How do Alpha Oscillations Shape the Perception of Pain? - An EEG-based Neurofeedback Study

Experimental Pain in Healthy Human Subjects Clinical Trial

Official title:

How do Alpha Oscillations Shape the Perception of Pain? - An EEG-based Neurofeedback Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05570695
• Other study ID #: 09/2022
• Status: Recruiting
• Phase: N/A
• Start date: October 2022
• Est. completion date: December 2023

Study information

• Verified date: October 2022
• Source: Technical University of Munich
• Contact: Markus Ploner, Prof. Dr. med.
• Phone: +49-89-4140-4608
• Email: markus.ploner[@]tum.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Pain is closely linked to alpha oscillations (8 -13 Hz) which are thought to represent a supra-modal, top-down mediated gating mechanism that shapes sensory processing. Consequently, alpha oscillations might also shape the cerebral processing of nociceptive input and eventually the perception of pain. To test this mechanistic hypothesis, the investigators designed a sham-controlled and double-blind electroencephalography (EEG)-based neurofeedback study. In a short-term neurofeedback training protocol, healthy participants will learn to up- and downregulate somatosensory alpha oscillations using attention. Subsequently, the investigators will investigate how this manipulation impacts experimental pain applied during neurofeedback. Using Bayesian statistics and mediation analysis, the investigators will test whether alpha oscillations mediate attention effects on pain perception. This approach promises causal insights into the role of alpha oscillations in shaping pain, and thereby extends previous correlative evidence. Beyond, it can aid the development of novel, non-invasive modulatory treatment approaches for chronic pain, which are urgently needed.

The prosed study protocol has been granted in-principle acceptance from PLOS Biology and the corresponding registration can be found at the OSF online repository [www.osf.io/qbkj2].

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: December 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• aged 18-45 years

• right-handedness (laterality quotient > 60 on the Edinburgh handedness inventory)

• good command of German

• written informed consent

• attendance at both sessions and compliance with instructions throughout the experiment

Exclusion Criteria:

• pregnancy

• neurological or psychiatric diseases (e.g., epilepsy, stroke, depression, anxiety disorders)

• severe general illnesses (e.g., tumors, diabetes)

• skin diseases (e.g., dermatitis, psoriasis or eczema)

• current or recurrent pain

• regular intake of medication (aside from contraception, thyroidal, and antiallergic medication)

• surgical procedures involving the head or spinal cord

• side-effects following previous thermal stimulation

• contact to a person with a SARS-CoV-2 infection within the last 2 weeks

• current symptoms of a cold or flu

Related Conditions & MeSH terms

• Experimental Pain in Healthy Human Subjects

Intervention

Behavioral:
• attention right training, ARTNF
In a first verum neurofeedback condition, participants will be instructed to focus attention on their right hand and the up-regulation of alpha oscillations in the right hemisphere relative to alpha oscillations in the left hemisphere will be incentivized through neurofeedback.
• attention left training, ALTNF
In a second verum neurofeedback condition, participants will be instructed to focus attention on their left hand and the down-regulation of right relative to left alpha oscillations will be incentivized.
• sham attention right training, ARTsham
During the first sham neurofeedback condition, participants will be instructed to focus attention on their right hand. However, the feedback signal will not mirror their brain activity. Instead, the feedback signal and the corresponding reward of the last matching verum condition completed by a previous participant, i.e., ARTNF for ARTsham, will be replayed (yoked feedback).
• sham attention left training, ALTsham
During the second sham neurofeedback condition, participants will be instructed to focus attention on their left hand. However, the feedback signal will not mirror their brain activity. Instead, the feedback signal and the corresponding reward of the last matching verum condition completed by a previous participant, i.e., ALTNF for ALTsham, will be replayed (yoked feedback).

Locations

Country	Name	City	State
Germany	Department of Neurology, Klinikum rechts der Isar, Technical University of Munich	Munich	Bavaria

Sponsors (3)

Lead Sponsor	Collaborator
Technical University of Munich	German Research Foundation, Studienstiftung des deutschen Volkes

Country where clinical trial is conducted

Germany, 

References & Publications (7)

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

Ploner M, Sorg C, Gross J. Brain Rhythms of Pain. Trends Cogn Sci. 2017 Feb;21(2):100-110. doi: 10.1016/j.tics.2016.12.001. Epub 2016 Dec 23. Review. — View Citation

Ros T, Enriquez-Geppert S, Zotev V, Young KD, Wood G, Whitfield-Gabrieli S, Wan F, Vuilleumier P, Vialatte F, Van De Ville D, Todder D, Surmeli T, Sulzer JS, Strehl U, Sterman MB, Steiner NJ, Sorger B, Soekadar SR, Sitaram R, Sherlin LH, Schönenberg M, Scharnowski F, Schabus M, Rubia K, Rosa A, Reiner M, Pineda JA, Paret C, Ossadtchi A, Nicholson AA, Nan W, Minguez J, Micoulaud-Franchi JA, Mehler DMA, Lührs M, Lubar J, Lotte F, Linden DEJ, Lewis-Peacock JA, Lebedev MA, Lanius RA, Kübler A, Kranczioch C, Koush Y, Konicar L, Kohl SH, Kober SE, Klados MA, Jeunet C, Janssen TWP, Huster RJ, Hoedlmoser K, Hirshberg LM, Heunis S, Hendler T, Hampson M, Guggisberg AG, Guggenberger R, Gruzelier JH, Göbel RW, Gninenko N, Gharabaghi A, Frewen P, Fovet T, Fernández T, Escolano C, Ehlis AC, Drechsler R, Christopher deCharms R, Debener S, De Ridder D, Davelaar EJ, Congedo M, Cavazza M, Breteler MHM, Brandeis D, Bodurka J, Birbaumer N, Bazanova OM, Barth B, Bamidis PD, Auer T, Arns M, Thibault RT. Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist). Brain. 2020 Jun 1;143(6):1674-1685. doi: 10.1093/brain/awaa009. — View Citation

Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, Weiskopf N, Blefari ML, Rana M, Oblak E, Birbaumer N, Sulzer J. Closed-loop brain training: the science of neurofeedback. Nat Rev Neurosci. 2017 Feb;18(2):86-100. doi: 10.1038/nrn.2016.164. Epub 2016 Dec 22. Review. Erratum in: Nat Rev Neurosci. 2019 May;20(5):314. — View Citation

Sorger B, Scharnowski F, Linden DEJ, Hampson M, Young KD. Control freaks: Towards optimal selection of control conditions for fMRI neurofeedback studies. Neuroimage. 2019 Feb 1;186:256-265. doi: 10.1016/j.neuroimage.2018.11.004. Epub 2018 Nov 10. — View Citation

Wallston KA, Wallston BS, DeVellis R. Development of the Multidimensional Health Locus of Control (MHLC) Scales. Health Educ Monogr. 1978 Spring;6(2):160-70. — View Citation

Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alpha asymmetry index (AAI) during neurofeedback	During neurofeedback, brain activity will be recorded continuously and the AAI will be extracted. Subsequently, AAIs will be compared between neurofeedback conditions. Details regarding the complete analysis pipeline can be found at the OSF online repository [www.osf.io/qbkj2].	During procedure (neurofeedback)
Primary	Pain ratings during neurofeedback (NRS; 1: 'no pain' to 100: 'worst tolerable pain')	At the end of each neurofeedback trial, participants will verbally rate the perceived intensity of a cutaneous laser stimulus. Subsequently, pain ratings will be compared between neurofeedback conditions. Details regarding the complete analysis pipeline can be found at the OSF online repository [www.osf.io/qbkj2].	During procedure (neurofeedback)
Primary	Pain-related brain responses during neurofeedback	During neurofeedback, brain activity will be recorded continuously, and the pain-related brain responses will be extracted. Subsequently, pain-related brain responses will be compared between neurofeedback conditions. Details regarding the complete analysis pipeline can be found at the OSF online repository [www.osf.io/qbkj2].	During procedure (neurofeedback)
Secondary	Motivation to participate in the training measured by a numerical rating scale (NRS; 1: 'very low' to 7: 'very high')	The motivation to participate in the training will be assessed using a self-report measure.	Before each session
Secondary	General self-efficacy (German version of the General Self-Efficacy Scale, GSE, minimum score: 10, maximum score: 40)	General self-efficacy will be assessed using the German version of the General Self-efficacy Scale.	Before each session
Secondary	Health-related locus of control (Multidimensional Health Locus of Control Scales, MHLC, minimum score: 3, maximum score: 15)	The health-related locus of control will be assessed using Multidimensional Health Locus of Control Scales.	Before each session
Secondary	Current positive or negative affect (Positive and Negative Affect Schedule, PNAS, minimum score: 10, maximum score: 50)	The current positive or negative affect will be assessed using the Positive and Negative Affect Schedule.	Before each session
Secondary	Perceived task demand (NRS; 1: 'very low' to 7: 'very high')	The perceived task demand will be assessed using a self-report measure.	After each condition
Secondary	Effort exerted (NRS; 1: 'very low' to 7: 'very high')	The effort exerted will be assessed using a self-report measure.	After each condition