Resting-state functional connectivity changes and pretreatment features associated with symptom improvement after cognitive behavioral therapy for bulimia nervosa

Bulimia nervosa (BN) is a serious eating disorder, and cognitive behavioral therapy (CBT) is the first-line treatment; however, remission rates remain modest, and the neural correlates of CBT response are unclear. Resting-state functional connectivity (rsFC) may clarify CBT-related brain changes and pretreatment correlates of response, yet longitudinal whole-brain rsFC studies in BN are lacking. Thirty Japanese women with BN (mean age, 33.6 ± 9.9 years) received multi-site CBT (enhanced CBT: n = 24; videoconference CBT: n = 4; guided internet-based CBT: n = 2). Resting-state fMRI and symptom measures, including the Eating Disorder Examination Questionnaire (EDE-Q), were obtained pre- and post-treatment, with an interval of 5.6 ± 1.5 months between assessments. Whole-brain region of interest (ROI)-to-ROI rsFC was computed and harmonized across sites. Multiple regression analyses adjusting for age and pretreatment psychotropic medication examined associations between improvement in EDE-Q global score and (1) rsFC changes and (2) pretreatment rsFC. Significance was assessed using seed-level FDR correction (q < 0.05), applied across all connections from each seed ROI to all target ROIs, and analysis-level FDR correction (q < 0.05), applied across all tested ROI-to-ROI connections. No associations survived analysis-level FDR correction across the ROI-to-ROI feature set. Exploratory seed-level findings indicated that greater improvement in EDE-Q global score was associated with decreased rsFC between the right orbitofrontal cortex and right posterior supramarginal gyrus, increased rsFC between the right anterior temporal fusiform cortex and cerebellar regions, and increased rsFC between the right caudate nucleus and right cerebellar hemisphere IX. Greater improvement was associated with stronger pretreatment rsFCs between the right superior parietal lobule and inferior frontal/temporo-occipital temporal regions, and between the left postcentral gyrus and bilateral temporo-occipital inferior temporal gyri. This exploratory longitudinal analysis suggests that symptom improvement following CBT-based treatment may be associated with ROI-to-ROI rsFC changes in regions implicated in reward processing and higher-order visual or affective processing. Pretreatment connectivity in regions related to somatosensory processing and cognitive control may be relevant to CBT responsiveness. These findings should be interpreted cautiously because they did not survive analysis-level FDR correction and require replication in larger controlled cohorts. Trial registration: UMIN000039841. Registered 18 March 2020. Bulimia nervosa is a serious eating disorder involving binge eating, purging, and intense concerns about body shape. While Cognitive Behavioral Therapy (CBT) is the leading treatment, only about half of patients achieve full recovery. We conducted this study to understand how therapy changes the brain’s "wiring" and why it works better for some people than others. We used brain scans to monitor 30 women before and after they completed therapy. Our results suggested that symptom improvement following CBT-based therapy was associated with changes in communication between brain regions involved in reward valuation and control or visual processing. We also found that some brain connectivity patterns before treatment were associated with later symptom improvement. These patterns were in areas responsible for how we perceive our bodies and how we exercise learning and self-control. Ultimately, this could help develop new treatments that more effectively target these specific brain regions and improve our understanding of why some patients benefit more from therapy than others. However, because this was a small study without a control group and the findings did not survive the most conservative correction for multiple comparisons, these results should be considered preliminary and further validation in larger controlled studies is needed.