White Matter Microstructural Alterations Research Articles

Neonatal genetic epilepsies display convergent white matter microstructural abnormalities.

White matter undergoes rapid development in the neonatal period. Its structure during and after development is influenced by neuronal activity. Pathological neuronal activity, as in seizures, might alter white matter, which in turn may contribute to network dysfunction. Neonatal epilepsy presents an opportunity to investigate seizures and early white matter development. Our objective was to determine whether neonatal seizures in the absence of brain injury or congenital anomalies are associated with altered white matter microstructure. In this retrospective case-control study of term neonates, cases had confirmed or suspected genetic epilepsy and normal brain magnetic resonance imaging (MRI) and no other conditions independently impacting white matter. Controls were healthy neonates with normal MRI results. White matter microstructure was assessed via quantitative mean diffusivity (MD). In 22 cases, MD was significantly lower in the genu of the corpus callosum, compared to 22 controls, controlling for gestational age and postmenstrual age at MRI. This finding suggests convergent abnormal corpus callosum microstructure in neonatal epilepsies with diverse suspected genetic causes. Further study is needed to determine the specific nature, causes, and functional impact of seizure-associated abnormal white matter in neonates, a potential pathogenic mechanism.

Brain substrates explain differences in the adoption and degree of financial digitalization

This study analyzes neural responses connected to trust and risk to explain financial digitalization decisions. It shows that brain responses distinctively inform differences in the adoption of digital financial channels that are not shown by any other sociodemographic or behavioral indicators. From a methodological standpoint, the study explores if usage patterns of digital financial channels and instruments are associated with psychological and biological indicators; it uses functional magnetic resonance imaging (fMRI) to investigate whether financial digitalization decisions are linked to the evoked brain response to the safety associated with video images of financial transactions through digitalized and non-digitalized channels; it conducts trust and risk neuro-experiments to identify their impact on financial digitalization decisions and it analyzes whether brain structure is linked to financial digitalization behavior. The findings suggest that high and low frequency users exhibit differences in brain function and also in volume and fractional anisotropy values. A higher frequency of use of financial digital financial services is associated with higher brain activation linked to insecurity (lower safety neural evoked responses during the video task and an altered white matter microstructure of the cingulum). Additionally, high frequency users of digital financial channels exhibit enhanced activation of brain areas linked to emotional processing during the trust game. These findings have important implications for the design of public policies to enhance financial inclusion through technology and the segmentation and service distribution strategies of private financial institutions.

Abnormal white matter tracts of insula in smokers.

Nicotine addiction is characterized as a neural circuit dysfunction, particularly with regard to the alterations in central reward pathways. The insula, a cortical region that is thought to play a central role in this reward circuitry, has been implicated in the maintenance of nicotine addiction. However, it remains largely unclear about the white matter (WM) microstructural alterations of insula in nicotine addiction and whether the WM alterations of insula could predict smoking cessation outcomes. In this study, 58 male nicotine-dependent smokers and 34 matched male nonsmoking controls were recruited. After a 12-week smoking cessation treatment with varenicline, 38 smokers relapsed, and 20 did not relapse. Diffusion tensor imaging and probabilistic tractography were used to investigate the differences of WM tracts of insula between smokers and nonsmokers. Relative to nonsmokers, in the left hemisphere, smokers showed lower fractional anisotropy (FA) in the fiber tracts of anterior insula cortex-to-nucleus accumbens and posterior insula cortex-to-nucleus accumbens; in the right hemisphere, smokers showed higher FA, and lower axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the fiber tracts of anterior insula cortex-to-medial orbitofrontal cortex, posterior insula cortex-to-medial orbitofrontal cortex, and posterior insula cortex-to-nucleus accumbens. However, there were no differences of WM diffusion properties between relapsers and nonrelapsers. This study is the first using probabilistic tractography to exclusively clarify the precise roles of insular WM tracts in smokers, which may provide new insights into the underlying neurobiology of nicotine addiction.

Additive and Synergistic Cardiovascular Disease Risk Factors and HIV Disease Markers' Effects on White Matter Microstructure in Virally Suppressed HIV.

It is unclear whether intermediate to high cardiovascular disease (CVD) risk and HIV disease status may have additive (ie, independent statistical effects concomitantly tested) or synergistic effects on white matter microstructure and cognition in virally suppressed HIV-infected (HIV+) men relative to sex and age-matched controls. Tertiary health care observational cohort. Eighty-two HIV+ men (mean age 55 ± 6 years, 10%-30% on various CVD drugs; 20% with previous CVD) and 40 HIV-uninfected (HIV-) men (none with previous CVD; 10%-20% on various CVD drugs) underwent diffusion tensor imaging and neuropsychological testing. A standard classification of intermediate to high CVD risk (CVD+ group) was based on the Framingham score ≥15% cutoff and/or a history of CVD. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified in 11 white matter tracts. Within the HIV- group, the CVD+ group had lower FA (P = 0.03) and higher MD (P = 0.003) in the corona radiata and higher MD in the corpus callosum (P = 0.02) and superior fasciculi (P = 0.03) than the CVD- group. Within the HIV+ group, the CVD+ group had lower FA in the superior fasciculi (P = 0.04) and higher MD in the uncinate fasciculus (P = 0.04), and lower FA (P = 0.01) and higher MD (P = 0.03) in the fornix than the CVD- group. The fornix alterations were also abnormal compared with the HIV- groups. The HIV+ CVD+ was more likely to have HIV-associated dementia. Older age, antihypertensive use, longer HIV duration, and higher C-reactive protein associated with lower FA and higher MD. Higher blood CD4 lymphocyte count and CD4/CD8 ratio associated with higher FA and lower MD. In virally suppressed HIV, CVD risk factors have a mostly additive contribution to white matter microstructural alterations, leading to a different distribution of injury in HIV- and HIV+ persons with CVD. There was also evidence of a synergistic effect of CVD and HIV factors on the fornix white matter injury.

Diffusion Tensor Imaging in Contact and Non-Contact University-Level Sport Athletes.

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

MR Imaging of SCA3/MJD.

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive autosomal dominantly inherited cerebellar ataxia characterized by the aggregation of polyglutamine-expanded protein within neuronal nuclei in the brain, which can lead to brain damage that precedes the onset of clinical manifestations. Magnetic resonance imaging (MRI) techniques such as morphometric MRI, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and magnetic resonance spectroscopy (MRS) have gained increasing attention as non-invasive and quantitative methods for the assessment of structural and functional alterations in clinical SCA3/MJD patients as well as preclinical carriers. Morphometric MRI has demonstrated typical patterns of atrophy or volume loss in the cerebellum and brainstem with extensive lesions in some supratentorial areas. DTI has detected widespread microstructural alterations in brain white matter, which indicate disrupted brain anatomical connectivity. Task-related fMRI has presented unusual brain activation patterns within the cerebellum and some extracerebellar tissue, reflecting the decreased functional connectivity of these brain regions in SCA3/MJD subjects. MRS has revealed abnormal neurochemical profiles, such as the levels or ratios of N-acetyl aspartate, choline, and creatine, in both clinical cases and preclinical cases before the alterations in brain anatomical structure. Moreover, a number of studies have reported correlations of MR imaging alterations with clinical and genetic features. The utility of these MR imaging techniques can help to identify preclinical SCA3/MJD carriers, monitor disease progression, evaluate response to therapeutic interventions, and illustrate the pathophysiological mechanisms underlying the occurrence, development, and prognosis of SCA3/MJD.

Material hardship, prefrontal cortex-amygdala structure, and internalizing symptoms in children.

Material hardship, or difficulty affording basic resources such as food, housing, utilities, and health care, increases children's risk for internalizing problems. The uncinate fasciculus (UNC) and two of the gray matter regions it connects-the orbitofrontal cortex (OFC) and amygdala-may play important roles in the neural mechanisms underlying these associations. We investigated associations among material hardship, UNC microstructure, OFC and amygdala structure, and internalizing symptoms in children. Participants were 5-9-year-old children (N=94, 61% female) from socioeconomically diverse families. Parents completed questionnaires assessing material hardship and children's internalizing symptoms. High-resolution, T1-weighted magnetic resonance imaging (n=51), and diffusion tensor imaging (n=58) data were acquired. UNC fractional anisotropy (FA), medial OFC surface area, and amygdala gray matter volume were extracted. Greater material hardship was significantly associated with lower UNC FA, smaller amygdala volume, and higher internalizing symptoms in children, after controlling for age, sex, and family income-to-needs ratio. Lower UNC FA significantly mediated the association between material hardship and internalizing symptoms in girls but not boys. These findings are consistent with the notion that material hardship may lead to altered white matter microstructure and gray matter structure in neural networks critical to emotion processing and regulation.

Structural MRI and tract-based spatial statistical analysis of diffusion tensor imaging in children with hemimegalencephaly.

To investigate the gross white matter abnormalities in the structural brain MR imaging as well as white matter microstructural alterations using tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) in both affected and contralateral cerebral hemispheres of children with hemimegalencephaly (HMEG). From 2003 to 2019, we retrospectively reviewed brain MR images in 20 children (11 boys, 2days-16.5years) with HMEG, focusing on gross white matter abnormalities. DTI was evaluated in 12 patients (8 boys, 3months-16.5years) with HMEG and 12 age-, sex-, and magnetic field strength-matched control subjects. TBSS analysis was performed to analyze main white matter tracts. Regions of significant differences in fractional anisotropy (FA) were determined between HMEG and control subjects and between affected and contralateral hemispheres of HMEG. Gross white matter abnormalities were noted in both affected (n = 20, 100%) and contralateral hemisphere (n = 4, 20%) of HMEG. FA values were significantly decreased in both hemispheres of HMEG, compared with control subjects (P < 0.05). Contralateral hemispheres of HMEG showed regions with significantly decreased FA values compared with affected hemispheres (P < 0.05). In addition to gross white matter abnormalities particularly evident in affected hemispheres, DTI analysis detected widespread microstructural alterations in both affected and contralateral hemispheres in HMEG suggesting HMEG may involve broader abnormalities in neuronal networks.

Detection of microstructural white matter alterations in functional gastrointestinal disorders assessed by diffusion kurtosis imaging.

Background and AimWe evaluated whether diffusion kurtosis and tensor imaging (DKI/DTI) could reveal microstructural alterations in the brains of patients with functional gastrointestinal disorders (FGIDs), and whether imaging findings were correlated with health‐related quality of life (HRQOL).MethodsTwelve patients with FGIDs fulfilling the Rome IV criteria, and seven healthy controls were examined using a 3 T magnetic resonance (MR) scanner. Tract‐based spatial statistics and regions of interest analyses were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) between patients with FGIDs versus controls. HRQOL was assessed in patients with FGIDs using the eight‐item short form of the Medical Outcome Study Questionnaire (SF‐8) and the Gastrointestinal Symptom Rating Scale.ResultsPatients with FGIDs had extensive, widespread regions of reduced MD in the white matter in comparison with healthy controls, whereas no significant differences were observed in MK and FA. No significant differences in deep gray matter for the MK, FA, and MD values were observed between patients with FGIDs and controls. In patients with FGIDs, the FA values in the globus pallidus had a significant and negative correlation with SF‐8 (a mental component summary) (r = −0.797, P = 0.01 uncorrected for multiple comparisons).ConclusionsDKI/DTI can help identify microstructural white matter alterations in patients with FGIDs. The FA values in the globus pallidus may be useful for a severity assessment of FGIDs.

Neuroimaging studies within Cognitive Genetics Collaborative Research Organization aiming to replicate and extend works of ENIGMA.

Reproducibility is one of the most important issues for generalizing the results of clinical research; however, low reproducibility in neuroimaging studies is well known. To overcome this problem, the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium, an international neuroimaging consortium, established standard protocols for imaging analysis and employs either meta‐ and mega‐analyses of psychiatric disorders with large sample sizes. The Cognitive Genetics Collaborative Research Organization (COCORO) in Japan promotes neurobiological studies in psychiatry and has successfully replicated and extended works of ENIGMA especially for neuroimaging studies. For example, (a) the ENIGMA consortium showed subcortical regional volume alterations in patients with schizophrenia (n = 2,028) compared to controls (n = 2,540) across 15 cohorts using meta‐analysis. COCORO replicated the volumetric changes in patients with schizophrenia (n = 884) compared to controls (n = 1,680) using the ENIGMA imaging analysis protocol and mega‐analysis. Furthermore, a schizophrenia‐specific leftward asymmetry for the pallidum volume was demonstrated; and (b) the ENIGMA consortium identified white matter microstructural alterations in patients with schizophrenia (n = 1,963) compared to controls (n = 2,359) across 29 cohorts. Using the ENIGMA protocol, a study from COCORO showed similar results in patients with schizophrenia (n = 696) compared to controls (n = 1,506) from 12 sites using mega‐analysis. Moreover, the COCORO study found that schizophrenia, bipolar disorder (n = 211) and autism spectrum disorder (n = 126), but not major depressive disorder (n = 398), share similar white matter microstructural alterations, compared to controls. Further replication and harmonization of the ENIGMA consortium and COCORO will contribute to the generalization of their research findings.

Stress-Induced Microstructural Alterations Correlate With the Cognitive Performance of Rats: A Longitudinal in vivo Diffusion Tensor Imaging Study.

Background: Stress-induced cellular changes in limbic brain structures contribute to the development of various psychopathologies. In vivo detection of these microstructural changes may help us to develop objective biomarkers for psychiatric disorders. Diffusion tensor imaging (DTI) is an advanced neuroimaging technique that enables the non-invasive examination of white matter integrity and provides insights into the microstructure of pathways connecting brain areas.Objective: Our aim was to examine the temporal dynamics of stress-induced structural changes with repeated in vivo DTI scans and correlate them with behavioral alterations.Methods: Out of 32 young adult male rats, 16 were exposed to daily immobilization stress for 3 weeks. Four DTI measurements were done: one before the stress exposure (baseline), two scans during the stress (acute and chronic phases), and a last one 2 weeks after the end of the stress protocol (recovery). We used a 4.7T small-animal MRI system and examined 18 gray and white matter structures calculating the following parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). T2-weighted images were used for volumetry. Cognitive performance and anxiety levels of the animals were assessed in the Morris water maze, novel object recognition, open field, and elevated plus maze tests.Results: Reduced FA and increased MD and RD values were found in the corpus callosum and external capsule of stressed rats. Stress increased RD in the anterior commissure and reduced MD and RD in the amygdala. We observed time-dependent changes in several DTI parameters as the rats matured, but we found no evidence of stress-induced volumetric alterations in the brains. Stressed rats displayed cognitive impairments and we found numerous correlations between the cognitive performance of the animals and between various DTI metrics of the inferior colliculus, corpus callosum, anterior commissure, and amygdala.Conclusions: Our data provide further support to the translational value of DTI studies and suggest that chronic stress exposure results in similar white matter microstructural alterations that have been documented in stress-related psychiatric disorders. These DTI findings imply microstructural abnormalities in the brain, which may underlie the cognitive deficits that are often present in stress-related mental disorders.

Changes of white matter microstructure after successful treatment of bipolar depression

BackgroundDiffusion tensor imaging (DTI) measures suggest a widespread alteration of white matter (WM) microstructure in patients with bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been confirmed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response. MethodsWe tested if changes in DTI measures of WM microstructure could parallel antidepressant response in a sample of 44 patients with a major depressive episode in course of BD, treated with chronoterapeutics for one week. We used both a tract-wise and a voxel-wise approach for the whole-brain extraction of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA). ResultsCompared to baseline level, at one-week follow up we observed a significant increase in average FA measures paralleled by a significant decrease in MD measures of several WM tracts including cingulum, corpus callosum, corona radiata, cortico-spinal tract, internal capsule, fornix and uncinate fasciculus. The degree of change was associated to clinical response. ConclusionsThis is the first study to show changes of individual DTI measures of WM microstructure in response to antidepressant treatment in BD. Our results add new evidence to warrant a role for chronotherapeutics as a first-line treatment for bipolar depression and contribute identifying generalizable neuroimaging-based biomarkers of antidepressant response.

Characterizing white matter connectivity in Alzheimer's disease and mild cognitive impairment: An automated fiber quantification analysis with two independent datasets

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive dementia. Diffusion tensor imaging (DTI) has been widely used to show structural integrity and delineate white matter (WM) degeneration in AD. The automated fiber quantification (AFQ) method is a fully automated approach that can rapidly and reliably identify major WM fiber tracts and evaluate WM properties. The main aim of this study was to assess WM integrity and abnormities in a cohort of patients with amnestic mild cognitive impairment (aMCI) and AD as well as normal controls (NCs). For this purpose, we first used AFQ to identify 20 major WM tracts and assessed WM integrity and abnormalities in a cohort of 120 subjects (39 NCs, 34 aMCI patients and 47 AD patients) in a discovery dataset and 122 subjects (43 NCs, 37 aMCI patients and 42 AD patients) in a replicated dataset. Pointwise differences along WM tracts were identified in the discovery dataset and simultaneously confirmed in the replicated dataset. Next, we investigated the utility of DTI measures along WM tracts as features to distinguish patients with AD from NCs via multilevel cross validation using a support vector machine. Correlation analysis revealed the identified microstructural WM alterations and classification output to be highly associated with cognitive ability in the patient groups, suggesting that they may be a robust biomarker of AD. This systematic study provides a pipeline to examine WM integrity and its potential clinical application in AD and may be useful for studying other neurological and psychiatric disorders.

White matter disruption in obsessive-compulsive disorder revealed by meta-analysis of tract-based spatial statistics.

Exploring white matter (WM) microstructural alterations is a momentous step for gaining insights about underlying mechanisms of obsessive-compulsive disorder (OCD) and improving the efficacy of therapies for this condition. Many tract-based spatial statistics (TBSS) studies have revealed abnormalities of fractional anisotropy (FA; an index of WM integrity) in OCD. However, research works have not drawn robust conclusions. Therefore, we integrated the findings of TBSS studies to identify the most consistent FA changes in OCD using meta-analytical approach. Online databases were systematically searched for all TBSS studies comparing FA between patients with OCD and controls. A coordinate-based meta-analysis was performed using anisotropic effect size version of the seed-based d mapping software. Meanwhile, meta-regression was used to explore the potential association of clinical characteristics with regional FA abnormalities. Our meta-analysis included 488 OCD patients and 519 controls across 17 datasets. FA reductions were identified in the genu of the corpus callosum and the left orbitofrontal WM in OCD patients relative to controls. Metaregression analyses showed that the FA in the left orbitofrontal WM was negatively and independently correlated with symptom severity and illness duration in patients withOCD. The current study provides a quantitative overview of TBSS findings in OCD and demonstrates the most prominent and replicable WM abnormalities in OCD are in the anterior part of the brain including interhemispheric connection and orbitofrontal region. Additionally, our findings suggest that FA reduction in the orbitofrontal WM might be a potential biomarker in predicting disease severity and progression in patients with OCD.

Peak Width of Skeletonized Water Diffusion MRI in the Neonatal Brain.

Preterm birth is closely associated with cognitive impairment and generalized dysconnectivity of neural networks inferred from water diffusion MRI (dMRI) metrics. Peak width of skeletonized mean diffusivity (PSMD) is a metric derived from histogram analysis of mean diffusivity across the white matter skeleton, and it is a useful biomarker of generalized dysconnectivity and cognition in adulthood. We calculated PSMD and five other histogram based metrics derived from diffusion tensor imaging (DTI) and neurite orientation and dispersion imaging (NODDI) in the newborn, and evaluated their accuracy as biomarkers of microstructural brain white matter alterations associated with preterm birth. One hundred and thirty five neonates (76 preterm, 59 term) underwent 3T MRI at term equivalent age. There were group differences in peak width of skeletonized mean, axial, and radial diffusivities (PSMD, PSAD, PSRD), orientation dispersion index (PSODI) and neurite dispersion index (PSNDI), all p < 10−4. PSFA did not differ between groups. PSNDI was the best classifier of gestational age at birth with an accuracy of 81±10%, followed by PSMD, which had 77±9% accuracy. Models built on both NODDI metrics, and on all dMRI metrics combined, did not outperform the model based on PSNDI alone. We conclude that histogram based analyses of DTI and NODDI parameters are promising new image markers for investigating diffuse changes in brain connectivity in early life.

Effects of Recreational GHB Use and Multiple GHB-Induced Comas on Brain Structure and Impulsivity.

Background and AimsThe regular use of gamma-hydroxybutyrate acid (GHB) can induce GHB-induced comas. Other substance use disorders are associated with alterations in brain structure and impulsivity. Here we aim to investigate if these are also modulated by either regular GHB use or GHB-induced comas.MethodsIn a sample of human males, structural and diffusion neuroimaging data were collected for 27 GHB users with ≥4 GHB-induced comas (GHB-Coma), 27 GHB users without GHB-induced comas (GHB-NoComa), and 27 polydrug users who never used GHB (No-GHB). The structural brain parameters were analyzed macroscopically using voxel-based morphometry and microscopically using tract-based spatial statistics (TBSS) and tractography. Impulsivity was assessed with the Barrat Impulsivity Scale.ResultsIn comparison to the other two groups, the GHB-Coma group showed a higher fractional anisotropy in the body of the corpus callosum and a lower mean diffusivity in the forceps minor (i.e., whole-brain TBSS analysis). No macrostructural differences nor microstructural differences, as assessed with tractography, were observed. The GHB-Coma group also reported higher impulsivity, which was more strongly associated with white matter volume and fractional anisotropy in tracts involved in impulse control (post-hoc analysis). GHB use per se was associated neither with differences in brain structure nor with impulsivity.ConclusionsThe results suggest that multiple GHB-induced comas, but not GHB use per se, are associated with microstructural alterations in white matter and with higher self-reported impulsivity, which in turn was associated with white matter tracts involved in impulse control.

Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = −0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

Polygenic Multiple Sclerosis Risk and Population-Based Childhood Brain Imaging.

ObjectiveMultiple sclerosis (MS) is a neurological disease with a substantial genetic component and immune‐mediated neurodegeneration. Patients with MS show structural brain differences relative to individuals without MS, including smaller regional volumes and alterations in white matter (WM) microstructure. Whether genetic risk for MS is associated with brain structure during early neurodevelopment remains unclear. In this study, we explore the association between MS polygenic risk scores (PRS) and brain imaging outcomes from a large, population‐based pediatric sample to gain insight into the underlying neurobiology of MS.MethodsWe included 8‐ to 12‐year‐old genotyped participants from the Generation R Study in whom T1‐weighted volumetric (n = 1,136) and/or diffusion tensor imaging (n = 1,088) had been collected. PRS for MS were calculated based on a large genome‐wide association study of MS (n = 41,505) and were regressed on regional volumes, global and tract‐specific fractional anisotropy (FA), and global mean diffusivity using linear regression.ResultsNo associations were observed for the regional volumes. We observed a positive association between the MS PRS and global FA (β = 0.098, standard error [SE] = 0.030, p = 1.08 × 10−3). Tract‐specific analyses showed higher FA and lower radial diffusivity in several tracts. We replicated our findings in an independent sample of children (n = 186) who were scanned in an earlier phase (global FA; β = 0.189, SE = 0.072, p = 9.40 × 10−3).InterpretationThis is the first study to show that greater genetic predisposition for MS is associated with higher global brain WM FA at an early age in the general population. Our results suggest a preadolescent time window within neurodevelopment in which MS risk variants act upon the brain. ANN NEUROL 2020;87:774–787

Neuroinflammation in Bipolar Depression.

Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.

Alterations of White Matter Microstructure in Subcortical Vascular Mild Cognitive Impairment with and without Depressive Symptoms.

Depressive symptoms were thought to increase the risk of vascular dementia. Previous studies reported widespread white matter damages in the subcortical vascular mild cognitive impairment (svMCI), but little is known about the mechanism of depressive symptoms in svMCI. In the current study, we aim to explore the white matter microstructural alterations in svMCI with depressive symptoms, and their associations with clinical measurements. Fifty-eight subjects including 18 svMCI with depression (svMCI+D), 17 svMCI without depression (svMCI-D), and 23 normal controls (NC) were included in the study. Voxel-based analyses were performed on fractional anisotropy (FA) and mean diffusivity (MD). Compared to NC, both svMCI groups showed decreased FA in the bilateral insula and the left precentral gyrus, and increased MD in the cerebellum. Compared to svMCI-D, svMCI+D showed increased FA in left precentral gyrus. Moreover, svMCI+D showed significant correlation between the increased MD in the cerebellum and the Hamilton Depression Rating Scale (HAMD) scores. Our findings of white matter alterations might be associated with executive function and memory performance in the svMCI patients. Moreover, the structural alterations in the cerebellum might underlie the mechanism of depressive symptoms in svMCI patients.