Effect of Cross Frequency tACS on Cognitive Control

Study Overview
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Brief Summary
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Investigation of frequency specific transcranial alternating current stimulation on cognitive control signals in frontal cortex

Detailed Description
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Previous evidence suggests that there are specific frequency bands associated with different aspects of cognitive control. In specific delta (2-4Hz) and beta (15-30Hz) are associated with increased levels of abstraction for learned rules; and theta (5-8Hz) and gamma (30-50Hz) has been associated with increased set-size or number of learned rules. Here we aim to find causal evidence in support of these previous correlational findings by applying cross-frequency transcranial alternating current stimulation (tACS) in the specific frequency bands previously shown to be task-relevant. In a crossover design, we stimulate subjects with either delta-beta or theta-gamma tACS during performance of a hierarchical cognitive control task that manipulates the level of abstraction and set-size of rules that must be learned in order to make the correct button press.

Official Title
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A Pilot Study Investigating the Effects of Cross Frequency Transcranial Alternating Current Stimulation on Cortical Oscillations Underlying Cognition

Conditions
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Cognitive Control, Executive Function

Intervention / Treatment
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* Device: Theta-gamma tACS
* Device: Delta-beta tACS
* Device: Sham tACS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between the ages of 18 and 35 years 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 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 and electroconvulsive therapy induced 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, malignancy) Prior brain surgery Any brain devices/implants, including cochlear implants and aneurysm clips History or current traumatic brain injury (For females) Pregnancy or breast feeding Personal or family history of mental/psychiatric disorder (e.g., anxiety, major depressive disorder, schizophrenia, etc.) Positive urine test for the following: Marijuana (THC), Cocaine (COC), Phencyclidine (PCP), Amphetamine (AMP), Ecstasy (MDMA), Methamphetamine (Mamp), Opiates (OPI), Oxycodone (OXY), Methadone (MTD), Barbiturates (BAR), Benzodiazepines (BZO), Buprenorphine (BUP), Tricyclic Antidepressants (TCA), Propoxyphene (PPX) 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
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Minimum Age: 18 Years
Maximum Age: 35 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: Healthy participants will receive three waveforms of transcranial alternating current stimulation (tACS). Delta-beta, Theta-gamma, and Sham.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theta-gamma, Delta-beta, Sham<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Theta-gamma tACS, then Delta-beta tACS, then Sham tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|
| Experimental: Theta-gamma, Sham, Delta-beta<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Theta-gamma tACS, then Sham tACS, then Delta-beta tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|
| Experimental: Delta-beta, Theta-gamma, Sham tACS<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Delta-beta tACS, then Theta-gamma tACS, then Sham tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|
| Experimental: Delta-beta, Sham, Theta-gamma tACS<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Delta-beta tACS, then Sham tACS, then Theta-gamma tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|
| Experimental: Sham, Delta-beta, Theta-gamma tACS<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Sham tACS, then Delta-beta tACS, then Theta-gamma tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|
| Experimental: Sham, Theta-gamma, Delta-beta tACS<br>Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. Sequence: Sham tACS, then Theta-gamma tACS, then Delta-beta tACS | Device: Theta-gamma tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Delta-beta tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>Device: Sham tACS<br>* NeuroConn technologies, direct current-stimulator plus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaction Time for Trials With High Abstraction Relative to Low Abstraction | For low abstraction conditions, subjects must memorize a color to button mapping. For high abstraction conditions, subject must make a perceptual judgement on the similarity of two objects based on either texture or shape as cued by a color. The reaction time difference between high and low abstraction conditions was hypothesized to decrease when delta-beta tACS was delivered. As a control for the placebo effect of stimulation, the difference between delta-beta tACS and sham tACS, or placebo, was used for statistical analysis. | through study completion, an average of 3 weeks | 
| Reaction Time for Trials With High Set-size Relative to Low Set-size | The reaction time difference between high and low set-size conditions was hypothesized to decrease when theta-gamma tACS is delivered. As a control for the placebo effect of stimulation, the difference between theta-gamma tACS and sham tACS, or placebo, was used for statistical analysis. | through study completion, an average of 3 weeks | 
| Delta Phase to Beta Amplitude Coupling Strength | Delta-beta tACS was hypothesized to increase cross frequency coupling strength (higher value) between the targeted frequency bands. Phase amplitude coupling between delta phase and beta amplitude was calculated for the two minute electrical brain recordings after stimulation. A null distribution was calculated by shuffling the beta amplitude time series relative to the delta phase time series and then calculating coupling strength. The outcome measure is the z-transformed value of the genuine phase amplitude coupling relative to the null distribution. | through study completion, an average of 3 weeks | 
| Theta Phase to Gamma Amplitude Coupling Strength | Theta-gamma tACS was hypothesized to increase cross frequency coupling strength (higher value) between the targeted frequency bands. Phase amplitude coupling between theta phase and gamma amplitude was calculated for the two minute electrical brain recordings after stimulation. A null distribution was calculated by shuffling the gamma amplitude time series relative to the theta phase time series and then calculating coupling strength. The outcome measure is the z-transformed value of the genuine phase amplitude coupling relative to the null distribution. | through study completion, an average of 3 weeks | 
| Percent Correct for Trials With High Abstraction Relative to Low Abstraction | For low abstraction conditions, subjects must memorize a color to button mapping. For high abstraction conditions, subject must make a perceptual judgement on the similarity of two objects based on either texture or shape as cued by a color. The accuracy difference between high and low abstraction conditions was hypothesized to decrease when delta-beta tACS was delivered. As a control for the placebo effect of stimulation, the difference between delta-beta tACS and sham tACS, or placebo, was used for statistical analysis. | through study completion, an average of 3 weeks | 
| Percent Correct for Trials With High Set-size Relative to Low Set-size | The accuracy difference between high and low set-size conditions was hypothesized to decrease when theta-gamma tACS is delivered. As a control for the placebo effect of stimulation, the difference between theta-gamma tACS and sham tACS, or placebo, was used for statistical analysis. | through study completion, an average of 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tACS, Cognitive Control, Executive Function