Promising neurostimulation routes for targeting the hippocampus to improve episodic memory: A review

This review aims to highlight modern neurostimulation approaches that are effectively activating the hippocampus and enhancing episodic memory performance. The hippocampus is a brain region known to play an essential role in episodic memory processes. However, as it is nestled deep within the brain, it has been a challenging target for traditional neurostimulation approaches, with studies reporting inconsistent memory effects. Recent studies suggest more than half of the electrical current from non-invasive transcranial electrical stimulation (tES) methods may be attenuated by the human scalp, skull, and cerebral spinal fluid. Thus, this review aims to highlight novel neurostimulation approaches that are showing promise as alternative routes for activating hippocampal circuitry. Early evidence suggests temporal interference, closed-loop and individualized protocols, sensory stimulation and peripheral nerve-targeted tES protocols warrant further investigation. These approaches each provide promising routes for activating the hippocampus by a) increasing its functional connectiveness to key brain regions, b) strengthening synaptic plasticity mechanisms, or c) enhancing neural entrainment specifically within and between theta and gamma frequencies in these regions. Importantly, these three functional mechanisms and the hippocampus' structural integrity are negatively impacted throughout the progression of Alzheimer's Disease, with episodic memory deficits likewise evident in early stages. Consequently, depending on further validation of the approaches reviewed here, these techniques could offer significant applied therapeutic value for patients suffering from memory deficits or neurodegenerative diseases including amnestic Mild Cognitive Impairment or Alzheimer's disease.