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.

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.

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.

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.

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.

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.

Neuroanatomical Correlates of Cognitive Tests in Young-onset MCI.

BACKGROUND: Mild Cognitive Impairment (MCI) is a heterogeneous condition characterised by cognitive changes that do not affect everyday functioning and may represent a predementia phase. Research on the neuroanatomical correlates of cognitive tests used to diagnose MCI is heterogeneous and has mainly focused on elderly populations of patients with MCI, usually well above the age of 65. However, the effect of ageing on brain structure is known to be substantial and to affect brain-behaviour associations in older people. We explored the brain correlates of different cognitive tests in a group of young-onset MCI (i.e., with symptoms onset before the age of 65) to minimise the effect of ageing on brain-behaviour associations. METHODS: Patients with a clinical diagnosis of young-onset MCI underwent extensive cognitive assessment and multimodal Magnetic Resonance Imaging (MRI) including high-resolution T1-weighted and Diffusion Tensor Imaging (DTI) sequences. Their scores on cognitive tests were related to measures of grey matter (GM) density and white matter (WM) integrity using, respectively, Voxel Based Morphometry (VBM) and Tract-Based Spatial Statistics (TBSS). RESULTS: 104 young-onset MCI were recruited. VBM and TBSS whole-brain correlational analyses showed that between-subject variability in cognitive performance was significantly associated with regional variability in GM density and WM integrity. While associations between cognitive scores and focal GM density in our young-onset MCI group reflected the well-known lateralization of verbal and visuo-spatial abilities on the left and right hemispheres respectively, the associations between cognitive scores and WM microstructural integrity were widespread and diffusely involved most of the WM tracts in both hemispheres. CONCLUSIONS: We investigated the structural neuroanatomical correlates of cognitive tests in young-onset MCI in order to minimise the effect of ageing on brain-behaviour associations.

Effect of number of diffusion-encoding directions in diffusion metrics of 5-year-olds using tract-based spatial statistical analysis.

Methodological aspects and effects of different imaging parameters on DTI (diffusion tensor imaging) results and their reproducibility have been recently studied comprehensively in adult populations. Although MR imaging of children's brains has become common, less interest has been focussed on researching whether adult-based optimised parameters and pre-processing protocols can be reliably applied to paediatric populations. Furthermore, DTI scalar values of preschool aged children are rarely reported. We gathered a DTI dataset from 5-year-old children (N = 49) to study the effect of the number of diffusion-encoding directions on the reliability of resultant scalar values with TBSS (tract-based spatial statistics) method. Additionally, the potential effect of within-scan head motion on DTI scalars was evaluated. Reducing the number of diffusion-encoding directions deteriorated both the accuracy and the precision of all DTI scalar values. To obtain reliable scalar values, a minimum of 18 directions for TBSS was required. For TBSS fractional anisotropy values, the intraclass correlation coefficient with two-way random-effects model (ICC[2,1]) for the subsets of 6 to 66 directions ranged between 0.136 [95%CI 0.0767;0.227] and 0.639 [0.542;0.740], whereas the corresponding values for subsets of 18 to 66 directions were 0.868 [0.815;0.913] and 0.995 [0.993;0.997]. Following the exclusion of motion-corrupted volumes, minor residual motion did not associate with the scalar values. A minimum of 18 diffusion directions is recommended to result in reliable DTI scalar results with TBSS. We suggest gathering extra directions in paediatric DTI to enable exclusion of volumes with motion artefacts and simultaneously preserve the overall data quality.

Test-retest reliability of diffusion tensor imaging scalars in 5-year-olds.

Diffusion tensor imaging (DTI) has provided great insights into the microstructural features of the developing brain. However, DTI images are prone to several artifacts and the reliability of DTI scalars is of paramount importance for interpreting and generalizing the findings of DTI studies, especially in the younger population. In this study, we investigated the intrascan test-retest repeatability of four DTI scalars: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 5-year-old children (N = 67) with two different data preprocessing approaches: a volume censoring pipeline and an outlier replacement pipeline. We applied a region of interest (ROI) and a voxelwise analysis after careful quality control, tensor fitting and tract-based spatial statistics. The data had three subsets and each subset included 31, 32, or 33 directions thus a total of 96 unique uniformly distributed diffusion encoding directions per subject. The repeatability of DTI scalars was evaluated with intraclass correlation coefficient (ICC(3,1)) and the variability between test and retest subsets. The results of both pipelines yielded good to excellent (ICC(3,1) > 0.75) reliability for most of the ROIs and an overall low variability (<10%). In the voxelwise analysis, FA and RD had higher ICC(3,1) values compared to AD and MD and the variability remained low (<12%) across all scalars. Our results suggest high intrascan repeatability in pediatric DTI and lend confidence to the use of the data in future cross-sectional and longitudinal studies.

Neural underpinnings of the slowness of information processing in patients with traumatic brain injury: insights from tract-based spatial statistics.

Slowness of information processing (SIP) is frequently reported after traumatic brain injury (TBI). Previous studies point toward a pivotal role of white matter damage on speed of information processing. However, little is known about the more comprehensive and ecological assessment of SIP in TBI. Here, we combined an ecological assessment of SIP with the use of tract-based spatial statistics (TBSS) on individuals' fractional anisotropy (FA) maps. Twenty-six moderate-to-severe patients with TBI (21 males and 5 females) participated in this study: 10 individuals were classified as not having SIP (SIP-) and 16 were classified as having SIP (SIP +). SIP + showed lower FA in bilateral anterior thalamic radiation, corticospinal tract, cingulum, and forceps, as well as in bilateral inferior fronto-occipital, inferior and superior longitudinal fasciculi and uncinate fasciculus. Overall, this result is consistent with and expands previous reports on information processing speed to a more comprehensive and ecological perspective on SIP in TBI.

Cognitive Deficit and White Matter Changes in Persons With Celiac Disease: A Population-Based Study.

BACKGROUND & AIMS: There is debate over the presence and prevalence of brain injury in patients with celiac disease. To validate previous reports, we investigated the prevalence of neuropsychological dysfunction in persons with celiac disease included in the National UK Biobank, which contains experimental medical data from 500,000 adults in the United Kingdom. METHODS: Biobank participants with celiac disease (n = 104; mean age, 63 years; 65% female) were matched with healthy individuals (controls, n = 198; mean age, 63 years; 67% female) for age, sex, level of education, body mass index, and diagnosis of hypertension. All participants were otherwise healthy. We compared scores from 5 cognitive tests and multiple choice responses to 6 questions about mental health between groups using the t test and chi-squared analyses. Groupwise analyses of magnetic resonance imaging brain data included a study of diffusion tensor imaging metrics (mean diffusivity, fractional anisotropy, radial diffusivity, axial diffusivity), voxel-based morphometry, and Mann-Whitney U comparisons of Fazekas grades. RESULTS: Compared with control individuals, participants with celiac disease had significant deficits in reaction time (P = .004), and significantly higher proportions had indications of anxiety (P = .025), depression (P = .015), thoughts of self-harm (P = .025), and health-related unhappiness (P = .010). Tract-based spatial statistics analysis showed significantly increased axial diffusivity in widespread locations, demonstrating white matter changes in the brains of participants with celiac disease. Voxel-based morphometry and Fazekas grade analyses did not differ significantly between groups. CONCLUSIONS: In an analysis of data from the UK Biobank, we found participants with celiac disease to have cognitive deficit, indications of worsened mental health, and white matter changes, based on analyses of brain images. These findings support the concept that celiac disease is associated with neurologic and psychological features.

Disease aggressiveness signatures of amyotrophic lateral sclerosis in white matter tracts revealed by the D50 disease progression model.

Numerous neuroimaging studies in amyotrophic lateral sclerosis (ALS) have reported links between structural changes and clinical data; however phenotypic and disease course heterogeneity have occluded robust associations. The present study used the novel D50 model, which distinguishes between disease accumulation and aggressiveness, to probe correlations with measures of diffusion tensor imaging (DTI). DTI scans of 145 ALS patients and 69 controls were analyzed using tract-based-spatial-statistics of fractional anisotropy (FA), mean- (MD), radial (RD), and axial diffusivity (AD) maps. Intergroup contrasts were calculated between patients and controls, and between ALS subgroups: based on (a) the individual disease covered (Phase I vs. II) or b) patients' disease aggressiveness (D50 value). Regression analyses were used to probe correlations with model-derived parameters. Case-control comparisons revealed widespread ALS-related white matter pathology with decreased FA and increased MD/RD. These affected pathways showed also correlations with the accumulated disease for increased MD/RD, driven by the subgroup of Phase I patients. No significant differences were noted between patients in Phase I and II for any of the contrasts. Patients with high disease aggressiveness (D50 < 30 months) displayed increased AD/MD in bifrontal and biparietal pathways, which was corroborated by significant voxel-wise regressions with D50. Application of the D50 model revealed associations between DTI measures and ALS pathology in Phase I, representing individual disease accumulation early in disease. Patients' overall disease aggressiveness correlated robustly with the extent of DTI changes. We recommend the D50 model for studies developing/validating neuroimaging or other biomarkers for ALS.

Microstructural changes in normal-appearing white matter in male sleep apnea patients are reversible after treatment: A pilot study.

Visually appreciable white matter (WM) changes have been described in obstructive sleep apnea (OSA). However, few data exist on the involvement of silent WM abnormalities. This prospective study investigated the microstructural integrity of normal-appearing white matter (NAWM) in male OSA patients before and after continuous positive airway pressure (CPAP) treatment, using a neuroimaging approach. Magnetic resonance imaging (MRI) was acquired from 32 participants (16 severe never-treated OSA and 16 controls). Diffusion tensor imaging (DTI) and Tract-Based Spatial Statistics (TBSS) were used to assess the microstructural NAWM changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). In order to evaluate the efficacy of the therapy, OSA patients underwent MRI evaluations at baseline and after 3 months of treatment (follow-up). CPAP treatment significantly increased the FA in NAWM of the brain stem, corpus callosum and bilateral internal capsule of OSA patients at follow-up compared to baseline (p < 0.05, TFCE-corrected). OSA patients also showed increases in AD in the corpus callosum, superior corona radiata, and internal capsule of the right hemisphere (p < 0.05, TFCE-corrected) after CPAP treatment. A significant negative correlation was found between the FA of the corona radiata, corpus callosum, internal capsule, limbic structures, and neuropsychological scores at follow-up evaluation. No significant differences were found in MD and RD of NAWM in our patients after treatment. Our results demonstrate that FA and AD of NAWM in major tracts such as the corpus callosum and the internal capsule increased significantly after CPAP treatment, as a potential beneficial effect of ventilatory therapy. The recovery of NAWM alterations might also be related to the improvement in the neurocognitive profile, suggesting that nonclearly visible WM alterations may contribute to the physiopathology of OSA-related cognitive impairment.

A typical antipsychotic treatment induced gradually expanding white matter alterations in healthy individuals with persistent auditory verbal hallucinations-an artificially controlled pilot study.

OBJECTIVE: The aim of this study was to explore the effects of atypical antipsychotics (AaPs) on brain white matter (WM) tracts in healthy individuals with auditory verbal hallucinations (Hi-AVHs). METHODS: We analyzed neuroimaging, AVH symptoms, and cognitive assessment data obtained from 39 Hi-AVHs who reported being distressed by persistent AVHs and volunteered to receive AaP treatment. We used tract-based spatial statistics (TBSS) and t tests to explore AaP pharmacotherapy effects on AVH symptoms and brain WM alterations in Hi-AVH subjects. RESULTS: TBSS and t tests revealed WM alterations after AaP treatment, relative to pretreatment observations. Although AaPs alleviated AVH symptoms, WM alterations in these subjects expanded over 8 months of AaP treatment, encompassing most major WM tracts by the end of the observation period, including the corpus callosum, arcuate fasciculus, cortico-spinal tracts, anterior commissure, and posterior commissure. CONCLUSIONS: The worsening of AaP-associated WM alterations observed in this study suggest that AaPs may not be a good choice for the treatment of Hi-AVHs despite their ability to alleviate AVHs.

Microstructural white matter abnormalities in hypothyroidism evaluation with diffusion tensor imaging tract-based spatial statistical analysis.

PURPOSE: Hypothyroidism is presented in a wide range from neuropsychiatric problems including depression, memory and cognitive disorders to poor motor coordination. Against the background of morphologic, functional and molecular changes on the white and grey matter of the brain, we aimed to investigate the effects of hypothyroidism on white matter (WM) integrity using tract-based spatial statistics (TBSS). METHODS: Eighteen patients with hyperthyroidism and 14 age-sex-matched healthy control subjects were included in this study. TBSS was used in the diffusion tensor imaging study for whole-brain voxel wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) of WM. RESULTS: When compared to the control group, the whole brain TBSS revealed extensive reductions of FA in the supratentorial WM including corticospinal tract, posterior limb of the internal capsule (PLIC), uncinate fasciculus, inferior longitudinal fasciculus (p < 0.005). The ROI analyses showed RD increment of superior longitudinal fasciculus, AD decrement of cingulum (CIN), external capsule, PLIC and corpus callosum (CC) in patients with hypothyroidism (p < 0.005). Autoimmune and non-autoimmune hypothyroidism patient subgroups showed a significant difference in terms of hippocampus FA, CIN MD, CC MD, CC AD, CIN RD, SLF RD, CC RD (p < 0.005). CIN FA values showed a negative correlation with the Beck Depression Inventory (p = 0.007, r = - 852). CONCLUSIONS: These preliminary results of TBSS analyses represented FA and AD decrement, and RD increment in several WM tracts and indicates the demyelination process underlying pathophysiology of clinical aspects of hypothyroidism.

White matter microstructure in youth with and at risk for bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) and familial risk for BD have been associated with aberrant white matter (WM) microstructure in the corpus callosum and fronto-limbic pathways. These abnormalities might constitute trait or state marker and have been suggested to result from aberrant maturation and to relate to difficulties in emotion regulation. METHODS: To determine whether WM alterations represent a trait, disease or resilience marker, we compared youth at risk for BD (n = 36 first-degree relatives, REL) to youth with BD (n = 36) and healthy volunteers (n = 36, HV) using diffusion tensor imaging. RESULTS: Individuals with BD and REL did not differ from each other in WM microstructure and, compared to HV, showed similar aberrations in the superior corona radiata (SCR)/corticospinal tract (CST) and the body of the corpus callosum. WM microstructure of the anterior CC showed reduced age-related in-creases in BD compared to REL and HV. Further, individuals with BD and REL showed in-creased difficulties in emotion regulation, which were associated with the microstructure of the anterior thalamic radiation. DISCUSSION: Alterations in the SCR/CST and the body of the corpus callosum appear to represent a trait marker of BD, whereas changes in other WM tracts seem to be a disease state marker. Our findings also support the role of aberrant developmental trajectories of WM microstructure in the risk architecture of BD, although longitudinal studies are needed to confirm this association. Finally, our findings show the relevance of WM microstructure for difficulties in emotion regulation-a core characteristic of BD.

Structural remodeling secondary to functional remodeling in advanced-stage peripheral facial neuritis.

BACKGROUND: Structural remodeling is a classic manifestation of disease decompensation. Facial synkinesis is the most troubling sequela of peripheral facial neuritis, and its structural remodeling, especially in white matter (WM), is still poorly understood. Therefore, understanding WM microstructure is important for predicting WM pathology and for early intervention in facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age, 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age, 33.21 ± 6.75 years old) were enrolled in this study. rs-fMRI data, diffusion tensor imaging (DTI) data, and Beck's Depression Inventory (BDI) data were collected, and tract-based spatial statistics (TBSS) and voxel-mirrored homotopic connectivity (VMHC) values were used to analyze changes in WM microstructure and interhemispheric coordination. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited significantly lower regional fractional anisotropy (FA) in the genu of the corpus callosum and the body of the corpus callosum, significantly higher regional FA in the retrolenticular part of the internal capsule, and significantly decreased VMHC values bilaterally in the orbital inferior frontal gyri, the fusiform gyri, the superior temporal gyri, the superior frontal gyri, and the supplementary motor areas. Furthermore, a lower regional FA in the genu of the corpus callosum was correlated with higher BDI scores in facial synkinesis patients. CONCLUSION: Structural remodeling, especially changes in white matter microstructure, may be the central mechanism for severe sequelae of peripheral facial neuritis.

White matter alterations in early Parkinson's disease: role of motor symptom lateralization.

INTRODUCTION: Parkinson's disease (PD) is a motor disorder that initially presents with unilateral symptoms. Widespread white matter (WM) alterations have been reported since the early stages of the disease. The aim of this study was to investigate WM alterations in right-dominant and left-dominant symptom PD patients (RPD and LPD, respectively) with respect to healthy controls (HC) by diffusion-weighted magnetic resonance imaging (MRI). METHODS: Thirty-eight subjects participated in this study: 12 RPD (median H&Y [IQR] = 1.5 [1.1-2], median UPDRS III [IQR] = 23 [7.8-25]), 9 LPD (median H&Y [IQR] = 1.5 [1-2.5], median UPDRS III [IQR] = 17 [12-22]), and 17 HC. All the participants were scanned on a 1.5-T MRI scanner. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were computed for all the subjects. Tract-based spatial statistics (TBSS) was performed for each diffusion parameter, to test WM differences between RPD, LPD, and HC (ANCOVA design). Family-wise error (FWE) correction was performed and p values lower than 0.05 were considered significant. RESULTS: No significant FA and RD differences were observed between RPD, LPD, and HC. Significantly increased MD and AD were observed in RPD with respect to HC within widespread WM regions, bilaterally. Conversely, no significant WM alterations were detected in LPD. CONCLUSION: WM integrity was found to be significantly altered in RPD but not in LPD, suggesting that LPD profile may be associated to more favorable prognosis. Since clinical laterality onset may affect the extent of WM integrity changes, it should be taken into account in neuroimaging studies investigating PD.

Serial MRI studies over 12 months using manual and atlas-based region of interest in patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of upper and lower motor neurons. There is a need for an imaging biomarker to track disease progression. Previously, magnetic resonance imaging (MRI) has shown loss of grey and white matter in the brain of patients with ALS compared to controls. We performed serial diffusion tractography imaging (DTI) study of patients with ALS looking for changes over time. METHODS: On all subjects (n = 15), we performed three MRI studies at 6 month intervals. DTI changes were assessed with tract-based spatial statistics (TBSS) and region of interest (ROI) studies. Cortic-spinal tract (CST) was selected for our ROI at the upper level; the posterior limb of internal capsule (PLIC), and a lower level in the pons. RESULTS: There was no significant change in DTI measures over 12 months of observation. Better correlation of manual and atlas-based ROI methods was found in the posterior limb of the internal capsule than the pons. CONCLUSION: While previous DTI studies showed significant differences between ALS subjects and controls, within individual subjects there is little evidence of progression over 12 months. This suggests that DTI is not a suitable biomarker to assess disease progression in ALS.

Altered integrity of corpus callosum in generalized epilepsy in relation to seizure lateralization after corpus callosotomy.

OBJECTIVE: Generalized-onset seizures are usually conceptualized as engaging bilaterally distributed networks with no clear focus. However, the authors previously reported a case series demonstrating that in some patients with generalized-onset seizures, focal seizure onset could be discovered after corpus callosotomy. The corpus callosum is considered to be a major pathway for seizure generalization in this group of patients. The authors hypothesized that, in patients with generalized-onset seizures, the structure of the corpus callosum could be different between patients who have lateralized seizures and those who have nonlateralized seizures after corpus callosotomy. The authors aimed to evaluate the structural difference through statistical analysis of diffusion tensor imaging (DTI) scalars between these two groups of patients. METHODS: Thirty-two patients diagnosed with generalized-onset motor seizures and without an MRI lesion were included in this study. Among them, 16 patients developed lateralized epileptic activities after corpus callosotomy, and the remaining 16 patients continued to have nonlateralized seizures after corpus callosotomy. Presurgical DTI studies were acquired to quantify the structural integrity of the corpus callosum. RESULTS: The DTI analysis showed significant reduction of fractional anisotropy (FA) and increase in radial diffusivity (RD) in the body of the corpus callosum in the lateralized group compared with the nonlateralized group. CONCLUSIONS: The authors' findings indicate the existence of different configurations of bilateral epileptic networks in generalized epilepsy. Generalized seizures with focal onset relying on rapid spread through the corpus callosum might cause more structural damage related to demyelination in the corpus callosum, showing reduced FA and increased RD. This study suggests that presurgical DTI analysis of the corpus callosum might predict the seizure lateralization after corpus callosotomy.