Diffeomorphic Anatomical Registration Research Articles

To explore the potential mechanisms of cognitive impairment in children with MRI-negative pharmacoresistant epilepsy due to focal cortical dysplasia: A pilot study from gray matter structure view

ObjectivesTo investigate the characteristics of brain structure in children with focal cortical dysplasia (FCD)-induced pharmacoresistant epilepsy, and explore the potential mechanisms of cognitive impairment from the view of gray matter alteration. Methods25 pharmacoresistant pediatric patients with pathologically confirmed focal cortical dysplasia (FCD), and 25 gender-matched healthy controls were included in this study. 3.0T MRI data and intelligence tests using the Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV) were generated for all subjects. Voxel-based morphometry (VBM)-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) and surface-based morphometry (SBM) analyses were performed to analyze gray matter volume and cortical structure. Two-sample t-tests were used to compare the differences in gray matter volume (P＜0.05, FWE) and cortical thickness (P＜0.001, FWE) between the two groups. Also, the Spearman rank correlation analyses were employed to determine the relationship between structural alterations and neuropsychological results. ResultsThe WISC-IV scores of the FCD group were significantly lower than those of the HC group in terms of full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) (all P＜0.01). Compared with the HC group, in the FCD group, the gray matter volume (GMV) reduced significantly in the left cerebellum_8, cerebellum_Crus2, and bilateral thalamus (P＜0.05, FWE); the GMV increased in the bilateral medial frontal gyrus, right precuneus, and left inferior temporal gyrus (P＜0.05, FWE), and the cortical thickness increased in the bilateral frontal, parietal, and temporal areas (P＜0.001, FWE). Correlation analyses showed that the age of seizure onset had positive correlations with the WISC-IV scores significantly. Meanwhile, the cortex thicknesses of the left pars opercularis gyrus, left middle temporal gyrus, and right inferior temporal gyrus had negative correlations with the WISC-IV scores significantly. ConclusionFCD patients showed subtle structural abnormalities in multiple brain regions, with significant involvement of the primary visual cortex and language function cortex. And we also demonstrated a crucial correlation between gray matter structural alteration and cognitive impairment.

A Potential Mechanism of Neurological Impairment in Children With Infantile Spasm: Based on Microanatomic Structure Analysis Employing Voxel-Based Morphometry and Surface-Based Morphometry

BackgroundInfantile epileptic spasms syndrome (IESS) would accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microwould accompany with severe neurological impairment. Our study aimed to explore the potential mechanism by employing voxel-based and surface-based morphometry to detect brain microanatomic structure alteration. MethodsThe IESS group had 21 males and 13 females (mean age: 17.7 ± 15.6 months), whereas the healthy controls group had 22 males and 10 females (mean age: 29.4 ± 18.7 months). High-resolution 3D T1WI was performed. Computational Anatomy Toolbox implemented in Statistical Parametric Mapping 12 was used to measure the gray matter and white matter volume, and the cortical thickness separately. Independent sample t test was used to assess between-group differences. IESS group was assessed using the Bayley Scales of Infant Development. ResultsThe IESS group showed a significantly decreased volume of gray matter in right middle temporal gyrus, inferior temporal gyrus, superior temporal gyrus, right fusiform, and bilateral precuneus (P < 0.001). There were no significant between-group differences with respect to white matter volume or cortical thickness (P > 0.001). The results of Bayley Scales of Infant Development showed that the Mental Development Index (MDI) and Psychomotor Development Index scores of children with IESS were almost concentrated in the range of <70. MDI score showed a positive correlation with gray matter reduction area in IESS group. ConclusionChildren with IESS had impaired cognitive and delayed motor development. And the decreased gray matter in the right temporal lobe, fusiform, and bilateral precuneus could be the potential anatomic basis for impaired function, such as hearing, visual, and language.

Gray matter differences associated with menopausal hormone therapy in menopausal women: a DARTEL-based VBM study

Menopausal hormone therapy (MHT) in women can reduce troublesome menopause symptoms and prevent cognitive decline. This cross-sectional study investigated the MHT-related effect on brain morphology and its association with sex hormones in menopausal women by using an optimized diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL)-based voxel-based morphometry (VBM) method. Twenty-one menopausal women without MHT (noMHT) and 20 menopausal women with MHT were included in this study. Magnetic resonance imaging data were processed using SPM 12 with DARTEL-based VBM whole brain analysis approach. A 2-sample t-test and analysis of covariance (ANCOVA) adjusting for age and total intracranial volume were used to compare GM volume between noMHT and MHT women. The association between MHT (treatment period, hormones levels) and brain volume variations were analyzed by Spearman correlation. MHT women showed significantly larger volumes of the superior/middle/inferior frontal gyri, hypothalamus, inferior temporal gyrus, parahippocampal gyrus, hippocampus, cerebellar cortex, postcentral gyrus, precuneus, angular gyrus, supplementary motor area, superior occipital gyrus, and precentral gyrus compared to the noMHT women. The volumes of the angular gyrus and hypothalamus in MHT women positively correlated with treatment period. On the other hand, the hypothalamic volume negatively correlated with FSH and LH levels, and the volumes of the inferior frontal gyrus, and angular gyrus negatively correlated with progesterone levels, respectively. MHT-treated women showed larger GM volume than noMHT women. The anatomical structures that showed greater volume in association with MHT included the deep brain areas, frontal, temporal, parietal, and occipital gyri.

Independent and additive contribution of white matter hyperintensities and Alzheimer’s disease pathology to basal forebrain cholinergic system degeneration

ObjectivesDegeneration of the cholinergic basal forebrain nuclei (CBFN) system has been studied extensively in Alzheimer's disease (AD). White matter hyperintensities are a hallmark of aging as well as a common co-morbidity of AD, but their contribution to CBFN degeneration has remained unclear. Therefore, we explored the influence of white matter hyperintensities within cholinergic subcortical-cortical projection pathways on CBFN volumes and regional gray matter volumes in AD and age- and gender-matched controls. MethodsWe analyzed magnetic resonance images (MRI) from 42 patients with AD and 87 age- and gender-matched control subjects. We assessed the white matter hyperintensity burden within the cholinergic projection pathways using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and applied probabilistic anatomical maps for the analysis of CBFN volumes, i.e. the Ch1-3 compartment and the Ch4 cell group (nucleus basalis of Meynert), by diffeomorphic anatomical registration using exponentiated lie algebra analysis of voxel-based morphometry. Using multiple linear regression analyses, we explored correlations between regional gray matter volumes and the extent of white matter hyperintensities or CBFN volumes in both groups. ResultsIn AD, all CBFN volumes were significantly smaller than in controls, and white matter hyperintensity burden within the cholinergic projection pathways was not correlated with CBFN volume. In controls, white matter hyperintensity burden within the cholinergic projection pathways was inversely correlated with CBFN volume when corrected for sex and total intracranial volume, but this correlation was no longer significant after correction for age. Voxel-wise multiple linear regression analyses using threshold-free cluster enhancement revealed that in controls, cholinergic pathway hyperintensities correlated with gray matter loss in perisylvian areas, whereas the were no effects in AD. Moreover, we found that CBFN volumes correlated with distinct regional cortical atrophy patterns in both groups. ConclusionOur results indicate that white matter hyperintensities and AD pathology contribute independently but additively to the degeneration of cholinergic basal forebrain structures. Whereas AD is primarily associated with CBFN volume loss, cholinergic degeneration associated with white matter hyperintensities appears to involve disruption of cholinergic cortical projection fibers with less pronounced effects on CBFN volumes.

Reorganization of the Brain Structural Covariance Network in Ischemic Moyamoya Disease Revealed by Graph Theoretical Analysis.

ObjectiveIschemic moyamoya (MMD) disease could alter the cerebral structure, but little is known about the topological organization of the structural covariance network (SCN). This study employed structural magnetic resonance imaging and graph theory to evaluate SCN reorganization in ischemic MMD patients.MethodForty-nine stroke-free ischemic MMD patients and 49 well-matched healthy controls (HCs) were examined by T1-MPRAGE imaging. Structural images were pre-processed using the Computational Anatomy Toolbox 12 (CAT 12) based on the diffeomorphic anatomical registration through exponentiated lie (DARTEL) algorithm and both the global and regional SCN parameters were calculated and compared using the Graph Analysis Toolbox (GAT).ResultsMost of the important metrics of global network organization, including characteristic path length (Lp), clustering coefficient (Cp), assortativity, local efficiency, and transitivity, were significantly reduced in MMD patients compared with HCs. In addition, the regional betweenness centrality (BC) values of the bilateral medial orbitofrontal cortices were significantly lower in MMD patients than in HCs after false discovery rate (FDR) correction for multiple comparisons. The BC was also reduced in the left medial superior frontal gyrus and hippocampus, and increased in the bilateral middle cingulate gyri of patients, but these differences were not significant after FDR correlation. No differences in network resilience were detected by targeted attack analysis or random failure analysis.ConclusionsBoth global and regional properties of the SCN are altered in MMD, even in the absence of major stroke or hemorrhagic damage. Patients exhibit a less optimal and more randomized SCN than HCs, and the nodal BC of the bilateral medial orbitofrontal cortices is severely reduced. These changes may account for the cognitive impairments in MMD patients.

Study of normal-tension glaucoma based on OCTA and VBM-DARTEL analysis.

The aim of the present study was to investigate the detection value of optical coherence tomography angiography (OCTA) and voxel-based morphometry with diffeomorphic anatomical registration through exponentiated lie algebra (VBM-DARTEL) in normal-tension glaucoma (NTG), as well as the correlation between the two functional indicators. A total of 30 patients (15 males, 15 females) with NTG and 30 (15 males, 15 females) age-, sex- and education-matched healthy controls underwent OCTA and 3.0 T MRI scanning. The OCTA technique was used to scan the optic disc area of all subjects and measure the density of blood vessels around the optic disc; 3.0 T MRI scanning was used to obtain MRI images of the brain structure and the VBM-DARTEL method was applied for image processing using Matlab7.11R2010b (MathWorks). Imaging data were compared between the groups using two-samples t-tests to identify differences in the density of blood vessels around the optic disc and the change in brain parenchyma. Correlation analysis was used to explore associations between the density of blood vessels around the optic disc and the change in brain parenchyma in NTG. The results indicated that the vascular density around the optic disc in the NTG group was significantly decreased compared with that in the control group; the vascular density was decreased with disease progression. The difference between the two groups was statistically significant (P<0.05). The VBM-DARTEL analysis indicated that the volume of the left middle frontal gyrus, right superior frontal gyrus, right precuneus, right angular gyrus and right middle occipital gyrus was decreased, whereas the volume of the right anterior central gyrus was increased. The area under the receiver operating characteristic curve for the local volume difference in brain parenchyma to predict the diagnosis of NTG was >0.7. The area of brain parenchyma reduction was positively correlated with the density of blood vessels around the optic disc (P<0.05), whereas the right anterior central gyrus was negatively correlated with vascular density. In conclusion, OCTA and VBM-DARTEL technology may facilitate non-invasive monitoring of changes in NTG structure and function, and provide non-invasive diagnostic imaging support in the early stage of the disease. These advantages are of great importance in the diagnosis and follow-up of NTG.

Effect of chronic alcohol consumption on brain structure in males with alcohol use disorder without a familiar history of alcoholism

Structural brain damages caused by chronic alcohol consumption have been extensively reported. However, the neuroimaging findings in people with alcohol use disorder (AUD) are relatively inconsistent. This inconsistency may be due to the influence of different variables that are not always considered, such as the presence of a family history of alcoholism (FHA). The main aim of this research is to study the gray (GM) and white matter (WM) volumes in male participants with AUD without FHA compared to healthy control males (HC) without FHA. For this study, we included 19 participants with AUD without FHA and 18 HC males without FHA. T1-weighted images were acquired with a General Electric Signa Exite 1.5 T scanner. GM and WM tissues were calculated using Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra (DARTEL). All analyses were controlled for age and total brain volume. The statistical threshold was calculated with AlphaSim and further adjusted to account for the non-isotropic smoothness of structural images, according to Hayasaka et al. (2004). The obtained main results showed that, relative to the HC group, the participants with AUD without FHA had significantly lower GM in several brain structures, reflecting relatively purely the effects of chronic alcohol intake on brain volume. GM structure integrity is relevant for the efficient functioning of low and high-order cognitive processes used in everyday life, and its damage seems to be related to the severity/intensity/chronicity of the AUD. As such, it becomes relevant to assess and follow brain structural changes through the dependence course.

Altered Brain Morphometry in Cerebral Small Vessel Disease With Cerebral Microbleeds: An Investigation Combining Univariate and Multivariate Pattern Analyses

PurposeThe 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).Materials and MethodsIn 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.ResultsIn 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.ConclusionOur 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.

Nonlinear registration as an effective preprocessing technique for Deep learning based classification of disease.

A number of machine learning (ML), and particularly in recent years, deep learning (DL) approaches have been proposed for automatic classification of Alzheimer's disease (AD) using brain structural magnetic resonance imaging (MRI) data. However, the data available are limited in the case of this specific disease. Training a DL model with a large number of feature parameters on a small dataset of MRI scans will likely lead to overfitting. Overfitting reduces the generality and efficiency of the model. In this study, we show that a traditional nonlinear transformation from native space to template space, as a preprocessing stage, is effective in reducing overfitting through the reduction of spatial variations in the input data. To evaluate this effectiveness, we compare two different pre-processing approaches for DL-based AD classification task: (1) affine registration and (2) nonlinear diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL). The results show that the accuracy of the nonlinear registration based approach is much higher than the affine registration based approach. Furthermore, from the classification results obtained with noisy images, DARTEL is less susceptible to noise than affine registration. In summary, our experimental results suggest that nonlinear transformation is a preferable preprocessing step for training DL-based AD classification models on limited size datasets.

Population-Average Brain Templates and Application to Automated Voxel-Wise Analysis Pipelines for Cynomolgus Macaque.

The growing number of neuroimaging studies of cynomolgus macaques require extending existing templates to facilitate species-specific application of voxel-wise neuroimaging methodologies. This study aimed to create population-averaged structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) templates for the cynomolgus macaques and apply the templates in fully automated voxel-wise analyses. We presented the development of symmetric and asymmetric MRI and DTI templates from a sample of 63 young male cynomolgus monkeys with the use of optimized template creation approaches. We also generated the associated average tissue probability maps and Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra templates for use with the Statistical Parametric Mapping (SPM), as well as the average fractional anisotropy/skeleton targets for incorporation into tract-based spatial statistics (TBSS) framework. Both asymmetric and symmetric templates in a standardized coordinate space demonstrated low bias and high contrast. Fully automated processing using SPM was accomplished for all native MRI datasets and demonstrated outstanding performance regarding skull-stripping, segmentation, and normalization when using the MRI templates. Automated normalization to the DTI template was excellently achieved for all native DTI images using the TBSS pipeline. The cynomolgus MRI and DTI templates are anticipated to provide a common platform for precise single-subject data analysis and facilitate comparison of neuroimaging findings in cynomolgus monkeys across studies and sites. It is also hoped that the procedures of template creation and fully-automated voxel-wise frameworks will provide a straightforward avenue for investigating brain function, development, and neuro-psychopathological disorders in non-human primate models.

Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms.

To investigate the gray matter (GM) alterations in patients with insomnia disorder (ID) at different severity stages and the relationship between GM alterations and sleep, mood, and cognitive measures. One hundred one ID patients and 63 healthy controls (HC) were included. Each patient underwent structural MRI and completed sleep-, mood-, and cognitive-related questionnaires. The ID patients were further grouped into subthreshold insomnia (SI) group and clinical insomnia (CI) group. We investigated changes in GM volumes in ID patients via diffeomorphic anatomical registration through exponentiated lie algebra voxel-based morphometry (DARTEL-VBM). We first compared voxel-wise differences in GM volumes between the HC group and the ID group. Analysis of variance was performed on individual GM maps in the SI, CI, and HC groups to further investigate the effects of different stages of ID severity on GM volumes. Multiple regression was used to model the relationship between altered GM volumes in SI and CI groups and clinical measures. GM hypertrophies in the left anterior and middle cingulate gyrus, right middle and inferior temporal gyrus, and right cerebellum Crus II were detected in ID. Increased GM volume in the right middle temporal gyrus was detected in the SI group, whereas all three regions in the CI group. Regression analysis showed that mood- and cognitive-related measures had a positive correlation with GM volumes, while sleep-related measures had a negative correlation with GM volumes in the CI group. Our findings of the progressively increased GM volumes in ID suggest that a hypertrophic cortical morphological mechanism may underlie the altered neuroanatomy induced by insomnia. • Insomnia-induced GM hypertrophies in the cingulate gyrus, temporal gyrus, and cerebellum Crus II. • The middle temporal gyrus was early detectable in the SI group. • The increased GM volumes in the CI group were correlated with clinical measures.

Customized FreeSurfer-based brain atlas for diffeomorphic anatomical registration through exponentiated lie algebra tool.

Digital brain template and atlas designed for a specific group provide advantages for the analysis and interpretation of neuroimaging data, but require a significant workload for development. We developed a simple method to create customized brain atlas for diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) tool using FreeSurfer-generated volume-of-interest (FSVOI) images and validated. 18F-florbetaben positron emission tomography (PET) and magnetic resonance (MR) imaging data were obtained from 248 participants of Alzheimer's disease spectrum (from cognitively normal to Alzheimer's disease dementia). To create a customized atlas, MR images of 84 amyloid-negative controls were first processed with FreeSurfer to obtain individual FSVOI and with DARTEL tool to create DARTEL template. Individual FSVOI images were spatially normalized, and each voxel was then labelled with a VOI label with maximum probability. Using these template and atlas, all images were normalized, and the regional standardized uptake value ratios (SUVR) were measured. 18F-florbetaben SUVR values measured with customized atlas showed excellent one-to-one correlation with SUVR measured with individual FSVOI in all regions, and thereby showed almost identical between-group comparison results and outperformed the classic methods. Customized FreeSurfer-based brain atlas for DARTEL tool is easy to create and useful for the analysis of PET and MR images with high adaptability and reliability for broad research purposes.

Lateral orbitofrontal gray matter abnormalities in subjects with problematic smartphone use.

Background and aimsSmartphone use is becoming commonplace and exerting adequate control over smartphone use has become an important mental health issue. Little is known about the neurobiology underlying problematic smartphone use. We hypothesized that structural abnormalities in the fronto-cingulate brain region could be implicated in problematic smartphone use, similar to that has been reported for Internet gaming disorder and Internet addiction. This study investigated fronto-cingulate gray matter abnormalities in problematic smartphone users, particularly those who spend time on social networking platforms.MethodsThe study included 39 problematic smartphone users with excessive use of social networking platforms via smartphone and 49 normal control male and female smartphone users. We conducted voxel-based morphometric analysis with diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm. Region of interest analysis was performed on the fronto-cingulate region to identify whether gray matter volume (GMV) differed between the two groups.ResultsProblematic smartphone users had significantly smaller GMV in the right lateral orbitofrontal cortex (OFC) than healthy controls, and there were significant negative correlations between GMV in the right lateral OFC and the Smartphone Addiction Proneness Scale (SAPS) score, including the SAPS tolerance subscale.ConclusionsThese results suggest that lateral orbitofrontal gray matter abnormalities are implicated in problematic smartphone use, especially in social networking platform overuse. Small GMV in the lateral OFC was correlated with an increasing tendency to be immersed in smartphone use. Our results suggest that orbitofrontal gray matter abnormalities affect regulatory control over previously reinforced behaviors and may underlie problematic smartphone use.

Ventral striatum and stuttering: Robust evidence from a case-control study applying DARTEL.

A prominent theory of developmental stuttering highlights (dys-)function of the basal ganglia (and in particular the ventral striatum) as a main neural mechanism behind this speech disorder. Although the theory is intriguing, studies on gray matter volume differences in the basal ganglia between people who stutter and control persons have reported heterogeneous findings, either showing more or less gray matter volume of the aforementioned brain structure across the brain's hemispheres. Moreover, some studies did not observe any differences at all.From today's perspective several of the earlier studies are rather underpowered and also used less powerful statistical approaches to investigate differences in brain structure between people who stutter and controls. Therefore, the present study contrasted a comparably larger sample of n = 36 people who stutter with n = 34 control persons and applied the state of the art DARTEL algorithm (Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra) to analyze the available brain data. In the present data set stuttering was associated with higher gray matter volume of the right caudate and putamen region of the basal ganglia in patients. Our observation strongly supports a recent finding reporting a larger nucleus accumbens in the right hemisphere in people who stutter when compared to control persons. The present findings are discussed in the context of both compensatory effects of the brain and putative therapeutic effects due to treatment of stuttering.

Brain grey matter volume reduction and anxiety-like behavior in lipopolysaccharide-induced chronic pulmonary inflammation rats: A structural MRI study with histological validation

While there have been multiple fMRI studies into the brain functional changes after acutely stimulated peripheral infection, knowledge for the effect of chronic peripheral infection on whole brain morphology is still quite limited. The present study was designed to investigate the brain structural and emotional changes after peripheral local infection initiated chronic systemic inflammation and the relationship between circulating inflammatory markers and brain grey matter. Specifically, in-vivo T2-weighted MRI was performed on rats with lipopolysaccharide (LPS)-induced chronic pulmonary inflammation (CPI) and those without. Grey matter volume was quantified using diffeomorphic anatomical registration through exponentiated lie (DARTEL) enhanced voxel-based morphometry followed by between-group comparison. Open field experiment was conducted to test the potential anxiety-like behaviors after CPI, along with the ELISA estimated inflammatory markers were correlated to grey matter volume. Guided by image findings, we undertook a focused histological investigation with immunefluorescence and Nissl staining. A widespread decrease of grey matter volume in CPI-model rats was revealed. 8 of the 12 measured inflammatory markers presented differential neuroanatomical correlation patterns with three of the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and CRP being the most notable. Lower grey matter volumes in some of the inflammatory markers related regions (amygdala, CA2 and cingulate cortex) were associated with more-severe anxiety-like behaviors. Furthermore, grey matter volumes in amygdala and CA3 were correlated negatively with the expressions of glial proteins (S100β and Nogo-A), while the grey matter volume in hypo-thalamus was changing positively with neural cell area. Overall, the neuroanatomical association patterns and the histopathology underpinning the MRI observations we demonstrated here would probably serve as one explanation for the cerebral and emotional deficits presented in the patients with CPI, which would furthermore yield new insights into the adverse effects the many other systemic inflammation and inflammatory autoimmune diseases would pose on brain morphology.

Thalamic atrophy and dysfunction in patients with mild-to-moderate traumatic diffuse axonal injury

Disrupted white matter structure has been established in patients with diffuse axonal injury (DAI), but morphological changes in gray matter and local intrinsic activity in the short and midterm (before 6 months) have not been documented in DAI patients. We hypothesized that regionally selective atrophy observed in deep gray matter in the short-term and mid-term periods in patients with mild-to-moderate DAI, local atrophy, and/or dysfunction would be related to clinical characteristics. We evaluated the changes in regional density and synchronization in 18 DAI patients separately using Diffeomorphic Anatomical Registration through Exponentiated Lie algebra-enhanced voxel-based morphometry and regional homogeneity (ReHo). Compared with the controls, DAI patients showed a decreased density in the bilateral thalami and decreased ReHo values in the ventral anterior and ventral lateral nuclei of the bilateral thalami. Pearson’s correlation analysis showed that decreased density in the bilateral thalami was correlated negatively with time since injury and decreased ReHo values in the ventral anterior and ventral lateral nuclei of the bilateral thalami were associated with a worsened motor assessment scale. These findings suggest that mild-to-moderate traumatic DAI within the short and midterm could lead to thalamic atrophy and that dysfunction in the bilateral thalami is associated with declining motor function. This study could potentially provide complementary evidence as an important element in longitudinal studies.

Preliminary evidence of altered gray matter volume in subjects with internet gaming disorder: associations with history of childhood attention-deficit/hyperactivity disorder symptoms.

Attention-deficit/hyperactivity disorder (ADHD) is commonly comorbid with Internet gaming disorder (IGD). Although childhood ADHD symptoms may decline during late brain maturation, structural alterations in some brain areas may persist into adulthood. This study investigated whether young adults with IGD and a history of childhood ADHD symptoms had gray matter volume (GMV) alterations that were distinct from subjects without a history of childhood ADHD. As an exploratory investigation, we conducted a whole-brain voxel-based morphometry with the diffeomorphic anatomical registration using an exponentiated Lie algebra algorithm and applied an uncorrected threshold at the voxel level for multiple comparisons. GMVs of IGD subjects with a history of childhood ADHD (IGDADHD+ group; n = 20; 24.5 ± 2.5years) were compared to those of subjects without a history of childhood ADHD (IGDADHD- group; n = 20; 23.9 ± 2.5years) and controls (n = 20; 22.7 ± 2.4years). Compared with controls, both IGD groups had a smaller GMV in the right anterior cingulate cortex, the left inferior frontal gyrus, and the left insula, yet had a larger GMV in the right angular gyrus. The IGDADHD+ group had a larger GMV in the right precuneus than the IGDADHD- group and controls. When controlling for other comorbid psychiatric symptoms, the IGDADHD+ group also had a smaller GMV in the right inferior frontal gyrus. In conclusion, we found that young adults with IGD and a history of childhood ADHD symptoms had characteristic GMV alterations, which may be linked with their manifestation of childhood ADHD.

Optimization of DARTEL Settings for the Detection of Alzheimer Disease.

Although Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced as an alternative to conventional voxel-based morphometry, there are scant data available regarding the optimal image-processing settings. The aim of this study was to optimize image-processing and ROI settings for the diagnosis of Alzheimer disease using DARTEL. Between May 2002 and August 2014, we selected 158 patients with Alzheimer disease and 198 age-matched healthy subjects; 158 healthy subjects served as the control group against the patients with Alzheimer disease, and the remaining 40 served as the healthy data base. Structural MR images were obtained in all the participants and were processed using DARTEL-based voxel-based morphometry with a variety of settings. These included modulated or nonmodulated, nonsmoothed or smoothed settings with a 4-, 8-, 12-, 16-, or 20-mm kernel size. A z score was calculated for each ROI, and univariate and multivariate logistic regression analyses were performed to determine the optimal ROI settings for each dataset. The optimal settings were defined as those demonstrating the highest χ2 test statistics in the multivariate logistic regression analyses. Finally, using the optimal settings, we obtained receiver operating characteristic curves. The models were verified using 10-fold cross-validation. The optimal settings were obtained using the hippocampus and precuneus as ROIs without modulation and smoothing. The average area under the curve was 0.845 (95% confidence interval, 0.788-0.902). We recommend using the precuneus and hippocampus as ROIs without modulation and smoothing for DARTEL-based voxel-based morphometry as a tool for diagnosing Alzheimer disease.

Differences in regional grey matter volumes in currently ill patients with anorexia nervosa.

Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel-based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty-six individuals with AN and 27 healthy controls underwent a T1-weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE-Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology.

Abnormal gray matter volume and impulsivity in young adults with Internet gaming disorder.

Reduced executive control is one of the central components of model on the development and maintenance of Internet gaming disorder (IGD). Among the various executive control problems, high impulsivity has consistently been associated with IGD. We performed voxel-based morphometric analysis with diffeomorphic anatomical registration by using an exponentiated Lie algebra algorithm (DARTEL) to investigate the relationship of gray matter abnormalities to impulsivity in IGD. Thirty-one young male adults whose excessive Internet gaming began in early adolescence, and 30 age-matched male healthy controls were examined. IGD subjects showed smaller gray matter volume (GMV) in brain regions implicated in executive control, such as the anterior cingulate cortex and the supplementary motor area. The GMVs in the anterior cingulate cortex and the supplementary motor area were negatively correlated with self-reporting scales of impulsiveness. IGD subjects also exhibited smaller GMV in lateral prefrontal and parietal cortices comprising the left ventrolateral prefrontal cortex and the left inferior parietal lobule when compared with healthy controls. The GMVs in the left ventrolateral prefrontal cortex were negatively correlated with lifetime usage of Internet gaming. These findings suggest that gray matter abnormalities in areas related to executive control may contribute to high impulsivity of young adults with IGD. Furthermore, alterations in the prefrontal cortex were related with long-term excessive Internet gaming during adolescence.