Human hippocampal responses to network intracranial stimulation vary with theta phase

  1. Sarah M Lurie  Is a corresponding author
  2. James E Kragel
  3. Stephan U Schuele
  4. Joel L Voss
  1. Northwestern University, United States
  2. University of Chicago, United States

Abstract

Hippocampal-dependent memory is thought to be supported by distinct connectivity states, with strong input to the hippocampus benefitting encoding and weak input benefitting retrieval. Previous research in rodents suggests that the hippocampal theta oscillation orchestrates the transition between these states, with opposite phase angles predicting minimal versus maximal input. We investigated whether this phase dependence exists in humans using network-targeted intracranial stimulation. Intracranial local field potentials were recorded from individuals with epilepsy undergoing medically necessary stereotactic electroencephalographic recording. In each subject, biphasic bipolar direct electrical stimulation was delivered to lateral temporal sites with demonstrated connectivity to hippocampus. Lateral temporal stimulation evoked ipsilateral hippocampal potentials with distinct early and late components. Using evoked component amplitude to measure functional connectivity, we assessed whether the phase of hippocampal theta predicted relatively high versus low connectivity. We observed an increase in the continuous phase-amplitude relationship selective to the early and late components of the response evoked by lateral temporal stimulation. The maximal difference in these evoked component amplitudes occurred across 180 degrees of separation in the hippocampal theta rhythm; i.e., the greatest difference in component amplitude was observed when stimulation was delivered at theta peak versus trough. The pattern of theta phase dependence observed for hippocampus was not identified for control locations. These findings demonstrate that hippocampal receptivity to input varies with theta phase, suggesting that theta phase reflects connectivity states of human hippocampal networks. These findings confirm a putative mechanism by which neural oscillations modulate human hippocampal function.

Data availability

All iEEG data and custom analysis scripts have been made publicly available on Zenodo (doi: 10.5281/zenodo.6342237)

The following data sets were generated

Article and author information

Author details

  1. Sarah M Lurie

    Northwestern University, Chicago, United States
    For correspondence
    smr.lurie@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2986-688X
  2. James E Kragel

    Department of Neurology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Stephan U Schuele

    Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Joel L Voss

    Department of Neurology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Neurological Disorders and Stroke (R01NS113804)

  • Joel L Voss

National Institute of Mental Health (F31MH125577)

  • Sarah M Lurie

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joshua Jacobs, Columbia University, United States

Ethics

Human subjects: All subjects provided written informed consent prior to participation. Study protocols were approved by the Northwestern University Institutional Review Board (STU00210599).

Version history

  1. Preprint posted: March 2, 2022 (view preprint)
  2. Received: March 5, 2022
  3. Accepted: November 30, 2022
  4. Accepted Manuscript published: December 1, 2022 (version 1)
  5. Version of Record published: December 8, 2022 (version 2)

Copyright

© 2022, Lurie et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,307
    views
  • 181
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sarah M Lurie
  2. James E Kragel
  3. Stephan U Schuele
  4. Joel L Voss
(2022)
Human hippocampal responses to network intracranial stimulation vary with theta phase
eLife 11:e78395.
https://doi.org/10.7554/eLife.78395

Share this article

https://doi.org/10.7554/eLife.78395

Further reading

    1. Neuroscience
    Ladan Shahshahani, Maedbh King ... Jörn Diedrichsen
    Research Article

    Functional magnetic resonance imaging (fMRI) studies have documented cerebellar activity across a wide array of tasks. However, the functional contribution of the cerebellum within these task domains remains unclear because cerebellar activity is often studied in isolation. This is problematic, as cerebellar fMRI activity may simply reflect the transmission of neocortical activity through fixed connections. Here, we present a new approach that addresses this problem. Rather than focus on task-dependent activity changes in the cerebellum alone, we ask if neocortical inputs to the cerebellum are gated in a task-dependent manner. We hypothesize that input is upregulated when the cerebellum functionally contributes to a task. We first validated this approach using a finger movement task, where the integrity of the cerebellum has been shown to be essential for the coordination of rapid alternating movements but not for force generation. While both neocortical and cerebellar activity increased with increasing speed and force, the speed-related changes in the cerebellum were larger than predicted by an optimized cortico-cerebellar connectivity model. We then applied the same approach in a cognitive domain, assessing how the cerebellum supports working memory. Enhanced gating was associated with the encoding of items in working memory, but not with the manipulation or retrieval of the items. Focusing on task-dependent gating of neocortical inputs to the cerebellum offers a promising approach for using fMRI to understand the specific contributions of the cerebellum to cognitive function.

    1. Neuroscience
    Anna Seggewisse, Michael Winding
    Insight

    The first neuronal wiring diagram of an insect nerve cord, which includes biological information on cell type and organisation, enables further investigation into premotor circuit function.