Organization and development of motor cortical circuits for speech production in stuttering - At its core, stuttering reflects disruption in speech motor control, influenced by cognitive, affective, and sensory factors that modulate the frequency and severity of speech disfluencies in individual speakers. Motor cortical circuit function and anatomy have been a focus of investigation relevant to the neural bases of stuttering, however our understanding of structure and functional differences in key motor cortical structures and their connections with other cortical and subcortical areas remain lacking. This, as well as a lack of studies to date to link brain-behavior relationships on an individual level, have hampered progress in understanding the neural bases of this complex disorder and hindered progress toward treatment development. The studies proposed in this application represent a substantive departure from the status quo by applying a novel integrative motor cortex anatomical framework to provide a mechanistic, functional neuroanatomical understanding of where and how breakdowns may occur in stuttering. Three newly discovered “inter-effector” areas (IEAs) that are interspersed between effector-specific areas along the primary motor cortex were shown to display distinct morphology and greater connectivity (relative to effector specific regions) to brain regions involved in cognitive control, sensory input processing, and movement intention. The IEAs likely support critical integrative functions for complex human actions, with particular relevance for speech production (and speech motor pathology like stuttering), since speech is the most complex and complexly integrative motor behavior that humans perform. Among the IEAs, the middle and inferior IEAs support integrative functions relevant to speech control. The proposed studies aim to examine morphology and functional connectivity of these two IEAs that will contribute to a fundamental shift in understanding the structure and function of key motor cortical regions and related circuits that support fluent speech production and areas of breakdown associated with stuttering. In aim 1, precision MRI mapping will be applied for the first time in this clinical population, expected to reveal critical new insights on individual-specific variations that are linked to behavioral heterogeneity associated with stuttering. In aim 2, activity and functional connectivity patterns of the IEAs will be examined during ecologically valid continuous speech tasks, and aim 3 will examine potential deviations in specific nodes and connectivity patterns of the IEAs during a developmentally sensitive period for speech and language acquisition. The proposed studies are completely novel directions that are expected to derive information that could shift the paradigm in conceptualizing the neural bases and intervention for stuttering. This new knowledge is significant, because it will help identify specific, individualized targets for future treatment development and preventative interventions that were unavailable before. Ultimately, the results from this research will have a potentially broad impact, leading to a better understanding of neural bases of speech motor control and development.
