Impact of Bariatric Surgery and Liraglutide on Cognitive-Behavioral Markers of Long-Term Weight Loss in Obesity

Experimental and meta-analytic neuroimaging studies have highlighted two primary brain networks whose functioning or structure is altered in patients with obesity: (i) the "cue-reactivity network," involved in sensory, hedonic, and motivational responses to food, and (ii) the "cue-regulation network," more prominently involved in attentional, decision-making, and inhibitory processes. In line with this theoretical framework, weight loss induced by pharmacological treatments or bariatric surgery is associated with a partial recovery of the functioning and structure of these brain networks.

Following a sleeve gastrectomy, obese patients exhibit reduced activity in the reward circuit and increased activity in the inhibitory control circuit in response to high-calorie food images, suggesting a normalization of brain responses to food after bariatric surgery. Moreover, these changes in brain functionality may be accompanied by increased gray matter density in the prefrontal cortex, which persists for up to 12 months following sleeve gastrectomy or Roux-en-Y gastric bypass.

Pharmacologically, the administration of glucagon-like peptide-1 receptor (GLP-1) agonists-such as liraglutide, semaglutide, and exenatide-has proven effective in treating diabetes and promoting weight loss. fMRI studies have shown that intravenous administration of exenatide (vs. placebo) in patients with obesity and type 2 diabetes reduces neurofunctional activity in key nodes of the cue-reactivity network (e.g., amygdala, putamen, insula) in response to high-calorie food images. Furthermore, this effect is nullified if exenatide administration is preceded by GLP-1 receptor blockade.

However, it remains unclear whether such surgical or pharmacological treatments are accompanied by changes in cognitive processes associated with reactivity to edible stimuli or behavioral inhibition, and whether these contribute to an improved post-operative response to satiety.

This research project thus aims to study the effects of bariatric surgery and liraglutide administration (in patients already selected for one of these procedures) on two cognitive-behavioral processes partially supported by distinct brain networks: automatic approach tendencies (underpinned by the cue-reactivity network) and behavioral inhibition (underpinned by the cue-regulation network). Additionally, the investigators aim to study how these processes may be modulated by satiety. The secondary objective of the project involves identifying cognitive-behavioral markers that could predict responses to these treatments.

Inclusion criteria

• Subjects of any ethnicity, aged between 20 and 60 years.
• BMI equal to or greater than 30 kg/m².
• No history of neurological or psychiatric disorders, as confirmed through medical history and neuropsychological screening.
• Signed informed consent and willingness to comply with all study procedures.
• Patients scheduled for surgery, treatment with liraglutide, or a dietary regimen.

Exclusion criteria

• Previous diagnosis of significant neurological conditions (e.g., brain injury or dementia) or major psychiatric disorders.
• Current or past psychopharmacological therapy, if prolonged.
• BMI lower than 30 kg/m².
• Lack of signed informed consent.
• Severe medical conditions, including but not limited to: hypertension, significant cardiac disease, or other disorders that may compromise patient safety.
• Confirmed pregnancy through self-report and/or breastfeeding.