Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study

Abstract

BACKGROUND Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study. OBJECTIVE To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity. METHODS This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed. EXPECTED OUTCOMES Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation. DISCUSSION This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.

Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies

“…As DBS has proven successful in well-selected patients for the treatment of movement disorders, such as PD and essential tremor, its indications are expanding to include intractable or severe neuropsychiatric conditions such as post-traumatic stress disorder (PTSD; Larkin et al, 2020 ), OCD ( Goodman et al, 2020 ), and impulsive behavior ( Wu et al, 2020 ). As DBS expands into neuropsychiatry, several questions and opportunities for development arise.…”

Can responsive deep brain stimulation be a cost‐effective treatment for severe obesity?

“…We chose to conduct analyses with a comparator group of LRYGB, as it associated with a larger BMI reduction than gastric sleeve procedures (and, therefore, is performed on patients with more severe obesity), and LRYGB was previously shown to be cost‐effective compared with laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding (46). Candidates for invasive neuromodulation for obesity may be patients who did not receive sufficient weight loss benefit from previous gastric bypass (21,41) and, therefore, may be considering revisional bariatric procedures. Past work has supported that revisional bariatric surgery is less safe than primary procedures, and, specifically, revisional LRYGB is associated with longer operative time and length of hospital stay compared with primary LRYGB (47).…”

Responsive nucleus accumbens deep brain stimulation restores eating control in severe obesity

“…Stimulation was delivered at 125 Hz in two 5 second bursts with a charge density of 0.5-1.5 𝜇C/cm. 17 Detections and stimulations occurred approximately 400 times/day with a stimulation limit set to 700 bouts (or approximately 117 min) per day in order to limit unnecessary stimulation at night. Based on the recording phase, each subject's device was programmed to detect brief increases in low-frequency activity in both the left and right ventral NAc (see appendix).…”

“…Finally, we implemented rDBS triggered by NAc electrophysiology identi ed in behavioral and naturalistic assessments, and report here initial results on the potential e cacy of this novel intervention. This study was performed under a U.S. Food and Drug Administration Investigational Device Exemption (G180079) using the NeuroPace Responsive Neurostimulation (RNS) System 17 .…”