Temporal interference stimulation of the hippocampus during sleep modulates memory consolidation
Poster No:
21
Submission Type:
Abstract Submission
Authors:
Prince Okyere1, Tobias Raufeisen1, Valeria Jaramillo1, Roi Cohen Kadosh1, Nir Grossman2, Derk-Jan Dijk1, Ullrich Bartsch1, Ines Violante3
Institutions:
1University of surrey, Guildford, Surrey, 2Imperial college, London, 3King's College London, London
First Author:
Co-Author(s):
Introduction:
Sleep-dependent memory consolidation is thought to rely on a temporally coordinated crosstalk between cortical slow waves (0.5-4 Hz), thalamocortical sleep spindles (12-15 Hz), and hippocampal ripples (80-120 Hz)(Staresina et al., 2015). Interactions between these rhythms are likely bidirectional, involving top-down and bottom-up mechanisms. Animal studies have demonstrated that augmenting hippocampal ripple activity with electrical stimulation enhances cortical slow waves and sleep spindles and improves memory performance (Maingret et al., 2016). However, research into hippocampal-cortical oscillatory coupling and sleep-dependent memory consolidation in humans remains largely correlational.
Here, we deployed Temporal Interference Stimulation (TIS), a novel non-invasive brain stimulation approach capable of selectively modulating activity of deep brain structures (Violante et al., 2023), to target the human hippocampus during sleep. We combined TIS with targeted memory reactivation (TMR) during the N2/N3 stages of an afternoon nap, while simultaneously recording brain activity using EEG. We hypothesised that the timing at which TIS was delivered would affect brain activity and memory consolidation.
Here, we deployed Temporal Interference Stimulation (TIS), a novel non-invasive brain stimulation approach capable of selectively modulating activity of deep brain structures (Violante et al., 2023), to target the human hippocampus during sleep. We combined TIS with targeted memory reactivation (TMR) during the N2/N3 stages of an afternoon nap, while simultaneously recording brain activity using EEG. We hypothesised that the timing at which TIS was delivered would affect brain activity and memory consolidation.
Methods:
Participants: N=28, (mean age: 26 y.o.,15 males) participated in two experimental sessions (MRI acquisition and nap).
Task: Associative memory task (word-image pairs). Words were presented auditorily, during pre-nap and nap.
TMR and TIS conditions: Words presented pre-nap (TMR Cues) were distributed into 4 categories: 1) simultaneous TIS and Cue (TIS+Cue), 2) TIS before Cue (TIS+Cue delayed), 3) Cue only (Cue) and 4) Non-Cue. Foils indicate novel words presented during the nap (Fig 1a).
TIS: 90 Hz beat frequency (f1=2000 Hz and f2=2090 Hz), I1=1 mA, I2=3 mA, 4 s duration, targeting left anterior hippocampus
EEG: 64-channel BrainProducts EEG. Preprocessing in EEGLAB toolbox. Sleep spindles detected through YASA toolbox (frequency: 12–16 Hz, durations: 0.5 - 3 s after presentation of Cue).
Task: Associative memory task (word-image pairs). Words were presented auditorily, during pre-nap and nap.
TMR and TIS conditions: Words presented pre-nap (TMR Cues) were distributed into 4 categories: 1) simultaneous TIS and Cue (TIS+Cue), 2) TIS before Cue (TIS+Cue delayed), 3) Cue only (Cue) and 4) Non-Cue. Foils indicate novel words presented during the nap (Fig 1a).
TIS: 90 Hz beat frequency (f1=2000 Hz and f2=2090 Hz), I1=1 mA, I2=3 mA, 4 s duration, targeting left anterior hippocampus
EEG: 64-channel BrainProducts EEG. Preprocessing in EEGLAB toolbox. Sleep spindles detected through YASA toolbox (frequency: 12–16 Hz, durations: 0.5 - 3 s after presentation of Cue).
Results:
1. TIS was successfully delivered during sleep and simultaneous EEG
Participants total average sleep was 49.48 ± 14.14 mins, N1=20.35 ± 12.11%, N2=69.42 ± 15.07%, N3=10.04 ± 14.57%, and REM=0.19± 0.99%. Sleep was not disrupted by stimulation (Fig. 1b). There was no difference in the amount of N2+N3 between stimulation conditions (F=1.13, p=0.33), and there was no difference in the number of words played across conditions (F=0.95, p=0.41, Fig. 1d); indicating successful delivery of TMR and TIS during a nap.
2.TIS timing influences spindle density
There was a significant main effect of condition on spindle density (F=5.89, p=0.005). TIS delivered synchronously with the presentation of the cue (TIS + Cue) significantly increased spindle density as compared to TIS + Cue delayed (p=0.001). Cue presentation significantly increased spindle density compared to TIS + Cue delayed (p=0.043). There was no significant difference between TIS with cue presentation and Cue presentation (p=0.246), (Fig.2a).
3.TIS timing affects memory consolidation
There was a significant main effect of condition on memory performance (F=2.61, p=0.049). Post-nap scores showed that when TIS was delivered synchronously with the presentation of the cue (TIS+Cue) there was a significant improvement in memory performance compared to the desynchronised (TIS + Cue delayed) (p=0.009), and Non-Cue conditions (p=0.043). No significant differences were observed between TIS+Cue and Cue presentation (p=0.313), between Cue and Non-Cue (p=0.312), and between Cue and TIS+Cue delayed (p=0.113), (Fig 2b).
Participants total average sleep was 49.48 ± 14.14 mins, N1=20.35 ± 12.11%, N2=69.42 ± 15.07%, N3=10.04 ± 14.57%, and REM=0.19± 0.99%. Sleep was not disrupted by stimulation (Fig. 1b). There was no difference in the amount of N2+N3 between stimulation conditions (F=1.13, p=0.33), and there was no difference in the number of words played across conditions (F=0.95, p=0.41, Fig. 1d); indicating successful delivery of TMR and TIS during a nap.
2.TIS timing influences spindle density
There was a significant main effect of condition on spindle density (F=5.89, p=0.005). TIS delivered synchronously with the presentation of the cue (TIS + Cue) significantly increased spindle density as compared to TIS + Cue delayed (p=0.001). Cue presentation significantly increased spindle density compared to TIS + Cue delayed (p=0.043). There was no significant difference between TIS with cue presentation and Cue presentation (p=0.246), (Fig.2a).
3.TIS timing affects memory consolidation
There was a significant main effect of condition on memory performance (F=2.61, p=0.049). Post-nap scores showed that when TIS was delivered synchronously with the presentation of the cue (TIS+Cue) there was a significant improvement in memory performance compared to the desynchronised (TIS + Cue delayed) (p=0.009), and Non-Cue conditions (p=0.043). No significant differences were observed between TIS+Cue and Cue presentation (p=0.313), between Cue and Non-Cue (p=0.312), and between Cue and TIS+Cue delayed (p=0.113), (Fig 2b).
Conclusions:
We show for the first time that it is feasible to perform simultaneous TIS and EEG recordings during sleep, and that we can detect and quantify electrophysiological signatures characteristic of NREM sleep. In addition, our results suggest that TIS to the hippocampus during sleep might interact with the processes of memory reactivation to modulate sleep-dependent memory consolidation.
Brain Stimulation:
Deep Brain Stimulation
Non-invasive Electrical/tDCS/tACS/tRNS 1
Learning and Memory:
Long-Term Memory (Episodic and Semantic) 2
Modeling and Analysis Methods:
EEG/MEG Modeling and Analysis
Keywords:
Electroencephaolography (EEG)
Memory
Sleep
Systems
Other - Temporal Interference; Hippocampus; TMR
1|2Indicates the priority used for review
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Provide references using APA citation style.
Staresina, B. P. (2015). Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nature Neuroscience, 18(11), 1679–1686.
Violante, I. R. (2023). Non-invasive temporal interference electrical stimulation of the human hippocampus. Nature Neuroscience, 26(11), 1994–2004.