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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: EC‐DBS caused a reversible modulation effect on functional connectivity in the hippocampal‐cortex network and episodic‐like memory performance.