The Neural Substrates of Impaired Feedback Control in P*

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DESCRIPTION (provided by applicant): Patients with Parkinson's disease (PD) have a variety of difficulties with speech production. These deficits may result from a reduced ability of PD patients (PDs) to use sensory feedback to control movement; a hypothesis consistent with studies showing that PDs have impaired vocal responses to changes in the pitch frequency or amplitude (volume) of auditory speech feedback. In the present proposal, the neural substrates of these impairments in speech feedback control are sought. Auditory feedback control of speech will be examined in PD and normal subjects vocalizing, while listening to perturbations of the frequency or amplitude (loudness) of the pitch in the auditory feedback of their speech. These perturbations will cause pitch-perturbation responses (PPRs); compensatory changes in pitch frequency or amplitude that are well characterized for normal subjects, but only minimally characterized for PDs. The study's first aim is to more fully-describe how PPRs of PDs and normals differ, and what pitch perturbation parameters cause the clearest differences. This will be accomplished by examining both PDs and normals in extensive psychophysical testing of their PPRs. After having determined what pitch perturbations most clearly diagnose the PPR deficits in PDs, the study's second aim will identify the neural systems involved in PPRs in PDs and normals. This will be done using fMRI scanning of PDs and normals producing or passively listening to PPRs. We will find CNS regions that are more active after PPRs than after unaltered vocalizations, but show no activity when the subject passively listens to a normal and pitch-perturbed speech. After finding areas of the CNS that appear involved in PPRs, the third aim of the study will be to determine the order of their neural activities resulting in a PPR. To examine this, we will induce PPRs in vocalizing PD and normal subjects, while using magnetoencephalography and electroencephalography to record the sequential activation of different brain regions following perturbation but preceding the PPR. Better understanding of the neural substrates of impaired speech feedback control in PDs will elucidate the pathophysiology of speech disorders associated with PD and promote refined targeting of treatments for those disorders.