Introduction: Depression and anxiety are among the most prominent non-motor symptoms in Parkinson’s disease (PD) and the pathophysiology underlying these symptoms remains largely unknown. We used permanent prefrontal cortex implants to investigate neural correlates of these symptoms and to develop a novel neurostimulation therapy for these mood symptoms of PD. This study focused on the orbito-frontal cortex (OFC), part of the cortico-striatal-thalamic circuit that has been implicated in major depression in previous non-invasive studies.
Methods: Two PD patients undergoing DBS surgery for motor fluctuations who also had moderate pre-operative anxiety and depression symptoms were enrolled in this study. In addition to bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) leads, both patients were implanted with a permanent 4-contact ECoG strip with at least 2 contacts covering the right OFC. The ECoG strip and ipsi-lateral DBS lead were attached to an Activa PC+S. Cortical and STN potentials were recorded during regular clinic visits either on or off Parkinsonian medication conditions. Patient1 was instructed to trigger recordings at home, during the presence of minimal and more severe anxiety or depression. Recordings were paired with assessments of mood based on visual analogue scales (VAS). The effect of acute (15min-24hr) OFC stimulation was also studied in patient1.
Results: We found: 1) a peak in the alpha/beta band in the power spectrum of the OFC potentials. 2) Dopaminergic medication did not consistently affect OFC signals, although it did reduce STN beta power. 3) The severity of depression and anxiety was significantly correlated with OFC beta power (p<0.01). 4) Acute OFC stimulation (3V, 80-100us, 100-180Hz) was associated with a reduction of these symptoms without inducing side effects.
Conclusions: These preliminary results suggest that OFC beta oscillations may be associated with anxiety and depression in PD, and indicate a potential therapeutic effect of OFC stimulation.
Patient Care: In contrast to the motor symptoms, the pathophysiology of anxiety and depressionin PD is largely unknown. None of the currently available therapies for the motor signs of PD (i.e. dopaminergic medication, DBS) alleviate these symptoms. It is therefore crucial to investigate the pathophysiology underlying these symptoms in order to develop a comprehensive treatment for these patients.
Learning Objectives: The aim of this study was to investigate neural correlates of anxiety and depression in PD, and to develop a novel neurostimulation therapy for these symptoms