Investigating the Functional Role of Medial Prefrontal Cortex During Memory Retrieval Using High-definition Transcranial Direct Current Stimulation

Emerging studies have started to focus on the medial prefrontal cortex’s (mPFC) role in memory function. Previous research revealed increased activity in mPFC, particularly during remote memory retrieval in humans. However, this link between mPFC and remote memory retrieval in human subjects is still a correlational-based relationship. In the current study, our goal is to determine a causal relationship between the mPFC and remote memory retrieval in humans using a non-invasive neuromodulation technique known as high-definition transcranial direct current stimulation (HD-tDCS). We applied HD-tDCS to participants during a remote memory retrieval task, which tested them on Swahili word pairs learned one week prior to the retrieval task. Our results demonstrated participants in the cathodal stimulation group performed significantly better than anodal and sham stimulation groups on the remote-memory retrieval task. Additionally, two sessions of resting-state electroencephalography (rs-EEG) were acquired before and after the HDtDCS paired remote-memory retrieval task. A positive correlation through a whole-brain correlation analysis was obtained between performance in the remote memory task and gamma frequency band activity in the posterior cingulate cortex (PCC), retrosplenial cortex (RSC), and hippocampus (HPC) after stimulation (post-rs-EEG – pre-rs-EEG). Our results provide, for the first time, evidence to support the existence of a causal relation between mPFC and remote memory retrieval in humans. Our data also suggests that cathodal stimulation in mPFC could potentially improve memory retrieval, presumably through an optimal range of excitation/inhibition (E/I) balance in mPFC, which benefits the process of remote memory retrieval.