Exploring the Modulatory Role of Brain State on the Prefrontal Response to Excitatory Stimulation

NCT ID: NCT06750614

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-03
• Study Completion Date: 2025-09-01

Brief Summary

Therapeutic repetitive transcranial magnetic stimulation (rTMS) for depression is well-supported, with multiple protocols approved by the United States Food and Drug Administration and global efforts aimed at boosting its antidepressant effects underway. However, there exists an under-reported aspect of clinical trials using rTMS: what are patients doing during each stimulation session? Here, the investigators begin this investigation with individuals without a history of depression nor other psychiatric diagnosis. The investigators focus on the underlying brain activity. The investigators will systematically assess the modulatory role of brain state on the brain's response to a session of rTMS by using a concurrent, non-invasive brain imaging setting: functional near-infrared spectroscopy (fNIRS), marking the first effort of its kind in this field.

Detailed Description

The scientific literature on rTMS rehabilitation is steadily growing and new treatment protocols that aim to optimize rehabilitation efficacy as well as efficiency are emerging. However, no consideration to what patients should be doing during rTMS treatment sessions is given. These details are typically omitted in the literature, and advice is not given in recent guidelines. When details are reported, patients are assumed to enter a relaxed state during treatment. This assumption is highly problematic, especially for MDD because depression is an internalizing disorder, wherein emotional and cognitive dyscontrol are major features linked with abnormal activity of the dorsolateral prefrontal cortex (DLPFC), the region being stimulated. Indeed, instructing patients to concentrate on thoughts that exacerbate their depressive symptoms during stimulation diminishes the antidepressant treatment effect, and cognitive neuroscience research suggests the importance of considering the initial brain state when conducting behavioral and neuroimaging experiments with TMS. Attention to what occurs during stimulation is highly relevant but usually omitted in neuropsychiatric rehabilitation research. This proposal is a systematic assessment of the modulatory role of brain state on the prefrontal response to rTMS in healthy participants. Results from this study will inform whether the clinical literature on therapeutic rTMS is mistaken for not controlling for brain state, and provide proof-of-concept for future clinical trials and collaborative research proposals (CRF) for the treatment of neuropsychiatric disorders.

Conditions

Healthy Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Mood

During concurrent iTBS/fNIRS, stimuli with positive, negative, and neutral valence will be presented to participants to induce the corresponding mood.

Group Type: ACTIVE_COMPARATOR

intermittent theta-burst stimulation (iTBS)

Intervention Type: DEVICE

In each visit, the intensity of the iTBS applied to the participant will be set at 70% of their individual resting motor threshold (rMT), with one session specifically targeting the left DLPFC.

Cognitive Task

During concurrent iTBS/fNIRS, the effects of participants' cognitive load will be assessed by performing the backward counting task.

Group Type: ACTIVE_COMPARATOR

intermittent theta-burst stimulation (iTBS)

Intervention Type: DEVICE

In each visit, the intensity of the iTBS applied to the participant will be set at 70% of their individual resting motor threshold (rMT), with one session specifically targeting the left DLPFC.

Relax

During concurrent iTBS/fNIRS, participants will be instructed to relax.

Group Type: ACTIVE_COMPARATOR

intermittent theta-burst stimulation (iTBS)

Intervention Type: DEVICE

In each visit, the intensity of the iTBS applied to the participant will be set at 70% of their individual resting motor threshold (rMT), with one session specifically targeting the left DLPFC.

Interventions

intermittent theta-burst stimulation (iTBS)

In each visit, the intensity of the iTBS applied to the participant will be set at 70% of their individual resting motor threshold (rMT), with one session specifically targeting the left DLPFC.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age 18 to 65
• Biological and mental health, based on a clinical interview
• Able to understand and follow instructions

Exclusion Criteria

• Major internal diseases, neurological disorders, or mental disorders
• Having a metal implant
• Hearing problems or in-ear ringing
• Pregnancy or breastfeeding
• Any conditions that will contraindicate to iTBS or fNIRS

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Hong Kong Polytechnic University

OTHER

Sponsor Role: lead

Responsible Party

Dr Georg Kranz

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Hong Kong Polytechnic University

Kowloon, , Hong Kong

Countries

Hong Kong

Other Identifiers

HSEARS20230324002

Identifier Type: -

Identifier Source: org_study_id