Executive Function
Conditions
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.
Interventions
DEVICETheta TMS
TMS will be administered at the frequency of each subject's endogenous theta oscillation (4-7Hz)
DEVICEAlpha TMS
TMS will be administered at the frequency of each subject's endogenous alpha oscillation (8-12 Hz)
DEVICEArrhythmic TMS
TMS will be administered arrhythmically; i.e. a sequence of pulses with randomized timing
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
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Remembered Items | 1 week | 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. |
| Amplitude of Neural Oscillations | 1 week | 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. |
| Response Time | 1 week | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants will receive TMS while performing a cognitive control task. In one stimulation session, the TMS coil will be placed over the frontal cortex on the scalp. In another session, the TMS coil will be placed over the parietal cortex on the scalp. During every session, participants receive Alpha TMS, Theta TMS, and Arrhythmic TMS. | 58 |
| Total | 58 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 22.2 years STANDARD_DEVIATION 3.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Number of Remembered Items | 1.8039 number of remembered items STANDARD_DEVIATION 0.4988 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 16 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 58 participants |
| Response Time | 0.8225 seconds STANDARD_DEVIATION 0.1605 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 50 |
| other Total, other adverse events | 25 / 53 | 25 / 50 |
| serious Total, serious adverse events | 0 / 53 | 0 / 50 |
Outcome results
Primary
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.
Time frame: 1 week
Population: 54 participants were randomized into the experiment arms. 5 participants did not complete both arms and are excluded from analysis. In addition, data from 2 participant was corrupted and 5 participants were excluded due to poor task performance. Analysis was run on 42 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMS to Frontal Cortex | Amplitude of Neural Oscillations | Theta TMS | 1.443 microvolts | Standard Deviation 1.227 |
| TMS to Frontal Cortex | Amplitude of Neural Oscillations | Alpha TMS | 0.489 microvolts | Standard Deviation 0.412 |
| TMS to Frontal Cortex | Amplitude of Neural Oscillations | Arrhythmic TMS | 0.944 microvolts | Standard Deviation 0.705 |
| TMS to Parietal Cortex | Amplitude of Neural Oscillations | Theta TMS | -0.201 microvolts | Standard Deviation 0.505 |
| TMS to Parietal Cortex | Amplitude of Neural Oscillations | Alpha TMS | 0.241 microvolts | Standard Deviation 1.045 |
| TMS to Parietal Cortex | Amplitude of Neural Oscillations | Arrhythmic TMS | -0.132 microvolts | Standard Deviation 0.6 |
p-value: <0.000001ANOVA
Primary
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.
Time frame: 1 week
Population: 54 participants were randomized into the experiment arms. 5 participants did not complete both arms and are excluded from analysis. In addition, data from 2 participant was corrupted and 5 participants were excluded due to poor task performance. Analysis was run on 42 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMS to Frontal Cortex | Number of Remembered Items | Theta TMS | 1.863 number of remembered items | Standard Deviation 0.613 |
| TMS to Frontal Cortex | Number of Remembered Items | Alpha TMS | 1.796 number of remembered items | Standard Deviation 0.495 |
| TMS to Frontal Cortex | Number of Remembered Items | Arrhythmic TMS | 1.803 number of remembered items | Standard Deviation 0.381 |
| TMS to Parietal Cortex | Number of Remembered Items | Theta TMS | 1.754 number of remembered items | Standard Deviation 0.524 |
| TMS to Parietal Cortex | Number of Remembered Items | Alpha TMS | 1.797 number of remembered items | Standard Deviation 0.572 |
| TMS to Parietal Cortex | Number of Remembered Items | Arrhythmic TMS | 1.864 number of remembered items | Standard Deviation 0.469 |
p-value: 0.263ANOVA
Primary
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.
Time frame: 1 week
Population: 54 participants were randomized into the experiment arms. 5 participants did not complete both arms and are excluded from analysis. In addition, data from 2 participant was corrupted and 5 participants were excluded due to poor task performance. Analysis was run on 42 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMS to Frontal Cortex | Response Time | Theta TMS | 0.728 seconds | Standard Deviation 0.157 |
| TMS to Frontal Cortex | Response Time | Alpha TMS | 0.711 seconds | Standard Deviation 0.162 |
| TMS to Frontal Cortex | Response Time | Arrhythmic TMS | 0.720 seconds | Standard Deviation 0.155 |
| TMS to Parietal Cortex | Response Time | Theta TMS | 0.714 seconds | Standard Deviation 0.154 |
| TMS to Parietal Cortex | Response Time | Alpha TMS | 0.710 seconds | Standard Deviation 0.162 |
| TMS to Parietal Cortex | Response Time | Arrhythmic TMS | 0.717 seconds | Standard Deviation 0.166 |
p-value: 0.399ANOVA