This is an exploratory neurophysiological study that will determine the impact of non-invasive brain stimulation on autonomic regulation, with a focus on gastrointestinal function. These studies should provide a basis for future brain-based neurotherapeutic strategies in patients with functional GI disorders.

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 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.

--This study description has been revised since its original posting. Because all study procedures are performed in all subjects, regardless of being a healthy subject or one with FD and/or IBS, rather than a three arm trial, this trial should be regarded as having a single arm study design.

Inclusion Criteria:

• Adults between age 21 and 60
• Participants without gastrointestinal symptoms (Healthy Subjects)
• Participants with gastrointestinal symptoms compatible with functional dyspepsia (FD) and or irritable bowel syndrome (IBS)

Exclusion Criteria:

• history of myocardial infarction, supplemental oxygen requirement, or diabetes
• history of chronic gastrointestinal symptoms (for healthy subjects 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
• Body-Mass-Index (BMI) > 35

There is no current plan to share with specific individuals, but individual participant data and supporting information (below) that are the basis for the published results will be made available after de-identification.

Beginning 3 months after article publication and up to 5 years thereafter.

Proposals to access trial data should be directed to the Principal Investigator (Dr. David Levinthal) at levinthald@upmc.edu, and if the researcher has a sound basis for the proposal, then requestors will be asked to sign a data access agreement (link to be determined).