Doctoral Dissertation Research: Neurobiological foundation of feedback-based adjustments in speech articulation: role of subcortical circuits

When speaking, the brain checks the accuracy of the sounds that are produced. This monitoring of auditory feedback is used to try and adjust speech movements in case the output does not sound correct. Thus, the brain tries to adapt its motor behavior based on the auditory input. This is known as auditory-motor adaptation. Situations where speech movements may not yield the correct sounds include wearing dentures, oral surgery, and developmental or acquired neurological disorders that affect mouth movements. Little is known about which brain parts are involved in speech auditory-motor adaptation or how the underlying mechanisms can be enhanced to optimize this learning. Such information is critical to understand basic brain function and to help millions of children and adults with temporary or permanent speech difficulties. Studies on limb movements suggest that connections between the brain's cortex and deeper (subcortical) structures play an important role. It is unclear, however, if those findings also apply to speech. This doctoral dissertation project studies the role of two subcortical structures by testing patients who, as part of their clinical treatment, have had electrodes implanted inside those structures (deep brain stimulation, DBS). Parkinson's disease (PD) and essential tremor (ET) patients have DBS electrodes implanted in the basal ganglia or thalamus, respectively. The project assesses differences in how the two groups of patients use auditory feedback to adjust their speech with the DBS device on or off. In some cases, the DBS device also allows brain activity to be directly recorded during the speech task. This research provides new insights into the role of the subcortical structures in speech auditory-motor adaptation. Overall, it improves the understanding of how the brain controls speech movements. It also has implications for understanding speech development during childhood and the decline of speech with aging. Lastly, it informs the development of novel treatments for individuals with speech impairments. To test how the brain adjusts speech based on auditory feedback, this doctoral dissertation project uses a behavioral adaptation paradigm that involves consistent perturbations of one or more resonance frequencies (formants) in the auditory feedback. For example, when the perturbation shifts the first formant (F1) upward, a speaker who produces the word "pet" hears "pat" in the altered auditory feedback. The brain then adjusts the involved speech movements to lower F1 in subsequent productions of "pet" (moving it closer to "pit") in order to partially compensate for the perturbation—a phenomenon known as speech auditory-motor adaptation. This project investigates the distinct roles of two subcortical structures, the subthalamic nucleus (STN) of the basal ganglia and the ventral intermediate nucleus (Vim) of the thalamus, in speech auditory-motor adaptation. STN and Vim are critical components of two important circuits that connect the cortex and different subcortical structures: one circuit between the cortex and the basal ganglia, and the other between the cortex and the cerebellum. STN and Vim are common Deep Brain Stimulation (DBS) implantation sites for patients with Parkinson’s Disease (PD) and essential tremor (ET), respectively. To elucidate the role of these nuclei in the adjustment of speech movements during auditory-motor adaptation, this project tests two forms of adaptation and contrasts the results with a non-adaptation form of speech motor learning. Specifically, patients with DBS electrodes at either STN or Vim complete (a) auditory-motor adaptation with a gradually introduced perturbation, (b) auditory-motor adaptation with a suddenly introduced perturbation, and (c) syllable sequence learning. The results provide direct evidence for the contribution of these nuclei in speech auditory-motor adaptation that has remained limited due to methodological barriers. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.