Autonomic Reactivity and Personalized Neurostimulation

Disorders of gut-brain interaction (DGBI) affect up to 25% of U.S. children. Patients often suffer from disabling, multisystem comorbidities that suggest a common root (sleep disturbances, fatigue, anxiety, etc). Yet, DGBI are defined and treated based on GI symptom origin (cyclic vomiting, dyspepsia, irritable bowel) rather than underlying pathophysiology. Many patients manifest comorbidities suggesting an underlying autonomic nervous system (ANS) dysregulation (palpitations, dizziness, cognitive dysfunction). Unfortunately, due to common features of anxiety and visceral hyperreactivity and lack of obvious pathology, children with DGBI are frequently diagnosed with psychosomatic or 'benign, functional disorders' and treated with empiric antidepressants despite lack of scientific support and risks of serious side effects. Little is known about the underlying brain-gut mechanisms linking these comorbidities. A lack of targeted treatment options naturally follows the paucity of mechanistic data. A dysregulated ANS response circuit via brainstem nuclei is linked to visceral hypersensitivity. As the team's prior research has shown, ANS regulation can be non-invasively measured via several validated indices of cardiac vagal tone. Using the novel vagal efficiency (VE) metric, the investigators have demonstrated inefficient vagal regulation in cyclic vomiting syndrome and pain-related DGBI and that low VE predicts response to non-invasive, auricular percutaneous electrical nerve field stimulation (PENFS) therapy. PENFS targets brainstem vagal afferent pathways and, along with brain-gut interventions such as hypnotherapy, are the only therapies currently proven effective for pediatric DGBI. Individualizing neurostimulation based on sensory thresholds while assessing dynamic ANS reactivity offers a path towards personalized medicine using the most effective therapies to date. This proposal will test the feasibility of an ANS tracking software in assessing real-time, autonomic regulation and providing individualized neurostimulation in children with nausea/vomiting and ANS imbalance.

The investigators hypothesize that children with cyclic vomiting syndrome (CVS) and chronic nausea/vomiting with concurrent symptoms of autonomic nervous system (ANS) dysregulation have reduced vagal efficiency (VE) that can be captured by the ANS Tracker software and modulated via adjustable percutaneous electrical nerve field stimulation (PENFS). Our overall goals are to: 1) expand knowledge on mechanisms of disorders of gut brain interaction involving VE and gastric function, 2) test a software that allows point of care VE assessment, 3) personalize PENFS parameters with real-time assessments of VE and gastric function, 4) combine and assess efficacy of two proven, effective therapies for DGBI that both modulate CNS.

The specific aims of this study are as follows:

Aim 1: Test the feasibility of real-time autonomic nervous system (ANS) tracking in children with nausea/vomiting and ANS dysregulation The investigators will test feasibility of assessing real-time ANS regulation by the VE metric using a novel ANS tracker software in response to posture shifts during PENFS with 1) standard and 2) personalized stimulation parameters based on sensory thresholds in female children with nausea/vomiting.

Aim 2: Compare efficacy and ANS changes with personalized PENFS +/- adjunctive hypnotherapy The investigators will assess outcomes of 6 weeks of personalized PENFS based on sensory threshold (Aim 1) vs. personalized PENFS with adjunctive hypnotherapy via weekly assessments of VE and symptom response. Baseline VE measurements will be correlated with outcomes to assess ability to predict treatment response.

Aim 3: Investigate dynamic gastric function in response to personalized PENFS The investigators will test real-time gastric function pre and post therapy (Aim 2 interventions) by advanced MRI in a subset of female patients vs. healthy controls.

Eligibility Criteria:
Inclusion Criteria:

* 11 to 18 years of age
* English speaking
* meeting Rome IV diagnostic criteria for cyclic vomiting syndrome or functional dyspepsia and willingness to participate and consent/assent to the study
* All subjects will have a constellation of chronic symptoms indicative of autonomic dysfunction for minimum 3 months: postural dizziness/lightheadedness, syncope, palpitations, fatigue, sleep disturbance, thermoregulatory abnormalities and cognitive impairment with upright position +/- abnormal autonomic testing if performed per standard of care as per American Autonomic Society consensus criteria.

Exclusion Criteria:

* Presence of organic disease that may explain symptoms
* Requirement for parenteral nutrition
* Developmental delays precluding accurate symptom report
* Severe dermatological condition or active infection of external or middle ear
* Implanted electrical device
* Severe mental health disorder not controlled by therapy (schizophrenia, bipolar disease, severe depression, post-traumatic distress disorder) and/or psychotic features which could influence symptom report or ANS measurements and result in adverse reactions to hypnosis therapy