Steven J. Eliades - US grants

DESCRIPTION (provided by applicant): The overall objective of this research is to understand how we listen to the sound of our own voice while talking and how we use this information to help control our speech. Humans have sophisticated mechanisms for self-monitoring of this vocal feedback during speech that allow for the detection and compensation for vocal errors. Degradation of this self-monitoring, such as following hearing loss, results in difficulty in acquiring and maintaining normal speech and impairs vocal communication. Recent work in both humans and primates has demonstrated a suppression of neural activity in the auditory cortex during vocalization that may play a role in self-monitoring. The origin and significance of this neural activity is unknown. This proposal focuses on determining the neural mechanism of self-monitoring during vocal production and its role in feedback vocal control, using both human subjects and a vocal primate model, the marmoset monkey. Aim 1 tests the hypothesis that suppressed neurons of the auditory cortex in marmosets exhibit self- monitoring activity, and that this neural activity can drive compensatory vocal control. Auditory cortex neurons are recorded from vocalizing marmosets while altering the frequency content of their vocal feedback to induce vocal compensation. Neural recording is followed by electrical stimulation of the auditory cortex in order to disrupt self-monitoring and resulting feedback compensation. These experiments will demonstrate how vocalization self-monitoring activity in the auditory cortex drives feedback vocal control. Aim 2 tests the hypothesis that frontal cortical areas, particularl pre-motor cortex, are the origin of the neural signals that cause vocal suppression in auditory cortex. Neurons in both frontal and auditory cortex of marmosets are recorded simultaneously and quantitative analyses applied to demonstrate neural connectivity between brain regions during vocal production. These results will demonstrate the neural pathways beyond auditory cortex that contribute to vocal self-monitoring. Aim 3 tests the hypothesis that human auditory cortex is necessary for self-monitoring and feedback vocal control of speech. Auditory cortex activity is recorded using intracranial electrocorticographic activity in patients undergoing neura monitoring for epilepsy surgery. Paralleling the animal experiments, electrical stimulation of cortex is performed during pitch-altered speech feedback to demonstrate the role of auditory cortex in feedback compensation. These experiments will have implications for understanding speech motor control and will allow mechanistic comparisons between human speech and animal vocalization. Such comparisons are critical as we attempt to translate results from animal neurophysiology towards understanding human speech production.

The overall objective of this research is to understand the role of sensory prediction in the auditory cortex. The ability to predict the sensory consequences of one?s actions plays an important role in shaping sensory coding and guiding behavior. In the auditory system, this prediction is used during vocal production, allowing us to monitor feedback of the sound of our voice. However, the neural mechanisms of this auditory self-monitoring are unknown. This proposal focuses on determining the mechanisms and neural circuits by which sensory prediction changes sensory coding in the auditory cortex during vocalization, and the behavioral role played by such predictions. We approach this using a novel vocal primate model, the marmoset monkey. Aim 1 focuses on the mechanisms of feedback encoding during vocalization, and tests the hypothesis that sensory prediction shapes auditory cortex responses to calculate an error signal between vocal feedback and the prediction. We record auditory cortex neurons in vocalizing marmosets while adjusting the frequency content of their vocal feedback using frequency shifts of varying direction and magnitude to measure sensitivity to feedback errors. To further investigate potential computational mechanisms by which sensory prediction shapes feedback coding, we measure frequency tuning changes in auditory cortex during vocalization compared to passive listening, and how these relate to predicted vocal acoustics. Aim 2 investigates the auditory cortical circuits involved in sensory prediction and feedback encoding, testing the hypothesis that the dorsal auditory pathway exhibits greater feedback sensitivity than early auditory cortex. We record responses to altered feedback during vocalization and compare responses between the dorsal ?where and how? pathway with primary auditory cortex (A1) and the ventral ?what? pathway. We further compare the strength of neural activity in predicting compensatory vocal changes during altered feedback. These results have important implications for validating current models of functional specializations within these higher-order auditory pathways. Aim 3 addresses the behavioral role of sensory prediction in auditory cortex, testing the hypothesis that activity within the auditory cortex is necessary for feedback-dependent vocal control. We combine frequency- shifted vocal feedback with pharmacologic inactivation of auditory cortex to determine if such manipulations disrupt behavioral compensation. We further compare effects of inactivation between hemispheres and sites of different frequency tuning. These experiments will demonstrate a causal role for the auditory cortex in feedback self-monitoring and resulting vocal control.