TY - JOUR
T1 - Altered Hierarchical Gradients of Intrinsic Neural Timescales in Mild Cognitive Impairment and Alzheimer’s Disease
AU - for Alzheimer’s Disease Neuroimaging Initiative
AU - Zhang, Aiying
AU - Wengler, Kenneth
AU - Zhu, Xi
AU - Horga, Guillermo
AU - Goldberg, Terry E.
AU - Lee, Seonjoo
N1 - Publisher Copyright:
Copyright © 2024 the authors.
PY - 2024/6/19
Y1 - 2024/6/19
N2 - Alzheimer’s disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the United States. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit. Such heterogeneity of the timescales forms a basis of the brain functional hierarchy and captures an aspect of circuit dynamics relevant to excitation/inhibition balance, which is broadly relevant for cognitive functions. Given that, we applied rs-fMRI to test whether distinct changes of INT at different hierarchies are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed-effect model was implemented to detect altered hierarchical gradients across populations followed by pairwise comparisons to identify regional differences. High similarities between AD and Converter were observed. Specifically, the inferior temporal, caudate, and pallidum areas exhibit significant alterations in both AD and Converter. Distinct INT-related pathological changes in MCI and AD were found. For AD/Converter, neural information is stored for a longer time in lower hierarchical areas, while higher levels of hierarchy seem to be preferentially impaired in MCI leading to a less pronounced hierarchical gradient. These results inform that the INT holds great potential as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.
AB - Alzheimer’s disease (AD) is a devastating neurodegenerative disease that affects millions of seniors in the United States. Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study neurophysiology in AD and its prodromal condition, mild cognitive impairment (MCI). The intrinsic neural timescale (INT), which can be estimated through the magnitude of the autocorrelation of neural signals from rs-fMRI, is thought to quantify the duration that neural information is stored in a local circuit. Such heterogeneity of the timescales forms a basis of the brain functional hierarchy and captures an aspect of circuit dynamics relevant to excitation/inhibition balance, which is broadly relevant for cognitive functions. Given that, we applied rs-fMRI to test whether distinct changes of INT at different hierarchies are present in people with MCI, those progressing to AD (called Converter), and AD patients of both sexes. Linear mixed-effect model was implemented to detect altered hierarchical gradients across populations followed by pairwise comparisons to identify regional differences. High similarities between AD and Converter were observed. Specifically, the inferior temporal, caudate, and pallidum areas exhibit significant alterations in both AD and Converter. Distinct INT-related pathological changes in MCI and AD were found. For AD/Converter, neural information is stored for a longer time in lower hierarchical areas, while higher levels of hierarchy seem to be preferentially impaired in MCI leading to a less pronounced hierarchical gradient. These results inform that the INT holds great potential as an additional measure for AD prediction, even a stable biomarker for clinical diagnosis.
KW - AD
KW - INT
KW - MCI
KW - rs-fMRI
UR - http://www.scopus.com/inward/record.url?scp=85196622349&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2024-23.2024
DO - 10.1523/JNEUROSCI.2024-23.2024
M3 - Article
C2 - 38658167
AN - SCOPUS:85196622349
SN - 0270-6474
VL - 44
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 25
M1 - e2024232024
ER -