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Title: Ketosis regulates K+ ion channels, strengthening brain-wide signaling disrupted by age
Aging is associated with impaired signaling between brain regions when measured using resting-state functional magnetic resonance imaging (fMRI). This age-related destabilization and desynchronization of brain networks reverses itself when the brain switches from metabolizing glucose to ketones. Here, we probe the mechanistic basis for these effects. First, we confirmed their robustness across measurement modalities using two datasets acquired from resting-state EEG (Lifespan: standard diet, 20–80 years, N = 201; Metabolic: individually weight-dosed and calorically-matched glucose and ketone ester challenge, μage = 26.9 ±11.2 years, N = 36). Then, using a multiscale conductance-based neural mass model, we identified the unique set of mechanistic parameters consistent with our clinical data. Together, our results implicate potassium (K+) gradient dysregulation as a mechanism for age-related neural desynchronization and its reversal with ketosis, the latter finding of which is consistent with direct measurement of ion channels. As such, the approach facilitates the connection between macroscopic brain activity and cellular-level mechanisms.  more » « less
Award ID(s):
1926781
PAR ID:
10508096
Author(s) / Creator(s):
; ; ; ; ; ;
Publisher / Repository:
MIT Press
Date Published:
Journal Name:
Imaging Neuroscience
Volume:
2
ISSN:
2837-6056
Page Range / eLocation ID:
1 to 14
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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