Sensory Evidence and Expectations in Pain Processing

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

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.

Study Overview

• Status: Completed
• Conditions: Experimental Pain in Healthy Human Participants
• Intervention / Treatment: Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy); Device: Visual cueing

Detailed Description

Not needed

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 81675
      • Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Expectation and experimental pain in humans

Device: Painful stimulation using a laser device (DEKA Stimul 1340, Calenzano, Italy); 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.; Device: Visual cueing; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: German Research Foundation
• Investigators: Principal Investigator: Markus Ploner, Prof Dr med, Department of Neurology, Klinikum rechts der Isar, TUM

Publications and helpful links

General Publications

• Bastos AM, Usrey WM, Adams RA, Mangun GR, Fries P, Friston KJ. Canonical microcircuits for predictive coding. Neuron. 2012 Nov 21;76(4):695-711. doi: 10.1016/j.neuron.2012.10.038.
• Bastos AM, Vezoli J, Bosman CA, Schoffelen JM, Oostenveld R, Dowdall JR, De Weerd P, Kennedy H, Fries P. Visual areas exert feedforward and feedback influences through distinct frequency channels. Neuron. 2015 Jan 21;85(2):390-401. doi: 10.1016/j.neuron.2014.12.018. Epub 2014 Dec 31.
• Buchel C, Geuter S, Sprenger C, Eippert F. Placebo analgesia: a predictive coding perspective. Neuron. 2014 Mar 19;81(6):1223-1239. doi: 10.1016/j.neuron.2014.02.042.
• de Lange FP, Heilbron M, Kok P. How Do Expectations Shape Perception? Trends Cogn Sci. 2018 Sep;22(9):764-779. doi: 10.1016/j.tics.2018.06.002. Epub 2018 Jun 29.
• Egner T, Monti JM, Summerfield C. Expectation and surprise determine neural population responses in the ventral visual stream. J Neurosci. 2010 Dec 8;30(49):16601-8. doi: 10.1523/JNEUROSCI.2770-10.2010.
• Fazeli S, Buchel C. Pain-Related Expectation and Prediction Error Signals in the Anterior Insula Are Not Related to Aversiveness. J Neurosci. 2018 Jul 18;38(29):6461-6474. doi: 10.1523/JNEUROSCI.0671-18.2018. Epub 2018 Jun 22.
• Geuter S, Boll S, Eippert F, Buchel C. Functional dissociation of stimulus intensity encoding and predictive coding of pain in the insula. Elife. 2017 May 19;6:e24770. doi: 10.7554/eLife.24770.
• Todorovic A, de Lange FP. Repetition suppression and expectation suppression are dissociable in time in early auditory evoked fields. J Neurosci. 2012 Sep 26;32(39):13389-95. doi: 10.1523/JNEUROSCI.2227-12.2012.
• Todorovic A, van Ede F, Maris E, de Lange FP. Prior expectation mediates neural adaptation to repeated sounds in the auditory cortex: an MEG study. J Neurosci. 2011 Jun 22;31(25):9118-23. doi: 10.1523/JNEUROSCI.1425-11.2011.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2020
• Primary Completion (ACTUAL): December 1, 2020
• Study Completion (ACTUAL): December 1, 2020

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (ACTUAL): March 5, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 30, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: pain; brain; electroencephalography; laser-evoked potentials; neural oscillations; predictive coding
• Other Study ID Numbers: 03/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pseudonymized individual participant data sets will be made available at the OSF online repository [https://osf.io/] upon publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No