Alterations in Decision-Making Neurocircuits during Hypoglycemia in Patients with T1DM

Prior work by our group and others have shown that, in response to hypoglycemia, individuals with T1DM have altered regional brain activity and resting state functional connectivity (FC) in reward and decision-making regions such as the orbitofrontal cortex (OFC) and insula. Recently, fMRI studies have found that performing trait-relevant tasks while measuring FC can provide a more accurate representation of cognitive function. Thus, we tested whether individuals with T1DM have different patterns of “task-amplified” FC in response to hypoglycemia compared to non-diabetic control subjects. Twenty-five individuals (17 T1DM, 7F/10M, age 36±3 years, BMI 26±1 kg/m2, HbA1c 7.2±0.2%, duration of DM 19±2 years and 8 healthy controls (HC) , 5F/3M, age 31±2 years, BMI 25±1 kg/m2, HbA1c 5.3±0.1%) underwent BOLD fMRI scanning for FC at rest and during the performance of a Card-Guessing Task to assess reward-based decision making. During scanning, glucose levels were controlled using a 2-step hyperinsulinemic euglycemic (90 mg/dl) -hypoglycemic (60 mg/dl) clamp. Seed-based analysis using a predefined region of interest in the OFC was performed. During resting state, there were no significant Group (HC, T1DM) X Session (euglycemia, hypoglycemia) interactions. In contrast, during the Card Guess task, there was a significant Group X Session interaction (P<0.001) in the dorsal anterior cingulate cortex (dACC) . Specifically, during the task, hypoglycemia elicited connectivity changes between the OFC and the dACC in healthy control subjects but not T1DM subjects. These findings suggest that task-amplified FC may be a more sensitive method to assess neurological differences in T1DM patients that are not apparent at rest. Moreover, because the OFC and dACC have direct neuronal connections and encode a variety of decision-making processes, these data highlight the need for better understanding of not only neurocognitive changes in patients with T1DM but also the factors contributing to these changes. Disclosure J.Deajon-jackson: None. E.Sanchez rangel: None. C.Lacadie: None. A.S.Greene: None. R.Belfort-deaguiar: Research Support; Fractyl Health, Inc. T.Constable: None. D.L.Rothman: None. J.J.Hwang: None. Funding National Institute of Health (DK020495)