Investigating Habenula Functional Connectivity and Reward-Related Activity in Obesity using Human Connectome Project Data

INTRODUCTION: The habenula, a brain region involved in aversion, might negatively modulate caloric intake. Functional Magnetic Resonance Imaging (fMRI) studies reported associations between weight loss and habenula functional connectivity. However, whether habenula resting state functional connectivity (rsFC) and reward-related activity is altered in obesity is yet unknown.

METHODS: Using data from the Human Connectome Project, we included 300 subjects with various BMIs and a healthy long-term blood glucose (HbA1c). Additionally, we investigated a potential BMI x HbA1c interaction in a separate cohort including subjects with prediabetes (n = 72). Habenula rsFC was assessed using a region of interest (ROI)-to-ROI analysis. Furthermore, a separate analysis using gambling task fMRI data focussed on reward-related habenular activity.

RESULTS: We did not find an association between BMI and habenular rsFC for any of the ROIs. For the exploratory analysis of the BMI x HbA1c effect, a significant interaction effect was found for the habenula-ventral tegmental area (VTA) connection, but this did not survive multiple comparisons correction. Monetary punishment compared to reward activated the bilateral habenula in the BMI sample, but this activity was not associated with BMI.

DISCUSSION: In conclusion, we did not find evidence for an association between BMI and habenula rsFC or reward-related activity. However, there might be an interaction between BMI and HbA1c for the habenula-VTA rsFC, suggestive of a role of habenula in glucose regulation. Future studies should focus on metabolic parameters in their experimental design, to confirm our findings and explore the precise role of the habenula in metabolism.