Measuring Plasticity in SFC/dACC Following Theta-Burst-Stimulation Using TMS

Study Overview
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Brief Summary
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This is a study to determine whether particular forms of brain-stimulation, applied to superior frontal cortex/preSMA can affect cognition and associated frontal theta oscillations. To perform this study, the investigators first measure brain activity and cognitive performance using BrainE, a cognitive task platform that assesses cognition on sustained attention, response inhibition, working memory, interference processing and emotion processing assessments. Next, the investigators apply brain-stimulation over a mid-frontal region associated with these tasks (mid-line frontal activity overlying superior frontal cortex/pre-SMA area). Finally, human subjects perform the BrainE task assessments again immediately after the brain-stimulation. The investigators compare the effects of brain stimulation on average frontal activity evoked across the cognitive tasks, and on the cognitive performance averaged across tasks. The investigators primarily compare the effects of two types of brain-stimulation against each other: intermittent Theta-Burst Stimulation (a protocol designed to excite brain activity) and continuous Theta-Burst-Stimulation (a stimulation protocol designed to inhibit brain activity).

Detailed Description
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Brain/Behavior Recordings: to measure brain activity as described above, the investigators first ask subjects to engage in a cognitive assessment set while measuring EEG activity. For this study, the assessment set consists of the following tasks: (1) sustained attention; (2) response inhibition; (2) visuo-spatial working-memory; (3) Flanker interference processing, and (4) emotional interference processing. This battery takes about 30 minutes to complete. 24 channel EEG recordings are performed simultaneous to the cognitive tasks. Subjects perform the BrainE cognitive assessment, then receive brain-stimulation, and will then immediately be tested on the BrainE assessment again. Brain-Stimulation: Each subject will be asked to come in twice for this study, separated by 1 week. On week one they will receive one stimulation protocol, and on the subsequent week they will receive the other (order determined randomly for each subject). The intermittent Theta-Burst-Stimulation protocol (iTBS) consists of a similar burst pattern (3 stimulation pulses 20ms apart; each burst applied every 200ms). However, after 10 bursts (2 seconds of stimulation) there is a pause for 8 seconds. 200 bursts are still applied, however due to the inter-burst intervals, this paradigm takes 200 seconds. The continuous Theta-Burst-Stimulation protocol (cTBS) consists of a burst of three stimulation pulses, applied 20ms apart; with each burst occurring every 200ms. Thus, every second participants receive 5 bursts. This continues for 40 seconds, such that participants in total receive 200 bursts or 600 pulses.

Official Title
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Estimating the Sensitivity of a Mobile Neuro-cognitive Platform (BrainE) to Detect Neural Plasticity and Cognitive Enhancements Following Theta-burst Stimulation to Superior Frontal/dACC TMS Stimulation.

Conditions
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Cognitive Control

Intervention / Treatment
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* Device: iTBS then cTBS
* Device: cTBS then iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adequate decisional capacity to make a choice about participating in this research study. Exclusion Criteria: No major active neurologic/psychiatric disease No contraindications for rTMS No behavioral/medical factors that increase risk of seizure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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
Interventional Model Description: The investigators will test the effects of two different interventions (iTBS, cTBS) on cognitive control. Each participant will receive both interventions, labeled A & B, separated a week apart.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iTBS then cTBS<br>Participants in this arm first receive the iTBS brain stimulation in week 1, then have a one-week washout period and then receive cTBS brain stimulation in week 2. intermittent Theta-Burst-Stimulation (iTBS) entails a 2 second train of stimuli (stimuli occurring as a 50 Hz burst of three pulses separated by 200ms). Each 2 second train is followed by an 8 second pause, followed by another 2 second train. In total, 20 trains will be delivered, for a total of 200 bursts and 600 total pulses. continuous Theta-Burst-Stimulation (cTBS) consists of a continuous stimulus train (stimuli occurring as a 50 Hz burst of three pulses separated by 200ms). In total, 200 bursts and 600 total pulses will be delivered. | Device: iTBS then cTBS<br>* repetitive transcranial magnetic stimulation applied with intermittent theta-burst stimulation protocol applied in week 1 and continuous theta-burst stimulation protocol applied in week 2.<br>|
| Experimental: cTBS then iTBS<br>Participants in this arm first receive the cTBS brain stimulation in week 1, then have a one-week washout period and then receive iTBS brain stimulation in week 2. | Device: cTBS then iTBS<br>* repetitive transcranial magnetic stimulation applied with continuous theta-burst stimulation protocol applied in week 1 and intermittent theta-burst stimulation protocol applied in week 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post vs. Pre Change in Mid-frontal Theta Oscillations for iTBS vs. cTBS Stimulation | Change in superior frontal stimulus-evoked theta oscillations were measure on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The evoked EEG response (mid-frontal theta FCz as a source for superior frontal theta) was averaged across all cognitive tasks to yield a global cognitive task-averaged signal that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS. | (Post-Pre) iTBS and (Post-Pre) cTBS signals were measured one week apart. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post vs. Pre Change in Cognitive Performance | Change in cognitive performance was measured on a set of cognitive tasks, specifically selective attention, response inhibition, working memory, interference processing and emotion processing tasks. The cognitive performance was averaged across all cognitive tasks to yield global cognitive task-averaged performance that was measured immediately before (Pre) and immediately after (Post) iTBS, and similarly immediately before (Pre) and immediately after (Post) cTBS. | (Post-Pre) iTBS and (Post-Pre) cTBS cognitive performance levels were measured one week apart. |