Vagal Nerve Stimulation for Interoception Modulation

We aim to assess and modulate gastric interoception in healthy adults using gastric and brain MRI, different meal volumes (Experiment 1), and transcutaneous auricular vagus nerve stimulation (taVNS) (Experiment 2). MR examinations will precede and immediately follow ingestion of a test meal (containing pineapple, with high manganese content, as a contrast agent), using real-time 3D cine MRI. Subjects will be scanned before ingestion and at 15, 45, and 75 minutes post-meal, in order to extract objective indices of gastric function. Functional MRI (fMRI) brain scans will be alternated to gastric MRI scans. Each subject will undergo 2 separate MRI visits, ingesting different doses of contrast meal in order to peripherally modulate gastric afference (Experiment 1), or receiving sham and active taVNS (Experiment 2), so to modulate visceral afference at the central level.Outcomes will assess the taVNS response of brainstem vagal neurocircuitry, as well as the impact of taVNS on fMRI connectivity patterns (fcMRI) of gastric afference, and link them to MRI-derived gastric outcomes, such as gastric emptying rate, gastric accommodation (fundic volumes), and gastric motility (peristaltic wave propagation).

• taVNS (Device): Active taVNS delivered to the external ear at a moderate, non-painful level.
• Sham taVNS (Device): Sham taVNS delivered to the external ear using zero-current.

Primary outcomes

• Neuroimaging [Visits 1,2,3 (2 hours)]: NTS connectivity
• Gastric Function [Visits 1,2,3 (2 hours)]: MRI-derived measures of gastric accommodation

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Male and female patients aged 18 and 65 years old (inclusive)
* Comprehension of instructions
* Avoidance of alcohol, nicotine, and caffeine for 25 hours prior to study session Exclusion Criteria:
* BMI (Body Mass Index) more than 32 and/or weight > 235 lbs. (limits of the MRI table)
* Any other significant medical disease (systemic or CNS), psychiatric disorder, or chronic pain condition/s
* Epilepsy or a prior history of seizures
* Psychotropic medications or other medications that effect neurovascular coupling (i.e. fMRI)
* Subjects taking illicit drugs or opioids
* Allergy to pineapple (used in the test meal during MRI)
* Contraindications for MRI: High magnetic fields may pose a serious health hazard to subjects with implanted ferromagnetic objects. Every subject in this study will be carefully screened before entering the high magnetic field shielded room to collect a precise outline of the subject's medical history. Subjects with the following characteristics/disease will not be eligible to participate in the study: -History of Head Trauma -Any metallic implants (e.g. braces or permanent retainers) -Tattoos with metallic ink above the nipple line -Surgical Aneurysm Clips -Cardiac Pacemaker -Prosthetic Heart Valve -Neurostimulator -Implanted pumps -Cochlear Implants -Metal rods, Plates -Screws -Recent Previous Surgery -IUD -Hearing Aid -Dentures (which might create NMR artifacts) -Metal Injury to eyes -Pregnancy or plans to become pregnant -Breast Feeding -Meniere's Disease -Transdermal (skin) patches such as NicoDerm (nicotine for tobacco dependence), Transderm Scop, or Ortho Evra (birth control) -Non-normally cycling females -Claustrophobia

• Roberta Sclocco, PhD, Principal investigator, Spaulding Rehabilitation Hospital

NIH grants: K01AT012208