Experimental Pain in Healthy Human Subjects
Conditions
Keywords
pain, neurofeedback, alpha, neural oscillations, attention, brain, registered report
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 \[www.osf.io/qbkj2\].
Interventions
BEHAVIORALattention 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.
BEHAVIORALattention 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.
BEHAVIORALsham 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).
BEHAVIORALsham 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).
Sponsors
German Research Foundation
Studienstiftung des deutschen Volkes
Technical University of Munich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alpha asymmetry index (AAI) during neurofeedback | During procedure (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 \[www.osf.io/qbkj2\]. |
| Pain ratings during neurofeedback (NRS; 1: 'no pain' to 100: 'worst tolerable pain') | During procedure (neurofeedback) | 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 \[www.osf.io/qbkj2\]. |
| Pain-related brain responses during neurofeedback | During procedure (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 \[www.osf.io/qbkj2\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Current positive or negative affect (Positive and Negative Affect Schedule, PNAS, minimum score: 10, maximum score: 50) | Before each session | The current positive or negative affect will be assessed using the Positive and Negative Affect Schedule. |
| Motivation to participate in the training measured by a numerical rating scale (NRS; 1: 'very low' to 7: 'very high') | Before each session | The motivation to participate in the training will be assessed using a self-report measure. |
| Effort exerted (NRS; 1: 'very low' to 7: 'very high') | After each condition | The effort exerted will be assessed using a self-report measure. |
| Perceived task demand (NRS; 1: 'very low' to 7: 'very high') | After each condition | The perceived task demand will be assessed using a self-report measure. |
| General self-efficacy (German version of the General Self-Efficacy Scale, GSE, minimum score: 10, maximum score: 40) | Before each session | General self-efficacy will be assessed using the German version of the General Self-efficacy Scale. |
| Health-related locus of control (Multidimensional Health Locus of Control Scales, MHLC, minimum score: 3, maximum score: 15) | Before each session | The health-related locus of control will be assessed using Multidimensional Health Locus of Control Scales. |
Countries
Germany
Outcome results
None listed