Gamma Transcranial Alternating Current Stimulation in Healthy Adults

NCT07095218 | Enrolling By Invitation

• 1 other identifier: E-10840098-202.3.02-2205
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Transcranial Alternating Current Stimulation (tACS), particularly at gamma frequencies, may enhance fast brain oscillations (especially gamma and possibly beta), while reducing slower rhythms such as theta. These effects are not confined to the stimulation site (e.g., the precuneus) but can extend to structurally and functionally connected regions, including the default mode network (DMN). Notably, 40 Hz gamma tACS applied to the left dorsolateral prefrontal cortex (DLPFC) has been associated with improvements in working memory and motor learning during reaction time tasks. While beta-frequency stimulation often shows no significant effect, gamma-frequency tACS has been shown to reduce response times. Gamma oscillations are commonly disrupted in neuropsychiatric disorders. These rhythms depend on a balance between excitation and inhibition, possibly linked to interneuron dysfunction. Abnormal gamma activity has been proposed as a biomarker for cognitive impairment. In this context, non-invasive rhythmic stimulation aiming to restore gamma activity is a promising cognitive enhancement strategy, though unlike pharmacological approaches, gamma-tACS has not yet been widely adopted in clinical practice. A meta-analysis of 56 studies emphasized that tACS outcomes vary with stimulation frequency, brain region, and timing protocols. Research suggests that the susceptibility of gamma oscillations to external modulation may provide insights into cognitive reserve, domain-specific processes, and Alzheimer's disease progression. Oscillatory changes may help predict conversion from MCI to Alzheimer's disease. However, evidence on the neural mechanisms of tACS remains limited and heterogeneous, and outcomes appear to depend on task type, frequency, and intensity. In this study, we will deliver a single 20-minute tACS session over the bilateral DLPFC using gamma frequencies (40 Hz, 80 Hz, and individualized gamma), and a theta-gamma coupling range (6-80 Hz). A sham group will also be included. The anodal electrode will be placed over F3, and the cathodal electrode over F4 (10-20 system). Cognitive performance will be assessed pre- and post-stimulation using neuropsychological tests, and EEG will measure theta-gamma phase-amplitude coupling and changes in oscillatory activity.

Conditions

Healhty

Keywords

gamma; tACS; theta-gamma coupling

Outcome Measures

Primary Outcomes (4)

• Öktem Verbal Memory Test

  Öktem Verbal Memory Test is a test of verbal memory processes, developed and validated by Öktem in 1992. It is designed to measure various variables related to memory.

  Before and immediately after applying Tacs

• Resting State EEG and TASK EEG

  The EEG recordings of the participants will be conducted using a BrainAmp 64-channel DC system. A 64-channel EasyCap will be used. AFz will serve as the ground electrode, and FCz will be used as the reference electrode. Impedance values will be maintained below 10 kOhm. EEG data will be recorded using the BrainVision Recorder software (Brain Products, Munich, Germany) with a band-pass filter set between 0.01 and 250 Hz.A 4-minute eyes-open and a 4-minute eyes-closed resting-state EEG recording will be conducted. EEG will also be recorded during the 2-back task and the memory task. 2-back Task: A visual n-back task will be administered to assess working memory. The task load will consist of 8-minute sessions. Memory Task: The memory task, which involves both encoding and retrieval of episodic information, will be examined using a visual memory paradigm presented to the participants.

  Before and immediately after applying Tacs

• Forward and Backward Digit Span

  This test, which is a subtest of the Wechsler Memory Scale, was developed to assess overall attention. It consists of two stages. The first stage evaluates the forward digit span, composed of random sequences ranging from 2 to 8 digits. In the second stage, the backward digit span is assessed using random sequences of 2 to 7 digits. In the first stage, numbers are read aloud with one-second intervals, and participants are expected to repeat the sequences exactly as presented. In the second stage, numbers are again read with one-second intervals, but participants are required to repeat the digits in reverse order. The test is terminated if the participant makes consecutive errors. The forward digit span assesses sustained attention, while the backward span also evaluates working memory performance.

  Before and immediately after applying Tacs

• Verbal fluency tests

  Verbal fluency tests measure the ability to generate words within a specific category over a limited time period. Verbal fluency performance has been associated not only with general language skills and semantic memory functions but also with executive functions such as attention, working memory, and processing speed. In this study, semantic and phonemic fluency tasks will be used.

  Before and immediately after applying Tacs

Other Outcomes (1)

• Montreal Cognitive Assessment (MoCA)

  Just before joining the study

Study Arms (5)

80 Hz Group

EXPERIMENTAL

transcranial alternating current stimulation (tACS) at 80 Hz gamma frequency will be applied to the bilateral dorsolateral prefrontal cortex (DLPFC) in a single 20-minute session.

Device: Application of Tacs

40 Hz Group

EXPERIMENTAL

transcranial alternating current stimulation (tACS) at 40 Hz gamma frequency will be applied to the bilateral dorsolateral prefrontal cortex (DLPFC) in a single 20-minute session.

Device: Application of Tacs

Individual gamma Group

EXPERIMENTAL

transcranial alternating current stimulation (tACS) at ındividual (Hz) gamma frequency will be applied to the bilateral dorsolateral prefrontal cortex (DLPFC) in a single 20-minute session.

Device: Application of Tacs

6-80 Hz Group

EXPERIMENTAL

transcranial alternating current stimulation (tACS) at 6-80 Hz will be applied to the bilateral dorsolateral prefrontal cortex (DLPFC) in a single 20-minute session.

Device: Application of Tacs

Sham Group

PLACEBO COMPARATOR

transcranial alternating current stimulation (tACS) at sham will be applied to the bilateral dorsolateral prefrontal cortex (DLPFC) in a single 20-minute session.

Device: Application of Tacs

Interventions

Application of Tacs DEVICE

In this study, a single 20-minute session of tACS will be administered over the bilateral dorsolateral prefrontal cortex (DLPFC) at various gamma frequencies (40 Hz, 80 Hz, individual gamma frequency) and in a theta-gamma coupling range (6-80 Hz). A sham stimulation group will also be included. The anodal surface electrode will be placed over the left DLPFC (F3 according to the 10-20 system), and the cathodal electrode over the right DLPFC (F4). Pre- and post-stimulation cognitive performance will be assessed using neuropsychological tests, while EEG will be used to evaluate theta-gamma phase-amplitude coupling and oscillatory changes.

40 Hz Group; 6-80 Hz Group; 80 Hz Group; Individual gamma Group; Sham Group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Being between 18 and 40 years of age
• Scoring above 25 on the Montreal Cognitive Assessment (MoCA)
• Being right-handed
• Having no history of neurological or psychiatric diagnosis

You may not qualify if:

• Having a neurological or psychiatric disorder
• Use of medications with sedative or stimulant effects
• Presence of metal brain implants or a pacemaker

Sponsors & Collaborators

• Medipol University: lead

Study Sites (1)

Medipol University

Istanbul, Turkey (Türkiye)

Location

Study Officials

• Lütfü Hanoğlu

  Medipol University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Msc

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 31, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): May 30, 2027
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

TU (1)