Dopamine and sensorimotor function in stuttering

Stuttering is a disorder of speech fluency that affects 3.5 million people in the USA alone. The primary symptoms consist of involuntary repetitions and prolongations of speech sounds, but many individuals who stutter also

experience negative effects on emotional and social well-being, academic and professional achievement, self-esteem, relationships, and overall quality of life. Thus, stuttering is a significant public health issue and there is a great need for increased efforts to translate recent discoveries from mechanistic neurophysiological studies

into evidence-based treatment options with potential for continuous optimization and personalization. Most existing treatments for stuttering still use approaches that are purely behavioral in nature and that are applied in a relatively generic manner across individuals. Unfortunately, the relapse rate for behavioral treatments for adults

who stutter has been estimated to be as high as 50-70%. We propose that there is a need for a clinical paradigm shift toward efficacious treatments based on contemporary insights from basic neuroscience. This requires, as a first step, carefully designed studies that identify key sensorimotor mechanisms that are amenable to realistic

intervention strategies. For example, interventions ranging from experimental manipulations of the speaker’s auditory feedback to pharmacological agents that regulate dopaminergic activity are widely known to induce

fluent speech, and such effects are supported by an extensive literature spanning several decades. Yet, in real-life clinical practice, the mechanisms of action of these methods are not understood and no progress has been made in improving their long-term clinical effects through empirically supported refinement and individualization.

The current proposal is grounded in the premise that reaching the goals for any promising intervention for stuttering is facilitated by demonstrating direct effects on neural sensorimotor mechanisms underlying the

disorder. The data from such studies can then form a much-needed translational link to develop subsequent full-scale clinical trials of the promising intervention. Recent research on the neuroscience of speech production has revealed atypical sensorimotor processing in children and adults who stutter (AWS). One set of processes that

differentiate stuttering and nonstuttering speakers relates to the central nervous system’s reliance on sensory predictions for movement planning and execution. In AWS and adults who do not stutter (ANS), we will use magnetoencephalography (MEG) imaging after either aripiprazole or placebo to examine the following indicators

of speech sensorimotor function - pre-speech auditory modulation (PSAM), speaking-induced suppression (SIS)

and its modulation by speech variability, and centering. These indicators will be studied during unaltered-feedback speech, choral speech, and altered-feedback speech. The outcome of this work will lay the foundation for future studies on novel stuttering interventions that use pharmacological agents that regulate dopamine

uptake either in isolation or in combination with existing behavioral treatments like fluency enhancement with auditory feedback manipulations or with future neuromodulation treatments. Project Summary/Abstract