Effects of Gamma-tACS on Memory and Sleep

Effects of Transcranial Alternating Current Stimulation (tACS) at Gamma Band Frequencies on Memory Recall and Sleep in Healthy Elderly Participants

The purpose of this clinical trial is to investigate the feasibility and efficacy of non-invasive transcranial alternating current stimulation (tACS) at gamma frequency in enhancing memory recall and modulating sleep network dynamics measured by at-home electroencephalography (EEG) in healthy elderly people. Eligible participants will first collect sleep EEG at home for one night to acclimate to the data collection during sleep. Participants are then randomized into first undergoing either tACS at gamma band frequencies (i.e. 40Hz) or tACS at a control frequency (i.e. 21Hz). Stimulation is administered in the lab during a cognitive testing battery that includes memorizing items. After a night of sleep with EEG at home, participants return to the lab the following day to measure memory recall. Recall is performed again after five days. This sequence of encoding during stimulation in the lab, sleep EEG at home for one night, and recall is then repeated for the other stimulation condition about a week later. Participants are wearing an actigraphy wristband throughout the study period.

Study Overview

• Status: Completed
• Conditions: Sleep; Aging; Cognitive Decline; Memory; Transcranial Alternating Current Stimulation
• Intervention / Treatment: Device: Gamma transcranial alternating current stimulation; Device: Control transcranial alternating current stimulation; Device: EEG headband; Device: Actigraphy wristband

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27516
      • Carolina Center for Neurostimulation

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• >50 years old

Exclusion Criteria:

• Implanted device or metal in head (including cochlear implant or other hearing aid), cardiac pacemaker or any other powered medical device
• Known neurological disease from history (epilepsy, sleep disorder (insomnia, sleep apnea, restless legs syndrome, parasomnia), stroke or transitory ischemic attack, cognitive impairment, neurodegenerative disease (for example Alzheimer's disease, Parkinson's disease or amyotrophic lateral sclerosis), immune-mediated disease of the central nervous system, chronic infectious brain disease, brain tumor, traumatic brain injury with loss of consciousness and/or intracranial bleeding, chronic pain with the need for daily analgesic use)
• Positive screening for epilepsy (questionnaire)
• Pathological Montreal Cognitive Assessment (MoCA <26/30 points)
• Brain surgery in the past (lifetime)
• Known psychiatric disorder from history (schizophrenia (lifetime), obsessive compulsive disorder (OCD; lifetime), borderline personality disorder (lifetime), anxiety disorder (lifetime), bipolar disorder (lifetime), psychosis (lifetime), eating disorder (lifetime), depression (within the last three months)
• Positive screening for anxiety disorder (GAD-7 ≥10/21 points) or positive screening for depression (PHQ-9 ≥5/27 points)
• Known other relevant medical condition from history (moderate to severe chronic obstructive pulmonary disease (COPD), abnormal kidney function (defined as estimated Glomerular Filtration Rate <60ml/min), current liver disease (defined as hepatitis and/or liver cirrhosis), cancer, diabetes mellitus, cardiac disease (heart failure, myocardial infarct, atrial fibrillation and revascularization - all within the last three months)
• Working in night shifts or going to bed after midnight on 3 or more nights per week
• Positive screening for sleep disorder (PSQI >5/21 points)
• Psychotropic treatment or illegal drugs (including cannabis) within the last three months
• Indication for alcohol use disorder: AUDIT score (Alcohol Use Disorders Identification Test; screening for unhealthy alcohol use) ≥7 for females and for males ≥ 65 years or ≥8 for males <65 years
• Not willing to abstain alcohol at least 24 hours before each study visit
• Pregnancy, planned pregnancy, fertility treatment planned or ongoing
• Having experienced an adverse event in the past after receiving Transcranial Magnetic Stimulation (TMS)
• If, after filling out a questionnaire on the participant's medical history that informs researchers of relevant events that marginally increase the risk of an adverse event occurring during TMS, researchers will exercise their expert judgement to determine whether that participant should be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First gamma (40Hz) stimulation, then active control (21Hz) stimulation; After collecting sleep EEG at home for one night to acclimate to the data collection during sleep, participants first receive gamma (40Hz) tACS on Day 1 followed by a 5-9 day washout. Participants then receive active control (21Hz) stimulation.	Device: Gamma transcranial alternating current stimulation; tACS (gamma frequency, 40Hz) during cognitive testing (about 40 minutes duration).; Other Names: DC-STIMULATOR MC Stimulator Plus; Device: Control transcranial alternating current stimulation; tACS (control frequency, 21Hz) during cognitive testing (about 40 minutes duration).; Other Names: DC-STIMULATOR MC Stimulator Plus; Device: EEG headband; At-home, ambulatory, single-channel EEG headband which records brain activity during sleep; Other Names: ULTEEMNite; Device: Actigraphy wristband; At-home, ambulatory, wrist-worn accelerometer which records levels of motor activity during the whole day
Experimental: First active control (21 Hz) stimulation, then gamma (40 Hz) stimulation; After collecting sleep EEG at home for one night to acclimate to the data collection during sleep, participants first receive active control (21Hz) tACS on Day 1 followed by a 5-9 day washout. Participants then receive gamma (40Hz) stimulation.	Device: Gamma transcranial alternating current stimulation; tACS (gamma frequency, 40Hz) during cognitive testing (about 40 minutes duration).; Other Names: DC-STIMULATOR MC Stimulator Plus; Device: Control transcranial alternating current stimulation; tACS (control frequency, 21Hz) during cognitive testing (about 40 minutes duration).; Other Names: DC-STIMULATOR MC Stimulator Plus; Device: EEG headband; At-home, ambulatory, single-channel EEG headband which records brain activity during sleep; Other Names: ULTEEMNite; Device: Actigraphy wristband; At-home, ambulatory, wrist-worn accelerometer which records levels of motor activity during the whole day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Tolerating Cognitive Testing During tACS	To establish acceptability of tACS combined with cognitive testing in healthy elderly participants and will be considered acceptable if at least >/= 80% of participants tolerate the procedure.	Baseline (Day 1)
Verbal Memory at Day 1	Participants will memorize 15 words ("Rey Auditory Verbal Learning Test") during gamma-tACS or control-tACS. They will be required to recall the words on the same day. The number of correctly remembered words will be recorded.	Baseline (Day 1)
Verbal Memory at Day 2	Participants will memorize 15 words ("Rey Auditory Verbal Learning Test") during gamma-tACS or control-tACS. They will be required to recall the words on the day after. The number of correctly remembered words will be recorded.	Follow-Up (Day 2)
Verbal Memory at Day 5	Participants will memorize 15 words ("Rey Auditory Verbal Learning Test") during gamma-tACS or control-tACS. They will be required to recall the words after 5 days. The number of correctly remembered words will be recorded.	Follow-Up (Day 5)
Associative Verbal Memory at Day 1	Participants will memorize 8 word-pairs during gamma-tACS or control-tACS. They will be required to recall the pairs on the same day. The number of correctly remembered word pairs will be recorded.	Baseline (Day 1)
Associative Verbal Memory at Day 2	Participants will memorize 8 word-pairs during gamma-tACS or control-tACS. They will be required to recall the pairs on the day after. The number of correctly remembered word pairs will be recorded.	Follow-Up (Day 2)
Associative Verbal Memory at Day 5	Participants will memorize 8 word-pairs during gamma-tACS or control-tACS. They will be required to recall the pairs after 5 days. The number of correctly remembered word pairs will be recorded.	Follow-Up (Day 5)
Amount of Slow Wave Sleep in Sleep-EEG	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on the amount of slow wave sleep (deep/delta sleep) occuring during the night after the intervention. The amount of slow wave sleep during the first two hours of sleep-EEG will be counted.	Baseline (Day 1)
Percentage of Participants in Which it is Possible to Obtain at Least 4 Hours EEG Recording	To establish feasibility of at-home use of a single-channel EEG device during sleep. This will be considered feasible if the device has been worn for at least 4 hours during the first night for >/= 80% of participants.	Baseline (Day 1)
Percentage of Participants Who Wear the EEG Device During All Three Nights for at Least 4 Hours	To establish acceptability of at-home use of the single-channel EEG device during multiple nights. Acceptability will be considered as given if the device has been worn for at least 4 hours during each of the three nights in >/=80% of participants.	Baseline (Day 1)
Amount of Sleep Spindles in Sleep-EEG	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on the number of sleep spindles occuring during the night after the intervention. Sleep spindles during the first two hours of sleep-EEG will be counted. A sleep spindle is defined as a train of sinusoidal waves with frequency 11-16 Hz and a duration of at least 0.5 seconds.	Baseline (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance in Phonematic Fluency-Correct Words	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on a phonematic fluency-task during 1 minute. The number of correct words will be calculated.	Baseline (Day 1), Follow-Up (Day 2)
Performance in Phonematic Fluency-Rule Breaks	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on a phonematic fluency-task during 1 minute. Number of correct words, number of perseverations and number of rule breaks will be calculated.	Baseline (Day 1), Follow-Up (Day 2)
Executive Functioning (Time to Complete Stroop Test)	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on the Stroop Color and Word Test during and on the day after the intervention. Time for test completion and errors will be calculated. Selective attention was evaluated with the Stroop Color Word Interference Test. In the interference portion of this test, the subject identifies the color of ink in which words ("red", "green", or "blue") are printed, requiring the subject to inhibit their natural tendency to read the word. A subject's score is the time taken to identify 50 stimulus items. The time taken to complete the maze is inversely proportional to the cognitive function.	Baseline (Day 1), Follow-Up (Day 2)
Performance in Phonematic Fluency-Perseverations	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on a phonematic fluency-task (i.e. production of words that start with a specific letter) during 1 minute. Number of correct words, number of perseverations and number of rule breaks will be calculated.	Baseline (Day 1), Follow-Up (Day 2)
Executive Functioning (Trail Making Test)	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on the Trail Making Test (TMT; connecting a set of numbers and numbers and letters as quickly as possible while maintaining accuracy) during and on the day after the intervention. The TMT (Part A and Part B) is a measure of visuomotor processing/sequencing speed. Participants must draw a line connecting numbers in ascending order as quickly as possible. Completion time in seconds is recorded (0-120, where lower scores represent better performance). Completion time of Part B is divided by completion time of Part A (Ratio B/A).	Baseline (Day 1), Follow-Up (Day 2)
Attentional Performance (TAP)	To investigate the effect of a single session of gamma-tACS (compared to control-tACS) on subtests of the Test of Attentional Performance (TAP) during and on the day after the intervention. Percentile ranks for the following subtests will be calculated: Alertness (reaction time under two conditions), Go/NoGo (stimuli that require a selective reaction, that is, to react or not to react), Divided Attention (a visual and an auditory task must be processed in parallel), Visual Scanning (a matrix-like arrangement of 5 x 5 stimuli is used, the aim being to detect whether this arrangement includes a critical stimulus or not).	Baseline (Day 1), Follow-Up (Day 2)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploration of a Relationship (Correlation) Between the Amount of Sleep Spindles and Slow Wave Sleep With Recall	A relationship is defined as a correlation (Pearson's) between memory recall performance (amount of words recalled) and sleep EEG features (especially spindles, slow waves), i.e., whether better memory recall is associated with more sleep spindles and more slow wave sleep in the night after stimulation.	Baseline (Day 1), Follow-Up (Day 2)
Exploration of a Relationship (Correlation) of Sleep-Wake-Schedule Changes and Type of Stimulation	To see whether there is a correlation (Pearson's) between type of stimulation/wearing EEG and the motor activity pattern (measured by actigraphy wristband).	Baseline (Day 1), Follow-Up (Day 2)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Flavio Frohlich, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2023
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): December 28, 2023

Study Registration Dates

• First Submitted: May 18, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 23-0597

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: Yes
• product manufactured in and exported from the U.S.: No