Probing Homeostatic Plasticity With Priming Theta-burst Stimulation of the Dorsolateral Prefrontal Cortex

NCT04031105 | Completed

• 1 other identifier: PolyU 251002/19M
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Priming stimulation is a highly promising tool to boost the beneficial effects of therapeutic repetitive transcranial magnetic stimulation (rTMS) in psychiatry. The potentiating effects of priming stimulation, however, depend on the time interval between the priming and the test stimulation. Although it is known that too short and too long intervals have no effects, systematic studies that identify the time needed to maximize efficacy have not yet been done. Thus, there is a need for studies to investigate the effects of priming stimulation in order to fully utilize the potential benefits and advantages of this promising new rTMS protocol. This study will systematically investigate the neuromodulatory process underlying priming stimulation to enhance metaplasticity in the left dorsolateral prefrontal cortex (DLPFC) - one of the main targets for therapeutic rTMS - in individuals with subclinical depression. The brain is a highly plastic organ and its activity can be influenced using rTMS. At the same time, the brain also has a mechanism - called homeostatic metaplasticity - which counteracts extreme plastic changes. Homeostatic metaplasticity therefore can limit the beneficial effects of brain stimulation interventions. However, priming stimulation protocols that include both a priming and a test stimulation session may utilize homeostatic metaplasticity to increase the beneficial effects of brain stimulation, although the optimal treatment parameters for priming are not known. Moreover, little is known about homeostatic metaplasticity in the DLPFC, an area that is particularly relevant for psychiatric conditions given its role in the top-down control of emotions. Here, the investigators will systematically study metaplasticity using priming theta-burst stimulation (TBS), a potent form of rTMS in the left DLPFC. Changes in blood oxygenation that signal brain activity changes will be assessed using functional near-infrared spectroscopy (fNIRS) at rest and during engagement in several cognitive tasks. The findings from this study will (1) elucidate the optimal time interval between priming and test stimulation; (2) elucidate the influence of priming TBS on emotion discrimination as well as executive function and its underlying brain activity in subclinical depression; and (3) validate homeostatic metaplasticity in the left DLPFC.

Conditions

Depression Minor

Outcome Measures

Primary Outcomes (2)

• Change in hemoglobin concentrations (Hb) during rest

  Oxy- and deoxy-hemoglobin (HbO, HHb) and total Hb will be acquired using functional near-infrared spectroscopy (fNIRS)

  Change from baseline Hb at 15 minutes post-stimulation

• Change in hemoglobin concentrations (Hb) while participants perform an emotion stroop task and verbal fluency task

  Oxy- and deoxy-hemoglobin (HbO, HHb) and total Hb will be acquired using functional near-infrared spectroscopy (fNIRS)

  Change from baseline Hb at 15 minutes after stimulation

Secondary Outcomes (3)

• Change in reaction time during emotion stroop task

  Change from baseline reaction times at 15 minutes after stimulation

• Change in the number of correctly responded colored words in the emotional Stroop task and correctly generated words in the verbal fluency task.

  Change from baseline score at 15 minutes after stimulation

• Change in the number of correctly recognized emotion

  Change from baseline score at 15 minutes after stimulation

Study Arms (4)

Condition 1

EXPERIMENTAL

Priming sham TBS, followed by iTBS after an inter-stimulation-interval (ISI) of 0 minutes

Device: Theta-burst stimulation (TBS)

Condition 2

EXPERIMENTAL

Priming cTBS, followed by iTBS after an ISI of 0 minutes

Device: Theta-burst stimulation (TBS)

Condition 3

EXPERIMENTAL

Priming cTBS, followed by iTBS after an ISI of 10 minutes

Device: Theta-burst stimulation (TBS)

Condition 4

EXPERIMENTAL

Priming cTBS, followed by iTBS after an ISI of 20 minutes

Device: Theta-burst stimulation (TBS)

Interventions

Theta-burst stimulation (TBS) DEVICE

intermittent (iTBS) and continuous (cTBS) will be applied at an intensity of 70% or 100%\* resting motor threshold (RMT) on the dorsolateral prefrontal cortex, position F3 (EEG 10-20 international system) \*The optimal %RMT will be evaluated in a pilot study before commencement of the main study

Also known as: Transcranial Magnetic Stimulation

Condition 1; Condition 2; Condition 3; Condition 4

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• age 18-35
• education level of primary six or above
• right-handedness
• normal or corrected-to-normal vision
• being able to understand the verbal instructions
• willingness to sign the informed consent form

You may not qualify if:

• a history of seizures
• current or past psychiatric disorders
• current or past severe internal or neurological illness
• history of substance dependence or abuse within the last 3 months
• intake of any medication known to affect the excitation threshold (i.e., benzodiazepines, anticonvulsants).

Sponsors & Collaborators

• Dr Georg Kranz: lead

Study Sites (1)

The Hong Kong Polytechnic University

Hong Kong, Hong Kong

Location

MeSH Terms

Interventions

Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not be told which arm they belong to
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized, single blind, parallel group experiment

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 24, 2019
• Study Start: May 23, 2021
• Primary Completion: January 16, 2024
• Study Completion: January 16, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)