Overview

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's dementia. Anxiety in PD is common, has major effects on quality of life and contributes to increased disability. The reported prevalence of anxiety in PD ranges widely and is estimated up to 40%. Treatment with oral medications is not always effective or tolerated. TMS has been shown to be effective and safe in anxiety and general anxiety disorder (GAD), but there is only limited data available for Transcranial Magnetic Stimulation (TMS) treatment of anxiety in PD. Area 8Av is a parcellation based on Human connectome project within the left prefrontal cortex and is associated with GAD. Given the area's associations with mood disorders, its functional connectivity with large-scale brain networks involved in PD, and its anatomical accessibility by TMS, this may be an important target for anxiety in PD.

Eligibility

Inclusion Criteria:

1. Subject has Idiopathic PD defined by the cardinal sign, bradykinesia, plus the presence of at least 1 of the following: resting tremor or rigidity and without any other known or suspected cause of Parkinsonism (according to MDS clinical diagnostic criteria for Parkinson's disease (42) Postuma et al, Movement Disorders 2015), confirmed by a fellowship trained movements disorder specialist.
2. Subject has a diagnosis of anxiety based on PAS (Parkinson's anxiety scale) score of ≥ 14
3. Subject is Hoehn & Yahr stage less than or equal to 3
4. Subject has a MOCA score ≥ 18
5. Subject is ≥ 40 and ≤ 90 years of age
6. Female subjects are post-menopausal or have a negative pregnancy test
7. The subject must be proficient in speaking, reading and understanding English in order to comply with procedural testing
8. Subject has provided informed written consent prior to participation. In the event that subject is legally unable to provide informed written consent due to deterioration in cognitive abilities, fully informed written consent must be provided by a legally authorized representative.
9. Subject is on a stable dose (at least 1 month prior to baseline visit) of antiparkinsonian agents and is willing to remain on this dose for the duration of the study. If the subject is on a anti-depressant or anti-anxiety medication, a stable dose without changes for 1 month is also required.

Exclusion Criteria:

1. Inability to tolerate imaging; contraindication of imaging due to implants or metal. This includes an implanted deep brain stimulation device.
2. Seizure disorder, active alcohol or substance use disorder.
3. Inability to speak and read English.
4. Anything else that, in the opinion of the PI/Clinician, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
5. Subject has atypical Parkinson's syndrome(s) due to drugs (e.g., metoclopramide, neuroleptics), metabolic neurogenetic disorders (e.g., Wilson's Disease), encephalitis, cerebrovascular disease, or degenerative disease (e.g., Progressive Supranuclear Palsy, Multiple System Atrophy, Corticobasal Degeneration, Lewy Body dementia)
6. Other forms of advanced dementia (PDD, AD), or MOCA <18
7. Subject has history of any of the following: moderate to severe pulmonary disease, poorly controlled congestive heart failure, significant cardiovascular and/or cerebrovascular events within previous 6 months, or any other clinically relevant abnormality that inclusion would pose a safety risk to the subject as determined by investigator.
8. Subject has history of any psychiatric illness that would pose a safety risk to the subject as determined by investigator.
9. Subject is currently taking sedative medications that are clinically contraindicated as determined by investigator.
10. Subject has undergone a recent change (<1 month) in their anti-parkinsonian medication, or anti-depressant medication or anti-anxiety medication at the baseline visit.
11. Safety risk to the subject as determined by investigator.
12. Subject has participated in a clinical trial investigation within 3 months of this study