Cognitive Control, Executive Function
Conditions
Keywords
tACS, Cognitive Control, Executive Function
Brief summary
Investigation of frequency specific transcranial alternating current stimulation on cognitive control signals in frontal cortex
Detailed description
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.
Interventions
DEVICETheta-gamma tACS
NeuroConn technologies, direct current-stimulator plus
DEVICEDelta-beta tACS
NeuroConn technologies, direct current-stimulator plus
DEVICESham tACS
NeuroConn technologies, direct current-stimulator plus
Sponsors
National Institute of Mental Health (NIMH)
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blinded. Neither the investigator nor the participants knows which form of stimulation is received.
Intervention model description
Healthy participants will receive three waveforms of transcranial alternating current stimulation (tACS). Delta-beta, Theta-gamma, and Sham.
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time for Trials With High Abstraction Relative to Low Abstraction | through study completion, an average of 3 weeks | 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. |
| Reaction Time for Trials With High Set-size Relative to Low Set-size | through study completion, an average of 3 weeks | 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. |
| Delta Phase to Beta Amplitude Coupling Strength | through study completion, an average of 3 weeks | 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. |
| Theta Phase to Gamma Amplitude Coupling Strength | through study completion, an average of 3 weeks | 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. |
| Percent Correct for Trials With High Abstraction Relative to Low Abstraction | through study completion, an average of 3 weeks | 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. |
| Percent Correct for Trials With High Set-size Relative to Low Set-size | through study completion, an average of 3 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Every participant will receive Theta-gamma tACS, Delta-beta tACS, and Sham tACS on separate sessions during performance of a computerized task. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 19.654 years STANDARD_DEVIATION 1.4951 |
| Baseline Delta Phase to Beta Amplitude Coupling | 0.0406 Z-score STANDARD_DEVIATION 0.3232 |
| Baseline Percent Correct Difference for Abstraction | 0.0679 percent correct STANDARD_DEVIATION 4.9692 |
| Baseline Percent Correct Difference for Set-Size | -1.0190 percent correct STANDARD_DEVIATION 4.4569 |
| Baseline Reaction Time Difference for Abstraction | 0.1637 seconds STANDARD_DEVIATION 0.1012 |
| Baseline Reaction Time Difference for Set-Size | 0.2272 seconds STANDARD_DEVIATION 0.0844 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 26 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 5 Participants |
| Theta Phase to Gamma Amplitude Coupling Strength | 0.0739 Z-score STANDARD_DEVIATION 0.4214 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 26 | 0 / 26 |
| other Total, other adverse events | 11 / 24 | 15 / 26 | 10 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 | 0 / 26 |
Outcome results
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant excluded from coupling analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Delta Phase to Beta Amplitude Coupling Strength | -0.0873 Z-score | Standard Deviation 0.3035 |
| Delta-beta tACS | Delta Phase to Beta Amplitude Coupling Strength | 0.1123 Z-score | Standard Deviation 0.2939 |
| Sham tACS | Delta Phase to Beta Amplitude Coupling Strength | -0.1250 Z-score | Standard Deviation 0.2651 |
p-value: 0.04t-test, 1 sided
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant excluded from behavioral analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Percent Correct for Trials With High Abstraction Relative to Low Abstraction | 0.5661 percent correct | Standard Deviation 3.1678 |
| Delta-beta tACS | Percent Correct for Trials With High Abstraction Relative to Low Abstraction | -0.2944 percent correct | Standard Deviation 7.4718 |
| Sham tACS | Percent Correct for Trials With High Abstraction Relative to Low Abstraction | 0.7246 percent correct | Standard Deviation 6.6416 |
p-value: 0.54t-test, 2 sided
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant excluded from behavioral analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Percent Correct for Trials With High Set-size Relative to Low Set-size | -2.2871 percent correct | Standard Deviation 2.9242 |
| Delta-beta tACS | Percent Correct for Trials With High Set-size Relative to Low Set-size | -4.3252 percent correct | Standard Deviation 6.8997 |
| Sham tACS | Percent Correct for Trials With High Set-size Relative to Low Set-size | -4.1667 percent correct | Standard Deviation 4.3264 |
p-value: 0.007t-test, 2 sided
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant excluded from behavioral analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Reaction Time for Trials With High Abstraction Relative to Low Abstraction | 0.1247 seconds | Standard Deviation 0.08 |
| Delta-beta tACS | Reaction Time for Trials With High Abstraction Relative to Low Abstraction | 0.1444 seconds | Standard Deviation 0.0832 |
| Sham tACS | Reaction Time for Trials With High Abstraction Relative to Low Abstraction | 0.1022 seconds | Standard Deviation 0.0947 |
p-value: 0.031t-test, 2 sided
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant excluded from behavioral analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Reaction Time for Trials With High Set-size Relative to Low Set-size | 0.1905 seconds | Standard Deviation 0.0676 |
| Delta-beta tACS | Reaction Time for Trials With High Set-size Relative to Low Set-size | 0.1853 seconds | Standard Deviation 0.1057 |
| Sham tACS | Reaction Time for Trials With High Set-size Relative to Low Set-size | 0.1888 seconds | Standard Deviation 0.076 |
p-value: 0.935t-test, 2 sided
Primary
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.
Time frame: through study completion, an average of 3 weeks
Population: One participant was excluded from coupling analysis because they did not follow task instructions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theta-gamma tACS | Theta Phase to Gamma Amplitude Coupling Strength | 0.1615 Z-score | Standard Deviation 0.3563 |
| Delta-beta tACS | Theta Phase to Gamma Amplitude Coupling Strength | 0.0706 Z-score | Standard Deviation 0.3496 |
| Sham tACS | Theta Phase to Gamma Amplitude Coupling Strength | 0.0577 Z-score | Standard Deviation 0.4043 |
p-value: 0.02t-test, 1 sided