- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05570695
How do Alpha Oscillations Shape the Perception of Pain? - An EEG-based Neurofeedback Study
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].
Study Overview
Status
Conditions
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Markus Ploner, Prof. Dr. med.
- Phone Number: +49-89-4140-4608
- Email: markus.ploner@tum.de
Study Locations
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Bavaria
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Munich, Bavaria, Germany, 81675
- Recruiting
- Department of Neurology, Klinikum rechts der Isar, Technical University of Munich
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Contact:
- Markus Ploner, Prof. Dr. med.
- Phone Number: +49-89-4140-4608
- Email: markus.ploner@tum.de
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: neurofeedback
Modulation of brain activity using verum and sham neurofeedback.
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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.
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.
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).
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).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Alpha asymmetry index (AAI) during neurofeedback
Time Frame: During procedure (neurofeedback)
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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].
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During procedure (neurofeedback)
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Pain ratings during neurofeedback (NRS; 1: 'no pain' to 100: 'worst tolerable pain')
Time Frame: During procedure (neurofeedback)
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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].
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During procedure (neurofeedback)
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Pain-related brain responses during neurofeedback
Time Frame: During procedure (neurofeedback)
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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].
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During procedure (neurofeedback)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Motivation to participate in the training measured by a numerical rating scale (NRS; 1: 'very low' to 7: 'very high')
Time Frame: Before each session
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The motivation to participate in the training will be assessed using a self-report measure.
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Before each session
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General self-efficacy (German version of the General Self-Efficacy Scale, GSE, minimum score: 10, maximum score: 40)
Time Frame: Before each session
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General self-efficacy will be assessed using the German version of the General Self-efficacy Scale.
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Before each session
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Health-related locus of control (Multidimensional Health Locus of Control Scales, MHLC, minimum score: 3, maximum score: 15)
Time Frame: Before each session
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The health-related locus of control will be assessed using Multidimensional Health Locus of Control Scales.
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Before each session
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Current positive or negative affect (Positive and Negative Affect Schedule, PNAS, minimum score: 10, maximum score: 50)
Time Frame: Before each session
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The current positive or negative affect will be assessed using the Positive and Negative Affect Schedule.
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Before each session
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Perceived task demand (NRS; 1: 'very low' to 7: 'very high')
Time Frame: After each condition
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The perceived task demand will be assessed using a self-report measure.
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After each condition
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Effort exerted (NRS; 1: 'very low' to 7: 'very high')
Time Frame: After each condition
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The effort exerted will be assessed using a self-report measure.
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After each condition
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Markus Ploner, Prof. Dr. med., Department of Neurology, Klinikum rechts der Isar, Technical University of Munich
Publications and helpful links
General Publications
- 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. doi: 10.1037//0022-3514.54.6.1063.
- 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.
- 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. Erratum In: Nat Rev Neurosci. 2019 May;20(5):314.
- 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, Schonenberg 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, Luhrs M, Lubar J, Lotte F, Linden DEJ, Lewis-Peacock JA, Lebedev MA, Lanius RA, Kubler 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, Gobel RW, Gninenko N, Gharabaghi A, Frewen P, Fovet T, Fernandez 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.
- 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.
- 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.
- 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. doi: 10.1177/109019817800600107.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 09/2022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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