Closed-Loop Brain Stimulation as a Potential Intervention for Cognitive Decline

NCT05907343 | Recruiting FDA Device

• 1 other identifier: STUDY00003055
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in older adults with and without cognitive impairment. The main questions it aims to answer are:

• whether it is possible to restore various cognitive functions in older adults by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and
• whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS. Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game. Researchers will compare the effects of closed-loop and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality.

Conditions

Mild Cognitive Impairment; Alzheimer Dementia (AD)

Keywords

MCI; Older adults; Cognitive control; Memory impairment; Memory enhancement

Outcome Measures

Primary Outcomes (1)

• Cognitive Assessment Batteries

  NIH Toolbox - Cognition Battery: A computerized battery assessing multiple cognitive domains. The primary metric for all subtests is the age- and education-adjusted T-score (normative mean = 50, standard deviation = 10). Includes: Dimensional Change Card Sort, Face-Name Associative Memory Test, Flanker Inhibitory Control and Attention Test, Picture Sequence Memory Test, Rey Auditory Verbal Learning Test, Pattern Comparison Processing Speed Test

  Up to 8 weeks after intervention

Secondary Outcomes (6)

• Accuracy of the BCI classifier output

  Up to 8 weeks after intervention

• Behavioral performance of the video game task

  Up to 8 weeks after intervention

• N-Back Task

  Up to 8 weeks after intervention.

• Affective Flexibility Task

  Up to 8 weeks after intervention

• Perseverative Thinking Questionnaire

  Up to 8 weeks after intervention

Study Arms (2)

Closed-Loop TBS

ACTIVE COMPARATOR

Device: Closed-loop TBS

Open-Loop TBS

ACTIVE COMPARATOR

Device: Open-loop TBS

Interventions

Closed-loop TBS DEVICE

A BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. The BCI delivers TBS with a real coil when its output indicates that the participant is not properly engaged in the video game.

Closed-Loop TBS

Open-loop TBS DEVICE

A BCI records and analyzes the participant's EEG as they perform cognitively demanding video game tasks. TBS with the real coil is delivered irrelevant of the BCI decoder output.

Open-Loop TBS

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Older adults
• Ages between 60 to 90 years
• Good general health
• Normal or corrected vision
• Completed elementary school education or able to understand middle school level experiment instructions
• Self reports cognitive complaints
• Cognitively normal young adults
• Ages between 18 to 35 years
• Good general health
• Normal or corrected vision
• Completed elementary school education or able to understand middle school level experiment instructions

You may not qualify if:

• Self-report of neurological or psychiatric diseases that could be contraindicated for TMS (e.g., personal history of epilepsy/seizure brain damage, history of fainting, bipolar disorder, schizophrenia, current substance use disorder, etc.).
• Medications that elevate seizure threshold (e.g., stimulant medication, high dose bupropion).
• Factors hindering EEG acquisition and rTMS delivery (e.g., skin infection, wounds, dermatitis, unable to access the scalp of the participant (e.g., unremovable wig).
• Current participation in amyloid infusion treatment for Alzheimer's disease.
• Do not have the capacity to provide informed consent and does not have a Legally Authorized Representative.
• Resting motor threshold below the power limit in the laboratory. (Will be check on the first visit)

Sponsors & Collaborators

• University of Texas at Austin: lead
• Texas Alzheimer's Research and Care Consortium: collaborator

Study Sites (1)

Health Discovery Building

Austin, Texas, 78712, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Memory Disorders

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• José del R. Millán, PhD

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

• Jared F. Benge, PhD, ABPP

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

• Crystal M. Lantrip, PhD, LP

  Neuropsychological Assessment Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José del R. Millán, PhD

CONTACT

512-232-8111; jose.millan@austin.utexas.edu

Minsu Zhang

CONTACT

512-840-9310; minsuzhang@austin.utexas.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 18, 2023
• Study Start: May 31, 2023
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become permanently available by the online publication date.
• Access Criteria: Any interested researcher will have access.

Locations

US (1)