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Alzheimer's disease (AD) is the most common form of dementia, progressively impairing memory and cognition. 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 abnormal biophysical mechanisms underlying these abnormal electrophysiological patterns, we estimated the parameters of a spectral graph-theory model (SGM). SGM is an analytic model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. The long-range excitatory time scale was associated with greater deficits in global cognition and was able to distinguish AD patients from controls with high accuracy. These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the spatiospectral signatures and cognition in AD.
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http://dx.doi.org/10.21203/rs.3.rs-2579392/v3 | DOI Listing |
iScience
September 2025
Instituto de Neurociencias CSIC-UMH, Alicante, Spain.
Explaining the macroscopic activity of a neuronal population from its microscopic properties poses a great challenge, not just because of the many local agents that play a role, but due to the impact of long-range connections from other brain regions. We used a computational model to explore how local and global components of a network shape the slow wave activity (SWA). A sensitivity analysis allowed us to explore how local properties and long-range connections shaped the SWA of a population and its neighbors.
View Article and Find Full Text PDFNat Commun
August 2025
Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences & The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
The precise structural and functional characteristics of input circuits targeting histaminergic neurons remain poorly understood. Here, using a rabies virus retrograde tracing system combined with fluorescence micro-optical sectioning tomography, we construct a 3D monosynaptic long-range input atlas of male mouse histaminergic neurons. We identify that the hypothalamus, thalamus, pallidum, and hippocampus constitute major input sources, exhibiting diverse spatial distribution patterns and neuronal type ratios.
View Article and Find Full Text PDFNat Commun
August 2025
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
A growing body of evidence shows that epileptic activity is frequently observed in patients with Alzheimer's disease (AD), implicating underlying excitatory-inhibitory imbalance. The distinction of whether the AD-epileptic phenotype represents a subset of patients or an underdiagnosed manifestation holds major therapeutic implications. Here, we quantified the excitatory-inhibitory imbalance in AD patients using magnetoencephalography and examined the relationships to AD pathophysiology-amyloid-beta and tau, and to epileptic activity.
View Article and Find Full Text PDFFront Netw Physiol
August 2025
Neural Information Processing Group, Fakultät IV, Technische Universität Berlin, Berlin, Germany.
The human brain is a complex dynamical system which displays a wide range of macroscopic and mesoscopic patterns of neural activity, whose mechanistic origin remains poorly understood. Whole-brain modelling allows us to explore candidate mechanisms causing the observed patterns. However, it is not fully established how the choice of model type and the networks' spatial resolution influence the simulation results, hence, it remains unclear, to which extent conclusions drawn from these results are limited by modelling artefacts.
View Article and Find Full Text PDFbioRxiv
July 2025
Neuroelectrics, Barcelona, Spain.
Functional brain networks exhibit both cooperative and competitive interactions, yet existing models-assuming purely excitatory long-range coupling-fail to account for the widespread anti-correlations observed in fMRI. Starting from a laminar neural mass framework, where each mass comprises distinct slow (alpha-band) and fast (gamma-band) oscillatory pyramidal subpopulations ( and ), we show how laminar-specific long-range excitatory projections across neural mass parcels can give rise to both cooperation and competition via cross-frequency envelope coupling. We demonstrate that homologous connections across parcels (e.
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