The Genetic Etiology of Parkinson's Disease Does Not Robustly Affect Subthalamic Physiology

Abstract

Background: It is unknown whether Parkinson's disease (PD) genetic heterogeneity, leading to phenotypic and pathological variability, is also associated with variability in the unique PD electrophysiological signature. Such variability might have practical implications for adaptive deep brain stimulation (DBS). Objective: The aim of our work was to study the electrophysiological activity in the subthalamic nucleus (STN) of patients with PD with pathogenic variants in different disease-causing genes. Methods: Electrophysiological data from participants with negative genetic tests were compared with those from GBA, LRRK2, and PRKN-PD. Results: We analyzed data from 93 STN trajectories (GBA-PD: 28, LRRK2-PD: 22, PARK-PD: 10, idiopathic PD: 33) of 52 individuals who underwent DBS surgery. Characteristics of β oscillatory activity in the dorsolateral motor part of the STN were similar for patients

A longitudinal electrophysiological and behavior dataset for PD rat in response to deep brain stimulation

“…This suggests that DBS may act through multiple synergetic mechanisms 15 , rather than simply inhibiting or exciting the basal ganglia nuclei. Dopamine depletion is accompanied by elevated beta-band oscillatory activity in the cortico-basal ganglia-thalamic motor control loop 16 – 20 . Although the mechanisms leading to the abnormal beta-band oscillatory activity are still unclear, the abnormal oscillatory activity also indicate that significant changes occur in the neural network and neuronal information transmission of the cortico-basal ganglia-thalamic loop.…”

Cognitive Effects of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease with GBA1 Pathogenic Variants

“…30 On average, GBA1-PD patients receive lower scores on cognitive tests at the time of operation. 42 Would an earlier referral of these patients to STN-DBS minimize the possible cognitive side effect of the procedure?…”

“…Pre‐operative cognitive impairments are a risk factor for accelerated post‐operative cognitive deterioration 30 . On average, GBA1 ‐PD patients receive lower scores on cognitive tests at the time of operation 42 . Would an earlier referral of these patients to STN‐DBS minimize the possible cognitive side effect of the procedure?…”

Reply to: “Subthalamic Physiology in Genetic Subtypes of Parkinson's Disease”

“…We thank Dr. Pal and his colleagues for their interesting comments. Our study 1 focused on the β oscillatory activity in the dorsolateral subthalamic nucleus (STN) 2 . This electrophysiological signature, which is correlated with the emergence of parkinsonian signs during OFFs, is the most extensively explored oscillatory activity in human patients with Parkinson's disease (PD).…”