Genetic approaches to understanding the causes of stuttering

Stuttering is a common but poorly understood speech disorder. Evidence accumulated over the past several decades has indicated that genetic factors are involved, and genetic linkage studies have begun to identify specific chromosomal loci at which causative genes are likely to reside. A detailed investigation of one such region on chromosome 12 has identified mutations in the GNPTAB gene that are associated with stuttering in large families and in the general population. Subsequent studies identified mutations in the functionally related GNPTG and NAGPA genes. Mutations in these genes disrupt the lysosomal targeting pathway that generates the Mannose 6-phosphate signal, which directs a diverse group of enzymes to their target location in the lysosome of the cell. While mutations in these three genes can be identified in less than 10% of cases of familial stuttering, this knowledge allows a variety of new studies that can help identify the neuropathology that underlies this disorder

Altered Auditory Feedback In-The-Ear Devices

Purpose: This study examined objective and subjective measures of the effect of a self-contained ear-level device delivering altered auditory feedback (AAF) for those who stutter 12 months following initial fitting with and without the device. Method: Nine individuals with developmental stuttering participated. In Experiment 1, the proportion of stuttering was examined during reading and monologue. A self-report inventory inquiring about behavior related to struggle, avoidance and expectancy associated with stuttering was examined in Experiment 2. In Experiment 3, naive listeners rated the speech naturalness of speech produced by the participants during reading and monologue. Results: The proportions of stuttering events were significantly (p < 0.05) reduced at initial fitting and remained so 12 months post follow-up. After using the device for 12 months, self- reported perception of struggle, avoidance and expectancy were significantly (p < 0.05) reduced relative to pre-fitting. Naive listeners rated the speech samples produced by those who stutter while wearing the device significantly more natural sounding than those produced without the device for both reading and monologue (p < 0.0001). Conclusions: These findings support the notion that a device delivering AAF is a viable therapeutic alternative in the treatment of stuttering

The state of the art in non-pharmacological interventions for developmental stuttering. Part 1: a systematic review of effectiveness

Background The growing range of available treatment options for people who stutter presents a challenge for clinicians, service managers and commissioners, who need to have access to the best available treatment evidence to guide them in providing the most appropriate interventions. While a number of reviews of interventions for specific populations or a specific type of intervention have been carried out, a broad-based systematic review across all forms of intervention for adults and children was needed to provide evidence to underpin future guidelines, inform the implementation of effective treatments and identify future research priorities. Aims To identify and synthesize the published research evidence on the clinical effectiveness of the broad range of non-pharmacological interventions for the management of developmental stuttering. Methods & Procedures A systematic review of the literature reporting interventions for developmental stuttering was carried out between August 2013 and April 2014. Searches were not limited by language or location, but were restricted by date to studies published from 1990 onwards. Methods for the identification of relevant studies included electronic database searching, reference list checking, citation searching and hand searching of key journals. Appraisal of study quality was performed using a tool based on established criteria for considering risk of bias. Due to heterogeneity in intervention content and outcomes, a narrative synthesis was completed. Main Contribution The review included all available types of intervention and found that most may be of benefit to at least some people who stutter. There was evidence, however, of considerable individual variation in response to these interventions. The review indicated that effects could be maintained following all types of interventions (although this was weakest with regard to feedback and technology interventions). Conclusions This review highlights a need for greater consensus with regard to the key outcomes used to evaluate stuttering interventions, and also a need for enhanced understanding of the process whereby interventions effect change. Further analysis of the variation in effectiveness for different individuals or groups is needed in order to identify who may benefit most from which intervention

Resting-State Brain Activity in Adult Males Who Stutter

Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them

Classification of Types of Stuttering Symptoms Based on Brain Activity

Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type