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

Dr Georg Kranz160 enrolled

Overview

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.

No detailed description

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Eligibility

Sex: ALLMin age: 18 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. age 18-35 2. education level of primary six or above 3. right-handedness 4. normal or corrected-to-normal vision 5. being able to understand the verbal instructions 6. willingness to sign the informed consent form Exclusion Criteria: 1. a history of seizures 2. current or past psychiatric disorders 3. current or past severe internal or neurological illness 4. ferromagnetic implants \<20cm from the head, cardiac pacemaker, deep brain stimulation and other common TMS exclusion criteria 5. history of substance dependence or abuse within the last 3 months 6. intake of any medication known to affect the excitation threshold (i.e., benzodiazepines, anticonvulsants).

Outcomes

Primary Outcomes

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)

Time frame: 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)

Time frame: Change from baseline Hb at 15 minutes after stimulation

Secondary Outcomes

Change in reaction time during emotion stroop task

Before and after stimulation, participants will perform a emotion stroop task. Participants are asked to indicate by button press in which color (red, yellow, blue, green) the word is presented on a computer screen,("c" for red, "v" for yellow, "n" for blue, "m" for green) . The total number and the reaction time of correct response will be recorded.

Time frame: 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.

Before and after stimulation, participants will perform an emotional Stroop task as described in Outcome 3. In addition, participants will also perform a verbal fluency task, In this task, participants are required to speak out as many unique words as possible during the word generation blocks, according to a given category (for example, name animals). The category will be presented at the center of the screen. The total number of correct answers will be recorded

Time frame: Change from baseline score at 15 minutes after stimulation

Change in the number of correctly recognized emotion

In addition, participants will perform an emotion-recognition accuracy task. They will be presented with 64 facial stimuli, consisting of sets of 16 sad, happy, fearful and neutral faces, in a randomized order. Faces will be presented for a maximum of 6s. Participants have to indicate the depicted emotion by button press (choice between 4 answers) within the presentation period.