Lateralized Memory Circuit Dropout In Alzheimer'S Disease Patients

Altered connectivity within neuronal networks is often observed in Alzheimer's disease. However, delineating pro-cognitive compensatory changes from pathological network decline relies on characterizing network and task effects together. In this study, we interrogated the dynamics of occipito-temporo-frontal brain networks responsible for implicit and explicit memory processes using high-density EEG and dynamic causal modelling. We examined source-localized network activity from patients with Alzheimer's disease (n=21) and healthy controls (n=21), while they performed both visual recognition (explicit memory) and implicit priming tasks. Parametric empirical Bayes analyses identified significant reductions in temporo-frontal connectivity and in subcortical visual input in patients, specifically in the left hemisphere during the recognition task. There was also slowing in frontal left hemisphere signal transmission during the implicit priming task, with significantly more distinct dropout in connectivity during the recognition task, suggesting that these network drop-out effects are affected by task difficulty. Furthermore, during the implicit memory task, increased right frontal activity was correlated with improved task performance in patients only, suggesting that right-hemisphere compensatory mechanisms may be employed to mitigate left-lateralized network dropout in Alzheimer's disease. Taken together, these findings suggest that Alzheimer's disease is associated with lateralized memory circuit dropout and potential compensation from the right hemisphere, at least for simpler memory tasks.