Modulation of the rat hippocampal‐cortex network and episodic‐like memory performance following entorhinal cortex stimulation

Entorhinal cortex (EC) deep brain stimulation (DBS) has shown a memory enhancement effect. However, its brain network modulation mechanisms remain unclear. The present study aimed to investigate the functional connectivity in the rat hippocampal-cortex network and episodic-like memory performance following EC-DBS.7.0 T functional MRI (fMRI) scans and episodic-like memory tests were performed 3 days and 28 days after EC-DBS in healthy rats. The fMRI data processing was focused on the power spectra, functional connectivity, and causality relationships in the hippocampal-cortex network. In addition, the exploration ratio for each object and the discrimination ratio of the "when" and "where" factors were calculated in the behavioral tests.EC-DBS increased the power spectra and the functional connectivity in the prefrontal- and hippocampal-related networks 3 days after stimulation and recovered 4 weeks later. Both networks exhibited a strengthened connection with the EC after EC-DBS. Further seed-based functional connectivity comparisons showed increased connectivity among the prefrontal cortex, hippocampus and EC, especially on the ipsilateral side of DBS. The dentate gyrus is a hub region closely related to both the EC and the prefrontal cortex and receives information flow from both. Moreover, acute EC-DBS also enhanced the discrimination ratio of the "where" factor in the episodic-like memory test on Day 3.EC-DBS caused a reversible modulation effect on functional connectivity in the hippocampal-cortex network and episodic-like memory performance.