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Impaired long-range excitatory time scale predicts abnormal neural oscillations and cognitive deficits in Alzheimer’s disease

Authors :
Parul Verma
Kamalini Ranasinghe
Janani Prasad
Chang Cai
Xihe Xie
Hannah Lerner
Danielle Mizuiri
Bruce Miller
Katherine Rankin
Keith Vossel
Steven W. Cheung
Srikantan S. Nagarajan
Ashish Raj
Source :
Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-15 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Background Alzheimer’s disease (AD) is the most common form of dementia, progressively impairing cognitive abilities. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify global abnormal biophysical mechanisms underlying the spatial and spectral electrophysiological patterns in AD, we estimated the parameters of a biophysical spectral graph model (SGM). Methods SGM is an analytic neural mass model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled neuronal mass models, the SGM is linear, available in closed-form, and parameterized by a small set of biophysical interpretable global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well-characterized clinical population of patients with AD (N = 88, age = 62.73 +/- 8.64 years) and a cohort of age-matched controls (N = 88, age = 65.07 +/- 9.92 years). Results Patients with AD showed significantly elevated long-range excitatory neuronal time scales, local excitatory neuronal time scales and local inhibitory neural synaptic strength. The long-range excitatory time scale had a larger effect size, compared to local excitatory time scale and inhibitory synaptic strength and contributed highest for the accurate classification of patients with AD from controls. Furthermore, increased long-range time scale was associated with greater deficits in global cognition. Conclusions These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the local spectral signatures and cognition in the human brain, and how it might be a parsimonious factor underlying altered neuronal activity in AD. Our findings provide new insights into mechanistic links between abnormal local spectral signatures and global connectivity measures in AD.

Details

Language :
English
ISSN :
17589193
Volume :
16
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Alzheimer’s Research & Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.1cc9785ecf4341a5b2a25b7f79619c43
Document Type :
article
Full Text :
https://doi.org/10.1186/s13195-024-01426-7