Department of Psychiatry

Research Team

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Research Topics:

Parkinson's Disease

Tourette's Syndrome

Spatial Memory Test

One line of our research is related to the effects of Type I Diabetes Mellitus (T1DM) on the brain and cognition.  We are especially interested in the effects of hypoglycemic (low blood sugar) episodes.  Severe hypoglycemic episodes are known to have cognitive consequences in children with T1DM, but the exact nature and extent of the effects and mechanism ("why") are unclear.  During our studies we have worked in close collaboration with Dr. Neil White, professor of Pediatrics and Medicine and Director of the Division of Endocrinology and Metabolism.

Previous Studies

In one study, we found that declarative memory (memory for information), but not other kinds of memory, was significantly worse in the T1DM group with a history of severe hypoglycemic episodes particularly on delayed recall trials.  We speculated that the medial temporal declarative memory system was primarily disturbed by the experience of severe hypoglycemia.

In another study, intensive therapy (IT) in children with T1DM was related to a 3-fold increase in rate of severe hypoglycemia, slowed reaction and response times and worse performance on long delay condition of the Spatial Delayed Response Task (SDR), compared to their peers undergoing standard therapy.  We concluded that a higher rate of severe hypoglycemia is related to decreased long-term spatial memory in children with T1DM.

In a follow-up study, we demonstrated that the number of previously experienced severe hypoglycemic episodes uniquely influenced long delay SDR performance for children with T1DM after controlling for age and age of onset (p<.01).  Number of episodes was not significantly related to short delay SDR or other task performance, suggesting that sensory, motor, short-term memory, encoding and sustained attention were intact.  We concluded that an increased number of severe hypoglycemic episodes selectively reduces long-term spatial memory in children with T1DM.

We have also found that after controlling for performance at baseline (the first test), age, and age of onset of diabetes, severe hypoglycemia uniquely contributed to long delay performance.  We concluded that severe hypoglycemia, measured prospectively, interferes with T1DM children’s long-term spatial memory.

Current Study

We are currently examining whether the effect of hypoglycemic episodes is visible in brain regions associated with memory, especially the hippocampus (see picture below).  The hippocampus is a cashew-shaped gray matter structure about two fingers wide and one finger long.  It is known to play a role in the "consolidation" of memory, or the conversion of short term into long term.

Hippocampus Outlined in Red (T1-weighted MRI image)

The hippocampus contains a high concentration of N-methyl-D-aspartate (NMDA) receptors.  These particular receptors may be vulnerable to hypoglycemic episodes.  If cells in the hippocampus are dying or shrinking due to hypoglycemia, we may be able to observe differences in the size of the hippocampi between diabetic patients and non-diabetic patients.  We may also be able to correlate the volume of the hippocampus with the number of hypoglycemic episodes, such that the more hypoglycemic episodes a diabetic patient has experienced, the smaller the hippocampi would be.

While we are especially interested in the effects of hypoglycemia, previous research suggests that high blood sugar (hyperglycemia) may also affect the brain and its functions.  Prolonged hyperglycemia is known to cause damage to peripheral nerves and blood vessels -- nerves within the brain and blood vessels supplying the brain may also be affected.  We are doing a type of MRI called Diffusion Tensor Imaging (DTI) that measures water flow in the brain to determine if hyperglycemia is associated with damage to white matter structures in the brain.

By taking into account the age that episodes occur, we may be able to determine if there is a "window of vulnerability".  The brain undergoes significant development during childhood, especially before the age of 5.  One question we would like to answer is: do extreme blood sugar episodes cause more problems if they happen at a younger age?

In this study, we are measuring blood sugar episodes prospectively for two years, and assessing cognitive/memory function and brain structure "before and after" two years have passed.

Interested in participating in this study?

CLICK HERE to find out more!

Diabetes Links

American Diabetes Association http://www.diabetes.org  "The nation's leading nonprofit health organization providing diabetes research, information and advocacy."

 

Diabetes on About.com  http://www.diabetes.about.com  Contains informative articles, message boards and chatrooms.

 

Children with Diabetes http://childrenwithdiabetes.com  An online community for kids, families, and adults with diabetes.

Disclaimer: The contents of the links listed have not been evaluated by Dr. Hershey or Washington University and should not be considered endorsed.  Always consult a doctor when making decisions that involve your health or medical treatment.