Modulation of Cognitive Control Signals in Prefrontal Cortex by Rhythmic Transcranial Magnetic Stimulation

Study Overview
=================
Brief Summary
-----------------
Purpose: In this study, the investigators will provide causal evidence for the role of alpha and theta oscillations in cognitive control. Participants: Participants must be healthy, between the ages of 18 and 35, right handed, able to provide informed consent, willing to comply with all study procedures, and be available for the duration of the study, speak and understand English. Procedures: Alpha and theta brain oscillations will be measured and then entrained using frequency specific rhythmic TMS during a retrospective cued cognitive control task.

Detailed Description
-----------------
Neural oscillations are proposed to be a mechanism of coordinating information processing across distributed regions of cortex. Different neural oscillations may correspond to different underlying neural computations. Noninvasive brain stimulation allows experimenters to modulate specific neural oscillations by targeting particular frequency bands. By collecting simultaneous electroencephalography (EEG), rhythmic transcranial magnetic stimulation (TMS) has been previously demonstrated to entrain neural oscillations at the frequency of stimulation. Furthermore, when the frequency of entrained neural oscillations is matched to the frequency of endogenous activity in a cognitive task, the brain stimulation improves behavioral performance. Therefore, noninvasive brain stimulation is a promising tool for improving cognition by inducing optimal neural activity via externally applied electromagnetic fields; e.g. cognitive control improvements. Previous evidence has implicated neural activity in the alpha band (8-12 Hz) in information suppression and activity in the theta band (4-7 Hz) in information prioritization. Cognitive control task paradigms have been shown to elicit distinct activity in both of these bands. In this task, the stimuli are lateralized to the right and left visual field during encoding. After a short delay, a cue informs participants which stimuli (right or left) will be tested. Previous evidence found that alpha activity in parietal cortex is generated contralateral to irrelevant stimuli-supporting the role of alpha in information suppression-while theta activity in frontal cortex increases with the number of stimuli to be remembered-supporting the role of theta in information prioritization. For the current study, the investigators propose to deliver rhythmic trains of TMS in either alpha frequency, theta frequency, or an arrhythmic control to modulate neural processing during a cognitive control task. By collecting simultaneous EEG with TMS, the investigators will be able to measure the entrained oscillations from rhythmic TMS. The goal of this experiment is to enhance the observed theta and alpha activity that is seen with the successful prioritization and suppression of information. To provide causal evidence that parietal cortex generates alpha activity and frontal cortex generates theta activity, the investigators will apply rhythmic TMS stimulation to two scalp locations: the anterior middle frontal gyrus and inferior intraparietal sulcus. By applying alpha frequency, theta frequency, and arrhythmic TMS at each location, the investigators will be able to examine the causal relationship of frontal theta oscillations in information prioritization and parietal alpha oscillations in information suppression.

Official Title
-----------------
Modulation of Alpha and Theta Oscillations in a Cognitive Control Retrospective Cue Task With Frequency Specific Rhythmic Transcranial Magnetic Stimulation

Conditions
-----------------
Executive Function

Intervention / Treatment
-----------------
* Device: Theta TMS
* Device: Alpha TMS
* Device: Arrhythmic TMS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy Between the ages of 18 and 35 Right handed Able to provide informed consent Willing to comply with all study procedures Available for the duration of the study Speak and understand English. Exclusion Criteria: Attention Deficit Hyperactivity Disorder (currently under treatment) Neurological disorders and conditions, including, but not limited to: History of epilepsy Seizures (except childhood febrile seizures) -Dementia History of stroke Parkinson's disease Multiple sclerosis Cerebral aneurysm Brain tumors Medical or neurological illness or treatment for a medical disorder that could interfere with study participation (e.g., unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment) Prior brain surgery -Any brain devices/implants, including cochlear implants and aneurysm clips -Cardiac pacemaker -Any other implanted electronic device -History of current traumatic brain injury -(For females) Pregnancy or breast feeding -Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMS to frontal cortex followed by TMS to parietal cortex<br>Participants will receive TMS while performing a cognitive control task. In their first stimulation session, the TMS coil will be placed over the frontal cortex on the scalp. In their second session, the TMS coil will be placed over the parietal cortex on the scalp. During every session, subjects receive Theta TMS, Alpha TMS, and Arrhythmic TMS. | Device: Theta TMS<br>* TMS will be administered at the frequency of each subject's endogenous theta oscillation (4-7Hz)<br>* Other names: MagProX100;Device: Alpha TMS<br>* TMS will be administered at the frequency of each subject's endogenous alpha oscillation (8-12 Hz)<br>* Other names: MagProX100;Device: Arrhythmic TMS<br>* TMS will be administered arrhythmically; i.e. a sequence of pulses with randomized timing<br>* Other names: MagProX100;|
| Experimental: TMS to parietal cortex followed by TMS to frontal cortex<br>Participants will receive TMS while performing a cognitive control task. In their first stimulation session, the TMS coil will be placed over the parietal cortex on the scalp. In their second session, the TMS coil will be placed over the frontal cortex on the scalp. During every session, subjects receive Theta TMS, Alpha TMS, and Arrhythmic TMS. | Device: Theta TMS<br>* TMS will be administered at the frequency of each subject's endogenous theta oscillation (4-7Hz)<br>* Other names: MagProX100;Device: Alpha TMS<br>* TMS will be administered at the frequency of each subject's endogenous alpha oscillation (8-12 Hz)<br>* Other names: MagProX100;Device: Arrhythmic TMS<br>* TMS will be administered arrhythmically; i.e. a sequence of pulses with randomized timing<br>* Other names: MagProX100;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Remembered Items | Participants make a button press on a keyboard to indicate if the probed items are matched or non-matched to the items held in memory after a retrospective cue is presented. The investigators calculate the percent correct for non-match conditions, defined as the hit rate, and the percent incorrect for match conditions, defined as the false alarm rate. The number of remembered items, often referred to as working memory capacity, is calculated as the number of items to be remembered (2, 3, or 4) times the hit rate minus the false alarm rate, divided by one minus the false alarm rate. The range of values is 0 to 4 where larger values mean better performance. For TMS to frontal cortex, working memory capacity is reported when the participant was cued to the right. For TMS to parietal cortex, working memory capacity is reported when the participant was cued to the left. | 1 week | 
| Amplitude of Neural Oscillations | The electrical activity of the brain is recorded during performance of the task and brain stimulation. The investigators will perform Morlet wavelet convolution on the recorded electrical signal to calculate the amplitude of neural oscillations in the frequency bands: theta (4-7 hertz) and alpha (8-12 hertz). The amplitude of neural oscillations is reported during the second half of stimulation in the region that is being stimulated. The amplitude is normalized for each participant as the percent change from the amplitude during the baseline period (before the task begins). For TMS to frontal cortex the amplitude of theta oscillations are reported and for TMS to parietal cortex the amplitude of alpha oscillations are reported. | 1 week | 
| Response Time | Participants make a button press on a keyboard to indicate if the probe items are matched or non-matched to the items held in memory after a retrospective cue is presented. The investigators will calculate the response time of this choice as the difference between the time of the button press and presentation of the probe. For TMS to frontal cortex, response time is reported when the participant was cued to the right. For TMS to parietal cortex, response time is reported when the participant was cued to the left. | 1 week |