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.
