Increased segregation of functional networks in developing brains.

A growing literature conceptualises typical brain development from a network perspective. However, largely due to technical and methodological challenges inherent in paediatric functional neuroimaging, there remains an important gap in our knowledge regarding the typical development of functional brain networks in "preschool" childhood (i.e., children younger than 6 years of age). In this study, we recorded brain oscillatory activity using age-appropriate magnetoencephalography in 24 children, including 14 preschool children aged from 4 to 6 years and 10 school children aged from 7 to 12 years. We compared the topology of the resting-state brain networks in these children, estimated using minimum spanning tree (MST) constructed from phase synchrony between beamformer-reconstructed time-series, with that of 24 adults. Our results show that during childhood the MST topology shifts from a star-like (centralised) toward a more line-like (de-centralised) configuration, indicating the functional brain networks become increasingly segregated. In addition, the increasing global network segregation is frequency-independent and accompanied by decreases in centrality (or connectedness) of cortical regions with age, especially in areas of the default mode network. We propose a heuristic MST model of "network space", which posits a clear developmental trajectory for the emergence of complex brain networks. Our results not only revealed topological reorganisation of functional networks across multiple temporal and spatial scales in childhood, but also fill a gap in the literature regarding neurophysiological mechanisms of functional brain maturation during the preschool years of childhood.

Abnormal time course of low beta modulation in non-fluent preschool children: A magnetoencephalographic study of rhythm tracking.

Stuttering is a disorder of speech affecting millions of people around the world. Whilst the exact aetiology of stuttering remains unknown, it has been hypothesised that it is a disorder of the neural mechanisms that support speech timing. In this article, we used magnetoencephalography (MEG) to examine activity from auditory regions of the brain in stuttering and non-stuttering children aged 3-9years. For typically developing children, we found that MEG oscillations in the beta band responded to rhythmic sounds with a peak near the time of stimulus onset. In contrast, stuttering children showed an opposite phase of beta band envelope, with a trough of activity at stimulus onset. These results suggest that stuttering may result from abnormalities in predictive brain responses which are reflected in abnormal entrainment of the beta band envelope to rhythmic sounds.

A conceptual lemon: theta burst stimulation to the left anterior temporal lobe untangles object representation and its canonical color.

Object recognition benefits greatly from our knowledge of typical color (e.g., a lemon is usually yellow). Most research on object color knowledge focuses on whether both knowledge and perception of object color recruit the well-established neural substrates of color vision (the V4 complex). Compared with the intensive investigation of the V4 complex, we know little about where and how neural mechanisms beyond V4 contribute to color knowledge. The anterior temporal lobe (ATL) is thought to act as a "hub" that supports semantic memory by integrating different modality-specific contents into a meaningful entity at a supramodal conceptual level, making it a good candidate zone for mediating the mappings between object attributes. Here, we explore whether the ATL is critical for integrating typical color with other object attributes (object shape and name), akin to its role in combining nonperceptual semantic representations. In separate experimental sessions, we applied TMS to disrupt neural processing in the left ATL and a control site (the occipital pole). Participants performed an object naming task that probes color knowledge and elicits a reliable color congruency effect as well as a control quantity naming task that also elicits a cognitive congruency effect but involves no conceptual integration. Critically, ATL stimulation eliminated the otherwise robust color congruency effect but had no impact on the numerical congruency effect, indicating a selective disruption of object color knowledge. Neither color nor numerical congruency effects were affected by stimulation at the control occipital site, ruling out nonspecific effects of cortical stimulation. Our findings suggest that the ATL is involved in the representation of object concepts that include their canonical colors.

Cortical oscillatory dysrhythmias in visual snow syndrome: a magnetoencephalography study.

Visual snow refers to the persistent visual experience of static in the whole visual field of both eyes. It is often reported by patients with migraine and co-occurs with conditions such as tinnitus and tremor. The underlying pathophysiology of the condition is poorly understood. Previously, we hypothesized that visual snow syndrome may be characterized by disruptions to rhythmical activity within the visual system. To test this, data from 18 patients diagnosed with visual snow syndrome, and 16 matched controls, were acquired using magnetoencephalography. Participants were presented with visual grating stimuli, known to elicit decreases in alpha-band (8-13 Hz) power and increases in gamma-band power (40-70 Hz). Data were mapped to source-space using a beamformer. Across both groups, decreased alpha power and increased gamma power localized to early visual cortex. Data from the primary visual cortex were compared between groups. No differences were found in either alpha or gamma peak frequency or the magnitude of alpha power, p > 0.05. However, compared with controls, our visual snow syndrome cohort displayed significantly increased primary visual cortex gamma power, p = 0.035. This new electromagnetic finding concurs with previous functional MRI and PET findings, suggesting that in visual snow syndrome, the visual cortex is hyperexcitable. The coupling of alpha-phase to gamma amplitude within the primary visual cortex was also quantified. Compared with controls, the visual snow syndrome group had significantly reduced alpha-gamma phase-amplitude coupling, p < 0.05, indicating a potential excitation-inhibition imbalance in visual snow syndrome, as well as a potential disruption to top-down 'noise-cancellation' mechanisms. Overall, these results suggest that rhythmical brain activity in the primary visual cortex is both hyperexcitable and disorganized in visual snow syndrome, consistent with this being a condition of thalamocortical dysrhythmia.

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.

Functional and Neuroanatomical Bases of Developmental Stuttering: Current Insights.

Affecting 5% of all preschool-aged children and 1% of the general population, developmental stuttering-also called childhood-onset fluency disorder-is a complex, multifactorial neurodevelopmental disorder characterized by frequent disruption of the fluent flow of speech. Over the past two decades, neuroimaging studies of both children and adults who stutter have begun to provide significant insights into the neurobiological bases of stuttering. This review highlights convergent findings from this body of literature with a focus on functional and structural neuroimaging results that are supported by theoretically driven neurocomputational models of speech production. Updated views on possible mechanisms of stuttering onset and persistence, and perspectives on promising areas for future research into the mechanisms of stuttering, are discussed.

A systematic literature review of neuroimaging research on developmental stuttering between 1995 and 2016.

PURPOSE: Stuttering is a disorder that affects millions of people all over the world. Over the past two decades, there has been a great deal of interest in investigating the neural basis of the disorder. This systematic literature review is intended to provide a comprehensive summary of the neuroimaging literature on developmental stuttering. It is a resource for researchers to quickly and easily identify relevant studies for their areas of interest and enable them to determine the most appropriate methodology to utilize in their work. The review also highlights gaps in the literature in terms of methodology and areas of research. METHODS: We conducted a systematic literature review on neuroimaging studies on developmental stuttering according to the PRISMA guidelines. We searched for articles in the pubmed database containing "stuttering" OR "stammering" AND either "MRI", "PET", "EEG", "MEG", "TMS"or "brain" that were published between 1995/​01/​01 and 2016/​01/​01. RESULTS: The search returned a total of 359 items with an additional 26 identified from a manual search. Of these, there were a total of 111 full text articles that met criteria for inclusion in the systematic literature review. We also discuss neuroimaging studies on developmental stuttering published throughout 2016. The discussion of the results is organized first by methodology and second by population (i.e., adults or children) and includes tables that contain all items returned by the search. CONCLUSIONS: There are widespread abnormalities in the structural architecture and functional organization of the brains of adults and children who stutter. These are evident not only in speech tasks, but also non-speech tasks. Future research should make greater use of functional neuroimaging and noninvasive brain stimulation, and employ structural methodologies that have greater sensitivity. Newly planned studies should also investigate sex differences, focus on augmenting treatment, examine moments of dysfluency and longitudinally or cross-sectionally investigate developmental trajectories in stuttering.

A systematic literature review of sex differences in childhood language and brain development.

The extent of sex differences in childhood language development is unclear. We conducted a systematic literature review synthesizing results from studies examining sex differences in brain structure and function relevant to language development during childhood. We searched PubMed and Scopus databases, and this returned a total of 46 published studies meeting criteria for inclusion that directly examined sex differences in brain development relevant to language function in children. The results indicate that: (a) sex differences in brain structure or function do not necessarily lead to differences in language task performance; (b) evidence for sex differences in brain and language development are limited; (c) when present, sex differences often interact with a variety of factors such as age and task. Overall, the magnitude of sexual dimorphism of brain developmental trajectories associated with language is not as significant as previously thought. Sex differences were found, however, in studies employing tighter age ranges. This suggests that sex differences may be more prominent during certain developmental stages but are negligible in other stages, likely due to different rates of maturation between the sexes. More research is needed to improve our understanding of how sex differences may arise due to the influence of sex hormones and developmental stages, and how these differences may lead to differences in various language task performance. These studies are expected to provide normative information that may be used in studies examining neurodevelopmental disorders that frequently affect more males than females, and also often affect language development.

Anomalous network architecture of the resting brain in children who stutter.

PURPOSE: We combined a large longitudinal neuroimaging dataset that includes children who do and do not stutter and a whole-brain network analysis in order to examine the intra- and inter-network connectivity changes associated with stuttering. Additionally, we asked whether whole brain connectivity patterns observed at the initial year of scanning could predict persistent stuttering in later years. METHODS: A total of 224 high-quality resting state fMRI scans collected from 84 children (42 stuttering, 42 controls) were entered into an independent component analysis (ICA), yielding a number of distinct network connectivity maps ("components") as well as expression scores for each component that quantified the degree to which it is expressed for each child. These expression scores were compared between stuttering and control groups' first scans. In a second analysis, we examined whether the components that were most predictive of stuttering status also predicted persistence in stuttering. RESULTS: Stuttering status, as well as stuttering persistence, were associated with aberrant network connectivity involving the default mode network and its connectivity with attention, somatomotor, and frontoparietal networks. The results suggest developmental alterations in the balance of integration and segregation of large-scale neural networks that support proficient task performance including fluent speech motor control. CONCLUSIONS: This study supports the view that stuttering is a complex neurodevelopmental disorder and provides comprehensive brain network maps that substantiate past theories emphasizing the importance of considering situational, emotional, attentional and linguistic factors in explaining the basis for stuttering onset, persistence, and recovery.

Behavioral and multimodal neuroimaging evidence for a deficit in brain timing networks in stuttering: a hypothesis and theory.

The fluent production of speech requires accurately timed movements. In this article, we propose that a deficit in brain timing networks is one of the core neurophysiological deficits in stuttering. We first discuss the experimental evidence supporting the involvement of the basal ganglia and supplementary motor area (SMA) in stuttering and the involvement of the cerebellum as a possible mechanism for compensating for the neural deficits that underlie stuttering. Next, we outline the involvement of the right inferior frontal gyrus (IFG) as another putative compensatory locus in stuttering and suggest a role for this structure in an expanded core timing-network. Subsequently, we review behavioral studies of timing in people who stutter and examine their behavioral performance as compared to people who do not stutter. Finally, we highlight challenges to existing research and provide avenues for future research with specific hypotheses.

"Shut up!" An electrophysiological study investigating the neural correlates of vocal inhibition.

A neural biomarker that can be applied to studies of oral communication disorders would provide a boon to researchers. While there has been much research conducted on manual response inhibition, very few studies have examined vocal response inhibition. To date, no study has examined the temporal aspects of vocal inhibition. Therefore, the present study attempted to identify the neural correlates of vocal response inhibition by recording electroencephalographic activity during a modified version of the stop signal task. We included an ignore signal condition matched for frequency and visual stimulation to the stop signal which importantly, was included in the same block of trials as the typical go and stop trials. Behavioural results showed that participants were able to inhibit a vocal response within approximately 324 ms. Statistical analysis of ERPs revealed that a positive component around 324 ms was significantly larger in amplitude during successfully stopped trials compared to in an ignore condition, particularly over a cluster of fronto-central electrodes. These results support the notion that the P3 component is a reliable index of vocal inhibition.