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

Executive Function Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03828734
• Other study ID #: 18-1789
• Secondary ID: R01MH111889
• Status: Completed
• Phase: N/A
• Start date: February 13, 2019
• Est. completion date: November 22, 2019

Study information

• Verified date: December 2019
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: November 22, 2019
• Est. primary completion date: November 22, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

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

Related Conditions & MeSH terms

• Executive Function

Intervention

Device:
• Theta TMS
TMS will be administered at the frequency of each subject's endogenous theta oscillation (4-7Hz)
• Alpha TMS
TMS will be administered at the frequency of each subject's endogenous alpha oscillation (8-12 Hz)
• Arrhythmic TMS
TMS will be administered arrhythmically; i.e. a sequence of pulses with randomized timing

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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

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. — View Citation

Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the inhibition-timing hypothesis. Brain Res Rev. 2007 Jan;53(1):63-88. Epub 2006 Aug 1. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Roux F, Uhlhaas PJ. Working memory and neural oscillations: a-? versus ?-? 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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	1 week
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.	1 week
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.	1 week