Abstract

Modulation of cognitive functions supporting human declarative memory is one of the grand challenges of neuroscience, and of vast importance for a variety of neuropsychiatric, neurodegenerative and neurodevelopmental diseases. Despite a recent surge of successful attempts at improving performance in a range of memory tasks, the optimal approaches and parameters for memory enhancement have yet to be determined. On a more fundamental level, it remains elusive how delivering electrical current in a given brain area leads to enhanced memory processing. Starting from the local and distal physiological effects on neural populations, the mechanisms of enhanced memory encoding, maintenance, consolidation, or recall in response to direct electrical stimulation are only now being unraveled. With the advent of innovative neurotechnologies for concurrent recording and stimulation intracranially in the human brain, it becomes possible to study both acute and chronic effects of stimulation on memory performance and the underlying neural activities. In this review, we summarize the effects of various invasive stimulation approaches for modulating memory functions. We first outline the challenges that were faced in the initial studies of memory enhancement and the lessons learned. Electrophysiological biomarkers are then reviewed as more objective measures of the stimulation effects than behavioral outcomes. Finally, we classify the various stimulation approaches into continuous and phasic modulation with open or closed loop for responsive stimulation based on analysis of the recorded neural activities. Although the potential advantage of closed-loop responsive stimulation over the classic open-loop approaches is inconclusive, we foresee the emerging results from ongoing longitudinal studies and clinical trials to shed light on both the mechanisms and optimal strategies for improving declarative memory. Adaptive stimulation based on the biomarker analysis over extended periods of time is proposed as a future direction for obtaining lasting effects on memory functions. Chronic tracking and modulation of neural activities intracranially through adaptive stimulation opens tantalizing new avenues to continually monitor and treat memory and cognitive deficits in a range of brain disorders.

Citations

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