Executive task-based brain function in children with type 1 diabetes: An observational study

• Published in: PLoS medicine 2019-12, Vol.16 (12), p.e1002979-e1002979
• Main Authors: Foland-Ross, Lara C, Buckingam, Bruce, Mauras, Nelly, Arbelaez, Ana Maria, Tamborlane, William V, Tsalikian, Eva, Cato, Allison, Tong, Gabby, Englert, Kimberly, Mazaika, Paul K, Reiss, Allan L
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Behavioral sciences; Biology and Life Sciences; Blood glucose; Blood Glucose - metabolism; Brain; Brain - physiopathology; Brain mapping; Brain research; Child; Children; Clinical trials; Cognition & reasoning; Cognitive ability; Deactivation; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes therapy; Disabilities; Endocrinology; Epidemiology; Executive function; Executive Function - physiology; Family medical history; Female; Functional magnetic resonance imaging; Future predictions; Glucose; Go/no-go discrimination learning; Humans; Interdisciplinary aspects; Magnetic Resonance Imaging - methods; Male; Medical research; Medicine and Health Sciences; Metabolism; Neuroimaging; Neuropsychological Tests; Observational studies; Physical Sciences; Psychiatry; Research and Analysis Methods; Scanning; Social Sciences; Studies; Supervision; Type 1 diabetes
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1002979

Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood. Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of "no-go > go" were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct "go" trials; r = -0.36, 95% CI -0.53 to -0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < -0.29, 95% CIs -0.47 to -0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = -0.22, 95% CI -0.41 to -0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI -0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown. These data indicate that increased recruitment of executive control areas i