White Matter Diffusion Metrics Research Articles

Frontal White Matter Changes and Craving Recovery in Inpatients With Heroin Use Disorder.

Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. White matter impairments in individuals with heroin use disorder (HUD) have been associated with drug craving, a reliable predictor of treatment outcomes; however, little is known about structural connectivity changes with inpatient treatment and abstinence in individuals with HUD. To assess white matter microstructure and associations with drug craving changes with inpatient treatment in individuals with HUD (effects of time and rescan compared with controls). This cohort study conducted from December 2020 to September 2022 included individuals recruited from urban inpatient treatment facilities treating HUD and surrounding communities in New York City. Participants with HUD were receiving medication-assisted treatment. Data were analyzed from October 2022 to March 2023. Between scans, inpatient individuals with HUD continued treatment and related clinical interventions. Control participants were scanned at similar time intervals. Changes in white matter diffusion metrics (fractional anisotropy and mean, axial, and radial diffusivities) assessed voxelwise with general linear models in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance). Thirty-four individuals with HUD (mean [SD] age, 40.5 [11.0] years; 9 women [36%]; 3 Black [9%], 17 White [50%], 14 other race or ethnicity [41%]) and 25 control (mean [SD] age, 42.1 [9.0]; 7 women [21%]; 8 Black [32%], 10 White [40%], 7 other race or ethnicity [28%]) were included. Main voxelwise findings showed HUD-specific white matter microstructure changes (1 - P > .949), including increased fractional anisotropy and decreased mean and radial diffusivities, encompassing mostly frontal major callosal, projection, and association tracts. The increased fractional anisotropy (r = -0.72, P < .001, slope SE = 9.0 × 10-4) and decreased mean diffusivity (r = 0.69, P < .001, slope SE = 1.25 × 10-6) and/or radial diffusivity (r = 0.67, P < .001, slope SE = 1.16 × 10-6) in the genu and body of the corpus callosum and left anterior corona radiata in individuals with HUD correlated with a reduction in baseline craving (voxelwise 1 - P > .949). No other white matter correlations with outcome variables reached significance. This cohort study of inpatients with HUD on medication-assisted treatment found whole-brain normalization of structural connectivity in frontal white matter pathways implicated in emotional regulation and top-down executive control. Observed associations with decreases in baseline craving further support the possibility of recovery, highlighting the relevance of these white matter markers to a major symptom of addiction, with implications for clinical outcome monitoring.

FRONTAL WHITE MATTER CHANGES INDICATE RECOVERY WITH INPATIENT TREATMENT IN HEROIN ADDICTION.

Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD. To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL). Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined). The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively. Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women). Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals. Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance). Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1-p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=-0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance. Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.

Blood pressure-related white matter microstructural disintegrity and associated cognitive function impairment in asymptomatic adults

Background and objectivesWe aimed to investigate the white matter (WM) microstructural/cytostructural disintegrity patterns related to higher systolic blood pressure (SBP), and whether they mediate SBP effects on cognitive performance in...

Differential association of antioxidative defense genes with white matter integrity in youth bipolar disorder

Oxidative stress is associated with white matter diffusion metrics in adults with bipolar disorder (BD). We examined the association of single-nucleotide polymorphisms in the oxidative stress system, superoxide dismutase-2 (SOD2) rs4880 and glutathione peroxidase-3 (GPX3) rs3792797 with fractional anisotropy (FA) and radial diffusivity (RD) in youth with BD. Participants included 104 youth (age 17.5 ± 1.7 years; 58 BD, 46 healthy controls). Saliva samples were obtained for genotyping, and diffusion tensor imaging was acquired. Voxel-wise whole-brain white matter diffusion analyses controlled for age, sex, and race. There were significant diagnosis-by-SOD2 rs4880 interaction effects for FA and RD in major white matter tracts. Within BD, the group with two copies of the G-allele (GG) showed lower FA and higher RD than A-allele carriers. Whereas within the control group, the GG group showed higher FA and lower RD than A-allele carriers. Additionally, FA was higher and RD was lower within the control GG group compared to the BD GG group. No significant findings were observed for GPX3 rs3793797. The current study revealed that, within matter tracts known to differ in BD, associations of SOD2 rs4880 GG genotype with both FA and RD differed between BD vs healthy control youth. The SOD2 enzyme encoded by the G-allele, has higher antioxidant capacity than the enzyme encoded by the A-allele. We speculate that the current findings of lower FA and higher RD of the BD GG group compared to the other groups reflects attenuation of the salutary antioxidant effects of GG genotype on white matter integrity in youth with BD, in part due to predisposition to oxidative stress. Future studies incorporating other genetic markers and oxidative stress biomarkers are warranted.

Artificial neural networks for non-linear age correction of diffusion metrics in the brain.

Human aging is characterized by progressive loss of physiological functions. To assess changes in the brain that occur with increasing age, the concept of brain aging has gained momentum in neuroimaging with recent advancements in statistical regression and machine learning (ML). A common technique to assess the brain age of a person is, first, fitting a regression model to neuroimaging data from a group of healthy subjects, and then, using the resulting model for age prediction. Although multiparametric MRI-based models generally perform best, models solely based on diffusion tensor imaging have achieved similar results, with the benefits of faster data acquisition and better replicability across scanners and field strengths. In the present study, we developed an artificial neural network (ANN) for brain age prediction based upon tract-based fractional anisotropy (FA). Consequently, we investigated if this age-prediction model could also be used for non-linear age correction of white matter diffusion metrics in healthy adults. The brain age prediction accuracy of the ANN (R 2 = 0.47) was similar to established multimodal models. The comparison of the ANN-based age-corrected FA with the tract-wise linear age-corrected FA resulted in an R 2 value of 0.90 [0.82; 0.93] and a mean difference of 0.00 [-0.04; 0.05] for all tract systems combined. In conclusion, this study demonstrated the applicability of complex ANN models to non-linear age correction of tract-based diffusion metrics as a proof of concept.

P188. Antioxidative Defense Genes and Diffusion Imaging in Youth Bipolar Disorder

Prior studies have highlighted that highly replicated anomalous white matter diffusion metrics, including fractional anisotropy (FA) and radial diffusivity (RD), are associated with oxidative stress in adults with BD. We examined the association of superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3), antioxidative single-nucleotide polymorphisms with FA and RD in youth with BD.

Predicting Attentional Vulnerability to Sleep Deprivation: A Multivariate Pattern Analysis of DTI Data.

BackgroundLarge individual differences exist in sleep deprivation (SD) induced sustained attention deterioration. Several brain imaging studies have suggested that the activities within frontal-parietal network, cortico-thalamic connections, and inter-hemispheric connectivity might underlie the neural correlates of vulnerability/resistance to SD. However, those traditional approaches are based on average estimates of differences at the group level. Currently, a neuroimaging marker that can reliably predict this vulnerability at the individual level is lacking.MethodsEfficient transfer of information relies on the integrity of white matter (WM) tracts in the human brain, we therefore applied machine learning approach to investigate whether the WM diffusion metrics can predict vulnerability to SD. Forty-nine participants completed the psychomotor vigilance task (PVT) both after resting wakefulness (RW) and after 24 h of sleep deprivation (SD). The number of PVT lapse (reaction time > 500 ms) was calculated for both RW condition and SD condition and participants were categorized as vulnerable (24 participants) or resistant (25 participants) to SD according to the change in the number of PVT lapses between the two conditions. Diffusion tensor imaging were acquired to extract four multitype WM features at a regional level: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) learning approach using leave-one-out cross-validation (LOOCV) was performed to assess the discriminative power of WM features in SD-vulnerable and SD-resistant participants.ResultsLSVM analysis achieved a correct classification rate of 83.67% (sensitivity: 87.50%; specificity: 80.00%; and area under the receiver operating characteristic curve: 0.85) for differentiating SD-vulnerable from SD-resistant participants. WM fiber tracts that contributed most to the classification model were primarily commissural pathways (superior longitudinal fasciculus), projection pathways (posterior corona radiata, anterior limb of internal capsule) and association pathways (body and genu of corpus callosum). Furthermore, we found a significantly negative correlation between changes in PVT lapses and the LSVM decision value.ConclusionThese findings suggest that WM fibers connecting (1) regions within frontal-parietal attention network, (2) the thalamus to the prefrontal cortex, and (3) the left and right hemispheres contributed the most to classification accuracy.

Systematic validation of structural brain networks in cerebral small vessel disease

Cerebral small vessel disease (SVD) is considered a disconnection syndrome, which can be quantified using structural brain network analysis obtained from diffusion MRI. Network analysis is a demanding analysis approach and the added benefit over simpler diffusion MRI analysis is largely unexplored in SVD. In this pre-registered study, we assessed the clinical and technical validity of network analysis in two non-overlapping samples of SVD patients from the RUN DMC study (n = 52 for exploration and longitudinal analysis and n = 105 for validation). We compared two connectome pipelines utilizing single-shell or multi-shell diffusion MRI, while also systematically comparing different node and edge definitions. For clinical validation, we assessed the added benefit of network analysis in explaining processing speed and in detecting short-term disease progression. For technical validation, we determined test-retest repeatability. Our findings in clinical validation show that structural brain networks provide only a small added benefit over simpler global white matter diffusion metrics and do not capture short-term disease progression. Test-retest reliability was excellent for most brain networks. Our findings question the added value of brain network analysis in clinical applications in SVD and highlight the utility of simpler diffusion MRI based markers.

White Matter Tract Neuroimaging and Serum Biomarker Analysis in Sports-related Concussion

Background: &#x0D; Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world, estimated to carry an annual global incidence of over 27 million cases. Mild TBI (mTBI), commonly known as concussion, is the mildest form of TBI and accounts for roughly 90% of all head injuries. Sports-related concussion (SRC) contributes significantly to this statistic with millions of athletes sustaining high-impact injuries in contact sports such as football, soccer, and lacrosse. By examining the white-matter microstructure, diffusion tensor imaging (DTI) has shown excellent capabilities for detecting pathophysiologic changes after SRC and monitoring symptom progression. Biomarkers including neurofilament light (NfL) and tau have been implicated in SRC and may provide insight into the duration of post-concussive symptoms. At this time, very few studies have been published evaluating the relationship between these serum biomarkers and alterations to DTI metrics. &#x0D; &#x0D; Methods: &#x0D; In the present study, we examined the association between serum biomarkers NfL and tau to further understand the relationship between these biomarkers and neuroimaging findings seen with diffusion tensor imaging (DTI) after exposure to a sports-related concussive event. &#x0D; &#x0D; Results: &#x0D; Serum tau levels decreased significantly at the 24-48h post-injury time point compared to 6h post-injury. Serum tau levels then elevated significantly at the asymptomatic time point in comparison to the 24-48h post-injury time point. The serum tau level was significantly associated with higher mean diffusivity (MD) in the white-matter tracts. Serum NfL had minimal associations with white matter diffusion metrics. &#x0D; &#x0D; Conclusion and Potential Impact: &#x0D; This research serves to better inform future investigations into the relationship between DTI metrics and serum biomarkers in the context of mTBI and SRC. This information may contribute to the development of a simple bedside serum analysis with potential to offer tremendous insight into the comprehensive brain health of patients who are being evaluated for SRC, thereby streamlining the therapeutic process and providing more accessible healthcare to patients in locations where advanced imaging techniques are not readily accessible.

Vascular health and diffusion properties of normal appearing white matter in midlife

In this study, we perform a region of interest diffusion tensor imaging and advanced diffusion complexity analysis of normal appearing white matter to determine the impact of vascular health on these diffusivity metrics in midlife adults. 77 participants (26 black, 35 female) at year 30 visit in the Coronary Artery Risk Development in Young Adults longitudinal study were scanned with an advanced diffusion-weighted imaging and fluid-attenuated inversion recovery protocol. Fractional anisotropy and non-linear diffusion complexity measures were estimated. Cumulative measures across 30 years (9 study visits) of systolic blood pressure, body mass index, glucose, smoking and cholesterol were calculated as the area under the curve from baseline up to year 30 examination. Partial correlation analyses assessed the association between cumulative vascular health measures and normal appearing white matter diffusion metrics in these participants. Midlife normal appearing white matter diffusion properties were significantly associated (P < 0.05) with cumulative exposure to vascular risk factors from young adulthood over the 30-year time period. Higher cumulative systolic blood pressure exposure was associated with increased complexity and decreased fractional anisotropy. Higher cumulative body mass index exposure was associated with decreased fractional anisotropy. Additionally, in the normal appearing white matter of black participants (P < 0.05), who exhibited a higher cumulative vascular risk exposure, fractional anisotropy was lower and complexity was higher in comparison to normal appearing white matter in white participants. Higher burden of vascular risk factor exposure from young adulthood to midlife is associated with changes in the diffusion properties of normal appearing white matter in midlife. These changes which may reflect axonal disruption, increased inflammation and/or increased glial proliferation, were primarily observed in both anterior and posterior normal appearing white matter regions of the corpus callosum. These results suggest that microstructural changes in normal appearing white matter are sensitive to vascular health during young adulthood and are possibly therapeutic targets in interventions focused on preserving white matter health across life.

Spaceflight-Associated Brain White Matter Microstructural Changes and Intracranial Fluid Redistribution

Spaceflight results in transient balance declines and brain morphologic changes; to our knowledge, the effect on brain white matter as measured by diffusion magnetic resonance imaging (dMRI), after correcting for extracellular fluid shifts, has not been examined. To map spaceflight-induced intracranial extracellular free water (FW) shifts and to evaluate changes in brain white matter diffusion measures in astronauts. We performed retrospective, longitudinal analyses on dMRI data collected between 2010 and 2015. Of the 26 astronauts' dMRI scans released by the National Aeronautics and Space Administration Lifetime Surveillance of Astronaut Health, 15 had both preflight and postflight dMRI scans and were included in the final analyses. Data were analyzed between 2015 and 2018. Seven astronauts completed a space shuttle mission (≤30 days) and 8 completed a long-duration International Space Station mission (≤200 days). The dMRI scans were acquired for clinical monitoring; in this retrospective analysis, we analyzed brain FW and white matter diffusion metrics corrected for FW. We also obtained scores from computerized dynamic posturography tests of balance to assess brain-behavior associations. Of the 15 astronauts included, the median (SD) age was 47.2 (1.5) years; 12 were men, and 3 were women. We found a significant, widespread increase in FW volume in the frontal, temporal, and occipital lobes from before spaceflight to after spaceflight. There was also a significant decrease in FW in the posterior aspect of the vertex. All FW changes were significant and ranged from approximately 2.5% to 4.0% across brain regions. We observed white matter changes in the right superior and inferior longitudinal fasciculi, the corticospinal tract, and cerebellar peduncles. All white matter changes were significant and ranged from approximately 0.75% to 1.25%. Spaceflight mission duration was associated with cerebellar white matter change, and white matter changes in the superior longitudinal fasciculus were associated with the balance changes seen in the astronauts from before spaceflight to after spaceflight. Free water redistribution with spaceflight likely reflects headward fluid shifts occurring in microgravity as well as an upward shift of the brain within the skull. White matter changes were of a greater magnitude than those typically seen during the same period with healthy aging. Future, prospective assessments are required to better understand the recovery time and behavioral consequences of these brain changes.

White matter microstructural alterations in clinically isolated syndrome and multiple sclerosis

This study aims to determine whether and how diffusion alteration occurs in the earliest stage of multiple sclerosis (MS) and the differences in diffusion metrics between CIS and MS by using the tract-based spatial statistics (TBSS) method based on diffusion tensor imaging (DTI). Thirty-six CIS patients (mean age ± SD: 34.0 years ± 12.6), 36 relapsing-remitting multiple sclerosis (RRMS) patients (mean age ± SD: 35.0 years ± 9.4) and 36 age- and gender-matched normal controls (NCs) were included in this study. Voxel-wise analyses were performed with TBSS using multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1) and radial diffusivity (λ23). In the CIS patients, TBSS analyses revealed diffusion alterations in a few white matter (WM) regions including the anterior thalamic radiation, corticospinal tract, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, body and splenium of the corpus callosum, internal capsule, external capsule, and cerebral peduncle. MS patients showed more widespread diffusion changes (decreased FA, increased λ1, λ23 and MD) than CIS. Exploratory analyses also revealed the possible associations between WM diffusion metrics and clinical variables (Expanded Disability Status Scale and disease duration) in the patients. This study provided imaging evidence for DTI abnormalities in CIS and MS and suggested that DTI can improve our knowledge of the path physiology of CIS and MS and clinical progression.

Associations of carotid arterial compliance and white matter diffusion metrics during midlife: modulation by sex.

Sex differences in cerebral white matter (WM) aging have been debated extensively over the past 2 decades without unequivocal resolution. We aimed to determine if the effects of age and arterial stiffness on WM microstructure differ between sexes. Artery elasticity via carotid artery compliance (CAC) and WM diffusion metrics via diffusion tensor image-derived fractional anisotropy (FA) and mean diffusivity (MD) were measured in 155 (87 females) middle-aged (40-62years) adults. Males demonstrated poorer water diffusion metrics in WM than women in the corpus callosum body, cingulum, and cingulum (hippocampal). Age and CAC had greater effects on WM water diffusion in males than females in midlife independent of education and cardiovascular risk factors. Sex-moderated age (cingulum FA, cingulum [hippocampal] MD, and uncinate MD, all p < 0.05) and CAC (cingulum FA, p < 0.05) related reductions in regional WM diffusion metrics. CAC mediated age-related associations in regional WM diffusion metrics (cingulum FA, cingulum MD, superior corona radiata MD, and uncinate MD, all p < 0.05) in males but not in females. Age and CAC were associated with WM diffusion metrics independent of cardiovascular risk factors. These associations appear to be stronger in males than in females.

Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study.

This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy.

Diffusion tensor imaging (DTI) findings in adult civilian, military, and sport-related mild traumatic brain injury (mTBI): a systematic critical review.

This review seeks to summarize diffusion tensor imaging (DTI) studies that have evaluated structural changes attributed to the mechanisms of mild traumatic brain injury (mTBI) in adult civilian, military, and athlete populations. Articles from 2002 to 2016 were retrieved from PubMed/MEDLINE, EBSCOhost, and Google Scholar, using a Boolean search string containing the following terms: "diffusion tensor imaging", "diffusion imaging", "DTI", "white matter", "concussion", "mild traumatic brain injury", "mTBI", "traumatic brain injury", and "TBI". We added studies not identified by this method that were found via manually-searched reference lists. We identified 86 eligible studies from English-language journals using, adult, human samples. Studies were evaluated based on duration between injury and DTI assessment, categorized as acute, subacute/chronic, remote mTBI, and repetitive brain trauma considerations. Since changes in brain structure after mTBI can also be affected by other co-occurring medical and demographic factors, we also briefly review DTI studies that have addressed socioeconomic status factors (SES), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD). The review describes population-specific risks and the complications of clinical versus pathophysiological outcomes of mTBI. We had anticipated that the distinct population groups (civilian, military, and athlete) would require separate consideration, and various aspects of the study characteristics supported this. In general, study results suggested widespread but inconsistent differences in white matter diffusion metrics (primarily fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) following mTBI/concussion. Inspection of study designs and results revealed potential explanations for discrepant DTI findings, such as control group variability, analytic techniques, the manner in which regional differences were reported, and the presence or absence of persistent functional disturbances. DTI research in adult mTBI would benefit from more standardized imaging and analytic approaches. We also found significant overlap in white matter abnormalities reported in mTBI with those commonly affected by SES or the presence of MDD and ADHD. We conclude that DTI is sensitive to a wide range of group differences in diffusion metrics, but that it currently lacks the specificity necessary for meaningful clinical application. Properly controlled longitudinal studies with consistent and standardized functional outcomes are needed before establishing the utility of DTI in the clinical management of mTBI and concussion.

Comparison of brain and spinal cord magnetic resonance imaging features in neuromyelitis optica spectrum disorders patients with or without aquaporin-4 antibody

BackgroundThe spinal cord and brain measurements are rarely investigated in neuromyelitis optica (NMO) patients with and without antibodies to aquaporin-4 (AQP4), directly compared to multiple sclerosis (MS) patients. ObjectivesTo investigate magnetic resonance imaging (MRI) features of both brain and spinal cord in NMO patients with and without antibodies to AQP4, compared with MS patients and healthy controls (HC). MethodsWe recruited 55 NMO including 30 AQP4 (+) and 25 AQP4 (−), 25 MS and 25 HC. Brain and spinal cord MRIs were obtained for each participant. Brain lesions (BL), whole brain and deep grey matter volumes (DGMV), white matter diffusion metrics and spinal cord lesions were measured and compared among groups. ResultsThe incidence of BL was lower in the AQP4 (+) group than in the AQP4 (−) and MS groups (p<0.05). In the AQP4 (+) group, there was a lower incidence of infratentorial lesions (ITL) and higher spinal cord lesions length than in the MS group (p<0.05). The thalamic and hippocampal volumes were smaller in the AQP4 (−) group and MS group than in the HC group (p<0.05). ConclusionsThe NMO patients with AQP4 (−) showed higher prevalence of BL, ITL, and similar spinal cord lesion length, compared to AQP4 (+), and demonstrated deep grey matter atrophy, suggesting an intermediate phenotype between that of typical MS and NMO.

White Matter Microstructure and Cognitive Function in Young Women With Polycystic Ovary Syndrome.

Context:Polycystic ovary syndrome (PCOS) is a disorder characterized by insulin resistance and hyperandrogenism, which leads to an increased risk of type 2 diabetes in later life. Androgens and insulin signaling affect brain function but little is known about brain structure and function in younger adults with PCOS.Objective:To establish whether young women with PCOS display altered white matter microstructure and cognitive function.Patients, interventions, and main outcome measures:Eighteen individuals with PCOS (age, 31 ± 6 y; body mass index [BMI] 30 ± 6 kg/m2) and 18 control subjects (age, 31 ± 7 y; BMI, 29 ± 6 kg/m2), matched for age, IQ, and BMI, underwent anthropometric and metabolic evaluation, diffusion tensor MRI, a technique especially sensitive to brain white matter structure, and cognitive assessment. Cognitive scores and white matter diffusion metrics were compared between groups. White matter microstructure was evaluated across the whole white matter skeleton using tract-based spatial statistics. Associations with metabolic indices were also evaluated.Results:PCOS was associated with a widespread reduction in axial diffusivity (diffusion along the main axis of white matter fibers) and increased tissue volume fraction (the proportion of volume filled by white or grey matter rather than cerebrospinal fluid) in the corpus callosum. Cognitive performance was reduced compared with controls (first principal component, t = 2.9, P = .007), reflecting subtle decrements across a broad range of cognitive tests, despite similar education and premorbid intelligence. In PCOS, there was a reversal of the relationship seen in controls between brain microstructure and both androgens and insulin resistance.Conclusions:White matter microstructure is altered, and cognitive performance is compromised, in young adults with PCOS. These alterations in brain structure and function are independent of age, education and BMI. If reversible, these changes represent a potential target for treatment.

Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults

Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid–femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults.

White matter integrity in premanifest and early Huntington's disease is related to caudate loss and disease progression

IntroductionHuntington's disease (HD) is associated with progressive loss of caudate and white matter volume and integrity. Our aim was to systematically assess interactions between these changes and genetic markers of disease progression; we are not aware of previous studies in which this has been explicitly tested. MethodsTract-based spatial statistics were used to assess: (a) differences between the white matter diffusion metrics (fractional anisotropy and mean diffusivity) of 17 premanifest and 19 early manifest HD gene carriers and 21 controls, and (b) the relationships between diffusion metrics, caudate and total white matter volume, and disease burden score and CAG repeat length. Caudate and total white matter volumes were quantified using FIRST and SIENAX respectively. Multiple regression analysis was used to assess which of the imaging metrics predicted disease severity in the HD subjects. ResultsDiffusion metrics were significantly altered in premanifest and early HD gene carriers in comparison with controls throughout the white matter skeleton. Correlations between diffusion and volumetric metrics and disease progression were also present. Together, caudate volume and mean white matter fractional anisotropy and mean diffusivity predicted disease burden score in the HD subjects. ConclusionsThe diffusion properties of white matter are extensively altered in HD, and are associated with markers of HD severity, and with caudate and white matter volumes. The correlation between diffusion metrics and white matter volume is stronger in HD subjects than in controls, but there is no such significant interaction for the correlation between diffusion and caudate volume: we propose that many of the changes in white matter diffusion in HD occur as a ‘normal’ physiological response to pathological caudate volume loss. We have defined the extent to which mean white matter fractional anisotropy, white matter volume and caudate volume are associated with disease burden score.

Anatomical Substrates of the Alerting, Orienting and Executive Control Components of Attention: Focus on the Posterior Parietal Lobe

Both neuropsychological and functional neuroimaging studies have identified that the posterior parietal lobe (PPL) is critical for the attention function. However, the unique role of distinct parietal cortical subregions and their underlying white matter (WM) remains in question. In this study, we collected both magnetic resonance imaging and diffusion tensor imaging (DTI) data in normal participants, and evaluated their attention performance using attention network test (ANT), which could isolate three different attention components: alerting, orienting and executive control. Cortical thickness, surface area and DTI parameters were extracted from predefined PPL subregions and correlated with behavioural performance. Tract-based spatial statistics (TBSS) was used for the voxel-wise statistical analysis. Results indicated structure-behaviour relationships on multiple levels. First, a link between the cortical thickness and WM integrity of the right inferior parietal regions and orienting performance was observed. Specifically, probabilistic tractography demonstrated that the integrity of WM connectivity between the bilateral inferior parietal lobules mediated the orienting performance. Second, the scores of executive control were significantly associated with the WM diffusion metrics of the right supramarginal gyrus. Finally, TBSS analysis revealed that alerting performance was significant correlated with the fractional anisotropy of local WM connecting the right thalamus and supplementary motor area. We conclude that distinct areas and features within PPL are associated with different components of attention. These findings could yield a more complete understanding of the nature of the PPL contribution to visuospatial attention.