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

NCT03828734 | Completed Results FDA Device

• 2 other identifiers: 18-1789R01MH111889
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Executive Function

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

TMS to frontal cortex followed by TMS to parietal cortex

EXPERIMENTAL

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; Device: Alpha TMS; Device: Arrhythmic TMS

TMS to parietal cortex followed by TMS to frontal cortex

EXPERIMENTAL

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; Device: Alpha TMS; Device: Arrhythmic TMS

Interventions

Theta TMS DEVICE

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

Also known as: MagProX100

TMS to frontal cortex followed by TMS to parietal cortex; TMS to parietal cortex followed by TMS to frontal cortex

Alpha TMS DEVICE

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

Also known as: MagProX100

TMS to frontal cortex followed by TMS to parietal cortex; TMS to parietal cortex followed by TMS to frontal cortex

Arrhythmic TMS DEVICE

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

Also known as: MagProX100

TMS to frontal cortex followed by TMS to parietal cortex; TMS to parietal cortex followed by TMS to frontal cortex

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27516, United States

Location

Related Publications (13)

• 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.

  PMID: 28343866 BACKGROUND

• 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.

  PMID: 24268290 BACKGROUND

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

  PMID: 26447583 BACKGROUND

• 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.

  PMID: 24684933 BACKGROUND

• 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.

  PMID: 16887192 BACKGROUND

• 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.

  PMID: 30075276 BACKGROUND

• 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.

  PMID: 29073084 BACKGROUND

• 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.

  PMID: 27697295 BACKGROUND

• 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.

  PMID: 21723129 BACKGROUND

• 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.

  PMID: 26042457 BACKGROUND

• 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.

  PMID: 20664082 BACKGROUND

• 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.

  PMID: 29538384 BACKGROUND

• 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.

  PMID: 21331668 BACKGROUND

Results Point of Contact

• Title: Justin Riddle, PhD
• Organization: University of North Carolina at Chapel Hill

justin_riddle@med.unc.edu

919-966-4755

Study Officials

• Flavio Frohlich, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 4, 2019
• Study Start: February 13, 2019
• Primary Completion: November 22, 2019
• Study Completion: November 22, 2019
• Last Updated: November 19, 2020
• Results First Posted: November 19, 2020

Record last verified: 2019-12

Locations

US (1)