In recent years, excessive impulsivity and impulse control disorders (ICDs), which commonly include pathological gambling, compulsive shopping, binge-eating, and hypersexuality, have been recognized as an important complication of Parkinson's disease (PD). Both impulsivity and ICDs negatively affect patients and their family quality of life and emotional well-being. In addition, ICDs are a cause of considerable increase in care burden. For these reasons, the problem of excessive impulsivity has become a crucial issue in regards to the care of PD patients. Dopamine-replacement therapy (DRT), in particular dopamine agonists and to a lesser extend l-dopa, have been recognized as a major factor in the increase in impulsivity in PD patients. Accordingly, the main treatment response currently is the decrease or removal of dopamine agonist medications, which however entails the risk of development of dopamine agonist withdrawal syndrome and of recurrence of more severe motor symptoms. However, when excessive impulsivity results from l-dopa alone not much can be done currently to control both motor symptoms and impulsivity. For these reasons, more research is critically needed to better understand the pathophysiology of impulsivity in PD, and to develop more effective care. Impulsivity in PD patients has been found to be composed of two main dimensions identified as motor impulsivity and decision-making impulsivity. This distinction suggests that different neural networks may be affected across PD patients. Accordingly, the limited effectiveness of current treatments of PD-related ICDs may be due to divergent pathophysiological mechanisms, as well as to the scarce understanding of how impulsivity modulates the brain networks associated with decision-making and response planning. Some studies have investigated the neural mechanisms of motor impulsivity in PD patients, and a few have investigated those of decision-making impulsivity. However, to our knowledge no study has ever been designed to investigate specifically how DRT affects the electrophysiological activity within the neural networks associated with the two main dimensions of impulsivity and how this information can prospectively improve patient care. With this project, we intend to begin to fill this gap. We plan to identify the neural signatures of impulsivity in controls and Parkinson's patients using magnetoencephalography (MEG), which provides high temporal resolution of oscillatory activity over the whole brain. Subjects will complete questionnaires relative to impulsivity and ICDs, and then perform two tasks ?go/no-go task and Iowa gambling task? assessing the two main dimensions of impulsivity (i.e., motor impulsivity and decision-making impulsivity, respectively) during MEG recording. Patients will be studied both on and off their DRT to determine its effect on the networks associated with each dimension of impulsivity. In addition, these data will be used to create neurophysiological models of the dimensions of impulsivity in PD patients and compare those to matched controls. Furthermore, we will identify the patterns of neural activity that covary with the level of dopamine-induced impulsivity. Advancing our understanding of the brain mechanisms associated with impulsivity in PD will provide a path to more individualized therapy and better outcomes. It will also define the network nodes involved in impulsivity and ICDs and therefore identify potential targets for future interventions by transcranial or deep brain stimulation.

Public Health Relevance

Parkinson's disease (PD) is a neurodegenerative disorder with motor symptoms that affects about 1 million people in the United States, with about 60,000 new cases every year. The Department of Veterans Affairs (VA) has recognized the link between PD and herbicides, such as Agent Orange, which many veterans have been exposed to. Consequently, treatment of PD is of major importance to the VA. An increase in impulsivity?and associated impulse control disorders?has been identified in recent years as a major potential complication of PD. The goal of the project is to investigate the patterns of neural oscillatory activity associated with impulse control in PD patients and how they are affected by the use of dopamine agonists. Subjects will be assessed using magnetoencephalography while they perform in tasks that probe two main dimensions of impulsivity? motor impulsivity and decision-making impulsivity. The outcome will provide new information about the pathophysiology of impulse control disorders in PD, which will help to advance treatment by medication.

National Institute of Health (NIH)
Veterans Affairs (VA)
Non-HHS Research Projects (I01)
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Special Emphasis Panel (ZRD1)
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Minneapolis VA Medical Center
United States
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