Neural subtypes of developmental stuttering

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Project Summary/Abstract While the behavioral heterogeneity of stuttering has been long recognized, very little is known about mechanisms underlying the heterogeneity. Without this knowledge, the complex etiology of stuttering cannot be fully understood, and the development of individualized treatment approaches will continue to be severely hindered. Our long-term goal is to develop neuroscience-based treatment approaches for developmental stuttering. In pursuit of this goal, the objective of the present application is to identify subtypes of children who stutter (CWS) based on neuroanatomical anomalies and characterize each subtype’s behavioral profiles and brain activity during speech production. The central hypothesis is that each neural subtype is associated with behavioral and brain activity changes consistent with its primary neuroanatomical anomalies. The rationale of this proposed project is that elucidating the neural subtypes of stuttering will help us understand the heterogeneity and neurological etiologies of the disorder, which is an important basis for developing new treatment approaches that target individual neurological deficits. We will test our central hypothesis by pursuing three specific aims. i) Identify subtypes of CWS based upon patterns of neuroanatomical anomalies. To achieve this aim, we will use a clustering method to analyze gray matter volume patterns in CWS. We hypothesize that CWS comprise neural subtypes, characterized by primary structural anomalies in the prefrontal areas, the basal ganglia thalamocortical circuit and the cerebellum. ii) Characterize behavioral profiles associated with each neural subtype. Based on contemporary models of speech motor control, we hypothesize that each neural subtype will differ in both stuttering behaviors, language ability, and speech motor performance depending on the functions of its primary neuroanatomical anomaly loci. iii) Characterize brain activity associated with speech production in each neural subtype. To achieve this aim, we will identify differences in brain activity between neural subtypes during overt continuous speech using functional magnetic resonance imaging. Our working hypothesis is that compared to controls, each neural subtype of CWS will exhibit reduced activation associated with its primary anatomical anomalies as well as their common input region, the left premotor areas. Upon successful completion of the proposed research, we expect to gain an expanded understanding of anatomical neural subtypes of stuttering, and for the first time, link behaviors and brain activity differences during speech production among the different subtypes. Better characterizing neural subtypes of stuttering would substantially contribute to our understanding of the heterogeneity of stuttering, which is an important step in elucidating the disorder’s complex etiology.