Descending modulatory control of sensory processing and its impact on wellbeing

Lead Research Organisation: Cardiff University
Department Name: Sch of Psychology


How do you feel? Warm? Loved? Hurt? In danger? Isolated? As humans, we frequently "look inward" in order to guide our actions. But what bodily senses inform this "looking inwards" (or, interoception)?
Thin nerve fibres arising in the skin carry a multitude of sensations to their relay in the spinal cord, including information about pain, warmth and pleasant touch. It is here in the spinal cord, specifically in an area called the dorsal horn, that these nerve fibres connect with nerve-bundle 'highways' carrying information to other parts of the spinal cord and the brain. Within the brain, the interoceptive information carried by these 'highways' finds targets in the brainstem (the brain's connection with the spinal cord) and areas of the cortex (the highly folded surface of the brain), and it is thought that these cortical targets are essential for generating interoceptive feelings and translating them into action (Craig, 2002).
But that isn't the end of the story. The connections between the spinal cord dorsal horn and the brain don't just go in one direction, indeed activity in the brain can also alter activity in the spinal cord dorsal horn (at least for pain). Expecting a drug to have a beneficial effect on a painful event (e.g. being pricked by an experimenter with a pin!) activates the brain areas mentioned above and by brain-to-cord connections, stops (inhibits) the thin nerve fibres (carrying pain information from the skin) from passing on their information to the spinal cord sensory 'highway' (carrying pain information to the brain) (Eippert et al., 2009a, 2009b). That is, pain information can be modified at the level of the spinal cord dorsal horn without the brain ever knowing about the pain!
There is an ever-increasing understanding of how the above phenomenon, descending modulation, affects pain processing and this was a key theme in my doctoral research. Far less in known about how descending modulation might alter other interoceptive sensations, e.g. pleasant touch, and this is the focus of my research going forward.
My thesis was an investigation into chronic pain in a condition called neuromyelitis optica (NMO). I used MRI to scan patients' brains and spinal cords and found that disease-related damage to a specific area of the spinal cord (the thoracic cord) is important in generating pain. I also found that NMO subjects have significant changes in their descending modulation brain networks. Some of these findings have already been published in academic journals and presented nationally and internationally. Support from the ESRC fellowship will allow further analysis of findings not yet published, including the intricacies of the pain modulating brain network and changes in the spinal cord "highways" that convey pain-relevant information to and from the brain. The ESRC fellowship will also provide the means to communicate my results to academics (via publications and presentations), but also to the general public through outreach events at Cardiff University.
Moving forward, to gain a better understanding of descending modulation and its activity at the level of the spinal cord dorsal horn and to place this in the context of socially relevant stimuli (i.e. pleasant touch), I have selected Cardiff University, a centre of excellence for psychology and with state-of-the-art MRI facilities. Using previous experience of spinal cord imaging, with the help of Cardiff's MRI physicists, and through collaborations with the Universities of Oxford and Bristol, I will establish spinal cord MRI as a practical tool in Cardiff University's Brain Research imaging Centre (CUBRIC). I will then test painful and non-painful stimuli (such as pin-pricks and brush strokes) to show that we can record meaningful MRI activity in the spinal cord. Under the mentorship of Professor Andrew Lawrence, I will conduct studies to observe descending modulation in varied psychological and social contexts, and in psychiatric disease.
Description Cardiff University Brain Research Imaging Centre (CUBRIC) is Wale's flagship neuroscience facility and home to world-leading expertise and technology. Until 2018 however (and as the unabbreviated name for the centre suggests), spinal cord imaging has not been a feature of the research performed here. My ERSC funded project provided the means to change this and CUBRIC is now able to acquire detailed images of spinal cord anatomy (standard and diffusion MRI), as well as real-time measures of spinal cord nerve tissue function (functional MRI).

With my lead, we are now very much a part of the national spinal cord imaging research community, with ongoing collaborations looking at sequence development with Bristol (CRIC) and Oxford's (FMRIB) imaging centres, hosting the first CUBRIC-CRIC-FMRIB symposium in CUBRIC in 2019. I am currently evaluating a new sequence forged by this collaboration with some exciting results to be published soon.

We are now also regular participators in the international spinal cord imaging effort, spearheaded by Julien Cohen-Adad (Polytechnique Montréal, Canada). Within this arena Cardiff has contributed newly acquired spinal cord data to a multi-centre international database which forms an important resource that will be used to evaluate consensus protocols for future spinal cord work worldwide.
Exploitation Route Cardiff's contributions to the internationally available standard spinal cord protocol database will be used as a benchmark by many future spinal cord imaging studies.

Our data on an improved spinal cord functional imaging protocol has now been accepted as an abstract/poster for the upcoming BNA 2021 Festival of Neuroscience, where it will be available to all attendees and of particular interest to spinal cord researchers.

Pilot data, generated during the award, has enabled me to obtain further competitive funding to pursue this research. In my current (new) post, I am continuing to establish whether affective touch stimuli have a unique representation in the cord that (a) can be dissociated from other sensory inputs and (b) be modulated by descending inputs in a manner similar to the placebo effect and pain.

Having established spinal cord imaging in Cardiff, researchers from many disciplines within the University will have the option of incorporating this technique into future imaging studies.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

Description One of the important impacts of my research as I engage with the general public is reinforcing the concept that chronic pain and some other 'psychological' disorders of sensory processing have very 'real' roots in neuronal circuits, and counter-intuitively are not always "all in our heads". Indeed some of the disordered processing occurs at the level of the spinal cord. I think this gives sufferers of relevant conditions an amount of solace and a healthier attitude towards seeking the appropriate help and avoiding self-blame, and makes non-sufferers less likely to judge someone who may well be in real distress as malingering.
First Year Of Impact 2018
Impact Types Cultural,Societal

Description 1st year medical student tutorials on 'general sensation', feedback implemented and suggestions taken on board for future tutorials
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact After delivering tutorials to the medical students on general sensation, my feedback has been used to modify the teaching documents to ensure they are (a) scientifically up-to-date and (b) relevant for the stage of training. I fed back directly to the module author and met with the director of year 1 medical training in Cardiff to discuss my ideas. I'm hopeful that this will enhance the learning experience of medical students in their early years and improve their clinical acumen when encountering patients with conditions relevant to the spinal cord.
Description Cardiff University - EPSRC Capital Award for Core Equipment
Amount £400,000 (GBP)
Funding ID EP/T024372/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 12/2019 
End 04/2021
Description NMHRI Conference Travel AWARDS
Amount £350 (GBP)
Organisation Cardiff University 
Sector Academic/University
Country United Kingdom
Start 12/2018 
End 07/2019
Title Functional MRI (fMRI) of the spinal cord - new sequence development and validation 
Description A new fMRI method that combines previous advances. Provides reduced field of view and corrections for image drop-out in the z-plane. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact Developed with CRIC (Bristol) and tested in CUBRIC. Validation of method being analysed by me in collaboration with CRIC and FMRIB (Oxford). Impacts: Reinforcing collaborative efforts with other UK based spinal cord researchers (esp. CUBRIC and CRIC). Paper being drafted. 
Title Somatosensory Testing Lab 
Description (see EPSRC funding entry under funding) I was the main author and convenor for a subsection of the EPSRC Core Equipment bid. The purpose of which is to fund a comprehensive somatosensory testing suite in CUBRIC, to enable us to perform detailed QST and to provide numerous noxious and non-noxious stimuli for use in the MRI environment. The main item funded is a set of thermodes that can deliver warm, cool, heat-pain and heat-cold stimuli, in and out of the scanner. It also includes pin-prick stimulators, Von Frey hairs, brushes, spatial discrimination stimuli, a pneumatic haptic-feedback device and an algometer. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2020 
Provided To Others? Yes  
Impact Equipment yet to be purchased. Significant interest from Cardiff University researchers in the fields of developmental neuroscience (see collaborations) and arthritis. 
Title Spinal Cord MRI Public Database 
Description Having brought together international spinal cord imaging experts to decide a consensus acquisition protocol, the database was populated from multinational datasets. It can now be used to evaluate reproducibility across different vendors and thus provide researchers with normative values and variability indices, allowing them to conduct power analyses before engaging into SC studies. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact ISMRM abstract: Quantitative MRI of the spinal cord: reproducibility and normative values across 40 sites. ISMRM Annual Meeting, April 18-23 2020. ( Paper in draft. Regular spinal cord workshops discussing the data already collected. 
Description FMRIB, University of Oxford 
Organisation University of Oxford
Department Oxford Centre for Functional MRI of the Brain (FMRIB)
Country United Kingdom 
Sector Academic/University 
PI Contribution Presentations to FMRIB pain group on pain and affective networks. Analysis of common dataset.
Collaborator Contribution Input on pain paradigms (e.g. suitable pain stimuli). Ongoing input and advice regarding analysis pipelines. Ongoing input and provision of scanner protocols.
Impact - Improved scanner functional imaging protocols - Presented abstract & poster for BNA 2019 and Neuropsig meetings
Start Year 2018
Description Max Planck Institute, Leipzig 
Organisation Max Planck Society
Department Max Plank Institute for Human Cognitive and Brain Sciences
Country Germany 
Sector Academic/University 
PI Contribution Sharing of knowledge and expertise with spinal cord and pain imaging researcher Dr Falk Eippert.
Collaborator Contribution Mutual sharing of acquisition and processing pipelines for SC imaging.
Impact - Improved subject positioning in scanner - Honing of pain stimulus protocol (block-design) - Improved efficiency of processing pipeline usage
Start Year 2019
Description Multi-center study using spinal cord consensus protocol Announcements 
Organisation École Polytechnique de Montréal
Country Canada 
Sector Academic/University 
PI Contribution Currently acquiring structural and diffusion images to in line with multi-centre study protocols.
Collaborator Contribution Provided baseline structural protocols, optimised for spinal cord imaging. These are used for registering functional and diffusion data. Provided optimised diffusion imaging protocols.
Impact - Publication drafted, planned for completion in April 2019. - This will also eventually result in a publicly shared database of standardised spinal cord data that international partners can used for quality control purposes and baselines for further research.
Start Year 2018
Description Brain Night, CUBRIC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Fliers and online adverts were distributed to the general public and within Cardiff University, inviting them to an evening at CUBRIC to discover facts about the brain and to explore the research performed within the centre.
I ran one of the interactive events ("how does colour affect taste perception"), and whilst distributing different coloured liquids for attendees to try, had many opportunities to discuss my own work, particularly my interest in how environment and social circumstance might alter pain perception.
Year(s) Of Engagement Activity 2018
Description Public Talk - "Public Uni", an opportunity for researchers to engage the general public with details from their research. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A short powerpoint-free talk for the general public, hosted by "Public Uni" in the Chapter Arts centre in Cardiff.
The idea behind the event is to provide the public with access to activities going on in Cardiff University, and to update them about recent research in an engaging manner.
Lots of questions were asked about the spinal cord, how it is engaged in complex sensory (±psychological) processing and there was a good amount of interest on Twitter.
Year(s) Of Engagement Activity 2019