Anomalous morphology in left hemisphere motor and premotor cortex of children who stutter.

Stuttering is a neurodevelopmental disorder that affects the smooth flow of speech production. Stuttering onset occurs during a dynamic period of development when children first start learning to formulate sentences. Although most children grow out of stuttering naturally, ∼1% of all children develop persistent stuttering that can lead to significant psychosocial consequences throughout one's life. To date, few studies have examined neural bases of stuttering in children who stutter, and even fewer have examined the basis for natural recovery versus persistence of stuttering. Here we report the first study to conduct surface-based analysis of the brain morphometric measures in children who stutter. We used FreeSurfer to extract cortical size and shape measures from structural MRI scans collected from the initial year of a longitudinal study involving 70 children (36 stuttering, 34 controls) in the 3-10-year range. The stuttering group was further divided into two groups: persistent and recovered, based on their later longitudinal visits that allowed determination of their eventual clinical outcome. A region of interest analysis that focused on the left hemisphere speech network and a whole-brain exploratory analysis were conducted to examine group differences and group × age interaction effects. We found that the persistent group could be differentiated from the control and recovered groups by reduced cortical thickness in left motor and lateral premotor cortical regions. The recovered group showed an age-related decrease in local gyrification in the left medial premotor cortex (supplementary motor area and and pre-supplementary motor area). These results provide strong evidence of a primary deficit in the left hemisphere speech network, specifically involving lateral premotor cortex and primary motor cortex, in persistent developmental stuttering. Results further point to a possible compensatory mechanism involving left medial premotor cortex in those who recover from childhood stuttering.

White matter developmental trajectories associated with persistence and recovery of childhood stuttering.

Stuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual's psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering has been reported. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3 and 12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel-wise to examine group and age-related differences using a linear mixed-effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum was found, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering. Hum Brain Mapp 38:3345-3359, 2017. © 2017 Wiley Periodicals, Inc.

Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from other states of consciousness.

Rapid eye movement (REM) sleep constitutes a distinct "third state" of consciousness, during which levels of brain activity are commensurate with wakefulness, but conscious awareness is radically transformed. To characterize the temporal and spatial features of this paradoxical state, we examined functional interactions between brain regions using fMRI resting-state connectivity methods. Supporting the view that the functional integrity of the default mode network (DMN) reflects "level of consciousness," we observed functional uncoupling of the DMN during deep sleep and recoupling during REM sleep (similar to wakefulness). However, unlike either deep sleep or wakefulness, REM was characterized by a more widespread, temporally dynamic interaction between two major brain systems: unimodal sensorimotor areas and the higher-order association cortices (including the DMN), which normally regulate their activity. During REM, these two systems become anticorrelated and fluctuate rhythmically, in reciprocally alternating multisecond epochs with a frequency ranging from 0.1 to 0.01 Hz. This unique spatiotemporal pattern suggests a model for REM sleep that may be consistent with its role in dream formation and memory consolidation.

Personal experience with narrated events modulates functional connectivity within visual and motor systems during story comprehension.

Past experience of everyday life activities, which forms the basis of our knowledge about the world, greatly affects how we understand stories. Yet, little is known about how this influence is instantiated in the human brain. Here, we used functional magnetic resonance imaging to investigate how past experience facilitates functional connectivity during the comprehension of stories rich in perceptual and motor details. We found that comprehenders' past experience with the scenes and actions described in the narratives selectively modulated functional connectivity between lower- and higher-level areas within the neural systems for visual and motor processing, respectively. These intramodal interactions may play an important role in integrating personal knowledge about a narrated situation with an evolving discourse representation. This study provides empirical evidence consistent with the idea that regions related to visual and motor processing are involved in the reenactment of experience as proposed by theories of embodied cognition.

Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process.

Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase-dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re-engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain.

Embodied comprehension of stories: interactions between language regions and modality-specific neural systems.

The embodied view of language processing proposes that comprehension involves multimodal simulations, a process that retrieves a comprehender's perceptual, motor, and affective knowledge through reactivation of the neural systems responsible for perception, action, and emotion. Although evidence in support of this idea is growing, the contemporary neuroanatomical model of language suggests that comprehension largely emerges as a result of interactions between frontotemporal language areas in the left hemisphere. If modality-specific neural systems are involved in comprehension, they are not likely to operate in isolation but should interact with the brain regions critical to language processing. However, little is known about the ways in which language and modality-specific neural systems interact. To investigate this issue, we conducted a functional MRI study in which participants listened to stories that contained visually vivid, action-based, and emotionally charged content. Activity of neural systems associated with visual-spatial, motor, and affective processing were selectively modulated by the relevant story content. Importantly, when functional connectivity patterns associated with the left inferior frontal gyrus (LIFG), the left posterior middle temporal gyrus (pMTG), and the bilateral anterior temporal lobes (aTL) were compared, both LIFG and pMTG, but not the aTL, showed enhanced connectivity with the three modality-specific systems relevant to the story content. Taken together, our results suggest that language regions are engaged in perceptual, motor, and affective simulations of the described situation, which manifest through their interactions with modality-specific systems. On the basis of our results and past research, we propose that the LIFG and pMTG play unique roles in multimodal simulations during story comprehension.

Denoising the speaking brain: toward a robust technique for correcting artifact-contaminated fMRI data under severe motion.

A comprehensive set of methods based on spatial independent component analysis (sICA) is presented as a robust technique for artifact removal, applicable to a broad range of functional magnetic resonance imaging (fMRI) experiments that have been plagued by motion-related artifacts. Although the applications of sICA for fMRI denoising have been studied previously, three fundamental elements of this approach have not been established as follows: 1) a mechanistically-based ground truth for component classification; 2) a general framework for evaluating the performance and generalizability of automated classifiers; and 3) a reliable method for validating the effectiveness of denoising. Here we perform a thorough investigation of these issues and demonstrate the power of our technique by resolving the problem of severe imaging artifacts associated with continuous overt speech production. As a key methodological feature, a dual-mask sICA method is proposed to isolate a variety of imaging artifacts by directly revealing their extracerebral spatial origins. It also plays an important role for understanding the mechanistic properties of noise components in conjunction with temporal measures of physical or physiological motion. The potentials of a spatially-based machine learning classifier and the general criteria for feature selection have both been examined, in order to maximize the performance and generalizability of automated component classification. The effectiveness of denoising is quantitatively validated by comparing the activation maps of fMRI with those of positron emission tomography acquired under the same task conditions. The general applicability of this technique is further demonstrated by the successful reduction of distance-dependent effect of head motion on resting-state functional connectivity.

Evidence for planning and motor subtypes of stuttering based on resting state functional connectivity.

We tested the hypothesis, generated from the Gradient Order Directions Into Velocities of Articulators (GODIVA) model, that adults who stutter (AWS) may comprise subtypes based on differing connectivity within the cortico-basal ganglia planning or motor loop. Resting state functional connectivity from 91 AWS and 79 controls was measured for all GODIVA model connections. Based on a principal components analysis, two connections accounted for most of the connectivity variability in AWS: left thalamus - left posterior inferior frontal sulcus (planning loop component) and left supplementary motor area - left ventral premotor cortex (motor loop component). A k-means clustering algorithm using the two connections revealed three clusters of AWS. Cluster 1 was significantly different from controls in both connections; Cluster 2 was significantly different in only the planning loop; and Cluster 3 was significantly different in only the motor loop. These findings suggest the presence of planning and motor subtypes of stuttering.

Brain activity during the preparation and production of spontaneous speech in children with persistent stuttering.

Speech production forms the basis for human verbal communication. Though fluent speech production is effortless and automatic for most people, it is disrupted in speakers who stutter, who experience difficulties especially during spontaneous speech and at utterance onsets. Brain areas comprising the basal ganglia thalamocortical (BGTC) motor loop have been a focus of interest in the context of stuttering, given this circuit's critical role in initiating and sequencing connected speech. Despite the importance of better understanding the role of the BGTC motor loop in supporting overt, spontaneous speech production, capturing brain activity during speech has been challenging to date, due to fMRI artifacts associated with severe head motions during speech production. Here, using an advanced technique that removes speech-related artifacts from fMRI signals, we examined brain activity occurring immediately before, and during, overt spontaneous speech production in 22 children with persistent stuttering (CWS) and 18 children who do not stutter (controls) in the 5-to-12-year age range. Brain activity during speech production was compared in two conditions: spontaneous speech (i.e., requiring language formulation) and automatic speech (i.e., overlearned word sequences). Compared to controls, CWS exhibited significantly reduced left premotor activation during spontaneous speech production but not during automatic speech. Moreover, CWS showed an age-related reduction in left putamen and thalamus activation during speech preparation. These results provide further evidence that stuttering is associated with functional deficits in the BGTC motor loop, which are exacerbated during spontaneous speech production.

Brain developmental trajectories associated with childhood stuttering persistence and recovery.

Stuttering is a neurodevelopmental disorder affecting 5-8 % of preschool-age children, continuing into adulthood in 1 % of the population. The neural mechanisms underlying persistence and recovery from stuttering remain unclear and little information exists on neurodevelopmental anomalies in children who stutter (CWS) during preschool age, when stuttering symptoms typically first emerge. Here we present findings from the largest longitudinal study of childhood stuttering to date, comparing children with persistent stuttering (pCWS) and those who later recovered from stuttering (rCWS) with age-matched fluent peers, to examine the developmental trajectories of both gray matter volume (GMV) and white matter volume (WMV) using voxel-based morphometry. A total of 470 MRI scans were analyzed from 95 CWS (72 pCWS and 23 rCWS) and 95 fluent peers between 3 and 12 years of age. We examined overall group and group by age interactions in GMV and WMV in preschool age (3-5 years old) and school age (6-12 years old) CWS and controls, controlling for sex, IQ, intracranial volume, and socioeconomic status. The results provide broad support for a possible basal ganglia-thalamocortical (BGTC) network deficit starting in the earliest phases of the disorder and point to normalization or compensation of earlier occurring structural changes associated with stuttering recovery.

Auditory rhythm discrimination in adults who stutter: An fMRI study.

Rhythm perception deficits have been linked to neurodevelopmental disorders affecting speech and language. Children who stutter have shown poorer rhythm discrimination and attenuated functional connectivity in rhythm-related brain areas, which may negatively impact timing control required for speech. It is unclear whether adults who stutter (AWS), who are likely to have acquired compensatory adaptations in response to rhythm processing/timing deficits, are similarly affected. We compared rhythm discrimination in AWS and controls (total n = 36) during fMRI in two matched conditions: simple rhythms that consistently reinforced a periodic beat, and complex rhythms that did not (requiring greater reliance on internal timing). Consistent with an internal beat deficit hypothesis, behavioral results showed poorer complex rhythm discrimination for AWS than controls. In AWS, greater stuttering severity was associated with poorer rhythm discrimination. AWS showed increased activity within beat-based timing regions and increased functional connectivity between putamen and cerebellum (supporting interval-based timing) for simple rhythms.

Neural activity during solo and choral reading: A functional magnetic resonance imaging study of overt continuous speech production in adults who stutter.

Previous neuroimaging investigations of overt speech production in adults who stutter (AWS) found increased motor and decreased auditory activity compared to controls. Activity in the auditory cortex is heightened, however, under fluency-inducing conditions in which AWS temporarily become fluent while synchronizing their speech with an external rhythm, such as a metronome or another speaker. These findings suggest that stuttering is associated with disrupted auditory motor integration. Technical challenges in acquiring neuroimaging data during continuous overt speech production have limited experimental paradigms to short or covert speech tasks. Such paradigms are not ideal, as stuttering primarily occurs during longer speaking tasks. To address this gap, we used a validated spatial ICA technique designed to address speech movement artifacts during functional magnetic resonance imaging (fMRI) scanning. We compared brain activity and functional connectivity of the left auditory cortex during continuous speech production in two conditions: solo (stutter-prone) and choral (fluency-inducing) reading tasks. Overall, brain activity differences in AWS relative to controls in the two conditions were similar, showing expected patterns of hyperactivity in premotor/motor regions but underactivity in auditory regions. Functional connectivity of the left auditory cortex (STG) showed that within the AWS group there was increased correlated activity with the right insula and inferior frontal area during choral speech. The AWS also exhibited heightened connectivity between left STG and key regions of the default mode network (DMN) during solo speech. These findings indicate possible interference by the DMN during natural, stuttering-prone speech in AWS, and that enhanced coordination between auditory and motor regions may support fluent speech.

Neuroanatomical anomalies associated with rare AP4E1 mutations in people who stutter.

Developmental stuttering is a common speech disorder with strong genetic underpinnings. Recently, stuttering has been associated with mutations in genes involved in lysosomal enzyme trafficking. However, how these mutations affect the brains of people who stutter remains largely unknown. In this study, we compared grey matter volume and white matter fractional anisotropy between a unique group of seven subjects who stutter and carry the same rare heterozygous AP4E1 coding mutations and seven unrelated controls without such variants. The carriers of the AP4E1 mutations are members of a large Cameroonian family in which the association between AP4E1 and persistent stuttering was previously identified. Compared to controls, mutation carriers showed reduced grey matter volume in the thalamus, visual areas and the posterior cingulate cortex. Moreover, reduced fractional anisotropy was observed in the corpus callosum, consistent with the results of previous neuroimaging studies of people who stutter with unknown genetic backgrounds. Analysis of gene expression data showed that these structural differences appeared at the locations in which expression of AP4E1 is relatively high. Moreover, the pattern of grey matter volume differences was significantly associated with AP4E1 expression across the left supratentorial regions. This spatial congruency further supports the connection between AP4E1 mutations and the observed structural differences.

Developmental Factors That Predict Head Movement During Resting-State Functional Magnetic Resonance Imaging in 3-7-Year-Old Stuttering and Non-stuttering Children.

Early childhood marks a period of dynamic neurocognitive development. Preschool-age coincides with the onset of many childhood disorders and is a developmental period that is frequently studied to determine markers of neurodevelopmental disorders. Magnetic resonance imaging (MRI) is often used to explore typical brain development and the neural bases of neurodevelopmental disorders. However, acquiring high-quality MRI data in young children is challenging. The enclosed space and loud sounds can trigger unease and cause excessive head movement. A better understanding of potential factors that predict successful MRI acquisition would increase chances of collecting useable data in children with and without neurodevelopmental disorders. We investigated whether age, sex, stuttering status, and childhood temperament as measured using the Child Behavioral Questionnaire, could predict movement extent during resting-state functional MRI (rs-fMRI) in 76 children aged 3-7 years, including 42 children who stutter (CWS). We found that age, sex, and temperament factors could predict motion during rs-fMRI scans. The CWS were not found to differ significantly from controls in temperament or head movement during scanning. Sex and age were significant predictors of movement. However, age was no longer a significant predictor when temperament, specifically effortful control, was considered. Controlling for age, boys with higher effortful control scores moved less during rs-fMRI procedures. Additionally, boys who showed higher negative affectivity showed a trend for greater movement. Considering temperament factors in addition to age and sex may help predict the success of acquiring useable rs-fMRI (and likely general brain MRI) data in young children in MR neuroimaging.

Association Between Gray Matter Volume Variations and Energy Utilization in the Brain: Implications for Developmental Stuttering.

Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism. Method High-resolution structural MRI scans were acquired from 26 persistent stuttering and 44 typically developing children. Voxel-based morphometry was used to quantify the between-group gray matter volume (GMV) differences across the whole brain. Group differences in GMV were then compared with published values for the pattern of glucose metabolism measured via F18 fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F18 fluorodeoxyglucose uptake was found in the left hemisphere (ρ = .36, p < .01), where speech-motor and language processing are typically localized. No such correlation was observed in the right hemisphere (ρ = .05, p = .70). Conclusions Corroborating our previous gene expression studies, the results of the current study suggest a potential connection between energy metabolism and stuttering. Brain regions with high energy utilization may be particularly vulnerable to anatomical changes associated with stuttering. Such changes may be further exacerbated when there are sharp increases in brain energy utilization, which coincides with the developmental period of rapid speech/language acquisition and the onset of stuttering during childhood. Supplemental Material https://doi.org/10.23641/asha.14110454.

Linking Lysosomal Enzyme Targeting Genes and Energy Metabolism with Altered Gray Matter Volume in Children with Persistent Stuttering.

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and 12-20% of stuttering cases may carry a mutation in one of four genes involved in intracellular trafficking. To better understand the relationship between genetics and neuroanatomical changes, we used gene expression data from the Allen Institute for Brain Science and voxel-based morphometry to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume between children with persistent stuttering (n = 26, and 87 scans) and their fluent peers (n = 44, and 139 scans). We found that the expression patterns of two stuttering-related genes (GNPTG and NAGPA) from the Allen Institute data exhibited a strong positive spatial correlation with the magnitude of between-group gray matter volume differences. Additional gene set enrichment analyses revealed that genes whose expression was highly correlated with the gray matter volume differences were enriched for glycolysis and oxidative metabolism in mitochondria. Because our current study did not examine the participants' genomes, these results cannot establish the direct association between genetic mutations and gray matter volume differences in stuttering. However, our results support further study of the involvement of lysosomal enzyme targeting genes, as well as energy metabolism in stuttering. Future studies assessing variations of these genes in the participants' genomes may lead to increased understanding of the biological mechanisms of the observed spatial relationship between gene expression and gray matter volume.

Neurofilament-lysosomal genetic intersections in the cortical network of stuttering.

The neurobiological underpinnings of stuttering, a speech disorder characterized by disrupted speech fluency, remain unclear. While recent developments in the field have afforded researchers the ability to pinpoint several genetic profiles associated with stuttering, how these specific genetic backgrounds impact neuronal circuits and how they generate or facilitate the emergence of stuttered speech remains unknown. In this study, we identified the large-scale cortical network that characterizes stuttering using functional connectivity MRI and graph theory. We performed a spatial similarity analysis that examines whether the topology of the stuttering cortical network intersects with genetic expression levels of previously reported genes for stuttering from the protein-coding transcriptome data of the Allen Human Brain Atlas. We found that GNPTG - a gene involved in the mannose-6-phosphate lysosomal targeting pathways - was significantly co-localized with the stuttering cortical network. An enrichment analysis demonstrated that the genes identified with the stuttering cortical network shared a significantly overrepresented biological functionality of Neurofilament Cytoskeleton Organization (NEFH, NEFL and INA). The relationship between lysosomal pathways, cytoskeleton organization, and stuttering, was investigated by comparing the genetic interactome between GNPTG and the neurofilament genes implicated in the current study. We found that genes of the interactome network, including CDK5, SNCA, and ACTB, act as functional links between lysosomal and neurofilament genes. These findings support the notion that stuttering is due to a lysosomal dysfunction, which has deleterious effects on the neurofilament organization of the speech neuronal circuits. They help to elucidate the intriguing, unsolved link between lysosomal mutations and the presence of stuttering.

Neuroanatomical Correlates of Childhood Stuttering: MRI Indices of White and Gray Matter Development That Differentiate Persistence Versus Recovery.

Purpose We review two recent neuroanatomical studies of children who stutter (CWS), one that examines white matter integrity and the other that focuses on cortical gray matter morphology. In both studies, we sought to examine differences between children whose stuttering persists ("persistent"), children who recovered from stuttering ("recovered"), and their nonstuttering peers ("controls"). Method Both of the reviewed studies use data from a large pediatric sample spanning preschool- to school-age children (3-10 years old at initial testing). Study 1 focused on surface-based measures of cortical size (thickness) and shape (gyrification) using structural magnetic resonance imaging, whereas Study 2 utilized diffusion tensor imaging to examine white matter integrity. Results In both studies, the main difference that emerged between CWS and fluent peers encompassed left hemisphere speech motor areas that are interconnected via the arcuate fasciculus. In the case of white matter integrity, the temporoparietal junction and posterior superior temporal gyrus, both connected via the left arcuate fasciculus, and regions along the corpus callosum that contain fibers connecting bilateral motor regions were significantly decreased in white matter integrity in CWS compared to controls. In the morphometric study, children who would go on to have persistent stuttering specifically had lower cortical thickness in ventral motor and premotor areas of the left hemisphere. Conclusion These results point to aberrant development of cortical areas involved in integrating sensory feedback with speech movements in CWS and differences in interhemispheric connectivity between the two motor cortices. Furthermore, developmental trajectories in these areas seem to diverge between persistent and recovered cases.

Stuttering Severity Modulates Effects of Non-invasive Brain Stimulation in Adults Who Stutter.

Stuttering is a neurodevelopmental disorder that manifests as frequent disruptions in the flow of speech, affecting 1% of adults. Treatments are limited to behavioral interventions with variable success and high relapse rates, particularly in adults. However, even in severe cases, fluency can be temporarily induced during conditions in which the speaker synchronizes his speech with external rhythmic cues, such as when reading in unison (choral speech) or with a metronome. Non-invasive neuromodulation techniques such as transcranial direct current stimulation (tDCS) have shown promise in augmenting the effects of behavioral treatment during motor and speech/language rehabilitation, but only one study to date has examined behavioral modulatory effects of tDCS in the context of stuttering. Using high-definition (HD)-tDCS electrodes, which improves focality of stimulation relative to conventional tDCS, we investigated the effects of tDCS on speech fluency and brain activation in 14 adults who stutter (AWS). Either anodal or sham stimulation was delivered on separate days over left supplementary motor area (SMA). During stimulation, participants read aloud in sync with a metronome. Measures of speech fluency and brain activity functional magnetic resonance imaging (fMRI) were collected before and after stimulation. No significant differences in brain activity or speech fluency were found when comparing active and sham stimulation. However, stuttering severity significantly modulated the effect of stimulation: active stimulation attenuated the atypically strong association between stuttering severity and right thalamocortical network activity, especially in more severe speakers. These preliminary results warrant additional research into potential application of HD-tDCS to modulate speech motor networks to enhance fluency in stuttering.

Reproducibility of axonal water fraction derived from the spherical mean diffusion weighted signal.

Recent years have seen growing interest in measuring axonal water fraction (AWF) using the spherical mean diffusion weighted signal, but information about the reproducibility of this method is needed before applying it in large-scale studies. The current study aims to evaluate the reproducibility of AWF derived from the spherical mean signal method. This retrospective study analyzed the Human Connectome Project (HCP) test-retest diffusion data of ten healthy adults. The diffusion scan was performed two times for each subject. Diffusion tensor imaging-based fractional anisotropy (FA) was calculated with b = 1000 s/mm2. AWF was calculated with b = 3000 s/mm2 using the spherical mean signal method. Gradient nonlinearities were corrected in both methods. Reproducibility was assessed using the reproducibility error, which is the percent absolute change relative to the mean. The mean reproducibility error of fractional anisotropy (FA) is 9.7 ±â€¯1.0% in white matter and 18.0 ±â€¯2.0% in gray matter. The mean reproducibility error of AWF is 4.6 ±â€¯0.6% in white matter and 7.0 ±â€¯1.5% in gray matter. Spherical mean signal-based AWF is more reproducible than FA for the HCP high resolution, low signal-to-noise ratio diffusion data.