Central effects of acute intranasal insulin on neuroimaging, cognitive, and behavioural outcomes: A systematic review

The distribution of insulin receptors throughout the brain implicates insulin in physiological functions and disease states, including cognition, appetite, mood, and metabolic disorders. Intranasally administered insulin offers a non-invasive approach for isolating and investigating brain insulin action. This systematic review synthesized the effects of acute intranasal insulin on neuroimaging, cognitive, and behavioural outcomes reported in 48 studies in adults. Age, sex, body mass index, and insulin resistance were found to moderate brain insulin action. Neuroimaging studies showed insulin affects brain activity, cerebral blood flow, and functional connectivity in regions like the hypothalamus, amygdala, and insula. Insulin also modified cognitive function, eating behaviour, and the stress response. Nonetheless, inconsistencies in study designs, dosages, and outcome measures necessitate standardized methodologies to better understand central insulin action. Taken together, insulin’s ability to modify stress and fear, appetite and eating behaviour, and cognitive function in both healthy and diseased individuals highlight its potential in the therapeutic and mechanistic exploration of highly prevalent psychiatric, metabolic, and cognitive conditions like mood disorders, obesity, and Alzheimer’s disease. [Display omitted] •Acute intranasal insulin affects brain activity, functional connectivity, and cerebral blood flow in key regions like the hypothalamus, amygdala, insula, and the striatum.•While cognition is likely impacted by intranasal insulin, the effects are difficult to synthesize due to heterogeneous outcome measures and intervention dosages.•Acute intranasal insulin modifies stress and fear response, eating behaviour, food preferences, and palatability in a sex-dependent manner.