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Ripple contributions to human memory: making the spiking content count

Nature Reviews Neuroscience volume 26, pages 698–714 (2025)Cite this article

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Abstract

Memories shape our sense of self and enable adaptive behaviour based on prior experiences, yet the neural mechanisms underlying memory formation and retrieval are not fully understood. Building on work in animal models and the unique opportunities afforded by intracranial recordings, a growing number of studies have focused on the contributions of awake ripples (transient neural oscillations 20–100 ms long in the 80–150 Hz range) to human memory. Here, we review the body of evidence linking awake ripples to human memory and highlight relevant insights as well as unresolved discrepancies between studies. On the basis of previous evidence from work in animals that ripples may provide a biomarker for bursts of underlying population spiking activity, we suggest that examining the underlying spike content of ripples may help clarify their role in human memory and resolve these discrepancies. Recent support for this notion comes from human studies that, similarly to the prior animal work, relate patterns of neuronal spiking activity to ripples. Thus, our ability to understand the role of ripples in human memory may benefit from fully understanding these spiking events.

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Fig. 1: Spontaneously occurring human ripples.
Fig. 2: Ripples during human memory encoding, post-encoding and recall.
Fig. 3: Ripples signal transient increases in spiking activity.
Fig. 4: Involvement of ripple-locked spike sequences at different memory stages.
Fig. 5: Ripple activity and the underlying spike content.

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Acknowledgements

This review was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.

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  1. These authors contributed equally: Joel Reithler, Kelsey K. Sundby.

Authors and Affiliations

  1. Cognitive Neuroscience Department, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands

    Joel Reithler

  2. Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA

    Kelsey K. Sundby & Kareem A. Zaghloul

Authors
  1. Joel Reithler
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  2. Kelsey K. Sundby
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  3. Kareem A. Zaghloul
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Contributions

J.R. and K.K.S. researched data for the article. All authors contributed substantially to discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Joel Reithler, Kelsey K. Sundby or Kareem A. Zaghloul.

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Nature Reviews Neuroscience thanks Jack Lin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Deep learning

A machine learning approach that uses multilayered artificial neural networks to learn from data.

Gamma oscillations

High-frequency (~30–100 Hz) rhythmic electrical signals in the brain that are associated with several cognitive processes, including attention and memory.

High-frequency oscillations

A broad class of transient bursts of neural activity typically with a frequency between 80 and 250 Hz. This category includes, but is not limited to, the narrower ripple band used in most human studies.

Interictal epileptiform discharges

(IEDs). Pathological electrical activity indicated by hypersynchronization across electrodes between seizures in individuals with epilepsy. Unlike physiological ripples, IEDs do not consist of multiple oscillation cycles and they result in broadband high-frequency changes rather than the narrow band peak characteristic of ripples.

Intracranial recordings

Recordings of the brain’s electrical activity from electrodes placed intracranially directly on the surface of the brain or in deeper brain tissue. In humans, this type of recording is only available in rare circumstances in which the recordings are expected to provide critical clinical insights.

Local field potential

(LFP). An electrophysiological signal that reflects the summed activity of a local population of neurons recorded with intracranial electrodes.

Neuronal assemblies

Groups of neurons that exhibit coordinated activity.

One-shot learning

The acquisition of memories and new associations from a single exposure.

Paired associate tasks

A paradigm commonly used in human memory research that typically consists of two phases: encoding and retrieval. During encoding, participants are instructed to try to remember the association between two items they are shown. During retrieval, participants are shown one member of a previously learned pair and asked to recall the associated member.

Place cell

A neuron, typically found in the hippocampus, that selectively fires when an animal is in a specific location within an environment.

Population spiking activity

(Also known as spike bursts). Synchronized population-level increases in the firing of single units.

Replay

The reoccurrence of neural activity patterns recorded during a previous experience, in which their temporal structure is retained (as opposed to ‘reactivations’ which are reinstatements of previous activity patterns lacking these temporal dynamics).

Ripples

Transient oscillations in neural activity 20–100 ms long with frequencies in the 80–150 Hz range.

Sharp wave-ripple complexes

Sets of interdependent neurophysiological events specifically recorded in hippocampal subfield CA1, characterized by a pronounced negative local field potential (LFP) deflection (sharp wave) reflecting afferent excitation accompanied by a transient high-frequency oscillation (ripple).

Slow oscillations

Low-frequency (<1 Hz) rhythmic electrical brain signals that typically arise during slow-wave sleep or deep anaesthesia.

Spikes

Recorded discharges of single units, captured in humans using depth microwires or arrays of microelectrodes placed over cortical regions.

Spindle

A short burst of brain activity of ~11–16 Hz that occurs during non-rapid eye movement (NREM) sleep and is thought to contribute to memory consolidation.

Systems consolidation

A process by which newly formed memory representations transition from storage in the hippocampus to the cortex.

Theta oscillations

Low-frequency (~4–8 Hz) rhythmic electrical signals in the brain associated with several memory processes.

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Reithler, J., Sundby, K.K. & Zaghloul, K.A. Ripple contributions to human memory: making the spiking content count. Nat. Rev. Neurosci. 26, 698–714 (2025). https://doi.org/10.1038/s41583-025-00971-w

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