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 cognitively healthy adults and older adults diagnosed with mild cognitive disorder (MCI). The main questions it aims to answer are:

• whether it is possible to restore various cognitive functions in older adults diagnosed with MCI 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 sham, 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

Keywords

MCI; Older adults; Cognitive control; Memory impairment

Outcome Measures

Primary Outcomes (13)

• Behavioral performance of the video game task

  The behavioral performance, pressing or not pressing a button, reflects the level of cognitive control performance of the subjects. It measures whether the participants made a correct decision, and their response time, in a given trial.

  Up to 1 hour after intervention

• Accuracy of the BCI classifier output

  The BCI classifier output reflects the presence or absence of the cognitive EEG patterns elicited during the cognitive videogame tasks. For each participant, the BCI outputs will be compared to their behavioral responses (pressing or not pressing a button).

  Up to 1 hour after intervention

• Cognitive assessment I: Montreal Cognitive Assessment

  Telephone version, Score range: 0 - 22\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment II: Hopkins Adult Reading Test

  Score range: 70 - 131\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment III: Multilingual Naming Test

  Score range: 0 - 32\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment IV: Animal Naming

  Score range: 0 - 40\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment V: Number Span

  * Forward, Score range: 0 - 14\* (Units on a Scale) * Backward, Score range: 0 - 14\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment VI: Trail Making Test

  Parts A and B, Score range: 10 - 300\*\* (Units on a Scale) (\*\* high scores = worse)

  Up to 8 weeks after intervention

• Cognitive assessment VII: Southwestern Assessment of Processing Speed

  Score range: 0 - 75\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment VIII: Hopkins Verbal Learning Test-Revised

  * Immediate Total, Score range: 0 - 36\* (Units on a Scale) * Delayed Recall, Score range:0 - 12\* (Units on a Scale) * Percent Retention, Score range:0 - 100\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment IX: Brief Visuospatial Memory Test-Revised

  * Immediate Total, Score range: 0 - 36\* (Units on a Scale) * Delayed Recall, Score range:0 - 12\* (Units on a Scale) * Percent Retention, Score range:0 - 100\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment X: Controlled Oral Word Association Test

  Score range: 0 - 80\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

• Cognitive assessment XI: Stroop Color and Word Test

  * Word, Score range: 0 - 140\* (Units on a Scale) * Color, Score range:0 - 120\* (Units on a Scale) * Color-Word, Score range:0 - 80\* (Units on a Scale) (\* high scores = better)

  Up to 8 weeks after intervention

Study Arms (3)

Sham TBS

ACTIVE COMPARATOR

Device: Sham TBS

Closed-Loop TBS

ACTIVE COMPARATOR

Device: Closed-loop TBS

Open-Loop TBS

ACTIVE COMPARATOR

Device: Open-loop TBS

Interventions

Sham 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 sham coil when its output indicates that the participant is not properly engaged in the video game.

Sham TBS

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:

• Cognitively normal younger 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
• Cognitively normal 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
• Score of 23 or higher on the Montreal Cognitive Assessment, a brief formal cognitive screening test, which is used to indicate absence of cognitive impairment
• Older adults with mild cognitive impairment (MCI)
• Ages between 60 to 90 years
• Diagnosis of MCI according to the National Institute on Aging - Alzheimer's Association (NIA-AA) criteria
• Good general health

You may not qualify if:

• Neurological or psychiatric diseases (e.g., personal history of epilepsy/seizure brain damage, multiple sclerosis, schizophrenia, substance use disorder, etc.).
• Current use of psychotropic medications with cognitive side effects (e.g., benzodiazepines, anticonvulsants, antipsychotics, etc.)
• Current use of cognitive enhancing medications (e.g., Adderall, Memantine, etc.)
• Factors hindering EEG acquisition and TMS delivery (e.g., skin infection, wounds, dermatitis, etc.)
• Factors hindering MRI acquisition (e.g., implants, metallic tattoos, etc.)

Sponsors & Collaborators

• University of Texas at Austin: lead

Study Sites (1)

Health Discovery Building

Austin, Texas, 78712, United States

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction; Memory Disorders

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• José del R. Millán, PhD

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

• Robin Hilsabeck, PhD, ABPP

  University of Texas at Austin

  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@utexas.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• 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: April 29, 2026

Record last verified: 2026-04

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)