Pathological neurons generate ripples at the UP-DOWN transition disrupting information transfer

Shennan A Weiss; Itzhak Fried; Jerome Engel Jr; Anatol Bragin; Shuang Wang; Michael R Sperling; Robert K S Wong; Yuval Nir; Richard J Staba

doi:10.1111/epi.17845

Pathological neurons generate ripples at the UP-DOWN transition disrupting information transfer

Epilepsia. 2024 Feb;65(2):362-377. doi: 10.1111/epi.17845. Epub 2023 Dec 14.

Authors

Shennan A Weiss^{1

2

3}, Itzhak Fried⁴, Jerome Engel Jr^{4

5

6

7

8}, Anatol Bragin⁵, Shuang Wang⁹, Michael R Sperling¹⁰, Robert K S Wong², Yuval Nir^{11

12

13

14}, Richard J Staba⁵

Affiliations

¹ Department of Neurology, State University of New York Downstate, Brooklyn, New York, USA.
² Departments of Physiology and Pharmacology, State University of New York Downstate, Brooklyn, New York, USA.
³ Department of Neurology, New York City Health + Hospitals/Kings County, Brooklyn, New York, USA.
⁴ Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁵ Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁶ Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁷ Departments of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁸ Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁹ Department of Neurology, Epilepsy Center, Second Affiliated Hospital of Medical College, Zhejiang University, Zhejiang, China.
¹⁰ Departments of Neurology and Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
¹¹ Departments of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹² Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
¹³ Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.
¹⁴ The Sieratzki-Sagol Center for Sleep Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

PMID: 38041560
PMCID: PMC10922301 (available on 2025-02-01)
DOI: 10.1111/epi.17845

Abstract

Objective: To confirm and investigate why pathological high-frequency oscillations (pHFOs), including ripples (80-200 Hz) and fast ripples (200-600 Hz), are generated during the UP-DOWN transition of the slow wave and if information transmission mediated by ripple temporal coupling is disrupted in the seizure-onset zone (SOZ).

Methods: We isolated 217 total units from 175.95 intracranial electroencephalography (iEEG) contact-hours of synchronized macro- and microelectrode recordings from 6 patients. Sleep slow oscillation (.1-2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the SOZ, HFOs and associated action potentials (APs) occur more often at the UP-DOWN transition. We also examined ripple temporal correlations using cross-correlograms.

Results: At the group level in the SOZ, HFO and HFO-associated AP probability was highest during the UP-DOWN transition of slow wave excitability (p < < .001). In the non-SOZ, HFO and HFO-associated AP was highest during the DOWN-UP transition (p < < .001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d = .11-.83) and fast ripples (d = .36-.90) at the UP-DOWN transition (p < .05 f.d.r. corrected), respectively. By comparison, also in the SOZ, 6.6% (d = .14-.30) and 8.5% (d = .33-.41) of units had significantly less firing during ripples and fast ripples at the UP-DOWN transition, respectively. Additional data shows that ripple and fast ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by >50% in the SOZ compared to the non-SOZ (N = 3).

Significance: The UP-DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. Ripple temporal correlations across brain regions may be important in memory consolidation and are disrupted in the SOZ, perhaps by pHFO generation.

Keywords: fast ripple; high-frequency oscillation; ripple; sleep; slow wave.

MeSH terms

Brain
Brain Waves* / physiology
Electrocorticography*
Electroencephalography
Humans
Parahippocampal Gyrus
Sleep / physiology

Abstract

MeSH terms

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