- Brain activity changes with changes in body temperature. Brain activity can be studied with
a procedure called transcranial magnetic stimulation (TMS). Researchers want to cool the
brain through the scalp using a cooling cap. They want to see if cooling changes the brain
and body s response to TMS.
- To look at the effects of cooling on the brain.
- Right-handed adults age 18-50 who can abstain from caffeine and tobacco.
- Participants will be screened with medical history and physical exam. They will be asked
about alcohol use, smoking, and substance abuse. They may take a pregnancy test. They
may have a magnetic resonance imaging (MRI) scan of the brain. For MRI, participants lie
on a table that slides in and out of a metal tube that takes pictures.
- Participants will have 3 outpatient visits. The following procedures will occur at each
- Participants will wear a cooling cap for up to 45 minutes. Cool water will flow through
the cap. It will feel like an ice pack in a towel. Their core temperature will be
monitored. Their temperature will also be measured under their tongue and on scalp,
stomach, forearm, and calf.
- Participants will have TMS before and after wearing the cap. A brief electrical current
will pass through a wire coil held on their scalp. Electrodes that detect muscle
movement will be placed on their hand. They will also have repetitive TMS, which uses
repeated magnetic pulses. Their wrist will also receive a shock.
The dysregulation of synaptic transmission in certain brain areas may be responsible for
some neurological disorders. It was demonstrated that synaptic transmission may be
modulated through repetitive transcranial magnetic stimulation (rTMS), and this may be a
component of the therapeutic effects of rTMS. However, rTMS utility is limited due to an
inability to focus the stimulation. Cooling was shown to reduce the neuronal activity in
targeted brain areas. The goal of this protocol is to examine the ability of cooling to
2. Study population
We intend to study 18 adult healthy volunteers on an outpatient basis. The accrual
ceiling requested is 23 subjects to allow for dropouts and screening failures.
We intend to perform a sub-study to develop a new method of plasticity induction
phase-triggered paired associative stimulation. This sub-study requires an additional
intended study population of 10 subjects who may be a sub-set of the initially requested
18 subjects from the main study. The additional accrual ceiling is 12 subjects to allow
for dropouts and screening
failures. The total ceiling for the entire protocol is 35.
We propose using rapid-rate paired associative stimulation (rPAS), modulated by applying
cooling to the scalp, to examine the effect of cooling on rTMS. Our hypothesis is that
cooling the brain will prevent the potentiation normally induced by rPAS. We will reduce
brain temperature by up to 1.5 degrees Celsius by applying a cooling helmet to the scalp
and then test the effect on potentiation by applying rPAS. One of our stopping criterion
will be reduction in measured temperature reduction by 2 degrees Celsius.
This study consists of one experiment with18 subjects. The experiment is divided into
three session visits, each to be carried out at least 1 day apart.
The control potentiation in response to rPAS without cooling will be measured during
session visit 1 by using the TMS-evoked motor evoked potential (MEP). In session visit
2, after applying a commercially available liquid cooling helmet for 45 minutes to
reduce the temperature of the underlying cerebral cortex by up to 1.5 degrees Celsius,
we will then assess the response to rPAS. In session 3, the MEP will be measured after
applying the cooling helmet but with the rPAS procedure substituted with a sham rPAS.
Session visit 3 is necessary to determine if there are any changes to the MEP in
response to cooling alone. Thus, in the three session visits, we will evaluate cooling
alone, rPAS alone, and the two together.
The proposed sub-study is to develop a method to improve the reliability of the primary
endpoint. The new method will utilize EEG phase-triggered paired associative
stimulation. Similarly to the rapid-rate paired associative stimulation (rPAS) used in
the main study, EEG phase-triggered paired associative stimulation also uses paired
median nerve stimulation with TMS to motor cortex. However, the stimuli are triggered
when the EEG is at a prespecified phase of the alpha-band (8-12 Hz) oscillation. The
sub-study to develop the optimal parameters of phase-triggered paired associative
stimulation will consist of 3 arms. Two active arms will trigger the paired median nerve
and motor cortex TMS according to the phase of the ongoing EEG. The first arm will
trigger the stimuli at the trough of the ongoing EEG (phase -90 if the EEG is modeled as
a sine wave). The second arm will trigger the stimul at the peak of the ongoing EEG
(phase +90). The third control arm will trigger the paired stimuli at a random delay
from the through of the ongoing EEG. This control arm serves to deliver paired stimuli
at a rate matched to the ongoing EEG, but stimulates at a random phase of each alpha
oscillation cycle. Our hypothesis is that stimulating at the through of the ongoing EEG
will result in increased plastic changes to the brain as measured through our TMS
outcome measures of single pulse MEPs, as compared to the control condition of random
phase stimulation. We also hypothesize that stimulating at the peak of the ongoing EEG
will result in a decrease in TMS outcome measures as compared to the control arm. This
will be a withinsubject design of 3 visits for each of the 10 sub-study subjects.
4. Outcome measures
The primary outcome measure will be the amplitude of MEPs induced by single TMS pulses
- INCLUSION CRITERIA:
To be eligible for this research study participants must:
- Be between 18 and 50 years of age.
- Be right-handed.
- Able to abstain from food or drinks containing caffeine 24 hours before the last 3
session visits. The screening visit does not require the ability to abstain from food
or drinks containing caffeine.
- Able to abstain from tobacco on the day of the last three session visits. The
screening visit doesn t require the ability to abstain from tobacco.
Participants will be excluded from this research study if they:
- Are taking medications of the following classes: antidepressants, anxiolytics,
anticonvulsants, antipsychotics, antiparkinson, hypnotics, stimulants, and
- Have a heart rate that exceeds 100 bpm (resting tachycardia).
- Have a history of psychiatric condition(s).
- Have a neurologic disorder such as a history of brain tumor, stroke, central nervous
system infection, epilepsy, cerebrovascular disease, dementia, head trauma, or
increased intracranial pressure.
- Have surgically or traumatically implanted metallic foreign bodies such as,
pacemakers, medication pumps, implanted hearing aids, defibrillators, metal plates in
the skull or metal implants in the skull or eyes (other than dental fillings),
intracardiac lines, or any other condition/device that might be physically hazardous
during TMS or magnetic resonance imaging (MRI), or might distort the images.
- Are unable to lie flat on back for up to 1 hour.
- Have claustrophobia or a feeling of discomfort from being in small, enclosed spaces of
enough severity to prevent MRI scanning.
- Are pregnant or have a positive pregnancy test before the research procedure due to
-the risks associated with MRI scans.
- Have abnormal findings in clinical MRI that we will do during the screening visit.
- Have any abnormal or focal finding on the neurological exam.<TAB>
- Have a known hearing loss.
- Have an alcohol or substance abuse problem, as determined by the Alcohol, Smoking and
Substance Abuse Screening Test (ASSIST).
- Have sensitivity to coldness.(main experiment only, not an exclusion for the sub-study
which does not utilize cooling)