Abstract

Loss of control (LOC) eating is pervasive in eating disorders and obesity. The presence of this phenotype appears to predict treatment-resistance, including to gastric bypass surgery. Cravings that precede LOC over food consumption present an opportunity for intervention in patients with the binge eating disorder (BED). Responsive deep brain stimulation (DBS) guided by low frequency changes in the nucleus accumbens was previously found to block binge-like eating behavior in mice. Following this preclinical work, in a first-in-human pilot study, we recorded nucleus accumbens electrophysiology during food cravings preceding LOC eating in two patients with BED and severe obesity (trial registration no. NCT03868670). We observed increased bilateral ventral NAc low frequency power and connectivity that appeared selective for states of food craving. We then used the peaks in nucleus accumbens electrophysiological signal that corresponded to increased low-frequency power to guide DBS delivery. Over 6 months, we observed improved self-control of food intake and weight loss in both patients. These findings provide early support for restoring inhibitory control with electrophysiologically-guided NAc DBS in the context of LOC. Further work with increased sample sizes is required to determine the scalability of this approach. Research Category and Technology and Methods: Translational Research: 1. Deep Brain Stimulation (DBS)

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