iTBS/fMRI Study of Hierarchical Control in the PFC

Study Overview
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Brief Summary
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The objective of this study is to examine the effect of transcranial magnetic stimulation (TMS) on the prefrontal cortex and posterior parietal cortex.

Detailed Description
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The Comprehensive Control Task (CCT) was designed to examine hierarchical control in a single, well-controlled factorial task. On each trial, participants view a letter surrounded by a colored shape at a particular screen location. Color cues the relevant feature, letter or location, for a block of trials. The first trial of a block requires a decision of whether the stimulus is the first position of a circular sequence (sequence start). Subsequent trials require a decision of whether the viewed stimulus follows the previous stimulus in a circular sequence (sequence 1-back). The letter sequence (T-A-B-L-E-T) and spatial sequence (Top-Bottom Right-Left-Right-Bottom Left-Top) are difficulty-matched. Shape cues the task to perform. Squares indicate the standard baseline task, and each block begins and ends with baseline trials. Different shapes indicate sub-tasks. In Switching blocks, shape-switches (e.g. from square to circle or circle to square) cue the sequence start task. Shape-repeats cue the sequence 1-back task. In Planning blocks, triangle shapes indicate that the stimulus can be ignored (automatic no response). All the while, the last square-shaped stimulus must be retained as a reference for the next square-shaped stimulus. Finally, in Dual blocks, diamond shapes indicate switching (sequence start) and also planning. The reversion back to square shapes requires sequence matching to the distal, previous square. The design is factorial with stimulus-domain x contextual control x temporal control orthogonally manipulated. Full details of the CCT have been previous described in Nee & D'Esposito, 2016; 2017. The focus in this study will be comparison of FPl-TMS, MFG-TMS, and S1-TMS in an interleaved fMRI-TMS-fMRI design. The logic is to test the apical status of the FPl/MFG through the extent to which TMS impacts other PFC areas and behavior. Each experiment will begin with 1 session of the CCT with fMRI to localize PFC targets. Each participant will then perform 3 counter-balanced sessions wherein a different site will be targeted by TMS followed immediately by fMRI on the CCT.

Official Title
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iTBS/fMRI Study of Hierarchical Control in the PFC

Conditions
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Transcranial Magnetic Stimulation

Intervention / Treatment
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* Device: transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18 and 30 Right-handed Native English speaker or fluent by the age of 6 Exclusion Criteria: History of psychiatric disorders History of neurological disorders Receiving medications for psychiatric or neurological disorders Familial history of epilepsy Taking any drugs or medications that are pro-epileptic Metal anywhere in the head excluding the mouth Tinnitus Women who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FPl-TMS<br>Transcranial magnetic stimulation to the lateral frontal pole. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds repeated every 10 seconds at 80% of active motor threshold. | Device: transcranial magnetic stimulation<br>* Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance.<br>|
| Experimental: MFG-TMS<br>Transcranial magnetic stimulation to the middle frontal gyrus. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds repeated every 10 seconds at 80% of active motor threshold. | Device: transcranial magnetic stimulation<br>* Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance.<br>|
| Active Comparator: S1-TMS<br>Transcranial magnetic stimulation to the primary somatosensory cortex. 600 pulses delivered in 50 Hz bursts every 5 Hz for 2 seconds repeated every 10 seconds at 80% of active motor threshold. | Device: transcranial magnetic stimulation<br>* Transcranial magnetic stimulation delivered to the scalp targeting specific brain structures via stereotactic guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PFC-PPC effective connectivity | effective connectivity among areas of the prefrontal and posterior parietal cortex in the blood oxygenation level dependent (BOLD) signal assessed with functional magnetic resonance imaging (fMRI) [note, this measure has no units] | baseline, pre-intervention and immediately after intervention | 
| Change in PFC-PPC activation | blood oxygenation level dependent (BOLD) signal in areas of the prefrontal and posterior parietal cortex assessed with functional magnetic resonance imaging (fMRI) [note, this measure has no units] | baseline, pre-intervention and immediately after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in temporal control speed | behavioral performance (reaction time in milliseconds) on conditions involving temporal control in the comprehensive control task | baseline, pre-intervention and immediately after intervention | 
| Change in temporal control accuracy | behavioral performance (percent correct) on conditions involving temporal control in the comprehensive control task | baseline, pre-intervention and immediately after intervention | 
| Change in contextual control speed | behavioral performance (reaction time in milliseconds) on conditions involving contextual control in the comprehensive control task | baseline, pre-intervention and immediately after intervention | 
| Change in contextual control accuracy | behavioral performance (reaction time in milliseconds) on conditions involving contextual control in the comprehensive control task | baseline, pre-intervention and immediately after intervention |