Objective: To systematically review the evidence linking basal ganglia local field potentials to non-motor symptoms in Parkinson’s disease.

Background: Deep brain stimulation for Parkinson’s disease is an effective treatment for medication-refractory motor symptoms, like motor fluctuations and tremor (1). Deep brain stimulation has also been associated with both improvements and deteriorations of several non-motor symptoms (2-4). Neurophysiological markers, or physiomarkers, associated with specific symptoms could improve deep brain stimulation programming (5). Significant progress has been made in understanding the physiomarkers of motor symptoms of Parkinson’s disease (6). We aimed to provide an overview of studies into physiomarkers of non-motor symptoms of Parkinson’s disease.

Method: A comprehensive search was conducted in the databases MEDLINE, Embase, Scopus, and Web of Science from inception to August 20, 2024. Studies were included if they focused on patients with idiopathic Parkinson’s disease treated with deep brain stimulation of the subthalamic nucleus (STN) or globus pallidus pars interna (GPi) and reported on the relationship between local field potentials and non-motor symptoms. The study risk of bias was evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST).

Results: The literature search yielded 1060 unique records. After screening on title and abstract, and subsequent full text review, twenty-one studies were included. Included studies focused on impulse control disorders (n=8), sleep-wake disorders (n=5), depressive symptoms (n=4), hypomania (n=1), cognitive dysfunction (n=3) and lower urinary tract symptoms (n=1). Theta and alpha power in the STN were frequently associated with neuropsychiatric symptoms and cognition function. Beta power in the STN and GPi was linked to sleep-wake disorders and urinary dysfunction. A visual overview of the results can be found in Figure 1.

Conclusion: Evidence on basal ganglia physiomarkers of non-motor symptoms in Parkinson’s disease remains limited. Further research is essential to develop patient-specific stimulation paradigms targeting non-motor symptoms, which could significantly improve the quality of life of individuals with Parkinson’s disease.

Visual overview of physiomarkers for NMS of PD.

References: 1. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63-73.
2. Dafsari HS, Reddy P, Herchenbach C, et al. Beneficial Effects of Bilateral Subthalamic Stimulation on Non-Motor Symptoms in Parkinson’s Disease. Brain Stimul. 2016;9(1):78-85
3. Zoon TJC, van Rooijen G, Balm G, et al. Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease: A Meta-Analysis. Mov Disord. 2021;36(2):317-26.
4. Jahanshahi M, Leimbach F, Rawji V. Short and Long-Term Cognitive Effects of Subthalamic Deep Brain Stimulation in Parkinson’s Disease and Identification of Relevant Factors. Journal of Parkinson’s Disease. 2022;12:2191-209.
5. Swinnen BEKS, Stam MJ, Buijink AWG, et al. Employing LFP recording to optimize stimulation location and amplitude in chronic DBS for Parkinson’s disease: A proof-of-concept pilot study. Deep Brain Stimulation. 2023;2:1-5.
6. van Wijk BCM, de Bie RMA, Beudel M. A systematic review of local field potential physiomarkers in Parkinson’s disease: from clinical correlations to adaptive deep brain stimulation algorithms. J Neurol. 2023;270(2):1162-77.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/basal-ganglia-physiomarkers-of-non-motor-symptoms-in-parkinsons-disease-a-systematic-review/