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

NCT ID: NCT05570695

Last Updated: 2024-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-01

Study Completion Date

2023-12-31

Brief Summary

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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 \[www.osf.io/qbkj2\].

Detailed Description

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Conditions

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Experimental Pain in Healthy Human Subjects

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Each participant will participate in 4 experimental conditions differing with respect to the administered neurofeedback training: (1) attention right training, ARTNF; (2) attention left training, ALTNF; (3) sham attention right training, ARTsham; (4) sham attention left training, ALTsham. During neurofeedback, noxious stimuli will be applied to the dorsum of the left hand using cutaneous laser stimulation (Nd:YAP laser, Stimul 1340, DEKA M.E.L.A. srl, Calenzano, Italy; stimulation settings: 4 ms duration, 7 mm stimulus diameter, 3.5 J laser intensity) while pain ratings will be recorded.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Double-blinding will be enabled through the usage of sham conditions which comprise an identical sequence of events as the verum conditions and participant-specific numeric codes encoding the order of conditions. During each session, these codes will automatically (1) determine the predefined training conditions and (2) generate file names. Thus, the experimenter will be blinded during data acquisition as well as during subsequent preprocessing and analysis steps.

Study Groups

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neurofeedback

Modulation of brain activity using verum and sham neurofeedback.

Group Type EXPERIMENTAL

attention right training, ARTNF

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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

Intervention Type BEHAVIORAL

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).

Interventions

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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.

Intervention Type BEHAVIORAL

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.

Intervention Type BEHAVIORAL

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).

Intervention Type BEHAVIORAL

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).

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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German Research Foundation

OTHER

Sponsor Role collaborator

Studienstiftung des deutschen Volkes

UNKNOWN

Sponsor Role collaborator

Technical University of Munich

OTHER

Sponsor Role lead

Responsible Party

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Markus Ploner

Professor of Human Pain Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Markus Ploner, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich

Locations

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Department of Neurology, Klinikum rechts der Isar, Technical University of Munich

Munich, Bavaria, Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 28025007 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32176800 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28003656 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30423429 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16887192 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 689890 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3397865 (View on PubMed)

Hohn VD, Tiemann L, Bott FS, May ES, Fritzen C, Nickel MM, Gil Avila C, Ploner M. Neurofeedback and attention modulate somatosensory alpha oscillations but not pain perception. PLoS Biol. 2025 Jan 23;23(1):e3002972. doi: 10.1371/journal.pbio.3002972. eCollection 2025 Jan.

Reference Type DERIVED
PMID: 39847605 (View on PubMed)

Other Identifiers

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09/2022

Identifier Type: -

Identifier Source: org_study_id

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