Hypothalamic nuclei activity and connectivity changes following a glucose challenge: a single subject fMRI study

Kurzfassung

Introduction: Hypothalamic neural circuits, which adjust efferent autonomic activity in the face of altered nutrient supply, have been implicated in the pathogenesis of obesity, obesity-associated hypertension, and type 2 diabetes mellitus. Recent advances in functional magnetic resonance imaging (fMRI) permit to capture hypothalamic activity changes in groups of subjects. Because the approach obscures interindividual variability in hypothalamic regulation, we studied individual hypothalamic activity and functional connectivity in a single subject during multiple glucose challenges in the MRI scanner. Methods: We conducted ten oral glucose tolerance tests at different days in the same healthy man (56 years, 64 kg, 1.77 m). We acquired functional images using a 3 T scanner before, and 10 and 45 min after glucose ingestion. Moreover, we measured plasma glucose and insulin levels at seven time points in three of the tests. Activity and functional connectivity changes were calculated using independent component analysis followed by a dual regression using an F-test and post-hoc two-sample t-tests. All analyses were corrected for multiple comparisons. Results: Plasma glucose (147.5 ± 8.4 mg/dl) peaked 30 min after glucose intake followed by an insulin maximum 15 min thereafter (45.7 ± 7.0 mU/l). We observed significant activity increases 45 min after glucose intake in the arcuate, paraventricular, and dorsomedial nuclei, as well as in the posterior hypothalamic area, infundibulum, and mamillary bodies. Moreover, the mamillary bodies increased their functional connectivity to the ventromedial, dorsomedial, and periventricular nuclei. Conclusion: Our results, which are consistent with previous animal experiments, show that fMRI can capture individual activity and connectivity changes in specific hypothalamic nuclei during a glucose challenge. Individual hypothalamic fMRI holds promise in delineating disease mechanisms in single patients