Local field potentials reveal reward processing and impulse control disorders in Parkinson’s disease

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Project Summary/Abstract This application seeks to characterize the electrophysiological activity of the basal ganglia during reward processing in people with Parkinson’s disease (PD) with and without comorbid impulse control disorders (ICDs). ICDs encompass excessive and uncontrollable behaviors including hypersexuality, pathological gambling, binge eating, compulsive buying, punding (repeating simple activities), and dopamine dysregulation syndrome. They affect up to one-third of PD patients and significantly impact quality of life. Although ICDs were previously attributed to dopamine replacement therapies in PD, an additional iatrogenic etiology is deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) – two FDA-approved and routinely- used DBS targets for the treatment of severe or medication-intolerant PD. Stemming from a lack of pathophysiological insight, there are no reliable strategies to curb these behaviors in PD. Therefore, the treatment of ICDs in PD today remains an unmet medical need. Although the mechanistic underpinnings of ICDs in PD are not fully known, there is a large body of evidence linking dysfunction in reward processing to both subclinical and clinically diagnosed impulsivity in PD. Namely, individuals with ICDs demonstrate a hypersensitivity to reward and a hyposensitivity to loss. Our objective is to identify electrophysiological markers of reward processing in the STN and GPi to characterize the role of these subcortical nuclei as they contribute to ICDs. To that end, we have successfully administered a reward processing game during PD DBS while simultaneously using the implanted STN or GPi DBS electrode as a recording device; we have discovered event- related and oscillatory changes in local field potentials (LFPs) (neuronal population-level activity) specific to reward in the STN and GPi. The central hypothesis of this proposal is that the STN and GPi participate in reward processing – measurable through LFPs – which can be used to differentiate individuals with and without ICDs. In Aim 1, we will examine LFPs in the STN and GPi during a reward processing game in awake, behaving PD patients undergoing DBS neurosurgery. In Aim 2, we will determine if the presence of clinically diagnosed ICDs affects LFPs measured in the STN and GPi during reward processing. This work is significant because it will implicate the basal ganglia in clinically significant reward processing through specific LFP changes. This work is innovative in that it will simultaneously uncover mechanisms of ICDs in PD and motivate novel therapeutic strategies for these disorders, particularly for patients receiving DBS implants.