Localization of stuttering based on causal brain lesions.

Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from the published literature of acquired neurogenic stuttering following stroke (n = 20, 14 males/six females, 16-77 years); (ii) a clinical single study cohort with acquired neurogenic stuttering following stroke (n = 20, 13 males/seven females, 45-87 years); and (iii) adults with persistent developmental stuttering (n = 20, 14 males/six females, 18-43 years). We used the first two datasets and lesion network mapping to test whether lesions causing acquired stuttering map to a common brain network. We then used the third dataset to test whether this lesion-based network was relevant to developmental stuttering. In our literature dataset, we found that lesions causing stuttering occurred in multiple heterogeneous brain regions, but these lesion locations were all functionally connected to a common network centred around the left putamen, including the claustrum, amygdalostriatal transition area and other adjacent areas. This finding was shown to be specific for stuttering (PFWE < 0.05) and reproducible in our independent clinical cohort of patients with stroke-induced stuttering (PFWE < 0.05), resulting in a common acquired stuttering network across both stroke datasets. Within the common acquired stuttering network, we found a significant association between grey matter volume and stuttering impact for adults with persistent developmental stuttering in the left posteroventral putamen, extending into the adjacent claustrum and amygdalostriatal transition area (PFWE < 0.05). We conclude that lesions causing acquired neurogenic stuttering map to a common brain network, centred to the left putamen, claustrum and amygdalostriatal transition area. The association of this lesion-based network with symptom severity in developmental stuttering suggests a shared neuroanatomy across aetiologies.

Erasmus clinical model of the onset and development of stuttering 2.0.

A clinical, evidence-based model to inform clients and their parents about the nature of stuttering is indispensable for the field. In this paper, we propose the Erasmus Clinical Model of Stuttering 2.0 for children who stutter and their parents, and adult clients. It provides an up-to-date, clinical model summary of current insights into the genetic, neurological, motoric, linguistic, sensory, temperamental, psychological and social factors (be it causal, eliciting, or maintaining) related to stuttering. First a review is presented of current insights in these factors, and of six scientific theories or models that have inspired the development of our current clinical model. Following this, we will propose the model, which has proven to be useful in clinical practice. The proposed Erasmus Clinical Model of Stuttering visualizes the onset and course of stuttering, and includes scales for stuttering severity and impact, to be completed by the (parent of) the person who stutters. The pathway of the model towards stuttering onset is based on predisposing and mediating factors. In most children with an onset of stuttering, stuttering is transient, but if stuttering continues, its severity and impact vary widely. The model includes the circle of Engel (1977), which visualizes unique interactions of relevant biological, psychological, and social factors that determine the speaker's experience of stuttering severity and its impact. Discussing these factors and their interaction with an individual client can feed into therapeutic targets. The model is supplemented by a lifeline casus.

The initiation of a hand grip is delayed by silently reading an incompatible syllable.

The movements of phonation structures (e.g., tongue) have been shown to facilitate compatible hand movements. For example, reaction time (RT) of precision and power hand grips (made with tips of thumb and finger vs. whole hand) are shortened with the production of syllables that share similar action features (e.g., employing the proximal vs. dorsal portion of the tongue, respectively). This effect is coined the articulation-grip correspondence (AGC) effect. However, it is not known if the AGC effect is due to action facilitation vs. interference, and if such facilitation/ interference is due to covertly or overtly reading the syllable. To answer the associated empirical questions, the present experiment involved participants initiating a precision or power grip without the covert/ overt reading of a syllable, or while covertly or overtly reading the syllable /ti/ or /ka/. In both the covert and overt reading conditions, there were longer RTs for precision grips with the syllable /ka/ than /ti/, and there were longer RTs for power grips with the syllable /ti/. In contrast, the syllable /ti/ or /ka/ did not alter precision or power grip RTs, respectively. These findings support the notion of articulation-grip interference but not facilitation and that such interference can be observed with covert (silent) reading.

Explicit benefits: Motor sequence acquisition and short-term retention in adults who do and do not stutter.

Motor sequencing skills have been found to distinguish individuals who experience developmental stuttering from those who do not stutter, with these differences extending to non-verbal sequencing behaviour. Previous research has focused on measures of reaction time and practice under externally cued conditions to decipher the motor learning abilities of persons who stutter. Without the confounds of extraneous demands and sensorimotor processing, we investigated motor sequence learning under conditions of explicit awareness and focused practice among adults with persistent development stuttering. Across two consecutive practice sessions, 18 adults who stutter (AWS) and 18 adults who do not stutter (ANS) performed the finger-to-thumb opposition sequencing (FOS) task. Both groups demonstrated significant within-session performance improvements, as evidenced by fast on-line learning of finger sequences on day one. Additionally, neither participant group showed deterioration of their learning gains the following day, indicating a relative stabilization of finger sequencing performance during the off-line period. These findings suggest that under explicit and focused conditions, early motor learning gains and their short-term retention do not differ between AWS and ANS. Additional factors influencing motor sequencing performance, such as task complexity and saturation of learning, are also considered. Further research into explicit motor learning and its generalization following extended practice and follow-up in persons who stutter is warranted. The potential benefits of motor practice generalizability among individuals who stutter and its relevance to supporting treatment outcomes are suggested as future areas of investigation.

Differences in implicit motor learning between adults who do and do not stutter.

Implicit learning allows us to acquire complex motor skills through repeated exposure to sensory cues and repetition of motor behaviours, without awareness or effort. Implicit learning is also critical to the incremental fine-tuning of the perceptual-motor system. To understand how implicit learning and associated domain-general learning processes may contribute to motor learning differences in people who stutter, we investigated implicit finger-sequencing skills in adults who do (AWS) and do not stutter (ANS) on an Alternating Serial Reaction Time task. Our results demonstrated that, while all participants showed evidence of significant sequence-specific learning in their speed of performance, male AWS were slower and made fewer sequence-specific learning gains than their ANS counterparts. Although there were no learning gains evident in accuracy of performance, AWS performed the implicit learning task more accurately than ANS, overall. These findings may have implications for sex-based differences in the experience of developmental stuttering, for the successful acquisition of complex motor skills during development by individuals who stutter, and for the updating and automatization of speech motor plans during the therapeutic process.

Complexity-Dependent Modulations of Beta Oscillations for Verbal and Nonverbal Movements.

Purpose The planning and execution of motor behaviors require coordination of neurons that are established through synchronization of neural activity. Movements are typically preceded by event-related desynchronization (ERD) in the beta range (15-30 Hz) primarily localized in the motor cortex, while movement onset is associated with event-related synchronization (ERS). It is hypothesized that ERD is important for movement preparation and execution, and ERS serves to inhibit movement and update the motor plan. The primary objective of this study was to determine to what extent movement-related oscillatory brain patterns (ERD and ERS) during verbal and nonverbal tasks may be affected differentially by variations in task complexity. Method Seventeen right-handed adult participants (nine women, eight men; M age = 25.8 years, SD = 5.13) completed a sequential button press and verbal task. The final analyses included data for 15 participants for the nonverbal task and 13 for the verbal task. Both tasks consisted of two complexity levels: simple and complex sequences. Magnetoencephalography was used to record modulations in beta band brain oscillations during task performance. Results Both the verbal and button press tasks were characterized by significant premovement ERD and postmovement ERS. However, only simple sequences showed a distinct transient synchronization during the premovement phase of the task. Differences between the two tasks were reflected in both latency and peak amplitude of ERD and ERS, as well as in lateralization of oscillations. Conclusions Both verbal and nonverbal movements showed a significant desynchronization of beta oscillations during the movement preparation and holding phase and a resynchronization upon movement termination. Importantly, the premovement phase for simple but not complex tasks was characterized by a transient partial synchronization. In addition, the data revealed significant differences between the two tasks in terms of lateralization of oscillatory modulations. Our findings suggest that, while data from the general motor control research can inform our understanding of speech motor control, significant differences exist between the two motor systems that caution against overgeneralization of underlying neural control processes.

White matter microstructural differences underlying beta oscillations during speech in adults who stutter.

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.

Effect of word phonetic properties on stuttering anticipation and speech production in adults who stutter.

PURPOSE: Stuttering anticipation is a significant factor in an individual's stuttering experience. People who stutter have reported words and sounds that they anticipate stuttering on. Attempts at understanding the association between stuttering anticipation and stuttering outcomes and the impact of phonetic properties on stuttering anticipation and overt stuttering have been insufficiently examined. This study aims to address these important issues. METHODS: Data were collected as part of a larger brain imaging study. Twenty adults who stutter rated a 414 word-list on stuttering anticipation. Participant-specific 'high' and 'low' anticipated words were selected. Twelve of the 20 participants returned for a second session 2-11 weeks later, during which they read the selected words again and stuttering occurrence was recorded. RESULTS: Among the 20 participants, three sub-groups with "high" (N = 6), "moderate" (N = 5) and "low" (N = 9) stuttering anticipation were identified. Significant "high stuttering" anticipation was found on consonants, plosives, bilabials and alveolars, as well as labials and coronals. In 5 of the 8 participants who stuttered during session 2, more than 80 % of words stuttered were previously rated with high anticipation. Consonants, plosives, bilabials and alveolars, and labials and coronals were the most frequently stuttered (>27 %). CONCLUSION: While not all adults who stutter demonstrate high word-specific stuttering anticipation, we found that more than half anticipated this to a high degree. Furthermore, both word-specific phonetic properties and stuttering anticipation impact stuttering occurrence. The inclusion of word-specific stuttering anticipation ratings may increase the likelihood of stuttering in experimental studies and improve treatment outcomes through individualized intervention.

Brain activation during non-habitual speech production: Revisiting the effects of simulated disfluencies in fluent speakers.

Over the past decades, brain imaging studies in fluently speaking participants have greatly advanced our knowledge of the brain areas involved in speech production. In addition, complementary information has been provided by investigations of brain activation patterns associated with disordered speech. In the present study we specifically aimed to revisit and expand an earlier study by De Nil and colleagues, by investigating the effects of simulating disfluencies on the brain activation patterns of fluent speakers during overt and covert speech production. In contrast to the De Nil et al. study, the current findings show that the production of voluntary, self-generated disfluencies by fluent speakers resulted in increased recruitment and activation of brain areas involved in speech production. These areas show substantial overlap with the neural networks involved in motor sequence learning in general, and learning of speech production, in particular. The implications of these findings for the interpretation of brain imaging studies on disordered and non-habitual speech production are discussed.

Assessing chronic fatigue syndrome: Self-reported physical functioning and correlations with physical testing.

The pathophysiology of chronic fatigue syndrome (CFS) remains unclear; no biomarkers have thus far been identified or physical tests designed to underpin its diagnosis. Assessment mainly uses Fukuda's criteria and is based on the exclusion of symptoms related to other diseases/syndromes, subjective self-reporting, and outcomes of self-report questionnaires. In order to improve the baseline assessment and progress evaluation of individuals suspected of CFS and using an association-oriented research strategy and a cross-correlational design, this study investigates possible associations between the performance on two physical tests, i.e. 'Timed Loaded Standing' (TLS), assessing trunk-arm endurance, and the 'Stops Walking with Eyes Closed while performing a secondary Cognitive Task' (SWECCT), measuring impaired automaticity of gait, and the results of two self-report questionnaires, the Checklist Individual Strength (CIS, total score and fatigue subscale score) and the physical functioning and vitality subscales of the Short Form Health Survey (SF-36) to gauge the participants' subjective feelings of fatigue and beliefs regarding their abilities to perform daily-life activities. Comparisons of the outcomes obtained in 27 female patients with a confirmed diagnosis of CFS revealed that trunk-arm endurance as measured with the TLS correlated with the SF-36 physical functioning subscale only (raw p value: 0.004). None of the other correlations were statistically significant. It is concluded that the TLS may have potential as an objective assessment tool to support the diagnosis and monitoring of treatment effects in CFS.

Exogenously triggered response inhibition in developmental stuttering.

PURPOSE: The purpose of the present study was to examine relations between children's exogenously triggered response inhibition and stuttering. METHOD: Participants were 18 children who stutter (CWS; mean age = 9;01 years) and 18 children who not stutter (CWNS; mean age = 9;01 years). Participants were matched on age (±3 months) and gender. Response inhibition was assessed by a stop signal task (Verbruggen, Logan, & Stevens, 2008). RESULTS: Results suggest that CWS, compared to CWNS, perform comparable to CWNS in a task where response control is externally triggered. CONCLUSIONS: Our findings seem to indicate that previous questionnaire-based findings (Eggers, De Nil, & Van den Bergh, 2010) of a decreased efficiency of response inhibition cannot be generalized to all types of response inhibition.

White matter tractography of the neural network for speech-motor control in children who stutter.

Stuttering is a neurodevelopmental speech disorder with a phenotype characterized by speech sound repetitions, prolongations and silent blocks during speech production. Developmental stuttering affects 1% of the population and 5% of children. Neuroanatomical abnormalities in the major white matter tracts, including the arcuate fasciculus, corpus callosum, corticospinal, and frontal aslant tracts (FAT), are associated with the disorder in adults who stutter but are less well studied in children who stutter (CWS). We used deterministic tractography to assess the structural connectivity of the neural network for speech production in CWS and controls. CWS had higher fractional anisotropy and axial diffusivity in the right FAT than controls. Our findings support the involvement of the corticostriatal network early in persistent developmental stuttering.

A preliminary study on the neural oscillatory characteristics of motor preparation prior to dysfluent and fluent utterances in adults who stutter.

PURPOSE: Recent literature on speech production in adults who stutter (AWS) has begun to investigate the neural mechanisms characterizing speech-motor preparation prior to speech onset. Compelling evidence has suggested that stuttering is associated with atypical processing within cortical and sub-cortical motor networks, particularly in the beta frequency range, that is effective before speech production even begins. Due to low stuttering frequency in experimental settings, however, the literature has so far predominantly reported on fluent speech production in AWS. Consequently, we have limited understanding of the way in which fluent speech processing in AWS is disturbed leading to a dysfluency. This preliminary study aims to characterize neural motor preparation prior to stuttered utterances in AWS. METHODS: Eight AWS participated in the study. A total of 336 stuttered utterances were compared to the participants' own fluent utterance productions. Beta oscillatory activity was analyzed with magnetoencephalography (MEG) and localized using minimum-variance beamforming. RESULTS: Preparation for speech production induced beta suppression in the bilateral premotor and motor cortex prior to speech onset. Although the data revealed some interesting trends, no significant differences between fluent and stuttered utterances were present. This may be due to a relatively low and variable number of stuttered trials analyzed in individual subjects. CONCLUSION: While the lack of significant differences may have resulted from the relatively low numbers of stuttered utterances across subjects, the observed trends demonstrated that the proposed methodology and experimental paradigm is a promising approach for future studies aiming to characterize differences between stuttered and fluent speech.

Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter.

Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15-25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population.

Effects of Age, Sex and Syllable Number on Voice Onset Time: Evidence from Children's Voiceless Aspirated Stops.

Voice onset time (VOT) is a temporal acoustic parameter that reflects motor speech coordination skills. This study investigated the patterns of age and sex differences across development of voice onset time in a group of 70 English-speaking children, ranging in age from 4.1 to 18.4 years, and 12 young adults. The effect of the number of syllables on VOT patterns was also examined. Speech samples were elicited by producing syllables /pa/ and /pataka/. Results supported previous findings showing that younger children produce longer VOT values with higher levels of variability. Markedly higher VOT values and increased variability were found for boys at ages between 8 and 11 years, confirming sex differences in VOT patterns and patterns of variability. In addition, all participants consistently produced shorter VOT with higher variability for multisyllables than monosyllables, indicating an effect of syllable number. Possible explanations for these findings and clinical implications are discussed.

The trajectory of gray matter development in Broca's area is abnormal in people who stutter.

The acquisition and mastery of speech-motor control requires years of practice spanning the course of development. People who stutter often perform poorly on speech-motor tasks thereby calling into question their ability to establish the stable neural motor programs required for masterful speech-motor control. There is evidence to support the assertion that these neural motor programs are represented in the posterior part of Broca's area, specifically the left pars opercularis. Consequently, various theories of stuttering causation posit that the disorder is related to a breakdown in the formation of the neural motor programs for speech early in development and that this breakdown is maintained throughout life. To date, no study has examined the potential neurodevelopmental signatures of the disorder across pediatric and adult populations. The current study aimed to fill this gap in our knowledge. We hypothesized that the developmental trajectory of cortical thickness in people who stutter would differ across the lifespan in the left pars opercularis relative to a group of control participants. We collected structural magnetic resonance images from 116 males (55 people who stutter) ranging in age from 6 to 48 years old. Differences in cortical thickness across ages and between patients and controls were investigated in 30 brain regions previously implicated in speech-motor control. An interaction between age and group was found for the left pars opercularis only. In people who stutter, the pars opercularis did not demonstrate the typical maturational pattern of gradual gray matter thinning with age across the lifespan that we observed in control participants. In contrast, the developmental trajectory of gray matter thickness in other regions of interest within the neural network for speech-motor control was similar for both groups. Our findings indicate that the developmental trajectory of gray matter in left pars opercularis is abnormal in people who stutter.

Atypical central auditory speech-sound discrimination in children who stutter as indexed by the mismatch negativity.

PURPOSE: Recent theoretical conceptualizations suggest that disfluencies in stuttering may arise from several factors, one of them being atypical auditory processing. The main purpose of the present study was to investigate whether speech sound encoding and central auditory discrimination, are affected in children who stutter (CWS). METHODS: Participants were 10 CWS, and 12 typically developing children with fluent speech (TDC). Event-related potentials (ERPs) for syllables and syllable changes [consonant, vowel, vowel-duration, frequency (F0), and intensity changes], critical in speech perception and language development of CWS were compared to those of TDC. RESULTS: There were no significant group differences in the amplitudes or latencies of the P1 or N2 responses elicited by the standard stimuli. However, the Mismatch Negativity (MMN) amplitude was significantly smaller in CWS than in TDC. For TDC all deviants of the linguistic multifeature paradigm elicited significant MMN amplitudes, comparable with the results found earlier with the same paradigm in 6-year-old children. In contrast, only the duration change elicited a significant MMN in CWS. CONCLUSIONS: The results showed that central auditory speech-sound processing was typical at the level of sound encoding in CWS. In contrast, central speech-sound discrimination, as indexed by the MMN for multiple sound features (both phonetic and prosodic), was atypical in the group of CWS. Findings were linked to existing conceptualizations on stuttering etiology. EDUCATIONAL OBJECTIVES: The reader will be able (a) to describe recent findings on central auditory speech-sound processing in individuals who stutter, (b) to describe the measurement of auditory reception and central auditory speech-sound discrimination, (c) to describe the findings of central auditory speech-sound discrimination, as indexed by the mismatch negativity (MMN), in children who stutter.

Age-related sex differences in language lateralization: A magnetoencephalography study in children.

It is well supported by behavioral and neuroimaging studies that typical language function is lateralized to the left hemisphere in the adult brain and this laterality is less well defined in children. The behavioral literature suggests there maybe be sex differences in language development, but this has not been examined systematically with neuroimaging. In this study, magnetoencephalography was used to investigate the spatiotemporal patterns of language lateralization as a function of age and sex. Eighty typically developing children (46 female, 34 male; 4-18 years) participated in an overt visual verb generation task. An analysis method called differential beamforming was used to analyze language-related changes in oscillatory activity referred to as low-gamma event-related desynchrony (ERD). The proportion of ERD over language areas relative to total ERD was calculated. We found different patterns of laterality between boys and girls. Boys showed left-hemisphere lateralization in the frontal and temporal language-related areas across age groups, whereas girls showed a more bilateral pattern, particularly in frontal language-related areas. Differences in patterns of ERD were most striking between boys and girls in the younger age groups, and these patterns became more similar with increasing age, specifically in the preteen years. Our findings show sex differences in language lateralization during childhood; however, these differences do not seem to persist into adulthood. We present possible explanations for these differences. We also discuss the implications of these findings for presurgical language mapping in children and highlight the importance of examining the question of sex-related language differences across development.

Changes in voice onset time and motor speech skills in children following motor speech therapy: Evidence from /pa/ productions.

This study evaluated changes in motor speech control and inter-gestural coordination for children with speech sound disorders (SSD) subsequent to Prompts for Restructuring Oral and Muscular Phonetic Targets (PROMPT) intervention. We measured the distribution patterns of voice onset time (VOT) for a voiceless stop (/p/) to examine the changes in inter-gestural coordination. Two standardized tests were used (Verbal Motor Production Assessment for Children (VMPAC), GFTA-2) to assess the changes in motor speech skills and articulation. Data showed positive changes in patterns of VOT with a lower pattern of variability. All children showed significantly higher scores for VMPAC, but only some children showed higher scores for GFTA-2. Results suggest that the proprioceptive feedback provided through PROMPT had a positive influence on speech motor control and inter-gestural coordination in voicing behavior. This set of VOT data for children with SSD adds to our understanding of the speech characteristics underlying speech motor control. Directions for future studies are discussed.

Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.

Children with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p ≤ 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p ≤ 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.