Tract-based Spatial Statistics Studies Research Articles

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.

Microstructural white matter abnormalities in pediatric and adult obsessive-compulsive disorder: A systematic review and meta-analysis.

ObjectiveTo identify the most prominent and replicable fractional anisotropy (FA) alterations of white matter associated with obsessive‐compulsive disorder (OCD) in tract‐based spatial statistics (TBSS) studies.MethodsWe reviewed previous TBSS studies (n = 20) in OCD and performed a meta‐analysis (n = 16) of FA differences.ResultsNo between‐group differences in FA were detected in the pooled meta‐analysis. However, reduced FA was identified in the genu and anterior body of corpus callosum (CC) in adult OCD. FA reductions in the anterior body of CC were associated with a later age of onset in adult patients with OCD. For pediatric OCD, decreased FA in earlier adolescence and increased FA in later adolescence were seemingly related to an altered trajectory of brain maturation.ConclusionsAbsent in the pooled sample but robust in adults, disrupted microstructural organization in the anterior part of CC indicates a bias of deficits toward connections in interhemispheric connections of rostral neocortical regions, which could lead to deficits of interhemispheric communication and thus contribute to cognitive and emotional deficits in adult OCD. The correlation between FA in the anterior body of CC and older illness onset suggests that patients with later adult onset of illness may represent a biologically distinct subgroup. For pediatric OCD, alterations in neurodevelopmental maturation may contribute to inconsistent patterns of FA alteration relative to controls during adolescence. While most studies of OCD have emphasized alterations of within hemisphere fronto‐striatal circuits, these results indicate that between hemisphere connectivity of this circuitry may also represent important pathophysiology of the illness.

White matter disruption in obsessive-compulsive disorder revealed by meta-analysis of tract-based spatial statistics.

Exploring white matter (WM) microstructural alterations is a momentous step for gaining insights about underlying mechanisms of obsessive-compulsive disorder (OCD) and improving the efficacy of therapies for this condition. Many tract-based spatial statistics (TBSS) studies have revealed abnormalities of fractional anisotropy (FA; an index of WM integrity) in OCD. However, research works have not drawn robust conclusions. Therefore, we integrated the findings of TBSS studies to identify the most consistent FA changes in OCD using meta-analytical approach. Online databases were systematically searched for all TBSS studies comparing FA between patients with OCD and controls. A coordinate-based meta-analysis was performed using anisotropic effect size version of the seed-based d mapping software. Meanwhile, meta-regression was used to explore the potential association of clinical characteristics with regional FA abnormalities. Our meta-analysis included 488 OCD patients and 519 controls across 17 datasets. FA reductions were identified in the genu of the corpus callosum and the left orbitofrontal WM in OCD patients relative to controls. Metaregression analyses showed that the FA in the left orbitofrontal WM was negatively and independently correlated with symptom severity and illness duration in patients withOCD. The current study provides a quantitative overview of TBSS findings in OCD and demonstrates the most prominent and replicable WM abnormalities in OCD are in the anterior part of the brain including interhemispheric connection and orbitofrontal region. Additionally, our findings suggest that FA reduction in the orbitofrontal WM might be a potential biomarker in predicting disease severity and progression in patients with OCD.

A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Characteristic patterns of white matter tract injury in sport-related concussion: An image based meta-analysis.

Sports-related concussion (SRC) is sustained by millions of people per year, yet the spatiotemporal patterns of white matter (WM) injury remain poorly understood. Several SRC studies have implemented the standardised approach Tract-Based Spatial Statistics (TBSS). The aim of this image-based meta-analysis was to identify consensus patterns of SRC-related WM injury across TBSS studies. We included studies comparing the diffusion MRI measurement fractional anisotropy (FA) in SRC or subconcussive injury vs. controls using TBSS, as FA is the most frequently examined diffusion tensor imaging metric. Authors of eligible studies were contacted to request unthresholded statistical map outputs from TBSS, and image-based meta-analyses were performed using Seed-Based d-Mapping. Eight studies contributed to our meta-analyses, comprising 174 SRC or subconcussive injury participants and 160 controls. Our primary meta-analysis (n=8), encompassing subjects with acute SRC (n=2), chronic SRC (n=4) and subconcussive injuries (n=2) revealed dominant bilateral increased FA in the superior longitudinal fasciculus (SLF) and internal capsule. Subconcussive injury was associated with small clusters of increased and decreased FA in the arcuate fasciculus compared to control. In acute SRC, we found diffuse foci of raised FA at WM/grey matter border-zone associated with the bilateral SLF and right inferior fronto-occipital fasciculus. In contrast, chronic SRC had a pattern of deep WM alteration, asymmetrically located in the right optic radiations and arcuate fasciculus. Our findings represent the most powerful analysis of TBSS data in SRC, supporting the use of this approach to analyse diffusion data. TBSS is sensitive to WM abnormalities resulting from SRC or subconcussive injury over a range of temporal and clinical scenarios. Our data show spatially concordant patterns of WM injury unique to subconcussive, acute and chronic phases, highlighting the future utility of diffusion MRI for concussion diagnosis.

Psychoradiologic abnormalities of white matter in patients with bipolar disorder: diffusion tensor imaging studies using tract-based spatial statistics

An increasing number of psychoradiology studies that use tract-based spatial statistics (TBSS) of diffusion tensor imaging have reported abnormalities of white matter in patients with bipolar disorder; however, robust conclusions have proven elusive, especially considering some important clinical and demographic factors. In the present study, we performed a quantitative meta-analysis of TBSS studies to elucidate the most consistent white-matter abnormalities in patients with bipolar disorder. We conducted a systematic search up to May 2017 for all TBSS studies comparing fractional anisotropy (FA) between patients with bipolar disorder and healthy controls. We performed anisotropic effect size–signed differential mapping meta-analysis. We identified a total of 22 data sets including 556 patients with bipolar disorder and 623 healthy controls. We found significant FA reductions in the genu and body of the corpus callosum in patients with bipolar disorder relative to healthy controls. No regions of increased FA were reported. In subgroup analyses, the FA reduction in the genu of the corpus callosum retained significance in patients with bipolar disorder type I, and the FA reduction in the body of the corpus callosum retained significance in euthymic patients with bipolar disorder. Meta-regression analysis revealed that the percentage of female patients was negatively correlated with reduced FA in the body of the corpus callosum. Data acquisition, patient characteristics and clinical variables in the included studies were heterogeneous. The small number of diffusion tensor imaging studies using TBSS in patients with bipolar disorder type II, as well as the lack of other clinical information, hindered the application of subgroup meta-analyses. Our study consistently identified decreased FA in the genu and body of the corpus callosum, suggesting that interhemispheric communication may be the connectivity most affected in patients with bipolar disorder.

Research Review: Diffusion tensor imaging studies of attention-deficit/hyperactivity disorder: meta-analyses and reflections on head motion.

Diffusion tensor imaging studies have shown atypical fractional anisotropy (FA) in individuals with attention-deficit/hyperactivity disorder (ADHD), albeit with conflicting results. We performed meta-analyses of whole-brain voxel-based analyses (WBVBA) and tract-based spatial statistics (TBSS) studies in ADHD, along with a qualitative review of TBSS studies addressing the issue of head motion, which may bias results. We conducted a systematic literature search (last search on April 1st, 2016) to identify studies comparing FA values between individuals with ADHD and typically developing (TD) participants. Signed differential mapping was used to compute effect sizes and integrate WBVBA and TBSS studies, respectively. TBSS datasets reporting no between-group motion differences were identified. We identified 14 WBVBA (ADHDn=314, TDn=278) and 13 TBSS datasets (ADHDn=557, TDn=568). WBVBA meta-analysis showed both significantly lower and higher FA values in individuals with ADHD; TBSS meta-analysis showed significantly lower FA in ADHD compared with TD in four clusters: two in the corpus callosum (isthmus and posterior midbody), one in right inferior fronto-occipital fasciculus, and one in left inferior longitudinal fasciculus. However, four of six datasets confirming no group-differences in motion showed no significant between-group FA differences. A growing diffusion tensor imaging (DTI) literature (total N=1,717) and a plethora of apparent findings suggest atypical interhemispheric connection in ADHD. However, FA results in ADHD should be considered with caution, since many studies did not examine potential group differences in head motion, and most of the studies reporting no difference in motion showed no significant results. Future studies should address head motion as a priority and assure that groups do not differ in head motion.

Disorganization of white matter architecture in major depressive disorder: a meta-analysis of diffusion tensor imaging with tract-based spatial statistics

White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.

Atlasing the frontal lobe connections and their variability due to age and education: a spherical deconvolution tractography study.

In neuroscience, there is a growing consensus that higher cognitive functions may be supported by distributed networks involving different cerebral regions, rather than by single brain areas. Communication within these networks is mediated by white matter tracts and is particularly prominent in the frontal lobes for the control and integration of information. However, the detailed mapping of frontal connections remains incomplete, albeit crucial to an increased understanding of these cognitive functions. Based on 47 high-resolution diffusion-weighted imaging datasets (age range 22-71 years), we built a statistical normative atlas of the frontal lobe connections in stereotaxic space, using state-of-the-art spherical deconvolution tractography. We dissected 55 tracts including U-shaped fibers. We further characterized these tracts by measuring their correlation with age and education level. We reported age-related differences in the microstructural organization of several, specific frontal fiber tracts, but found no correlation with education level. Future voxel-based analyses, such as voxel-based morphometry or tract-based spatial statistics studies, may benefit from our atlas by identifying the tracts and networks involved in frontal functions. Our atlas will also build the capacity of clinicians to further understand the mechanisms involved in brain recovery and plasticity, as well as assist clinicians in the diagnosis of disconnection or abnormality within specific tracts of individual patients with various brain diseases.

Functionally relevant white matter degradation in multiple sclerosis: a tract-based spatial meta-analysis.

To identify statistical consensus between published studies for distribution and functional relevance of tract white matter (WM) degradation in multiple sclerosis (MS). By systematically searching online databases, tract-based spatial statistics studies were identified that compared fractional anisotropy (FA; a marker for WM integrity) in MS patients to healthy control subjects, correlated FA in MS patients with physical disability, or correlated FA in MS patients with cognitive performance. Voxelwise meta-analysis was performed by using the Signed Differential Mapping method for each comparison. Moderating effects of mean age, mean physical disability score, imager magnet strength, lesion load, and number of diffusion directions were assessed by means of meta-regression. Meta-analysis was performed on data from 495 patients and 253 control subjects across 12 studies. MS diagnosis was significantly associated with widespread lower tract FA (nine studies; largest cluster, 4379 voxels; z = 7.1; P < .001). Greater physical disability was significantly associated with lower FA in the right posterior cingulum, left callosal splenium, right inferior fronto-occipital fasciculus, and left fornix crus (six studies; 323 voxels; z = 1.7; P = .001). Impaired cognition was significantly associated with lower FA in the callosal genu, thalamus, right posterior cingulum, and fornix crus (seven studies; largest cluster, 980 voxels; z = 2.5; P < .001). WM damage is widespread in MS with differential and only minimally overlapping distributions of low FA that relates to physical disability and cognitive impairment. The higher number of clusters of lower FA in relation to cognition and their higher z scores suggest that cerebral WM damage may have a greater relevance to cognitive dysfunction than physical disability in MS, and that low anterior callosal and thalamic FA have specific importance to cognitive status.

MRI of carriers of the apolipoprotein E e4 allele–evidence for structural differences in normal‐appearing brain tissue in e4+ relative to e4– young adults

Apolipoprotein E is a protein involved in cholesterol and lipid transport. The gene coding for this protein has three different alleles: e2, e3 and e4. The e4 allele is recognised as a significant risk factor for the development of Alzheimer's disease in later life. Paradoxically, behavioural and functional evidence has demonstrated that the e4 allele may confer a cognitive advantage to the carrier in youth. In this article, a range of sophisticated and novel structural imaging techniques were used to identify subtle differences in the brain tissue of groups of young e4 and homozygous e3 carriers that might support this paradox. Using voxel-based morphometry of high-resolution structural MR images, we identified a higher white matter volume ratio in e4 relative to homozygous e3 carriers. Furthermore, diffusion tensor imaging and tract-based spatial statistics studies identified increases in axial diffusivity and mode of anisotropy in carriers of the e4 allele. In addition, quantitative magnetisation transfer data were analysed using tract-based spatial statistics. Evidence of a trend towards an increased transverse relaxation time of the bound proton pool was detected in e4 carriers, indicative of altered white matter composition. These changes were found to correlate with indices of cognitive performance across the two groups, supporting the notion that such subtle differences in white matter integrity may confer neural advantages that contribute to cognitive outcomes and, potentially, to performance differences, such as observed here in a test of verbal fluency and reported previously by other researchers. Copyright © 2013 John Wiley & Sons, Ltd.

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. DTI was performed in 78 healthy subjects aged 8-21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence. In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age. These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.

Acquisition and voxelwise analysis of multi-subject diffusion data with Tract-Based Spatial Statistics

There is much interest in using magnetic resonance diffusion imaging to provide information on anatomical connectivity in the brain by measuring the diffusion of water in white matter tracts. Among the measures, the most commonly derived from diffusion data is fractional anisotropy (FA), which quantifies local tract directionality and integrity. Many multi-subject imaging studies are using FA images to localize brain changes related to development, degeneration and disease. In a recent paper, we presented a new approach, tract-based spatial statistics (TBSS), which aims to solve crucial issues of cross-subject data alignment, allowing localized cross-subject statistical analysis. This works by transforming the data from the centers of the tracts that are consistent across a study's subjects into a common space. In this protocol, we describe the MRI data acquisition and analysis protocols required for TBSS studies of localized change in brain connectivity across multiple subjects.