Surgery-induced reduction in inflammation relates to improved neural inhibitory control in obesity

Obesity is associated with impaired inhibitory control and low-grade systemic inflammation. Systemic inflammation adversely affects neurocognitive performance. Here, we investigate the effects of metabolic bariatric surgery on systemic inflammation and its influence on neural mechanisms underlying inhibitory control. In a sample of 47 individuals with severe obesity, we assessed inhibitory control processing pre- and 2 years post-bariatric surgery by probing neural activation and connectivity during an fMRI Stroop task. We investigated whether surgery-induced changes in plasma markers of systemic inflammation were related to changes in altered neural responses. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. Longitudinal analyses revealed decreased Stroop-related activation in the caudate nucleus and the left insula following surgery. These activation changes were accompanied by inflammation-related changes in functional coupling with medial superior frontal regions. Specifically, greater post-surgery decreases in leptin (pro-inflammatory) were associated with decreased connectivity between the anterior insula and the medial superior frontal regions, while increases in macrophage migration inhibitory factor (MIF, potentially neuroprotective) were linked to enhanced connectivity between the caudate nucleus and the medial superior frontal gyrus. Importantly, improved functional coupling between the caudate nucleus and the medial superior frontal gyrus was predictive of better task performance. Our findings suggest that surgery-induced reductions in systemic inflammation may improve inhibitory control in individuals with obesity by promoting neural changes in inflammation-sensitive brain regions and their functional interactions. This protocol was prospectively registered with the Dutch Trial Register Onderzoekmetmensen.nl, with trial number NTR29050.