Cerebral Cortical Influences on Autonomic Function

The overall goal of this study is to determine the impact of non-invasive brain stimulation
on autonomic function in human subjects without functional gastrointestinal disorders and in
subjects with Irritable Bowel Syndrome (IBS) or Functional Dyspepsia (FD).

Aim 1: Determine whether repetitive transcranial magnetic stimulation (rTMS) of specific
cortical areas alters physiologic measures of gastrointestinal and cardiac function.

The investigators will use rTMS to transiently induce changes in neural excitability within
specific cortical regions identified as being linked to autonomic regulation. Based on
preliminary neuroanatomical data, one of the leading candidate cortical areas associated with
sympathetic regulation lies within the trunk representation of the primary motor cortex.
Thus, the investigators first plan on targeting this region of the primary motor cortex with
rTMS and assess the effect of various parameters of rTMS on gastrointestinal and cardiac
function in healthy human subjects. The investigators will then perform additional
experiments using rTMS targeted to other specific cortical sites, such as the dorsal premotor
area and rostral cingulate cortex that have also been linked to autonomic control. Each of
these identified cortical regions may make unique contributions to autonomic reactivity.

Aim 2: Determine whether the effects of targeted rTMS on autonomic function are mediated
through a specific branch of the autonomic nervous system.

In different sessions, the investigators will use FDA-approved pharmacological agents
(hyoscyamine and metoprolol) to help determine whether the observed autonomic effects of
cortical TMS are mediated primarily through the sympathetic or parasympathetic branches of
the autonomic nervous system.

Aim 3: Determine whether patients with functional gastrointestinal disorders demonstrate
altered physiological reactivity to targeted rTMS.

The investigators will use the optimal parameters of rTMS and regions of interest determined
in Aim 1 to assess the gastrointestinal and cardiac reactivity in participants with
functional dyspepsia (FD) and/or irritable bowel syndrome (IBS). These physiological
responses will be correlated with assessments of disease severity, mood, and quality of life.
In different sessions, the investigators will use FDA-approved pharmacological agents
(hyoscyamine and metoprolol) to help determine whether any observed differences in
physiological reactivity to targeted rTMS are primarily mediated through sympathetic or
parasympathetic control.

Inclusion Criteria:

- Adults between age 18 and 75

- Participants without a history of gastrointestinal disorders (control group)

- Participants with functional dyspepsia (FD group)

- Participants with moderate-to-severe irritable bowel syndrome (defined by IBS symptom
severity scores (IBS-SSS) greater than 250) (IBS group)

Exclusion Criteria:

- history of myocardial infarction, supplemental oxygen requirement, or diabetes

- history of chronic gastrointestinal symptoms (for healthy control population only)

- history of gastric surgery

- psychosis or altered cognitive status

- history of head injury, metal in the skull, stroke, or a history of seizures

- implantable devices, such as a pacemaker or nerve stimulator

- current use of the following medications or use of substances which are known to lower
the seizure threshold: amitriptyline (Elavil), nortriptyline (Pamelor), imipramine
(Tofranil), doxepin (Sinequan), clozapine (Clozaril), chlorpromazine (Thorazine),
amphetamines or methamphetamine, Ecstasy, Ketamine, Angel Dust/phencyclidine (PCP),
cocaine, or 3 or more alcoholic drinks per day

- pregnancy