Threshold-free Cluster Enhancement Research Articles

Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation.

Introduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification.Methods: Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement.Results: Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma.Conclusions: This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.

Within-network brain connectivity in Crohn's disease patients with gadolinium deposition in the cerebellum.

Patients with Crohn's disease (CD) undergo multiple gadolinium-based contrast agent injections across their lifespan to enhance signal intensity of the intestinal wall and differentiate active from quiescent inflammatory disease. Thus, CD patients are prone to gadolinium accumulation in the brain and represent a non-neurological population to explore gadolinium-related brain toxicity. Possible effects are expected to be greater on the cerebellar network due to the high propensity of the dentate nucleus to accumulate gadolinium. Herein, we provide a whole-brain network analysis of resting-state fMRI dynamics in long-term quiescent CD patients with normal renal function and MRI evidence of gadolinium deposition in the brain. Fifteen patients with CD and 16 healthy age- and gender-matched controls were enrolled in this study. Relevant resting-state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data. An unpaired two-sample t test (with age and sex as nuisance variables) was used to investigate between different RSNs. Clusters were determined by using threshold-free cluster enhancement and a family-wise error corrected cluster significance threshold of p < 0.05. Patients showed significantly decreased resting-state functional connectivity (p < 0.05, FWE corrected) of several regions of the right frontoparietal (FPR) and the dorsal attention (DAN) RSNs. No differences between the two groups were found in the functional connectivity maps of all the other RSNs, including the cerebellar network. Our findings suggest a non-significant impact of gadolinium deposition on within-network cerebellar functional connectivity of long-term quiescent CD patients.

Cerebello-cerebral connectivity in idiopathic generalized epilepsy.

The present study aims to investigate structural and functional connectivity (SC and FC) in cerebello-cerebral circuit in idiopathic generalized epilepsy (IGE). Diffusion tensor imaging and resting-state imaging data were collected from 57 patients with IGE and 66 controls in the present study. First, we performed bidirectional probabilistic fiber tracking between cerebellum and cerebral cortex, consisting of cerebellar efferent and afferent fibers. Then, strength of structural connectivity (SCS), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) were extracted and compared between groups. Finally, cerebellar FC with cerebral cortex was evaluated with seeding at dentate nucleus. Between-group comparisons were performed using t tests with a significant level setting at p < 0.05 with threshold-free cluster enhancement correction. The patients with IGE showed decreased SCS in cerebellar efferent fibers to sensorimotor cortex in anterior corona radiate and increased SCS in efferent fibers to occipital cortex in posterior corona radiata. The SCS in cerebellar afferent fibers in corticospinal tract from frontal and in retrolenticular part of the internal capsule from occipital cortices were increased in IGE, and SCS in afferent fibers in posterior limb of internal capsule from parietal cortex was decreased. Decreased FA and increased MD and RD were observed in cerebello-cerebral tracts. Besides, decreased cerebellar FC with putamen and motor cortex was observed in IGE. The patients with IGE demonstrated distinct alterations in efferent and afferent pathways between cerebellum and different cerebral cortices, which might be the pathological anatomical basis for cerebellar modulation effect on epileptic activities and contribute to motor deficits. • IGE showed decreased SCS in cerebellar efferent fibers to the sensorimotor cortex and increased SCS in efferent fibers to the occipital cortex. • Patients demonstrated increased SCS in cerebellar afferent fibers from the frontal and the occipital cortex and decreased SCS in afferent fibers from parietal cortex. • Decreased FC between motor-related regions and dentate nucleus was observed in IGE.

Examining Microstructural White Matter Differences between Children with Typical and Those with Delayed Recovery Two Weeks Post-Concussion

Delayed recovery from concussion can dramatically affect a child's social, emotional, and educational development, yet little is known about what causes some children to recover faster than others. The contribution of white matter disruption in children with delayed recovery has been hypothesized, but findings are limited by methodological issues such as: small heterogeneous samples, bias toward children with delayed recovery, and inconsistencies in timing of brain imaging, both within and between studies. The aim of the present study was to assess diffusion neuroimaging correlates of delayed recovery post-concussion in children. A prospective, longitudinal, observational cohort study was conducted at a statewide tertiary pediatric hospital. Forty-three children who presented to the emergency department (ED) with concussion (defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport) underwent magnetic resonance imaging (MRI) at a 2 weeks post-injury and were classified as either normally recovering (n = 26) or delayed recovering (n = 17). Diffusion imaging comparison using voxelwise tract-based spatial statistics (TBSS) analysis found no difference between the groups in fractional anisotropy, axial diffusion, radial diffusion, or mean diffusivity metrics (p > 0.05 threshold-free cluster enhancement [TFCE] corrected). Post-hoc tract-based Bayesian analysis found evidence for the null in 11 unique white matter tracts (Bayes factor >3). These findings indicate that delayed recovery from post-concussive symptoms in children is unlikely to be caused by white matter microstructural damage.

Default Mode Network Connectivity and Social Dysfunction in Major Depressive Disorder

Though social functioning is often hampered in Major Depressive Disorder (MDD), we lack a complete and integrated understanding of the underlying neurobiology. Connectional disturbances in the brain’s Default Mode Network (DMN) might be an associated factor, as they could relate to suboptimal social processing. DMN connectional integrity, however, has not been explicitly studied in relation to social dysfunctioning in MDD patients. Applying Independent Component Analysis and Dual Regression on resting-state fMRI data, we explored DMN intrinsic functional connectivity in relation to social dysfunctioning (i.e. composite of loneliness, social disability, small social network) among 74 MDD patients (66.2% female, Mean age = 36.9, SD = 11.9). Categorical analyses examined whether DMN connectivity differs between high and low social dysfunctioning MDD groups, dimensional analyses studied linear associations between social dysfunction and DMN connectivity across MDD patients. Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used for statistical thresholding and multiple comparisons correction (P < 0.05). The analyses cautiously linked greater social dysfunctioning among MDD patients to diminished DMN connectivity, specifically within the rostromedial prefrontal cortex and posterior superior frontal gyrus. These preliminary findings pinpoint DMN connectional alterations as potentially germane to social dysfunction in MDD, and may as such improve our understanding of the underlying neurobiology.

Default mode network functional connectivity after multiple concussions in children and adolescents

Abstract The default mode network (DMN), a set of brain regions, has been shown to be affected post-concussion. Objective This cross-sectional study aims to elucidate if children and adolescents with multiple concussions demonstrate long-term alterations in DMN functional connectivity (FC). Method Participants (N = 57, 27 girls and 30 boys; 8-19 years old, M age = 14.7, SD = 2.8) were divided into three groups (orthopedic injury [OI] n = 20; one concussion n = 16; multiple concussions n = 21, M = 3.2 concussions, SD = 1.7) and seen on average 31.6 months post-injury (range 4.3-130.7 months; SD = 19.4). They underwent a resting-state functional magnetic resonance imaging scan. Parents completed the ADHD rating scale-5 for children and adolescents. Children and parents completed the post-concussion symptom inventory (PCSI). Results Anterior and posterior DMN components were extracted from the fMRI data for each participant using FSL’s MELODIC and dual regression. We tested for pairwise group differences within each DMN component in FSL’s Randomize (5000 permutations) using threshold-free cluster enhancement to estimate cluster activation, controlling for age, sex, and symptoms of inattention. FC of the anterior DMN was significantly reduced in the group with multiple concussions compared to the two other groups, whereas there were no significant group differences on FC of the posterior DMN. There were no significant associations between DMN FC and PCSI scores. Conclusions These results suggest reduced FC in the anterior DMN in youth with multiple concussions, but no linear association with post-concussive symptoms.

Altered frontal white matter microstructure is associated with working memory impairments in adolescents with congenital heart disease: A diffusion tensor imaging study.

Children and adolescents with congenital heart disease (CHD) are at risk for mild to moderate cognitive impairments. In particular, impaired working memory performance has been found in CHD patients of all ages. Working memory is an important domain of higher order cognitive function and is crucial for everyday activities, with emerging importance in adolescence. However, the underlying neural correlate of working memory impairments in CHD is not yet fully understood. Diffusion tensor imaging and tract based spatial statistics analyses were conducted in 47 adolescent survivors of childhood cardiopulmonary bypass surgery (24 females) and in 44 healthy controls (24 females) between 11 and 16 years of age (mean age=13.9, SD=1.6). Fractional anisotropy (FA) of white matter diffusion was compared between groups and was correlated with working memory performance, derived from the Wechsler Intelligence Scale for Children-IV. CHD patients had significantly poorer working memory compared to controls (p=0.001). Widespread bilateral reduction in FA was observed in CHD patients compared to healthy controls (threshold-free cluster enhancement (TFCE) corrected p < 0.05). This reduction in FA was present both in cyanotic and acyanotic CHD patients compared to healthy controls (both p < 0.001). The FA reduction in the frontal lobe, mainly in the forceps minor, was associated with poorer working memory performance in both patients with CHD and healthy controls (TFCE corrected p < 0.05). The current findings underline that in CHD patients, irrespective of disease severity, disrupted or delayed maturation of white matter may persist into adolescence and is associated with working memory impairments, particularly if present in the frontal lobe. Adolescence, which is a crucial period for prefrontal brain maturation, may offer a window of opportunity for intervention in order to support the maturation of frontal brain regions and therefore improve higher order cognitive function in patients with CHD.

Cluster failure or power failure? Evaluating sensitivity in cluster-level inference

Pioneering work in human neuroscience has relied on the ability to map brain function using task-based fMRI, but the empirical validity of these inferential methods is still being characterized. A recent landmark study by Eklund and colleagues showed that popular multiple comparison corrections based on cluster extent suffer from unexpectedly low specificity (i.e., high false positive rate). Yet that study’s focus on specificity, while important, is incomplete. The validity of a method depends also on its sensitivity (i.e., true positive rate or power), yet the sensitivity of cluster correction remains poorly understood. Here, we assessed the sensitivity of gold-standard nonparametric cluster correction by resampling real data from five tasks in the Human Connectome Project and comparing results with those from the full “ground truth” datasets (n ​= ​480–493). Critically, we found that sensitivity after correction is lower than may be practical for many fMRI applications. In particular, sensitivity to medium-sized effects (|Cohen’s d| ​= ​0.5) was less than 20% across tasks on average, about three times smaller than without any correction. Furthermore, cluster extent correction exhibited a spatial bias in sensitivity that was independent of effect size. In comparison, correction based on the Threshold-Free Cluster Enhancement (TFCE) statistic approximately doubled sensitivity across tasks but increased spatial bias. These results suggest that we have, until now, only measured the tip of the iceberg in the activation-mapping literature due to our goal of limiting the familywise error rate through cluster extent-based inference. There is a need to revise our practices to improve sensitivity; we therefore conclude with a list of modern strategies to boost sensitivity while maintaining respectable specificity in future investigations.

Widespread White Matter Aberrations Are Associated with Phonemic Verbal Fluency Impairment in Chronic Traumatic Brain Injury.

Microstructural white matter (WM) disruption and resulting abnormal structural connectivity form a potential underlying pathology in traumatic brain injury (TBI). Herein, to determine the potential mechanism of cognitive deterioration in TBI, we examined the association of damage to specific WM tracts with cognitive function in TBI patients. We recruited 18 individuals with mild-to-moderate/severe TBI in the chronic phase and 17 age-matched controls. We determined the pattern of WM aberrations in TBI using tract-based spatial statistics (TBSS) and then examined the relationship between cognitive impairment and WM damage using the threshold-free cluster enhancement correction in TBSS. TBSS analysis showed that TBI patients exhibited WM aberrations in a wide range of brain regions. In the majority of these regions, lower fractional anisotropy (FA) largely overlapped with increased radial diffusivity, but not with axial diffusivity. Further, voxel-wise correction in TBSS demonstrated that higher FA values were associated with better performance in the phonemic verbal fluency task (VFT) in widespread WM regions, but not with the semantic VFT. Despite variation in the magnitude and location of brain injury between individual cases, chronic TBI patients exhibited widespread WM aberrations. We confirmed the findings of previous studies that WM integrity is lower across the spectrum of TBI severity in chronic subjects compared to controls. Further, phonemic VFT may be a more sensitive cognitive measure of executive dysfunction associated with WM aberrations in TBI compared with semantic VFT.

A diffusion-weighted imaging tract-based spatial statistics study of autism spectrum disorder in preschool-aged children

BackgroundThe core symptoms of autism spectrum disorder (ASD) are widely theorized to result from altered brain connectivity. Diffusion-weighted magnetic resonance imaging (DWI) has been a versatile method for investigating underlying microstructural properties of white matter (WM) in ASD. Despite phenotypic and etiological heterogeneity, DWI studies in majority male samples of older children, adolescents, and adults with ASD have largely reported findings of decreased fractional anisotropy (FA) across several commissural, projection, and association fiber tracts. However, studies in preschool-aged children (i.e., < 30–40 months) suggest individuals with ASD have increased measures of WM FA earlier in development.MethodsWe analyzed 127 individuals with ASD (85♂, 42♀) and 54 typically developing (TD) controls (42♂, 26♀), aged 25.1–49.6 months. Voxel-wise effects of ASD diagnosis, sex, age, and their interaction on DWI measures of FA, mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were investigated using tract-based spatial statistics (TBSS) while controlling mean absolute and relative motion.ResultsCompared to TD controls, males and females with ASD had significantly increased measures of FA in eight clusters (threshold-free cluster enhancement p < 0.05) that incorporated several WM tracts including regions of the genu, body, and splenium of the corpus callosum, inferior frontal-occipital fasciculi, inferior and superior longitudinal fasciculi, middle and superior cerebellar peduncles, and corticospinal tract. A diagnosis by sex interaction was observed in measures of AD across six significant clusters incorporating areas of the body, genu, and splenium of the corpus collosum. In these tracts, females with ASD showed increased AD compared to TD females, while males with ASD showed decreased AD compared to TD males.ConclusionsThe current findings support growing evidence that preschool-aged children with ASD have atypical measures of WM microstructure that appear to differ in directionality from alterations observed in older individuals with the condition. To our knowledge, this study represents the largest sample of preschool-aged females with ASD to be evaluated using DWI. Microstructural differences associated with ASD largely overlapped between sexes. However, differential relationships of AD measures indicate that sex likely modulates ASD neuroanatomical phenotypes. Further longitudinal study is needed to confirm and quantify the developmental relationship of WM structure in ASD.

Applying the D50 disease progression model to gray and white matter pathology in amyotrophic lateral sclerosis.

Therapeutic management and research in Amyotrophic Laterals Sclerosis (ALS) have been limited by the substantial heterogeneity in progression and anatomical spread that are endemic of the disease. Neuroimaging biomarkers represent powerful additions to the current monitoring repertoire but have yielded inconsistent associations with clinical scores like the ALS functional rating scale. The D50 disease progression model was developed to address limitations with clinical indices and the difficulty obtaining longitudinal data in ALS. It yields overall disease aggressiveness as time taken to reach halved functionality (D50); individual disease covered in distinct phases; and calculated functional state and calculated functional loss as acute descriptors of local disease activity. It greatly reduces the noise of the ALS functional rating scale and allows the comparison of highly heterogeneous disease and progression subtypes. In this study, we performed Voxel-Based Morphometry for 85 patients with ALS (60.1±11.5 years, 36 female) and 62 healthy controls. Group-wise comparisons were performed separately for gray matter and white matter using ANCOVA testing with threshold-free cluster enhancement. ALS-related widespread gray and white matter density decreases were observed in the bilateral frontal and temporal lobes (p<0.001, family-wise error corrected). We observed a progressive spread of structural alterations along the D50-derived phases, that were primarily located in frontal, temporal and occipital gray matter areas, as well as in supratentorial neuronal projections (p<0.001 family-wise error corrected). ALS patients with higher overall disease aggressiveness (D50 < 30 months) showed a distinct pattern of supratentorial white matter density decreases relative to patients with lower aggressiveness; no significant differences were observed for gray matter density (p<0.001 family-wise error corrected). The application of the D50 disease progression model separates measures of disease aggressiveness from disease accumulation. It revealed a strong correlation between disease phases and in-vivo measures of cerebral structural integrity. This study underscores the proposed corticofugal spread of cerebral pathology in ALS. We recommend application of the D50 model in studies linking clinical data with neuroimaging correlates.

White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study.

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n = 23), weight-recovered women with a past diagnosis of AN (recAN: n = 23), and age-matched healthy control women (HC: n = 24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxelwise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold-free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Clusterwise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for clusterwise AD and RD. Trait-based increases in diffusivity, changes in which have been associated with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.

Evaluating Alternative Correction Methods for Multiple Comparison in Functional Neuroimaging Research.

A significant challenge for fMRI research is statistically controlling for false positives without omitting true effects. Although a number of traditional methods for multiple comparison correction exist, several alternative tools have been developed that do not rely on strict parametric assumptions, but instead implement alternative methods to correct for multiple comparisons. In this study, we evaluated three of these methods, Statistical non-Parametric Mapping (SnPM), 3DClustSim, and Threshold Free Cluster Enhancement (TFCE), by examining which method produced the most consistent outcomes even when spatially-autocorrelated noise was added to the original images. We assessed the false alarm rate and hit rate of each method after noise was applied to the original images.

Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue

Post-stroke fatigue has a significant impact on stroke survivors’ mental and physical well-being. Our recent clinical trial showed significant reduction of post-stroke fatigue with modafinil treatment, however functional connectivity changes in response to modafinil have not yet been explored in stroke survivors with post-stroke fatigue. Twenty-eight participants (multidimensional fatigue inventory-20 ≥ 60) had MRI scans at baseline, and during modafinil and placebo treatment. Resting-state functional MRI data were obtained, and independent component analysis was used to extract functional networks. Resting-state functional connectivity (rsFC) was examined between baseline, modafinil and placebo treatment using permutation testing with threshold-free cluster enhancement. Overall twenty-eight participants (mean age: 62 ± 14.3, mean baseline MFI-20: 72.3 ± 9.24) were included. During modafinil treatment, increased rsFC was observed in the right hippocampus (p = 0.004, 11 voxels) compared to placebo. This coincided with lower rsFC in the left frontoparietal (inferior parietal lobule, p = 0.023, 13 voxels), somatosensory (primary somatosensory cortex; p = 0.009, 32 voxels) and mesolimbic network (temporal pole, p = 0.016, 35 voxels). In conclusion, modafinil treatment induces significant changes in rsFC in post-stroke fatigue. This modulation of rsFC may relate to a reduction of post-stroke fatigue; however, the relationship between sensory processing, neurotransmitter expression and fatigue requires further exploration.

Abnormal resting-state regional homogeneity in unmedicated bipolar II disorder

BackgroundPrevious studies demonstrated that patients with bipolar disorder (BD) exhibited abnormal neural activity in multiple brain regions. However, no study has been conducted to identify regional intrinsic neural activity changes in BD II. In the present study, we used the regional homogeneity (ReHo) approach to explore the regional abnormal neural activity in bipolar II disorder MethodsOne hundred unmedicated patients with BD II depression and 100 healthy controls (HC) underwent the resting-state functional magnetic resonance imaging. The ReHo values of each voxel was calculated in the whole brain. The two-sample t-test and threshold-free cluster enhancement (TFCE) correction were applied for the ReHo analysis. ResultsCompared with the HC group, the BD II group showed significantly decreased ReHo in the left orbitofrontal cortex, and increased ReHo in the right precentral gyrus, right supplementary motor area and bilateral middle occipital gyrus (P < .05, TFCE corrected). LimitationsThis study lacks the evidence of brain structural changes, and used the cross-sectional design which did not explore local alterations of remitted and manic patients. ConclusionOur findings revealed abnormal local intrinsic neural activity during resting state which may contribute to the pathophysiology of bipolar II disorder. Particularly the disrupted balance between the prefrontal cortex and primary sensorimotor regions provides evidence for the unique pathological mechanism underlying BD.

Microstructural White Matter Alterations in Mild Cognitive Impairment and Alzheimer's Disease : Study Based on Neurite Orientation Dispersion and Density Imaging (NODDI).

To investigate microstructural alterations in white matter in mild cognitive impairment (MCI) and Alzheimer's disease (AD) using neurite orientation dispersion and density imaging (NODDI) and to assess the potential diagnostic performance of NODDI-derived parameters. In this study 14 MCI patients, 14 AD patients, and 14 healthy controls (HC) were recruited. The diffusion tensor imaging(DTI)-derived fractional anisotropy (FA) and NODDI-derived neurite density index (NDI), orientation dispersion index (ODI), and volume fraction of isotropic water molecules (Viso) were calculated from the diffusion data. The tract-based spatial statistics (TBSS) method was used for statistical analysis with one-way ANOVA. The correlations between the parameter values and mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scores were examined. Areceiver operating characteristic (ROC) curve was conducted to assess the diagnostic performance of different parameters. Compared with the HC group, the NDI and ODI values decreased significantly and the Viso values were significantly increased in the MCI and AD groups (p < 0.01, threshold-free cluster enhancement (TFCE)-corrected); however, there were no significant differences in FA values in the MCI group. The NDI, ODI, and Viso values of multiple fibers were significantly correlated with MMSE and MoCA scores. For the diagnosis of AD, the area under the ROC curve (AUC) for the NDI value of the splenium of corpus callosum was larger than the FA value (AUC = 0.885, 0.714, p = 0.042). The AUC of the Viso value of the right cerebral peduncle was larger than FA value (AUC = 0.934, 0.531, p = 0.004). The NDI is more sensitive to white matter microstructural changes than FA and NODDI could be superior to DTI in the diagnosis of AD.

Ischemic Stroke in Pontine and Corona Radiata: Location Specific Impairment of Neural Network Investigated With Resting State fMRI.

Objective: This study aims to investigate location-specific functional remodeling following ischemic stroke in pons and corona radiata.Methods: This study was approved by the local Institutional Review Board. Written consent was obtained from each of the participants prior to the MRI examination. Thirty six subjects with first ever acute ischemic stroke in pons (PS, n = 15, aged 62.8 ± 11.01 years) or corona radiata (CRS, n = 21, aged 59.33 ± 13.84 years) as well as 30 age and sex matched healthy controls (HC, n = 30, aged 60 ± 6.43 years) were examined with resting state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and degree centrality (DC) were calculated using a voxel-based approach. Intergroup differences in ReHo and DC were explored using a permutation test with a threshold-free cluster enhancement (PT TFCE, number of permutations = 1,000, family-wise error rate (FWER) < 0.05).Results: ReHo and DC alterations were identified in distributed anatomies for both PS and CRS groups. DC mainly increased in the bilateral anterior and posterior cingulate cortex, the inferior frontal-orbital gyrus, and decreased in the bilateral cuneus, calcarine, and the precuneus, while ReHo mainly decreased in the precentral and the postcentral gyri, inferior parietal lobules, precuneus, posterior cingulate cortex, and the superior occipital gyrus. PS and CRS groups were not significantly different in ReHo or DC (FWER > 0.05).Conclusions: Focal ischemic stroke in pons or corona radiata leads to extensive alterations in the functional network centrality. IS-induced network remodeling is more anatomy-specific than pathway-specific, which may underpin the clinicotopographical profiles during the disease dynamic. Approaches targeting neural pathway and functional connectivity may shed light on a better characterization and management innovation of ischemic stroke.

Whole-brain microstructural white matter alterations in borderline personality disorder patients.

Borderline personality disorder (BPD) is a psychiatric condition associated with the impairment of the frontolimbic network. However, a growing body of studies suggests that brain dysfunction underling BPD could involve other brain areas. We explored the whole-brain white matter (WM) organization in BPD patients to clarify the structural pattern underlying the disease and its relationship with clinical features. Fourteen BPD patients and 14 healthy controls underwent a multidimensional clinical assessment and diffusion tensor imaging acquisition. Measures of fractional anisotropy (FA) and mean, axial and radial (RD) diffusivity were collected, and alterations in the WM were assessed using the voxelwise approach, including substance and alcohol abuse as covariates. Voxelwise regression analysis was performed to identify associations between microstructural changes and clinical feature in BPD. Group comparisons showed alterations only for FA and RD: FA decreased in the right posterior hemisphere, while RD increased bilaterally and widespread in anterior and posterior areas (p<0.05, threshold-free cluster enhancement corrected). Moreover, WM alterations of the corpus callosum were related to anxiety in BPD group. Our data support the idea that structural alterations underling BPD also involve cortico-cortical pathways, corticothalamic and corticostriatal tracts, suggesting that the frontolimbic model should be reinterpreted. © 2019 John Wiley & Sons, Ltd.

A search for cortical correlates of trait impulsivity in Parkinson´s disease

BackgroundImpulsivity is an enduring personality trait that is highly relevant for the development of neuropsychiatric disorders. Although impulse control disorders (ICD) are well-characterized non-motor features in Parkinson’s disease (PD), mainly related to medication, little is known about neural correlates reflecting trait aspects of impulsivity in PD patients. Here, we address the question whether motor, attentional and non-planning components, measured by the Barratt Impulsiveness Scale (BIS-11), are distinctly related to cortical thickness and cortical folding abnormalities in PD when compared to age-matched healthy controls (HC). MethodWe investigated cortical thickness (CT) and complexity of cortical folding (CCF) in 22 PD patients with moderately advanced disease stages without ICD and 18 HC using high-resolution structural magnetic resonance imaging (MRI) data. Surface-based data analysis was driven by CAT12 toolbox. ResultsPD patients showed widespread CT loss in frontal, cingulate, temporo-parietal and occipital regions (FDR corrected at p < 0.05 using threshold-free cluster enhancement). Significant differences in CCF between groups were not found. Using a multiple regression model, CT in inferior and superior frontal, anterior cingulate and precentral regions significantly predicted BIS attentional subscores (p = 0.041). ConclusionThese data suggest a specific cortical trajectory associated with impulsivity in moderately advanced staged PD patients. The attentional dimension of trait impulsivity appears to be specifically related to CT, in contrast to alterations of early neurodevelopmental markers, i. e. CCF. Our results shed light on structural correlates of trait impulsivity in PD patients and establish a baseline for future research into neural risk factors potentially predisposing to ICD development.

Left temporal plane growth predicts language development in newborns with congenital heart disease.

Congenital heart defects are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits in higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. Forty-four newborns were included in our study, of whom 33 were diagnosed with dextro-transposition of the great arteries and 11 with other forms of severe congenital heart defects. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 ± 7.03 days apart. MRI was performed in natural sleep on a 3.0 T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation-based morphometry, we calculated brain growth rate maps reflecting average daily growth occurring between pre- and postoperative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the Heschl's gyrus, anterior planum temporale and language score at 12 months of age, corrected for demographic variables (P = 0.018, t = 5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacted with this correlation, longer hospitalization resulted in faster enlargement of the internal CSF spaces. Our longitudinal cohort study provides evidence for the early importance of left-dominant perisylvian regions in auditory and language development before direct postnatal exposure to native language. In congenital heart disease patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at 1 year of age.