White Matter Microstructural Integrity Research Articles

Age-related Differences in Response Inhibition Are Mediated by Frontoparietal White Matter but Not Functional Activity.

Healthy older adults often exhibit lower performance but increased functional recruitment of the frontoparietal control network during cognitive control tasks. According to the cortical disconnection hypothesis, age-related changes in the microstructural integrity of white matter may disrupt inter-regional neuronal communication, which in turn can impair behavioral performance. Here, we use fMRI and diffusion-weighted imaging to determine whether age-related differences in white matter microstructure contribute to frontoparietal over-recruitment and behavioral performance during a response inhibition (go/no-go) task in an adult life span sample (n = 145). Older and female participants were slower (go RTs) than younger and male participants, respectively. However, participants across all ages were equally accurate on the no-go trials, suggesting some participants may slow down on go trials to achieve high accuracy on no-go trials. Across the life span, functional recruitment of the frontoparietal network within the left and right hemispheres did not vary as a function of age, nor was it related to white matter fractional anisotropy (FA). In fact, only frontal FA and go RTs jointly mediated the association between age and no-go accuracy. Our results therefore suggest that frontal white matter cortical "disconnection" is an underlying driver of age-related differences in cognitive control, and white matter FA may not fully explain functional task-related activation in the frontoparietal network during the go/no-go task. Our findings add to the literature by demonstrating that white matter may be more important for certain cognitive processes in aging than task-related functional activation.

Understanding the impact of congenital infections and perinatal viral exposures on the developing brain using white matter magnetic resonance imaging: a scoping review

BackgroundMagnetic Resonance Imaging (MRI)-based imaging techniques are useful for assessing white matter (WM) structural and microstructural integrity in the context of infection and inflammation. The purpose of this scoping review was to assess the range of work on the use of WM neuroimaging approaches to understand the impact of congenital and perinatal viral infections or exposures on the developing brain.MethodsThis scoping review was conducted according to the Arksey and O’ Malley framework. A literature search was performed in Web of Science, Scopus and PubMed for primary research articles published from database conception up to January 2022. Studies evaluating the use of MRI-based WM imaging techniques in congenital and perinatal viral infections or exposures were included. Results were grouped by age and infection.ResultsA total of 826 articles were identified for screening and 28 final articles were included. Congenital and perinatal infections represented in the included studies were cytomegalovirus (CMV) infection (n = 12), human immunodeficiency virus (HIV) infection (n = 11) or exposure (n = 2) or combined (n = 2), and herpes simplex virus (HSV) infection (n = 1). The represented MRI-based WM imaging methods included structural MRI and diffusion-weighted and diffusion tensor MRI (DWI/ DTI). Regions with the most frequently reported diffusion metric group differences included the cerebellar region, corticospinal tract and association fibre WM tracts in both children with HIV infection and children who are HIV-exposed uninfected. In qualitative imaging studies, WM hyperintensities were the most frequently reported brain abnormality in children with CMV infection and children with HSV infection.ConclusionThere was evidence that WM imaging techniques can play a role as diagnostic and evaluation tools assessing the impact of congenital infections and perinatal viral exposures on the developing brain. The high sensitivity for identifying WM hyperintensities suggests structural brain MRI is a useful neurodiagnostic modality in assessing children with congenital CMV infection, while the DTI changes associated with HIV suggest metrics such as fractional anisotropy have the potential to be specific markers of subtle impairment or WM damage in neuroHIV.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (β=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB.

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study

BackgroundSodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD.MethodsGenetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations.ResultsA lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively.ConclusionsSGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.

Assessment of white matter microstructure integrity in subacute postconcussive vestibular dysfunction using NODDI

Abstract Vestibular symptoms, such as dizziness and balance impairment, are frequently reported following mild traumatic brain injury (mTBI) and are associated with a protracted recovery, yet the underlying neuroanatomical substrates remain unclear. The present study utilized advanced diffusion MRI (dMRI) techniques including both conventional diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate microstructural white matter integrity in individuals with postconcussive vestibular dysfunction (PCVD) within the subacute injury period (median of 35 days from injury; IQR of 23). Study participants included 23 individuals with subacute PCVD and 37 healthy control subjects who underwent imaging and comprehensive clinical vestibular testing. Between-group voxelwise analysis of differences in white matter revealed areas of higher intra-neurite volume fraction (VIn) and isotropic volume fraction (VIso) within PCVD subjects compared to controls, which involved overlapping regions within the left hemisphere of the brain. Affected areas of higher VIn and VIso included the superior longitudinal fasciculus (SLF) and superior and posterior corona radiata (SCR and PCR, respectively). We examined the relationship between clinical vestibular measures and diffusion metrics including DTI (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD] and axial diffusivity [AD]) and NODDI (intraneurite volume fraction [VIn], isotropic volume fraction [VIso], dispersion anisotropy [DA], orientation dispersion indexTotal/Primary/Secondary [ODIT/P/S]) within 32 regions-of-interest. Clinical vestibular measures included self-reported measures, including the Dizziness Handicap Inventory, Visual Vertigo Analog Scale, and Vestibular/Ocular-Motor Screening, as well as objective vestibular testing using the sensory organization test. Significant correlations were found with clinical measures across all diffusion maps (except DA), within various regions of interest (ROIs), including SLF, SCR, and PCR. These results implicate several important association bundles that may potentiate sensory processing dysfunction related to PCVD. Whether these neuroanatomical differences found within the subacute phase of PCVD are in response to injury or represent preexisting structural variations that increase vulnerability to sensory processing dysfunction is unclear and remains an active area of study.

Diffusion Tensor Tractography in Patient with Cervical Spondylosis and Correlation with Clinical Findings

Introduction: Diffusion tensor imaging is a non-invasive advanced method that provides information on white matter microstructural integrity. Fractional anisotropy and apparent diffusion coefficient have been used to quantify the degree of axonal damage and demyelination. The study aims to assess the role of diffusion tensor parameters in detecting early myelopathic changes and correlate them with clinical findings. Methods: This cross-sectional prospective study including 60 patients with clinical history of cervical myelopathy was carried out at the Department of Radiology from June 2021 to July 2022. Nurick score was used to assess the severity clinically and diffusion tensor images of the cervical spine were obtained using 3 Tesla MRI. These diffusion tensor values at the level of maximum stenosis were compared with those of the non-stenotic level. A correlation between the diffusion tensor parameters and clinical Nurick score was done. Results: The fractional anisotropy values were significantly lower (0.51 ± 0.14 vs 0.76 ± 0.47) and apparent diffusion coefficient values were significantly higher (1.20 ± 0.20 vs 1.04 ± 0.12) at the level of maximum stenosis compared with non-stenotic levels. There was a moderate positive and strong negative correlation between the apparent diffusion coefficient and fractional anisotropy values with the Nurick score. Conclusions: A significant reduction in the fractional anisotropy and an increase in apparent diffusion coefficient values at the level of stenosis was observed in individuals without a high T2 signal within the cord. Thus, these parameters might have a potential role in the early diagnosis of cervical spondylotic myelopathy

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Subclinical Metabolic and Cardiovascular Factors and Brain White Matter Microstructural Integrity in Young Women.

Women who have experienced pregnancy complications, specifically preeclampsia and gestational diabetes, have well documented increased risks of cardiovascular, metabolic, and neurological disease later in life. This study examined how specific cardiovascular and metabolic risk factors for preeclampsia assessed in a non-pregnant state were associated with brain white matter microstructural integrity. This study examined sixty-two healthy women (mean age 31 ± 5years) who received metabolic and cardiovascular assessments as well as multiple modality MRI imaging. Participants were either nulliparous (n = 31) or had a history of preterm preeclampsia (n = 31). Imaging included acquisition Diffusion Tensor Imaging (DTI) to assess white matter integrity within the brain. We hypothesized that healthy, young, non-pregnant women with cardiovascular and metabolic profiles suggesting elevated risk would have decreased white matter integrity, represented by lower Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) estimates in the posterior cortical areas of the brain. We observed increased white matter degradation (lower FA and increased MD) in posterior and occipital tracts, commissural fibers, and subcortical structures in women with increased adiposity, worse measures of cardiovascular and metabolic function, including greater insulin resistance (HOMA-IR), hyperlipidemia, elevated blood pressure, and increased arterial stiffness. The relationships detected between subclinical cardiovascular and metabolic phenotypes and increased white matter disruption at a young age, outside of pregnancy, are indicative that adverse changes are detectable long before cognitive clinical presentation. This may suggest that many of the long-term cardiovascular and metabolic risks of aging are influenced by physiologic aging trajectories rather than damage caused by pregnancy complications.

485 Investigating the Impact of Inflammation on White Matter Tracts using Diffusion Tensor Imaging that may Contribute to Motivational Deficits and Negative Symptoms in Patients with Schizophrenia

OBJECTIVES/GOALS: Previous research has linked inflammation to changes in brain reward circuitry and subsequent negative symptoms in patients with schizophrenia. This project aims to understand brain-immune interactions using diffusion tensor imaging (DTI) to investigate the impact of inflammatory markers on white matter (WM) tracts. METHODS/STUDY POPULATION: Patients with schizophrenia, ages 18 to 45, were recruited at Grady Hospital in Atlanta, GA. All subjects were stable outpatients and underwent extensive medical screening to rule out medical causes of acute inflammation. DTI data was collected from 39 participants on a 3-Tesla Siemens scanner. Blood was collected between 9-11AM for later assay of serum inflammatory markers. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). A diffusion tensor imaging model will be fitted with the data to generate well-known diffusion tensor measures (fractional anisotropy and mean diffusivity). Linear regression will be used to analyze the relationship between DTI measures and inflammation (C-Reactive Protein, CRP), controlling for possible confounders. RESULTS/ANTICIPATED RESULTS: The hypothesis of this proposal is that decreased microstructural integrity in WM tracts between the nucleus accumbens (NAc) and insula will be associated with increased inflammation, which in turn are associated with increased negative symptoms. Negative symptoms include deficits in motivation/pleasure as well as diminished expressivity, and are strongly associated with poor functional outcomes. Based on previous data from this sample demonstrating relationships between CRP and negative symptoms as well as CRP and fMRI functional connectivity between the NAc and insula, we anticipate results that demonstrate similar relationships with WM microstructural integrity, such as functional anisotropy and mean diffusivity. DISCUSSION/SIGNIFICANCE: Given the lack of treatment options for negative symptoms, this research will provide key data to further our understanding of the potential role of inflammation on neural circuits that underlie these symptoms, including WM integrity. This research also has the potential to inform future anti-inflammatory therapies for patients with schizophrenia.

Associating white matter microstructural integrity and improvements in reactive stepping in people with Parkinson's Disease.

Reactive steps are rapid responses after balance challenges. People with Parkinson's Disease (PwPD) demonstrate impaired reactive stepping, increasing fall-risk. Although PwPD can improve steps through practice, the neural mechanisms contributing to improved reactive stepping are poorly understood. This study investigated white-matter correlates of responsiveness to reactive step training in PwPD. In an eighteen-week multiple-baseline study, participants (n = 22) underwent baseline assessments (B1 and B2 two-weeks apart), a two-week training protocol, and post-training assessments immediately (P1) and two-months (P2) post-training. Assessments involved three backward reactive step trials, measuring anterior-posterior margin of stability (AP MOS), step length, and step latency. Tract-Based Spatial Statistics correlated white-matter integrity (fractional anisotropy (FA) and radial diffusivity (RD)) with retained (P2-B2) and immediate improvements (P1-B2) in stepping. Significant and sustained improvements in step length and AP MOS were observed. Greater retention of step length improvement correlated with increased FA in the left anterior thalamic radiation (ATR), left posterior thalamic radiation (PTR), left superior longitudinal fasciculus (SLF), and right inferior longitudinal fasciculus (ILF). Step latency retention was associated with lower RD in the left posterior corona radiata and left PTR. Immediate improvements in AP MOS correlated with increased FA of the right ILF, right SLF, and right corticospinal tract. Immediate step length improvements were associated with increased FA in right and left ATR and right SLF. These findings highlight the importance of white-matter microstructural integrity in motor learning and retention processes in PD and could aid in identifying individuals with PD who would benefit most from balance rehabilitation.

Predictive Utility of Diffusion MRI After Mild Traumatic Brain Injury in Civilian Populations: A Systematic Review.

A considerable number of people experience persisting symptoms and functional limitations after mild traumatic brain injury (mTBI). It is unclear whether subtle white matter changes contribute to this phenomenon. In this systematic review, the authors evaluated whether microstructural white matter indices on advanced MRI are related to clinical dysfunction among patients without abnormalities on standard brain computed tomography (CT) or MRI (uncomplicated mTBI). A search of multiple databases was performed. Studies with individuals who experienced blast-related, sports-related, or multiple mTBIs were excluded. Diffusion tensor imaging (DTI) and susceptibility-weighted imaging (SWI) metrics and cognitive, neuropsychiatric, or functional outcome measures were extracted from each study. Thirteen studies were selected (participants with mTBI, N=553; healthy control group, N=438). Seven DTI studies evaluated cognitive function, with five reporting significant correlations between reduced white matter integrity and deficits in attention, processing speed, and executive function at 6-12 months after injury (three studies included only individuals with uncomplicated mTBI). Four studies found significant correlations between DTI metrics and persistent postconcussive symptoms after 3-12 months (one study included only individuals with uncomplicated mTBI). Two SWI studies reported conflicting findings regarding the relationship between the presence of microbleeds and postconcussive symptoms. The results revealed that indices of microstructural white matter integrity may relate to clinical presentation 3-12 months after injury in uncomplicated mTBI. However, analysis methods and brain regions studied varied across studies. Further research is needed to identify relationships between white matter indices in specific brain regions and symptom persistence beyond 12 months.

Association of Blood Pressure With Brain White Matter Microstructural Integrity Assessed With MRI Diffusion Tensor Imaging in Healthy Young Adults.

High blood pressure (BP) in middle-aged and older adults is associated with a brain white matter (WM) microstructural abnormality. However, little evidence is available in healthy young adults. We investigated the associations between high BP and WM microstructural integrity in young adults. This study included 1015 healthy young adults (542 women, 22-37 years) from the Human Connectome Project. Brachial systolic and diastolic BP were measured using a semiautomatic or manual sphygmomanometer. Diffusion-weighted magnetic resonance imaging was acquired to obtain diffusion tensor imaging metrics of free water (FW) content, FW-corrected WM fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Using whole-brain voxel-wise linear regression models and ANCOVA, we examined associations of BP and hypertension stage with diffusion tensor imaging metrics after adjusting for age, sex, education, body mass index, smoking status, alcohol consumption history, and differences in the b value used for diffusion magnetic resonance imaging. Systolic and diastolic BP of the sample (mean±SD) were 122.8±13.0 and 76.0±9.9 mm Hg, respectively. Associations of BP with diffusion tensor imaging metrics revealed regional heterogeneity for FW-corrected fractional anisotropy. High BP and high hypertension stage were associated with higher FW and lower FW-corrected axial diffusivity, FW-corrected radial diffusivity, and FW-corrected mean diffusivity. Moreover, associations of high diastolic BP and hypertension stage with high FW were found only in men not in women. High BP in young adults is associated with altered brain WM microstructural integrity, suggesting that high BP may have damaging effects on brain WM microstructural integrity in early adulthood, particularly in men.

Sex-Specific Distributed White Matter Microarchitectural Alterations in Preadolescent Youths With Anxiety Disorders: A Mega-Analytic Study.

Anxiety disorders are among the most common psychiatric disorders in youths and emerge during childhood. This is also a period of rapid white matter (WM) development, which is critical for efficient neuronal communication. Previous work in preadolescent children with anxiety disorders demonstrated anxiety disorder-related reductions in WM microstructural integrity (fractional anisotropy [FA]) in the uncinate fasciculus (UF), the major WM tract facilitating prefrontal cortical-limbic structural connectivity. Importantly, this association was found only in boys with anxiety disorders. To confirm this finding and more comprehensively understand WM changes in childhood anxiety, this mega-analytic study characterizes WM alterations related to anxiety disorders and sex in the largest sample of preadolescent children to date. Diffusion tensor imaging data from published studies of preadolescent children with anxiety disorders and healthy volunteers (ages 8-12) (N=198) were combined with a new data set (N=97) for a total sample of 165 children with anxiety disorders and 132 healthy volunteers. Children with anxiety disorders met DSM-5 criteria for current generalized, separation, and/or social anxiety disorder. Analyses of tractography and voxel-wise data assessed between-group differences (anxiety disorder vs. healthy volunteer), effects of sex, and their interaction. Tract-based and voxel-wise analyses confirmed a significant reduction in UF FA in boys but not girls with anxiety disorders. Results also demonstrated other significant widespread anxiety disorder-related WM alterations specifically in boys, including in multiple commissural, association, projection, and brainstem regions. In addition to confirming male-specific anxiety disorder-related reductions in UF FA, the results demonstrate that anxiety disorders in boys and not girls are associated with broadly distributed WM alterations across the brain. These findings support further studies focused on understanding the extent to which WM alterations in boys with anxiety disorders are involved in pathophysiological processes that mediate anxiety disorders. The findings also suggest the possibility that WM microarchitecture could serve as a novel treatment target for childhood anxiety disorders.

Reduced white matter maturation in the central auditory system of children living with HIV.

School-aged children experience crucial developmental changes in white matter (WM) in adolescence. The human immunodeficiency virus (HIV) affects neurodevelopment. Children living with perinatally acquired HIV (CPHIVs) demonstrate hearing and neurocognitive impairments when compared to their uninfected peers (CHUUs), but investigations into the central auditory system (CAS) WM integrity are lacking. The integration of the CAS and other brain areas is facilitated by WM fibers whose integrity may be affected in the presence of HIV, contributing to neurocognitive impairments. We used diffusion tensor imaging (DTI) tractography to map the microstructural integrity of WM between CAS regions, including the lateral lemniscus and acoustic radiation, as well as between CAS regions and non-auditory regions of 11-year-old CPHIVs. We further employed a DTI-based graph theoretical framework to investigate the nodal strength and efficiency of the CAS and other brain regions in the structural brain network of the same population. Finally, we investigated associations between WM microstructural integrity outcomes and neurocognitive outcomes related to auditory and language processing. We hypothesized that compared to the CHUU group, the CPHIV group would have lower microstructural in the CAS and related regions. Our analyses showed higher mean diffusivity (MD), a marker of axonal maturation, in the lateral lemniscus and acoustic radiations, as well as WM between the CAS and non-auditory regions predominantly in frontotemporal areas. Most affected WM connections also showed higher axial and radial diffusivity (AD and RD, respectively). There were no differences in the nodal properties of the CAS regions between groups. The MD of frontotemporal and subcortical WM-connected CAS regions, including the inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and internal capsule showed negative associations with sequential processing in the CPHIV group but not in the CHUU group. The current results point to reduced axonal maturation in WM, marked by higher MD, AD, and RD, within and from the CAS. Furthermore, alterations in WM integrity were associated with sequential processing, a neurocognitive marker of auditory working memory. Our results provide insights into the microstructural integrity of the CAS and related WM in the presence of HIV and link these alterations to auditory working memory.

Disentangling the neurobiological bases of temporal impulsivity in Huntington's disease.

Despite its impact on daily life, impulsivity in Huntington's disease (HD) is understudied as a neuropsychiatric symptom. Our aim is to characterize temporal impulsivity in HD and to disentangle the white matter correlate associated with impulsivity. Forty-seven HD individuals and 36 healthy controls were scanned and evaluated for temporal impulsivity using a delay-discounting (DD) task and complementary Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Diffusion tensor imaging was employed to characterize the structural connectivity of three limbic tracts: the uncinate fasciculus (UF), the accumbofrontal tract (NAcc-OFC), and the dorsolateral prefrontal cortex connectig the caudate nucleus (DLPFC-cn). Multiple linear regression analyses were applied to analyze the relationship between impulsive behavior and white matter microstructural integrity. Our results revealed altered structural connectivity in the DLPC-cn, the NAcc-OFC and the UF in HD individuals. At the same time, the variability in structural connectivity of these tracts was associated with the individual differences in temporal impulsivity. Specifically, increased structural connectivity in the right NAcc-OFC and reduced connectivity in the left UF were associated with higher temporal impulsivity scores. The present findings highlight the importance of investigating the spectrum of temporal impulsivity in HD. As, while less prevalent than other psychiatric features, this symptom is still reported to significantly impact the quality of life of patients and caregivers. This study provides evidence that individual differences observed in temporal impulsivity may be explained by variability in limbic frontostriatal tracts, while shedding light on the role of sensitivity to reward in modulating impulsive behavior through the selection of immediate rewards.

Knowledge atlas of white matter microstructure: a bibliometric analysis.

White matter microstructure is valued for being an indicator of neural network integrity, which plays an indispensable role in the execution of advanced brain functions. Although the number of publications has increased in the past 10 years, no comprehensive analysis has yet been conducted of this field. Therefore, this study aimed to identify the research hotspots and trends in research on white matter microstructure using a bibliometric analysis of the related literature published from 2013 to 2022. VOSviewer and CiteSpace were used to objectively analyze the research articles concerning white matter microstructure, which were retrieved from the Web of Science Core Collection (WoSCC). A total of 5,806 publications were obtained, with the number of published articles increasing annually over the past decade. The United States, China, the United Kingdom, and Canada maintained the top positions worldwide and had strong cooperative relationships. The top institution and journal were Harvard Medical School and Neuroimage, respectively. Alexander Leemans, Marek Kubicki, and Martha E Shenton were the most productive authors. Thematic keywords mainly included "diffusion tensor imaging" (DTI), "white matter integrity", and "connectivity". The keyword analysis revealed that DTI has a critical role in detecting white matter microstructure integrity and that fractional anisotropy is the main parameter in the assessment process. Keyword burst detection identified four research hotspots: movement, distortion correction, voxelwise analysis, and fixel-based analysis. This bibliometric analysis provided a systematic understanding of the research on white matter microstructure and identified the current frontiers. This may help clinicians and researchers comprehensively identify hotspots and trends in this field.

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study.

Scarce evidence is available to elucidate the association between the abnormal microstructure of white matter (WM) and cognitive performance in patients with orthostatic hypotension (OH). This study investigated the microstructural integrity of WM in patients with mild OH (MOH) and severe OH (SOH) and evaluated the association of abnormal WM microstructure with the broad cognitive domains and cognition-related plasma biomarkers. Our study included 72 non-OH (NOH), 17 MOH, and 11 SOH participants. Across the groups, the WM integrity was analyzed by neurite orientation dispersion and density imaging (NODDI), and differences in WM microstructure were evaluated by nonparametric tests and post hoc models. The correlations between WM microstructure and broad cognitive domains and cognition-related plasma biomarkers were assessed by Spearman's correlation analysis. The abnormal WM microstructure was localized to the WM fiber bundles in MOH patients but distributed widely in SOH cohorts (p < 0.05). Further analysis showed that the neurite density index of the left cingulate gyrus was negatively associated with amyloid β-40, glial fibrillary acidic protein, neurofilament light chain, phospho-tau181 (p < 0.05) but positively with global cognitive function (MOCA, MMSE, AER-III), memory, attention, language, language fluency, visuospatial function and amyloid β-40 / amyloid β-42 (p < 0.05). Additionally, other abnormal WM microstructures of OH were associated with broad cognitive domains and cognition-related plasma biomarkers to varying degrees. The findings evidence that abnormal WM microstructures may present themselves as early as in the MOH phase and that these structural abnormalities are associated with cognitive functions and cognition-related plasma biomarkers.

Sex Differences in the Association of Age at Hypertension Diagnosis With Brain Structure.

Sex differences exist in the likelihood of cognitive decline. The age at hypertension diagnosis is a unique contributor to brain structural changes associated with cerebral small vessel disease. However, whether this relationship differs between sexes remains unclear. Therefore, our objective was to evaluate sex differences in the association between the age at hypertension diagnosis and cerebral small vessel disease-related brain structural changes. We used data from the UK Biobank to select participants with a known age at hypertension diagnosis and brain magnetic resonance imaging (n=9430) and stratified them by sex and age at hypertension diagnosis. Control participants with magnetic resonance imaging scans but no hypertension were chosen at random matched by using propensity score matching. For morphological brain structural changes, generalized linear models were used while adjusting for other vascular risk factors. For the assessment of white matter microstructure, principal component analysis led to a reduction in the number of fractional anisotropy variables, followed by regression analysis with major principal components as outcomes. Males but not females with a younger age at hypertension diagnosis exhibited lower brain gray and white matter volume compared with normotensive controls. The volume of white matter hyperintensities was greater in both males and females with hypertension than normotensive controls, significantly higher in older females with hypertension. Compared with normotensive controls, white matter microstructural integrity was lower in individuals with hypertension, which became more prominent with increasing age. Our study demonstrates that the effect of hypertension on cerebral small vessel disease-related brain structure differs by sex and by age at hypertension diagnosis.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. Children ages 8-12years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. White matter microstructure is related to affective behavior in children with SOR.