Impulsivity in Parkinson Disease

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Neurobiology and Anatomy, 2015.Parkinson Disease (PD) is a degenerative neurological disease characterized by the loss of nigrostriatal dopamine neurons. Cardinal symptoms of the disease include resting tremor, rigidity, bradykinesia and postural instability which can be seen as symptoms of over-inhibition. When treated with dopaminergic medications (MEDS) or subthalamic nucleus deep brain stimulation (STN DBS) PD patients may develop one or more Impulse Control Disorders (ICDs) such as pathological gambling or hypersexuality. While the precise etiology of these disorders is not known, they have been characterized as failures of inhibition. We hypothesized that both forms of therapy increase impulsive behavior even in PD subjects without clinically apparent ICD’s. We employed three tasks designed to investigate response selection, inhibition, and impulsive choice: a Go/No-Go task, a Stop Signal Task (SST) and a Delay Discounting (DD) task. We further aimed to clarify the relationships between task performance and a number of measures including disease severity, apathy, and self-perceived autonomy. We report that both MEDS and STN DBS contribute to impulsivity in PD and shift the balance towards habitual behavior over than goal-directed behavior, although in distinct and dissociable ways. MEDS result in the nonselective reinforcement of frontal-subcortical and direct pathway circuits, undermining experience and self-control, and resulting in increased discounting and improved Reaction Times. STN DBS impairs the ability of the STN to integrate frontal and striatal inputs and reduces STN output, thereby improving Movement Times, impairing switching behavior and resulting in decreased STN-induced slowing in high-conflict situations. Our results highlight the contributions of, and communication between, the Basal Ganglia and the Frontal Cortex in response inhibition and impulsive choice. Furthermore, we discuss the bioethical challenges and imperatives to treating impulsivity in the context of PD