Connectivity Patterns of Subthalamic Stimulation Influence Pain Outcomes in Parkinson's Disease

Abstract

Background: Pain is highly prevalent in Parkinson's disease and is associated with significant reduction in health-related quality of life. Subthalamic deep brain stimulation can produce significant pain relief in a subset of patients after surgery. However, the mechanism by which deep brain stimulation modulates sensory function in Parkinson's disease remains uncertain.Objective: To describe the motor and pain outcomes of deep brain stimulation applied to a series of patients with Parkinson's disease and to determine whether the structural connectivity between the volume of tissue activated and different regions of the brain was associated with the changes of these outcomes after surgery.Methods: Data from a long-term prospective cohort of 32 Parkinson's disease patients with subthalamic stimulation were combined with available human connectome to identify connections consistently associated with clinical improvement (Unified Parkinson Disease Rating Scale), pain intensity, and experimental cold pain threshold after surgery. Results:The connectivity between the volume of tissue activated and a distributed network of sensory brain regions (prefrontal, insular and cingulate cortex, and postcentral gyrus) was inversely correlated with pain intensity improvement and reduced sensitivity to cold pain after surgery (p < 0.01). The connectivity strength with the supplementary motor area positively correlated with motor and pain threshold improvement (p < 0.05).Conclusions: These data suggest that the pattern of the connectivity between the region stimulated and specific brain cortical area might be responsible, in part, for the successful control of motor and pain symptoms by subthalamic deep brain stimulation in Parkinson's disease.

A Meta-Analysis of the Effect of Subthalamic Nucleus-Deep Brain Stimulation in Parkinson's Disease-Related Pain

“…Therefore, we suggest that the results are due to the following two aspects: (i) STN-DBS does not change the pain network in a short time. It requires long-term stimulation to reshape the pain network and gradually increase the pain threshold of a patient (Pautrat et al, 2018 ; Cury et al, 2020 ; Dogru Huzmeli et al, 2020 ). (ii) Usually, the network of pain in patients includes inner pathways related to emotions and outer pathways related to nociceptive stimuli.…”

Computational Modelling of Deep Brain Stimulation for Parkinson's Disease: A Critical Review

“…While most investigations of the origins of PD movement disorder (MD) focus exclusively on the basal ganglia (BG) (commonly the pallidal-STN loop), other circuitry, notably the thalamus, corticothalamic loop, and the BG-cortico-thalamic loop, may contribute to pathological BG processing and therefore are all open to test by modelling (see Figure 1 in van Albada et al [8]). Likewise, it should not be ignored that DBS for non-MD symptoms such as pain may be valuable sources for DBS PD for MD model calibration and validation [51].…”

“…This work supports the orthodromic theory of DBS PD that, with SNc dopaminergic neuronal loss, GPe inhibition of STN weakens, producing elevated synchrony, in turn producing PD MD symptoms by blocking normal BG-MC signaling. DBS to dorsolateral STN or GPi reduces BG-thalamo-cortical synchrony and synchrony within the cortical motor areas, as indicated by beta-band power, thus removing the 'information block', restoring normal BG-MC signaling via thalamo-cortical projections [20,21,51]. If further studies reinforce this conclusion, it is a major clarification of DBS PD MoA and would help to focus modelers' efforts, beginning with reproducing the results of Johnson et al and incorporating the required parameters as a calibration of models including the motor cortex.…”

Perspective Chapter: Functional Human Brain Connectome in Deep Brain Stimulation (DBS) for Parkinson’s Disease (PD)

“…Growing evidence has showed that depending on the symptoms, connectomic DBS can act on different circuits in the brain. In this way, the neuromodulation surgery can affect both motor and non-motor functions (Table 2) [23,45,61,[72][73][74][75][76][77][78][79].…”