Cholinergic blockade reveals a role for human hippocampal theta in memory encoding but not retrieval

Overview

1. Department of Biomedical Engineering, Columbia University, New York, United States
2. Department of Neurological Surgery, University of Texas Southwestern, Dallas, United States
3. Department of Anesthesiology, University of Texas Southwestern, Dallas, United States
4. Department of Neurological Surgery, Columbia University, New York, United States

Abstract

Cholinergic dysfunction is a hallmark of Alzheimer’s disease and other memory disorders. Yet, the neurophysiological mechanisms linking cholinergic signaling to memory remain poorly understood. In this study, we administered scopolamine, a muscarinic cholinergic antagonist, to neurosurgical patients with intracranial electrodes as they performed an associative recognition memory task. When scopolamine was present at encoding, we observed disruptions to hippocampal slow theta oscillations (2–4 Hz), with selective impairments to recollection-based memory. However, when scopolamine was present during retrieval alone, we observed disruptions to slow theta without impaired memory performance. These disruptions included dose-dependent reductions in theta power, theta phase reset, and encoding–retrieval pattern reinstatement. Together, our results challenge the notion that theta oscillations are necessary for memory retrieval, and instead suggest that theta universally reflects an encoding-related neural state. These findings motivate updates to current models of acetylcholine’s role in memory and may inform future therapies targeting rhythmic biomarkers of memory dysfunction.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above.

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

• zenodo:23327706, at Zenodo; found in “Data availability”

Data availability

The data supporting the findings of this study are openly available in Zenodo at https://doi.org/10.5281/zenodo.23327706. All data analyses were performed in Python (3.6), using publicly available software for the analysis of human electrophysiology data (https://github.com/pennmem/ptsa [DePalatis et al., 2026] and https://github.com/pennmem/cmlreaders [DePalatis et al., 2025]). Other custom code is available at https://github.com/tgedankien/AR_scopolamine (copy archived at Gedankien, 2026).

The following dataset was generated:

Gedankien T, Kriegel J, Zabeh E, McDonagh D, Lega B, Jacobs J. 2026. Cholinergic blockade reveals a role for human hippocampal theta in memory encoding but not retrieval. Zenodo.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 12 November 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 6 authors, 1 keyword, 62 references.

Cite

This paper

Gedankien, T., Kriegel, J., Zabeh, E., McDonagh, D., Lega, B. C., & Jacobs, J. (2026). Cholinergic blockade reveals a role for human hippocampal theta in memory encoding but not retrieval. eLife, 14, RP108972.

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41467-023-41025-y [code]

Acetylcholine modulates the temporal dynamics of human theta oscillations during memory.

Journal: Nature communications

In common: 28 references

[2] doi:10.1038/s41467-025-62553-9 [code]

Theta-phase locking of single neurons during human spatial memory.

Journal: Nature communications

In common: cognitive, 9 references

[3] doi:10.7554/elife.80633 [code]

Phase separation of competing memories along the human hippocampal theta rhythm.

Journal: eLife

In common: cognitive, 7 references

[4] doi:10.1038/s41467-024-44877-0 [code]

Distinguishing examples while building concepts in hippocampal and artificial networks.

Journal: Nature communications

In common: 6 references

[5] doi:10.7554/elife.85753 [code]

MTL neurons phase-lock to human hippocampal theta.

Journal: eLife

In common: 6 references

[6] doi:10.1371/journal.pbio.3003268 [code]

Transfer of motor learning is associated with patterns of activity in the default mode network.

Journal: PLoS biology

In common: 5 references

[7] doi:10.1523/eneuro.0333-22.2023 [code]

Interaction between Theta Phase and Spike Timing-Dependent Plasticity Simulates Theta-Induced Memory Effects.

Journal: eNeuro

In common: 5 references

[8] doi:10.1016/j.celrep.2025.116443

Modulation of speed-dependent acetylcholine release in the hippocampus by spatial task engagement.

Journal: Cell reports

In common: cognitive, 4 references

[9] doi:10.7554/elife.80661 [code]

Hippocampal place cell remapping occurs with memory storage of aversive experiences.

Journal: eLife

In common: 4 references

[10] doi:10.1016/j.neuron.2026.05.004 [code]

A learning-evoked slow-oscillatory architecture paces population activity for offline reactivation across the human medial temporal lobe.

Journal: Neuron

In common: 4 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

<!-- oscr-badge:start -->
[![OSCR](https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine.svg)](https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine)
<!-- oscr-badge:end -->

.. oscr-badge:start

.. image:: https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine.svg
   :target: https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine
   :alt: OSCR

.. oscr-badge:end

<!-- oscr-badge:start -->
<a href="https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine"><img src="https://openscicode.org/badge/repo/github.com/tgedankien/ar_scopolamine.svg" alt="OSCR"></a>
<!-- oscr-badge:end -->

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: code errors and mismatches between the code and the paper about this paper and its code, from readers and its authors, beside the paper and its tracing map.

Report a mismatch between the code and the paper · Report a code error (signed in)

Reproductions: reports from readers who ran the authors' code and did not get the paper's result, what they ran, with which environment, commit and data.

Report a reproduction failure (signed in)

Versions of its code: the releases of its code tied to a version of this paper (the preprint, the accepted manuscript, the version of record…), each with the tracing map versioned with it.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.