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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05907343
• Other study ID #: STUDY00003055
• Status: Recruiting
• Phase: N/A
• Start date: May 31, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2023
• Source: University of Texas at Austin
• Contact: José del R. Millán, PhD
• Phone: 512-232-8111
• Email: jose.millan[@]austin.utexas.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Cognitively normal younger adults

1. Ages between 18 to 35 years

2. Good general health

3. Normal or corrected vision

4. Completed elementary school education or able to understand middle school level experiment instructions

• Cognitively normal older adults

1. Ages between 60 to 90 years

2. Good general health

3. Normal or corrected vision

4. Completed elementary school education or able to understand middle school level experiment instructions

5. 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)

1. Ages between 60 to 90 years

2. Diagnosis of MCI according to the National Institute on Aging - Alzheimer's Association (NIA-AA) criteria

3. Good general health

4. Normal or corrected vision

5. Completed elementary school education or able to understand middle school level experiment instructions

Exclusion Criteria:

1. Neurological or psychiatric diseases (e.g., personal history of epilepsy/seizure brain damage, multiple sclerosis, schizophrenia, substance use disorder, etc.).

2. Current use of psychotropic medications with cognitive side effects (e.g., benzodiazepines, anticonvulsants, antipsychotics, etc.)

3. Current use of cognitive enhancing medications (e.g., Adderall, Memantine, etc.)

4. Factors hindering EEG acquisition and TMS delivery (e.g., skin infection, wounds, dermatitis, etc.)

5. Factors hindering MRI acquisition (e.g., implants, metallic tattoos, etc.)

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Device:
• Sham TBS
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.
• Closed-loop TBS
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.
• Open-loop TBS
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.

Locations

Country	Name	City	State
United States	Health Discovery Building	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas at Austin

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Cognitive assessment II: Hopkins Adult Reading Test	Score range: 70 - 131* (Units on a Scale); (* high scores = better)	Up to 8 weeks after intervention
Primary	Cognitive assessment III: Multilingual Naming Test	Score range: 0 - 32* (Units on a Scale); (* high scores = better)	Up to 8 weeks after intervention
Primary	Cognitive assessment IV: Animal Naming	Score range: 0 - 40* (Units on a Scale); (* high scores = better)	Up to 8 weeks after intervention
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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