Acetylcholine modulates the temporal dynamics of human theta oscillations during memory

Tamara Gedankien, Ryan Joseph Tan, Salman Ehtesham Qasim, Haley Moore, David McDonagh, Joshua Jacobs () and Bradley Lega ()
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Tamara Gedankien: Columbia University
Ryan Joseph Tan: University of Texas Southwestern
Salman Ehtesham Qasim: Icahn School of Medicine at Mount Sinai
Haley Moore: University of Texas Southwestern
David McDonagh: University of Texas Southwestern
Joshua Jacobs: Columbia University
Bradley Lega: University of Texas Southwestern

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract The cholinergic system is essential for memory. While degradation of cholinergic pathways characterizes memory-related disorders such as Alzheimer’s disease, the neurophysiological mechanisms linking the cholinergic system to human memory remain unknown. Here, combining intracranial brain recordings with pharmacological manipulation, we describe the neurophysiological effects of a cholinergic blocker, scopolamine, on the human hippocampal formation during episodic memory. We found that the memory impairment caused by scopolamine was coupled to disruptions of both the amplitude and phase alignment of theta oscillations (2–10 Hz) during encoding. Across individuals, the severity of theta phase disruption correlated with the magnitude of memory impairment. Further, cholinergic blockade disrupted connectivity within the hippocampal formation. Our results indicate that cholinergic circuits support memory by coordinating the temporal dynamics of theta oscillations across the hippocampal formation. These findings expand our mechanistic understanding of the neurophysiology of human memory and offer insights into potential treatments for memory-related disorders.

Date: 2023
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DOI: 10.1038/s41467-023-41025-y

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