Functional connectivity of insula, basal ganglia, and prefrontal executive control networks during hypoglycemia in type 1 diabetes

Nicolas R. Bolo, Gail Musen, Donald C. Simonson, Lisa D. Nickerson, Veronica L. Flores, Tamar Siracusa, Brandon Hager, In Kyoon Lyoo, Perry F. Renshaw, Alan M. Jacobson

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic– hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia.

Original languageEnglish
Pages (from-to)11012-11023
Number of pages12
JournalJournal of Neuroscience
Issue number31
StatePublished - 5 Aug 2015

Bibliographical note

Publisher Copyright:
© 2015 the authors.


  • Executive control resting-state network
  • Functional connectivity
  • Functional magnetic resonance imaging
  • Hypoglycemia
  • Independent component analysis
  • Type 1 diabetes


Dive into the research topics of 'Functional connectivity of insula, basal ganglia, and prefrontal executive control networks during hypoglycemia in type 1 diabetes'. Together they form a unique fingerprint.

Cite this