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Sustained attention is a cognitive function with known links to academic success and mental health disorders such as attention/deficit-hyperactivity disorder (ADHD). Several functional networks are critical to sustained attention, however the association between white matter maturation in tracts linking functional nodes and sustained attention in typical and atypical development is unknown. 309 diffusion-weighted imaging scans were acquired from 161 children and adolescents (80 ADHD, 81 control) at up to three timepoints over ages 9-14. A fixel-based analysis approach was used to calculate mean fiber density and fiber-bundle cross section in tracts of interest. Sustained attention was measured using omission errors and response time variability on the out-of-scanner sustained attention to response task. Linear mixed effects models examined associations of age, group and white matter metrics with sustained attention. Greater fiber density in the bilateral superior longitudinal fasciculus (SLF) I and right SLF II was associated with fewer attention errors in the control group only. In ADHD and control groups, greater fiber density in the left ILF and right thalamo-premotor pathway, as well as greater fiber cross-section in the left SLF I and II and right SLF III, was associated with better sustained attention. Relationships were consistent across the age span. Results suggest that greater axon diameter or number in the dorsal and middle SLF may facilitate sustained attention in neurotypical children but does not assist those with ADHD potentially due to disorder-related alterations in this region. Greater capacity for information transfer across the SLF was associated with attention maintenance in 9-14-year-olds regardless of diagnostic status, suggesting white matter macrostructure may also be important for attention maintenance. White matter and sustained attention associations were consistent across the longitudinal study, according with the stability of structural organization over this time. Future studies can investigate modifiability of white matter properties through ADHD medications.

Previous Diffusion Tensor Imaging (DTI) studies in children suggest that developmental improvements in inhibitory control is largely mediated by the degree of white matter organisation within a right-lateralised network of fronto-basal-ganglia regions. Recent advances in diffusion imaging analysis now permit greater biological specificity, both in identifying specific fibre populations within a voxel, as well as in the underlying microstructural properties of that white matter. In the present work, employing a novel fixel-based analysis (FBA) framework, we aimed to comprehensively investigate microstructure within the fronto-basal-ganglia circuit in childhood, and its contribution to inhibition performance. Diffusion MRI data were obtained from 43 healthy children and adolescents aged 9–11 years (10.42 ± .41 years, 18 females). Response inhibition for each participant was assessed using the Stop-signal Task (SST) and quantified as a Stop–Signal Reaction Time (SSRT). All steps relevant to FBA were implemented in MRtrix3Tissue, a fork of the MRtrix3 software library. The fronto-basal-ganglia circuit were delineated using probabilistic tractography to identify the tracts connecting the subthalamic nucleus, pre-supplementary motor area and the inferior frontal gyrus. Connectivity-based fixel enhancement (CFE) was then used to assess the association between fibre density (FD) and fibre cross-section (FC) with inhibitory ability. Significant negative associations were identified for FD in both the right and left fronto-basal-ganglia circuit whereby greater FD was associated with better inhibition performance (e.g., reduced SSRTs). This effect was specifically localised to clusters of fixels within white matter proximal to the right subthalamic nucleus. We did not report any meaningful associations between SSRT and FC. Whilst findings are broadly consistent with prior DTI evidence, current results suggest that SSRT is predominantly facilitated by subcortical microstructure of the connections projecting from the subthalamic nucleus to the cortical regions of the network. Our findings extend current understanding of the role of white matter in childhood response inhibition.

Response inhibition refers to the cancelling of planned (or restraining of ongoing) actions and is required in much of our everyday life. Response inhibition appears to improve dramatically in early development and plateau in adolescence. The fronto-basal-ganglia network has long been shown to predict individual differences in the ability to enact response inhibition. In the current study, we examined whether developmental trajectories of fiber-specific white matter properties of the fronto-basal-ganglia network was predictive of parallel developmental trajectories of response inhibition. 138 children aged 9-14 completed the stop-signal task (SST). A subsample of 73 children underwent high-angular resolution diffusion MRI data for up to three time points. Performance on the SST was assessed using a parametric race modelling approach. White matter organization of the fronto-basal-ganglia circuit was estimated using fixel-based analysis. Contrary to predictions, we did not find any significant associations between maturational trajectories of fronto-basal-ganglia white matter and developmental improvements in SST performance. Findings suggest that the development of white matter organization of the fronto-basal-ganglia and development of stopping performance follow distinct maturational trajectories.

Recent work in healthy adults suggests that white matter organization within the superior longitudinal fasciculus (SLF) may, at least partly, explain individual differences in fine motor skills. The SLF is also often implicated in the neurobiology underlying attention deficit hyperactivity disorder (ADHD) as part of the attention network connecting frontal and parietal regions. While ADHD is primarily characterized by inattention, impulsivity and/or hyperactivity, atypical fine motor control is a common comorbid feature. This study aimed to investigate the association between reduced fine motor skills in ADHD and microstructural properties within the SLF. Participants were 55 right-handed children with ADHD and 61 controls aged 9–11 years. Fine motor control was assessed using the Grooved Pegboard task. Children underwent high angular resolution diffusion MRI. Following pre-processing, constrained spherical deconvolution tractography was performed to delineate the three SLF branches bilaterally. Children with ADHD showed significantly poorer fine motor performance relative to controls in the non-dominant hand, indicated by significantly slower left handed Grooved Pegboard task performance. This slower response time for the non-dominant (left) hand was significantly associated with reduced apparent fibre density within the right SLF I, and reduced right SLF I, II and III volume. This finding was independent of spatial attention performance. These data support previous reports indicating that children with ADHD have poorer fine motor performance than controls in their non-dominant hand, and indicates that the neurobiological basis for impaired fine motor control may involve white matter properties within the contralateral SLF. This suggests that white matter properties in fronto-parietal areas may have broader implications than attention.

While mentally simulated actions activate similar neural structures to overt movement, the role of the primary motor cortex (PMC) in motor imagery remains disputed. The aim of the study was to use continuous theta burst stimulation (cTBS) to modulate corticospinal activity to investigate the putative role of the PMC in implicit motor imagery in young adults with typical and atypical motor ability. A randomized, double blind, sham-controlled, crossover, offline cTBS protocol was applied to 35 young adults. During three separate sessions, adults with typical and low motor ability (developmental coordination disorder [DCD]), received active cTBS to the PMC and supplementary motor area (SMA), and sham stimulation to either the PMC or SMA. Following stimulation, participants completed measures of motor imagery (i.e., hand rotation task) and visual imagery (i.e., letter number rotation task). Although active cTBS significantly reduced corticospinal excitability in adults with typical motor ability, neither task performance was altered following active cTBS to the PMC or SMA, compared to performance after sham cTBS. These results did not differ across motor status (i.e., typical motor ability and DCD). These findings are not consistent with our hypothesis that the PMC (and SMA) is directly involved in motor imagery. Instead, previous motor cortical activation observed during motor imagery may be an epiphenomenon of other neurophysiological processes and/or activity within brain regions involved in motor imagery. This study highlights the need to consider multi-session theta burst stimulation application and its neural effects when probing the putative role of motor cortices in motor imagery.

Previous studies investigating white matter organization in attention deficit hyperactivity disorder (ADHD) have adopted diffusion tensor imaging (DTI). However, attempts to derive pathophysiological models from this research have had limited success, possibly reflecting limitations of the DTI method. This study investigated the organization of white matter tracts in ADHD using fixel based analysis (FBA), a fiber specific analysis framework that is well placed to provide novel insights into the pathophysiology of ADHD. High angular diffusion weighted imaging and clinical data were collected in a large paediatric cohort (N = 144; 76 with ADHD; age range 9–11 years). White matter tractography and FBA were performed across 14 white matter tracts. Permutation based inference testing (using FBA derived measures of fiber density and morphology) assessed differences in white matter tract profiles between children with and without ADHD. Analysis further examined the association between white matter properties and ADHD symptom severity. Relative to controls, children with ADHD showed reduced white matter connectivity along association and projection pathways considered critical to behavioral control and motor function. Increased ADHD symptom severity was associated with reduced white matter organization in fronto-pontine fibers projecting to and from the supplementary motor area. Providing novel insight into the neurobiological foundations of ADHD, this is the first research to uncover fiber specific white matter alterations across a comprehensive set of white matter tracts in ADHD using FBA. Findings inform pathophysiological models of ADHD and hold great promise for the consistent identification and systematic replication of brain differences in this disorder.

Atypical white matter (WM) microstructure is commonly implicated in the neuropathophysiology of autism spectrum disorder (ASD). Fixel based analysis (FBA), at the cutting-edge of diffusion-weighted imaging, can account for crossing WM fibers and can provide indices of both WM micro- and macrostructure. We applied FBA to investigate WM structure between 25 (12 males, 13 females) adults with ASD and 24 (12 males, 12 females) matched controls. As the role of biological sex on the neuropathophysiology of ASD is of increasing interest, this was also explored. There were no significant differences in WM micro- or macrostructure between adults with ASD and matched healthy controls. When data were stratified by sex, females with ASD had reduced fiber density and cross-section (FDC), a combined metric comprised of micro- and macrostructural measures, in the corpus callosum, a finding not detected between the male sub-groups. We conclude that micro- and macrostructural WM aberrations are present in ASD, and may be influenced by biological sex.

Recent neuroimaging studies have reported atypical neural activation in children with Developmental Coordination Disorder (DCD) during tasks assessing manual dexterity. However, small sample sizes and subtle differences in task parameters have led to inconsistent findings, rendering interpretation difficult. The aim of the present meta-analysis was to quantitatively summarize this body of evidence using activation likelihood estimation (ALE) analysis to identify reliable regions of differential neural activation in children with DCD, compared to age-matched controls. Seven studies that adopted fMRI to compare children with and without DCD during manual performance were identified following a literature search. All were included in the ALE analysis. Compared to controls, children with DCD showed reduced activation during a manual dexterity task in the middle frontal gyrus, superior frontal gyrus, cerebellum, supramarginal gyrus, and inferior parietal lobule. Children with DCD showed greater activation in parts of the thalamus. Findings provide much needed clarification into the possible neural contributors to atypical manual dexterity in DCD and highlight the need for neuroimaging studies to include manual performance outcomes.

Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organisation. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "fixel-based analysis" (FBA) framework that implements bespoke solutions to this end, and has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to fixel-based analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of current fixel-based analysis studies (until August 2020), categorised across a broad range of neuroscientific domains, listing key design choices and summarising their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the fixel-based analysis framework, and outline some directions and future opportunities.

This study examined whether the P1, N1, and P3 ERP components would be sensitive to sequence learning effects on the serial reaction time task. On this task, participants implicitly learn a visuospatial sequence. Participants in this study were 35 healthy adults. Reaction time (RT) data revealed that, at the group level, participants learned the sequence. Specifically, RT became faster following repeated exposure to the visuospatial sequence and then slowed down in a control condition. Analyses of ERP data revealed no evidence for sequence learning effects for the N1 or P3 component. However, sequence learning effects were observed for the P1 component. Mean P1 amplitude mirrored the RT data. The analyses showed that P1 amplitude significantly decreased as participants were exposed to the sequence but then significantly increased in the control condition. This suggests that visuospatial sequence learning can modulate visual attention levels. Specifically, it seems that, as sequence knowledge is acquired, fewer demands are placed on visual attention resources.

Purpose Despite the important role of manual dexterity in child development, the neurobiological mechanisms associated with manual dexterity in childhood remain unclear. We leveraged fixel-based analysis (FBA) to examine the longitudinal association between manual dexterity and the development of white matter structural properties in the corticospinal tract (CST). Methods High angular diffusion weighted imaging (HARDI) data were acquired for 44 right-handed typically developing children (22 female) aged 9-13 across two timepoints (timepoint 1: mean age 10.5 years ± 0.5 years, timepoint 2: 11.8 ± 0.5 years). Manual dexterity was assessed using the Grooved Pegboard Test, a widely used measure of manual dexterity. FBA-derived measures of fiber density and morphology were generated for the CST at each timepoint. Connectivity-based fixel enhancement and mixed linear modelling were used to examine the longitudinal association between manual dexterity and white matter structural properties of the CST. Results Longitudinal mixed effects models showed that greater manual dexterity of the dominant hand was associated with increased fiber cross-section in the contralateral CST. Analyses further demonstrated that the rate of improvement in manual dexterity was associated with the rate of increase in fiber cross-section in the contralateral CST between the two timepoints. Conclusion Our longitudinal data suggest that the development of manual dexterity in late childhood is associated with maturation of the CST. These findings significantly enhance our understanding of the neurobiological systems that subserve fine motor development and provide an important step toward mapping normative trajectories of fine motor function against microstructural and morphological development in childhood.

This is the first review to quantitatively summarise evidence evaluating MI functioning in children with DCD compared to controls based on the hand rotation task (HRT). Specifically, MI performance was assessed using three different behavioural performance measures on the HRT (i.e., reaction time, accuracy and efficiency). Eight studies were included for quantitative analysis, yielding data for 176 and 198 children with and without DCD respectively. While children with DCD consistently used MI across all measures of the task, they continually demonstrated reductions in HRT performance relative to controls. Additionally, group differences appeared to be strongest and more commonly detected when using the IES (mean inverse efficiency-IES) metric on the HRT. These effects did not differ statistically as a function of instruction type. In support of the internal modelling deficit hypothesis, group effects suggested children with DCD demonstrate broad reductions in HRT performance relative to controls. However, consideration of effect size and study level analysis showed the ability for an individual study to detect these effects differs considerably depending on the outcome metric adopted.

This study aimed to evaluate the ‘inhibitory deficit’ hypothesis of developmental coordination disorder (DCD). We adopted a multifaceted approach, investigating two distinct, yet complimentary facets of motor inhibition: action restraint and action cancellation. This was achieved using carefully constructed versions of the ‘Go/No-go’ and ‘Stop-signal’ tasks, respectively. The sample comprised 11 young adults with DCD aged between 18 and 30 years of age and 11 typically developing, age-matched controls. Participants completed both the ‘Go/No-go’ and ‘Stop-signal’ tasks to assess action restraint and action cancellation respectively. Individuals with DCD were less efficient than their typically developing peers at performing both action restraint and action cancellation, indicated by significantly reduced action restraint efficiency index scores on the ‘Go/No-go’ task and a trend towards longer stop-signal reaction times on the ‘Stop-signal’ task. This work clarifies disparate evidence speaking to the integrity of action restraint in DCD and provides the first account of action cancellation in DCD using a purpose-built measure. In support of the inhibitory deficit hypothesis of DCD, our results suggest that young adults with DCD experience broad difficulties with engaging inhibitory mechanisms during motor behaviour.

Neurocomputational models of reaching indicate that efficient purposive correction of movement midflight (e.g., online control) depends on one's ability to generate and monitor an accurate internal (neural) movement representation. In the first study to test this empirically, the authors investigated the relationship between healthy young adults' implicit motor imagery performance and their capacity to correct their reaching trajectory. As expected, after controlling for general reaching speed, hierarchical regression demonstrated that imagery ability was a significant predictor of hand correction speed; that is, faster and more accurate imagery performance associated with faster corrections to reaching following target displacement at movement onset. They argue that these findings provide preliminary support for the view that a link exists between an individual's ability to represent movement mentally and correct movement online efficiently.

Event Abstract: ACNS-2012 Australasian Cognitive Neuroscience Conference, Brisbane, Australia, 29 Nov - 2 Dec, 2012

Event Abstract: ACNS-2012 Australasian Cognitive Neuroscience Conference, Brisbane, Australia, 29 Nov - 2 Dec, 2012