificial heart valves, cochlear implants or shrapnel fragments, any individual who
was a welder or metal worker. Participants will also be excluded if they are
uncomfortable in small closed spaces (i.e. claustrophobia) or are not able to lie
comfortably on their back for up to two hours

- Pregnancy or plans to become pregnant in the next two months

- Members of the Behavioral Neurology Unit, NINDS

- Use of illegal drugs in the past year

- Consumption of more than 7 alcoholic drinks a week for females or 14 alcoholic drinks
a week for males.

There is no general exclusion for NIH employees. Inclusion/exclusion criteria will be
checked before enrollment in each sub-study to ensure that participants remain eligible.