DOI: 10.5061/dryad.np5hqc064
title: Somatotopic organization of brainstem analgesic circuitry

description: Rationale: By conducting a placebo analgesia conditioning paradigm using a
 falsely labelled and described cream, 93 pain-free participants believed
 this cream could reduce the intensity of painful heat applied to either
 their face, arm, or leg. In reality, this “lidocaine” cream was a placebo,
 and the temperature of a thermode surreptitiously lowered whenever placed
 onto this cream relative to a control Vaseline cream site. During
 collection of images of brainstem activity using a 7-Tesla Magnetic
 Resonance Imaging scanner, both the placebo and control cream sites
 received identical temperatures, with a decrease in perceived pain
 intensity during the placebo cream site stimulation being a placebo
 analgesia response. We analysed activity changes in the PAG and an area
 that the PAG contacts to inhibit pain, the rostral ventromedial medulla
 (RVM), during analgesia responses on the face, arm, and leg. Further,
 using the hidden application of a third cream to a separate body site, we
 explored whether analgesia was restricted to the area of stimulation or
 whether it was more widespread. Results: Our findings show that analgesia
 evoked on the face, arm, and leg changes activity in a somatotopically
 organized fashion, i.e. face analgesia is towards the rostral (top) of the
 PAG and RVM, arm and leg analgesia represented more caudally (lower).
 These somatotopically organized analgesic responses occurred on opposite
 sides of the PAG but at the same locations as pain activity changes, and
 the analgesia was restricted to the site where conditioning was applied.
description: # Somatotopic organization of brainstem analgesic circuitry Dataset DOI:
 [10.5061/dryad.np5hqc064](10.5061/dryad.np5hqc064) These data accompany
 the submission "Somatotopic Organization of Brainstem Analgesic
 Circuitry" - including behavioural pain and expectancy ratings, and
 raw 7-Tesla brain imaging datasets for conditioned placebo analgesia
 evoked on the face, arm, or leg. This readme file explains the content of
 each folder, and any further questions regarding the data can be sent
 directly to the first or corresponding author.  ## Description of the data
 and file structure Human 7-Tesla functional MRI data of conditioned
 placebo analgesia evoked on the face, arm, or leg.  Accompanying Excel
 provides average pain intensity data during each fMRI sequence, as well as
 demographic data including age and sex.  Functional sequences consisted of
 a block design with 134 dynamic scans included in each 4D nifti file for
 responder and nonresponder groups of each skin site. Each sequence
 consisted of eight blocks of pain stimuli, separated by inter-trial
 intervals.  Model timings: 6-38 = Baseline, 39-42 = Stimulus 1, 52-55 =
 Stimulus 2, 64-67 = Stimulus 3, 77-80 = Stimulus 4, 89-92 = Stimulus 5,
 102-105 = Stimulus 6, 115-118 = Stimulus 7, 127-130 = Stimulus 8.  A
 canonical HRF curve was applied to all data prior to the generation of 1st
 level GLMs, with a TR = 2.5 seconds As part of the data upload, all
 participants' fMRI series went through a defacing procedure, whereby
 a manual mask was derived for each participant encompassing identifiable
 facial structures, inverted, and applied as an inclusion mask to each
 individual 4D series, thereby masking out all facial features.  ### Files
 and variables #### File: adu8846_Pain_Ratings_and_Demography.xlsx
 **Description:** Pain intensity ratings and demography for each
 participant in the responder or nonresponder group for placebo analgesia
 evoked on the right side of the face, arm, or leg. During each functional
 sequence, the position of a thermal probe was moved between a portion of
 these skin sites where either a control or inert placebo
 "lidocaine" cream had been applied. #### File:
 Defaced_Leg_Placebo_Responders.7z **Description:** Leg Responder group,
 organized into separate "control" and "placebo" 4D
 Nifti files for the two independent fMRI sequences.  #### File:
 Defaced_Leg_Placebo_Nonresponders.7z **Description:** Leg Nonresponder
 group, organized into separate "control" and "placebo"
 4D Nifti files for the two independent fMRI sequences.  #### File:
 Defaced_Face_Placebo_Nonresponders.7z **Description:** Face Nonresponder
 group, organized into separate "control" and "placebo"
 4D Nifti files for the two independent fMRI sequences.  #### File:
 Defaced_Arm_Placebo_Nonresponders.7z **Description:** Arm Nonresponder
 group, organized into separate "control" and "placebo"
 4D Nifti files for the two independent fMRI sequences.  #### File:
 Defaced_Face_Placebo_Responders.7z **Description:** Face Responder group,
 organized into separate "control" and "placebo" 4D
 Nifti files for the two independent fMRI sequences.  #### File:
 Defaced_Arm_Placebo_Responders.7z **Description:** Arm Responder group,
 organized into separate "control" and "placebo" 4D
 Nifti files for the two independent fMRI sequences.  #### File:
 DisciplineSpecificMetadata.json **Description:** Information regarding
 ethical approval and point of contact for data queries, MRI sequence
 acquisition, and experimental design structure.  ##### Variables * Ongoing
 pain intensity  ## Code/software Respiratory and Physiological noise
 modelling and
 removal: [https://www.sciencedirect.com/science/article/pii/S1053811912000845](https://www.sciencedirect.com/science/article/pii/S1053811912000845) Synthetic Distortion Correction: [https://github.com/MASILab/SynBOLD-DisCo](https://github.com/MASILab/SynBOLD-DisCo) Brainstem isolation and normalization: [https://www.diedrichsenlab.org/imaging/suit.htm](https://www.diedrichsenlab.org/imaging/suit.htm) Image processing pipeline: 1. Slice timing correction 2. Motion correction 3. Physiological and respiratory noise modelled and removed  4. Linear detrending  5. Motion parameter noise removed  6. 1mm isotropic reslice 7. T1 coregistration  8. Synthetic distortion correction  9. SUIT brainstem isolation 10. SUIT normalization 11. 0.5mm isotropic reslice 12. Spatial smoothing 1mm FWHM  Steps 1, 2, 4, 5, 6, 7, 11, and 12 can be performed in any standard installation of Matlab with the statistical parametric mapping (SPM12) toolbox installed Step 3 requires the DRIFTER toolbox linked above Step 8 requires the SynBOLD DisCO pipeline linked above  Steps 9,10 require the SUIT toolbox linked above ## Access information Data was derived from the following sources: * These data were collected at a research imaging facility using a 7-Tesla MRI scanner by the first and corresponding author ## Human subjects data Consent was attained for future use of de-identified functional imaging data, in this instance uploaded to the public domain. Image de-identification was performed through DICOM to Nifti conversion, stripping the header information from individual participant data. Participants have been coded as "participant 1, 2, ..." in both nifti imaging and behavioural datasets.