Brain Activation During Working Memory Is Altered in Type 1 Diabetes During Hypoglycemia

  1. Donald C. Simonson3,7
  1. 1Brain Imaging Center, McLean Hospital, Belmont, Massachusetts
  2. 2Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  3. 3Harvard Medical School, Boston, Massachusetts
  4. 4Research Division, Joslin Diabetes Center, Boston, Massachusetts
  5. 5Research Institute, Winthrop-University Hospital, Mineola, New York
  6. 6Department of Psychiatry, University of Utah, Salt Lake City, Utah
  7. 7Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts
  1. Corresponding author: Nicolas R. Bolo, nbolo{at}


OBJECTIVE We investigated the effects of acute hypoglycemia on working memory and brain function in type 1 diabetes.

RESEARCH DESIGN AND METHODS Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during a hyperinsulinemic clamp, we compared brain activation responses with a working-memory task (WMT) in type 1 diabetic subjects (n = 16) and age-matched nondiabetic control subjects (n = 16) during euglycemia (5.0 mmol/L) and hypoglycemia (2.8 mmol/L). Behavioral performance was assessed by the percentage of correct responses.

RESULTS During euglycemia, WMTs activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R2 = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups.

CONCLUSIONS BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes.

  • Received April 14, 2011.
  • Accepted August 25, 2011.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

No Related Web Pages