Brain Function Differences in Children With Type 1 Diabetes: A Functional MRI Study of Working Memory

Abstract

Glucose is a primary fuel source to the brain, yet the influence of dysglycemia on neurodevelopment in children with type 1 diabetes remains unclear. We examined brain activation using functional MRI in 80 children with type 1 diabetes (mean ± SD age 11.5 ± 1.8 years; 46% female) and 47 children without diabetes (control group) (age 11.8 ± 1.5 years; 51% female) as they performed a visuospatial working memory (N-back) task. Results indicated that in both groups, activation scaled positively with increasing working memory load across many areas, including the frontoparietal cortex, caudate, and cerebellum. Between groups, children with diabetes exhibited reduced performance on the N-back task relative to children in the control group, as well as greater modulation of activation (i.e., showed greater increase in activation with higher working memory load). Post hoc analyses indicated that greater modulation was associated in the diabetes group with better working memory function and with an earlier age of diagnosis. These findings suggest that increased modulation may occur as a compensatory mechanism, helping in part to preserve working memory ability, and further, that children with an earlier onset require additional compensation. Future studies that test whether these patterns change as a function of improved glycemic control are warranted.

Figure 1

Visuospatial working memory (N-back) task. Participants were required to monitor a series of stimuli and to respond using a button press whenever a circle was presented in the center of the screen (0-back) or in the same position as the one or two previous screens (1-back and 2-back, respectively). Red arrows indicate timing of correct button press.

Figure 2

A: Regions showing significant modulation of activation by working memory load in children with type 1 diabetes (T1D) (top) and children in the control group (middle) and areas showing a significant increase in modulation in activation among children with type 1 diabetes relative to control subjects (bottom). Values indicate slice numbers. B: Mean parameter estimates for each working memory load condition, averaged across significant voxels in between-group analyses. Voxel-wise significance maps are thresholded at Z > 3.1, with a cluster significance threshold of P = 0.01, corrected for multiple comparisons. Images are presented according to neurological convention (left = left).

Figure 3

Scatter plots showing associations between modulation strength (adjusted for age, sex, and site) and illness and behavioral and glycemic measures in children with diabetes. Values on the y-axis represent the parameter estimate for the modulated regressor adjusted for age, sex, and scan site, centered around the estimate mean. Higher modulation values indicate greater linear increases in activation with higher working memory load. For BRIEF, higher scores indicate worse parent-reported working memory. For WJ-III (WJ3), higher scores indicate better inductive reasoning.