MRI Guided Closed-loop TMS-EEG

NCT06050603 | Recruiting

• 1 other identifier: SUN-5474
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this interventional study is to develop an individualized approach using transcranial magnetic stimulation (TMS) in a high-precision manner. This approach will use TMS to modulate brain activity at multiple locations simultaneously. Functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) will record the responses and guide the stimulation. Specifically, the placement and orientation of TMS coils will be tailored to stimulate the targeted functional brain areas informed by fMRI. To maximize the interventional effect, stimulation pulses will be delivered based on EEG oscillations.

Conditions

Normal Physiology; Amnestic Mild Cognitive Impairment

Keywords

Transcranial Magnetic Stimulation; Memory Impairments

Outcome Measures

Primary Outcomes (3)

• Functional connectivity measured by fMRI

  Functional connectivity during resting state and psychological tasks

  At baseline and immediately after treatment

• Response accuracy to psychological tasks

  accuracy, or rate of conditioned responses

  At baseline and immediately after treatment

• Reaction times

  At baseline and immediately after treatment

Secondary Outcomes (1)

• EEG functional connectivity

  At baseline and immediately after treatment

Study Arms (2)

Experimental_Aim1: Healthy Volunteers

EXPERIMENTAL

All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects.

Device: TMS

Experimental_Aim2: Amnestic Mild Cognitive Impairment

EXPERIMENTAL

All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects.

Device: TMS

Interventions

TMS DEVICE

The target locations of TMS will be cortical regions defined by either anatomical landmarks or functional regions derived from the individual's functional and structural MRI for Aim 1. TMS target locations for Aim 2 and 3 are determined by Aim 1's results. These TMS target regions will be guided by a navigation system. TMS will be parametrically varied with combinations of pulse strength and frequencies based on experimental conditions. TMS strength will be referred to the resting motor threshold (rMT), which will be determined independently for each participant. TMS pulses will be delivered at fixed time instants for Aim 2 and at time instants based on the phase of oscillatory neural activity for Aim 3.

Experimental_Aim1: Healthy Volunteers; Experimental_Aim2: Amnestic Mild Cognitive Impairment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages between 18 and 65 years;
• Healthy with no history of neurological impairment;
• Normal or correct-to-normal vision.
• Age 50-80 years;
• MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia;
• Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5;
• Normal or correct-to-normal vision.

You may not qualify if:

• Women who are pregnant or breastfeeding;
• History of seizure (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain tumor, brain surgery, head injury, known structural brain lesion;
• Have metal in the eye or skull area, brain stimulator, surgical metal, clips in the brain, cochlear implants, mental fragments in the eye, as these make TMS unsafe;
• Have non-MRI compatible metal in the body, for example metallic (forromagnetic) implants (e.g., cardiac pacemaker, aneurysm clip);
• Subjects who are uncomfortable in small closed spaces (have claustrophobia), unable to lie comfortably supine for up to 1 hour, and would feel uncomfortable in the MRI machine;
• Participation in any other study involving non-invasive brain stimulation less than two weeks ago;
• Abnormal findings on neurological examination that we will perform.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Study Officials

• Fa-Hsuan Lin, PhD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fa-Hsuan Lin, PhD

CONTACT

416-480-6100; fhlin@sri.utoronto.ca

Hsin-Ju Lee, PhD

CONTACT

416-480-6100; hsinju.lee@utoronto.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: It is a within-subjects design, which means that all subjects will receive both individualized stimulation based on their functional results and generic stimulation based on the results of a meta-analysis.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior scientist

Study Record Dates

• First Submitted: September 3, 2023
• First Posted: September 22, 2023
• Study Start: September 7, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

CA (1)