Study reveals that the default mode network in children with Type 1 diabetes does not switch off when focusing on a task

A study led by Stanford scientists at Stanford University School of Medicine has shown that children with Type 1 diabetes show slight but important differences in brain function compared with those who don’t suffer from the disease.

The study, in PLOS Medicine, is the first of its kind to evaluate what occurs in the brains of children with diabetes during a cognitive task.

Abnormal brain activity

The researchers used functional magnetic resonance imaging scans when the children’s brains were at work to measure brain function. Compared to children without the disease, the children with diabetes displayed a set of abnormal brain-activity patterns that have been seen in many other disorders, including a cognitive decline in ageing, concussion, attention-deficit hyperactivity disorder and multiple sclerosis.

The study also reported that abnormal brain-activity patterns were more pronounced in children who had lived with diabetes for longer.

Lara Foland-Ross, PhD, senior research associate at the Centre for Interdisciplinary Brain Sciences Research at Stanford said: “Our findings suggest that, in children with Type 1 diabetes, the brain isn’t being as efficient as it could.”

Foland-Ross shares lead authorship of the paper with Bruce Buckingham, MD, professor emeritus of paediatrics at Stanford.

Allan Reiss, MD, study’s senior author and professor of psychiatry and behavioural sciences at Stanford said: “The takeaway from our study is that, despite a lot of attention from endocrinologists to this group of patients, and real improvements in clinical guidelines, children with diabetes are still at risk of having learning and behavioural issues that are likely associated with their disease.”

Blood sugar affects brain development

Type 1 diabetes occurs when the pancreas fails to make insulin, a hormone that helps regulate blood sugar. To combat this, patients are given insulin via injections or an insulin pump. But even with treatment, their blood levels of glucose – the main sugar in blood – fluctuate much more than in healthy individuals.

Foland-Ross explains: “Kids with diabetes have chronic swings in blood glucose levels, and glucose is important for brain development.”

Brain cells need a steady supply of glucose for fuel. Earlier work revealed brain-structure changes and mild performance impairment on cognitive tasks in children with Type 1 diabetes, but the mechanism had never been studied.

Study methodology

93 children with type 1 diabetes had fMRI brain scans conducted. The children were assessed across five sites: Nemours Children’s Health System in Jacksonville, Florida; Stanford; Washington University in St Louis; the University of Iowa; and Yale.

An additional 57 children who did not have the disease composed the control group. All participants were between 7 and 14 years old. Standard behavioural and cognitive tests were given to all the children before brain scanning.

Whilst in the fMRI scanner, the children performed a cognitive task called “go/no-go” where different letters of the alphabet were shown in random order, and participants were asked to press a button in response to every letter except “X.” The task is often used in brain-scanning studies to evaluate what is happening in the brain while participants are concentrating.

The results showed that the children with diabetes performed the task as accurately as those in the control group, but their brains were behaving differently.

In children with diabetes, the default-mode network, which is the brain’s “idle” system, was not shutting off during the task. To compensate for the abnormal activation of the default-mode network, the brain’s executive control networks, responsible for aspects of self-regulation and concentration, were working harder than normal in the children with diabetes.

These abnormalities were more pronounced in children who had been diagnosed with diabetes at younger ages, suggesting that the problem may worsen with time.

Foland-Ross said: “The longer the exposure you have to dynamic changes in blood glucose levels, the greater the alterations in brain function with respect to the default-mode network.”

Studies in adults with diabetes suggest that in the later stages of the disease, the brain eventually loses its ability to compensate for this problem.

What’s next?

Scientists want to study whether achieving better blood glucose concentrations through treatment with a closed-loop artificial pancreas benefits children’s brain function. These devices electronically couple a blood glucose sensor to an insulin pump that automatically adjusts insulin delivery.

Reiss said: “We hope that with improvements in devices for diabetes treatment, these findings will either decrease in severity or go away. With better blood sugar control, children’s brains might be able to recover normal activity.

“Young brains have the most potential for plasticity and repair, but children also have a long time to live with the consequences, if problems with brain function persist.”

The paper’s other Stanford co-authors are Gabby Tong, an affiliate at the Center for Interdisciplinary Brain Sciences Research at Stanford, and Paul Mazaika, PhD, associate director of computational neuroimaging at the centre. Researchers at all study sites also contributed to the work.

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New findings out of the University of Tübingen show that, on top of its benefits for metabolism, mood, and general health, exercise also improves brain function. In recent studies, researchers learned that obese and overweight individuals are prone to insulin resistance in the brain, where it provides information about current nutritional status, as well as the rest of the body. So researchers wanted to know whether exercise can improve insulin sensitivity in the brain and improve cognition in overweight individuals.

In the current study, led by Dr. Stephanie Kullmann, 22 sedentary adults with overweight or obesity (an average BMI of 31) underwent two brain scans before and after an 8-week exercise intervention, including cycling and walking. Brain function was measured before and after using an insulin nasal spray to investigate insulin sensitivity of the brain. Participants were also assessed for cognition, mood, and peripheral metabolism.

Even though the exercise intervention only resulted in a marginal weight loss, brain functions important for metabolism “normalized” only after 8-weeks. Exercise increased regional blood flow in areas of the brain important for motor control and reward processes, both of which depend on the neurotransmitter dopamine. Dopamine is an important neurotransmitter for learning new motor skills and in reward-related learning and this research shows that exercise significantly improves dopamine-related brain function. One area in particular, the striatum, had enhanced sensitivity to insulin after the 8-weeks of exercise such that the brain response of a person with obesity after exercise training resembled the response of a person with normal-weight. Interestingly, the greater the improvement in brain function, the more belly fat a person lost during the course of the exercise intervention. Behaviorally, participants reported an improvement in mood and task switching, which is an indicator for improved executive function.

“The bottom line is that exercise improves brain function”, said Kullmann. “And increasing insulin sensitivity in dopamine-related brain regions through exercise may help decrease the risk of a person to develop type 2 diabetes, along with the benefits for mood and cognition”.

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