UNASSIGNED: Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear.
UNASSIGNED: We applied Warped Bayesian Linear Regression normative models to T1-weighted magnetic resonance imaging data and mapped inter-individual variability in person-specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive-compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter-regional connections, specific brain regions, and spatially extended brain networks.
UNASSIGNED: The specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large-scale networks in up to 35% of individuals.
UNASSIGNED: The prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxel-wise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders.

OBJECTIVE: In this study, we aimed to compare the Fazekas scoring system and quantitative white matter hyperintensity volume in the classification of white matter hyperintensity severity using a fully automated analysis software to investigate the reliability of quantitative evaluation.
METHODS: Patients with suspected cognitive impairment who underwent medical examinations at our institution between January 2010 and May 2021 were retrospectively examined. White matter hyperintensity volumes were analyzed using fully automated analysis software and Fazekas scoring (scores 0-3). Using one-way analysis of variance, white matter hyperintensity volume differences across Fazekas scores were assessed. We employed post-hoc pairwise comparisons to compare the differences in the mean white matter hyperintensity volume between each Fazekas score. Spearman\'s rank correlation test was used to investigate the association between Fazekas score and white matter hyperintensity volume.
RESULTS: Among the 839 patients included in this study, Fazekas scores 0, 1, 2, and 3 were assigned to 68, 198, 217, and 356 patients, respectively. White matter hyperintensity volumes significantly differed according to Fazekas score (F=623.5, p<0.001). Post-hoc pairwise comparisons revealed significant differences in mean white matter hyperintensity volume between all Fazekas scores (p<0.05). We observed a significantly positive correlation between the Fazekas scores and white matter hyperintensity volume (R=0.823, p<0.01).
CONCLUSIONS: Quantitative white matter hyperintensity volume and the Fazekas scores are highly correlated and may be used as indicators of white matter hyperintensity severity. In addition, quantitative analysis may be more effective in classifying advanced white matter hyperintensity lesions than the Fazekas classification.

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Premenstrual dysphoric disorder (PMDD) is a mood disorder for which selective progesterone receptor modulator (SPRM) treatment has been demonstrated to be beneficial. The neural signatures of this treatment have been so far identified as greater fronto-cingulate reactivity during aggressive response to provocation, but no changes in terms of gray matter structure. White matter has recently been found to differ between patients with PMDD and healthy controls. The present study thus sought to investigate the relationship between white matter volume and SPRM treatment in patients with PMDD. A pharmaco-neuroimaging study was conducted on patients with PMDD participating in a randomized controlled trial. Participants underwent magnetic resonance imaging before and after treatment randomization to ulipristal acetate (an SPRM), or placebo, for three months. The interaction effect of treatment by time on white matter volume (WMV) was assessed. Voxel based morphometry analyses were performed on both a whole brain exploratory level and on regions of interest. No treatment effect was observed on WMV in any region, including the anterior thalamic radiations, cingulum, forceps minor, fornix, inferior fronto-occipital fasciculus, superior cerebellar peduncle, superior longitudinal fasciculus, and uncinate fasciculus. This is the first finding to indicate that no white matter volume alterations follow three-month progesterone antagonism, suggesting that white matter volume does not participate in symptom relief upon SPRM treatment for PMDD.

UNASSIGNED: Longer sleep duration in infancy supports cognitive and affective functioning - likely through effects on brain development. From childhood through old age, there is evidence for a close link between sleep and brain volume. However, little is known about the association between sleep duration and brain volume in infancy, a developmental period of unprecedented brain maturation. This study aimed to close this gap by assessing sleep duration across the first year of life and gray and white matter volume at 12-mo age.
UNASSIGNED: Infant sleep duration trajectories across the first year of life were based on maternal reports at 1, 3, 6, 9, and 12 months of age. Infant specific trajectories were generated by running a logarithmic regression for each infant and residualizing the resulting slopes for their intercept. Structural magnetic resonance imaging (MRI) scans were acquired at 12-mo age. Gray and white matter volume estimates were residualized for intracranial volume and age at scan.
UNASSIGNED: Data to calculate sleep trajectories was available for 112 infants. Overall, sleep duration decreased over the course of the first year of life and was best described by a logarithmic function. Of these infants, data on brain volume was available for 45 infants at 12-mo age. Infants whose sleep duration decreased less during the first year of life relative to their intercept had, on average, greater white matter volume (β = .36, p = .02). Furthermore, average sleep duration across the first year of life, and sleep duration specifically at 6 and 9 months were positively associated with white matter volume. Sleep duration during the first year of life was not significantly associated with gray matter volume at 12-mo age.
UNASSIGNED: Sufficient sleep duration may benefit infant white matter development - possibly by supporting myelination. The fact that sleep duration was not associated with gray matter volume is in line with preclinical studies suggesting that sleep may be crucial for the balance between synaptogenesis and synaptic pruning but not necessarily relate to a net increase in gray matter volume. Supporting sleep during periods of rapid brain development and intervening in case of sleep problems may have long-term benefits for cognitive function and mental health.

UNASSIGNED: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group.
UNASSIGNED: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term.
UNASSIGNED: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05).
UNASSIGNED: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.

UNASSIGNED: White matter hyperintensities (WMH) are a key imaging feature of cerebral small-vessel disease (CSVD). However, there is a lack of standardized methods for determining WMH volume, and the value of total white matter (WM) volume in the assessment of cognitive impairment in patients with CSVD remains unknown.
UNASSIGNED: We aimed to explore the correlations of WMH volume and WM volume with cognitive dysfunction and its components in patients with CSVD. We also aimed to compare the value of the Fazekas score, WMH volume, and ratio of WMH volume to total WM volume in the assessment of cognitive dysfunction.
UNASSIGNED: The study included 99 patients with CSVD. Patients were categorized into following groups based on MoCA scores: patients with mild cognitive impairment and those without. Brain magnetic resonance images were processed to investigate differences in WMH and WM volumes between the groups. Logistic regression analysis was used to determine whether these two factors were independent risk factors for cognitive dysfunction. Correlation analysis was used to examine the relationships of WMH and WM volume with different types of cognitive impairment. Receiver operating characteristic curves were used to compare the effectiveness of the WMH score, WMH volume, and WMH to WM ratio for evaluating cognitive dysfunction.
UNASSIGNED: There were significant differences in age, education level, WMH volume, and WM volume between the groups (P < 0.05). After adjusting for age and education, the multivariate logistic analysis indicated that both WMH volume and WM volume were independent risk factors for cognitive dysfunction. Correlation analysis indicated that WMH volume was mainly related to cognition involving the visual space and delayed recall. WM volume was not strongly associated with different types of cognitive dysfunction. The WMH to WM ratio was the strongest predictor, with an area under the curve value of 0.800 and a 95% confidence interval of 0.710-0.891.
UNASSIGNED: Increases in WMH volume may aggravate cognitive dysfunction in patients with CSVD, and a higher WM volume may reduce the effect of WMH volume on cognitive function to a certain extent. The ratio of WMH to total WM volume may reduce the impact of brain atrophy, allowing for more accurate evaluation of cognitive dysfunction in older adults with CSVD.

BACKGROUND: Patients with acquired, idiopathic olfactory dysfunction (OD) commonly undergo magnetic resonance imaging (MRI) evaluation to rule out intracranial pathologies. This practice is highly debated given the expense of MRI relative to the probability of detecting a treatable lesion. This, combined with the increasing use of MRI in research to investigate the mechanisms underlying OD, provided the impetus for this comprehensive review.
OBJECTIVE: The purpose of this systematic review was to both assess the utility of MRI in diagnosis of idiopathic OD and to describe MRI findings among mixed OD etiologies to better understand its role as a research tool in this patient population.
METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for studies with original MRI data for patients with OD was completed. Studies exclusively investigating patients with neurocognitive deficits or those studying traumatic or congenital etiologies of OD were excluded.
RESULTS: From 1758 candidate articles, 33 studies were included. Four studies reviewed patients with idiopathic OD for structural pathologies on MRI, of which 17 of 372 (4.6%) patients had a potential central cause identified, and 3 (0.8%) had an olfactory meningioma or olfactory neuroblastoma. Fourteen studies (42.4%) reported significant correlation between olfactory bulb volume and olfactory outcomes, and 6 studies (18.8%) reported gray matter volume reduction, specifically in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal, and piriform cortex areas, in patients with mixed OD etiologies. Functional MRI studies reported reduced brain activation and functional connectivity in olfactory network areas.
CONCLUSIONS: MRI uncommonly detects intracranial pathology in patients with idiopathic OD. Among patients with mixed OD etiologies, reduced olfactory bulb and gray matter volume are the most common abnormal findings on MRI. Further research is required to better understand the role of MRI and its cost-effectiveness in patients with acquired, idiopathic OD.

Recently, the abuse of ketamine has soared. Therefore, it is of great importance to study its potential risks. The effects of prolonged ketamine on the brain can be observationally studied in chronic recreational users. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. We searched the following electronic databases: Medline, Embase and PsycINFO We screened 11,438 records and 16 met inclusion criteria, totaling 440 chronic recreational ketamine users (2-9.7 years; mean use 2.4 g/day), 259 drug-free controls and 44 poly-drug controls. Long-term recreational ketamine use was associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity. The observed differences in both structural and functional neuroanatomy between ketamine users and controls may explain some of its long-term cognitive and psychiatric side effects, such as memory impairment and executive functioning. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse.

UNASSIGNED: The objective of this study was to evaluate whether altered gray matter volume (GMV) and white matter volume (WMV) are associated with the presence of cerebral microbleeds (CMBs) in cerebral small vessel disease (CSVD).
UNASSIGNED: In this study, we included 26 CSVD patients with CMBs (CSVD-c), 43 CSVD patients without CMBs (CSVD-n) and 39 healthy controls. All participants underwent cognitive assessment testing. Both univariate analysis and multivariate pattern analysis (MVPA) approaches were applied to investigate differences in brain morphometry among groups.
UNASSIGNED: In univariate analysis, GMV and WMV differences were compared among groups using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL). Compared to healthy controls, the CSVD-c group and CSVD-n group showed significantly lower GMV than the control group in similar brain clusters, mainly including the right superior frontal gyrus (medial orbital), left anterior cingulate gyrus, right inferior frontal gyrus (triangular part) and left superior frontal gyrus (medial), while the CSVD-n group also showed significantly lower WMV in the cluster of the left superior frontal gyrus (medial). No significant GMV or WMV differences were found between the CSVD-c group and the CSVD-n group. Specifically, we applied the multiple kernel learning (MKL) technique in MVPA to combine GMV and WMV features, yielding an average of >80% accuracy for three binary classification problems, which was a considerable improvement over the individual modality approach. Consistent with the univariate analysis, the MKL weight maps revealed default mode network and subcortical region damage associated with CSVD compared to controls. On the other hand, when classifying the CSVD-c group and CSVD-n group in the MVPA analysis, we found that some WMVs were highly weighted regions (left olfactory cortex and right middle frontal gyrus), which hinted at the presence of different white matter alterations in the CSVD-c group.
UNASSIGNED: Our findings not only suggested that the localized alterations in GMV and WMV appeared to be associated with the pathophysiology of CSVD but also indicated that altered brain morphometry could be a potential discriminative pattern to detect CSVD at the individual level.