Clinical trial NCT04296968: Sensory Evidence and Expectations in Pain Processing
Official title: The Role of Sensory Evidence and Expectations in the Cerebral Processing of Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Experimental Pain in Healthy Human Participants
Keywords: pain
electroencephalography
laser-evoked potentials
neural oscillations
brain
predictive coding
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2020-03-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief summary: 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: Not needed

Eligibility criteria: 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

Primary outcomes:
measure: Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximum tolerable pain')
timeFrame: During 40 minutes of the experimental paradigm
measure: Oscillatory and evoked brain responses pre- and post-stimulus
timeFrame: During 40 minutes of the experimental paradigm
Secondary outcomes:
measure: SCRs (µS)
timeFrame: During 40 minutes of the experimental paradigm
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Neurology, Klinikum rechts der Isar, Technische Universität München
state: Bavaria
Study officials:
affiliation: Department of Neurology, Klinikum rechts der Isar, TUM
name: Markus Ploner, Prof Dr med
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.