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

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reliably and consistently improves limb motor symptoms of Parkinson’s disease (PD). Conversely, speech outcomes as quantified by instrumental measures of speech production and metrics of functional communication vary tremendously with impaired outcome a frequent occurrence. This variability is evident in studies examining the direct effects of stimulation (i.e., stimulation ON vs. OFF) and the few longitudinal studies investigating the chronic effects of DBS (i.e., pre vs. post DBS surgery). Understanding the source of these variable speech outcomes is critically important for pre-operative counseling, optimizing therapeutic effects of DBS, and ultimately for developing targeted and effective speech management protocols. In a rare longitudinal speech study, Tripoliti et al., (2014) concluded that lower pre-operative intelligibility, longer disease duration, and medially placed left hemisphere active electrode contact predicted intelligibility one year post-surgery with DBS ON. It is important to note that of these 3 variables, only electrode contact position can be manipulated to optimize speech. Collectively, extant STN-DBS speech outcome studies, including Tripoliti et al., (2014), have limitations in the form of: 1) failure to comprehensively quantify outcomes using both validated metrics of functional communication and instrumental measures of speech, 2) limited participant numbers, and 3) lack of explicit, mechanistic understanding of the role of STN in speech. Knowledge of the role of STN in speech production is essential to improve speech outcomes following STN-DBS. Neural models of speech either fail to elaborate the specific role of STN or omit STN entirely. To address this knowledge gap, we conducted an intraoperative pilot study investigating STN neuronal activation accompanying speech produced during awake microelectrode recording-guided DBS surgery. In some patients, we identified STN firing rate changes in the opposite direction during speech (i.e. STN suppression) versus limb (i.e. STN activation) motor tasks. Furthermore, we found that the patients demonstrating this discordant firing pattern later showed deleterious impact of direct STN stimulation (i.e., ON vs. OFF) on functional communication. These pilot data provide preliminary evidence for a direct role of STN in speech. Our long-term objective is to define the role of STN in speech with the goal of reducing the disparity in speech and limb outcomes following STN-DBS. This project will integrate direct neuronal recordings from STN with prospective and longitudinal evaluation of 80 participants with bilateral STN-DBS before, during, and 6 and 12 months after surgery. At each time point we will comprehensively quantify speech and limb motor outcomes. 40 PD participants without DBS will be studied concurrently as a control group.