Impaired sensory filtering as a mechanism of Parkinson's disease

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PROJECT SUMMARY Conventional models of Parkinson’s disease (PD) dysfunction do not account for sensory feedback, which is both clearly represented in the basal ganglia and clearly impaired in PD. Despite the critical importance of this feedback to normal movement, the contribution of impaired sensory processing to PD pathophysiology is unknown. Our long-term goal is to clarify the role of sensory feedback in the production of pathological motor commands in PD. This research could help reveal the neural basis of both PD pathology and its treatment, leading to more efficient clinical practices, driving the development of novel therapeutic technologies, and helping to alleviate the enormous burdens of PD on patients and providers. In healthy people, the motor system will automatically ignore sensory feedback that is not directly relevant to the current behavioral goal. In this proposal, we seek to determine whether the basal ganglia participate in this goal-directed sensory filtering, and whether this process is impaired in PD. This phenomenon could potentially provide a framework to explain PD motor symptoms with a single underlying cause: normal sensory feedback is not filtered appropriately, which reduces the ability of the motor system to produce normal commands. Underdamped sensory feedback could produce excessive transcortical reflexes in rigidity, corrupt the brain’s internal models and interfere with movement planning in bradykinesia, and even produce tremor via stochastic resonance (a phenomenon common in nonlinear neural systems in which a sub-threshold oscillation is amplified by noise). Whether or not our specific hypotheses are supported, the experimental paradigms of this study will generate unparalleled data and insights into sensorimotor integration in the human brain. If our hypotheses are correct, however, we will further provide a framework for an unprecedented mechanistic model of PD symptom generation and a roadmap towards improved treatment.