Changes in cerebral activity and connectivity induced by transcranial stimulation of the dorsolateral prefrontal cortex in healthy humans

Noninvasive brain stimulation techniques are being explored for the treatment
of various neurologic and psychiatric conditions such as depression,
schizophrenia, Parkinson disease, dystonia, Alzheimer*s disease, and stroke.
The general idea is that by artificially modifying synaptic strength with
stimulation it is possible to induce plasticity and long-lasting changes in
brain response. Two different techniques are now widely used for this endeavor:
repetitive transcranial magnetic stimulation (rTMS) and transcranial direct
current stimulation (tDCS). rTMS has been approved as an efficient treatment to
alleviate symptoms of treatment-resistant depression by the Food and Drug
Administration as well as by the relevant instances in Europe and Canada.
Clinical trials targeting other populations are underway, notably in
schizophrenia, with a study conducted in the North of The Netherlands under the
lead of Prof. Andre Aleman, and targeting the dorsolateral prefrontal cortex
(DLPFC) of patients with schizophrenia with either rTMS or tDCS to try
alleviating apathy. Although clinical trials and treatments are underway, we
still have very limited knowledge of the neural effects of transcranial brain
stimulation as applied in these protocols.

Here we will test the hypothesis that stimulating DLPFC with either rTMS or
tDCS during one single session affects the functional connectivity of the
DLPFC, and is associated with an increase of activation in connected areas of
the cerebrum and basal ganglia. We further want to evaluate differences in
neural activation induced by the two techniques.

Participants in the study will be randomly assigned to one of four groups. Two
groups will receive real brain stimulation (rTMS or tDCS) and two other groups
will receive sham stimulation (sham rTMS or sham tDCS). Before and just after
brain stimulation, participants will undergo an MRI scanning session. During
the MRI sessions their brain activity will be recorded at rest and during task
performance. Prior to the stimulation, participants will also fill in a few
questionnaires and perform cognitive tests. The stimulation protocols used for
tDCS and rTMS in this study are identical to those used in the ongoing clinical
trial (METC 2013-137 * *Randomized controlled trial of neurostimulation
treatment for apathy in schizophrenia*), so that the conclusions of the current
research can be used to inform the results obtained in patients with
schizophrenia after treatment.

Participants in the study will go through 4 steps that will take place across
two different days less than a week apart. During the first step, participants
will undergo a pre-stimulation MRI scanning session. This session will last for
1h. After the MRI, participants will fill out questionnaires and perform
cognitive tests assessing executive functions and fluid intelligence. This
session will last for about 1h. On the second day, participants will undergo
brain stimulation (tDCS, sham tDCS, rTMS, or sham rTMS). The stimulation
session will last for about 30 minutes. Just after the stimulation,
participants will be brought again in the MRI scanner for the post-stimulation
session, which is identical to the pre-stimulation session and lasts for 1h.
The total duration of the study for one participant is 4 hours. The experiment
will not involve more than minimal risks for the participants. MRI is a
standard brain imaging technique with no known negative effects on health. The
only risks are for subjects with cardiac pacemaker and metal implants. These
individuals will not be allowed to participate. In terms of burden, MRI
involves lying still in a confined environment during one hour. In addition,
during data acquisition, the MRI scanner makes a loud noise, and although
participants are provided with earplugs, the residual noise can be a burden for
some individuals.
During the tDCS procedure participants are exposed to a very low electrical
current of 2 mA. The use of tDCS to date has not resulted in significant
adverse effects, apart from mild headache or a mild tingling sensation
underneath the electrodes. During the rTMS procedure participants are exposed
to a magnetic field strength lower than 1.5 Tesla limited to a small brain
region at a maximum depth of 2 cm. The application of rTMS is considered safe
as long as it follows published safety guidelines. However, the risk of
inducing seizure cannot be completely excluded. In consequence, participants
with increased risk of seizure will not be allowed in the study, and safety
procedures are planned in case such an event should occur.
The study is not intended to benefit the participants directly.
Participants will receive a compensation for their contribution.