| Summary: | Central insulin resistance (IR) influences striatal dopamine (DA) tone, an important determinant of behavioral self-regulation. We hypothesized that an association exists between the degree of peripheral IR and impulse control, mediated by the impact of IR on brain circuits controlling the speed of executing "go" and/or "stop" responses. We measured brain activation and associated performance on a stop signal task (SST) in obese adults with type 2 diabetes (age, 48.1 ± 6.9 yrs (mean ± SD); BMI, 36.5 ± 4.0 kg/m2; HOMA-IR, 7.2 ± 4.1; 12 male, 18 female). Increasing IR, but not BMI, was a predictor of shorter critical stop signal delay (cSSD), a measure of the time window during which a go response can be successfully countermanded (R2 = 0.12). This decline was explained by an IR-associated increase in go speed (R2 = 0.13) with little impact of IR or BMI on stop speed. Greater striatal fMRI activation contrast in stop error (SE) compared with stop success (SS) trials (CONSE>SS) was a significant predictor of faster go speeds (R2 = 0.33, p = 0.002), and was itself predicted by greater IR (CONSE>SS vs HOMA-IR: R2 = 0.10, p = 0.04). Furthermore, this impact of IR on striatal activation was a significant mediator of the faster go speeds and greater impulsivity observed with greater IR. These findings suggest a neural mechanism by which IR may increase impulsivity and degrade behavioral self-regulation.
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