Electrical Nerve Stimulation During Sleep for Memory Consolidation

Effects of 2 Hz and 120 Hz Transcutaneous Electrical Nerve Stimulation During Sleep on Procedural Memory and Working Memory: A Randomized, Sham-Controlled, Crossover Study

The purpose of this study is to investigate the effects of transcutaneous electrical nerve stimulation (eTNS) applied during sleep on memory consolidation and brain-body physiological coupling. Healthy college students will participate in four overnight sleep sessions in a standard sleep laboratory.

Before going to sleep, participants will learn and complete two cognitive tasks: a motor sequence tapping task to assess procedural memory, and an N-back task to assess working memory. During the night, participants will receive either 2 Hz eTNS, 120 Hz eTNS, or a sham (placebo) stimulation on their forehead in a randomized order. Throughout the night, researchers will record their sleep using polysomnography (PSG), along with continuous monitoring of heart rate (ECG) and breathing (respiration). Upon waking the next morning, participants will be re-tested on both memory tasks.

The primary objective is to determine whether eTNS during sleep can improve behavioral performance on procedural and working memory tasks overnight. Secondary objectives include analyzing the stimulation's effects on specific sleep brain wave patterns (such as slow oscillations and sleep spindles) and exploring the coupling mechanisms between brain activity, heart rhythms (Heartbeat Evoked Potentials), and respiration during sleep.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers (HV); Memory Consolidation; Sleep Physiology
• Intervention / Treatment: Device: 120 Hz Transcutaneous Electrical Nerve Stimulation; Device: 2 Hz Transcutaneous Electrical Nerve Stimulation; Device: Sham Stimulation (Placebo)

Detailed Description

This study utilizes a randomized, double-blind, sham-controlled, within-subject crossover design to evaluate the modulatory effects of transcutaneous electrical nerve stimulation (eTNS) during sleep on memory consolidation and cardiopulmonary-brain coupling.

Healthy young adults will be recruited and rigorously screened to exclude those with sleep disorders, neurological or psychiatric conditions, or recent use of medications affecting sleep or cognition. Each participant will complete four overnight sessions in a standard soundproof and lightproof sleep laboratory, separated by 5-7 days. The first night serves as an adaptation night with no stimulation or data collection. The subsequent three nights involve experimental recordings under varying stimulation conditions (2 Hz eTNS, 120 Hz eTNS, and sham stimulation) applied in a randomized order.

Experimental Procedure:

On experimental nights, participants will arrive at the laboratory at 21:00. Prior to sleep, participants will undergo a training and baseline testing phase for two distinct cognitive tasks: a procedural memory task (the classic sequential finger-tapping task) and a working memory task (the 2- to 5-back task). Following the pre-sleep tasks, participants will be fitted with polysomnography (PSG) equipment, electrocardiogram (ECG) sensors, and respiratory monitors. Lights-out is scheduled for 23:00. Upon awakening between 07:00 and 08:00 the following morning, participants will be re-tested on both the sequential finger-tapping task and the N-back task to assess overnight memory consolidation.

Stimulation Parameters:

During sleep, eTNS will be delivered via a three-channel current source stimulator connected to self-adhesive silicone electrodes placed above the left and right eyebrows. The stimulation consists of biphasic rectangular pulses with a 250 μs pulse width. For the active conditions (120 Hz or 2 Hz), the current is delivered in cycles of 30 seconds on and 30 seconds off. The current intensity will be titrated to a subjective score of 3-4 on a numerical rating scale (NRS), perceived as a mild tingling sensation that does not disrupt sleep. The sham condition delivers current only for the first two minutes (the first two cycles) to mimic the initial sensation of the active conditions. All stimulations automatically terminate after a maximum duration of 8 hours.

Data Collection and Analysis Framework:

Continuous PSG recording (including standard EEG, EOG, and EMG based on the international 10-20 system) will be synchronized with simultaneous ECG and respiration data. The study will primarily compare the pre- and post-sleep behavioral improvements across the three stimulation conditions. Furthermore, the neurophysiological data will be analyzed to extract sleep structural features, slow oscillation (SO) and sleep spindle metrics, and complex physiological interactions. Specific focus will be placed on SO-spindle coupling, SO-respiration coupling, and Heartbeat Evoked Potentials (HEP) to elucidate the underlying neural and autonomic mechanisms by which peripheral stimulation influences cognitive functions during sleep.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xue-Juan Yang; Phone Number: 13227038185; Email: xjyang@xidian.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 71000
      • Recruiting
      • Xidian University
      • Contact: Xue-Juan Yang; Phone Number: 13227038185; Email: xjyang@xidian.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy young adults (e.g., college students), aged generally between 18 and 30 years.
2. Right-handed.
3. Body Mass Index (BMI) ≤ 30 kg/m^2.
4. Capable of fully comprehending the experimental procedures and voluntarily signing the informed consent form.

Exclusion Criteria:

1. History or current presence of neurological disorders, psychiatric disorders, or brain damage.
2. History or current presence of cardiovascular diseases (e.g., arrhythmias or abnormal nocturnal heart rate).
3. Presence of depressive or anxiety symptoms (assessed by Patient Health Questionnaire-9 [PHQ-9] score > 9, or Generalized Anxiety Disorder-7 [GAD-7] score > 9).
4. Presence of sleep disturbances or poor sleep quality (assessed by Insomnia Severity Index [ISI] score > 8, or Pittsburgh Sleep Quality Index [PSQI] score > 10).
5. Any medication use within the past six months that could affect stress responses, cognitive abilities, or sleep architecture.
6. History of smoking or alcohol abuse.
7. Known skin allergies to conductive paste, medical tape, or silicone electrodes.
8. Female participants who are in their menstrual period during the scheduled experimental sessions (sessions must be strategically scheduled to avoid this period).
9. Inability or refusal to abstain from caffeine, tea, and alcohol for at least 24 hours prior to and during the experimental sessions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 120 Hz Transcutaneous Electrical Nerve Stimulation	Device: 120 Hz Transcutaneous Electrical Nerve Stimulation; Participants will receive 120 Hz transcutaneous electrical nerve stimulation (eTNS) during nighttime sleep. The stimulation is delivered via a current source stimulator connected to self-adhesive silicone electrodes placed above the left and right eyebrows. The stimulation consists of biphasic rectangular pulses with a 250 μs pulse width at a frequency of 120 Hz. It is delivered in continuous cycles of 30 seconds on and 30 seconds off. Before sleep, the current intensity is individually titrated to elicit a mild tingling sensation (corresponding to a score of 3-4 on a numerical rating scale) that will not disrupt the participant's sleep. The stimulation protocol automatically terminates after a duration of 8 hours.
Experimental: 2 Hz Transcutaneous Electrical Nerve Stimulation	Device: 2 Hz Transcutaneous Electrical Nerve Stimulation; Participants will receive 2 Hz transcutaneous electrical nerve stimulation (eTNS) during nighttime sleep. The stimulation is delivered via a current source stimulator connected to self-adhesive silicone electrodes placed above the left and right eyebrows. The stimulation consists of biphasic rectangular pulses with a 250 μs pulse width at a frequency of 2 Hz. It is delivered in continuous cycles of 30 seconds on and 30 seconds off. Before sleep, the current intensity is individually titrated to elicit a mild tingling sensation (corresponding to a score of 3-4 on a numerical rating scale) that will not disrupt the participant's sleep. The stimulation protocol automatically terminates after a duration of 8 hours.
Placebo Comparator: Sham Stimulation (Placebo)	Device: Sham Stimulation (Placebo); Participants will receive a sham stimulation designed to serve as a placebo control. The equipment setup, including the placement of self-adhesive silicone electrodes above the left and right eyebrows, is identical to the active eTNS conditions. The current intensity is initially adjusted before sleep to elicit the same mild tingling sensation (a score of 3-4 on a numerical rating scale). However, to maintain double-blinding without providing a therapeutic dose, the stimulator only delivers current output during the first 2 minutes of the night (i.e., exactly two cycles of 30 seconds on and 30 seconds off). After these initial 2 minutes, the current output ceases entirely for the remainder of the 8-hour sleep period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Procedural Memory Performance	Procedural memory consolidation will be assessed using the classic sequential finger-tapping task (SFTT). Performance improvement is calculated as the difference in speed (number of correct sequences typed) and accuracy between the pre-sleep training/testing session and the post-sleep testing session. A larger positive difference indicates better procedural memory consolidation overnight.	Assessed pre-sleep (approx. 21:00-22:00) and post-sleep (approx. 07:00-08:00 the following morning), representing an overnight interval of approximately 10 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Working Memory Performance	Working memory performance will be assessed using the 2- to 5-back task. Outcome metrics include reaction time and accuracy (hit rate and false alarm rate). The overnight change is calculated by comparing the performance in the post-sleep testing session to the pre-sleep baseline session. Higher accuracy and shorter reaction times indicate improved working memory function.	Assessed pre-sleep (approx. 21:00-22:00) and post-sleep (approx. 07:00-08:00 the following morning), representing an overnight interval of approximately 10 hours.
Sleep Architecture and Sleep Efficiency	Sleep architecture will be derived from PSG scoring according to the American Academy of Sleep Medicine (AASM) criteria. Key metrics include Total Sleep Time (TST), Sleep Efficiency (SE, calculated as TST divided by Time in Bed), and the percentage of time spent in different sleep stages (N1, N2, N3, and REM sleep). This ensures the stimulation does not negatively disrupt normal sleep patterns.	Continuously recorded during the 8-hour nighttime sleep period.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep Slow Oscillation (SO) Density and Amplitude	Extracted from continuous Polysomnography (PSG) recordings (specifically at C3 and C4 channels). SO density (number of slow oscillations per minute) and peak-to-peak amplitude will be analyzed during Non-Rapid Eye Movement (NREM) sleep stages 2 and 3 to evaluate the depth and quality of slow-wave sleep.	Continuously recorded during the 8-hour nighttime sleep period (from lights out at 23:00 to waking up between 07:00 and 08:00).
Sleep Spindle Density and Amplitude	Extracted from PSG recordings at central electrodes (C3, C4). Fast sleep spindle density (number of spindles per minute) and amplitude will be calculated during NREM sleep stages 2 and 3.	Continuously recorded during the 8-hour nighttime sleep period.
Slow Oscillation-Spindle Coupling	This coupling will be evaluated by calculating the SO-spindle coupling ratio (the proportion of spindles coupled with SOs relative to the total number of spindles) and the preferred phase angle of spindle maxima relative to the SO phase. This metric reflects the coordination of memory-related brain rhythms.	Continuously recorded during the 8-hour nighttime sleep period.
Brain-Body Coupling: SO-Respiration Synchronization	Evaluated by analyzing the phase-locking or temporal synchronization between respiratory phases (extracted from simultaneous respiratory monitor data) and the occurrence/phase of sleep slow oscillations (extracted from EEG) during NREM sleep.	Continuously recorded during the 8-hour nighttime sleep period.
Brain-Body Coupling: Heartbeat Evoked Potentials (HEP)	HEP amplitude will be calculated by time-locking the EEG signals to the R-peaks of the simultaneous electrocardiogram (ECG) data during sleep. This measure assesses the cortical representation of afferent cardiac signals and heart-brain interactions.	Continuously recorded during the 8-hour nighttime sleep period.

Collaborators and Investigators

• Sponsor: Xidian University

Study record dates

Study Major Dates

• Study Start (Estimated): June 16, 2026
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Polysomnography; Working Memory; Transcutaneous Electrical Nerve Stimulation; eTNS; Procedural Memory; Slow Oscillations; Sleep Spindles; Heartbeat Evoked Potentials
• Other Study ID Numbers: 20260615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No