UAB Department of Neurosurgery Assistant Professor Zachary Irwin, Ph.D., recently received a $1.1 million R01 grant from the National Institutes of Health Research to investigate the impacts of sensory deficits on movement in patients with Parkinson's Disease. This grant will fund his research over the next three years. 

Irwin’s 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. 

"This project is the beginning of an exciting research avenue for me and hopefully for the movement disorders field,” says Irwin. “The question we are trying to answer is ‘do some of the classic motor symptoms of Parkinson's Disease such as slow movements, rigidity, and tremor actually result from altered sensory processing?’ We're going to find out!"

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. Irwin’s long-term goal is to clarify the role of sensory feedback in the production of pathological motor commands in PD.

In healthy people, the motor system will automatically ignore sensory feedback that is not directly relevant to the current behavioral goal. Irwin seeks 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 Irwin’s specific hypotheses are supported, the experimental paradigms of this study will generate unparalleled data and insights into sensorimotor integration in the human brain. If the hypotheses are correct, however, Irwin intends to further provide a framework for an unprecedented mechanistic model of PD symptom generation and a roadmap towards improved treatment.