Theta Phase-specific TMS to Modulate Prefrontal Activity

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the causal link between the phase of ongoing theta oscillations in the prefrontal cortex and approach/avoidance (Ap/Av) behavior in adults using theta phase-specific transcranial magnetic stimulation (TMS).

Detailed Description
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Approach/avoidance (Ap/Av) behavior is a reliable marker of the emotional processes in the human brain and a robust predictor of mood disorders. Although existing scientific studies found a correlation between the approach/avoidance behavior and ongoing theta activity (3-7 Hz) in the left dorsolateral prefrontal cortex, the causal evidence of the phase-dependent role and strength of association between the prefrontal theta oscillations and approach/avoidance behavior are still unclear. Here, we will monitor brain oscillations in real-time non-invasively using electroencephalography during the approach/avoidance test and modulate theta peaks or troughs with transcranial magnetic stimulation. These data will provide novel understanding of the mechanisms of emotional processing in human brain.

Official Title
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The Effects of Closed-loop TMS-EEG on Immediate Prefrontal Activity and Approach/Avoidance Behavior

Conditions
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Approach/Avoidance Behavior

Intervention / Treatment
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* Device: Transcranial magnetic stimulation (TMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 65 years old. Confident level of English language. Exclusion Criteria: Chronic condition that requires pharmacological treatment over the course of study participation. Metallic or electric implant in the head, neck, or chest area or otherwise MRI-noncompatible implants. History or evidence of seizures, head injuries with loss of consciousness, chronic neurological or mental disorder. Pregnancy or breast-feeding. History or evidence of alcohol or drug addiction.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMS over the left prefrontal cortex<br>Transcranial magnetic stimulation (TMS) will be administrated with a figure-8 coil over the left dorsolateral prefrontal cortex (DLPFC) at the intensity of up to 120% of the individualized resting motor threshold (rMT). Stimulation will be performed during and for the duration of the cognitive test. Up to three TMS pulses will be delivered at the beginning of every test trial (each trial duration is 2-6 seconds). The total duration of the cognitive testing and stimulation per session is approximately 40 minutes (in 4 blocks with breaks in-between). | Device: Transcranial magnetic stimulation (TMS)<br>* TMS will be performed at either peaks or troughs of ongoing prefrontal theta oscillations (3-7 Hz) concurrently with the cognitive test at the beginning of every test trial. Theta oscillations will be monitored in real-time at the left dorsolateral prefrontal cortex using electroencephalography (EEG).<br>|
| Sham Comparator: TMS over the head vertex<br>Transcranial magnetic stimulation (TMS) will be administrated with a figure-8 coil over the head vertex at the intensity of up to 120% of the individualized resting motor threshold (rMT). Stimulation will be performed during and for the duration of the cognitive test. Up to three TMS pulses will be delivered at the beginning of every test trial (each trial duration is 2-6 seconds). The total duration of the cognitive testing per session is approximately 40 minutes (in 4 blocks with breaks in-between). | Device: Transcranial magnetic stimulation (TMS)<br>* TMS will be performed at either peaks or troughs of ongoing prefrontal theta oscillations (3-7 Hz) concurrently with the cognitive test at the beginning of every test trial. Theta oscillations will be monitored in real-time at the left dorsolateral prefrontal cortex using electroencephalography (EEG).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction times in the Approach/Avoidance test | Reaction times (in milliseconds) in the Approach/Avoidance test during transcranial magnetic stimulation (TMS) at the peak vs. trough phases of ongoing prefrontal theta activity. | Immediate effect during stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amplitude of TMS evoked potentials | Amplitude of transcranial magnetic stimulation (TMS)-evoked potentials (in microvolts) in ongoing electroencephalography (EEG) in the left prefrontal cortex during the stimulation at the peak vs. trough phases of ongoing prefrontal theta activity. | Immediate effect during stimulation |