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Task-related fMRI BOLD response to hyperinsulinemia in healthy older adults
Victoria J. Williams, … , David H. Salat, Steven E. Arnold
Victoria J. Williams, … , David H. Salat, Steven E. Arnold
Published June 18, 2019
Citation Information: JCI Insight. 2019;4(14):e129700. https://doi.org/10.1172/jci.insight.129700.
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Clinical Medicine Aging Endocrinology

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

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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).

Authors

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

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Figure 1

Spatial overlap of task-related fMRI activation for 2-back greater than 0-back trials during insulin and saline conditions analyzed separately.

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Spatial overlap of task-related fMRI activation for 2-back greater than ...
(A) Conjunction map showing the spatial overlap from 1-sample group mean analyses of task-related activation for 2-back to 0-back trials for insulin and saline conditions analyzed separately (n = 9; P < 0.01, corrected). An expected pattern of task-related activation was observed across both conditions largely involving frontal and parietal regions, although the spatial extent of activation was 1.8 times larger during insulin compared with saline condition. (B) Results from each 2-back to 0-back contrast analyzed separately by experimental condition (insulin and saline) contributing to the conjunction map above, resampled onto the cortical surface for ease of viewing.

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