Modulation of Human Memory by Deep Brain Stimulation of the Entorhinal-Hippocampal Circuitry

Abstract

Neurological disorders affecting human memory present a major scientific, medical, and societal challenge. Direct or indirect deep brain stimulation (DBS) of the entorhinal-hippocampal system, the brain's major memory hub, has been studied in people with epilepsy or Alzheimer's disease, intending to enhance memory performance or slow memory decline. Variability in the spatiotemporal parameters of stimulation employed to date notwithstanding, it is likely that future DBS for memory will employ closed-loop, nuanced approaches that are synergistic with native physiological processes. The potential for editing human memory-decoding, enhancing, incepting, or deleting specific memories-suggests exciting therapeutic possibilities but also raises considerable ethical concerns.

Stimulation of the right entorhinal white matter enhances visual memory encoding in humans

“…It is possible, therefore, that the right white matter stimulation enhanced visual recognition in this task in the same manner as it did for the others. We anticipate that for memory tasks that depend on the processing of non-spatial verbal material, stimulation applied in the left hemisphere may also provide modulatory effects on memory [37], consistent with related findings in prior studies [38].…”

“…Earlier studies of intracranial MTL stimulation in humans have yielded mixed results regarding the efficacy of short-term electrical stimulation for memory enhancement [reviewed in [22] and [37]]. A few studies involving electrical stimulation of the fornix white matter, the chief efferent pathway of the hippocampus, suggested memory enhancement [13,14], though these should be considered with caution, due to the small sample size, divergent results (i.e.…”

Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson’s Disease Using Bidirectional Deep-Brain-Computer Interfaces

“…The advances in discovery, innovation, and collaboration have led to the next generation of fully embedded investigative bidirectional dBCIs, in which both single and dual-threshold control policy algorithms are available (Percept™, Summit™ RC+S, Medtronic PLC, Minneapolis, MN, USA). Evolution in the understanding of relevant inputs and control policies in the first generation bidirectional dBCIs for PD and epilepsy has fueled similar discoveries for treatment of other neuropsychiatric disorders (Kundu et al, 2018 ; Rudebeck et al, 2019 ; Senova et al, 2019 ; Mankin and Fried, 2020 ). Advances in the understanding of the oscillopathies and circuitopathies of neuropsychiatric diseases are developing in parallel with advances in bidirectional dBCI technology.…”

Theta-burst stimulation entrains frequency-specific oscillatory responses

“…In addition to better understanding the anatomical factors which determine how the brain responds to TBS, we must also account for variability in the temporal domain. There is mounting evidence that the effects of stimulation are contingent on the endogenous neural activity near the stimulation site and elsewhere in the brain 19,20 . For example, it is possible that volleys of TBS must arrive in-phase with endogenous theta oscillations to exert their maximal effect, or that strong oscillations must not already be present in stimulated tissue.…”

“…Though an important piece of the TBS puzzle, there are also immediate neural responses to brief stimulation events that go unexplored in these paradigms. Understanding such real-time changes in neural dynamics -particularly at the level of intracranial electrophysiology -is crucial if TBS is to be applied in closed-loop paradigms for cognitive enhancement or therapeutic effect 13,19,20 . Moreover, the brain's response to exogenous perturbations could shed light on the fundamental nature of oscillatory local eld potentials, an area of intense study but with limited explanatory models.…”