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Background: Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. Objectives: We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Methods: Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. Results: A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). Conclusions: This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Lower urinary tract (LUT) symptoms are reported in more than 80% of patients with multiple sclerosis (MS), most commonly an overactive bladder (OAB). The relationship between brain white matter (WM) changes in MS and OAB symptoms is poorly understood. Objectives: We aim to evaluate (i) microstructural WM differences across MS patients (pwMS) with OAB symptoms, patients without LUT symptoms, and healthy subjects using diffusion tensor imaging (DTI), and (ii) associations between clinical OAB symptom scores and DTI indices. Methods: Twenty-nine female pwMS [mean age (SD) 43.3 years (9.4)], including seventeen with OAB [mean age (SD) 46.1 years (8.6)] and nine without LUT symptoms [mean age (SD) 37.5 years (8.9)], and fourteen healthy controls (HCs) [mean age (SD) 48.5 years (20)] were scanned in a 3T MRI with a DTI protocol. Additionally, clinical scans were performed for WM lesion segmentation. Group differences in fractional anisotropy (FA) were evaluated using tract-based spatial statistics. The Urinary Symptom Profile questionnaire assessed OAB severity. Results: A statistically significant reduction in FA (p = 0.004) was identified in microstructural WM in pwMS, compared with HCs. An inverse correlation was found between FA in frontal and parietal WM lobes and OAB scores (p = 0.021) in pwMS. Areas of lower FA, although this did not reach statistical significance, were found in both frontal lobes and the rest of the non-dominant hemisphere in pwMS with OAB compared with pwMS without LUT symptoms (p = 0.072). Conclusions: This study identified that lesions affecting different WM tracts in MS can result in OAB symptoms and demonstrated the role of the WM in the neural control of LUT functions. By using DTI, the association between OAB symptom severity and WM changes were identified, adding knowledge to the current LUT working model. As MS is predominantly a WM disease, these findings suggest that regional WM involvement, including of the anterior corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and superior frontal-occipital fasciculus and a non-dominant prevalence in WM, can result in OAB symptoms. OAB symptoms in MS correlate with anisotropy changes in different white matter tracts as demonstrated by DTI. Structural impairment in WM tracts plays an important role in LUT symptoms in MS.

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BackgroundThe 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+).Methods3T 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.ResultsTract-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.DiscussionThese 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.

Abstract Aim Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear. Methods We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on‐road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract‐based spatial statistics. Results The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people. Conclusion Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents.

Little is known about neuropsychological research on patients with acoustic neuroma (AN), especially cognitive neuropsychology. We aim to compare the cognitive function of patients with AN and healthy controls (HCs) and explore possible underlying mechanisms. Various neuropsychological assessments were performed on all participants. Tract-based spatial statistics (TBSS) was used to compare DTI metrics such as fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Correlation analysis was analyzed between DTI metrics and cognitive scales. Compared with the HC group, the AN group performed worse in the neuropsychological evaluations, and TBSS analysis showed widespread alteration of the FA, AD, RD, and MD, which correlated with the cognitive function. These white matter tracts include minor forceps, major forceps, anterior thalamic radiation, superior longitudinal fasciculus, corticospinal tract, and right inferior fronto-occipital fasciculus. Meanwhile, we found for the first time that cognitive decline was related to the decrease of FA in minor forceps, which can be used as a neurobiological marker of cognitive impairment in patients with AN. The occurrence of cognition impairment is common in patients with AN. Including neuropsychological evaluation in the routine clinical assessment and appropriate treatment may strengthen clinical management and improve the quality of life of patients. [ABSTRACT FROM AUTHOR]

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.

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract Background Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk. Methods We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation). Results MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses. Conclusions Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD.

The present study was designed to systemically evaluate changes in the diffusion tensor imaging (DTI)-derived parameters of iNPH (idiopathic normal pressure hydrocephalus) patients with different responses to the tap test (TT), and to correlate cognitive impairment with white matter (WM) degeneration. This study included 22 iNPH patients and 14 healthy controls with structural magnetic resonance imaging (MRI) and DTI scanning. DTI was used to explore the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for all participants. DTI parameters were evaluated using an ROI (region of interest)-based and tract-based spatial statistics (TBSS) approach. Neuropsychological assessments and the idiopathic normal pressure hydrocephalus grading scoring scale (iNPHGS) were performed. Compared to the TT non-responders, the TT responders group had significantly lower FA values in the corpus callosum, cingulum cingulate gyrus, superior longitudinal fasciculus, and lower AD values in the right cingulum cingulate gyrus and the left posterior thalamic radiation. Besides, the MD values were significantly increased in the corpus callosum, left anterior corona radiata, and the RD values in the corpus callosum and cingulum cingulate gyrus. In addition, the cognitive improvement was negatively correlated with FA of the corpus callosum, cingulum cingulate gyrus, and MD values of the genu of corpus callosum. While, the cognitive improvement was positively related to the AD of the cingulum cingulate gyrus, superior longitudinal, and RD values of the corpus callosum, cingulum cingulate gyrus and uncinate fasciculus. The ROI specific WM lesions in iNPH patients are the underlying basis for cognitive impairment.

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging. [ABSTRACT FROM AUTHOR]

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging.

Population aging has become a serious social problem. Accordingly, many researches are focusing on changes in brains of the elderly. In this study, we used multiple parameters to analyze age-related changes in white matter fibers. A sample cohort of 58 individuals was divided into young and middle-age groups and tract-based spatial statistics (TBSS) were used to analyze the differences in fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD) between the two groups. Deterministic fiber tracking was used to investigate the correlation between fiber number and fiber length with age. The TBSS analysis revealed significant differences in FA, MD, AD, and RD in multiple white matter fibers between the two groups. In the middle-age group FA and AD were lower than in young people, whereas the MD and RD values were higher. Deterministic fiber tracking showed that the fiber length of some fibers correlated positively with age. These fibers were observed in the splenium of corpus callosum (SCC), the posterior limb of internal capsule (PLIC), the right posterior corona radiata (PCR_R), the anterior corona radiata (ACR), the left posterior thalamic radiation (include optic radiation; PTR_L), and the left superior longitudinal fasciculus (SLF_L), among others. The results showed that the SCC, PLIC, PCR_R, ACR, PTR_L, and SLF_L significantly differed between young and middle-age people. Therefore, we believe that these fibers could be used as image markers of age-related white matter changes.

Population aging has become a serious social problem. Accordingly, many researches are focusing on changes in brains of the elderly. In this study, we used multiple parameters to analyze age-related changes in white matter fibers. A sample cohort of 58 individuals was divided into young and middle-age groups and tract-based spatial statistics (TBSS) were used to analyze the differences in fractional anisotropy (FA), mean diffusion (MD), axial diffusion (AD), and radial diffusion (RD) between the two groups. Deterministic fiber tracking was used to investigate the correlation between fiber number and fiber length with age. The TBSS analysis revealed significant differences in FA, MD, AD, and RD in multiple white matter fibers between the two groups. In the middle-age group FA and AD were lower than in young people, whereas the MD and RD values were higher. Deterministic fiber tracking showed that the fiber length of some fibers correlated positively with age. These fibers were observed in the splenium of corpus callosum (SCC), the posterior limb of internal capsule (PLIC), the right posterior corona radiata (PCR_R), the anterior corona radiata (ACR), the left posterior thalamic radiation (include optic radiation; PTR_L), and the left superior longitudinal fasciculus (SLF_L), among others. The results showed that the SCC, PLIC, PCR_R, ACR, PTR_L, and SLF_L significantly differed between young and middle-age people. Therefore, we believe that these fibers could be used as image markers of age-related white matter changes. [ABSTRACT FROM AUTHOR]

Analysis of scalar maps obtained by diffusion tensor imaging (DTI) produce valuable information about the microstructure of the brain white matter. The DTI scanning of child populations, compared with adult groups, requires specifically designed data acquisition protocols that take into consideration the trade-off between the scanning time, diffusion strength, number of diffusion directions, and the applied analysis techniques. Furthermore, inadequate normalization of DTI images and non-robust tensor reconstruction have profound effects on data analyses and may produce biased statistical results. Here, we present an acquisition sequence that was specifically designed for pediatric populations, and describe the analysis steps of the DTI data collected from extremely preterm-born young school-aged children and their age- and gender-matched controls. The protocol utilizes multiple software packages to address the effects of artifacts and to produce robust tensor estimation. The computation of a population-specific template and the nonlinear registration of tensorial images with this template were implemented to improve alignment of brain images from the children.

• The first meta-analysis of whole-brain voxel-based DTI studies in childhood maltreatment. • Anisotropic effect-size signed differential mapping was used to examine regions of altered FA in maltreated individuals relative to controls. • Neural pathways linking fronto-limbic and occipital visual areas involved in processing the abusive experience are specifically compromised. We conducted the first meta-analysis of whole-brain voxel-based DTI studies in childhood maltreatment to elucidate regions of white matter (WM) microstructure abnormality relative to non-maltreated controls. Fourteen DTI datasets were included, comprising 386 individuals with childhood maltreatment and 612 non-maltreated controls. Anisotropic effect-size signed differential mapping, a voxel-based meta-analytic method, was used to examine regions of altered fractional anisotropy (FA) in maltreated individuals relative to controls. Maltreated individuals had significantly reduced FA in the left anterior thalamic radiation and bilateral fornix, optic radiations, inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus, along with the anterior portions of the corpus callosum. There were no regions with increased FA. Decreased FA in the callosal genu and body remained in subgroup analyses of unmedicated and drug-free participants. Findings suggest that childhood maltreatment is associated with widespread WM microstructural abnormalities particularly evident in the fornix, corpus callosum and optic radiations, where the neural pathways linking fronto-limbic and occipital visual cortices presumably involved in conveying and processing the (aversive) experience may be compromised in this population. [ABSTRACT FROM AUTHOR]

Microstructural white matter (WM) disruption and resulting abnormal structural connectivity form a potential underlying pathology in traumatic brain injury (TBI). Herein, to determine the potential mechanism of cognitive deterioration in TBI, we examined the association of damage to specific WM tracts with cognitive function in TBI patients. We recruited 18 individuals with mild-to-moderate/severe TBI in the chronic phase and 17 age-matched controls. We determined the pattern of WM aberrations in TBI using tract-based spatial statistics (TBSS) and then examined the relationship between cognitive impairment and WM damage using the threshold-free cluster enhancement correction in TBSS. TBSS analysis showed that TBI patients exhibited WM aberrations in a wide range of brain regions. In the majority of these regions, lower fractional anisotropy (FA) largely overlapped with increased radial diffusivity, but not with axial diffusivity. Further, voxel-wise correction in TBSS demonstrated that higher FA values were associated with better performance in the phonemic verbal fluency task (VFT) in widespread WM regions, but not with the semantic VFT. Despite variation in the magnitude and location of brain injury between individual cases, chronic TBI patients exhibited widespread WM aberrations. We confirmed the findings of previous studies that WM integrity is lower across the spectrum of TBI severity in chronic subjects compared to controls. Further, phonemic VFT may be a more sensitive cognitive measure of executive dysfunction associated with WM aberrations in TBI compared with semantic VFT. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) and Alzheimer's disease (AD) are associated with divergent differences in grey matter volume, white matter diffusion, and functional connectivity. However, it is unknown at what disease stage these differences emerge. Here, we investigate whether divergent differences in grey matter volume, white matter diffusion, and functional connectivity are already apparent between cognitively healthy carriers of pathogenic FTD mutations, and cognitively healthy carriers at increased AD risk.Methods: We acquired multimodal magnetic resonance imaging (MRI) brain scans in cognitively healthy subjects with (n=39) and without (n=36) microtubule-associated protein Tau (MAPT) or progranulin (GRN) mutations, and with (n=37) and without (n=38) apolipoprotein E ε4 (APOE4) allele. We evaluated grey matter volume using voxel-based morphometry, white matter diffusion using tract-based spatial statistics (TBSS), and region-to-network functional connectivity using dual regression in the default mode network and salience network. We tested for differences between the respective carriers and controls, as well as for divergence of those differences. For the divergence contrast, we additionally performed region-of-interest TBSS analyses in known areas of white matter diffusion differences between FTD and AD (i.e., uncinate fasciculus, forceps minor, and anterior thalamic radiation).Results: MAPT/GRN carriers did not differ from controls in any modality. APOE4 carriers had lower fractional anisotropy than controls in the callosal splenium and right inferior fronto-occipital fasciculus, but did not show grey matter volume or functional connectivity differences. We found no divergent differences between both carrier-control contrasts in any modality, even in region-of-interest analyses.Conclusions: Concluding, we could not find differences suggestive of divergent pathways of underlying FTD and AD pathology in asymptomatic risk mutation carriers. Future studies should focus on asymptomatic mutation carriers that are closer to symptom onset to capture the first specific signs that may differentiate between FTD and AD. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a severe mental illness characterised by reduced grey matter (GM) volumes and cortical thickness, and disrupted white matter (WM) microstructure. Activation of indoleamine 2,3-dioxygenase following a pro-inflammatory state could increase the amount of tryptophan (Trp) converted to kynurenine (Kyn) possibly leading to the production of detrimental catabolites of the Kyn pathway with neurotoxic effects. We investigated if peripheral levels of Trp-and Kyn and the breakdown of Trp-into Kyn (Kyn/Trp-ratio) are related to WM and GM integrity in BD.Methods: Peripheral levels of Trp-and Kyn were analysed in 72 patients with BD and 33 controls. Patients also underwent MRI in a Philips 3T scanner.Results: Patients showed higher Kyn levels and Kyn/Trp-ratio compared to controls. MRI analyses performed in patients with BD showed a negative association between the Kyn/Trp-ratio and the integrity of corpus callosum microstructure, the volume of the amygdala and cortical thickness in fronto-parietal regions.Limitation: The lack of information on the levels of downstream metabolites of Kyn prevent us to confirm the possible unbalance between quinolinic and kynurenic acids as well as their possible relationship with changes in GM and WM markers. The activation of the Kyn pathway as suggested by the increased Kyn/Trp-ratio may lead to an imbalance of the neurotoxic vs the neuroprotective arm of the biochemical pathway, resulting in significant changes in GM and WM regions of brain areas strongly implicated in the pathophysiology of BD, such as amygdala and corpus callosum. [ABSTRACT FROM AUTHOR]

• This study assessed white matter alterations and their associations with behavior & memory in adolescents with BPD. • Adolescents with BPD had white matter deficits in the cortical-limbic and cortical-thalamus circuits. • Preserved visual working memory may protect against non-suicidal self-injurious behavior in adolescents with BPD. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Tract-based spatial statistics (TBSS) is suitable for the assessment of voxel-wise changes in fiber integrity in WM tracts in the entire brain. Longitudinal TBSS analyses of early multiple sclerosis (MS) using 3 Tesla magnetic resonance imaging (MRI) are not common.Objective: To characterize microstructural WM alterations at initial diagnosis in clinically isolated syndrome (CIS) and early MS at baseline and longitudinally over 2 years.Methods: DTI (Diffusion tensor imaging) at 3 Tesla was used to evaluate 106 therapy-naive patients with CIS or definite MS at baseline and at 1-year (N = 83) and 2-year (N = 43) follow-up compared to healthy controls (HC, N = 49). TBSS was used for voxel-wise analyses of the DTI indices of fractional anisotropy (FA) and radial, mean, and axial diffusivity (RD, MD, AD) for cross-sectional and longitudinal comparisons. Mean values of FA, RD, and cluster voxel numbers were extracted from significant clusters using an atlas-based approach. Correlations with disability (EDSS) were calculated for FA and RD changes related to affected brain regions.Results: Reductions in FA compared to HC were found at baseline in patients with CIS and RRMS and involved most supra- and infratentorial WM tracts. In the cerebellum and cerebral peduncles, these changes negatively correlated with EDSS after 2 years. FA changes in patients with CIS and RRMS evolved in the second year, particularly in the descending projection pathways and the cerebellum, and were significantly associated with EDSS. RD alterations compared to HC were undetectable in patients at baseline but were observed after 1 year and were exacerbated during the second year in all major supratentorial WM tracts, the corpus callosum, and the cerebellum. FA did not change between baseline and year 1 follow-up, but longitudinal investigation between the first and second year revealed combined dynamic FA and RD changes in the corpus callosum and corona radiata.Conclusion: TBSS of diffusion metrics at initial diagnosis and at 2-year follow-up showed microstructural WM pathology and associations between FA reduction and future disability, respectively. Combined longitudinal changes in FA and RD occurred in specific structures, where RD increases likely reflected progressing axonal degeneration. The distinct temporal dynamics of FA and RD, implying constancy during the first year, supports early therapeutic intervention for CIS and RRMS.

Background: Tract-based spatial statistics (TBSS) is suitable for the assessment of voxel-wise changes in fiber integrity in WM tracts in the entire brain. Longitudinal TBSS analyses of early multiple sclerosis (MS) using 3 Tesla magnetic resonance imaging (MRI) are not common. Objective: To characterize microstructural WM alterations at initial diagnosis in clinically isolated syndrome (CIS) and early MS at baseline and longitudinally over 2 years. Methods: DTI (Diffusion tensor imaging) at 3 Tesla was used to evaluate 106 therapy-naive patients with CIS or definite MS at baseline and at 1-year (N = 83) and 2-year (N = 43) follow-up compared to healthy controls (HC, N = 49). TBSS was used for voxel-wise analyses of the DTI indices of fractional anisotropy (FA) and radial, mean, and axial diffusivity (RD, MD, AD) for cross-sectional and longitudinal comparisons. Mean values of FA, RD, and cluster voxel numbers were extracted from significant clusters using an atlas-based approach. Correlations with disability (EDSS) were calculated for FA and RD changes related to affected brain regions. Results: Reductions in FA compared to HC were found at baseline in patients with CIS and RRMS and involved most supra- and infratentorial WM tracts. In the cerebellum and cerebral peduncles, these changes negatively correlated with EDSS after 2 years. FA changes in patients with CIS and RRMS evolved in the second year, particularly in the descending projection pathways and the cerebellum, and were significantly associated with EDSS. RD alterations compared to HC were undetectable in patients at baseline but were observed after 1 year and were exacerbated during the second year in all major supratentorial WM tracts, the corpus callosum, and the cerebellum. FA did not change between baseline and year 1 follow-up, but longitudinal investigation between the first and second year revealed combined dynamic FA and RD changes in the corpus callosum and corona radiata. Conclusion: TBSS of diffusion metrics at initial diagnosis and at 2-year follow-up showed microstructural WM pathology and associations between FA reduction and future disability, respectively. Combined longitudinal changes in FA and RD occurred in specific structures, where RD increases likely reflected progressing axonal degeneration. The distinct temporal dynamics of FA and RD, implying constancy during the first year, supports early therapeutic intervention for CIS and RRMS. [ABSTRACT FROM AUTHOR]

Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients.This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).

DTI studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression. In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration. DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (

Highlights • BMI associates with DTI measures of WM integrity in schizophrenia. • Normal weight group showed higher AD and FA than the obese group in large portions of the WM skeleton. • The relationship was not significantly different between males and females. • Obesity might contribute to the pathophysiology of schizophrenia, exerting a detrimental action on structural connectivity. Abstract Background White matter (WM) alterations have been consistently described in patients with schizophrenia and correlated with the severity of psychotic symptoms and cognitive impairment. Obesity has been reported in over 40% of patients with schizophrenia and has been associated with cognitive deficits, cardiovascular diseases, metabolic alterations, and overall mortality. Moreover, studies among healthy subjects and subjects at risk for psychosis reported an influence of Body Mass Index (BMI) on structural connectivity. We therefore hypothesized that obesity and overweight could further disrupt WM integrity of patients affected by schizophrenia. Methods Eighty-eight schizophrenia patients were evaluated for BMI. We divided the sample in overweight/obese and normal weight groups. We then performed whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA). Results A significant difference between the two groups was observed: normal weight patients showed higher AD and a higher FA trend compared to obese patients in several fibers’ tracts including longitudinal fasciculus, uncinate fasciculus, corona radiata, thalamic radiation, fronto-occipital fasciculus, cingulum and corpus callosum. Conclusions Elevated BMI might contribute to WM disruption of schizophrenia by hampering structural connectivity in critical cortico-limbic networks, known to play a crucial role in neurocognitive functioning, emotional processing and psychopathology whose dysfunction are prominent features of the disorder. [ABSTRACT FROM AUTHOR]

Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants. Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex. Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated. Highlights - T2DM patients without MCI demonstrated no obvious brain volume decrease. - Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients. - Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected. - The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients. This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinical trials.gov/). [ABSTRACT FROM AUTHOR]

Abstract: Background: Childhood adversity (CA) leads to greater vulnerability for psychopathology by causing structural as well as functional brain abnormalities. Recent findings on gray matter effects point towards the importance of identifying CA outcome as a function of different CA types, varying in the dimensions of threat and deprivation. Using diffusion tensor imaging, we investigate whether different forms of CA impact differently on white matter connectivity in a healthy cohort not confounded by other aspects of disease. Methods: In 120 healthy young males, we assessed different forms of maltreatment during childhood with the Childhood Trauma Questionnaire (CTQ). Fractional anisotropy (FA) and mean diffusivity (MD) images were generated and projected onto a white matter skeleton using tract‐based spatial statistics. Correlational analysis between FA, MD, and CTQ subscores was then performed using voxelwise statistics. Results: Of all CTQ‐subscores, only physical neglect (PN) predicted a decrease of FA but not MD in the bilateral anterior thalamic radiation around the middle frontal gyrus and the right inferior fronto‐occipital fasciculus, the inferior longitudinal fasciculus, the cingulum and precuneus. Reduced FA in the posterior cingulum was related to the effects of PN during childhood on anxiety levels at trend level. Conclusions: PN may have severe consequences and should be considered equally important to more active forms of abuse. FA changes, particularly in the cingulum, actually appear to a functional consequence and are linked to trait anxiety, a personality dimension that is suggested to be a transdiagnostic risk factor of affective disorders. Potentially this reveals a mechanistic chain that forms one pathyway from CA to disease. [ABSTRACT FROM AUTHOR]

Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord. We further conducted correlation analyses between DTI data and clinical characteristics. Results: TBSS analysis in HSP patients showed significantly decreased fractional anisotropy of the corpus callosum and the corticospinal tract compared to healthy controls. ROI-based analysis confirmed significantly lower FA in HSP compared to controls in the internal capsule (0.77 vs. 0.80, p = 0.048), the corpus callosum (0.84 vs. 0.87, p = 0.048) and the cervical spinal cord (0.72 vs. 0.79, p = 0.003). FA values of the cervical spinal cord significantly correlated with disease duration. Conclusion: DTI metrics of the corticospinal tract from the internal capsule to the cervical spine suggest microstructural damage and axonal degeneration of motor neurons. The CST at the level of the cervical spinal cord is thereby more severely affected than the intracranial part of the CST, suggesting an ascending axonal degeneration of the CST. Since there is a significant correlation with disease duration, FA may serve as a future progression marker for assessment of the disease course in HSP.

Diffusion tensor imaging (DTI) studies in chronic schizophrenia have found widespread but often inconsistent patterns of white matter abnormalities. These studies have typically used the conventional measure of fractional anisotropy, which can be contaminated by extracellular free-water. A recent free-water imaging study reported reduced free-water corrected fractional anisotropy (FAT) in chronic schizophrenia across several brain regions, but limited changes in the extracellular volume. The present study set out to validate these findings in a substantially larger sample. Tract-based spatial statistics (TBSS) was performed in 188 healthy controls and 281 chronic schizophrenia patients. Forty-two regions of interest (ROIs), as well as average whole-brain FAT and FW were extracted from free-water corrected diffusion tensor maps. Compared to healthy controls, reduced FAT was found in the chronic schizophrenia group in the anterior limb of the internal capsule bilaterally, the posterior thalamic radiation bilaterally, as well as the genu and body of the corpus callosum. While a significant main effect of group was observed for FW, none of the follow-up contrasts survived correction for multiple comparisons. The observed FAT reductions in the absence of extracellular FW changes, in a large, multi-site sample of chronic schizophrenia patients, validate the pattern of findings reported by a previous, smaller free-water imaging study of a similar sample. The limited number of regions in which FAT was reduced in the schizophrenia group suggests that actual white matter tissue degeneration in chronic schizophrenia, independent of extracellular FW, might be more localized than suggested previously. [ABSTRACT FROM AUTHOR]

Automated analysis of diffusion tensor imaging (DTI) data is an appealing way to process large datasets in an unbiased manner. However, automation can sometimes be linked to a lack of interpretability. Two whole-brain, automated and voxelwise methods exist: voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). In VBA, the amount of smoothing has been shown to influence the results. TBSS is free of this step, but a projection procedure is introduced to correct for residual misalignments. This projection assigns the local highest fractional anisotropy (FA) value to the mean FA skeleton, which represents white matter tract centers. For both methods, the normalization procedure has a major impact. These issues are well documented in humans but, to our knowledge, not in rodents. In this study, we assessed the quality of three different registration algorithms (ANTs SyN, DTI-TK and FNIRT) using study-specific templates and their impact on automated analysis methods (VBA and TBSS) in a rat pup model of diffuse white matter injury presenting large unilateral deformations. VBA and TBSS results were stable and anatomically coherent across the three pipelines. For VBA, in regions around the large deformations, interpretability was limited because of the increased partial volume effect. With TBSS, two of the three pipelines found a significant decrease in axial diffusivity (AD) at the known injury site. These results demonstrate that automated voxelwise analyses can be used in an animal model with large deformations. [ABSTRACT FROM AUTHOR]

Background: 22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia.Methods: Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/-2 years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed.Results: Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale.Conclusion: Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms. [ABSTRACT FROM AUTHOR]

Background Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may thus influence the development of brain functions. The main objective of this study was to examine the effect of Val158Met (rs4680) polymorphism of Catechol- O-Methyltransferase ( COMT) gene on white matter connectivity in healthy adults. Methods We used a whole-brain diffusion-weighted imaging method with Tract-Based Spatial Statistics ( TBSS) analysis to examine white matter structural integrity in intrinsic brain networks on a sample of healthy subjects ( N = 82). Results Results revealed a sex-specific effect of COMT on corpus callosum ( CC): in males only, Val homozygotes had significantly higher fractional anisotropy ( FA) compared to Met-carriers. Volume-of-interest analysis showed a genotype by sex interaction on FA in genu and rostral midbody of CC, whereby Val males demonstrated higher FA than Met females. Conclusions These results demonstrate the key effect of genes by sex interaction, rather than their individual contribution, on the corpus callosum anatomy. [ABSTRACT FROM AUTHOR]

Background: We previously reported widespread microstructural deficits of brain white matter in alcohol-dependent individuals (ALC) compared to light drinkers in a small 1.5T diffusion tensor imaging study employing tract-based spatial statistics. Using a larger dataset acquired at 4T, the present study is an extension that investigated the effects of alcohol consumption, abstinence from alcohol, and comorbid cigarette smoking on white matter microstructure.Methods: Tract-based spatial statistics were performed on 20 1-week-abstinent ALC, 52 1-month-abstinent ALC, and 30 controls. Regional measures of fractional anisotropy (FA) and mean diffusivity (MD) in the significant clusters were compared by Analysis of Covariance. The metrics were correlated with substance use history and behavioral measures.Results: 1-week-abstinent ALC showed lower FA than controls in the corpus callosum, right cingulum, external capsule, and hippocampus. At 1 month of abstinence, only the FA in the body of the corpus callosum of ALC remained significantly different from controls. Some regional FA deficits correlated with more severe measures of drinking and smoking histories but only weakly with mood and impulsivity measures.Conclusion: White matter microstructure is abnormal during early abstinence in alcohol dependent treatment seekers and recovers into the normal range within about four weeks. The compromised white matter was related to substance use severity, mood, and impulsivity. Our findings suggest that ALC may benefit from interventions that facilitate normalization of DTI metrics to maintain abstinence, via smoking cessation, cognitive-based therapy, and perhaps pharmacology to support remyelination. [ABSTRACT FROM AUTHOR]

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel-based analysis are highly dependent on the user-hypothesis and parameter settings for implementation. In contrast, tract-based spatial statistics (TBSS) allows for reliable voxel-wise analysis via the projection of diffusion-derived parameters onto an alignment-invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI-derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats ( N = 6). FA values remained unchanged 2-4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post-stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post-stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo-normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke. [ABSTRACT FROM AUTHOR]

Objectives: The main goal of this study was to investigate and compare the neural substrate of two children's profiles of high intelligence quotient (HIQ). Methods: Two groups of HIQ children were included with either a homogeneous (Hom-HIQ: n = 20) or a heterogeneous IQ profile (Het-HIQ: n = 24) as defined by a significant difference between verbal comprehension index and perceptual reasoning index. Diffusion tensor imaging was used to assess white matter (WM) microstructure while tract-based spatial statistics (TBSS) analysis was performed to detect and localize WM regional differences in fractional anisotropy (FA), mean diffusivity, axial (AD), and radial diffusivities. Quantitative measurements were performed on 48 regions and 21 fiber-bundles of WM. Results: Hom-HIQ children presented higher FA than Het-HIQ children in widespread WM regions including central structures, and associative intra-hemispheric WM fasciculi. AD was also greater in numerous WM regions of Total-HIQ, Hom-HIQ, and Het-HIQ groups when compared to the Control group. Hom-HIQ and Het-HIQ groups also differed by their hemispheric lateralization in AD differences compared to Controls. Het-HIQ and Hom-HIQ groups showed a lateralization ratio (left/right) of 1.38 and 0.78, respectively. Conclusions: These findings suggest that both inter- and intra-hemispheric WM integrity are enhanced in HIQ children and that neural substrate differs between Hom-HIQ and Het-HIQ. The left hemispheric lateralization of Het-HIQ children is concordant with their higher verbal index while the relative right hemispheric lateralization of Hom-HIQ children is concordant with their global brain processing and adaptation capacities as evidenced by their homogeneous IQ. [ABSTRACT FROM AUTHOR]

Recent studies of long-term anabolic-androgenic steroid (AAS) users reported amygdala structural and functional connectivity abnormalities. We assessed white matter microstructure in the inferior-fronto-occipital fasciculus (IFOF), a major associative bundle of the amygdala network. Diffusion weighted images acquired from 9 male long-term AAS users and 8 matched controls aged 36–51 years old were processed using a standardized pipeline (Tract-Based Spatial Statistics). Group differences were examined using linear regression with adjustment for age and current testosterone level. Compared to nonusers, AAS users exhibited significantly higher fractional anisotropy (FA) in the IFOF. Users showed markedly greater FA than nonusers on the left IFOF but only a modest, nonsignificant difference on the right IFOF. Moreover, FA was positively associated with lifetime cumulative AAS dose. Our results suggest that long-term AAS use alters IFOF white matter organization and integrity, which in turn might affect amygdala-related processes such as reward system function. Accordingly, further studies are needed to replicate findings in larger subject groups to determine the functional significance of the FA abnormality. [ABSTRACT FROM AUTHOR]

Background Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that reflects the Brownian motion of water molecules constrained within brain tissue. Fractional anisotropy (FA) is one of the most commonly measured DTI parameters, and can be applied to quantitative analysis of white matter as tract-based spatial statistics (TBSS) and voxel-wise analysis. Purpose To show an association between metallic implants and the results of statistical analysis (voxel-wise group comparison and TBSS) for fractional anisotropy (FA) mapping, in DTI of healthy adults. Material and Methods Sixteen healthy volunteers were scanned with 3-Tesla MRI. A magnetic keeper type of dental implant was used as the metallic implant. DTI was acquired three times in each participant: (i) without a magnetic keeper (FAnon1); (ii) with a magnetic keeper (FAimp); and (iii) without a magnetic keeper (FAnon2) as reproducibility of FAnon1. Group comparisons with paired t-test were performed as FAnon1 vs. FAnon2, and as FAnon1 vs. FAimp. Results Regions of significantly reduced and increased local FA values were revealed by voxel-wise group comparison analysis (a P value of less than 0.05, corrected with family-wise error), but not by TBSS. Conclusion Metallic implants existing outside the field of view produce artifacts that affect the statistical analysis (voxel-wise group comparisons) for FA mapping. When statistical analysis for FA mapping is conducted by researchers, it is important to pay attention to any dental implants present in the mouths of the participants. [ABSTRACT FROM AUTHOR]

Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia. [ABSTRACT FROM AUTHOR]

We investigated common structural and network changes across the sporadic amyotrophic lateral sclerosis (ALS)-frontotemporal dementia (FTD) continuum. Based on cluster analysis using the frontotemporal assessment battery, 51 patients with sporadic ALS were subdivided into three groups: 25 patients with ALS with cognitive deficiency (ALS-CD); seven patients who satisfied FTD criteria (ALS-FTD), and 19 patients with ALS with normal cognitive function (ALS-NC). Compared with the controls, gray matter images from patients with ALS-FTD showed atrophic changes in the following order of severity: caudate head, medial frontal gyrus, thalamus, amygdala, putamen, and cingulate gyrus (peak level, uncorrectedp < 0.001). The caudate head was significant at the cluster level using FWE correction (p < 0.05). Diffusion tensor imaging with tract-based spatial statistics revealed white matter changes in the areas surrounding the caudate head, the internal capsule, and the anterior horn of the lateral ventricle in the ALS-CD and ALS-FTD. Probabilistic diffusion tractography showed a significant decrease in structural connectivity between the caudate head and the dorsomedial frontal cortex and the lateral orbitofrontal cortex, even in the ALS-NC. Our results indicated that the caudate head and its networks were the most vulnerable to lesion in sporadic ALS-FTD-spectrum patients associated with cognitive decline with FTD features. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to conduct a preliminary investigation of the white matter characteristics in patients with psychogenic non-epileptic seizures (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3 T in 16 patients with PNES and 16 age- and sex-matched healthy controls (HC). All patients with PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid neurological or psychiatric conditions. DTI indices including fractional anisotropy (FA), and mean diffusivity (MD) were calculated and compared between patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS). Significantly higher FA values were observed in patients with PNES in the left corona radiata, left internal and external capsules, left superior temporal gyrus, as well as left uncinate fasciculus (UF) ( P <0.05; corrected for multiple comparisons). There was no significant change in other indices between patients with PNES and HCs. These findings suggest that patients with PNES have significantly altered white matter structural connectivity when compared to age- and sex-matched HCs. These abnormalities are present in left hemispheric regions associated with emotion regulation and motor pathways. While the relationship between the pathophysiology of PNES and these abnormalities is not entirely clear, this work provides an initial basis to guide future prospective studies. [ABSTRACT FROM AUTHOR]

This paper presents a fractional anisotropy asymmetry (FAA) method to detect the asymmetry of white matter (WM) integrity and its correlation with the side of seizure origin for partial onset temporal lobe epilepsy (TLE) using diffusion tensor image (DTI). In this study, FAA analysis is applied to 30 patients of partial TLE (15 left, 15 right) and 14 matched normal controls. Specifically, after registering all the images with the JHU-DTI-MNI template the average FA value of each FA skeleton section is calculated using the tract-based spatial statistics (TBSS) method. Then, FAA is calculated to quantify the WM diffusivity asymmetry of the corresponding region-pairs between the left and right hemispheres. Using FAA the regional asymmetry contributing significantly to the group differences of controls and left/right TLE, as well as the left and right TLE, is identified. As a comparison, the ROI-based average FA values for WM and corresponding FAAs are also calculated. TBSS-based analysis reflects the average of local maximal FA values along the white matter skeleton sections, and ROI-based analysis shows the average of WM FA values within each anatomical region. The FAA statistical results indicated that the FA values of anatomical region-pairs are asymmetric in the ipsilateral hemisphere with seizure origin against the contralateral hemisphere. Particularly, FAA values within the temporal lobe (superior, middle, and inferior temporal WM) are significantly different between the left and right TLE patients, consistently found from both analysis methods. The study suggests that FAA values can be potentially used to identify the seizures of origin of TLE and to help understand the relationship between fiber tracts with the side of seizure origin of TLE. [ABSTRACT FROM AUTHOR]

Abstract: There has been an increasing interest in white matter abnormalities in patients with anorexia nervosa (AN). However, to date, there have been only a few diffusion tensor imaging (DTI) studies investigating AN, and the results are inconsistent. In this study, we employed tract-based spatial statistics (TBSS), a robust technique for whole-brain analysis of DTI data, to detect white matter abnormalities in AN patients compared with healthy controls. Seventeen women with AN and 18 age matched healthy women were included. The mean body mass index of patients was 13.6kg/m2 (controls: 19.9kg/m2). DTI data were acquired on a 3-Tesla magnetic resonance imaging system. Fractional anisotropy (FA) and mean diffusivity (MD) maps were calculated from the DTI data of each patient, and voxel-wise group comparisons of FA and MD were performed using TBSS. Compared with the healthy comparisons, the patients showed a significantly higher MD value in the fornix and lower FA value in the left cerebellum. We also found significant positive correlations between the mean FA value of the left cerebellar hemisphere cluster and BMI, as well as between the mean MD value of the cluster in the anterior body of the fornix and the duration of illness. The results suggest that the white matter abnormalities in the fornix and the cerebellum may be related to the pathophysiology of AN. [Copyright &y& Elsevier]

Humans vary substantially in their ability to learn new motor skills. Here, we examined inter-individual differences in learning to play the piano, with the goal of identifying relations to structural properties of white matter fiber tracts relevant to audio-motor learning. Non-musicians ( n = 18) learned to perform three short melodies on a piano keyboard in a pure audio-motor training condition (vision of their own fingers was occluded). Initial learning times ranged from 17 to 120 min (mean ± SD: 62 ± 29 min). Diffusion-weighted magnetic resonance imaging was used to derive the fractional anisotropy (FA), an index of white matter microstructural arrangement. A correlation analysis revealed that higher FA values were associated with faster learning of piano melodies. These effects were observed in the bilateral corticospinal tracts, bundles of axons relevant for the execution of voluntary movements, and the right superior longitudinal fasciculus, a tract important for audio-motor transformations. These results suggest that the speed with which novel complex audio-motor skills can be acquired may be determined by variability in structural properties of white matter fiber tracts connecting brain areas functionally relevant for audio-motor learning. Hum Brain Mapp 35:2483-2497, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective: To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology. Study design: A population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development–Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91). Results: EPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls. Conclusion: Cognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels. [Copyright &y& Elsevier]

Abstract: Although diffusion tensor imaging (DTI) studies have reported fractional anisotropy (FA) abnormalities in multiple white matter (WM) regions in schizophrenia, relationship between abnormal FA and negative symptoms has not been fully explored. DTI data were acquired from twenty-four patients with chronic schizophrenia and twenty-five healthy controls. Regional brain abnormalities were evaluated by conducting FA comparisons in the cerebral and each lobar WMs between groups. Focal abnormalities were also evaluated with a voxel-wise tract specific method. Associations between structural WM changes and negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS). The patient group showed decreased FA in the cerebrum, especially in the frontal lobe, compared with controls. A voxel-wise analysis showed FA decreases in almost all WM tracts in schizophrenia. Correlation analyses demonstrated negative relationships between FA in the cerebrum, particularly in the left hemisphere, and SANS global and global rating scores (Anhedonia–Asociality, Attention, and Affective-Flattening), and also associations between FA of left frontal lobe and SANS global score, Anhedonia–Asociality, and Attention. This study demonstrates that patients with chronic schizophrenia evince widespread cerebral FA abnormalities and that these abnormalities, especially in the left hemisphere, are associated with negative symptoms. [Copyright &y& Elsevier]

Abstract: Background: The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure. Methods: To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography. Results: Morphological analysis revealed an “inverted-U” shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles. Conclusion: In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression. [Copyright &y& Elsevier]