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

NCT05570695 | Completed

• 1 other identifier: 09/2022
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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

Conditions

Experimental Pain in Healthy Human Subjects

Keywords

pain; neurofeedback; alpha; neural oscillations; attention; brain; registered report

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (6)

• Motivation to participate in the training measured by a numerical rating scale (NRS; 1: 'very low' to 7: 'very high')

  Before each session

• General self-efficacy (German version of the General Self-Efficacy Scale, GSE, minimum score: 10, maximum score: 40)

  Before each session

• Health-related locus of control (Multidimensional Health Locus of Control Scales, MHLC, minimum score: 3, maximum score: 15)

  Before each session

• Current positive or negative affect (Positive and Negative Affect Schedule, PNAS, minimum score: 10, maximum score: 50)

  Before each session

• Perceived task demand (NRS; 1: 'very low' to 7: 'very high')

  After each condition

Study Arms (1)

neurofeedback

EXPERIMENTAL

Modulation of brain activity using verum and sham neurofeedback.

Behavioral: attention right training, ARTNF; Behavioral: attention left training, ALTNF; Behavioral: sham attention right training, ARTsham; Behavioral: sham attention left training, ALTsham

Interventions

attention right training, ARTNF 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.

neurofeedback

attention left training, ALTNF 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.

neurofeedback

sham attention right training, ARTsham 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).

neurofeedback

sham attention left training, ALTsham 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).

neurofeedback

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Technical University of Munich: lead
• German Research Foundation: collaborator
• Studienstiftung des deutschen Volkes: collaborator

Study Sites (1)

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

Munich, Bavaria, 81675, Germany

Location

Related Publications (8)

• 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.

  PMID: 28025007 BACKGROUND

• 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.

  PMID: 32176800 BACKGROUND

• 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.

  PMID: 28003656 BACKGROUND

• 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.

  PMID: 30423429 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

• 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.

  PMID: 689890 BACKGROUND

• 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.

  PMID: 3397865 BACKGROUND

• 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.

  PMID: 39847605 DERIVED

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Markus Ploner, Prof. Dr. med.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Human Pain Research

Model Details: 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.

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: October 7, 2022
• Study Start: October 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Immediately after publication

Locations

DE (1)