Sensory Evidence and Expectations in Pain Processing

Study Overview
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Brief Summary
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Pain is a highly complex and subjective phenomenon which is not only rooted in sensory information but also shaped by cognitive processes such as expectation. However, the interaction of brain activity cording sensory information and expectation in pain processing are not completely understood. Predictive coding models postulate specific hypothesis about the interplay between bottom-up sensory information and top-down expectations in terms of prediction errors and predictions, respectively. They further implicate brain oscillations at different frequencies, which play a crucial role in processing prediction errors and predictions. More specifically, recent evidence in visual and auditory modalities suggests that predictions are reflected by alpha (8-13 Hz) and beta oscillations (14-30 Hz) and prediction errors by gamma oscillations (60-100 Hz). However, for the processing of pain, these frequency-specific relationships have not been addressed so far. The current project aims to investigate brain activity which reflects predictions, prediction errors and sensory evidence in pain processing using a cueing paradigm. To this end, we will apply painful stimuli with low and high intensity to the dorsum of the left hand in 50 healthy subjects. A visual cue, preceding to each painful stimulus, will predict the intensity of the consecutive painful stimulus (low vs. high) with a probability of 75%. After each painful stimulus, participants will be asked to rate the perceived pain intensity. Electroencephalography (EEG) and skin conductance will be recorded continuously during anticipation and stimulation intervals. This paradigm enables us to compare pain-associated brain responses of validly and invalidly cued trials, i.e. the representation of the prediction error, on the one hand. On the other hand, brain activity related to predictions can be investigated in the anticipation interval preceding to the painful stimulus by comparing trials with low and high intensity cues. Further, we will compare models including predictions, prediction error and sensory evidence to ascertain the involvement of each brain response in processing sensory information and expectation. Results of the study promise to elucidate the interplay of predictions, predictions errors and sensory evidence in pain processing and how they differentially relate to neural oscillations at different frequency bands and pain-evoked responses.

Detailed Description
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Not needed

Official Title
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The Role of Sensory Evidence and Expectations in the Cerebral Processing of Pain

Conditions
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Experimental Pain in Healthy Human Participants

Intervention / Treatment
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* Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy)
* Device: Visual cueing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Right-handedness Written informed consent 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 Surgical procedures involving the head or spinal cord Metal (except titanium) or electronic implants Side-effects following previous thermal stimulation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Each participant will participate in one experimental session with a duration of 40 minutes. The experimental paradigm consists of 160 painful stimuli of two intensities (low and high), which will be applied using a laser stimulation device (DEKA Stimul 1340, Calenzano, Italy). Preceding to each painful stimulus, visual cues will be presented indicating the intensity of the subsequent stimulus with an accuracy of 75%. After each painful stimulus, participants will be prompted to verbally rate the pain intensity on a scale ranging from 0 ('no pain') to 100 ('maximum tolerable pain'). Brain activity and autonomic activity will be recorded simultaneously using EEG and skin conductance responses (SCRs), respectively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Expectation and experimental pain in humans<br> | Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy)<br>* In the experimental paradigm, 160 painful stimuli of two intensities (3 J, 3.5 J) will be applied to the dorsum of the left hand using the laser device listed above.<br>Device: Visual cueing<br>* Preceding to each painful stimulus, visual cues (e.g., blue dot and yellow square) will be presented on a screen indicating the intensity of the subsequent stimulus (low and high intensity) with an accuracy of 75%. The contingencies of the visual cues will be explicitly stated to the participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain') | 160 painful stimuli will be applied to the participants' left hand. Participants will be asked to verbally rate the perceived pain intensity of each stimulus on a numerical rating scale (see above). | During 40 minutes of the experimental paradigm | 
| Oscillatory and evoked brain responses pre- and post-stimulus | EEG including 64 channels will be recorded. In offline analyses, power of oscillatory brain activity will be quantified in the alpha (8-13 Hz), beta (14-30 Hz) and gamma (60-100 Hz) frequency bands. In addition, laser-evoked potentials (LEPs) will be quantified with regard to amplitudes and latencies. | During 40 minutes of the experimental paradigm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SCRs (µS) | SCRs will be recorded using two electrodes attached to the index and middle finger of the left hand. | During 40 minutes of the experimental paradigm | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, electroencephalography, laser-evoked potentials, neural oscillations, brain, predictive coding