Social Decision Making in Parkinson's Disease

Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinsons Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Pramipexole. For the off-DAA visit, participants will receive a placebo. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications to reduce circulating drugs and residual drug effects. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinson's Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take 1mg of Pramipexole 1 hour before the scan. For the off-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take a placebo 1 hour before the scan. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

Eligibility Criteria:
Inclusion Criteria:

* Age 45-80
* Ability to give informed consent
* Idiopathic Parkinson's disease
* Currently taking dopamine agonist therapy
* Mild symptom severity (Hoehn \& Yahr ≤ 3)
* Disease duration of \<12 years
* Demonstrated positive response to dopamine therapy

Exclusion Criteria:

* Medications classes that influence GABA concentrations: benzodiazepines, cholinesterase inhibitors, antipsychotics, opioids, and MAO inhibitors
* History of substance abuse or use of any psychostimulants (other than caffeine) in the last 6 months or more than 4 times in lifetime
* Current tobacco (or nicotine use) or alcohol intake greater than 8 ounces of whiskey or equivalent per week
* Comorbid neurological disorders (e.g., stroke, peripheral neuropathy, seizure disorder) or history of head trauma (other than a single concussion)
* Unstable medical condition, \[e.g., diabetes or pulmonary disease, significant medical condition, including high blood pressure (systolic B.P. \> 135, Diastolic B.P. \> 85), or any hepatic, renal, cardiovascular, hematological, endocrine or ophthalmological condition\]
* History of major psychiatric illness (including any affective disorder, substance use disorder, psychotic disorder, or eating disorder)
* Dementia
* Deep brain stimulation
* Contraindications to 3 Tesla MRI, e.g., extreme obesity, claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body
* Dyskinesia or tremor that would cause severe motion artifact during MRI scan
* Clear indication of secondary gain