Memory Enhancement in Aging With Closed-Loop tACS

Personalized Memory Enhancement in Aging: Pattern-Optimized tACS With Closed-Loop Precision Modulation

This project optimizes high-resolution tACS to improve memory in healthy older adults, advancing drug-free approaches for ADRD. We test stimulation schedules and develop an adaptive, brain-guided tACS system to strengthen memory-supporting networks.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging; Memory; Noninvasive Brain Stimulation
• Intervention / Treatment: Device: Peak Frequency; Device: Phase Lag; Device: Peak Frequency + Phase Lag; Device: Non-Adpative

Detailed Description

Cognitive decline, especially in memory and executive control, poses an escalating public health challenge as the population ages, contributing to loss of independence, reduced quality of life, and increased healthcare costs associated with Alzheimer's disease and related dementias (ADRD). Despite decades of research, there are few effective, non-pharmacological interventions capable of slowing or reversing these cognitive losses. Transcranial alternating current stimulation (tACS) has recently emerged as a promising, safe, and non-invasive technique for modulating neural rhythms that support memory. However, existing approaches remain limited by one-size-fits-all stimulation schedules that fail to account for individual brain connectivity patterns or dynamic fluctuations in cognitive state.

This project aims to advance precision neuromodulation for cognitive aging by optimizing and personalizing high-resolution tACS protocols to enhance memory in older adults. Building on strong pilot data demonstrating the feasibility of personalized and adaptive stimulation, we will use multimodal imaging (EEG and fMRI) to track changes in frontotemporal synchrony, specifically theta-gamma phase-amplitude coupling and theta phase synchronization, that are known to support memory formation and retrieval.

Aim 2 will develop and test a connectivity-guided closed-loop tACS system that continuously monitors neural synchronization in the frontotemporal network and adjusts stimulation parameters in real time. This adaptive framework is designed to tailor stimulation to each participant's evolving brain state, enabling more efficient and individualized cognitive enhancement than static approaches.

By integrating behavioral, electrophysiological, and neuroimaging measures with adaptive control algorithms, this research will identify reliable biomarkers of responsiveness, elucidate causal mechanisms linking neural synchrony to memory, and yield a new class of personalized, connectivity-guided interventions for cognitive decline. The findings will lay a foundation for scalable, non-invasive, and mechanism-driven treatments for ADRD and age-related memory loss, advancing the broader NIH mission of promoting healthy cognitive aging.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert Reinhart, PhD; Phone Number: (617) 353-9481; Email: rmgr@bu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 65 years of age or older
• normal or corrected-to-normal vision
• color vision

Exclusion Criteria:

• pregnant
• metal implants in head
• implanted electronic devices
• history of neurological problems or head injury
• skin sensitivity
• claustrophobia
• dementia (normal Montreal Cognitive Assessment > 25)
• depression (normal Geriatric Depression Scale < 10)
• history of psychosis
• cognitive deficits (MoCA>25)
• any psychoactive medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peak Frequency	Device: Peak Frequency; Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp tailored to individual peak frequency with the goal of modulating levels of neuronal excitability.
Experimental: Phase Lag	Device: Phase Lag; Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp tailored to individual phase lag with the goal of modulating levels of neuronal excitability.
Experimental: Peak Frequency + Phase Lag	Device: Peak Frequency + Phase Lag; Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp tailored to individual peak frequency and phase lag with the goal of modulating levels of neuronal excitability.
Experimental: Non-Adaptive	Device: Non-Adpative; Device: High definition transcranial electrical current stimulation Low-intensity, noninvasive application of electrical current to the human scalp not tailored to individual peak frequency or phase lag with the goal of modulating levels of neuronal excitability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EEG phase locking value (PLV) during working memory retention	Phase locking value between frontotemporal EEG electrodes within the theta frequency band during the memory retention interval of the visual working memory task	Baseline, Day 2
Interruption suppression measured behaviorally	Memory accuracy performance difference between interruption and control trials on the interruption working memory task	Baseline, Day 2
EEG phase amplitude coupling (PAC) during working memory retention	Theta phase gamma amplitude cross-frequency coupling at temporal EEG electrodes during the memory retention interval of the visual working memory task	Baseline, Day 2

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus
• Investigators: Principal Investigator: Robert Reinhart, PhD, Boston University Charles River Campus

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2028
• Primary Completion (Estimated): January 31, 2031
• Study Completion (Estimated): January 31, 2031

Study Registration Dates

• First Submitted: July 18, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 4230E_4

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.: Yes