Clinical pain and functional network topology in Parkinson\u2019s disease: a resting-state fMRI study

Annemarie Vlaar,Brónagh McCoy,Linda Douw,Jan Theeuwes,Henry Weinstein,Erik Scherder,Gwenda Engels

doi:10.1007/s00702-018-1916-y

Abstract

Pain is an important non-motor symptom in Parkinson’s disease (PD), but its underlying pathophysiological mechanisms are still unclear. Research has shown that functional connectivity during the resting-state may be involved in persistent pain in PD. In the present cross-sectional study, 24 PD patients (both during on and off medication phase) and 27 controls participated. We assessed pain with the colored analogue scale and the McGill pain questionnaire. We examined a possible pathophysiological mechanism with resting-state fMRI using functional network topology, i.e., the architecture of functional connections. We took betweenness centrality (BC) to assess hubness, and global efficiency (GE) to assess integration of the network. We aimed to (1) assess the differences between PD patients and controls with respect to pain and resting-state network topology, and (2) investigate how resting-state network topology (BC and GE) is associated with clinical pain in both PD patients and controls. Results show that PD patients experienced more pain than controls. GE of the whole brain was higher in PD patients (on as well as off medication) compared to healthy controls. GE of the specialized pain network was also higher in PD patients compared to controls, but only when patients were on medication. BC of the pain network was lower in PD patients off medication compared to controls. We found a positive association between pain and GE of the pain network in PD patients off medication. For healthy controls, a negative association was found between pain and GE of the pain network, and also between pain and BC of the pain network. Our results suggest that functional network topology differs between PD patients and healthy controls, and that this topology can be used to investigate the underlying neural mechanisms of pain symptoms in PD.

Highlights

Parkinson’s disease (PD) was for a long time mainly considered a motor disease, with rigidity, bradykinesia and resting tremor as its cardinal symptoms
Our results on functional network topology indicate that PD patients had a higher efficiency of the whole brain off medication as well as on medication compared to healthy controls
Global efficiency of the pain network was higher compared to controls, but only when PD patients were on medication

Summary

Introduction

Parkinson’s disease (PD) was for a long time mainly considered a motor disease, with rigidity, bradykinesia and resting tremor as its cardinal symptoms. There has been growing interest in the non-motor symptoms of PD (Postuma et al 2015), which may be or more incapacitating than the motor symptoms themselves (Chaudhuri et al 2006) Pain is one such non-motor symptom that is present in about two-thirds of PD patients (Defazio et al 2008; Broen et al 2012), and puts an additional burden on patients’ quality of life (Quittenbaum and Grahn 2004; Shibley et al 2008; Buhmann et al 2017). During the past few decades, possible neural substrates of pain have been studied extensively, resulting in a potential network of connected brain areas that is thought to underlie the processing and experience of pain (Tracey and Mantyh 2007). Many of the areas involved in this NPS are congruent with areas previously associated with pain, such as the insula, ACC, PFC, thalamus and SII (Tracey and Mantyh 2007)

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