White matter alterations in mild cognitive impairment revealed by meta-analysis of diffusion tensor imaging using tract-based spatial statistics.

The neuropathological mechanism of mild cognitive impairment (MCI) remains unclarified. Diffusion tensor imaging (DTI) studies revealed white matter (WM) microarchitecture alterations in MCI, but consistent findings and conclusions have not yet been drawn. The present coordinate-based meta-analysis (CBMA) of tract-based spatial statistics (TBSS) studies aimed to identify the most prominent and robust WM abnormalities in patients with MCI. A systematic search of relevant studies was conducted through January 2022 to identify TBSS studies comparing fractional anisotropy (FA) between MCI patients and healthy controls (HC). We used the seed-based d mapping (SDM) software to achieve the CBMA and analyze regional FA alterations in MCI. Meta-regression analysis was subsequently applied to explore the potential associations between clinical variables and FA changes. MCI patients demonstrated significantly decreased FA in widely distributed areas in the corpus callosum (CC), including the genu, body, and splenium of the CC, as well as one cluster in the left striatum. FA in the body of the CC and in three clusters in the splenium of the CC was negatively associated with the mean age. Additionally, FA in the genu of the CC and in three clusters in the splenium of the CC had negative correlations with the MMSE scores. Disrupted integrities of the CC and left striatum might play vital roles in the process of cognitive decline. These findings enhanced our understanding of the neural mechanism underlying WM neurodegeneration in MCI and provided perspectives for the early detection and intervention of dementia.Registration number: CRD42022235716.

Altered topology of individual brain structural covariance networks in major depressive disorder.

BACKGROUND: The neurobiological pathogenesis of major depression disorder (MDD) remains largely controversial. Previous literatures with limited sample size utilizing group-level structural covariance networks (SCN) commonly generated mixed findings regarding the topology of brain networks. METHODS: We analyzed T1 images from a high-powered multisite sample including 1173 patients with MDD and 1019 healthy controls (HCs). We used regional gray matter volume to construct individual SCN by utilizing a novel approach based on the interregional effect size difference. We further investigated MDD-related structural connectivity alterations using topological metrics. RESULTS: Compared to HCs, the MDD patients showed a shift toward randomization characterized by increased integration. Further subgroup analysis of patients in different stages revealed this randomization pattern was also observed in patients with recurrent MDD, while the first-episode drug naïve patients exhibited decreased segregation. Altered nodal properties in several brain regions which have a key role in both emotion regulation and executive control were also found in MDD patients compared with HCs. The abnormalities in inferior temporal gyrus were not influenced by any specific site. Moreover, antidepressants increased nodal efficiency in the anterior ventromedial prefrontal cortex. CONCLUSIONS: The MDD patients at different stages exhibit distinct patterns of randomization in their brain networks, with increased integration during illness progression. These findings provide valuable insights into the disruption in structural brain networks that occurs in patients with MDD and might be useful to guide future therapeutic interventions.

Altered White Matter Integrity in ADHD Revealed by Meta-analysis of Tract-based Spatial Statistics.

OBJECTIVE: We conducted an updated coordinate-based meta-analysis (CBMA) to determine the most prominent and robust white matter (WM) abnormalities in ADHD based on tract-based spatial statistics (TBSS) findings. METHOD: The seed-based d mapping (SDM) software was applied to compare regional fractional anisotropy (FA) alterations in ADHD. Subgroup meta-analyses in the pure ADHD without comorbidity subgroup, the children and adolescents subgroup, and the adults subgroup were also explored, respectively. Meta-regression analysis was subsequently used to examine potential correlations between demographics and FA changes. RESULTS: Only one cluster in the splenium of corpus callosum (CC) exhibited age-related FA decrease in ADHD individuals in the pooled meta-analysis. The adults ADHD subgroup revealed two clusters with reduced FA lied in the splenium and body of CC. CONCLUSION: This updated CBMA confirmed the WM abnormalities in the splenium of CC in ADHD, and improved our understanding of the pathogenesis of this neurodevelopmental disorder.

The effects of childhood maltreatment on cortical thickness and gray matter volume: a coordinate-based meta-analysis.

Childhood maltreatment has been suggested to have an adverse impact on neurodevelopment, including microstructural brain abnormalities. Existing neuroimaging findings remain inconsistent and heterogeneous. We aim to explore the most prominent and robust cortical thickness (CTh) and gray matter volume (GMV) alterations associated with childhood maltreatment. A systematic search on relevant studies was conducted through September 2022. The whole-brain coordinate-based meta-analysis (CBMA) on CTh and GMV studies were conducted using the seed-based d mapping (SDM) software. Meta-regression analysis was subsequently applied to investigate potential associations between clinical variables and structural changes. A total of 45 studies were eligible for inclusion, including 11 datasets on CTh and 39 datasets on GMV, consisting of 2550 participants exposed to childhood maltreatment and 3739 unexposed comparison subjects. Individuals with childhood maltreatment exhibited overlapped deficits in the median cingulate/paracingulate gyri simultaneously revealed by both CTh and GM studies. Regional cortical thinning in the right anterior cingulate/paracingulate gyri and the left middle frontal gyrus, as well as GMV reductions in the left supplementary motor area (SMA) was also identified. No greater regions were found for either CTh or GMV. In addition, several neural morphology changes were associated with the average age of the maltreated individuals. The median cingulate/paracingulate gyri morphology might serve as the most robust neuroimaging feature of childhood maltreatment. The effects of early-life trauma on the human brain predominantly involved in cognitive functions, socio-affective functioning and stress regulation. This current meta-analysis enhanced the understanding of neuropathological changes induced by childhood maltreatment.

Distinct functional brain abnormalities in insomnia disorder and obstructive sleep apnea.

Insomnia disorder (ID) and obstructive sleep apnea (OSA) are the two most prevalent sleep disorders worldwide, but the pathological mechanism has not been fully understood. Functional neuroimaging findings indicated regional abnormal neural activities existed in both diseases, but the results were inconsistent. This meta-analysis aimed to explore concordant regional functional brain changes in ID and OSA, respectively. We conducted a coordinate-based meta-analysis (CBMA) of resting-state functional magnetic resonance imaging (rs-fMRI) studies using the anisotropic effect-size seed-based d mapping (AES-SDM) approach. Studies that applied regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) or fractional ALFF (fALFF) to analyze regional spontaneous brain activities in ID or OSA were included. Meta-regressions were then applied to investigate potential associations between demographic variables and regional neural activity alterations. Significantly increased brain activities in the left superior temporal gyrus (STG.L) and right superior longitudinal fasciculus (SLF.R), as well as decreased brain activities in several right cerebral hemisphere areas were identified in ID patients. As for OSA patients, more distinct and complicated functional activation alterations were identified. Several neuroimaging alterations were functionally correlated with mean age, duration or illness severity in two patients groups revealed by meta-regressions. These functionally altered areas could be served as potential targets for non-invasive brain stimulation methods. This present meta-analysis distinguished distinct brain function changes in ID and OSA, improving our knowledge of the neuropathological mechanism of these two most common sleep disturbances, and also provided potential orientations for future clinical applications.Registration number: CRD42022301938.

Cortical thickness abnormalities in autism spectrum disorder.

The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate-based meta-analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD.

Alterations in resting-state whole-brain functional connectivity pattern similarity in bipolar disorder patients.

BACKGROUND: Previous neuroimaging studies have extensively demonstrated many signs of functionally spontaneous local neural activity abnormalities in bipolar disorder (BD) patients using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to identify the changes of voxel-wise whole-brain functional connectivity pattern and its corresponding functional connectivity changes remain largely unclear in BD patients. The current study aimed to investigate the voxel-wise changes of functional connectivity patterns in BD patients using publicly available data from the UCLA CNP LA5c Study. METHODS: A total of 45 BD patients and 115 healthy control subjects were finally included and whole-brain functional connectivity homogeneity (FcHo) was calculated from their rs-fMRI. Moreover, the alterations of corresponding functional connectivity were subsequently identified using seed-based resting-state functional connectivity analysis. RESULTS: Individuals with BD exhibited significantly lower FcHo values in the left middle temporal gyrus (MTG) when compared with controls. Functional connectivity findings further indicated decreased functional connectivities between left MTG and cluster 1 (left superior temporal gyrus, extend to middle temporal gyrus, rolandic operculum), cluster 2 (right postcentral, extend to right precentral) in BD patients. The mean FcHo values of left MTG were positively correlated with insomnia, middle scores and appetite increase scores. The mean functional connectivities of left MTG to cluster 1 were negatively correlated with grandiose delusions scores. While the functional connections between left MTG with cluster 2 were negatively correlated with delusions of reference and positively correlated with insomnia, middle scores in BD patients. CONCLUSIONS: Our findings suggested that abnormal FcHo and functional connections in those areas of the brain involving DMN and SMN networks might play a crucial role in the neuropathology of BD.

Identifying Changes of Brain Regional Homogeneity and Cingulo-Opercular Network Connectivity in First-Episode, Drug-Naïve Depressive Patients With Suicidal Ideation.

Objective: Adult patients with major depressive disorder (MDD) may not actively reveal their suicidal ideation (SI). Therefore, this study is committed to finding the alterations in the cingulo-opercular network (CON) that are closely related to SI with multi-imaging methods, thus providing neuroimaging basis for SI. Method: A total of 198 participants (129 MDD patients and 69 healthy controls) were recruited and evaluated with the Montgomery-Asberg Depression Rating Scale (MADRS). The healthy individuals formed the HC group, while the MDD patients were subdivided into no SI MDD (NSI, n = 32), mild SI MDD (MSI, n = 64), and severe SI MDD (SSI, n = 33) according to their MADRS item 10. We obtained MRI data of all participants and applied regional homogeneity (ReHo) analysis to verify a previous finding that links CON abnormality to SI. In addition, we employed the structural covariance network (SCN) analysis to investigate the correlation between abnormal structural connectivity of CON and SI severity. Results: Compared to those of the HC group, MDD ReHo values and gray matter volume (GMV) were consistently found abnormal in CON. ReHo values and GMV of the right orbital inferior frontal gyrus (ORBinf.R) in the MDD group decreased with the increase of SI. Compared to the HC group, the MDD patients showed enhanced structural connectivity of three pairs of brain regions in CON [ACC.L-left superior frontal gyrus (SFG.L), SFG.L-left middle temporal gyrus (MTG.L), and the SFG.L-left post-central gyrus (PoCG.L)]. Compared with that of the NSI and MSI groups, the structural connectivity of three pairs of brain regions in CON is enhanced in the SSI groups [ORBinf.L-right ventral posterior cingulate gyrus (VPCC.R), VPCC.R-SFG.R, and SFG.R-PoCG.R]. Conclusion: Our findings showed the distinctive ReHo, GMV, and SCN pattern of CON in MDD patients with SI; and with the severity of suicide, abnormal brain regions increased. Our finding suggested that MDD patients with different severity of SI have different neuroimaging changes.

Age-related heterogeneity revealed by disruption of white matter structural networks in patients with first-episode untreated major depressive disorder: WM Network In OA-MDD.

The clinical treatment and prognosis of major depressive disorder (MDD) are limited by the high degree of disease heterogeneity. It is unclear whether there is a potential network mechanism for age-related heterogeneity. We aimed to uncover the heterogeneity of the white matter (WM) network at different ages of onset and its correlation with different symptom characteristics. 85 first-episode MDD patients and 84 corresponding healthy controls (HCs) were recruited and underwent diffusion tensor imaging scans. Structural network characteristics were analyzed using graph theory methods. We observed an accelerated age-related decline of the WM network in MDD patients compared with HCs. Distinct symptom-related networks were identified in three MDD groups with different onset-age. For early-onset MDD (18-29 years; EOD), higher guilt and loss of interest were correlated with the insula, and inferior parietal lobe which in default mode network and salience network. For mid-term-onset MDD (30-44 years; MOD), higher somatic symptoms were correlated with thalamus which in cortico-striatal-thalamic-cortical circuit. For later-onset MDD (45-60 years; LOD), poor sleep symptoms were correlated with the caudate in the basal ganglia, which suggests the cingulate operculum network in the control of sleep. These results supported a circuit-based heterogeneity associated with the age of onset in MDD. Understanding this circuit-based heterogeneity might help to develop a new target for clinical treatment strategies.

Altered White Matter Microstructures in Type 2 Diabetes Mellitus: A Coordinate-Based Meta-Analysis of Diffusion Tensor Imaging Studies.

Objective: Type 2 diabetes mellitus (T2DM) is often accompanied by cognitive decline and depressive symptoms. Numerous diffusion tensor imaging (DTI) studies revealed microstructural white matter (WM) abnormalities in T2DM but the findings were inconsistent. The present study aimed to conduct a coordinate-based meta-analysis (CBMA) to identify statistical consensus of DTI studies in T2DM. Methods: We performed a systematic search on relevant studies that reported fractional anisotropy (FA) differences between T2DM patients and healthy controls (HC). The anisotropic effect size seed-based d mapping (AES-SDM) approach was used to explore WM alterations in T2DM. A meta-regression was then used to analyze potential influences of sample characteristics on regional FA changes. Results: A total of eight studies that comprised 245 patients and 200 HC, along with 52 coordinates were extracted. The meta-analysis identified FA reductions in three clusters including the left inferior network, the corpus callosum (CC), and the left olfactory cortex. Besides, FA in the CC was negatively correlated with body mass index (BMI) in the patients group. Conclusions: T2DM could lead to subtle WM microstructural alterations, which might be associated with cognitive deficits or emotional distress symptoms. This provides a better understanding of the pathophysiology of neurodegeneration and complications in T2DM. Systematic Review Registration: Registered at PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number: CRD42020218737.

Altered white matter structural networks in drug-naïve patients with obsessive-compulsive disorder.

White matter (WM) alteration is considered to be a vital neurological mechanism of obsessive-compulsive disorder (OCD). However, little is known regarding the changes in topological organization of WM structural network in OCD. We acquired diffusion tensor imaging (DTI) datasets from 28 drug-naïve OCD patients and 28 well-matched healthy controls (HC). A deterministic fiber tracking approach was used to construct the whole-brain structural connectome. Group differences in global and nodal topological properties as well as rich-club organizations were compared by using graph theory analysis. The relationship between the altered network metrics and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was calculated. Compared with controls, OCD patients exhibited a significantly decreased small-worldness (σ), normalized clustering coefficient (γ) and shortest path length (Lp), as well as an increased global efficiency (Eglob). The nodal efficiency (Enodal) was found to be reduced in the left middle frontal gyrus, and increased in the right parahippocampal gyrus and bilateral putamen in OCD patients. Besides, OCD patients showed increased rich-club, feeder and local connection strength, and the connection strength of the rich-club was positively correlated with the total Y-BOCS score. Our findings emphasized a central role for the complicatedly changed topological architecture of brain structural networks in the pathological mechanism underlying OCD.

Microstructural white matter abnormalities in obsessive-compulsive disorder: A coordinate-based meta-analysis of diffusion tensor imaging studies.

BACKGROUND: There are no conclusive diffusion tensor imaging (DTI) findings on obsessive-compulsive disorder (OCD) for now. We conducted a comprehensive meta-analysis of DTI studies to identify white matter (WM) microarchitecture changes in OCD, and also to compare the results differences between the two most frequently used methods (voxel-based analysis, VBA versus tract-based spatial statistics, TBSS) for DTI data. METHODS: A systematic search was performed on relevant studies that reported fractional anisotropy (FA) alterations between patients with OCD and healthy controls (HC). Seed-based d mapping (SDM) was applied to analyze microstructural WM abnormalities in OCD patients. Subgroup meta-analysis was subsequently performed to explore methodological differences between VBA and TBSS approaches. RESULTS: A total of 30 studies (with 31 datasets) that comprised 855 patients and 875 HC were identified. OCD patients exhibited significantly decreased FA in the right cerebellar hemispheric lobule, corpus callosum (CC), left superior frontal gyrus (orbital part), right gyrus rectus, left superior longitudinal fasciculus and right lenticular nucleus in the pooled meta-analysis. The VBA subgroup showed lower FA in several brain regions while the TBSS subgroup only exhibited significant FA reductions in the CC. CONCLUSION: According to the pooled meta-analysis, OCD patients presented microstructural abnormalities in distributed WM tracts. However, heterogeneous results were found between VBA and TBSS studies.

Roles of 5,10-Methylenetetrahydrofolate Reductase C677T Polymorphisms in First-Episode, Drug-Naive Adult Patients With Depression.

5,10-Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is considered as a predisposition and promising genetic candidate to major depressive disorder (MDD), as it is associated with impaired one-carbon cycles, which may be involved in the pathogenesis of depression. Cortical thickness (CT) and subcortical structure volumes have been extensively studied in MDD and have been proposed as one of the phenotypes for MDD. We intend to discuss the association between CT, subcortical structure volume, and MTHFR C677T polymorphism in first-episode, treatment-naive patients with MDD. In this study, 127 adult patients with MDD and 101 age- and gender-matched healthy controls (HCs) were included. All subjects underwent T1-weighted MRI, MTHFR C677T genotyping, and FreeSurfer software-based morphological analysis. MDD patients have been detected to have significantly decreased volumes in the left nucleus accumbens (P < 0.001). The MTHFR 677 T allele carriers manifested with thinner CT in the left caudal anterior cingulate cortex (cACC, P = 0.009) compared with CC genotype. There were significant genotype-by-diagnosis interactions for the CT in the left cACC (P = 0.009), isthmus cingulate (P = 0.002), medial orbitofrontal lobe (P = 0.012), posterior cingulate (P = 0.030), and the right lateral orbitofrontal lobe (P = 0.012). We also found a trend in the interaction effect on the volume of the left putamen (P = 0.050). Our results revealed that MTHFR C677T polymorphism may be involved in the dysfunction of limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuits mediating emotion processing, which may contribute to pathogenesis of MDD.

Tryptophan hydroxylase-2 polymorphism is associated with white matter integrity in first-episode, medication-naïve major depressive disorder patients.

Considerable evidence suggests that the tryptophan hydroxylase-2 (TPH2) gene is associated with the pathophysiology of major depressive disorder (MDD). In the present study, we investigated alterations of white matter (WM) integrity and the impact of TPH2 polymorphism on WM in a sample of 118 first-episode, medication-naïve, MDD patients and 118 well-matched healthy controls. Whole brain analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). The results showed that the MDD group had significantly reduced FA values for the genu and body of the corpus callosum (CC) and the bilateral anterior corona radiate (ACR). In the MDD patient group, the GG homozygote subgroup exhibited a widespread reduction of FA (uncorrected) and significantly reduced FA in the left retrolenticular portion of the internal capsule and left superior longitudinal fasciculus (SLF) compared with those of the T carriers (GT/TT) (FWE corrected). No significant correlation was found between the FA values in any brain region and the patients' clinical variables. Our findings demonstrate the presence of abnormal white matter integrity in untreated patients with first-episode depression. TPH2-rs4570625 polymorphisms may be involved in the pathological mechanism of WM microarchitecture in patients.

Support Vector Machine Classification of Obsessive-Compulsive Disorder Based on Whole-Brain Volumetry and Diffusion Tensor Imaging.

Magnetic resonance imaging (MRI) methods have been used to detect cerebral anatomical distinction between obsessive-compulsive disorder (OCD) patients and healthy controls (HC). Machine learning approach allows for the possibility of discriminating patients on the individual level. However, few studies have used this automatic technique based on multiple modalities to identify potential biomarkers of OCD. High-resolution structural MRI and diffusion tensor imaging (DTI) data were acquired from 48 OCD patients and 45 well-matched HC. Gray matter volume (GMV), white matter volume (WMV), fractional anisotropy (FA), and mean diffusivity (MD) were extracted as four features were examined using support vector machine (SVM). Ten brain regions of each feature contributed most to the classification were also estimated. Using different algorithms, the classifier achieved accuracies of 72.08, 61.29, 80.65, and 77.42% for GMV, WMV, FA, and MD, respectively. The most discriminative gray matter regions that contributed to the classification were mainly distributed in the orbitofronto-striatal "affective" circuit, the dorsolateral, prefronto-striatal "executive" circuit and the cerebellum. For WMV feature and the two feature sets of DTI, the shared regions contributed the most to the discrimination mainly included the uncinate fasciculus, the cingulum in the hippocampus, corticospinal tract, as well as cerebellar peduncle. Based on whole-brain volumetry and DTI images, SVM algorithm revealed high accuracies for distinguishing OCD patients from healthy subjects at the individual level. Computer-aided method is capable of providing accurate diagnostic information and might provide a new perspective for clinical diagnosis of OCD.

Cortical thickness and white matter integrity abnormalities in obsessive-compulsive disorder: A combined multimodal surface-based morphometry and tract-based spatial statistics study.

BACKGROUND: Cerebral morphological abnormalities may play a key role in pathogenesis of obsessive-compulsive disorder (OCD). However, few studies have used multimodal imaging strategies to investigate alterations of cortical morphometry and white matter (WM) integrity. This study aimed to evaluate cortical thickness, cortical and subcortical volume, and WM integrity characteristics in OCD patients comprehensively. METHODS: We acquired magnetic resonance imaging (MRI) scans from 52 OCD patients and 46 well-matched healthy controls (HCs). Cortical thickness and cortical and subcortical volume were measured using the surface-based morphometry (SBM) approach. We also evaluated fractional anisotropy (FA) and mean diffusivity (MD) derived from diffusion tensor imaging (DTI) using tract-based spatial statistics (TBSS). The disease severity was evaluated by score of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). For those brain regions exhibiting altered structure, correlations between alterations and clinical symptoms severity were analyzed in all patients and medication-naïve patients, respectively. RESULTS: Compared with controls, OCD patients exhibited cortical thinning in right posterior cingulate cortex (PCC), as well as significantly decreased FA values in the genu and body of corpus callosum (CC). In medication-naïve patients group, the total Y-BOCS score and obsession score were significantly negative correlated with right PCC cortical thickness. CONCLUSIONS: OCD patients demonstrated symptom-related reduced cortical thickness structural alteration of the right PCC, and altered WM integrity in the genu and body of CC. Medication seems could alleviate the alteration of cortical thickness but not WM integrity. Combined multimodal neuroimaging methods may provide a more comprehensive perspective to clarify the pathological mechanism of OCD.