Tract-based Spatial Statistics Research Articles

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

Facial emotion recognition function and white matter microstructural alterations in drug-naive, comorbidity-free autism.

Individuals with autism spectrum disorder have deficits in facial emotion recognition and white matter microstructural alterations. Nonetheless, most previous studies were confounded by different variables, such as psychiatric comorbidities and psychotropic medications used by ASD participants. Also, it remains unclear how exactly FER deficits are related to white matter microstructural alterations in ASD. Accordingly, we aimed to investigate the FER functions, white matter microstructure, and their relationship in drug-naive and comorbidity-free ASD individuals. 59 ASD individuals and 59 typically developed individuals were included, where 46 ASD and 50 TD individuals completed FER tasks. Covariance analysis showed scores were lower in both basic and complex FER tasks in the ASD group. Tract-Based Spatial Statistics showed FA values in widespread white matter fibers were lower in the ASD group than in the TD group, including forceps major and forceps minor of the corpus callosum, anterior thalamic radiation, corticospinal tract, cingulum, inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus. Moreover, in the TD group but not the ASD group, the performance in the complex FER task was negatively correlated with the FA value in some white matter fibers, including forceps major of the corpus callosum, ATR, CT, cingulum, IFOF, ILF, SLF. Our study suggests children with ASD may experience deficits in facial emotion recognition and exhibit alterations in white matter microstructure. More importantly, our study indicates that white matter microstructural alterations may be involved in FER deficits in children with ASD.

Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis

Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.

Heading during the season and its potential impact on brain structure and neurocognitive performance in high-level male football players: an observational study

ObjectiveTo investigate potential effects of heading on the neurocognitive performance and the white matter (WM) of the brain in high-level adult male football players. DesignProspective longitudinal. MethodFootball players engaging in the highest football leagues in Germany were included. Neurocognitive performance tests and diffusion tensor imaging (DTI) were executed before and after the observation period. Video recordings of each training session and each match play during the observation period were analyzed regarding heading exposure and characteristics. Four DTI measures from tract-based spatial statistics (fractional anisotropy, mean, axial, and radial diffusivity) were investigated. Associations between heading variables and DTI and neurocognitive parameters were tested subsequently. Results8052 headers of 22 players (19.9 ± 2.7 years) were documented in a median of 16.9 months. The individual total heading number ranged from 57 to 943 (median: 320.5). Header characteristics differed between training sessions and matches. Neurocognitive performance (n = 22) and DTI measures (n = 14) showed no significant differences from pre- to post-test. After correction for multiple comparisons, no significant correlations with the total heading number were found. However, the change in fractional anisotropy in the splenium of the corpus callosum correlated significantly with the total amount of long-distance headers (Pearson's r = −0.884; p < 0.0001). ConclusionOver the median observation period of 16.9 months, DTI measures and neurocognitive performance remained unchanged. To elucidate the meaning of the association between individual change in fractional anisotropy and long-distance headers further investigations with larger samples, longer observations, and various cohorts regarding age and level of play are required.

Multimodal neural correlates of dispositional resilience among healthy individuals

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience’s neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.

Combined diffusion tensor imaging and quantitative susceptibility mapping to characterize normal-appearing white matter in self-limited epilepsy with centrotemporal spikes.

In brain development, Myelination is the characteristic feature of white matter maturation, which plays an important role in efficient information transmitting. The white matter abnormality has been reported to be associated with self-limited epilepsy with centrotemporal spikes (SeLECTS). This study aimed to detect the altered white matter region in the SeLECTS patients by the combination of diffusion tensor imaging (DTI) and quantitative susceptibility mapping (QSM) technique. 27 children with SeLECTS and 23 age- and gender-matched healthy children were enrolled. All participants were scanned with 3.0-T MRI to acquire the structure, diffusion and susceptibility-weighted data. The susceptibility and diffusion weighted data were processed to obtain quantitative susceptibility map and fraction anisotropy (FA) map. Then voxel-wise tract-based spatial statistics (TBSS) were used to analyze quantitative susceptibility and FA data. Both DTI and QSM revealed extensive white matter alterations in the frontal, parietal, and temporal lobes in SeLECTS patients. The overlapped region of DTI and QSM analyses was located in the fiber tracts of the corona radiata. The FA values in this overlapped region were negatively correlated with the magnetic susceptibility values. Our results suggest that TBSS-based QSM can be employed as a novel approach for characterizing alterations in white matter in SeLECTS. And the combination of QSM and DTI can provide a more comprehensive evaluation of white matter integrity by utilizing different biophysical features.

Atypical brain structural connectivity and social cognition in childhood maltreatment and peer victimisation.

Childhood maltreatment (CM) is associated with neurobiological aberrations and atypical social cognition. Few studies have examined the neural effects of another common early-life interpersonal stressor, namely peer victimisation (PV). This study examines the associations between tract aberrations and childhood interpersonal stress from caregivers (CM) and peers (PV), and explores how the observed tract alterations are in turn related to affective theory of mind (ToM). Data from 107 age-and gender-matched youths (34 CM [age = 19.9 ± 1.68; 36%male], 35 PV [age = 19.9 ± 1.65; 43%male], 38 comparison subjects [age = 20.0 ± 1.66; 42%male] were analysed using tractography and whole-brain tract-based spatial statistics (TBSS). At the whole-brain level using TBSS, the CM group had higher fractional anisotropy (FA) than the PV and comparison groups in a cluster of predominantly limbic and corpus callosal pathways. Segmented tractography indicated the CM group had higher FA in right uncinate fasciculus compared to both groups. They also had smaller right anterior thalamic radiation (ATR) tract volume than the comparison group and higher left ATR FA than the PV group, with these metrics associated with higher emotional abuse and enhanced affective ToM within the CM group, respectively. The PV group had lower inferior fronto-occipital fasciculus FA than the other two groups, which was related to lower affective ToM within the PV group. Findings suggest that exposure to early-life stress from caregivers and peers are differentially associated with alterations of neural pathways connecting the frontal, temporal and occipital cortices involved in cognitive and affective control, with possible links to their atypical social cognition.

Lipocalin-type prostaglandin D synthase: a glymphopathy marker in idiopathic hydrocephalus.

Idiopathic normal pressure hydrocephalus in elderly people is considered a form of glymphopathy caused by malfunction of the waste clearance pathway, called the glymphatic system. Tau is a representative waste material similar to amyloid-β. During neurodegeneration, lipocalin-type prostaglandin D synthase (L-PGDS), a major cerebrospinal fluid (CSF) protein, is reported to act as a chaperone that prevents the neurotoxic aggregation of amyloid-β. L-PGDS is also a CSF biomarker in idiopathic normal pressure hydrocephalus and significantly correlates with tau concentration, age, and age-related brain white matter changes detected by magnetic resonance imaging. To investigate this glymphopathy, we aimed to analyze white matter changes and contributing factors in vivo and their interactions ex vivo. Cerebrospinal tap tests were performed in 60 patients referred for symptomatic ventriculomegaly. Patients were evaluated using an idiopathic normal pressure hydrocephalus grading scale, mini-mental state examination, frontal assessment battery, and timed up-and-go test. The typical morphological features of high convexity tightness and ventriculomegaly were measured using the callosal angle and Evans index, and parenchymal white matter properties were evaluated with diffusion tensor imaging followed by tract-based spatial statistics. Levels of CSF biomarkers, including tau, amyloid-β, and L-PGDS, were determined by ELISA, and their interaction, and localization were determined using immunoprecipitation and immunohistochemical analyses. Tract-based spatial statistics for fractional anisotropy revealed clusters that positively correlated with mini-mental state examination, frontal assessment battery, and callosal angle, and clusters that negatively correlated with age, disease duration, idiopathic normal pressure hydrocephalus grading scale, Evans index, and L-PGDS. Other parameters also indicated clusters that correlated with symptoms, microstructural white matter changes, and L-PGDS. Tau co-precipitated with L-PGDS, and colocalization was confirmed in postmortem specimens of neurodegenerative disease obtained from the human Brain Bank. Our study supports the diagnostic value of L-PGDS as a surrogate marker for white matter integrity in idiopathic normal pressure hydrocephalus. These results increase our understanding of the molecular players in the glymphatic system. Moreover, this study indicates the potential utility of enhancing endogenous protective factors to maintain brain homeostasis.

White matter biomarker for predicting de novo Parkinson's disease using tract-based spatial statistics: a machine learning-based model.

Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

Brain white matter changes and their associations with non-motor dysfunction in orthostatic hypotension in α-synucleinopathy: A NODDI study.

The specific non-motor symptoms associated with α-synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α-synucleinopathies experiencing OH, alongside their association with other non-motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α-synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non-motor functional impairments in α-synucleinopathies. This study recruited 49 individuals diagnosed with α-synucleinopathies, stratified into an α-OH group (n = 24) and an α-NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract-based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores. The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α-OH group as compared to both the α-NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety-depression ratings (p < 0.05). Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non-motor functional impairments.

Alterations of the cerebral microstructure in patients with noise-induced hearing loss: A diffusion tensor imaging study.

To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). Overall, 122 patients with NIHL (mild [MP, n=79], relatively severe patients [including moderate and severe; RSP, n=32], and undetermined [lost to follow-up, n=11]) and 84 healthy controls (HCs) were enrolled. All clinical data, including age, education level, hearing threshold, occupation type, noise exposure time, and some scale scores (including the Mini-Mental State Examination [MMSE], tinnitus handicap inventory [THI], and Hamilton Anxiety Scale [HAMA]), were collected and analyzed. All participants underwent T1WI3DFSPGR and DTI, and tract-based spatial statistics and region of interest (ROI) analysis were used for assessment. The final sample included 71 MP, 28 RSP, and 75 HCs. The HAMA scores of the three groups were significantly different (p<.05). The noise exposure times, hearing thresholds, and HAMA scores of the MP and RSP were significantly different (p<.05). The noise exposure time was positively correlated with the hearing threshold and negatively correlated with the HAMA scores (p<.05), whereas the THI scores were positively correlated with the hearing threshold (p<.05). DTI analysis showed that all DTI parameters (fractional anisotropy [FA], axial diffusivity [AD], mean diffusivity [MD], and radial diffusivity [RD]) were significantly different in the left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF) for the three groups (p<.05). In addition, the FA values were significantly lower in the bilateral corticospinal tract (CST), right fronto-pontine tract (FPT), right forceps major, left superior longitudinal fasciculus (temporal part) (SLF), and left cingulum (hippocampus) (C-H) of the MP and RSP than in those of the HCs (p<.05); the AD values showed diverse changes in the bilateral CST, left IFOF, right anterior thalamic radiation, right external capsule (EC), right SLF, and right superior cerebellar peduncle (SCP) of the MP and RSP relative to those of the HC (p<.05). However, there were no significant differences among the bilateral auditory cortex ROIs of the three groups (p>.05). There was a significant negative correlation between the FA and HAMA scores for the left IFOF/ILF, right FPT, left SLF, and left C-H for the three groups (p<.05). There was a significant positive correlation between the AD and HAMA scores for the left IFOF/ILF and right EC of the three groups (p<.05). There were significantly positive correlations between the RD/MD and HAMA scores in the left IFOF/ILF of the three groups (p<.05). There was a significant negative correlation between the AD in the right SCP and noise exposure time of the MP and RSP groups (p<.05). The AD, MD, and RD in the left ROI were significantly positively correlated with hearing threshold in the MP and RSP groups (p<.05), whereas FA in the right ROI was significantly positively correlated with the HAMA scores for the three groups (p<.05). The changes in the white matter (WM) microstructure may be related to hearing loss caused by noise exposure, and the WM structural abnormalities in patients with NIHL were mainly located in the syndesmotic fibers of the temporooccipital region, which affected the auditory and language pathways. This confirmed that the auditory pathways have abnormal structural connectivity in patients with NIHL.

Associating white matter microstructural integrity and improvements in reactive stepping in people with Parkinson's Disease.

Reactive steps are rapid responses after balance challenges. People with Parkinson's Disease (PwPD) demonstrate impaired reactive stepping, increasing fall-risk. Although PwPD can improve steps through practice, the neural mechanisms contributing to improved reactive stepping are poorly understood. This study investigated white-matter correlates of responsiveness to reactive step training in PwPD. In an eighteen-week multiple-baseline study, participants (n = 22) underwent baseline assessments (B1 and B2 two-weeks apart), a two-week training protocol, and post-training assessments immediately (P1) and two-months (P2) post-training. Assessments involved three backward reactive step trials, measuring anterior-posterior margin of stability (AP MOS), step length, and step latency. Tract-Based Spatial Statistics correlated white-matter integrity (fractional anisotropy (FA) and radial diffusivity (RD)) with retained (P2-B2) and immediate improvements (P1-B2) in stepping. Significant and sustained improvements in step length and AP MOS were observed. Greater retention of step length improvement correlated with increased FA in the left anterior thalamic radiation (ATR), left posterior thalamic radiation (PTR), left superior longitudinal fasciculus (SLF), and right inferior longitudinal fasciculus (ILF). Step latency retention was associated with lower RD in the left posterior corona radiata and left PTR. Immediate improvements in AP MOS correlated with increased FA of the right ILF, right SLF, and right corticospinal tract. Immediate step length improvements were associated with increased FA in right and left ATR and right SLF. These findings highlight the importance of white-matter microstructural integrity in motor learning and retention processes in PD and could aid in identifying individuals with PD who would benefit most from balance rehabilitation.

Association of homocysteine with white matter dysconnectivity in schizophrenia

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman’s ρ = −.330, P = 0.016) but not in the HC group (Spearman’s ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

Neurite Orientation Dispersion and Density Imaging (NODDI) of Brain Microstructure in Adolescent Cannabis and Nicotine Use.

Despite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure. A total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex. NTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes. NTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.

White matter microstructure in transmasculine and cisgender adolescents: A multiparametric and multivariate study.

Adolescence is a sensitive developmental period for neural sex/gender differentiation. The present study used multiparametric mapping to better characterize adolescent white matter (WM) microstructure. WM microstructure was investigated using diffusion tensor indices (fractional anisotropy; mean, radial, and axial diffusivity [AD]) and quantitative T1 relaxometry (T1) in hormone therapy naïve adolescent cisgender girls, cisgender boys, and transgender boys (i.e., assigned female at birth and diagnosed with gender dysphoria). Diffusion indices were first analyzed for group differences using tract-based spatial statistics, which revealed a group difference in AD. Thus, two multiparametric and multivariate analyses assessed AD in conjunction with T1 relaxation time, and with respect to developmental proxy variables (i.e., age, serum estradiol, pubertal development, sexual attraction) thought to be relevant to adolescent brain development. The multivariate analyses showed a shared pattern between AD and T1 such that higher AD was associated with longer T1, and AD and T1 strongly related to all five developmental variables in cisgender boys (10 significant correlations, r range: 0.21-0.73). There were fewer significant correlations between the brain and developmental variables in cisgender girls (three correlations, r range: -0.54-0.54) and transgender boys (two correlations, r range: -0.59-0.77). Specifically, AD related to direction of sexual attraction (i.e., gynephilia, androphilia) in all groups, and T1 related to estradiol inversely in cisgender boys compared with transgender boys. These brain patterns may be indicative of less myelination and tissue density in cisgender boys, which corroborates other reports of protracted WM development in cisgender boys. Further, these findings highlight the importance of considering developmental trajectory when assessing the subtleties of neural structure associated with variations in sex, gender, and sexual attraction.

Microstructural abnormality of white matter tracts in rheumatoid arthritis

BackgroundStructural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. ObjectivesTo automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. MethodsThis single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. ResultsCompared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. ConclusionsWe report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Diffusion tensor imaging of white-matter structural features of maltreating mothers and their associations with intergenerational chain of childhood abuse

Child abuse causes lifelong adverse outcomes for both physical and mental health, although many are resilient. Efforts to prevent this issue from the parental side require an understanding of the neurobiological basis that leads abusive parents to perpetrate abuse and the influence of the intergenerational chain of childhood abuse. Therefore, this study was conducted to compare the brain white-matter fiber structures between 11 maltreating mothers who had been recognized as having conducted child abuse prior to the intervention and 40 age-matched control mothers using tract-based spatial statistics. There was a significantly reduced axial diffusivity (AD) and a similar trend in fractional anisotropy (FA) in the right corticospinal tract in maltreating mothers compared to control mothers. Therefore, maltreating mothers may have excessive control over the forcefulness of voluntary movements. These features also decreased as the number of childhood abuse experiences increased, suggesting that an intergenerational chain of child abuse may also be involved. Other aspects observed were that the higher the current depressive symptoms, the lower the AD and FA values; however, they were not related to parental practice or empathy. These results corroborate the neurobiological features that perpetrate behaviors in abusive mothers.

Alterations in the white matter structure of major depressive disorder patients and their link to childhood trauma.

Major Depressive Disorder (MDD) is significantly influenced by childhood trauma (CT), affecting brain anatomy and functionality. Despite the unique disease trajectory in MDD patients with CT, the underlying neurobiological mechanisms remain unclear. Our objective is to investigate CT's impact on the white matter structure of the brain in patients with MDD. This research employed tract-based spatial statistics (TBSS) to detect variations between groups in Fractional Anisotropy (FA) throughout the whole brain in 71 medication-free MDD patients and 97 HCs. Participants filled out the Childhood Trauma Questionnaire (CTQ) and assessments for depression and anxiety symptoms. The relationship between FA and CTQ scores was explored with partial correlation analysis, adjusting for factors such as age, gender, educational background, and length of illness. Compared to HCs, the MDD group showed decreased FA values in the right posterior limb of the internal capsule (PLIC), the inferior fronto-occipital fasciculus (IFOF), and bilateral superior longitudinal fasciculus (SLF). Simple effects analysis revealed that compared to HC-CT, the MDD-CT group demonstrated decreased FA values in right PLIC, IFOF, and bilateral SLF. The MDD-nCT group showed decreased FA values in right PLIC and IFOF compared to HC-nCT. The total scores and subscale scores of CTQ were negatively correlated with the FA in the right SLF. The right SLF may potentially be influenced by CT during the brain development of individuals with MDD. These results enhance our knowledge of the role of the SLF in the pathophysiology of MDD and the neurobiological mechanisms by which CT influences MDD.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (β = 0.433, P < 0.001) and a longer disease duration (β = 0.438, P < 0.001). WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

Impact of truncating diffusion MRI scans on diffusional kurtosis imaging.

Diffusional kurtosis imaging (DKI) extends diffusion tensor imaging (DTI), characterizing non-Gaussian diffusion effects but requires longer acquisition times. To ensure the robustness of DKI parameters, data acquisition ordering should be optimized allowing for scan interruptions or shortening. Three methodologies were used to examine how reduced diffusion MRI scans impact DKI histogram-metrics: 1) the electrostatic repulsion model (OptEEM); 2) spherical codes (OptSC); 3) random (RandomTRUNC). Pre-acquired diffusion multi-shell data from 14 female healthy volunteers (29±5 years) were used to generate reordered data. For each strategy, subsets containing different amounts of the full dataset were generated. The subsampling effects were assessed on histogram-based DKI metrics from tract-based spatial statistics (TBSS) skeletonized maps. To evaluate each subsampling method on simulated data at different SNRs and the influence of subsampling on in vivo data, we used a 3-way and 2-way repeated measures ANOVA, respectively. Simulations showed that subsampling had different effects depending on DKI parameter, with fractional anisotropy the most stable (up to 5% error) and radial kurtosis the least stable (up to 26% error). RandomTRUNC performed the worst while the others showed comparable results. Furthermore, the impact of subsampling varied across distinct histogram characteristics, the peak value the least affected (OptEEM: up to 5% error; OptSC: up to 7% error) and peak height (OptEEM: up to 8% error; OptSC: up to 11% error) the most affected. The impact of truncation depends on specific histogram-based DKI metrics. The use of a strategy for optimizing the acquisition order is advisable to improve DKI robustness to exam interruptions.