Abstract Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for Parkinson disease. One of the main concerns when considering this therapy is the possibility of worsening cognitive changes. Deficits in word production ability, often measured as verbal fluency, is the most frequently reported cognitive change after STN-DBS. However, the mechanism remains poorly understood, largely due to our lack of knowledge on the role of the basal ganglia (BG) in language production. To fully understand the mechanisms of word- production deficits and the role of the STN in language we first need to define the language profile of STN- DBS. The overarching purpose of this proposal is to comprehensively evaluate language changes after STN- DBS and understand what part of the process of word production is affected. By evaluating patients with unilateral implants, our project will provide a more refined understanding of the role of the BG laterality in language changes (Aim 1). The role of the BG in motor program selection through modulation of the frontal cortex is well established. Within the BG, the STN plays a significant role in this process by inhibiting or delaying inappropriate options. Language models suggest a similar process where multiple lexical options are activated, and efficient inhibition of the incorrect ones is a necessary step for a timely outcome to occur. We will determine if changes in word production deficits are related to impairments in inhibition by correlating changes with verbal and non-verbal inhibitory tasks (Aim 2). Finally, we will assess the role of STN connectivity to language cortical areas, particularly the inferior frontal gyrus, and to what extent disruptions of that connectivity due to DBS affects language performance (Aim 3). Overall, this project will build on a comprehensive language assessment and network science to advance translational and personalized research in Parkinson disease as well as other forms of aphasia. It will advance knowledge on the cognitive and language changes in STN-DBS, provide mechanistic information about language processing and determine markers for DBS-related cognitive changes.

Narrative The proposed research is relevant to public health because its primary objective is to understand one of the most common side effects from deep brain stimulation in Parkinson disease: word-production difficulties. This study proposes a novel approach to the effects of DBS by evaluating language comprehensively and focusing on the network changes that occur and are amenable to neuromodulation. The project is relevant to NIH's mission because it utilizes an innovative individualized mechanistic approach designed to expand the understanding of the role of the subthalamic nucleus in language and the cognitive side effects of DBS.