Bariatric surgery induces alterations in effective connectivity between the orbitofrontal cortex and limbic regions in obese patients

Obese subjects show enhanced brain responses in motivation and reward neurocircuitry encompassing sensory and somatic integration-interception, motivation-reward (striatal), emotion, and memory processes, which attenuate frontal region activation during food cues. Bariatric surgery (BS) is the only reliable treatment for morbid obesity. Unfortunately, it is unknown how BS affects neurocircuitry after weight loss. We aimed to examine effects of BS on the basal activity of brain areas involved in reward and motivation processing, emotion, memory, and gut-brain interaction. We combined resting-state fMRI with amplitude of low-frequency fluctuation (ALFF) and Granger causality analysis (GCA) to assess interactions between regions within the frontal-mesolimbic circuitry in 16 obese subjects (OB) and 22 normal-weight (NW) subjects. The OB group was studied at baseline and 1 month post BS. Comparisons between OB and NW, and pre- and post BS showed significant differences in ALFF in areas involved in drive (caudate, orbitofrontal cortex (OFC)), arousal (thalamus), and conditioning/memory (amygdala, hippocampus) ($P<0.05$, FDR correction). GCA revealed that in the OB group, the OFC had greater connectivity to limbic regions (amygdala, hippocampus, and medial thalamus) and the caudate. Post BS, the connectivity of the OFC to limbic regions decreased, whereas the connectivity from the amygdala and hippocampus to the caudate and thalamus was enhanced, particularly in subjects with lower body mass index (BMI). OFC activation in the OB group was associated with BMI prior to surgery, and changes in OFC post surgery were associated with alterations in BMI. Overall, the functional connectivity of the OFC was significantly decreased. As it is important for salience attribution and connected to limbic brain regions involved with emotional reactivity and conditioning after BS, its significant association with BMI changes indicates the contribution of OFC changes to the improved control of eating behavior after surgery.