Title: Descending modulatory control of sensory processing and its impact on wellbeing
Funder: Economic and Social Research Council

Abstract: 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.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL;MENTAL HEALTH