Mapping Excitation/Inhibition with MEG in early Alzheimer’s Disease

We will investigate alterations in E/I balance using magnetoencephalography (MEG) in a large cohort spanning the AD continuum, including healthy individuals, participants with a family history of AD, subjective cognitive decline, mild cognitive impairment, and AD. Resting-state MEG recordings will be source reconstructed, and E/I balance will be characterized by the aperiodic exponent across 74 cortical regions. Spatial patterns of MEG-derived E/I will be correlated with open-access normative glutamatergic and GABAergic receptor density maps obtained from PET. In this way, we will assess whether macroscale neurotransmitter distributions predict the spatial organization of electrophysiological E/I in healthy individuals, and whether this coupling is disrupted in at-risk and clinical populations. We expect to observe increased E/I imbalance alongside a reduced correspondence between MEG-derived metrics and neurotransmitter distributions with disease progression.