Neural network modelling reveals changes in directional connectivity between cortical and hypothalamic regions with increased BMI

• Published in: International Journal of Obesity Vol. 45; no. 11; pp. 2447 - 2454
• Main Authors: Voigt, Katharina, Razi, Adeel, Harding, Ian H., Andrews, Zane B., Verdejo-Garcia, Antonio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2021; Nature Publishing Group
• Subjects: 59/36; 631/378/1488/393; 692/499; Adult; Appetite; Body Mass Index; Body weight; Brain mapping; Cortex (insular); Depletion; Development and progression; Epidemiology; Excitation; Female; Functional magnetic resonance imaging; Health aspects; Health Promotion and Disease Prevention; Humans; Hunger; Hypothalamus; Hypothalamus (anterior); Hypothalamus - abnormalities; Hypothalamus - physiopathology; Information flow; Internal Medicine; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - statistics & numerical data; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Metabolic Diseases; Modelling; Neostriatum; Nerve Net - abnormalities; Nerve Net - physiopathology; Neural circuitry; Neural networks; Obesity; Overweight; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - abnormalities; Prefrontal Cortex - physiopathology; Public Health; Satiety; Australia
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/s41366-021-00918-y

Background/Objectives Obesity has been ascribed to corticostriatal regions taking control over homeostatic areas. To test this assumption, we applied an effective connectivity approach to reveal the direction of information flow between brain regions and the valence of connections (excitatory versus inhibitory) as a function of increased BMI and homeostatic state. Subjects/Methods Forty-one participants (21 overweight/obese) underwent two resting-state fMRI scans: after overnight fasting (hunger) and following a standardised meal (satiety). We used spectral dynamic causal modelling to unravel hunger and increased BMI-related changes in directed connectivity between cortical, insular, striatal and hypothalamic regions. Results During hunger, as compared to satiety, we found increased excitation of the ventromedial prefrontal cortex over the ventral striatum and hypothalamus, suggesting enhanced top-down modulation compensating energy depletion. Increased BMI was associated with increased excitation of the anterior insula over the hypothalamus across the hunger and satiety conditions. The interaction of hunger and increased BMI yielded decreased intra-cortical excitation from the dorso-lateral to the ventromedial prefrontal cortex. Conclusions Our findings suggest that excess weight and obesity is associated with persistent top-down excitation of the hypothalamus, regardless of homeostatic state, and hunger-related reductions of dorso-lateral to ventromedial prefrontal inputs. These findings are compatible with eating without hunger and reduced self-regulation views of obesity.