Work

Neurophysiological signatures of default mode network dysfunction and cognitive decline in Alzheimer's disease

Year: 2025

Type: article

Abstract: BACKGROUND: Neural hyper-excitability and network dysfunction are neurophysiological hallmarks of Alzheimer's disease (AD) in animal studies, but their presence and clinical relevance in humans remain poorly understood METHOD: We introduce a novel perturbation-based approach combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), alongside resting-state EEG (rsEEG), to investigate neurophysiological basis of default mode network (DMN) dysfunction in early AD. RESULT: While rsEEG revealed global neural slowing and disrupted synchrony, these measures reflected widespread changes in brain neurophysiology without network-specific insights. In contrast, TMS-EEG identified network-specific local hyper-excitability in the parietal DMN and disrupted connectivity with frontal DMN regions, which uniquely predicted distinct cognitive impairments and mediated the link between structural brain integrity and cognition. CONCLUSION: Our findings provide critical insights into how network-specific neurophysiological disruptions contribute to AD-related cognitive dysfunction. Perturbation-based assessments hold promise as novel markers of early detection, disease progression, and target engagement for disease-modifying therapies aiming to restore abnormal neurophysiology in AD.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70856_097238

Author: Mouhsin Shafi

Institutions: Beth Israel Deaconess Medical Center, Berenson Allen Center for Noninvasive Brain Stimulation

Language: English

Topic: Transcranial Magnetic Stimulation Studies

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,200