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There is robust evidence implicating inhibitory deficits as a fundamental behavioural phenotype in children with attention-deficit/hyperactivity disorder (ADHD). However, prior studies have not directly investigated the role in which white matter properties within the fronto-basal-ganglia circuit may play in the development of inhibitory control deficits in this group. Combining recent advancements in brain-behavioural modelling, we mapped the development of stop-signal task (SST) performance and fronto-basal-ganglia maturation in a longitudinal sample of children aged 9-14 with and without ADHD. In a large sample of 135 ADHD and 138 non-ADHD children, we found that the ADHD group had poorer inhibitory control (i.e., longer stop-signal reaction times) across age compared to non-ADHD controls. When applying the novel parametric race model, this group effect was driven by higher within-subject variability (sigma) and higher number of extreme responses (tau) on stop trials. The ADHD group also displayed higher within-subject variability on correct responses to go stimuli. Moreover, we observed the ADHD group committing more task-based failures such as responding on stop trials (trigger failures) and omissions on go trials (go failures) compared to non-ADHD controls, suggesting the contribution of attentional lapses to poorer response inhibition performance. In contrast, longitudinal modelling of fixel-based analysis measures revealed no significant group differences in the maturation of fronto-basal-ganglia fibre cross-section in a subsample (74 ADHD and 73 non-ADHD children). Finally, brain-behavioural models revealed that age-related changes in fronto-basal-ganglia morphology (fibre cross-section) were significantly associated with reductions in the variability of the correct go-trial responses (sigma.true) and skew of the stop-trial distribution (tauS). However, this effect did not differ between ADHD and typically developing children. Overall, our findings support the growing consensus suggesting that attentional deficits subserve ADHD-related inhibitory dysfunction. Furthermore, we show novel evidence suggesting that while children with ADHD are consistently performing worse on the SST than their non-affected peers, they appear to have comparable rates of neurocognitive maturation across this period., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury-related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes. Additionally, development of reliable biomarkers of mild TBI or repeated subconcussive impacts has been slow, likely due, in part, to subtle effects of injury and the aforementioned variability. The ENIGMA Consortium has established a framework for global collaboration that has resulted in the largest-ever neuroimaging studies of multiple psychiatric and neurological disorders. Here we describe the organization, recent progress, and future goals of the Brain Injury working group., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Changes in brain morphology are hypothesized to be an underlying process that drive the widespread pain and motor impairment in patients with chronic neck pain. However, no earlier research assessed whole-brain cortical morphology in these patients. This case-control study assesses group-differences in whole-brain morphology between female healthy controls (HC; n = 34), and female patients with chronic idiopathic neck pain (CINP; n = 37) and whiplash-associated disorders (CWAD; n = 39). Additionally, the associations between whole-brain morphology and motor performance including balance, strength, and neuromuscular control were assessed. Cortical volume, thickness, and surface area were derived from high resolution T1-weighted images. T2*-weighted images were obtained to exclude traumatic brain injury. Vertex-wise general-linear-model-analysis revealed cortical thickening in the left precuneus and increased volume in the left superior parietal gyrus of patients with CINP compared to HC, and cortical thickening of the left superior parietal gyrus compared to HC and CWAD. Patients with CWAD showed a smaller cortical volume in the right precentral and superior temporal gyrus compared to HC. ANCOVA-analysis revealed worse neuromuscular control in CWAD compared to HC and CINP, and in CINP compared to HC. Patients with CWAD showed decreased levels of strength and sway area compared to CINP and HC. Partial correlation analysis revealed significant associations between the volume of the precentral gyrus, and neuromuscular control and strength together with an association between the volume of the superior temporal gyrus and strength. Our results emphasize the role of altered gray matter alterations in women with chronic neck pain, and its association with pain and motor impairment., (© 2019 Wiley Periodicals, Inc.)

Graph analysis was used to study the effects of accelerated intermittent theta burst stimulation (aiTBS) on the brain's network topology in medication-resistant depressed patients. Anatomical and resting-state functional MRI (rs-fMRI) was recorded at baseline and after sham and verum stimulation. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). Using various graph measures, the different effects of sham and verum aiTBS were calculated. It was also investigated whether changes in graph measures were correlated to clinical responses. Furthermore, by correlating baseline graph measures with the changes in HDRS in terms of percentage, the potential of graph measures as biomarker was studied. Although no differences were observed between the effects of verum and sham stimulation on whole-brain graph measures and changes in graph measures did not correlate with clinical response, the baseline values of clustering coefficient and global efficiency showed to be predictive of the clinical response to verum aiTBS. Nodal effects were found throughout the whole brain. The distribution of these effects could not be linked to the strength of the functional connectivity between the stimulation site and the node. This study showed that the effects of aiTBS on graph measures distribute beyond the actual stimulation site. However, additional research into the complex interactions between different areas in the brain is necessary to understand the effects of aiTBS in more detail., (© 2018 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

This study evaluated the effect of a multidisciplinary treatment program for children with obesity (OB) on motor competence, executive functioning (EF), and brain structure. Nineteen children with OB (7-11 years), who attended a multidisciplinary treatment program consisting of diet restriction, cognitive behavioral therapy, and physical activity, were compared with an age-matched control group of 24 children with a healthy weight (HW), who did not follow any treatment. For both groups, anthropometric measurements and tests of motor competence and EF were administered twice, with 5 months between pretest and posttest. Additionally, children's brain structure was assessed by performing a magnetic resonance imaging (MRI) scan at the pretest and posttest, which included a T1 anatomical scan, diffusion MRI scan, and magnetization transfer imaging scan. Compared to HW controls, children with OB lost a considerable amount of their body mass (p ≤ .001) and significantly improved their balance skills (p ≤ .001), while no transfer effects of the program were observed for EF. Furthermore, the program resulted in a significant increase in total (p ≤ .001) and cerebellar (p ≤ .001) gray matter volume in children with OB, while no change was observed in the HW controls. Finally, only weak to moderate (nonsignificant) correlations could be observed between structural brain alterations, weight-related changes, and behavioral improvements. Altogether, this is the first longitudinal study showing behavioral and structural brain alterations in response to a multidisciplinary weight loss program for children with OB. Our findings support the need for multidimensional intervention (and prevention) measures for children with OB to deal with this multifactorial health problem., (© 2018 Wiley Periodicals, Inc.)

Recent evidence has shown the presence of a "rich club" in the brain, which constitutes a core network of highly interconnected and spatially distributed brain regions, important for high-order cognitive processes. This study aimed to map the rich club organization in 17 young patients with moderate to severe TBI (15.71 ± 1.75 years) in the chronic stage of recovery and 17 age- and gender-matched controls. Probabilistic tractography was performed on diffusion weighted imaging data to construct the edges of the structural connectomes using number of streamlines as edge weight. In addition, the whole-brain network was divided into a rich club network, a local network and a feeder network connecting the latter two. Functional outcome was measured with a parent questionnaire for executive functioning. Our results revealed a significantly decreased rich club organization (p values < .05) and impaired executive functioning (p < .001) in young patients with TBI compared with controls. Specifically, we observed reduced density values in all three subnetworks (p values < .005) and a reduced mean strength in the rich club network (p = .013) together with an increased mean strength in the local network (p = .002) in patients with TBI. This study provides new insights into the nature of TBI-induced brain network alterations and supports the hypothesis that the local subnetwork tries to compensate for the biologically costly subnetwork of rich club nodes after TBI., (© 2018 Wiley Periodicals, Inc.)

Mapping gray matter (GM) pathology in Parkinson's disease (PD) with conventional MRI is challenging, and the need for more sensitive brain imaging techniques is essential to facilitate early diagnosis and assessment of disease severity. GM microstructure was assessed with GM-based spatial statistics applied to diffusion kurtosis imaging (DKI) and neurite orientation dispersion imaging (NODDI) in 30 participants with PD and 28 age- and gender-matched controls. These were compared with currently used assessment methods such as diffusion tensor imaging (DTI), voxel-based morphometry (VBM), and surface-based cortical thickness analysis. Linear discriminant analysis (LDA) was also used to test whether subject diagnosis could be predicted based on a linear combination of regional diffusion metrics. Significant differences in GM microstructure were observed in the striatum and the frontal, temporal, limbic, and paralimbic areas in PD patients using DKI and NODDI. Significant correlations between motor deficits and GM microstructure were also noted in these areas. Traditional VBM and surface-based cortical thickness analyses failed to detect any GM differences. LDA indicated that mean kurtosis (MK) and intra cellular volume fraction (ICVF) were the most accurate predictors of diagnostic status. In conclusion, DKI and NODDI can detect cerebral GM abnormalities in PD in a more sensitive manner when compared with conventional methods. Hence, these methods may be useful for the diagnosis of PD and assessment of motor deficits. Hum Brain Mapp 38:3704-3722, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Successfully switching between tasks is critical in many daily activities. Age-related slowing of this switching behavior has been documented extensively, but the underlying neural mechanisms remain unclear. Here, we investigated the contribution of brain white matter changes associated with myelin alterations to age-related slowing of switching performance. Diffusion tensor imaging derived radial diffusivity (RD) and magnetization transfer imaging derived magnetization transfer ratio (MTR) were selected as myelin sensitive measures. These metrics were studied in relation to mixing cost (i.e., the increase in reaction time during task blocks that require task switching) on a local-global switching task in young (n = 24) and older (n = 22) adults. Results showed that higher age was associated with widespread increases in RD and decreases in MTR, indicative of white matter deterioration, possibly due to demyelination. Older adults also showed a higher mixing cost, implying slowing of switching performance. Finally, mediation analyses demonstrated that decreases in MTR of the bilateral superior corona radiata contributed to the observed slowing of switching performance with increasing age. These findings provide evidence for a role of cortico-subcortical white matter changes in task switching performance deterioration with healthy aging. Hum Brain Mapp 37:4084-4098, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI., (© 2015 Wiley Periodicals, Inc.)

Schizophrenia is often regarded as a "dysconnectivity" disorder and recent work using graph theory has been used to better characterize dysconnectivity of the structural connectome in schizophrenia. However, there are still little data on the topology of connectomes in less severe forms of the condition. Such analysis will identify topological markers of less severe disease states and provide potential predictors of further disease development. Individuals with psychotic experiences (PEs) were identified from a population-based cohort without relying on participants presenting to clinical services. Such individuals have an increased risk of developing clinically significant psychosis. 123 individuals with PEs and 125 controls were scanned with diffusion-weighted MRI. Whole-brain structural connectomes were derived and a range of global and local GT-metrics were computed. Global efficiency and density were significantly reduced in individuals with PEs. Local efficiency was reduced in a number of regions, including critical network hubs. Further analysis of functional subnetworks showed differential impairment of the default mode network. An additional analysis of pair-wise connections showed no evidence of differences in individuals with PEs. These results are consistent with previous findings in schizophrenia. Reduced efficiency in critical core hubs suggests the brains of individuals with PEs may be particularly predisposed to dysfunction. The absence of any detectable effects in pair-wise connections illustrates that, at less severe stages of psychosis, white-matter alterations are subtle and only manifest when examining network topology. This study indicates that topology could be a sensitive biomarker for early stages of psychotic illness., (© 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.)

The study on structural brain asymmetries in healthy individuals plays an important role in our understanding of the factors that modulate cognitive specialization in the brain. Here, we used fiber tractography to reconstruct the left and right hemispheric networks of a large cohort of 346 healthy participants (20-86 years) and performed a graph theoretical analysis to investigate this brain laterality from a network perspective. Findings revealed that the left hemisphere is significantly more "efficient" than the right hemisphere, whereas the right hemisphere showed higher values of "betweenness centrality" and "small-worldness." In particular, left-hemispheric networks displayed increased nodal efficiency in brain regions related to language and motor actions, whereas the right hemisphere showed an increase in nodal efficiency in brain regions involved in memory and visuospatial attention. In addition, we found that hemispheric networks decrease in efficiency with age. Finally, we observed significant gender differences in measures of global connectivity. By analyzing the structural hemispheric brain networks, we have provided new insights into understanding the neuroanatomical basis of lateralized brain functions., (Copyright © 2014 Wiley Periodicals, Inc.)

Suppressing and flexibly adapting actions are a critical part of our daily behavioral repertoire. Traumatic brain injury (TBI) patients show clear impairments in this type of action control; however, the underlying mechanisms are poorly understood. Here, we tested whether white matter integrity of cortico-subcortical pathways could account for impairments in task switching, an important component of executive functioning. Twenty young adults with TBI and eighteen controls performed a switching task requiring attention to global versus local stimulus features. Diffusion weighted images were acquired and whole brain tract-based spatial statistics (TBSS) were used to explore where white matter damage was associated with switching impairment. A crossing fiber model and probabilistic tractography further identified the specific fiber populations. Relative to controls, patients with a history of TBI had a higher switch cost and were less accurate. The TBI group showed a widespread decline in fractional anisotropy (FA) throughout the TBSS skeleton. FA in the superior corona radiata showed a negative relationship with switch cost. More specifically, this involved cortico-subcortical loops with the (pre-)supplementary motor area and superior frontal gyrus. These findings provide evidence for damage to frontal-subcortical projections in TBI, which is associated with task switching impairments., (Copyright © 2013 Wiley Periodicals, Inc.)

The ability to suppress and flexibly adapt motor behavior is a fundamental mechanism of cognitive control, which is impaired in traumatic brain injury (TBI). Here, we used a combination of functional magnetic resonance imaging and diffusion weighted imaging tractography to study changes in brain function and structure associated with motor switching performance in TBI. Twenty-three young adults with moderate-severe TBI and twenty-six healthy controls made spatially and temporally coupled bimanual circular movements. A visual cue signaled the right hand to switch or continue its circling direction. The time to initiate the switch (switch response time) was longer and more variable in the TBI group and TBI patients exhibited a higher incidence of complete contralateral (left hand) movement disruptions. Both groups activated the basal ganglia and a previously described network for task-set implementation, including the supplementary motor complex and bilateral inferior frontal cortex (IFC). Relative to controls, patients had significantly increased activation in the presupplementary motor area (preSMA) and left IFC, and showed underactivation of the subthalamic nucleus (STN) region. This altered functional engagement was related to the white matter microstructural properties of the tracts connecting preSMA, IFC, and STN. Both functional activity in preSMA, IFC, and STN, and the integrity of the connections between them were associated with behavioral performance across patients and controls. We suggest that damage to these key pathways within the motor switching network because of TBI, shifts the patients toward the lower end of the existing structure-function-behavior spectrum., (Copyright © 2012 Wiley Periodicals, Inc.)

When manipulating objects with both hands, the corpus callosum (CC) is of paramount importance for interhemispheric information exchange. Hence, CC damage results in impaired bimanual performance. Here, healthy young adults performed a complex bimanual dial rotation task with or without augmented visual feedback and according to five interhand frequency ratios (1:1, 1:3, 2:3, 3:1, 3:2). The relation between bimanual task performance and microstructural properties of seven CC subregions (i.e., prefrontal, premotor/supplementary motor, primary motor, primary sensory, occipital, parietal, and temporal) was studied by means of diffusion tensor imaging (DTI). Findings revealed that bimanual coordination deteriorated in the absence as compared to the presence of augmented visual feedback. Simple frequency ratios (1:1) were performed better than the multifrequency ratios (non 1:1). Moreover, performance was more accurate when the preferred hand (1:3-2:3) as compared to the nonpreferred hand (3:1-3:2) moved faster and during noninteger (2:3-3:2) as compared to integer frequency ratios (1:3-3:1). DTI findings demonstrated that bimanual task performance in the absence of augmented visual feedback was significantly related to the microstructural properties of the primary motor and occipital region of the CC, suggesting that white matter microstructure is associated with the ability to perform bimanual coordination patterns in young adults., (Copyright © 2011 Wiley Periodicals, Inc.)

Traumatic brain injury (TBI) is a major cause of impairment and functional disability in children and adolescents, including deterioration in fine as well as gross motor skills. The aim of this study was to assess deficits in sensory organization and postural ability in a young group of TBI patients versus controls by using quantitative force-platform recordings, and to test whether balance deficits are related to variation in structural properties of the motor and sensory white matter pathways. Twelve patients with TBI and 14 controls (aged 8-20 years) performed the Sensory Organisation Test (SOT) protocol of the EquiTest (Neurocom). All participants were scanned using Diffusion Tensor Imaging (DTI) along with standard anatomical scans. Quantitative comparisons of DTI parameters (fractional anisotropy, axial and radial diffusivity) between TBI patients and controls were performed. Correlations between DTI parameters and SOT balance scores were determined. Findings revealed that the TBI group scored generally lower than the control group on the SOT, indicative of deficits in postural control. In the TBI group, reductions in fractional anisotropy were noted in the cerebellum, posterior thalamic radiation, and corticospinal tract. Degree of white matter deterioration was highly correlated with balance deficits. This study supports the view that DTI is a valuable tool for assessing the integrity of white matter structures and for selectively predicting functional motor deficits in TBI patients., ((c) 2009 Wiley-Liss, Inc.)