It is now generally accepted that diabetes increases the risk for cognitive impairment, but the precise mechanisms are poorly understood. A critical problem in linking diabetes to cognitive impairment is that patients often have multiple comorbidities (e.g., obesity, hypertension) that have been independently linked to cognitive deficits. In the study reported here we focused on young adults with and without type 1 diabetes who were virtually free of such comorbidities. The two groups were matched on major health and demographic factors, and all participants completed a verbal working memory task during magnetoencephalographic brain imaging. We hypothesized that patients would have altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures. Accordingly, we found that patients had significantly stronger neural responses in the superior parietal cortices during memory encoding and significantly weaker activity in parietal-occipital regions during maintenance compared with control subjects. Moreover, disease duration and glycemic control were both significantly correlated with neural responses in various brain regions. In conclusion, young healthy adults with type 1 diabetes already have aberrant neural processing relative to their peers without diabetes, using compensatory responses to perform the task, and glucose management and duration may play a central role.

Type 1 diabetes has been associated with alterations in attentional processing and other cognitive functions, and previous studies have found alterations in both brain structure and function in affected patients. However, these previous neuroimaging studies have generally examined older patients, particularly those with major comorbidities known to affect functioning independent of diabetes. The primary aim of the current study was to examine the neural dynamics of selective attention processing in a young group of patients with type 1 diabetes who were otherwise healthy (i.e., without major comorbidities). Our hypothesis was that these patients would exhibit significant aberrations in attention circuitry relative to closely matched controls. The final sample included 69 participants age 19–35 years old, 35 with type 1 diabetes and 34 matched nondiabetic controls, who completed an Eriksen flanker task while undergoing magnetoencephalography. Significant group differences in flanker interference activity were found across a network of brain regions, including the anterior cingulate, inferior parietal cortices, paracentral lobule, and the left precentral gyrus. In addition, neural activity in the anterior cingulate and the paracentral lobule was correlated with disease duration in patients with type 1 diabetes. These findings suggest that alterations in the neural circuitry underlying selective attention emerge early in the disease process and are specifically related to type 1 diabetes and not common comorbidities. These findings highlight the need for longitudinal studies in large cohorts to clarify the clinical implications of type 1 diabetes on cognition and the brain.

Type 1 diabetes (T1D) has been linked to alterations in both brain structure and function. However, the neural basis of the most commonly reported neuropsychological deficit in T1D, psychomotor speed, remains severely understudied. To begin to address this, the current study focuses on the neural dynamics underlying motor control using magnetoencephalographic (MEG) imaging. Briefly, 40 young adults with T1D who were clear of common comorbidities (e.g., vascular disease, retinopathy, etc.) and a demographically-matched group of 40 controls without T1D completed an arrow-based flanker movement task during MEG. The resulting signals were examined in the time-frequency domain and imaged using a beamforming approach, and then voxel time series were extracted from peak responses to evaluate the dynamics. The resulting time series were statistically examined for group and conditional effects using a rigorous permutation testing approach. Our primary hypothesis was that participants with T1D would have altered beta and gamma oscillatory dynamics within the primary motor cortex during movement, and that these alterations would reflect compensatory processing to maintain adequate performance. Our results indicated that the group with T1D had a significantly stronger post-movement beta rebound (PMBR) contralateral to movement compared to controls, and a smaller neural flanker effect (i.e., difference in neural activity between conditions). In addition, a significant group-by-condition interaction was observed in the ipsilateral beta event-related desynchronization (bERD) and the ipsilateral PMBR. We also examined the relationship between oscillatory motor response amplitude and reaction time, finding a differential effect of the driving oscillatory responses on behavioral performance by group. Overall, our findings suggest compensatory activity in the motor cortices is detectable early in the disease in a relatively healthy sample of adults with T1D. Future studies are needed to examine how these subtle effects on neural activity in young, otherwise healthy patients affect outcomes in aging.

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Type 1 diabetes affects the structure and function of the brain, with psychomotor speed as the most commonly reported deficit. The current study sought to uncover the dynamics underlying motor processing in the brain of adults with type 1 diabetes using an arrow-based Flanker task. Adults (ages 19-35, N = 39) with type 1 diabetes and no major complications and a matched control group (N = 40) underwent magnetoencephalography (MEG) while performing the task. During the task, participants were presented with a row of five arrows facing right or left, and participants were instructed to respond by button press to the direction of the middle arrow. Analyses focused on the time period around movement execution to examine motor-related dynamics. Time series analyses were performed on the peak beta and gamma responses from the motor cortices. An ANOVA model and follow-up regression analyses were used to delineate the predictive value of each neural response in driving behavioral outcomes. Subsequent t-tests between frequent (3+ episodes per week) and infrequent (0-1 episodes per week) hypoglycemic groups were performed to examine response differences within the adults with type 1 diabetes. Responses driving behavior differed between adults with and without type 1 diabetes. In adults with type 1 diabetes, beta frequency responses were significant predictors of reaction time, where greater ipsilateral recruitment led to faster reaction times (b = .58, t = 3.64, p = .001). In contrast, gamma drove behavioral outcomes in the control group (b = -.43, t = -2.96, p = .005). Further, within group analyses revealed that more frequent episodes of hypoglycemia were associated with alterations specific to beta responses during the pre-movement baseline period (p < .05). These results show frequency specific alterations in motor dynamics in adults with type 1 diabetes, with an added effect of increased hypoglycemia. These findings strongly indicate that diabetes directly impacts motor control components in the brain, regulating behavioral outcomes. Disclosure C.M. Embury: None. V.A. Were: None. G.H. Lord: None. A. Drincic: Board Member; Self; Corcept Therapeutics. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi US. T.W. Wilson: None. Funding National Institutes of Health (R01MH103220, R01MH116782)