Role of Subthalamic nucleus in Speech and Movement among people with Parkinson’s as Revealed by Intraoperative Recordings and Deep Brain Stimulation

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PROJECT SUMMARY / ABSTRACT Parkinson's disease (PD) is an increasingly prevalent progressive neurodegenerative disorder that leads to disabling motor, speech, and cognitive symptoms that reduce quality of life for patients and their families. As the prevalence of PD increases, so too does the use of deep brain stimulation (DBS) as a surgical treatment option when medications fail to control motor fluctuations or side effects from medications limit their efficacy. As many as 15% of the more than 1 million American PD patients are felt to be candidates for DBS. The subthalamic nucleus (STN) is the most common target utilized for DBS and limb motor outcomes after STN-DBS show reliable and consistent improvement in properly selected patients. On the other hand speech motor outcomes after STN-DBS are unpredictable and more patients experience deterioration of speech than those that notice improved speech. An estimated 40% of STN-DBS patients notice worsened speech and with declines significant enough to reduce quality of life. Furthermore, few effective treatments exist to provide sustained improvement in speech performance for those with impaired speech. In order to optimize and develop better treatments for those living with PD, it is necessary to better understand the role of STN in speech as contemporary mechanistic models of human speech production omit STN. Here we study 80 PD patients undergoing bilateral STN-DBS along with 40 non-surgical PD control subjects to address existing critical knowledge gaps. We will document speech performance of both groups through functional communication ability (i.e. objective measures of intelligibility and a validated survey tool for quantifying communication participation) and instrumental speech (i.e. acoustic) measures pre-surgery, 6- and 12-months post-surgery with all subjects off PD medications and with the STN-DBS subjects evaluated with stimulation ON & OFF at both post-operative timepoints. Direct neuronal recordings will be obtained during DBS implantation surgery during both speech and limb motor tasks to define speech-specific STN neurophysiology. In addition, we will perform regression analyses using baseline patient factors and intraoperative physiology findings to identify factors leading to the speech outcomes we will document, and test the feasibility of low frequency DBS in reversing DBS- induced speech declines. To our knowledge, this data will be the first of its kind to evaluate patients before, during, and after surgery with the goals of both directly defining the role of STN in speech and predicting speech outcome after STN-DBS. Such knowledge will provide mechanistic insights that cannot be obtained using other techniques and will guide development of new treatments of impaired speech in PD.