MULTI-ITEM BUFFET: NAC ELECTROPHYSIOLOGY DURING IN-LAB LOC EATING. In this assessment, we investigated each subject’s LOC by modeling the at-risk environment in a controlled setting20. Using mood provocation (see appendix), we assessed LOC (1–5 Likert severity scale) during presentation of a high calorie buffet of the subject’s preferred foods while recording synchronized video-NAc LFP (Local Field Potential) activity. Analogous to our pre-clinical work, we analyzed and compared bite onset during the buffet to standard meals. Results showed low-frequency power increases immediately prior to LOC eating. Specifically, increases in left ventral NAc low-frequency (2–8 Hz) power were observed for both subjects during LOC immediately preceding (within 2 seconds) the videoed bite onset (see appendix) (mean ± s.e. dB power [V2/Hz]: Subject 1, 2.4 ± 1.5, n = 16 bites; Subject 2, 5.6 ± 3.1, n = 12 bites). In contrast, increases in low-frequency power were not observed immediately prior to bites during standard meals (Subject 1, 0.6 ± 1.0, n = 15 bites; Subject 2, 0.3 ± 0.9, n = 11 bites) (Fig. 1C, Student’s t-test, p < 0.05). There were no statistical changes in any of the other recorded frequency bands in either subject (Student’s t-test, p > 0.05).
AMBULATORY ASSESSMENT: NAC ELECTROPHYSIOLOGY DURING REAL-WORLD LOC EATING EVENTS. We analyzed electrophysiology acquired during real-world behavioral states (see appendix) to validate the lab findings. Low-frequency power increases during LOC eating were corroborated with real-world assessments. Specifically, significantly higher low-frequency oscillatory power (Fig. 2A) in bilateral ventral NAc was found during subject-reported LOC eating events (craving-red trace, mean ± s.e. power [V2/Hz]: Subject 1, left NAc: 0.21 ± 0.11, right NAc: 0.16 ± 0.06, n = 10 events; Subject 2, left NAc: 0.58 ± 0.14, right NAc: 0.21 ± 0.07, n = 71 events) when compared to control periods (control-black trace, Subject 1, left NAc: 0.1 ± 0.04, right NAc: 0.04 ± 0.01, n = 9 events; Subject 2, left NAc: 0.19 ± 0.04, right NAc: 0.09 ± 0.04, n = 80 events) and periods of hunger (hunger-blue trace, Subject 1, left NAc: 0.06 ± 0.01, right NAc: 0.03 ± 0.01, n = 13 events; Subject 2, left NAc: 0.27 ± 0.11, right NAc: 0.11 ± 0.03, n = 37 events) (Fig. 2A, one-way ANOVA, Subject 1, left NAc: f = 3.50, P = 0.04, right NAc: f = 4.95, P = 0.03; Subject 2, left NAc: f = 5.14, P = 0.02, right NAc: f = 0.07, P = 0.93). Consistent with the in-clinic tasks, there were no differences in any other frequency band during at-risk moments in the ambulatory setting.
SIGNAL DETECTION: BILATERAL NAC DETECTION. For each subject, we programmed the device to detect brief increases in low-frequency activity in both the left and right ventral NAc. To confirm that the signal being detected was in the low-frequency range, we analyzed the power spectra of the NAc LFP activity in the 5 seconds prior to a detection and found that the Area detectors (see appendix) were detecting low-frequency activity in the left and right ventral NAc (Fig. 2B). For this analysis, we compared detection made in stored LFPs during reported LOC eating events and awake events. For Subject 1, increased low-frequency power compared to baseline NAc LFP signal (average 2-minute window ) was identified in 74.4% (67/90) of reported LOC eating event detections and 63.2% (84/133) of the awake detections (X2(1,N = 223) = 24.54,p < 0.05). For Subject 2, increased low-frequency power was identified in 76.9% (30/39) reported LOC eating event detections and 45.8% (22/48) awake detections (X2(1,N = 87) = 14.82,p < 0.05).
CHANGE in LOC EATING and Weight. Both subjects reported an increased sense of self-regulation and control over food intake specific to cravings and related eating behavior. Further, both subjects showed a decrease in the reported frequency of LOC eating events from baseline to 6-months post-stimulation (i.e. the primary endpoint), as assessed by the Eating Disorder Examination (EDE), and LOC severity, as assessed by the Eating Loss of Control Scale, across the 28-day period during the baseline month compared to 6-months post-stimulation month (LOC Frequency: Subject 1 = 80% decrease; Subject 2 = 87% decrease; LOC episode severity: Subject 1: 9-point improvement (p = 0.09); Subject 2: 15-point improvement (p = 0.05)) (Fig. 3A,B). Notably, by the end of the 6-month follow-up period, Subject 1 exhibited substantial improvement in BED severity, while Subject 2 no longer met criteria for BED (i.e., fewer than average of 4 binge eating events per-month over the prior consecutive 3 months for no more BE diagnosis), which met our primary endpoint (Fig. 3C). Corroborating their subjective reports (Fig. 3), 6-month outcomes showed a decrease in body weight (kg and % reduction) and BMI for both subjects: Subject 1 = -5.9 kg, -4.5%, and − 2.2 kg/m2, respectively; Subject 2 = -8.2 kg, -5.8%, and − 2.9 kg/m2, respectively)(Fig. 3D,E).