Soo Eun Chang

Evidence of Left Inferior Frontal–Premotor Structural and Functional Connectivity Deficits in Adults Who Stutter

The neurophysiological basis for stuttering may involve deficits that affect dynamic interactions among neural structures supporting fluid speech processing. Here, we examined functional and structural connectivity within corticocortical and thalamocortical loops in adults who stutter. For functional connectivity, we placed seeds in the left and right inferior frontal Brodmann area 44 (BA44) and in the ventral lateral nucleus (VLN) of the thalamus. Subject-specific seeds were based on peak activation voxels captured during speech and nonspeech tasks using functional magnetic resonance imaging. Psychophysiological interaction (PPI) was used to find brain regions with heightened functional connectivity with these cortical and subcortical seeds during speech and nonspeech tasks. Probabilistic tractography was used to track white matter tracts in each hemisphere using the same seeds. Both PPI and tractrography supported connectivity deficits between the left BA44 and the left premotor regions, while connectivity among homologous right hemisphere structures was significantly increased in the stuttering group. No functional connectivity differences between BA44 and auditory regions were found between groups. The functional connectivity results derived from the VLN seeds were less definitive and were not supported by the tractography results. Our data provide strongest support for deficient left hemisphere inferior frontal to premotor connectivity as a neural correlate of stuttering.

Neural network connectivity differences in children who stutter

Affecting 1% of the general population, stuttering impairs the normally effortless process of speech production, which requires precise coordination of sequential movement occurring among the articulatory, respiratory, and resonance systems, all within millisecond time scales. Those afflicted experience frequent disfluencies during ongoing speech, often leading to negative psychosocial consequences. The aetiology of stuttering remains unclear; compared to other neurodevelopmental disorders, few studies to date have examined the neural bases of childhood stuttering. Here we report, for the first time, results from functional (resting state functional magnetic resonance imaging) and structural connectivity analyses (probabilistic tractography) of multimodal neuroimaging data examining neural networks in children who stutter. We examined how synchronized brain activity occurring among brain areas associated with speech production, and white matter tracts that interconnect them, differ in young children who stutter (aged 3-9 years) compared with age-matched peers. Results showed that children who stutter have attenuated connectivity in neural networks that support timing of self-paced movement control. The results suggest that auditory-motor and basal ganglia-thalamocortical networks develop differently in stuttering children, which may in turn affect speech planning and execution processes needed to achieve fluent speech motor control. These results provide important initial evidence of neurological differences in the early phases of symptom onset in children who stutter.

White matter neuroanatomical differences in young children who stutter

The ability to express thoughts through fluent speech production is a most human faculty, one that is often taken for granted. Stuttering, which disrupts the smooth flow of speech, affects 5% of preschool-age children and 1% of the general population, and can lead to significant communication difficulties and negative psychosocial consequences throughout ones lifetime. Despite the fact that symptom onset typically occurs during early childhood, few studies have yet examined the possible neural bases of developmental stuttering during childhood. Here we present a diffusion tensor imaging study that examined white matter measures reflecting neuroanatomical connectivity (fractional anisotropy) in 77 children [40 controls (20 females), 37 who stutter (16 females)] between 3 and 10 years of age. We asked whether previously reported anomalous white matter measures in adults and older children who stutter that were found primarily in major left hemisphere tracts (e.g. superior longitudinal fasciculus) are also present in younger children who stutter. All children exhibited normal speech, language, and cognitive development as assessed through a battery of assessments. The two groups were matched in chronological age and socioeconomic status. Voxel-wise whole brain comparisons using tract-based spatial statistics and region of interest analyses of fractional anisotropy were conducted to examine white matter changes associated with stuttering status, age, sex, and stuttering severity. Children who stutter exhibited significantly reduced fractional anisotropy relative to controls in white matter tracts that interconnect auditory and motor structures, corpus callosum, and in tracts interconnecting cortical and subcortical areas. In contrast to control subjects, fractional anisotropy changes with age were either stagnant or showed dissociated development among major perisylvian brain areas in children who stutter. These results provide first glimpses into the neuroanatomical bases of early childhood stuttering, and possible white matter developmental changes that may lead to recovery versus persistent stuttering. The white matter changes point to possible structural connectivity deficits in children who stutter, in interrelated neural circuits that enable skilled movement control through efficient sensorimotor integration and timing of movements.

Evidence for a rhythm perception deficit in children who stutter.

Stuttering is a neurodevelopmental disorder that affects the timing and rhythmic flow of speech production. When speech is synchronized with an external rhythmic pacing signal (e.g., a metronome), even severe stuttering can be markedly alleviated, suggesting that people who stutter may have difficulty generating an internal rhythm to pace their speech. To investigate this possibility, children who stutter and typically-developing children (n=17 per group, aged 6-11 years) were compared in terms of their auditory rhythm discrimination abilities of simple and complex rhythms. Children who stutter showed worse rhythm discrimination than typically-developing children. These findings provide the first evidence of impaired rhythm perception in children who stutter, supporting the conclusion that developmental stuttering may be associated with a deficit in rhythm processing.

Corpus callosum differences associated with persistent stuttering in adults.

Recent studies have implicated anatomical differences in speech-relevant brain regions of adults who stutter (AWS) compared to normally fluent adults (NFA). The present study focused on the region of the corpus callosum (CC) which is involved in interhemispheric processing between the left and right cerebral hemispheres. Two-dimensional segmentation of area and voxel-based morphometry were used to evaluate the corpus callosum. Results revealed that the rostrum and anterior midbody of the CC were larger in AWS than NFA. In addition, the overall callosa area was larger in AWS than NFA. The group comparison of white matter volume showed a cluster of increased white matter volume predominantly encompassing the rostrum across the midline portion in AWS. These results potentially reflect anatomical changes associated with differences in the hemispheric distribution of language processes that have been reported previously in AWS.

Similarities in speech and white matter characteristics in idiopathic developmental stuttering and adult-onset stuttering

Adult-onset stuttering (AS) typically occurs following neurological and/or psychological trauma, considered different from developmental stuttering (DS), which starts during early childhood with few if any new cases reported after adolescence. Here we report four cases of AS, two with apparent psychological trigger and two without, none with evidence of neurological injury, and none conforming to previously reported characteristics of psychogenic stuttering. We asked whether this group of AS would have similar speech and neuroanatomical characteristics to those with DS. We conducted blinded analyses of speech samples in both AS cases and 14 cases of DS on type, frequency, and loci of disfluencies. Diffusion tensor imaging (DTI) was conducted to compare white matter tracts using fractional anisotropy (FA). We found that AS did not differ significantly from DS in any of the speech characteristics measured. On DTI, DS had significantly increased FA relative to controls in the right superior longitudinal tract. AS cases showed a similar trend for increases in these regions when compared to controls. The results of this study suggest that symptoms of idiopathic stuttering can begin during adulthood, and that similar neuroanatomical differences from controls may be associated with both developmental and adult onset idiopathic stuttering.

Research updates in neuroimaging studies of children who stutter

In the past two decades, neuroimaging investigations of stuttering have led to important discoveries of structural and functional brain differences in people who stutter, providing significant clues to the neurological basis of stuttering. One major limitation, however, has been that most studies so far have only examined adults who stutter, whose brain and behavior likely would have adopted compensatory reactions to their stuttering; these confounding factors have made interpretations of the findings difficult. Developmental stuttering is a neurodevelopmental condition, and like many other neurodevelopmental disorders, stuttering is associated with an early childhood onset of symptoms and greater incidence in males relative to females. More recent studies have begun to examine children who stutter using various neuroimaging techniques that allow examination of functional neuroanatomy and interaction of major brain areas that differentiate children who stutter compared with age-matched controls. In this article, I review these more recent neuroimaging investigations of children who stutter, in the context of what we know about typical brain development, neuroplasticity, and sex differences relevant to speech and language development. Although the picture is still far from complete, these studies have potential to provide information that can be used as early objective markers, or prognostic indicators, for persistent stuttering in the future. Furthermore, these studies are the first steps in finding potential neural targets for novel therapies that may involve modulating neuroplastic growth conducive to developing and maintaining fluent speech, which can be applied to treatment of young children who stutter.

Arrhythmic song exposure increases ZENK Expression in auditory cortical areas and nucleus taeniae of the adult zebra finch

Rhythm is important in the production of motor sequences such as speech and song. Deficits in rhythm processing have been implicated in human disorders that affect speech and language processing, including stuttering, autism, and dyslexia. Songbirds provide a tractable model for studying the neural underpinnings of rhythm processing due to parallels with humans in neural structures and vocal learning patterns. In this study, adult zebra finches were exposed to naturally rhythmic conspecific song or arrhythmic song. Immunohistochemistry for the immediate early gene ZENK was used to detect neural activation in response to these two types of stimuli. ZENK was increased in response to arrhythmic song in the auditory association cortex homologs, caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM), and the avian amygdala, nucleus taeniae (Tn). CMM also had greater ZENK labeling in females than males. The increased neural activity in NCM and CMM during perception of arrhythmic stimuli parallels increased activity in the human auditory cortex following exposure to unexpected, or perturbed, auditory stimuli. These auditory areas may be detecting errors in arrhythmic song when comparing it to a stored template of how conspecific song is expected to sound. CMM may also be important for females in evaluating songs of potential mates. In the context of other research in songbirds, we suggest that the increased activity in Tn may be related to the value of song for assessing mate choice and bonding or it may be related to perception of arrhythmic song as aversive.

Relation between functional connectivity and rhythm discrimination in children who do and do not stutter

Our ability to perceive and produce rhythmic patterns in the environment supports fundamental human capacities ranging from music and language processing to the coordination of action. This article considers whether spontaneous correlated brain activity within a basal ganglia-thalamocortical (rhythm) network is associated with individual differences in auditory rhythm discrimination. Moreover, do children who stutter with demonstrated deficits in rhythm perception have weaker links between rhythm network functional connectivity and rhythm discrimination? All children in the study underwent a resting-state fMRI session, from which functional connectivity measures within the rhythm network were extracted from spontaneous brain activity. In a separate session, the same children completed an auditory rhythm-discrimination task, where behavioral performance was assessed using signal detection analysis. We hypothesized that in typically developing children, rhythm network functional connectivity would be associated with behavioral performance on the rhythm discrimination task, but that this relationship would be attenuated in children who stutter. Results supported our hypotheses, lending strong support for the view that (1) children who stutter have weaker rhythm network connectivity and (2) the lack of a relation between rhythm network connectivity and rhythm discrimination in children who stutter may be an important contributing factor to the etiology of stuttering.

Auditory-motor adaptation is reduced in adults who stutter but not in children who stutter

Previous studies have shown that adults who stutter produce smaller corrective motor responses to compensate for unexpected auditory perturbations in comparison to adults who do not stutter, suggesting that stuttering may be associated with deficits in integration of auditory feedback for online speech monitoring. In this study, we examined whether stuttering is also associated with deficiencies in integrating and using discrepancies between expected and received auditory feedback to adaptively update motor programs for accurate speech production. Using a sensorimotor adaptation paradigm, we measured adaptive speech responses to auditory formant frequency perturbations in adults and children who stutter and their matched nonstuttering controls. We found that the magnitude of the speech adaptive response for children who stutter did not differ from that of fluent children. However, the adaptation magnitude of adults who stutter in response to auditory perturbation was significantly smaller than the adaptation magnitude of adults who do not stutter. Together these results indicate that stuttering is associated with deficits in integrating discrepancies between predicted and received auditory feedback to calibrate the speech production system in adults but not children. This auditory-motor integration deficit thus appears to be a compensatory effect that develops over years of stuttering.