Effect of Dopamine on Specific Processing of Shame and Embarrassment in Parkinson's Disease

University Hospital, Geneva30 enrolled

Overview

Shame and embarrassment are two self-conscious emotions frequently experienced by Parkinson's disease (PD) patients. Shame and embarrassment scores strongly correlate with patient's quality of life, anxiety and depression ratings. However, the neurobiology of shame and embarrassment in PD and the influence of dopaminergic replacement therapy (DRT) is poorly understood. The aim of this study is to characterize how brain structures and neuronal networks involved in Parkinson's disease-related shame, non-Parkinson's disease related shame and neutral control scenarios, are modulated by dopaminergic replacement therapy. For this purpose, functional MRI and connectivity measures between the basal ganglia and shame-related network will be analyzed while PD patients will perform a shame-induction task during both ON- (i.e. during the effect of DRT) and OFF-DRT (i.e. during the withdrawal of DRT) conditions. Correlation with clinical measures will be made.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Parkinson Disease

Interventions

Assessments in ON and OFF levodopa stateBEHAVIORAL

Neurological assessment, neuropsychological assessment, and fMRI in ON and OFF levodopa state

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of Parkinson's disease (PD) based on United Kingdom Parkinson's Disease Society Brain Bank Criteria * Patients in the PD phase called "motor and non-motor fluctuations stage". * Presence of motor and non-motor fluctuations are based on: 1. For motor fluctuations: a score of 1 on item 4.1 and/or 1 on item 4.3 of the Movement Disorder Society Unified Parkinson's Disease Rating Scale IV 2. For non-motor fluctuations: a score of 2 on item III of the Behavioral Assessment of Parkinson's Disease * To be on dopaminergic replacement therapy. Healthy controls: subjects without any known central nervous system (CNS) lesion or CNS clinical signs on examination Exclusion Criteria: * Age greater than 80 years * Dementia or mild cognitive impairment based on a score \<26 on the MOCA * Ongoing depression with suicidal ideation * Any clinically meaningful non-stable renal, hepatic, cardiovascular, respiratory cerebrovascular disease or other serious progressive physical diseases * Participating in a pharmacological study * Any MRI contraindications * Intolerable "OFF" states when the effects of the PD medication wear off (e.g., severe pain, anxiety, depression at the end of the dose or in the morning upon waking) * Inability to provide informed consent (legal guardianship) * Inability to speak or read French.

Outcomes

Primary Outcomes

Difference in BOLD activity in ON versus OFF state

Difference in brain Blood Oxygenation Level Dependent (BOLD) activity between ON-levodopa versus OFF-levodopa patients, as well as age-matched healthy controls during the imaginary ideation of PD-shame related scenarios, non-PD shame related scenarios as well as neutral scenarios.

Time frame: fMRI at rest and during a shame induction task, 1 hour in ON state and 1 hour in OFF state