Predicting Alzheimer's disease severity by means of TMS–EEG coregistration

Clinical manifestations of Alzheimer's disease (AD)are associated with a breakdown in large-scale communication, such that AD may be considered as a “disconnection syndrome.” An established method to test effective connectivity is the combination of transcranial magnetic stimulation with electroencephalography (TMS–EEG)because the TMS-induced cortical response propagates to distant anatomically connected regions. To investigate whether prefrontal connectivity alterations may predict disease severity, we explored the relationship of dorsolateral prefrontal cortex connectivity (derived from TMS–EEG)with cognitive decline (measured with Mini Mental State Examination and a face–name association memory task)in 26 patients with AD. The amplitude of TMS–EEG evoked component P30, which was found to be generated in the right superior parietal cortex, predicted Mini Mental State Examination and face–name memory scores: higher P30 amplitudes predicted poorer cognitive and memory performances. The present results indicate that advancing disease severity might be associated with effective connectivity increase involving long-distance frontoparietal connections, which might represent a maladaptive pathogenic mechanism reflecting a damaged excitatory–inhibitory balance between anterior and posterior regions.