Multiparameter Optimized tES for Memory in Aging

Concurrent Multiparameter Optimized Noninvasive Brain Stimulation for Working Memory in Aging

With an aging population worldwide, it is critical to develop effective interventions promoting healthy cognitive aging. Transcranial electrical stimulation (tES) is a promising but not fully realized noninvasive brain stimulation approach that could improve memory. This study investigates the behavioral and electrocortical effects of personalized tES in aging to determine whether whether optimal dosing, electrode placements, and waveforms elicit stronger responses.

Study Overview

• Status: Withdrawn
• Conditions: Healthy Aging
• Intervention / Treatment: Device: Transcranial electrical stimulation

Detailed Description

With an aging population worldwide, it is critical to develop effective interventions promoting healthy cognitive aging. A key component of healthy cognition is intact working memory, an executive neural process holding information temporarily. With increasing age, working memory capacity decreases and is associated with a loss of independence, thus incentivizing the need to retain a healthy working memory capacity. In addition to facilitating healthy aging, developing a method that improves working memory could help those diagnosed with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), which is currently is the 6th leading cause of death in the US and has an annual economic burden of $305 billion.

A potential approach to improve working memory is transcranial electrical stimulation (tES), a noninvasive brain stimulation method using scalp electrodes to deliver low electrical currents of 2 milliamps (mA) over the cortical target. While some prior studies have shown that prefrontal tES can improve working memory in older adults, there are small meta-analytic effect sizes and no FDA-approved indications to date. These mixed results could be due to applying one-size-fits-all and suboptimal tES parameters. In this study, the investigators will test the effects of personalized parameters, including dosing, electrode positioning, and waveforms compared to standard tES and placebo.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 50 - 85 y.o.
• Endorse good health with no history of mental or physical illness
• Willingness to adhere to the study schedule and assessments
• Able to read consent document and provide informed consent.
• English is a first or primary fluent language.

Exclusion Criteria:

• Any current psychiatric diagnosis or current Clinical Global Impression ratings of psychiatric illness > 1
• Neurodevelopmental disorders, history of Central Nervous System (CNS) disease, concussion, overnight hospitalization, or other neurologic sequela, tumors, seizures, meningitis, encephalitis, or abnormal CT or MRI of the brain
• Any psychotropic medication is taken within 5 half-lives of procedure time
• Any head trauma resulting in loss of consciousness
• Visual impairment (except the use of glasses)
• Inability to complete cognitive testing
• Active participation or plan for enrollment in another evidence-based clinical trial affecting the psychosocial function
• Repeated abuse or dependence upon drugs (excluding nicotine and caffeine) or taking medications including stimulants, modafinil, thyroid medication, or steroids
• Implanted devices/ferrous metal of any kind
• History of seizure or epilepsy, currently taking medications that lower seizure thresholds
• Claustrophobia or other conditions that would prevent the MRI assessment.
• Pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short term).
• Urine Pregnancy Test: If the subject is a woman of childbearing potential and /or a man capable of fathering a child before, during, and/or after participation precautions should be taken. Examples of acceptable methods of birth control for participants involved in the study include birth control pills, patches, Intrauterine Devices (IUD), condoms, sponges, diaphragm with spermicide, or avoiding sexual activity that could cause the subject to become pregnant.
• Inability to adhere to the treatment schedule.
• Inability to fit the wearable device to the user's head.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized tES stimulation #1; tES will be applied with personalized parameters in condition #1 for approximately 20 minutes.	Device: Transcranial electrical stimulation; We will administer active transcranial electrical stimulation in one of the 4 active stimulation conditions and 1 sham stimulation condition.
Experimental: Personalized tES stimulation #2; tES will be applied with personalized parameters in condition #2 for approximately 20 minutes.	Device: Transcranial electrical stimulation; We will administer active transcranial electrical stimulation in one of the 4 active stimulation conditions and 1 sham stimulation condition.
Experimental: Personalized tES stimulation #3; tES will be applied with personalized parameters in condition #3 for approximately 20 minutes.	Device: Transcranial electrical stimulation; We will administer active transcranial electrical stimulation in one of the 4 active stimulation conditions and 1 sham stimulation condition.
Experimental: Standard tES; Standard tES will be applied in condition #4 for approximately 20 minutes.	Device: Transcranial electrical stimulation; We will administer active transcranial electrical stimulation in one of the 4 active stimulation conditions and 1 sham stimulation condition.
Sham Comparator: Sham tES stimulation; A sham (placebo) comparison condition will be applied in condition #5 for approximately 20 minutes.	Device: Transcranial electrical stimulation; We will administer active transcranial electrical stimulation in one of the 4 active stimulation conditions and 1 sham stimulation condition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrocortical EEG changes pre- to post-tES	Observe effects of each tES condition within each of the 5 sessions, as measured by TMS-EEG	1 year
N-back working memory changes pre- to post-tES	Observe effects of each tES condition within each of the 5 sessions on the N-back memory task	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of side effects from tES	Questionnaire regarding headache, scalp sensation, and other common side effects of tES on a scale of 0-10.	1 year

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Kevin Caulfield, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: April 17, 2024
• First Submitted That Met QC Criteria: June 30, 2024
• First Posted (Actual): July 9, 2024

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: Pro00133951

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