Diffusion Basis Spectrum Imaging of White Matter in Schizophrenia and Bipolar Disorder.

Background: Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies. Methods: We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n = 27), schizophrenia (SCZ, n = 21), and bipolar disorder (BPD, n = 21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants. Results: In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups. Conclusion: Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.

Alteration of fractional anisotropy in preterm-born individuals: a systematic review and meta-analysis.

BACKGROUD: Neurological disorders are common in preterm (PT) born individuals. Diffusion tensor imaging (DTI) studies using tract-based spatial statistics (TBSS) effectively detect microstructural white matter (WM) abnormalities in the brain. We conducted this systematic review to integrate the findings of TBSS studies to determine the most consistent WM alterations in PT born individuals. METHODS: PubMed, Embase, Web of Science and Science Direct were searched. DTI studies using TBSS in PT born individuals were screened up to October 2022. The systematic review included studies reporting alterations in FA values for the entire brain in a stereotactic space, with three coordinates (x, y, z), according to the seed-based d mapping method. RESULTS: The search strategy identified seventeen studies that fulfilled our inclusion criteria, with a total of 911 PT-born individuals and 563 matched controls were analysed. Of the seventeen studies, eight were dedicated to 650 adults, five to 411 children and four to 413 infants. Ten studies recruited 812 individuals born very prematurely (GA <29 weeks), six studies recruited 386 moderately premature individuals (GA = 29-32 weeks) and one study recruited 276 individuals born late prematurely (GA >32 weeks). This meta-analysis of six studies including 388 individuals highlighted four brain regions in which fractional anisotropy (FA) was lower in PT group than in people born at term. The quantitative meta-analysis found that the most robust WM alterations were located in the corpus callosum (CC), the bilateral thalamus and the left superior longitudinal fasciculus (SLF) II. Significant changes in FA reflect WM abnormalities in PT born individuals from infant to young adulthood. CONCLUSIONS: Significant changes in FA reflect WM abnormalities in individuals born PT from infancy to young adulthood. The abnormal development of the CC, bilateral thalamus and left SLF may play a vital role in the neurodevelopment of PT individuals.

Neurological disorders are prevalent in preterm (PT) born individuals. The use of tract-based spatial statistics (TBSS) in diffusion tensor imaging (DTI) studies has proven effective in detecting microstructural abnormalities of the white matter (WM) of the brain. In order to determine the most consistent alterations in WM among those born prematurely, we have screened DTI studies using TBSS in this PT born population up until October 2022. The meta-analysis identified four brain regions where fractional anisotropy (FA) was lower in the PT group than in those born at term. The quantitative meta-analysis identified the corpus callosum, the bilateral thalamus and the left superior longitudinal fasciculus II. As the most robust WM alterations. Various studies have demonstrated the links between PT birth, intelligence quotient, gestational age and subject age.

Effects of Adapted Physical Activity on White Matter Integrity in Patients with Schizophrenia.

Schizophrenia is associated with changes in white matter (WM) integrity and with reduced life expectancy, in part because of the cardiometabolic side effects of antipsychotics. Physical activity (PA) has emerged as a candidate lifestyle intervention that is safe and effective. The study aimed to assess how an adapted PA program delivered remotely by web (e-APA) improved WM integrity in patients with schizophrenia (SZPs) and healthy controls (HCs) and to evaluate associations among WM integrity, cardiorespiratory fitness, and symptom severity. This longitudinal study was conducted over 16 weeks with 31 participants (18 SZPs and 13 HCs). Diffusion tensor imaging and tract-based spatial statistics were employed to assess WM integrity. Cardiorespiratory fitness was measured by maximal oxygen uptake (VO2max), and assessments for clinical symptoms included the Positive and Negative Syndrome Scale, Self-evaluation of Negative Symptoms and the Brief Negative Syndrome Scale (BNSS). Only the SZPs had significantly increased WM integrity after the e-APA program, with increased fractional anisotropy and decreased radial diffusivity in fasciculi involved in motor functions and language process. Furthermore, decreased negative symptoms assessed with BNSS were associated with greater WM integrity following the program. These findings suggest that e-APA may improve WM integrity abnormalities and support e-APA as a promising therapeutic strategy.

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

OBJECTIVE: To explore the changes in the cerebral microstructure of patients with noise-induced hearing loss (NIHL) using diffusion tensor imaging (DTI). METHOD: 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. RESULTS: 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). CONCLUSION: 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.

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

Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.

Microstructural abnormality of white matter tracts in rheumatoid arthritis.

BACKGROUND: Structural 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. OBJECTIVES: To automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. METHODS: This 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. RESULTS: Compared 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. CONCLUSIONS: We 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.

Association of white matter microstructural alteration with non-suicidal self-injury behavior and visual working memory in adolescents with borderline personality disorder.

BACKGROUND: Non-suicidal self-injurious behavior (NSSI) is the core characteristic of adolescent borderline personality disorder (BPD) and visual working memory is involved in the pathological processes of BPD. This study aimed to investigate alterations in white matter microstructure and their association with NSSI and visual working memory in adolescents with BPD. METHODS: 53 adolescents diagnosed with BPD and 39 healthy controls (HCs) were enrolled. White matter microstructure was assessed with the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). Correlation analysis was performed to assess the association between FA/MD and core features of BPD. A mediation analysis was performed to test whether the effects of white matter alterations on NSSI could be mediated by visual working memory. RESULTS: Adolescents with BPD showed a reduced FA and an increased MD in the cortical-limbic and cortical-thalamus circuit when compared to the HCs (p < 0.05). Increased MD was positively correlated with NSSI, impulse control and identity disturbance (p < 0.05), and was negatively correlated with the score of visual reproduction. Reserved visual working memory masked the effects of white matter microstructural alterations on NSSI behavior. CONCLUSIONS: White matter microstructural deficits in the cortical-limbic and cortical-thalamus circuits may be associated with NSSI and visual working memory in adolescents with BPD. Reserved visual working memory may protect against NSSI.

Diffusion tensor imaging reveals distributed white matter abnormalities in primary trigeminal neuralgia: Tract-based spatial statistics study.

BACKGROUND: Primary trigeminal neuralgia (PTN) is a prevalent chronic pain disorder whose pathogenesis is not limited to the trigeminal system. Despite the significant advances in uncovering underlying mechanisms, there is a paucity of comprehensive and consistent data regarding the role of white matter throughout the entire brain in PTN. METHODS: We performed a prospective case-control study. Sixty patients with PTN and 28 age- and sex-matched healthy controls were evaluated using diffusion tensor imaging (DTI). A tract-based spatial statistical approach was performed to investigate white matter impairment in patients with PTN with several metrics, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Additionally, ROI-based analysis was performed for each white matter tract to compare FA values between groups with correction for patient age and sex. Correlations between DTI data and nerve root compression severity, as well as pain severity, were also evaluated in patients with PTN. RESULTS: Our analysis demonstrated a widespread and symmetrical reduction in FA values among TN patients when compared to the control group (p < 0.05). Specifically, this FA decrease was predominantly observed in regions such as the corona radiata, internal capsule, optic radiation, and thalami, as well as structures within the posterior fossa, notably the cerebellar peduncles. No statistically significant differences were found between patients and the control group during the MD, AD and RD map analyses. ROI-based analysis did not reveal statistically significant changes in FA values in white matter tracts (p > 0.05 in all comparisons, FDR-corrected); however, there were trends towards FA value decreases in the internal capsule (p = 0.08, FDR-corrected) and inferior fronto-occipital fasciculus (p = 0.09, FDR-corrected). CONCLUSIONS: Our findings indicate the presence of microstructural abnormalities in white matter among individuals with primary trigeminal neuralgia, which may potentially play a role in the development and progression of the condition.

Neuroanatomical differences in Latinx children from rural farmworker families and urban non-farmworker families and related associations with pesticide exposure.

Exposure to pesticides in humans may lead to changes in brain structure and function and increase the likelihood of experiencing neurodevelopmental disorders. Despite the potential risks, there is limited neuroimaging research on the effects of pesticide exposure on children, particularly during the critical period of brain development. Here we used voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) from magnetic resonance images (MRI) to investigate neuroanatomical differences between Latinx children (n = 71) from rural, farmworker families (FW; n = 48) and urban, non-farmworker families (NFW; n = 23). Data presented here serves as a baseline for our ongoing study examining the longitudinal effects of living in a rural environment on neurodevelopment and cognition in children. The VBM analysis revealed that NFW children had higher volume in several distinct regions of white matter compared to FW children. Tract-based spatial statistics (TBSS) of DTI data also indicated NFW children had higher fractional anisotropy (FA) in several key white matter tracts. Although the difference was not as pronounced as white matter, the VBM analysis also found higher gray matter volume in selected regions of the frontal lobe in NFW children. Notably, white matter and gray matter findings demonstrated a high degree of overlap in the medial frontal lobe, a brain region predominantly linked to decision-making, error processing, and attention functions. To gain further insights into the underlying causes of the observed differences in brain structure between the two groups, we examined the association of organochlorine (OC) and organophosphate (OP) exposure collected from passive dosimeter wristbands with brain structure. Based on our previous findings within this data set, demonstrating higher OC exposure in children from non-farmworker families, we hypothesized OC might play a critical role in structural differences between NFW and FW children. We discovered a significant positive correlation between the number of types of OC exposure and the structure of white matter. The regions with significant association with OC exposure were in agreement with the findings from the FW-NFW groups comparison analysis. In contrast, OPs did not have a statistically significant association with brain structure. This study is among the first multimodal neuroimaging studies examining the brain structure of children exposed to agricultural pesticides, specifically OC. These findings suggest OC pesticide exposure may disrupt normal brain development in children, highlighting the need for further neuroimaging studies within this vulnerable population.

Tract- and gray matter- based spatial statistics show white matter and gray matter microstructural differences in autistic males.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition commonly studied in the context of early childhood. As ASD is a life-long condition, understanding the characteristics of brain microstructure from adolescence into adulthood and associations to clinical features is critical for improving outcomes across the lifespan. In the current work, we utilized Tract Based Spatial Statistics (TBSS) and Gray Matter Based Spatial Statistics (GBSS) to examine the white matter (WM) and gray matter (GM) microstructure in neurotypical (NT) and autistic males. Methods: Multi-shell diffusion MRI was acquired from 78 autistic and 81 NT males (12-to-46-years) and fit to the DTI and NODDI diffusion models. TBSS and GBSS were performed to analyze WM and GM microstructure, respectively. General linear models were used to investigate group and age-related group differences. Within the ASD group, relationships between WM and GM microstructure and measures of autistic symptoms were investigated. Results: All dMRI measures were significantly associated with age across WM and GM. Significant group differences were observed across WM and GM. No significant age-by-group interactions were detected. Within the ASD group, positive relationships with WM microstructure were observed with ADOS-2 Calibrated Severity Scores. Conclusion: Using TBSS and GBSS our findings provide new insights into group differences of WM and GM microstructure in autistic males from adolescence into adulthood. Detection of microstructural differences across the lifespan as well as their relationship to the level of autistic symptoms will deepen to our understanding of brain-behavior relationships of ASD and may aid in the improvement of intervention options for autistic adults.

TBSS++: A novel computational method for Tract-Based Spatial Statistics.

Diffusion-weighted magnetic resonance imaging (dMRI) is widely used to assess the brain white matter. One of the most common computations in dMRI involves cross-subject tract-specific analysis, whereby dMRI-derived biomarkers are compared between cohorts of subjects. The accuracy and reliability of these studies hinges on the ability to compare precisely the same white matter tracts across subjects. This is an intricate and error-prone computation. Existing computational methods such as Tract-Based Spatial Statistics (TBSS) suffer from a host of shortcomings and limitations that can seriously undermine the validity of the results. We present a new computational framework that overcomes the limitations of existing methods via (i) accurate segmentation of the tracts, and (ii) precise registration of data from different subjects/scans. The registration is based on fiber orientation distributions. To further improve the alignment of cross-subject data, we create detailed atlases of white matter tracts. These atlases serve as an unbiased reference space where the data from all subjects is registered for comparison. Extensive evaluations show that, compared with TBSS, our proposed framework offers significantly higher reproducibility and robustness to data perturbations. Our method promises a drastic improvement in accuracy and reproducibility of cross-subject dMRI studies that are routinely used in neuroscience and medical research.

Multi-spectral diffusion MRI mega-analysis in genetic generalized epilepsy: Relation to outcomes.

BACKGROUND AND OBJECTIVES: Genetic generalized epilepsy (GGE) is the most common form of generalized epilepsy. Although individual patients with GGE typically present without structural alterations, group differences have been demonstrated in GGE and some GGE subtypes like juvenile myoclonic epilepsy (GGE-JME). Previous studies usually involved only small cohorts from single centers and therefore could not assess imaging markers of multiple GGE subtypes. METHODS: We performed a diffusion MRI mega-analysis in 192 participants consisting of 126 controls and 66 patients with GGE from four different cohorts and two different epilepsy centers. We applied whole-brain multi-site harmonization and analyzed fractional anisotropy (FA), as well as mean, radial and axial diffusivity (MD/RD/AD) to assess differences between controls, patients with GGE and the common GGE subtypes, i.e. GGE with generalized tonic-clonic seizures only (GGE-GTCS), GGE-JME and absence epilepsy (GGE-AE). We also analyzed relationships with patients' response to anti-seizure-medication (ASM). RESULTS: Relative to controls, we identified decreased anisotropy and increased RD in patients with GGE. We found no significant effects of disease duration, age of onset or seizure frequency on diffusion metrics. Patients with JME had increased MD and RD when compared to controls, while patients with GGE-GTCS showed decreased MD/AD when compared to controls. Compared to patients with GGE-AE, patients with GGE-GTCS had lower AD/MD. Compared to patients with GGE-GTCS, patients with GGE-JME had higher MD/RD and AD. Moreover, we found lower FA in patients with refractory when compared to patients with non-refractory GGE in the right cortico-spinal tract, but no significant differences in patients with active versus controlled epilepsy. DISCUSSION: We provide evidence that clinically defined GGE as a whole and GGE-subtypes harbor marked microstructural differences detectable with diffusion MRI. Moreover, we found an association between microstructural changes and treatment resistance. Our findings have important implications for future full-resolution multi-site studies when assessing GGE, its subtypes and ASM refractoriness.

Whole brain surface-based morphometry and tract-based spatial statistics in migraine with aura patients: difference between pure visual and complex auras.

Background: The migrainous aura has different clinical phenotypes. While the various clinical differences are well-described, little is known about their neurophysiological underpinnings. To elucidate the latter, we compared white matter fiber bundles and gray matter cortical thickness between healthy controls (HC), patients with pure visual auras (MA) and patients with complex neurological auras (MA+). Methods: 3T MRI data were collected between attacks from 20 patients with MA and 15 with MA+, and compared with those from 19 HCs. We analyzed white matter fiber bundles using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) and cortical thickness with surface-based morphometry of structural MRI data. Results: Tract-based spatial statistics showed no significant difference in diffusivity maps between the three subject groups. As compared to HCs, both MA and MA+ patients had significant cortical thinning in temporal, frontal, insular, postcentral, primary and associative visual areas. In the MA group, the right high-level visual-information-processing areas, including lingual gyrus, and the Rolandic operculum were thicker than in HCs, while in the MA+ group they were thinner. Discussion: These findings show that migraine with aura is associated with cortical thinning in multiple cortical areas and that the clinical heterogeneity of the aura is reflected by opposite thickness changes in high-level visual-information-processing, sensorimotor and language areas.

Self-reported Fatigue was Associated with Increased White-matter Alterations in Long-term Traumatic Brain Injury and Posttraumatic Stress Disorder Patients.

Fatigue is a long-lasting problem in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), with limited research that investigated the fatigue-related white-matter changes within TBI and/or PTSD cohorts. This exploratory cross-sectional study used diffusion tensor imaging (DTI) and neuropsychological data collected from 153 male Vietnam War veterans, as part of the Alzheimer's Disease Neuroimaging Initiative - Department of Defense, and were divided clinically into control veterans, PTSD, TBI, and with both TBI and PTSD (TBI + PTSD). The existence of fatigue was defined by the question "Do you often feel tired, fatigued, or sleepy during the daytime?". DTI data were compared between fatigue and non-fatigue subgroups in each clinical group using tract-based spatial statistics voxel-based differences. Fatigue was reported in controls (29.55%), slightly higher in TBI (52.17%, PBenf = 0.06), and significantly higher in both TBI + PTSD (66.67%, PBenf = 0.001) and PTSD groups (79.25%, PBenf < 0.001). Compared to non-fatigued subgroups, no white-matter differences were observed in the fatigued subgroups of control or TBI, while the fatigued PTSD subgroup only showed increased diffusivity measures (i.e., radial and axial), and the fatigued TBI + PTSD subgroup showed decreased fractional anisotropy and increased diffusivity measures (PFWE ≤ 0.05). The results act as preliminary findings suggesting fatigue to be significantly reported in TBI + PTSD and PTSD decades post-trauma with a possible link to white-matter microstructural differences in both PTSD and TBI + PTSD. Future studies with larger cohorts and detailed fatigue assessments would be required to identify the white-matter changes associated with fatigue in these cohorts.

Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults.

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the "disconnection hypothesis" of cognitive aging.

Sex differences, asymmetry, and age-related white matter development in infants and 5-year-olds as assessed with tract-based spatial statistics.

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of 5 years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5 wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tract-based spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seem to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.

Robust associations between white matter microstructure and general intelligence.

Few tract-based spatial statistics (TBSS) studies have investigated the relations between intelligence and white matter microstructure in healthy (young) adults, and those have yielded mixed observations, yet white matter is fundamental for efficient and accurate information transfer throughout the human brain. We used a multicenter approach to identify white matter regions that show replicable structure-function associations, employing data from 4 independent samples comprising over 2000 healthy participants. TBSS indicated 188 voxels exhibited significant positive associations between g factor scores and fractional anisotropy (FA) in all 4 data sets. Replicable voxels formed 3 clusters, located around the left-hemispheric forceps minor, superior longitudinal fasciculus, and cingulum-cingulate gyrus with extensions into their surrounding areas (anterior thalamic radiation, inferior fronto-occipital fasciculus). Our results suggested that individual differences in general intelligence are robustly associated with white matter FA in specific fiber bundles distributed across the brain, consistent with the Parieto-Frontal Integration Theory of intelligence. Three possible reasons higher FA values might create links with higher g are faster information processing due to greater myelination, more direct information processing due to parallel, homogenous fiber orientation distributions, or more parallel information processing due to greater axon density.

Insulin resistance disrupts white matter microstructure and amplitude of functional spontaneous activity in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is linked to several structural and functional brain alterations. In addition, BD patients have a three-fold increased risk of developing insulin resistance, which is associated with neural changes and poorer BD outcomes. Therefore, we investigated the effects of insulin and two derived measures (insulin resistance and sensitivity) on white matter (WM) microstructure, resting-state (rs) functional connectivity (FC), and fractional amplitude of low-frequency fluctuation (fALFF). METHODS: BD patients (n = 92) underwent DTI acquisition, and a subsample (n = 22) underwent rs-fMRI. Blood samples were collected to determine insulin and glucose levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were computed. DTI data were analyzed via tract-based spatial statistics and threshold-free cluster enhancement. From rs-fMRI data, both ROI-to-ROI FC matrices and fALFF maps were extracted. RESULTS: Insulin showed a widespread negative association with fractional anisotropy (FA) and a positive effect on radial diffusivity (RD) and mean diffusivity (MD). HOMA-IR exerted a significant effect on RD in the right superior longitudinal fasciculus, whereas QUICKI was positively associated with FA and negatively with RD and MD in the left superior longitudinal fasciculus, left anterior corona radiata, and forceps minor. fALFF was negatively modulated by insulin and HOMA-IR and positively associated with QUICKI in the precuneus. No significant results were found in the ROI-to-ROI analysis. CONCLUSION: Our findings suggest that WM microstructure and functional alterations might underlie the effect of IR on BD pathophysiology, even if the causal mechanisms need to be further investigated.

Shared and distinct white matter abnormalities in adolescent-onset schizophrenia and adolescent-onset psychotic bipolar disorder.

BACKGROUND: While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need. METHODS: Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence. RESULTS: Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age. CONCLUSIONS: We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.

The alterations of spontaneous neural activities and white matter microstructures in anti-N-methyl-D-aspartate receptor encephalitis: a resting-state fMRI and DTI study.

BACKGROUND AND PURPOSE: Limited studies had jointly excavated the structural and functional changes in cognitive deficit in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patients. We aimed to explore these changes in anti-NMDAR patients and their effect on cognitive function. METHODS: Twenty-three patients and 25 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, diffusion tensor imaging scanning, and neuroethology tests. The significantly differentiated brain regions via the fractional amplitude of low-frequency fluctuation (fALFF) were defined as regions of interest (ROIs). Granger causal, functional connectivity, and tract-based spatial statistical analyses were applied to explore the functional changes in ROIs and assess the structural changes. RESULTS: HCs outperformed patients in Montreal Cognitive Assessment. The fALFF values of right gyrus rectus (RGR) in patients were significantly reduced. The fractional anisotropy (FA) values of WM in the genu of corpus callosum and right superior corona radiata were significantly decreased and positively associated with neuroethology testing scores. The Granger causal connectivity (GCC) from the left inferior parietal lobule to RGR was significantly decreased and positively associated with inherent vigilance. Indicated by the multiple linear regression result, decreased FA value of the right superior corona radiata might be a reliable marker that reflects the cognitive impairment. CONCLUSIONS: Significant changes in spontaneous neural activities, GCC, and WM structures in anti-NMDAR encephalitis were reported. These findings promote the understanding of underlying relationships between cerebral function, structural network alterations, and cognitive dysfunction.