Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS

Abstract

Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits.

Sub-Optimal Learning of Tactile-Spatial Predictions in Patients with Complex Regional Pain Syndrome

“…This was achieved by statistically predicting behaviour (RTs) from factors in the experimental design (validating the task) and from simulations of the computational model (validating the model). Specifically, RTs were modulated by both top-down (spatial change probability) and bottom-up (spatial change distance) factors, in a manner consistent with their putative role as markers of precision-weighted PEs in the brain (Kuttikat et al, 2018, 2016a). Subsequently, the computational model was able to simulate (reproduce) these condition-effects on behaviour and individual differences in these condition effects.…”

“…Numerous behavioural studies have revealed links between pain and deficits in spatial discrimination of tactile stimuli (Förderreuther et al, 2004; Lewis and Schweinhardt, 2012; Pleger et al, 2006). Those studies, coupled with initial findings of altered somatotopic mapping of the affected (painful) limb in the primary somatosensory cortex (S1) in CRPS (Di Pietro et al, 2013; Kuttikat et al, 2016a), have motivated therapies focussed on S1 re-mapping, for example tactile discrimination training (Moseley et al, 2008). However, more recent high-resolution functional Magnetic Resonance Imaging (fMRI) studies have failed to replicate somatotopic abnormalities of S1 (Di Pietro et al, 2015; Mancini et al, 2018; van Velzen et al, 2016).…”

“…However, more recent high-resolution functional Magnetic Resonance Imaging (fMRI) studies have failed to replicate somatotopic abnormalities of S1 (Di Pietro et al, 2015; Mancini et al, 2018; van Velzen et al, 2016). This has led to further hypotheses of deficits in higher-order mechanisms to explain sensory symptoms in CRPS (Kuttikat et al, 2016a; Popkirov et al, 2018).…”

Taking the sting out of CRPS: bee venom to treat complex regional pain syndrome

“…The impact of altered pain self-regulation might be to increase pain perception and sensitivity. Frontal cortex involvement in CRPS is supported by the effectiveness of cognitive behavioural therapy in its management [6].…”

Complex regional pain syndrome and functional neurological disorders – time for reconciliation

“…Bidirectional hierarchical models based on Bayesian inference have recently been formulated for both FND36 and CRPS 45. They necessitate a rethinking for both disorders in which outdated ideas of ‘psychogenic versus neurogenic’ have to be shaken off permanently.…”