Control of working memory by phase–amplitude coupling of human hippocampal neurons
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1.
California Institute of Technology
Abstract
Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3,4,5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.
Copyright and License
© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Acknowledgement
We thank the patients who volunteered to participate in this study; the members of the clinical teams at Cedars-Sinai Medical Center, J. Chung, L. Bateman, and the staff at Toronto Western Hospital and John’s Hopkins School of Medicine for patient management and care and support of data acquisition; T. Rusch, J. Minxha and S. Fusi for discussion; N. Chandravadia for data processing; and I. Reucroft for data acquisition. This study was supported by a German National Academy of Sciences Leopoldina Postdoctoral fellowship (to J.D.), a Center for Neural Science and Medicine at Cedars-Sinai Postdoctoral fellowship (to J.D.), the BRAIN initiative through the National Institute of Neurological Disorders and Stroke (U01NS103792 and U01NS117839 to U.R.) and the National Science Foundation (BCS-2219800 to U.R.).
Contributions
J.D., J.K. and U.R. conceived the project. J.D., J.K., A.G.P.S. and Y.S. performed experiments. J.D., J.K. and U.K. performed data analyses. C.M.R. provided patient care and supported data acquisition. M.K. managed the data release and demo code. T.A.V., W.S.A. and A.N.M. managed patients and performed surgeries. J.D. and U.R. wrote the manuscript with input from all of the authors. J.D. and U.R. acquired funding.
Data Availability
All data used in this study are publicly available in the DANDI Archive59 (https://dandiarchive.org/dandiset/000673). The published dataset contains the timestamps and waveforms of the sorted neurons, LFPs, electrode coordinates, behavioural data, as well as the stimuli, triggers, experimental parameters, anonymized patient metadata of each session.
Extended Data Fig. 2 Additional PAC analyses.
Extended Data Fig. 3 Theta-high gamma PAC control analyses in the hippocampus.
Data Availability
Example code to reproduce the results is published at GitHub81 (https://github.com/rutishauserlab/SBCAT-release-NWB) and Zenodo67 (https://doi.org/10.5281/zenodo.10494533).
Conflict of Interest
The authors declare no competing interests.
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Additional details
- ISSN
- 1476-4687
- German National Academy of Sciences Leopoldina
- Cedars-Sinai Medical Center
- National Institutes of Health
- U01NS103792
- National Institutes of Health
- U01NS117839
- National Science Foundation
- BCS-2219800
- Caltech groups
- Division of Biology and Biological Engineering