Accumbens connectivity during deep-brain stimulation differentiates loss of control from physiologic behavioral states

Abstract

Background: Loss of control (LOC) eating, the subjective sense that one cannot control what or how much one eats, characterizes binge-eating behaviors pervasive in obesity and related eating disorders. Closed-loop deep-brain stimulation (DBS) for binge eating should predict LOC and trigger an appropriately timed intervention. Objective/hypothesis: This study aimed to identify a sensitive and specific biomarker to detect LOC onset for DBS. We hypothesized that changes in phase-locking value (PLV) predict the onset of LOC-associated cravings and distinguish them from potential confounding states. Methods: Using DBS data recorded from the nucleus accumbens (NAc) of two patients with binge eating disorder (BED) and severe obesity, we compared PLV between inter- and intra-hemispheric NAc subregions for three behavioral conditions: craving (associated with LOC eating), hunger (not associated with LOC), and sleep. Results: In both patients, PLV in the high gamma frequency band was significantly higher for craving compared to sleep and significantly higher for hunger compared to craving. Maximum likelihood classifiers achieved accuracies above 88% when differentiating between the three conditions. Conclusions: High-frequency inter- and intra-hemispheric PLV in the NAc is a promising biomarker for closed-loop DBS that differentiates LOC-associated cravings from physiologic states such as hunger and sleep. Future trials should assess PLV as a LOC biomarker across a larger cohort and a wider patient population transdiagnostically.

Keywords

• Nucleus accumbens
• Loss of control
• Obesity
• Binge-eating
• Deep brain stimulation
• Phase-locking value