Anxiety in Parkinson’s disease: using fMRI to evaluate amygdala networks in the on and off dopamine state

PROJECT SUMMARY Anxiety is a top unmet need in people with Parkinson's disease (PD) associated with high levels of distress, caregiver burden, lower quality of life, and disruption of usual activities. Diagnosis and treatment of anxiety in PD is complicated due to its association with dopamine fluctuations, comorbidity with depression, and lack of evidence-based treatments. The result is that anxiety often goes undiagnosed and untreated, or is treated with inappropriate, potentially dangerous medications. The goal of the proposed study is to understand the brain networks involved in anxiety, test how they are affected by dopamine fluctuations resulting from the treatment of PD motor symptoms with dopaminergic agents, and determine if anxiety and depression have dissociable neural networks in PD. The study aims to achieve these goals using detailed psychiatric and neuropsychological assessments as well as high-resolution functional magnetic resonance imaging (fMRI) methods in PD patients with anxiety, PD patients without anxiety or other psychiatric conditions, and healthy controls. A targeted fMRI activation task will be employed designed to tax medial temporal lobe networks including the amygdala. High-resolution resting- state fMRI will be used to assess connectivity between amygdala and local and whole brain cortical networks. Completing these assessments both during the on and off-dopamine medication state will further help determine whether anxiety and underlying amygdala networks are altered by fluctuations in dopamine levels. Together the proposed studies will provide key insights into the role of the amygdala, its subregions, and its networks in the experience of anxiety in PD. The results will determine whether anxiety and depression are dissociable conditions in PD subserved by distinct amygdala subregions and networks in PD. Finally, this work could additionally provide a target for the development of new therapeutic interventions for anxiety in PD.