Control of working memory by phase-amplitude coupling of human hippocampal neurons

Jonathan Daume; Jan Kamiński; Andrea G P Schjetnan; Yousef Salimpour; Umais Khan; Michael Kyzar; Chrystal M Reed; William S Anderson; Taufik A Valiante; Adam N Mamelak; Ueli Rutishauser

doi:10.1038/s41586-024-07309-z

Control of working memory by phase-amplitude coupling of human hippocampal neurons

Nature. 2024 Apr 17. doi: 10.1038/s41586-024-07309-z. Online ahead of print.

Authors

Jonathan Daume^{1

2

3}, Jan Kamiński^{4

5}, Andrea G P Schjetnan⁶, Yousef Salimpour⁷, Umais Khan⁴, Michael Kyzar⁴, Chrystal M Reed⁸, William S Anderson⁷, Taufik A Valiante⁶, Adam N Mamelak⁴, Ueli Rutishauser^{9

10

11

12}

Affiliations

¹ Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. jonathan.daume@cshs.org.
² Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. jonathan.daume@cshs.org.
³ Center for Neural Science and Medicine, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. jonathan.daume@cshs.org.
⁴ Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵ Center of Excellence for Neural Plasticity and Brain Disorders: BRAINCITY, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
⁶ Krembil Research Institute and Division of Neurosurgery, University Health Network (UHN), University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA. ueli.rutishauser@cshs.org.
¹⁰ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. ueli.rutishauser@cshs.org.
¹¹ Center for Neural Science and Medicine, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. ueli.rutishauser@cshs.org.
¹² Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. ueli.rutishauser@cshs.org.

PMID: 38632400
DOI: 10.1038/s41586-024-07309-z

Abstract

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference^1,2. 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 memory^1,2, with frontal control managing maintenance of working memory content in storage-related areas^3-5. 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.