Brain insulin action increases communication in reward associated brain regions independent of age and peripheral insulin sensitivity in healthy adults

Abstract

Insulin action in the brain effects behavioral and metabolic processes. Specifically, insulin acts on dopamine levels in the striatum, which is part of the brain reward network. We investigated if intranasal insulin administration (INI) acts on the communication of the reward network in healthy adults, and if this is influenced by peripheral insulin sensitivity and age. Methods: Using a randomized within-participant design, 66 healthy adults (35 women, BMI 18–49 kg/m2, age 21–69 years, insulin sensitivity index (ISI)-Matsuda: 3.0-62.5) underwent a resting state MRI measurement before and 30 minutes after INI or placebo spray administration. Connectivity analysis was undertaken using the regions: Ventral tegmental area; Dorsolateral prefrontal cortex (DLPFC); Dorsal, and Ventral Striatum (DS, VS); Hypothalamus, with age, BMI, waist-to-hip ratio, and ISI controlled for as covariates. Partial correlations were used to analyse if age and ISI influence insulin action in the brain. Results: Connectivity analyses showed a time by condition interaction (Pcorrected<0.001), with significan-tly increased connectivity within the reward network after INI (Pcorrected =0.042). Specifically, between DS and VS (T(60)=2.82, Pcorrected=0.02); and between DS and DLPFC (T(60)=2.17, Pcorrected =0.06; P-uncorrected=0.006). No difference in connectivity was observed in the placebo condition. No associations were observed with age and ISI. Conclusion: We could show that intranasal insulin affects communication within the reward network by increasing striatal functional connectivity. These effects were independent of age and peripheral insulin sensitivity. Whether brain insulin responsiveness in the reward network impacts eating behaviour is a matter for further investigation.