White Matter Microstructural Changes Research Articles

White matter abnormalities in first-episode patients with depersonalization/derealization disorder: A tract-based spatial statistics study

BackgroundNeuroimaging studies on depersonalization / derealization disorder (DPD) have revealed that there are structural and functional alterations across numerous brain regions. However, to date, the exact white matter abnormalities that are associated with different clinical symptoms and cognitive impairments in first-episode, drug-naïve patients with DPD remain unclear. MethodsOverall, 25 first-episode, drug-naïve patients with DPD and 23 healthy controls were recruited and underwent DTI scans. The tract-based spatial statistics analysis was conducted in order to determine white matter microstructural changes between the two groups. Correlation analysis was conducted between the fractional anisotropy (FA) of abnormal WM fibers and the total score of the 30-item Cambridge Depersonalization Scale (CDS-30), cognitive assessments. ResultsPatients with DPD demonstrated higher FA in the right corpus callosum (CC), and posterior corona radiate (CR), compared to healthy controls. The FA in the right CC demonstrated a positive correlation with total score of CDS-30, numbing, unreality of self, perceptual alterations, and temporal disintegration, respectively. FA in the right CR region indicated a positive correlation with the total score of CDS-30, unreality of self, perceptual alterations, and temporal disintegration, respectively. Furthermore, FA in the right CR region was found to be negatively correlated with the Continuous Performance Test and the Stroop color-word test. ConclusionThe altered white matter microstructure and cognitive impairments of medication naïve DPD patients were observed. Abnormalities in the integrity of CC and CR were associated with severity of symptoms and cognitive impairments, which may provide a potential biomarker for clinical studies on DPD.

Brain volumes and white matter microstructure in 8- to 10-year-old children born with fetal growth restriction

BackgroundFetal growth restriction caused by placental insufficiency is associated with increased risk of poor neurodevelopment, even in the absence of specific perinatal brain injury. Placental insufficiency leads to chronic hypoxaemia that may alter cerebral tissue organisation and maturation.ObjectiveThe aim of this study was to assess the effects fetal growth restriction and fetal haemodynamic abnormalities have on brain volumes and white matter microstructure at early school age.Materials and methodsThis study examined 32 children born with fetal growth restriction at 24 to 40 gestational weeks, and 27 gestational age-matched children, who were appropriate for gestational age. All children underwent magnetic resonance imaging (MRI) at the age of 8–10 years. Cerebral volumes were analysed, and tract-based spatial statistics and atlas-based analysis of white matter were performed on 17 children born with fetal growth restriction and 14 children with birth weight appropriate for gestational age.ResultsChildren born with fetal growth restriction demonstrated smaller total intracranial volumes compared to children with normal fetal growth, whereas no significant differences in grey or white matter volumes were detected. On atlas-based analysis of white matter, children born with fetal growth restriction demonstrated higher mean and radial diffusivity values in large white matter tracts when compared to children with normal fetal growth.ConclusionChildren ages 8–10 years old born with fetal growth restriction demonstrated significant changes in white matter microstructure compared to children who were appropriate for gestational age, even though no differences in grey and white matter volumes were detected. Poor fetal growth may impact white matter maturation and lead to neurodevelopmental impairment later in life.

Association between Changes in White Matter Microstructure and Cognitive Impairment in White Matter Lesions.

This study investigated the characteristics of cognitive impairment in patients with white matter lesions (WMLs) caused by cerebral small vessel disease and the corresponding changes in WM microstructures. Diffusion tensor imaging (DTI) data of 50 patients with WMLs and 37 healthy controls were collected. Patients were divided into vascular cognitive impairment non-dementia and vascular dementia groups. Tract-based spatial statistics showed that patients with WMLs had significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values throughout the WM areas but predominately in the forceps minor, forceps major (FMA), bilateral corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus (ILF), and anterior thalamic radiation, compared to the control group. These fiber bundles were selected as regions of interest. There were significant differences in the FA, MD, AD, and RD values (p < 0.05) between groups. The DTI metrics of all fiber bundles significantly correlated with the Montreal Cognitive Assessment (p < 0.05), with the exception of the AD values of the FMA and ILF. Patients with WMLs showed changes in diffusion parameters in the main WM fiber bundles. Quantifiable changes in WM microstructure are the main pathological basis of cognitive impairment, and may serve as a biomarker of WMLs.

White matter characteristics in the early and late stages of bipolar disorder: A diffusion tensor imaging study

BackgroundBipolar disorder (BD) is characterized by recurrent mood episodes that may progress over time. Staging models may be used to follow the long-term course of BD. BD is associated with microstructural changes in white matter (WM). This study aims to compare the WM integrity within patients groups who are in different stages of BD and healthy controls and investigate whether WM integrity changes may be a biomarker that can be used in the clinical staging of BD. MethodsThe study sample included euthymic 54 patients diagnosed with BD according to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) and 27 healthy volunteers. Early-stage patients (n = 26) were determined as patients who have not had any mood episodes after the first manic episode, and late-stage patients (n = 28) determined as patients with recurrent mood episodes. MRI was performed using a 1.5 Tesla MR system and DTI sequences were acquired. ResultsRegion of interest (ROI) analyses showed that late-stage patients had significantly reduced fractional anisotropy (FA) in the right sagittal stratum and genu of the corpus callosum compared with healthy controls and early-stage patients. Regression models show that corpus callosum genu and right sagittal stratum FA values are predictive for the late-stage patient group. LimitationsThere are some limitations of the ROI method. The cross-sectional design is another limitation of this study. ConclusionsWM integrity of corpus callosum genu and right sagittal stratum may be a biomarker for clinical staging of BD. Identifying stage-specific biomarkers may help us predict the neuroprogressive course of BD. Longitudinal studies would be required to detect stage-specific biomarkers.

338 Diffusion Basis Spectrum Imaging (DBSI) Prognosticates Outcomes for Cervical Spondylotic Myelopathy after Surgery

OBJECTIVES/GOALS: Diffusion basis spectrum imaging (DBSI) allows for detailed evaluation of white matter microstructural changes present in cervical spondylotic myelopathy (CSM). Our goal is to utilize multidimensional clinical and quantitative imaging data to characterize disease severity and predict long-term outcomes in CSM patients undergoing surgery. METHODS/STUDY POPULATION: A single-center prospective cohort study enrolled fifty CSM patients who underwent surgical decompression and twenty healthy controls from 2018-2021. All patients underwent diffusion tensor imaging (DTI), DBSI, and complete clinical evaluations at baseline and 2-years follow-up. Primary outcome measures were the modified Japanese Orthopedic Association score (mild [mJOA 15-17], moderate [mJOA 12-14], severe [mJOA 0-11]) and SF-36 Physical and Mental Component Summaries (PCS and MCS). At 2-years follow-up, improvement was assessed via established MCID thresholds. A supervised machine learning classification model was used to predict treatment outcomes. The highest-performing algorithm was a linear support vector machine. Leave-one-out cross-validation was utilized to test model performance. RESULTS/ANTICIPATED RESULTS: A total of 70 patients – 20 controls, 25 mild, and 25 moderate/severe CSM patients – were enrolled. Baseline clinical and DTI/DBSI measures were significantly different between groups. DBSI Axial and Radial Diffusivity were significantly correlated with baseline mJOA and mJOA recovery, respectively (r=-0.33, p&lt;0.01; r=-0.36, p=0.02). When predicting baseline disease severity (mJOA classification), DTI metrics alone performed with 38.7% accuracy (AUC: 72.2), compared to 95.2% accuracy (AUC: 98.9) with DBSI metrics alone. When predicting improvement after surgery (change in mJOA), clinical variables alone performed with 33.3% accuracy (AUC: 0.40). When combining DTI or DBSI parameters with key clinical covariates, model accuracy improved to 66.7% (AUC: 0.65) and 88.1% (AUC: 0.95) accuracy, respectively. DISCUSSION/SIGNIFICANCE: DBSI metrics correlate with baseline disease severity and outcome measures at 2-years follow-up. Our results suggest that DBSI may serve as a valid non-invasive imaging biomarker for CSM disease severity and potential for postoperative improvement.

Effects of aerobic versus cognitively demanding exercise interventions on brain structure and function in healthy children-Results from a cluster randomized controlled trial.

The beneficial effects of physical activity on neurocognitive functioning in children are considered to be facilitated by physical activity‐induced changes in brain structure and functioning. In this study, we examined the effects of two 14‐week school‐based exercise interventions in healthy children on white matter microstructure and brain activity in resting‐state networks (RSNs) and whether changes in white matter microstructure and RSN activity mediate the effects of the exercise interventions on neurocognitive functioning. A total of 93 children were included in this study (51% girls, mean age 9.13 years). The exercise interventions consisted of four physical education lessons per week, focusing on either aerobic or cognitively demanding exercise and were compared with a control group that followed their regular physical education program of two lessons per week. White matter microstructure was assessed using diffusion tensor imaging in combination with tract‐based spatial statistics. Independent component analysis was performed on resting‐state data to identify RSNs. Furthermore, neurocognitive functioning (information processing and attention, working memory, motor response inhibition, interference control) was assessed by a set of computerized tasks. Results indicated no Group × Time effects on white matter microstructure or RSN activity, indicating no effects of the exercise interventions on these aspects of brain structure and function. Likewise, no Group × Time effects were found for neurocognitive performance. This study indicated that 14‐week school‐based interventions regarding neither aerobic exercise nor cognitive‐demanding exercise interventions influence brain structure and brain function in healthy children. This study was registered in the Netherlands Trial Register (NTR5341).

Accelerated decline in white matter microstructure in subsequently impaired older adults and its relationship with cognitive decline.

Little is known about a longitudinal decline in white matter microstructure and its associations with cognition in preclinical dementia. Longitudinal diffusion tensor imaging and neuropsychological testing were performed in 50 older adults who subsequently developed mild cognitive impairment or dementia (subsequently impaired) and 200 cognitively normal controls. Rates of white matter microstructural decline were compared between groups using voxel-wise linear mixed-effects models. Associations between change in white matter microstructure and cognition were examined. Subsequently impaired individuals had a faster decline in fractional anisotropy in the right inferior fronto-occipital fasciculus and bilateral splenium of the corpus callosum. A decline in right inferior fronto-occipital fasciculus fractional anisotropy was related to a decline in verbal memory, visuospatial ability, processing speed and mini-mental state examination. A decline in bilateral splenium fractional anisotropy was related to a decline in verbal fluency, processing speed and mini-mental state examination. Accelerated regional white matter microstructural decline is evident during the preclinical phase of mild cognitive impairment/dementia and is related to domain-specific cognitive decline.

Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates

Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular interactions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR1) in relation to DTI metrics and gestational age at scan. To the best of our knowledge, this is the first study to assess developmental WM trajectories in NHPs using quantitative relaxometry and the first to directly compare DTI and relaxometry metrics during infancy. We demonstrate that qR1 exhibits robust logarithmic growth, unfolding in a posterior-anterior and medial-lateral fashion, similar to DTI metrics. On a within-subject level, DTI metrics and qR1 are highly correlated, but are largely unrelated on a between-subject level. Unlike DTI metrics, gestational age at birth (time in utero) is a strong predictor of early postnatal qR1 levels. Whereas individual differences in DTI metrics are maintained across the first year of life, this is not the case for qR1. These results point to the similarities and differences in using quantitative relaxometry and DTI in developmental studies, providing a basis for future studies to characterize the unique processes that these measures reflect at the cellular and molecular level.

Neural diffusion tensor imaging metrics correlate with clinical measures in people with relapsing-remitting MS.

Diffusion tensor imaging (DTI) can detect microstructural changes of white matter in multiple sclerosis (MS) and might clarify mechanisms responsible for disability. Thus, we aimed to compare DTI metrics in relapsing-remitting MS patients (RRMS) with healthy controls (HCs), and explore the correlations between DTI metrics, total brain white matter (TBWM) and white matter lesion (WML) with clinical parameters compared to volumetric measures. 37 RRMS patients and 19 age/sex-matched HCs were included. All participants had clinical assessments, structural and diffusion scans on a 3T MRI. Volumetric and white matter DTI metrics; fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD and AD) were estimated and correlated with clinical parameters. The mean group differences were calculated using t-tests, and univariate correlations with Pearson correlation coefficients. Compared to HCs, statistically significant increases in MD (+3.6%), RD (+4.8%), AD (+2.7%) and a decrease in FA (-4.3%) for TBWM in RRMS was observed (p < .01). MD and RD in TBWM and AD in WML correlated moderately with disability status. Volumetric segmentation indicated a decrease in the total brain volume, GM and WM(-5%) with a reciprocal increase in CSF(+26%) in RRMS(p < .01). Importantly, DTI parameters showed a medium correlation with cognitive domains in contrast to white matter-related volumetric measurements in RRMS(Pearson correlation, p < .05). Our study shows a correlation of DTI metrics with clinical symptoms of MS, in particular cognition. More generally, these findings indicated that DTI is a useful and unique technique for evaluating the clinical features of white matter disease and warrants further investigation into its clinical role.

Priming cardiovascular exercise improves complex motor skill learning by affecting the trajectory of learning-related brain plasticity

In recent years, mounting evidence from animal models and studies in humans has accumulated for the role of cardiovascular exercise (CE) in improving motor performance and learning. Both CE and motor learning may induce highly dynamic structural and functional brain changes, but how both processes interact to boost learning is presently unclear. Here, we hypothesized that subjects receiving CE would show a different pattern of learning-related brain plasticity compared to non-CE controls, which in turn associates with improved motor learning. To address this issue, we paired CE and motor learning sequentially in a randomized controlled trial with healthy human participants. Specifically, we compared the effects of a 2-week CE intervention against a non-CE control group on subsequent learning of a challenging dynamic balancing task (DBT) over 6 consecutive weeks. Structural and functional MRI measurements were conducted at regular 2-week time intervals to investigate dynamic brain changes during the experiment. The trajectory of learning-related changes in white matter microstructure beneath parieto-occipital and primary sensorimotor areas of the right hemisphere differed between the CE vs. non-CE groups, and these changes correlated with improved learning of the CE group. While group differences in sensorimotor white matter were already present immediately after CE and persisted during DBT learning, parieto-occipital effects gradually emerged during motor learning. Finally, we found that spontaneous neural activity at rest in gray matter spatially adjacent to white matter findings was also altered, therefore indicating a meaningful link between structural and functional plasticity. Collectively, these findings may lead to a better understanding of the neural mechanisms mediating the CE-learning link within the brain.

Plasma phosphorylated-tau181 levels reflect white matter microstructural changes across Alzheimer's disease progression.

Alzheimer's Disease (AD) is characterized by cognitive impairments that hinder daily activities and lead to personal and behavioral problems. Plasma hyperphosphorylated tau protein at threonine 181 (p-tau181) has recently emerged as a new sensitive tool for the diagnosis of AD patients. We herein investigated the association of plasma P-tau181 and white matter (WM) microstructural changes in AD. We obtained data from a large prospective cohort of elderly individuals participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI), which included baseline measurements of plasma P-tau181 and imaging findings. A subset of 41 patients with AD, 119 patients with mild cognitive impairments (MCI), and 43 healthy controls (HC) was included in the study, all of whom had baseline blood P-tau181 levels and had also undergone Diffusion Tensor Imaging. The analysis revealed that the plasma level of P-tau181 has a positive correlation with changes in Mean Diffusivity (MD), Radial Diffusivity (RD), and Axial Diffusivity (AxD), but a negative with Fractional Anisotropy (FA) parameters in WM regions of all participants. There is also a significant association between WM microstructural changes in different regions and P-tau181 plasma measurements within each MCI, HC, and AD group. In conclusion, our findings clarified that plasma P-tau181 levels are associated with changes in WM integrity in AD. P-tau181 could improve the accuracy of diagnostic procedures and support the application of blood-based biomarkers to diagnose WM neurodegeneration. Longitudinal clinical studies are also needed to demonstrate the efficacy of the P-tau181 biomarker and predict its role in structural changes.

Investigation of white matter and grey matter alteration in the monkey brain following ischemic stroke by using diffusion tensor imaging.

Investigation of stroke lesion has mostly focused on grey matter (GM) in previous studies and white matter (WM) degeneration during acute stroke is understudied. In the present study, monkeys were utilized to investigate the alterations of GM and WM in the brain following ischemic occlusion using diffusion tensor imaging (DTI). Permanent middle cerebral artery occlusion (pMCAO) was induced in rhesus monkeys (n=6) with an interventional approach. Serial DTI was conducted on a clinical 3T in the hyperacute phase (2-6 hours), 48, and 96 hours post occlusion. Regions of interest in GM and WM of lesion areas were selected for data analysis. Mean diffusivity (MD), radial diffusivity (RD), and axial Diffusivity (AD) in WM decreased substantially during hyperacute stroke, as similar as those seen in GM. No obvious fractional anasotropy (FA) changes were seen in GM and WM during hyper acute phase. until 48 hours post stroke when significant fiber losses were oberved also. Pseudo-normalization of MD, AD, and RD was seen at 96 hours. Pathological changes of WM and GM were observed in ischemic areas at 8, 48, and 96 hours post stroke. Relative changes of MD, AD and RD of WM were correlated negatively with infarction volumes at 6 hours post stroke. The present study revealed the microstructural changes in gray matter and white matter of monkey brains during acute stroke by using DTI. The preliminary results suggest axial and radial diffusivity (AD and RD) may be sensitive surrogate markers to assess specific microstructural changes in white matter during hyper-acute stroke.

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

BackgroundVariation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA). MethodsData were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. ResultsClinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax = 1.092, standardized effect[SE] = 0.044, pFWE = 0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax = 3.775, SE = 0.051, pFWE = 0.019). ConclusionsAberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

R2* relaxometry analysis for mapping of white matter alteration in Parkinson’s disease with mild cognitive impairment

BackgroundR2* relaxometry analysis combined with quantitative susceptibility mapping (QSM), which has high sensitivity to iron deposition, can distinguish microstructural changes of the white matter (WM) and iron deposition, thereby providing a sensitive and biologically specific measure of the WM owing to the changes in myelin and its surrounding environment. This study aimed to explore the microstructural WM alterations associated with cognitive impairment in patients with Parkinson’s disease (PD) using R2* relaxometry analysis combined with QSM. Materials and methodsWe enrolled 24 patients with PD and mild cognitive impairment (PD-MCI), 22 patients with PD and normal cognition (PD-CN), and 19 age- and sex-matched healthy controls (HC). All participants underwent Montreal Cognitive Assessment (MoCA) and brain magnetic resonance imaging, including structural three-dimensional T1-weighted images and multiple spoiled gradient echo sequence (mGRE). The R2* and susceptibility maps were estimated from the multiple magnitude images of mGRE. The susceptibility maps were used for verifying iron deposition in the WM. The voxel-based R2* of the entire WM and its correlation with cognitive performance were analyzed. ResultsIn the voxel-based group comparisons, the R2* in the PD-MCI group was lower in some WM regions, including the corpus callosum, than R2* in the PD-CN and HC groups. The mean susceptibility values in almost all brain regions were negative and close-to-zero values, indicating no detectable paramagnetic iron deposition in the WM of all subjects. There was a significant positive correlation between R2* and MoCA in some regions of the WM, mainly the corpus callosum and left hemisphere. ConclusionR2* relaxometry analysis for WM microstructural changes provided further biologic insights on demyelination and changes in the surrounding environment, supported by the QSM results demonstrating no iron existence. This analysis highlighted the potential for the early evaluation of cognitive decline in patients with PD.

Microstructural changes in prodromal dementia with Lewy bodies compared to normal ageing: Multiparametric quantitative MRI evidences.

Dementia with Lewy bodies (DLB) patients show few significant macroscopic structural changes, especially at the early stages of the disease, making quantitative MRI especially interesting to explore more subtle changes that are not detectable by conventional volumetric techniques. Microstructural alterations have been reported in DLB at the dementia stage, but no study to date was conducted in prodromal patients. Here, quantitative MRI data were collected from 46 DLB prodromal patients and 20 healthy elderly subjects, who also underwent a detailed clinical examination including the Mayo Clinic Fluctuation Scale. We conducted voxel-wise between-group comparisons in diffusion tensor imaging (DTI) metrics and in R2* mapping, along with a multivariate analysis combining the two modalities. We highlighted multiple grey matter and white matter microstructural changes in DLB patients at the prodromal stage, compared to control subjects. Our multivariate analysis identified three distinct regional patterns of DTI and R2* changes (anterior, anteromedial, posterior) in DLB patients, that could reflect different neuropathological processes across brain regions. We also observed an association between R2* alterations in the thalamus, and the severity of fluctuations, in the DLB group. These preliminary findings are promising and require future investigations to better understand the biological underpinnings of microstructural alterations.

Neuroanatomical markers of psychotic experiences in adolescents: A machine-learning approach in a longitudinal population-based sample

It is important to identify accurate markers of psychiatric illness to aid early prediction of disease course. Subclinical psychotic experiences (PEs) are important risk factors for later mental ill-health and suicidal behaviour. This study used machine learning to investigate neuroanatomical markers of PEs in early and later stages of adolescence.Machine learning using logistic regression using Elastic Net regularization was applied to T1-weighted and diffusion MRI data to classify adolescents with subclinical psychotic experiences vs. controls across 3 timepoints (Time 1:11–13 years, n = 77; Time 2:14–16 years, n = 56; Time 3:18–20 years, n = 40). Neuroimaging data classified adolescents aged 11–13 years with current PEs vs. controls returning an AROC of 0.62, significantly better than a null model, p = 1.73e-29. Neuroimaging data also classified those with PEs at 18–20 years (AROC = 0.59;P = 7.19e-10) but performance was at chance level at 14–16 years (AROC = 0.50).Left hemisphere frontal regions were top discriminant classifiers for 11–13 years-old adolescents with PEs, particularly pars opercularis. Those with future PEs at 18–20 years-old were best distinguished from controls based on left frontal regions, right-hemisphere medial lemniscus, cingulum bundle, precuneus and genu of the corpus callosum (CC).Deviations from normal adolescent brain development in young people with PEs included an acceleration in the typical pattern of reduction in left frontal thickness and right parietal curvature, and accelerated progression of microstructural changes in right white matter and corpus callosum. These results emphasise the importance of multi-modal analysis for understanding adolescent PEs and provide important new insights into early phenotypes for psychotic experiences.

White matter diffusivity and its correlations to state measures of psychopathology in male refugees with posttraumatic stress disorder

Post-traumatic stress disorder (PTSD) is a heterogenous condition and the underlying neurobiology is still poorly understood. In this study, we tested the hypothesis that PTSD is associated with microstructural changes in white matter (WM) fibre tracts that connect regions involved in emotional processing, memory, attention, and language. Furthermore, we examined how different response patterns to individualized trauma-provoking stimuli related to underlying WM microstructure. Sixty-nine trauma-affected male refugees with PTSD (N = 38) or without PTSD (N = 31) underwent clinical assessments and diffusion-weighted magnetic resonance imaging (DWI) of the whole brain at 3 Tesla. Diffusion tensor metrics were computed from DWI data and used to characterize regional white-matter microstructure. An automated tract segmentation method was used to extract diffusion tensor metrics from subject-based reconstructions of tract segments (ROI), including uncinate fasciculus (UF), cingulum bundle (CB), superior longitudinal fasciculus (SLF) in three subdivisions (SLF I - III), and fibre bundles connecting orbito-frontal cortex to striatum (OF-ST). Outside the scanner we obtained measures of immediate (state) arousal, avoidance and dissociation symptoms assessed in response to auditory exposure to a personal traumatic memory. Using mean FA of the middle part of each ROI, mixed ANOVA revealed a significant interaction between group, ROI and hemisphere. Post-hoc comparisons showed that, relative to refugees without PTSD, refugees with PTSD had lower FA in right CB, left SLF-I, bilateral OF-ST and bilateral SLF-II. Mean FA scaled negatively with avoidance in right CB while mean FA in bilateral UF scaled positively with individual scores reflecting dissociation symptoms. The results support a pathophysiological model of PTSD that implicates limbic structures, prefrontal cortex and striatum. The results also emphasize the need to consider PTSD’s multifaceted manifestations when searching for functional-structural relationships.

The effect of polygenic risk on white matter microstructural degeneration in Parkinson's disease: A longitudinal Diffusion Tensor Imaging study.

This study was undertaken to investigate the effect of genetic risk on whole brain white matter (WM) integrity in patients with Parkinson disease (PD). Data were acquired from the Parkinson's Progression Markers Initiative (PPMI) database. Polygenic load was estimated by calculating weighted polygenic risk scores (PRS) using (i) all available 26 PD-risk single nucleotide polymorphisms (SNPs) (PRS1) and (ii) 23 SNPs with minor allele frequency (MAF) >0.05 (PRS2). According to the PRS2, and combined with clinical and diffusion tensor imaging (DTI) data over 3-year follow-up, 60 PD patients were screened and assigned to the low-PRS group (n=30) and high-PRS group (n=30) to investigate intergroup differences in clinical profiles and WM microstructure measured by DTI cross-sectionally and longitudinally. PRS were associated with younger age at onset in patients with PD (PRS1, Spearman ρ=-0.190, p=0.003; PRS2, Spearman ρ=-0.189, p=0.003). The high-PRS group showed more extensive WM microstructural degeneration compared with the low-PRS group, mainly involving the anterior thalamic radiation (AThR) and inferior fronto-occipital fasciculus (IFOF) (p<0.05). Furthermore, WM microstructural changes in AThR correlated with declining cognitive function (r=-0.401, p=0.028) and increasing dopaminergic deficits in caudate (r=-0.405, p=0.030). These findings suggest that PD-associated polygenic load aggravates the WM microstructural degeneration and these changes may lead to poor cognition with continuous dopamine depletion. This study provides advanced evidence that combined with a cumulative PRS and DTI methods may predict disease progression in PD patients.

Widespread White Matter Microstructure Alterations Based on Diffusion Tensor Imaging and Diffusion Kurtosis Imaging in Patients With Pontine Infarction.

Neurological deficits after stroke are closely related to white matter microstructure damage. However, secondary changes in white matter microstructure after pontine infarction (PI) in the whole brain remain unclear. This study aimed to investigate the correlation of diffusion kurtosis imaging (DKI)-derived diffusion and kurtosis parameters of abnormal white matter tracts with behavioral function in patients with chronic PI. Overall, 60 patients with unilateral chronic PI (33 patients with left PI and 27 patients with right PI) and 30 normal subjects were recruited and underwent DKI scans. Diffusion parameters derived from diffusion tensor imaging (DTI) and DKI and kurtosis parameters derived from DKI were obtained. Between-group differences in multiple parameters were analyzed to assess the changes in abnormal white matter microstructure. Moreover, we also calculated the sensitivities of different diffusion and kurtosis parameters of DTI and DKI for identifying abnormal white matter tracts. Correlations between the DKI-derived parameters in secondary microstructure changes and behavioral scores in the PI were analyzed. Compared with the NC group, both left PI and right PI groups showed more extensive perilesional and remote white matter microstructure changes. The DKI-derived diffusion parameters showed higher sensitivities than did the DTI-derived parameters. Further, DKI-derived diffusion and kurtosis parameters in abnormal white matter regions were correlated with impaired motor and cognitive function in patients with PI. In conclusion, PI could lead to extensive white matter tracts impairment in perilesional and remote regions. Further, the diffusion and kurtosis parameters could be complementary for identifying comprehensive tissue microstructural damage after PI.

Corticospinal tract and motor cortex degeneration in pure hereditary spastic paraparesis type 4 (SPG4)

Objective: SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive retrograde degeneration, or “dying-back” phenomenon, of the corticospinal tract’s longest axons. Neuroimaging studies mainly focus on white matter changes and, although previous studies reported cortical thinning in complicated HSP forms, cortical changes remain unclear in SPG4 patients. This work aimed to compare changes in white matter microstructure and cortical thickness between 12 SPG4 patients and 22 healthy age-matched controls. We also explore whether white matter alterations are related to cortical thickness and their correlation with clinical symptoms. Methods: we used fixel-based analysis, an advanced diffusion-weighted imaging technique, and probabilistic tractography of the corticospinal tracts. We also analyzed cortical morphometry using whole-brain surface-based and atlas-based methods in sensorimotor areas. Results: SPG4 patients showed bilateral involvement in the corticospinal tracts; this was more intense in the distal portion than in the upper segments and was associated with the degree of clinical impairment. We found a significant correlation between disease severity and fiber density and cross-section of the corticospinal tracts. Furthermore, corticospinal tract changes were significantly correlated with bilateral cortical thinning in the precentral gyrus in SPG4 patients. Conclusions: Our data point to axonal damage of the corticospinal motor neurons in SPG4 patients might be related to cortical thinning in motor regions.