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Executive FunctionNCT03828734

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

A study testing Theta TMS, Alpha TMS and Arrhythmic TMS in people with Executive Function, run by University of North Carolina, Chapel Hill at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 35 yearsHealthy volunteers can take part
Conditions the study is for
Executive Function
What is being tested?
Theta TMS, Alpha TMS and Arrhythmic TMS
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteUnited States
Study dates
13 Feb 2019to 22 Nov 2019
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 35 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 9Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27516

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Theta TMS, Alpha TMS, Arrhythmic TMS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Theta TMSDevice

    Also called MagProX100

    TMS will be administered at the frequency of each subject's endogenous theta oscillation (4-7Hz)

  • Alpha TMSDevice

    Also called MagProX100

    TMS will be administered at the frequency of each subject's endogenous alpha oscillation (8-12 Hz)

  • Arrhythmic TMSDevice

    Also called MagProX100

    TMS will be administered arrhythmically; i.e. a sequence of pulses with randomized timing

Study groups in NCT03828734
Study groupRoleWhat they receive
TMS to frontal cortex followed by TMS to parietal cortexExperimentalParticipants 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.
Receives: Device: Theta TMS; Device: Alpha TMS; Device: Arrhythmic TMS
TMS to parietal cortex followed by TMS to frontal cortexExperimentalParticipants 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.
Receives: Device: Theta TMS; Device: Alpha TMS; Device: Arrhythmic TMS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 week

  2. 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.

    Measured: 1 week

  3. 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.

    Measured: 1 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start13 Feb 2019
  3. Primary completion22 Nov 2019
  4. Study completion22 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03828734
Sponsor's protocol ID
18-1789
Other IDs
R01MH111889
Status last verified
Dec 2019
First submitted
29 Jan 2019
Last updated
19 Nov 2020
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes

Publications

  • Albouy P, Weiss A, Baillet S, Zatorre RJ. Selective Entrainment of Theta Oscillations in the Dorsal Stream Causally Enhances Auditory Working Memory Performance. Neuron. 2017 Apr 5;94(1):193-206.e5. doi: 10.1016/j.neuron.2017.03.015. Epub 2017 Mar 23.

    PubMed 28343866
  • Roux F, Uhlhaas PJ. Working memory and neural oscillations: alpha-gamma versus theta-gamma codes for distinct WM information? Trends Cogn Sci. 2014 Jan;18(1):16-25. doi: 10.1016/j.tics.2013.10.010. Epub 2013 Nov 19.

    PubMed 24268290
  • Fries P. Rhythms for Cognition: Communication through Coherence. Neuron. 2015 Oct 7;88(1):220-35. doi: 10.1016/j.neuron.2015.09.034.

    PubMed 26447583
  • Hanslmayr S, Matuschek J, Fellner MC. Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation. Curr Biol. 2014 Apr 14;24(8):904-9. doi: 10.1016/j.cub.2014.03.007. Epub 2014 Mar 27.

    PubMed 24684933
  • Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res Rev. 2007 Jan;53(1):63-88. doi: 10.1016/j.brainresrev.2006.06.003. Epub 2006 Aug 1.

    PubMed 16887192
  • Popov T, Popova P, Harkotte M, Awiszus B, Rockstroh B, Miller GA. Cross-frequency interactions between frontal theta and posterior alpha control mechanisms foster working memory. Neuroimage. 2018 Nov 1;181:728-733. doi: 10.1016/j.neuroimage.2018.07.067. Epub 2018 Jul 31.

    PubMed 30075276
  • Reinhart RMG. Disruption and rescue of interareal theta phase coupling and adaptive behavior. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):11542-11547. doi: 10.1073/pnas.1710257114. Epub 2017 Oct 9.

    PubMed 29073084
  • Romei V, Thut G, Silvanto J. Information-Based Approaches of Noninvasive Transcranial Brain Stimulation. Trends Neurosci. 2016 Nov;39(11):782-795. doi: 10.1016/j.tins.2016.09.001. Epub 2016 Sep 30.

    PubMed 27697295
  • Thut G, Veniero D, Romei V, Miniussi C, Schyns P, Gross J. Rhythmic TMS causes local entrainment of natural oscillatory signatures. Curr Biol. 2011 Jul 26;21(14):1176-85. doi: 10.1016/j.cub.2011.05.049. Epub 2011 Jun 30.

    PubMed 21723129
  • Wallis G, Stokes M, Cousijn H, Woolrich M, Nobre AC. Frontoparietal and Cingulo-opercular Networks Play Dissociable Roles in Control of Working Memory. J Cogn Neurosci. 2015 Oct;27(10):2019-34. doi: 10.1162/jocn_a_00838. Epub 2015 Jun 4.

    PubMed 26042457
  • Wang XJ. Neurophysiological and computational principles of cortical rhythms in cognition. Physiol Rev. 2010 Jul;90(3):1195-268. doi: 10.1152/physrev.00035.2008.

    PubMed 20664082
  • Wolinski N, Cooper NR, Sauseng P, Romei V. The speed of parietal theta frequency drives visuospatial working memory capacity. PLoS Biol. 2018 Mar 14;16(3):e2005348. doi: 10.1371/journal.pbio.2005348. eCollection 2018 Mar.

    PubMed 29538384
  • Rouder JN, Morey RD, Morey CC, Cowan N. How to measure working memory capacity in the change detection paradigm. Psychon Bull Rev. 2011 Apr;18(2):324-30. doi: 10.3758/s13423-011-0055-3.

    PubMed 21331668

Questions about this trial

What is this clinical trial studying?

A study testing Theta TMS, Alpha TMS and Arrhythmic TMS in people with Executive Function, run by University of North Carolina, Chapel Hill at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Remembered Items (time frame: 1 week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03828734, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2020.

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