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.

Contemporary clinical conversations about stuttering: What does brain imaging research mean to clinicians?

PURPOSE: To discuss among neuroscientists and community speech-language pathologists what brain imaging research means to clinicians. METHOD: Two university neuroscientists and two speech-language pathologists in private practice discussed the matter. Written conversational turns in an exchange were limited to 100 words each. When that written dialogue was concluded, each participant provided 200 words of final reflection about the matter. RESULT: For now, neuroscience treatments are not available for clinicians to use. But sometime in the future, a critical mass of neuroscientists will likely produce such treatments. The neuroscientists expressed diverse views about the methods that might be used for that to occur. CONCLUSION: Neuroscience does have practical clinical application at present and, in a way, that does not exclude a concurrent influence of the social model of disability. As such, the current practices of clinicians are supported by basic neuroscience research.

Knowns and unknowns about the neurobiology of stuttering.

Stuttering occurs in early childhood during a dynamic phase of brain and behavioral development. The latest studies examining children at ages close to this critical developmental period have identified early brain alterations that are most likely linked to stuttering, while spontaneous recovery appears related to increased inter-area connectivity. By contrast, therapy-driven improvement in adults is associated with a functional reorganization within and beyond the speech network. The etiology of stuttering, however, remains enigmatic. This Unsolved Mystery highlights critical questions and points to neuroimaging findings that could inspire future research to uncover how genetics, interacting neural hierarchies, social context, and reward circuitry contribute to the many facets of stuttering.

Brain response to errors in children who stutter.

PURPOSE: Heightened rates of social anxiety have been reported in adults who stutter (AWS), but it is unclear whether anxiety is heightened also in children who stutter (CWS). Objective neurophysiological responses such as the error-related negativity (ERN) have been associated with anxiety, and ERN was reported to be increased in AWS. In this study, we examined whether ERN and error positivity (Pe) are increased in CWS. We further characterized ERN associations with age and anxiety in CWS relative to children who do not stutter (CWNS). METHODS: EEG data were recorded from twenty-four CWS and twenty-four matched CWNS aged 3-9 years as they performed a Go/No-Go task. Parent-reported anxiety, and child-reported speech-associated attitude measures were collected. Linear regression models tested the effects of age, group, and their interaction, and the effects of anxiety, group, and their interaction on ERN and Pe. RESULTS: Contrary to expectations, no ERN or Pe difference were observed between CWS and CWNS. However, larger ERN amplitudes were associated with older age in CWS but not CWNS, suggesting altered development of the error monitoring system in CWS. Association of Pe with anxiety also differed between groups: smaller Pe amplitudes were associated with higher level of parent-reported child anxiety in CWNS but not in CWS. Neither anxiety nor self-reported communication attitude differed between groups. CONCLUSIONS: Brain responses to errors were overall comparable between CWS and CWNS. However, CWS differed in how error monitoring responses varied with age and with anxiety levels. More research is warranted to examine how these factors contribute to persistent stuttering.

Neural oscillatory activity and connectivity in children who stutter during a non-speech motor task.

BACKGROUND: Neural motor control rests on the dynamic interaction of cortical and subcortical regions, which is reflected in the modulation of oscillatory activity and connectivity in multiple frequency bands. Motor control is thought to be compromised in developmental stuttering, particularly involving circuits in the left hemisphere that support speech, movement initiation, and timing control. However, to date, evidence comes from adult studies, with a limited understanding of motor processes in childhood, closer to the onset of stuttering. METHODS: We investigated the neural control of movement initiation in children who stutter and children who do not stutter by evaluating transient changes in EEG oscillatory activity (power, phase locking to button press) and connectivity (phase synchronization) during a simple button press motor task. We compared temporal changes in these oscillatory dynamics between the left and right hemispheres and between children who stutter and children who do not stutter, using mixed-model analysis of variance. RESULTS: We found reduced modulation of left hemisphere oscillatory power, phase locking to button press and phase connectivity in children who stutter compared to children who do not stutter, consistent with previous findings of dysfunction within the left sensorimotor circuits. Interhemispheric connectivity was weaker at lower frequencies (delta, theta) and stronger in the beta band in children who stutter than in children who do not stutter. CONCLUSIONS: Taken together, these findings indicate weaker engagement of the contralateral left motor network in children who stutter even during low-demand non-speech tasks, and suggest that the right hemisphere might be recruited to support sensorimotor processing in childhood stuttering. Differences in oscillatory dynamics occurred despite comparable task performance between groups, indicating that an altered balance of cortical activity might be a core aspect of stuttering, observable during normal motor behavior.

A comparison of structural morphometry in children and adults with persistent developmental stuttering.

This cross-sectional study aimed to differentiate earlier occurring neuroanatomical differences that may reflect core deficits in stuttering versus changes associated with a longer duration of stuttering by analysing structural morphometry in a large sample of children and adults who stutter and age-matched controls. Whole-brain T1-weighted structural scans were obtained from 166 individuals who stutter (74 children, 92 adults; ages 3-58) and 191 controls (92 children, 99 adults; ages 3-53) from eight prior studies in our laboratories. Mean size and gyrification measures were extracted using FreeSurfer software for each cortical region of interest. FreeSurfer software was also used to generate subcortical volumes for regions in the automatic subcortical segmentation. For cortical analyses, separate ANOVA analyses of size (surface area, cortical thickness) and gyrification (local gyrification index) measures were conducted to test for a main effect of diagnosis (stuttering, control) and the interaction of diagnosis-group with age-group (children, adults) across cortical regions. Cortical analyses were first conducted across a set of regions that comprise the speech network and then in a second whole-brain analysis. Next, separate ANOVA analyses of volume were conducted across subcortical regions in each hemisphere. False discovery rate corrections were applied for all analyses. Additionally, we tested for correlations between structural morphometry and stuttering severity. Analyses revealed thinner cortex in children who stutter compared with controls in several key speech-planning regions, with significant correlations between cortical thickness and stuttering severity. These differences in cortical size were not present in adults who stutter, who instead showed reduced gyrification in the right inferior frontal gyrus. Findings suggest that early cortical anomalies in key speech planning regions may be associated with stuttering onset. Persistent stuttering into adulthood may result from network-level dysfunction instead of focal differences in cortical morphometry. Adults who stutter may also have a more heterogeneous neural presentation than children who stutter due to their unique lived experiences.

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.

Combined Cognitive Training and Transcranial Direct Current Stimulation in Neuropsychiatric Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Treatments for cognitive dysfunction in neuropsychiatric conditions are urgently needed. Cognitive training and transcranial direct current stimulation (tDCS) hold promise, and there is growing interest in combined or multimodal treatments, though studies to date have had small samples and inconsistent results. METHODS: A systematic review and meta-analysis was completed. Retained studies included cognitive training combined with active or sham tDCS in a neuropsychiatric population and reported a posttreatment cognitive outcome. Meta-analyses included effect sizes comparing cognitive training plus active tDCS and cognitive training plus sham tDCS in 5 cognitive domains. Risk of bias in included studies and across studies was explored. RESULTS: Fifteen studies were included: 10 in neurodegenerative disorders and 5 in psychiatric disorders (n = 629). There were several tDCS montages, though two-thirds of studies placed the anode over the left dorsolateral prefrontal cortex. A wide variety of cognitive training types and outcome measures were reported. There was a small, statistically significant effect of combined treatment on measures of attention/working memory, as well as small and non-statistically significant effects favoring combined treatment on global cognition and language. There was no evidence of bias in individual studies but some evidence of nonreporting or small-study bias across studies. CONCLUSIONS: These results may provide preliminary support for the efficacy of combined cognitive training and tDCS on measures of attention/working memory. More data are needed, particularly via studies that explicitly align the cognitive ability of interest, stimulation target, training type, and outcome measures.

Dissecting structural connectivity of the left and right inferior frontal cortex in children who stutter.

Inferior frontal cortex pars opercularis (IFCop) features a distinct cerebral dominance and vast functional heterogeneity. Left and right IFCop are implicated in developmental stuttering. Weak left IFCop connections and divergent connectivity of hyperactive right IFCop regions have been related to impeded speech. Here, we reanalyzed diffusion magnetic resonance imaging data from 83 children (41 stuttering). We generated connection probability maps of functionally segregated area 44 parcels and calculated hemisphere-wise analyses of variance. Children who stutter showed reduced connectivity of executive, rostral-motor, and caudal-motor corticostriatal projections from the left IFCop. We discuss this finding in the context of tracing studies from the macaque area 44, which leads to the need to reconsider current models of speech motor control. Unlike the left, the right IFCop revealed increased connectivity of the inferior posterior ventral parcel and decreased connectivity of the posterior dorsal parcel with the anterior insula, particularly in stuttering boys. This divergent connectivity pattern in young children adds to the debate on potential core deficits in stuttering and challenges the theory that right hemisphere differences might exclusively indicate compensatory changes that evolve from lifelong exposure. Instead, early right prefrontal connectivity differences may reflect additional brain signatures of aberrant cognition-emotion-action influencing speech motor control.

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.

Charting brain growth and aging at high spatial precision.

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.

Tract profiles of the cerebellar peduncles in children who stutter.

Cerebellar-cortical loops comprise critical neural circuitry that supports self-initiated movements and motor adjustments in response to perceived errors, functions that are affected in stuttering. It is unknown whether structural aspects of cerebellar circuitry are affected in stuttering, particularly in children close to symptom onset. Here we examined white matter diffusivity characteristics of the three cerebellar peduncles (CPs) based on diffusion MRI (dMRI) data collected from 41 children who stutter (CWS) and 42 controls in the 3-11 years range. We hypothesized that CWS would exhibit decreased fractional anisotropy (FA) in the right CPs given the contralateral connectivity of the cerebellar-cortical loops and past reports of structural differences in left cortical areas in stuttering speakers. Automatic Fiber Quantification (AFQ) was used to track and segment cerebellar white matter pathways and to extract diffusivity measures. We found significant group differences for FA in the right inferior CP (ICP) only: controls showed significantly higher FA in the right ventral ICP compared to CWS, controlling for age, sex, and verbal IQ. Furthermore, FA of right ICP was negatively correlated with stuttering frequency in CWS. These results suggest an early developmental difference in the right ICP for CWS compared to age-matched peers, which may indicate an alteration in error processing, a function previously linked to the ICP. Lower FA here may impact error monitoring and sensory input processing to guide motor corrections. Further longitudinal investigations in children may provide additional insights into how CP development links to stuttering persistence and recovery.

Predicting Persistent Developmental Stuttering Using a Cumulative Risk Approach.

PURPOSE: The purpose of this study was to explore how well a cumulative risk approach, based on empirically supported predictive factors, predicts whether a young child who stutters is likely to develop persistent developmental stuttering. In a cumulative risk approach, the number of predictive factors indicating a child is at risk to develop persistent stuttering is evaluated, and a greater number of indicators of risk are hypothesized to confer greater risk of persistent stuttering. METHOD: We combined extant data on 3- to 5-year-old children who stutter from two longitudinal studies to identify cutoff values for continuous predictive factors (e.g., speech and language skills, age at onset, time since onset, stuttering frequency) and, in combination with binary predictors (e.g., sex, family history of stuttering), used all-subsets regression and receiver operating characteristic curves to compare the predictive validity of different combinations of 10 risk factors. The optimal combination of predictive factors and the odds of a child developing persistent stuttering based on an increasing number of factors were calculated. RESULTS: Based on 67 children who stutter (i.e., 44 persisting and 23 recovered) with relatively strong speech-language skills, the predictive factor model that yielded the best predictive validity was based on time since onset (≥ 19 months), speech sound skills (≤ 115 standard score), expressive language skills (≤ 106 standard score), and stuttering severity (≥ 17 Stuttering Severity Instrument total score). When the presence of at least two predictive factors was used to confer elevated risk to develop persistent stuttering, the model yielded 93% sensitivity and 65% specificity. As a child presented with a greater number of these four risk factors, the odds for persistent stuttering increased. CONCLUSIONS: Findings support the use of a cumulative risk approach and the predictive utility of assessing multiple domains when evaluating a child's risk of developing persistent stuttering. Clinical implications and future directions are discussed.

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.

Lexical diversity and lexical skills in children who stutter.

PURPOSE: Numerous "small N" studies of language ability in children who stutter have produced differing conclusions. We combined test and spontaneous language data from a large cohort of children who stutter (CWS) and typically fluent peers, gathered from independent laboratories across the US, to appraise a variety of lexical measures. METHOD: Standardized receptive and expressive vocabulary test data and spontaneous language samples from 99 pairs of CWS (ages 25-100 months), and age-, gender-, and SES-matched children who do not stutter (CWNS) were compared. Language sample transcripts were analyzed with four measures of lexical diversity. Correlations between lexical diversity measures and expressive vocabulary scores were also calculated. RESULTS: On standardized tests of both receptive and expressive vocabulary, there were significant differences between CWS and CWNS. In contrast, on spontaneous language measures of lexical diversity, CWS did not differ in their lexical diversity, across analyses, compared to CWNS. Three of the four lexical diversity analyses, MATTR, VocD, and NDW, were significantly correlated with each other. CONCLUSIONS: We were able to confirm prior findings of relative disadvantage on standardized vocabulary tests for a very large sample of well-matched CWS. However, spontaneous language measures of lexical diversity did not distinguish the groups. This relative weakness in CWS may emerge from task differences: CWS are free to encode their own spontaneous utterances but must comply with explicit lexical prompts in standardized testing situations.

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.

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.