The role of the cerebellum in speech

PROJECT SUMMARY Cerebellar ataxia (CA), caused by degeneration of or insult to the cerebellum almost always results in dysarthria, a speech motor impairment that results in reduced intelligibility and naturalness, significantly impacting quality of life. A mechanistic understanding of the cerebellar contribution to speech as well as how damage to this subcortical structure impacts cerebral speech networks is poorly understood. Consequently, at present there are no evidence-based treatments to improve speech production in CA. Our central objective is to close this critical gap by determining how cerebellar dysfunction impairs the neural control of speech, a crucial foundational step to enable development of mechanism-based treatments for CA speech impairments. Our central hypothesis is that the cerebellum plays a critical role in the feedforward control of speech, the ability to produce speech without monitoring its sensory outcomes. Specifically, the cerebellum is involved in the: 1) generation of sensory predictions used for feedforward control and 2) updating of these predictions following feedback errors (i.e., mismatch between predicted and actual feedback) to maintain an accurate internal model for feedforward control. While feedforward control may provide a general characterization of how the cerebellum contributes to speech production, we hypothesize that different subregions of the cerebellum are associated with specific, and dissociable aspects of speech production such as articulation, pitch, and timing. We further hypoth- esize that cerebellar damage has little direct effect on feedback control, the ability to use sensory signals to guide and correct ongoing actions patients may develop idiosyncratic changes in feedback control as a compen- satory mechanism for impaired feedforward control. In two aims, we test these hypotheses by analyzing the relationship between cerebellar degeneration, speech symptoms, and specific motor control impairments (Aim 1) and examining the role of the cerebellum in the broader speech production network (Aim 2). Across these aims, we will address a striking clinical observation, namely the wide heterogeneity observed in CA patients in terms of their dysarthria, a phenomenon that is poorly understood. We evaluate three promising sources that may underlie this heterogeneity: 1) differences in the specific locations of degeneration/pathology, 2) differences in CA etiology, and 3) compensatory changes in control that may develop secondary to cerebellar damage itself. We will use speech psychophysics in conjunction with magnetoencephalography (MEG) imaging to examine the consequences of cerebellar damage on electro- physiological responses in the cerebral cortex associated with speech motor control and learning in three model cohorts: 1) patients with CA, 2) patients with acute cerebellar stroke (ACS), and 3) healthy speakers in whom cerebellar function is transiently perturbed by continuous theta-burst transcranial magnetic stimulation (cTBS).