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Major depressive disorder (MDD) is a clinically heterogeneous disorder. Its mechanism is still unknown. Although the altered intersubject variability in functional connectivity (IVFC) within gray‐matter has been reported in MDD, the alterations to IVFC within white‐matter (WM‐IVFC) remain unknown. Based on the resting‐state functional MRI data of discovery (145 MDD patients and 119 healthy controls [HCs]) and validation cohorts (54 MDD patients, and 78 HCs), we compared the WM‐IVFC between the two groups. We further assessed the meta‐analytic cognitive functions related to the alterations. The discriminant WM‐IVFC values were used to classify MDD patients and predict clinical symptoms in patients. In combination with the Allen Human Brain Atlas, transcriptome‐neuroimaging association analyses were further conducted to investigate gene expression profiles associated with WM‐IVFC alterations in MDD, followed by a set of gene functional characteristic analyses. We found extensive WM‐IVFC alterations in MDD compared to HCs, which were associated with multiple behavioral domains, including sensorimotor processes and higher‐order functions. The discriminant WM‐IVFC could not only effectively distinguish MDD patients from HCs with an area under curve ranging from 0.889 to 0.901 across three classifiers, but significantly predict depression severity (r = 0.575, p = 0.002) and suicide risk (r = 0.384, p = 0.040) in patients. Furthermore, the variability‐related genes were enriched for synapse, neuronal system, and ion channel, and predominantly expressed in excitatory and inhibitory neurons. Our results obtained good reproducibility in the validation cohort. These findings revealed intersubject functional variability changes of brain WM in MDD and its linkage with gene expression profiles, providing potential implications for understanding the high clinical heterogeneity of MDD. [ABSTRACT FROM AUTHOR]

Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white‐matter fibers in the brain. However, few studies have focused on white‐matter functional changes in schizophrenia. Considering that converging evidence suggests that white‐matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white‐matter network‐level interactions in antipsychotic‐naive first‐episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white‐matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network‐level interactions among these 11 white‐matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network‐based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white‐matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white‐matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white‐matter functional abnormalities. [ABSTRACT FROM AUTHOR]

Researchers in the field of child neurology are increasingly looking to supplement clinical trials of motor rehabilitation with neuroimaging in order to better understand the relationship between behavioural training, brain changes, and clinical improvements. Randomised controlled trials are typically accompanied by sample size calculations to detect clinical improvements but, despite the large cost of neuroimaging, not equivalent calculations for concurrently acquired imaging neuroimaging measures of changes in response to intervention. To aid in this regard, a power analysis was conducted for two measures of brain changes that may be indexed in a trial of rehabilitative therapy for cerebral palsy: cortical thickness of the impaired primary sensorimotor cortex, and fractional anisotropy of the impaired, delineated corticospinal tract. Power for measuring fractional anisotropy was assessed for both region-of-interest-seeded and fMRI-seeded diffusion tractography. Taking into account practical limitations, as well as data loss due to behavioural and image-processing issues, estimated required participant numbers were 101, 128 and 59 for cortical thickness, region-of-interest-based tractography, and fMRI-seeded tractography, respectively. These numbers are not adjusted for study attrition. Although these participant numbers may be out of reach of many trials, several options are available to improve statistical power, including careful preparation of participants for scanning using mock simulators, careful consideration of image processing options, and enrolment of as homogeneous a cohort as possible. This work suggests that smaller and moderate sized studies give genuine consideration to harmonising scanning protocols between groups to allow the pooling of data. [ABSTRACT FROM AUTHOR]

Background: Alexithymia has been frequently associated with major depression disorders (MDD). Yet little is known about the exact relationship of alexithymia and MDD. In order to explore this subject matter, the neural connectivity associated with alexithymia in people with MDD and matched nonclinical controls were compared.Methods: Twenty-two females diagnosed with first-episode MDD and twenty-one matched nonclinical controls were MRI brain-scanned with diffusion-tensor-imaging and resting-state-functional-imaging methods, and self-reported the Chinese 20-item Toronto Alexithymia Scale.Results: Voxel-wise multiple regression analysis showed a group interaction effect regarding the correlation between white-matter-connectivity and alexithymia. Significant correlations were observed at the corpus-callosum in MDDs and at the right superior-longitudinal-fasciculus in the controls. These findings were then used to derive seeds for analyzing resting-state-functional-connectivity in each group separately. The results further revealed that alexithymia in MDDs were associated with reduced functional-connectivity in the right precentral-gyrus and several regions of the brain on the right which are associated with cognitive regulation in the default-mode-network. In contrast, among the control subjects, alexithymia was correlated with increased functional-connectivity between the right inferior-frontal-gyrus-triangularis and the right superior-occipital-lobe, which is associated with emotional response to external stimuli.Limitations: Better participant selection, especially recruitment of medication-free samples, and the engagement of additional alexithymia assessments, should be considered in future investigations.Conclusions: These findings supported our a priori hypothesis that MDDs and controls have distinct white-matter correlates of alexithymia, and these corresponded to the existing proposed neural correlates for the cognitive and affective characteristics of alexithymia respectively. Extended impacts of these microstructural changes on remote functional networks might help explain the distinct behavioral characteristics of alexithymia for these groups, as well as implications for therapeutic intervention of MDD. [ABSTRACT FROM AUTHOR]

Coeliac disease (CD) is an autoimmune disease of small intestine associated with sensitivity to gluten. The clinical manifestations are often of gastrointestinal nature, although the disease may be present asymptomatically as well. It is a chronic disease and in the absence of overt neurological involvement, extended gluten exposure may give rise to silent or subtle morphological and white-matter changes in central nervous system. The present study investigates such changes using brain volumetry and the assessment of white-matter tissue in CD patients without neurological symptoms. Seventeen CD patients without any neurological involvement were included in the study and went under neurological evaluation and anatomical MRI. Individual gray- and white-matter, and subcortical structure volumes were acquired for using automated volumetric analyses. The observed white-matter hyperintensities (WMH) evaluated using Age-Related White-Matter Changes scale. Findings show a bilateral decrease in cortical gray-matter and caudate nuclei volumes in CD compared to controls. Negative correlations were found between the duration of the disease and the volumes of the affected regions. Cerebellum was seemingly unaffected. In addition, significantly higher proportion of WMH was found in CD patients, specifically in bilateral frontal and occipitoparietal cortices. We observed a significant gray-matter and caudate nucleus atrophy in the CD patients in the absence of marked neurological symptoms. Present findings point out to a need for histopathological investigations potentially focusing on anti-TG2 antibodies, and serial volumetric analyses on the CD-related cortical and subcortical changes. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral white matter hyperintensities (WMHs) detected on magnetic resonance imaging scans are frequently seen in both Alzheimer's disease (AD) and depression patients and believed to play an important role in cognition and mood. Depressive symptoms and depression may accompany AD in all stages of the disease. The aim of the study was to evaluate the relationship of regional WMHs with depressive symptoms, cognitive status, medial temporal lobe atrophy, and daily living activities in early-stage AD patients. Methods: Forty-five patients with very mild or mild AD were examined. All subjects underwent MRI and were assessed by the Geriatric Depression Scale (GDS) and the Addenbrooke's Cognitive Examination-Revised (ACE-R) for the evaluation of depressive symptom severity and cognitive status, respectively. The patients were divided into two groups based on the selected cut-off point in the GDS. CDR sum of the boxes (CDR-sb) scores were calculated as a measure of activities of daily living (ADLs). MRI T2-FLAIR slices were used to rate the white-matter lesions according to the Age-Related White Matter Changes Rating Scale, assessing the WMHs in frontal, parietooccipital, temporal, infratentorial and basal ganglia areas individually. Medial temporal lobe atrophy was assessed with high-resolution T1 images using visual rating scale. Results: In the depressive group, frontal WMH scores were found to be higher than in the non-depressive group (p=0.006). ACE-r, CDR-sb and medial temporal lobe atrophy scores did not differ among the groups. CDR-sb scores showed a significant correlation with frontal WMH scores (left frontal WMH r=0.439, p=0.003, right frontal AMH r=0.459, p=0.001). Linear regression models revealed the effect of WMHs on depressive symptoms among the other factors including age, functionality and atrophy in the medial temporal areas. Discussion: Our findings underscore the potential role of regional, particularly frontal AMHs in depressive symptoms and functionality of the early AD patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Structural abnormalities in the callosal fibers connecting the heteromodal association areas of the prefrontal and temporoparietal cortices bilaterally have been suggested to play a role in the etiology of schizophrenia. Aims: To investigate for geometric abnormalities in these callosal fibers in schizophrenia patients by using a novel Diffusion-Tensor Imaging (DTI) metric of fiber geometry named Shape-Normalized Dispersion (SHD). Methods: DTIs (3T, 51 gradient directions, 1.7mm isotropic voxels) were acquired from 26 schizophrenia patients and 23 matched healthy controls. The prefrontal and temporoparietal fibers of the corpus callosum were extracted by means of whole-brain tractography, and their mean SHD calculated. Results: The schizophrenia patients exhibited subnormal levels of SHD in the prefrontal callosal fibers when controlling for between-group differences in Fractional Anisotropy. Reduced SHD could reflect either irregularly turbulent or inhomogeneously distributed fiber trajectories in the corpus callosum. Conclusions: The results suggest that the transcallosal misconnectivity thought to be associated with schizophrenia could reflect abnormalities in fiber geometry. These abnormalities in fiber geometry could potentially be underpinned by neurodevelopmental irregularities. [Copyright &y& Elsevier]

Background: Schizophrenia is believed to result from abnormal functional integration of neural processes thought to arise from aberrant brain connectivity. However, evidence for anatomical dysconnectivity has been equivocal, and few studies have examined axonal fiber connectivity in schizophrenia at the level of whole-brain networks. Methods: Cortico-cortical anatomical connectivity at the scale of axonal fiber bundles was modeled as a network. Eighty-two network nodes demarcated functionally specific cortical regions. Sixty-four direction diffusion tensor-imaging coupled with whole-brain tractography was performed to map the architecture via which network nodes were interconnected in each of 74 patients with schizophrenia and 32 age- and gender-matched control subjects. Testing was performed to identify pairs of nodes between which connectivity was impaired in the patient group. The connectional architecture of patients was tested for changes in five network attributes: nodal degree, small-worldness, efficiency, path length, and clustering. Results: Impaired connectivity in the patient group was found to involve a distributed network of nodes comprising medial frontal, parietal/occipital, and the left temporal lobe. Although small-world attributes were conserved in schizophrenia, the cortex was interconnected more sparsely and up to 20% less efficiently in patients. Intellectual performance was found to be associated with brain efficiency in control subjects but not in patients. Conclusions: This study presents evidence of widespread dysconnectivity in white-matter connectional architecture in a large sample of patients with schizophrenia. When considered from the perspective of recent evidence for impaired synaptic plasticity, this study points to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: In this study stereotaxic injections of the vasoconstrictive peptide endothelin-1 (ET-1) were used to create infarcts in the white matter of the internal capsule underlying sensorimotor cortex in rats. Resulting deficits were assessed using established sensorimotor tests conducted on each rat before and after the ET-1-induced infarct. After a 14-day survival period, histological examination revealed tissue necrosis and demyelination in the infarcted white matter of ET-1-injected rats, but not saline-injected control rats. Infarcts resulted in measurable sensorimotor deficits in rats that received ET-1 injections. The same sensorimotor tests showed no deficits in surgical-control rats. The present model of white matter infarct should be valuable in examining the underlying mechanisms of subcortical ischemic stroke and to evaluate potential therapeutic interventions. [Copyright &y& Elsevier]