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BACKGROUND: Emerging evidence suggests that traumatic brain injury (TBI) is a major risk factor for developing neurodegenerative disease later in life. Quantitative susceptibility mapping (QSM) has been used by an increasing number of studies in investigations of pathophysiological changes in TBI. However, generating artefact-free quantitative susceptibility maps in brains with large focal lesions, as in the case of moderate-to-severe TBI (ms-TBI), is particularly challenging. To address this issue, we utilized a novel two-pass masking technique and reconstruction procedure (two-pass QSM) to generate quantitative susceptibility maps (QSMxT; Stewart et al., 2022, Magn Reson Med.) in combination with the recently developed virtual brain grafting (VBG) procedure for brain repair (Radwan et al., 2021, NeuroImage) to improve automated delineation of brain areas. We used QSMxT and VBG to generate personalised QSM profiles of individual patients with reference to a sample of healthy controls. METHODS: Chronic ms-TBI patients (N = 8) and healthy controls (N = 12) underwent (multi-echo) GRE, and anatomical MRI (MPRAGE) on a 3T Siemens PRISMA scanner. We reconstructed the magnetic susceptibility maps using two-pass QSM from QSMxT. We then extracted values of magnetic susceptibility in grey matter (GM) regions (following brain repair via VBG) across the whole brain and determined if they deviate from a reference healthy control group [Z-score < -3.43 or > 3.43, relative to the control mean], with the aim of obtaining personalised QSM profiles. RESULTS: Using two-pass QSM, we achieved susceptibility maps with a substantial increase in quality and reduction in artefacts irrespective of the presence of large focal lesions, compared to single-pass QSM. In addition, VBG minimised the loss of GM regions and exclusion of patients due to failures in the region delineation step. Our findings revealed deviations in magnetic susceptibility measures from the HC group that differed across

Importance: Traumatic brain injury (TBI) is known to cause widespread neural disruption in the cerebrum. However, less is known about the association of TBI with cerebellar structure and how such changes may alter executive functioning. Objective: To investigate alterations in subregional cerebellum volume and cerebral white matter microstructure after pediatric TBI and examine subsequent changes in executive function. Design, Setting, and Participants This retrospective cohort study combined 12 data sets (collected between 2006 and 2020) from 9 sites in the Enhancing Neuroimaging Genetics Through Meta-Analysis Consortium Pediatric TBI working group in a mega-analysis of cerebellar structure. Participants with TBI or healthy controls (some with orthopedic injury) were recruited from trauma centers, clinics, and institutional trauma registries, some of which were followed longitudinally over a period of 0.7 to 1.9 years. Healthy controls were recruited from the surrounding community. Data analysis occurred from October to December 2022. Exposure Accidental mild complicated-severe TBI (msTBI) for those in the TBI group. Some controls received a diagnosis of orthopedic injury. Main Outcomes and Measures Volume of 18 cerebellar lobules and vermal regions were estimated from 3-dimensional T1-weighted magnetic resonance imaging (MRI) scans. White matter organization in 28 regions of interest was assessed with diffusion tensor MRI. Executive function was measured by parent-reported scores from the Behavior Rating Inventory of Executive Functioning. Results: A total of 598 children and adolescents (mean [SD] age, 14.05 [3.06] years; range, 5.45-19.70 years; 386 male participants [64.5%]; 212 female participants [35.5%]) were included in the study, with 314 participants in the msTBI group, and 284 participants in the non-TBI group (133 healthy individuals and 151 orthopedically injured individuals). Significantly smaller total cerebellum volume (d = −0.37; 95% CI, −0.52 to −

Graph theoretical analysis of the structural connectome has been employed successfully to characterize brain network alterations in patients with traumatic brain injury (TBI). However, heterogeneity in neuropathology is a well-known issue in the TBI population, such that group comparisons of patients against controls are confounded by within-group variability. Recently, novel single-subject profiling approaches have been developed to capture inter-patient heterogeneity. We present a personalized connectomics approach that examines structural brain alterations in five chronic patients with moderate to severe TBI who underwent anatomical and diffusion magnetic resonance imaging. We generated individualized profiles of lesion characteristics and network measures (including personalized graph metric GraphMe plots, and nodal and edge-based brain network alterations) and compared them against healthy reference cases (N = 12) to assess brain damage qualitatively and quantitatively at the individual level. Our findings revealed alterations of brain networks with high variability between patients. With validation and comparison to stratified, normative healthy control comparison cohorts, this approach could be used by clinicians to formulate a neuroscience-guided integrative rehabilitation program for TBI patients, and for designing personalized rehabilitation protocols based on their unique lesion load and connectome.

Assault is the leading preventable cause of death, traumatic brain injury (TBI), and associated mental health problems. The COVID-19 pandemic has had a profound impact on patterns of interpersonal violence across the world. In this retrospective cross-sectional study, we analysed medical records of 1232 assault victims (domestic violence: 111, random assault: 900, prison assault: 221) with head injuries who presented to the emergency department (ED) at St Vincent's Hospital in Melbourne, Australia, a city with one of the longest and most severe COVID-19 restrictions worldwide. We examined changes in prevalence in the assault group overall and in domestic violence, random assault, and prison assault victims, comparing data from 19.5 months before and after the first day of COVID-19 restrictions in Melbourne. Moreover, we investigated differences driven by demographic factors (Who: age group, sex, and nationality) and clinical variables (Where: assault location, and When: time of arrival to the ED and time from moment of injury until presentation at ED). Descriptive statistics and chi-square analyses were performed. We found the COVID-19 pandemic significantly affected the Where of assault-related TBI, with a shift in the location of assaults from the street to the home, and the increase at home being driven by random assaults on middle-aged adults. Overall, we observed that 86% of the random assault cases were males, whereas 74% of the domestic assault cases were females. Meanwhile, nearly half (44%) of the random assault victims reported alcohol consumption versus a fifth (20%) of domestic violence victims. These findings will have direct implications for developing screening tools and better preventive and ameliorative interventions to manage the sequelae of assault TBI, particularly in the context of future large-scale health crises or emergencies.

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.

Item does not contain fulltext, Upper-limb virtual rehabilitation (VR) in adult acquired brain injury (ABI) is based largely on systems administered on a one-to-one basis. Multi-user interaction between co-located participants may offer advantages over single-user methods. The present study examined the feasibility of deploying a co-located VR system (Resonance) in a clinical setting. Following a baselining period, 5 patients with ABI completed 12 Resonance sessions over 4-6 weeks. Feasibility criteria included recruitment, intervention delivery, attrition, user experience, and suitability of outcome measures. Individual participant motor proficiency (box and blocks task) was examined using a time-series analysis with reliable change indices and curve fitting. All feasibility criteria were satisfied, with positive reports of user experience. Repeated collection of outcome measures was successfully integrated into the training schedule. Time-series analysis was successfully conducted, providing a detailed account of individual training-related change. Within a clinical setting, it was feasible to deliver Resonance and regularly monitor motor function. User feedback regarding the co-located VR intervention was generally positive, but expectations regarding the level of immersion may need to be managed. Individual time-series analysis is recommended as an adjunct to group-based analysis in future VR research. These findings can inform the design of a clinical trial.

Introduction There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. Methods and analysis This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. Ethics and dissemination The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).

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 organization. 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, which implements bespoke solutions to this end. It 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 all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities.Copyright © 2021

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. Young TBI patients suffer from gross motor deficits, such as postural control deficits, which can severely compromise their daily life activities. However, little attention has been devoted to uncovering the underlying white matter changes in response to training in TBI. In this study, we used longitudinal fixel-based analysis (FBA), an advanced diffusion imaging analysis technique, to investigate the effect of a balance training program on white matter fibre density and morphology in a group of young TBI patients. METHODS: Young patients with moderate-to-severe TBI (N = 17, 10 females, mean age = 13 ± 3 years) and age-matched controls (N = 17) underwent a home-based balance training program. Diffusion MRI scans together with gross motor assessments, including the gross motor items of the Bruininks-Oseretsky Test of Motor Proficiency, the Activities-Specific Balance Confidence (ABC) Scale, and the Sensory Organization Test (SOT) were administered before and at completion of 8-weeks of training. We used FBA to compare microstructural differences in fibre density (FD), macrostructural (morphological) changes in fibre cross-section (FC), and the combined FD and FC (FDC) metric across the whole brain. We then performed a longitudinal analysis to test whether training restores the white matter in the regions found to be damaged before treatment. RESULTS: Whole-brain fixel-based analysis revealed lower FD and FC in TBI patients compared to the control group across several commissural tracts, association fibres and projection fibres, with FD reductions of up to 50%. Following training, TBI patients showed a significant interaction effect between Group and Time for the SOT test, as well as significant increases in macrostructural white matter (i.e., FC & FDC) in left sensorimotor tracts. The amount of change in FC and FDC over time was, h

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 organization. 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, which implements bespoke solutions to this end. It 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 all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities.

INTRODUCTION: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. METHODS AND ANALYSIS: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).

Objective: Evidence from adult literature shows the involvement of cortical grey matter areas of the frontoparietal lobe and the white matter bundle, the superior longitudinal fasciculus (SLF) in motor planning. This is yet to be confirmed in children. Method: A multimodal study was designed to probe the neurostructural basis of childhood motor planning. Behavioural (motor planning), magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) data were acquired from 19 boys aged 8–11 years. Motor planning was assessed using the one and two colour sequences of the octagon task. The MRI data were preprocessed and analysed using FreeSurfer 6.0. Cortical thickness and cortical surface area were extracted from the caudal middle frontal gyrus (MFG), superior frontal gyrus (SFG), precentral gyrus (PcG), supramarginal gyrus (SMG), superior parietal lobe (SPL) and the inferior parietal lobe (IPL) using the Desikan–Killiany atlas. The DWI data were preprocessed and analysed using ExploreDTI 4.8.6 and the white matter tract, the SLF was reconstructed. Results: Motor planning of the two colour sequence was associated with cortical thickness of the bilateral MFG and left SFG, PcG, IPL and SPL. The right SLF was related to motor planning for the two colour sequence as well as with the left cortical thickness of the SFG. Conclusion: Altogether, morphology within frontodorsal circuity, and the white matter bundles that support communication between them, may be associated with individual differences in childhood motor planning.

Introduction Numerous studies have found associations between characteristics of urban environments and risk factors for dementia and cognitive decline, such as physical inactivity and obesity. However, the contribution of urban environments to brain and cognitive health has been seldom examined directly. This cohort study investigates the extent to which and how a wide range of characteristics of urban environments influence brain and cognitive health via lifestyle behaviours in mid-aged and older adults in three cities across three continents. Methods and analysis Participants aged 50 79 years and living in preselected areas stratified by walkability, air pollution and socioeconomic status are being recruited in Melbourne (Australia), Barcelona (Spain) and Hong Kong (China) (n=1800 total; 600 per site). Two assessments taken 24 months apart will capture changes in brain and cognitive health. Cognitive function is gauged with a battery of eight standardised tests. Brain health is assessed using MRI scans in a subset of participants. Information on participants' visited locations is collected via an interactive web-based mapping application and smartphone geolocation data. Environmental characteristics of visited locations, including the built and natural environments and their by-products (e.g., air pollution), are assessed using geographical information systems, online environmental audits and self-reports. Data on travel and lifestyle behaviours (e.g., physical and social activities) and participants' characteristics (e.g., sociodemographics) are collected using objective and/or self-report measures. Ethics and dissemination The study has been approved by the Human Research Ethics Committee of the Australian Catholic University, the Institutional Review Board of the University of Hong Kong and the Parc de Salut Mar Clinical Research Ethics Committee of the Government of Catalonia. Results will be communicated through standard scientific channels. Methods will be

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (fMRI) repetition suppression (RS) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well-validated fMRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA). While univariate whole brain analysis in healthy adults showed uni-modal RS effects within the supplementary motor area, no evidence for cross-modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MNs across the human brain consider the use of MVPA.

Contains fulltext : 183008.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 178215.pdf (publisher's version ) (Open Access), Aim: To better understand the neural and performance factors that may underlie developmental coordination disorder (DCD), and implications for a multi-component account. Method: A systematic review of the experimental literature published between June 2011 and September 2016 was conducted using a modified PICOS (population, intervention, comparison, outcomes, and study type) framework. A total of 106 studies were included. Results: Behavioural data from 91 studies showed a broad cluster of deficits in the anticipatory control of movement, basic processes of motor learning, and cognitive control. Importantly, however, performance issues in DCD were often shown to be moderated by task type and difficulty. As well, we saw new evidence of compensatory processes and strategies in several studies. Neuroimaging data (15 studies, including electroencephalography) showed reduced cortical thickness in the right medial orbitofrontal cortex and altered brain activation patterns across functional networks involving prefrontal, parietal, and cerebellar regions in children with DCD than those in comparison groups. Data from diffusion-weighted magnetic resonance imaging suggested reduced white matter organization involving sensorimotor structures and altered structural connectivity across the whole brain network. Interpretation: Taken together, results support the hypothesis that children with DCD show differences in brain structure and function compared with typically developing children. Behaviourally, these differences may affect anticipatory planning and reduce automatization of movement skill, prompting greater reliance on slower feedback-based control and compensatory strategies. Implications for future research, theory development, and clinical practice are discussed.

Contains fulltext : 175859.pdf (Publisher’s version ) (Open Access), Purpose: This paper discusses the merits of a hybrid model of developmental coordination disorder (DCD), one that integrates cognitive neuroscience and ecological systems approaches. More specifically, we present an integrative summary of recent empirical work on DCD that enlist behavioural and neuroimaging methods and propose a theoretical interpretation through the lens of a hybrid model. Findings: The review identifies two current hypotheses of DCD that find consistent support: the internal modelling deficit (IMD) and mirror neuron system (MNS) accounts. However, motor performance and brain activation patterns are not expressed in a uniform way under these hypotheses - motor deficits are manifested variously as a function of specific task and environmental constraints and condition severity. Moreover, we see evidence of compensatory processes and strategies. Summary: Taken together, results support the broad hypothesis that children with DCD show distinct motor control deficits and differences in neural structure and function compared with typically developing children. However, researchers still have difficulty ascribing causation. The proposed hybrid (multi-component) model of DCD can help researchers generate novel hypotheses about specific mechanisms, explaining the constellation of deficits that is shown experimentally and observed clinically. This model can be applied to cognate disorders of childhood that affect movement and design of intervention.

Contains fulltext : 173220.pdf (publisher's version ) (Closed access), Traumatic brain injury (TBI) often leads to impairments in gait performance. However, the underlying neurostructural pathology of these gait deficits is poorly understood. We aimed to investigate regional gray matter (GM) volume in young moderate-to-severe TBI participants (n = 19; age 13 years 11 months +/-3 years 1 month), compared with typically developing (TD) participants (n = 30; 14 years 10 months +/-2 years 2 months), and assess whether reduced volume was related to impaired gait performance in TBI participants. Cortical and subcortical GM structures involved in the neural control of gait were selected as regions of interest (ROIs) and their volume was extracted using Freesurfer. Moreover, established spatiotemporal markers of gait impairments in TBI participants, including step length asymmetry, step length variability, and double support time, were obtained using an electronic walkway. Compared with TD participants, TBI participants showed increased double support time, step length asymmetry, and step length variability, suggesting a reduced gait control. Secondly, in TBI participants, reduced volumes were demonstrated in overall subcortical GM and individual subcortical ROIs, including the hippocampus, cerebellar cortex, putamen, and thalamus. Moreover, in the TBI group, volume losses in subcortical ROIs were highly inter-correlated, indicating that atrophy tends to occur in combined subcortical structures. Finally, it was demonstrated, for the first time, that gait abnormalities in TBI subjects were associated with reduced volume in specific GM structures, including the hippocampus, thalamus, and the cerebellar, superior frontal, paracentral, posterior cingulate, and superior parietal cortices. The present study is an important first step in the understanding of the neurostructural pathology underlying impaired gait in TBI patients.

Contains fulltext : 157727.pdf (publisher's version ) (Closed access), This paper examines how current understandings of childhood participation and motor development provide opportunities for using new technologies (such as virtual reality—VR) for children with neurodevelopmental disorders. Specifically, the International Classification of Functioning, Disability and Health is used to conceptualize the role of technology in treatment across body structures and body function, activity performance, and participation (WHO 2007, 2012). First, we review the particular motor control and learning mechanisms that have been implicated in children with atypical motor development, like DCD. This section will highlight avenues for targeted remediation. Next, VR-based rehabilitation systems are reviewed in relation to neurodevelopmental disorders, focusing first on CP and second on more recent applications for children with DCD. We describe the evolution of particular design innovations in virtual rehabilitation including recent advances using tangible interfaces, as well as other methods targeting cognitive function more specifically. Benefits of these various treatments will be viewed through the lens of current theory and evaluated at the level of child and family outcomes. Finally, we consider the broader aspects of the potential for technological innovation in rehabilitation and its impact on brain function, activity competence, and longer-term participation.

Item does not contain fulltext, BACKGROUND: Children with impaired motor coordination (or DCD) have difficulty using motor imagery. We have suggested that this difficulty is explained by the internal modeling deficit (IMD) hypothesis of DCD. Our previous training study lent support for this hypothesis by showing that a computerized imagery training protocol (involving action observation, and mental- and overt-rehearsal) was equally effective to perceptual-motor therapy (PMT) in promoting motor skill acquisition. AIMS: The study presented here was designed to replicate and extend this finding, targeting a select group of children with moderate-to-severe DCD. METHODS AND PROCEDURES: All 36 children with DCD who participated were referred to the study and scored below the 10th percentile for their age on the Movement Assessment Battery for Children (MABC). Using a randomized control trial, the referred children were assigned randomly to one of three groups using a blocked procedure: imagery training, perceptual-motor training (PMT), and wait-list control. Motor proficiency was measured using the MABC, pre and post-training. Individual training consisted of 60-min sessions, conducted once a week for 5 weeks. Results : Results showed that the imagery protocol was equally effective as PMT in promoting motor skill acquisition, with moderate-to-large effect sizes. Individual differences showed that the majority of children in the two intervention groups improved their motor performance significantly. CONCLUSIONS: Overall, these results further support the use of motor imagery protocols in the treatment of DCD, and tentative support for the IMD hypothesis. Developmental and dose issues in the implementation of imagery-based intervention are discussed.

Item does not contain fulltext, INTRODUCTION: Previous research indicates that children with Developmental Coordination Disorder (DCD) show deficits performing online corrections, an issue exacerbated by adding inhibitory constraints; however, cross-sectional data suggests that these deficits may reduce with age. Using a longitudinal design, the aim of the study presented here was to model the coupling that occurs between inhibitory systems and (predictive) online control in typically developing children (TDC) and in those with Developmental Coordination Disorder (DCD) over an extended period of time, using a framework of interactive specialization. We predicted that TDC would show a non-linear growth pattern, consistent with re-organisation in the coupling during the middle childhood period, while DCD would display a developmental lag. METHOD: A group of 196 children (111 girls and 85 boys) aged between 6 and 12years participated in the study. Children were classified as DCD according to research criteria. Using a cohort sequential design, both TDC and DCD groups were divided into age cohorts. Predictive (online) control was defined operationally by performance on a Double-Jump Reaching Task (DJRT), which was assessed at 6-month intervals over two years (5 time points in total). Inhibitory control was examined using an anti-jump condition of the DJRT paradigm whereby children were instructed to touch a target location in the hemispace opposite a cued location. RESULTS: For the TDC group, model comparison using growth curve analysis revealed that a quadratic trend was the most appropriate fit with evidence of rapid improvement in anti-reach performance up until middle childhood (around 8-9years of age), followed by a more gradual rate of improvement into late childhood and early adolescence. This pattern was evident on both chronometric and kinematic measures. In contrast, for children with DCD, a linear function provided the best to fit on the key metrics, with a slower rate of improvement than c

9 juni 2015, Item does not contain fulltext, Elements is a table-top virtual reality system designed for rehabilitation of upper-limb function in populations with neuro-cognitive deficits. It includes two sets of virtual task environment (VEs). The first are 'goal-directed VEs' whereby participants move tangible user interfaces (TUIs) to visually-cued locations, while receiving augmented feedback (as shown in Figures 1, 2). The second set of VEs are purely exploratory in nature. Small sample trials of Elements for adult TBI patients [1, 2], and children with hemiparesis [3] have yielded positive results for skill acquisition and neuro-cognitive function. Our present aims are fine-tuning the design and performance of Elements and conducting larger multi-centre studies to assess its efficacy.

Contains fulltext : 154331.pdf (publisher's version ) (Open Access), We investigated whether balance control in young TBI patients can be promoted by an 8-week balance training program and whether this is associated with neuroplastic alterations in brain structure. The cerebellum and cerebellar peduncles were selected as regions of interest because of their importance in postural control as well as their vulnerability to brain injury. Young patients with moderate to severe TBI and typically developing (TD) subjects participated in balance training using PC-based portable balancers with storage of training data and real-time visual feedback. An additional control group of TD subjects did not attend balance training. Mean diffusivity and fractional anisotropy were determined with diffusion MRI scans and were acquired before, during (4 weeks) and at completion of training (8 weeks) together with balance assessments on the EquiTest(R) System (NeuroCom) which included the Sensory Organization Test, Rhythmic Weight Shift and Limits of Stability protocols. Following training, TBI patients showed significant improvements on all EquiTest protocols, as well as a significant increase in mean diffusivity in the inferior cerebellar peduncle. Moreover, in both training groups, diffusion metrics in the cerebellum and/or cerebellar peduncles at baseline were predictive of the amount of performance increase after training. Finally, amount of training-induced improvement on the Rhythmic Weight Shift test in TBI patients was positively correlated with amount of change in fractional anisotropy in the inferior cerebellar peduncle. This suggests that training-induced plastic changes in balance control are associated with alterations in the cerebellar white matter microstructure in TBI patients.

Item does not contain fulltext, Traumatic brain injury (TBI) can lead to deficits in gait and posture, which are often asymmetric. A possible factor mediating these deficits may be asymmetry in strength of the leg muscles. However, muscle strength in the lower extremities has rarely been investigated in (young) TBI patients. Here, we investigated associations between lower-extremity muscle weakness, strength asymmetry, and impairments in gait and posture in young TBI patients. A group of young patients with moderate-to-severe TBI (n=19; age, 14 years 11 months +/-2 years) and a group of typically developing subjects (n=31; age, 14 years 1 month+/-3 years) participated in this study. A force platform was used to measure postural sway to quantify balance control during normal standing and during conditions of compromised visual and/or somatosensory feedback. Spatiotemporal gait parameters were assessed during comfortable and fast-speed walking, using an electronic walkway. Muscle strength in four lower-extremity muscle groups was measured bilaterally using a handheld dynamometer. Findings revealed that TBI patients had poorer postural balance scores across all sensory conditions, as compared to typically developing subjects. During comfortable and fast gait, TBI patients demonstrated a lower gait velocity, longer double-support phase, and increased step-length asymmetry. Further, TBI patients had a reduced strength of leg muscles and an increased strength asymmetry. Correlation analyses revealed that asymmetry in muscle strength was predictive of a poorer balance control and a more variable and asymmetric gait. To the best of our knowledge, this is the first study to measure strength asymmetry in leg muscles of a sample of TBI patients and illustrate the importance of muscular asymmetry as a potential marker and possible risk factor of impairments in control of posture and gait.

Suicidal behavior constitutes a major public health problem. Based on the stress-diathesis model, biological correlates of a diathesis might help to predict risk after stressor-exposure. Structural changes in cortical and subcortical areas and their connections have increasingly been linked with the diathesis. The current study identified structural network changes associated with a diathesis using a whole-brain approach by examining the structural connectivity between regions in euthymic suicide attempters (SA). In addition, the association between connectivity measures, clinical and genetic characteristics was investigated. We hypothesized that SA showed lower connectivity strength, associated with an increased severity of general clinical characteristics and an elevated expression of short alleles in serotonin polymorphisms. Thirteen euthymic SA were compared with fifteen euthymic non-attempters and seventeen healthy controls (HC). Clinical characteristics and three serotonin-related genetic polymorphisms were assessed. Diffusion MRI together with anatomical scans were administered. Preprocessing was performed using Explore DTI. Whole brain tractography of the diffusion-weighted images was followed by a number of streamlines-weighted network analysis using NBS. The network analysis revealed decreased connectivity strength in SA in the connections between the left olfactory cortex and left anterior cingulate gyrus. Furthermore, SA had increased suicidal ideation, hopelessness and self-reported depression, but did not show any differences for the genetic polymorphisms. Finally, lower connectivity strength between the right calcarine fissure and the left middle occipital gyrus was associated with increased trait anxiety severity (rs = -0.78, p < 0.01) and hopelessness (rs = -0.76, p < 0.01). SA showed differences in white matter network connectivity strength associated with clinical characteristics. Together, these variables could play an important role in pre

© 2015. Graph theory (GT) is a powerful framework for quantifying topological features of neuroimaging-derived functional and structural networks. However, false positive (FP) connections arise frequently and influence the inferred topology of networks. Thresholding is often used to overcome this problem, but an appropriate threshold often relies on a priori assumptions, which will alter inferred network topologies.Four common network metrics (global efficiency, mean clustering coefficient, mean betweenness and smallworldness) were tested using a model tractography dataset. It was found that all four network metrics were significantly affected even by just one FP. Results also show that thresholding effectively dampens the impact of FPs, but at the expense of adding significant bias to network metrics.In a larger number (n= 248) of tractography datasets, statistics were computed across random group permutations for a range of thresholds, revealing that statistics for network metrics varied significantly more than for non-network metrics (i.e., number of streamlines and number of edges). Varying degrees of network atrophy were introduced artificially to half the datasets, to test sensitivity to genuine group differences. For some network metrics, this atrophy was detected as significant (p<. 0.05, determined using permutation testing) only across a limited range of thresholds.We propose a multi-threshold permutation correction (MTPC) method, based on the cluster-enhanced permutation correction approach, to identify sustained significant effects across clusters of thresholds. This approach minimises requirements to determine a single threshold a priori. We demonstrate improved sensitivity of MTPC-corrected metrics to genuine group effects compared to an existing approach and demonstrate the use of MTPC on a previously published network analysis of tractography data derived from a clinical population.In conclusion, we show that there are large biases and instab