SUN-684 - Increased Interoceptive Drive and Reduced Cognitive–Attentional Engagement in Patients Carrying BBS-VUS: A Functional MRI Study

Background
Functional MRI (fMRI) captures BOLD (blood-oxygen-level–dependent) signal changes as a marker for neural activity. In obesity research, it is used to study how the brain responds to food and reward. Functional MRI studies demonstrate that obesity is associated with increased activation of reward-related regions (striatum, orbitofrontal cortex) and reduced prefrontal inhibitory control.
Methods
We evaluated 4 patients with morbid obesity carrying BBS-associated VUS variants (1 male, BMI 36.6 ± 3.95 kg/m2, 26.2 ± 5.67 yrs.) and 8 lean controls (4 males, 22.32 ± 2.96 kg/m2, 22.5 ± 5.11yrs.). Participants were scanned on a 3T Siemens Prisma MRI scanner equipped with a 64-channel head coil. During fMRI, participants viewed a continuous ~12-minute sequence of four movie excerpts (~3 minutes each), separated by ~20-second fixation periods. Two clips depicted social interactions (The Social Network, The Internship), and two depicted food-related content (Ratatouille, The Reservation). Stimuli were presented passively via E-Prime without explicit task demands.
Results
Food-related vs. social-related movie clips.
BBS showed greater activation than controls in the left posterior insula (interoception) for food-related vs. social-related movie clips, 99 voxels; Z = 3.53; p = 0.041.
Food-related clips relative to baseline
Controls showed greater activation than BBS participants for food-related clips relative to baseline in the right medial temporal lobe, including the hippocampus and parahippocampal gyrus, extending into the lingual gyrus, 225 voxels; Z = 3.80; p = 3.46×10⁻⁵
Social clips relative to baseline
Controls exhibited greater activation than BBS participants for social clips relative to baseline in the bilateral superior parietal lobule (SPL) and precentral gyrus (PCG), 327 voxels; Z = 3.85; p = 1.37×10⁻⁶.

Discussion
BBS participants showed increased activation of the insula in response to food vs. social stimuli, suggesting heightened interoceptive processing and visceral processing of food-related cues and a stronger internal drive in response to food cues.
In contrast, controls demonstrated greater activation in the medial temporal lobe during food stimuli, indicating stronger memory and contextual processing of food.
For social stimuli, controls showed greater activation in parietal and motor regions, consistent with better attention and engagement in social processing.
These results suggest that individuals with BBS show greater interoceptive response to food and reduced cognitive and attentional processing for both food and social stimuli. Given the small sample size (n = 12), findings are preliminary.
Conclusion
Unlike simple obesity, which is more reward-driven, BBS may involve increased interoceptive drive and reduced cognitive engagement, indicating a distinct mechanism of hyperphagia.

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