Apathy in Parkinson Disease TMS Study

Participants will be asked to come for 3 study visits.

During visit 1, after being informed about the study and potential risks, all patients giving written informed consent will undergo a brief cognitive assessment, a movement examination, and answer questionnaires. Additionally, the individual motor threshold will be determined for each participant. Visit 1 will take 2-3 hours.

Visits 2 and 3 will involve:

• completing questionnaires,
• performing a task where fictitious rewards can be earned by squeezing a dynamometer,
• recording brain activity with an electroencephalogram (EEG), and
• receiving transcranial magnetic stimulation (TMS). Visits 2 and 3 will take approximately 3 hours each and will be separated from each other by at least 3 weeks.

Inclusion criteria

• Diagnosis of idiopathic Parkinson Disease.
• At least 4 years of symptoms.
• On dopaminergic medication for Parkinson Disease.
• Stable on dopaminergic medication and other medications which may influence apathy (such as selective serotonin re-uptake inhibitors, stimulant medications) for at least 4 weeks prior to first study visit and remain stable throughout the study period.
• Hospital's study-specific informed consent must be obtained.
• Must have capacity to provide informed consent in English.
• For female participants, confirmation that they have not had a menstrual period in over 12 months, or that they will use an effective form of contraception during the study.

Exclusion criteria

• Inability to provide informed consent.
• Inability to perform effort task (determined during the titration session).
• Presence of dementia (Montreal Cognitive Assessment (MoCA) score < 21).
• History of epilepsy or brain surgery.
• Severe tremor or dyskinesia that would interfere with EEG (determined by the PI).
• Patients with clinically significant medical or neurological conditions which may be an alternative cause of parkinsonism such as repeated brain injury, anti-dopaminergic medications, anoxic brain injury, or significant basal ganglia strokes.
• Presence of other known central nervous system disease that may interfere with performance or interpretation of EEG or TMS.
• Presence of any implanted metal devices including, but not limited to, pacemakers, deep brain stimulators, vagal nerve stimulators, bladder stimulators, or cochlear implants.
• Presence of medical contraindications to TMS such as implanted stimulators, history of mania or bipolar disorder, history of epilepsy.