Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults

Victoria J. Williams, Bianca A. Trombetta, Rabab Z. Jafri, Aaron M. Koenig, Chase D. Wennick, Becky C. Carlyle, Laya Ekhlaspour, Rexford S Ahima, Steven J. Russell, David H. Salat, Steven E. Arnold

Research output: Contribution to journalArticle

Abstract

BACKGROUND. There is growing evidence to suggest that the brain is an important target for insulin action and that states of insulin resistance may extend to the CNS, with detrimental effects on cognitive functioning. Although the effect of systemic insulin resistance on peripheral organs is well studied, the degree to which insulin affects brain function in vivo remains unclear. METHODS. This randomized, single-blinded, 2-way–crossover, sham-controlled, pilot study determined the effects of hyperinsulinemia on functional MRI (fMRI) brain activation during a 2-back working memory task in 9 healthy older adults (aged 57–79 years). Each participant underwent 2 clamp procedures (an insulin infusion and a saline placebo infusion, with normoglycemia maintained during both conditions) to examine the effects of hyperinsulinemia on task performance and associated blood oxygen level–dependent (BOLD) signal using fMRI. RESULTS. Hyperinsulinemia (compared with saline control) was associated with an increase in both the spatial extent and relative strength of task-related BOLD signal during the 2-back task. Further, the degree of increased task-related activation in select brain regions correlated with greater systemic insulin sensitivity as well as decreased reaction times and performance accuracy between experimental conditions. CONCLUSION. Together, these findings provide evidence of insulin action in the CNS among older adults during periods of sustained cognitive demand, with the greatest effects noted for individuals with highest systemic insulin sensitivity. FUNDING. This work was funded by the NIH (5R21AG051958, 2016).

Original languageEnglish (US)
Article numbere129700
JournalJCI Insight
Volume4
Issue number14
DOIs
StatePublished - Jul 25 2019

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Hyperinsulinism
Insulin Resistance
Magnetic Resonance Imaging
Insulin
Oxygen
Brain
Task Performance and Analysis
Short-Term Memory
Reaction Time
Placebos

ASJC Scopus subject areas

  • Medicine(all)

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Williams, V. J., Trombetta, B. A., Jafri, R. Z., Koenig, A. M., Wennick, C. D., Carlyle, B. C., ... Arnold, S. E. (2019). Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults. JCI Insight, 4(14), [e129700]. https://doi.org/10.1172/jci.insight.129700

Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults. / Williams, Victoria J.; Trombetta, Bianca A.; Jafri, Rabab Z.; Koenig, Aaron M.; Wennick, Chase D.; Carlyle, Becky C.; Ekhlaspour, Laya; Ahima, Rexford S; Russell, Steven J.; Salat, David H.; Arnold, Steven E.

In: JCI Insight, Vol. 4, No. 14, e129700, 25.07.2019.

Research output: Contribution to journalArticle

Williams, VJ, Trombetta, BA, Jafri, RZ, Koenig, AM, Wennick, CD, Carlyle, BC, Ekhlaspour, L, Ahima, RS, Russell, SJ, Salat, DH & Arnold, SE 2019, 'Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults', JCI Insight, vol. 4, no. 14, e129700. https://doi.org/10.1172/jci.insight.129700
Williams VJ, Trombetta BA, Jafri RZ, Koenig AM, Wennick CD, Carlyle BC et al. Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults. JCI Insight. 2019 Jul 25;4(14). e129700. https://doi.org/10.1172/jci.insight.129700
Williams, Victoria J. ; Trombetta, Bianca A. ; Jafri, Rabab Z. ; Koenig, Aaron M. ; Wennick, Chase D. ; Carlyle, Becky C. ; Ekhlaspour, Laya ; Ahima, Rexford S ; Russell, Steven J. ; Salat, David H. ; Arnold, Steven E. / Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults. In: JCI Insight. 2019 ; Vol. 4, No. 14.
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