Relationship Between Cortical Planning Activity and Disordered Spoken Interaction

Project Summary While considerable progress has been made investigating the neural mechanisms underlying speech articulation, less is known about how the brain plans spoken language. Efficient, rapid speech planning is critical for enabling turn-taking interactions during conversation. Planning dysfunction has been linked to several disorders, including Parkinson disease (PD). To investigate the neural foundations of this key cognitive process, the Long lab recently used electrocorticography (ECoG) to identify a compact frontal network that is selectively active during the planning of both structured and spontaneous spoken exchanges. A central component of this network is the caudal middle frontal gyrus (cMFG), which represents a novel language planning area. The study also used direct electrical stimulation to perturb cMFG which caused preparatory deficits such as response errors and reaction times. These results indicate that cMFG is a critical speech-related planning region, yet raise important clinical questions. Do neuropathologies that impact patients’ speech also affect cMFG function? And how do the interventions we use to treat these diseases affect cMFG? Thus, dissecting cMFG function at a neural circuit level will yield fundamental insights into the neural mechanisms of language generation and its relationship with different neuropathologies. In this proposal, I therefore focus on the relationships between neuropathology, speech planning, cMFG function, and neuromodulatory treatment in patients with PD by utilizing the access provided by awake insertion of deep brain stimulation (DBS) electrodes. PD is a devastating neurodegenerative disorder caused by the loss of dopaminergic neurons. In addition to motor symptoms such as bradykinesia and tremor, PD patient exhibit speech dysfunction. The mechanism speech deficits in PD are poorly understood, but preliminary work implicates impaired speech planning. Furthermore, the effect of DBS therapy, a mainstay of PD treatment that significantly improves motor symptoms, is unclear – evidence demonstrates that only a subset of patients experiences long-term improvement in speech function despite an improvement in the motor functions required for speech such as laryngeal motion, suggesting a limited ability to improve the higher-order process of speech planning. Here I will leverage the diversity of patients at our center undergoing the placement of DBS electrodes to compare cMFG function in patients with PD and other neuropathologies, such as cervical dystonia and essential tremor, that do not significantly affect speech planning, to determine the effect of PD and DBS therapy on cMFG function and clinical speech function in PD patients. I will therefore test the central hypothesis that cMFG planning activity is perturbed in PD, and a predictor of patients’ speech improvement with DBS therapy.