Cerebral White Matter Microstructure Research Articles

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.

White matter microstructure alterations in type 2 diabetes mellitus and its correlation with cerebral small vessel disease and cognitive performance

Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

Current Auditory Hallucinations Are Not Associated With Specific White Matter Diffusion Alterations in Schizophrenia

Abstract Background and Hypothesis Studies have linked auditory hallucinations (AH) in schizophrenia spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI). Study Design We included patients with SCZ with (AH+; n = 59) and without (AH−; n = 81) current AH, and 140 age- and sex-matched controls. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from 39 fiber tracts. We used principal component analysis (PCA) to identify general factors of variation across fiber tracts and DTI metrics. Regression models adjusted for sex, age, and age2 were used to compare tract-wise DTI metrics and PCA factors between AH+, AH−, and healthy controls and to assess associations with clinical characteristics. Study Results Widespread differences relative to controls were observed for MD and RD in patients without current AH. Only limited differences in 2 fiber tracts were observed between AH+ and controls. Unimodal PCA factors based on MD, RD, and AD, as well as multimodal PCA factors, differed significantly relative to controls for AH−, but not AH+. We did not find any significant associations between PCA factors and clinical characteristics. Conclusions Contrary to previous studies, DTI metrics differed mainly in patients without current AH compared to controls, indicating a widespread neuroanatomical distribution. This challenges the notion that altered DTI metrics within the LAPC is a specific feature underlying AH.

Regional White Matter Hyperintensities are Associated with Diminished Blood Flow and Microstructure in Middle Age

AbstractBackgroundWhite matter hyperintensities (WMH) are areas of increased signal visualized on T2‐weighted FLAIR magnetic resonance imaging (MRI), thought to reflect macrostructural damage due to small vessel cerebrovascular disease. Previous work established an association of WMH severity, particularly in posterior regions, with risk and progression of AD in late onset and genetic forms of AD, suggesting a vascular component to disease pathogenesis and course. Examination of the emergence and correlates of cerebrovascular changes in middle age, a critical time when vascular risk appears to be most penetrant, can give insight into mechanisms linking vascular brain injury and risk for AD. In the current study, we examined the association of cerebral blood flow (CBF) and white matter microstructure with total and regional WMH volume in middle‐aged, community dwelling adults.MethodFour hundred and ninety‐two middle‐aged participants (55+/‐11 age = 28 ‐85 years) from the community‐based Offspring Study of Mechanisms for Racial Disparities in Alzheimer’s Disease received multi‐modal MRI scanning. Regional WMH volumes were derived with in‐house software that labeled clusters of voxels within a hyperintense intensity distribution. Pulsed arterial spin labeling (PASL) sequences were processed to quantify CBF. Fractional anisotropy (FA) maps were obtained from diffusion weighted data. Total and regional WMH volumes were used as predictors for whole brain voxel‐wise correlation analyses in separate models for CBF and FA.ResultThere were negative associations between WMH volume and CBF in frontal, parietal, and occipital regions. Higher white matter hyperintensity volume was associated with lower FA, particularly in the periventricular region.ConclusionWe found associations of increased WMH volume with diminished blood flow and white matter microstructure. Future studies are needed to explain the relationship between these changes and the risk of cognitive impairment in middle aged adults and risk for AD.

Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive Symptoms.

White matter of the human brain is influenced by common genetic variations and shaped by neural activity-dependent experiences. Variations in microstructure of cerebral white matter across individuals and even across fiber tracts might underlie differences in cognitive capacity and vulnerabilities to mental disorders. The frontoparietal and cingulo-opercular networks of the brain constitute the central system supporting cognitive functions, and functional connectivity of these networks has been used to distinguish individuals known as "functional fingerprinting." The frontal aslant tract (FAT) that passes through the two networks has been implicated in executive functions. However, whether FAT can be used as a "structural fingerprint" to distinguish individuals and predict an individual's cognitive function and dysfunction is unknown. Here we investigated the fingerprinting property of FAT microstructural profiles using three independent diffusion MRI datasets with repeated scans on human participants including both females and males. We found that diffusion and geometric profiles of FAT can be used to distinguish individuals with a high accuracy. Next, we demonstrated that fractional anisotropy in different FAT segments predicted distinct cognitive functions, including working memory, inhibitory control, and relational reasoning. Finally, we assessed the contribution of altered FAT microstructural profiles to cognitive dysfunction in unmedicated patients with obsessive-compulsive disorders. We found that the altered microstructure in FAT was associated with the severity of obsessive-compulsive symptoms. Collectively, our findings suggest that the microstructural profiles of FAT can identify individuals with a high accuracy and may serve as an imaging marker for predicting an individual's cognitive capacity and disease severity.SIGNIFICANCE STATEMENT The frontoparietal network and cingulo-opercular network of the brain constitute a dual-network architecture for human cognitive functions, and functional connectivity of these two networks can be used as a "functional fingerprint" to distinguish individuals. However, the structural underpinnings of these networks subserving individual heterogeneities in their functional connectivity and cognitive ability remain unknown. We show here that the frontal aslant tract (FAT) that passes through the two networks distinguishes individuals with a high accuracy. Further, we demonstrate that the diffusion profiles of FAT predict distinct cognitive functions in healthy subjects and are associated with the clinical symptoms in patients with obsessive-compulsive disorders. Our findings suggest that the FAT may serve as a unique structural fingerprint underlying individual cognitive capability.

Mechanisms of Cognitive Improvement After Carotid Endarterectomy: Results of an Autopsy

To develop a clinically meaningful definition of cognitive change before and after carotid endarterectomy (CEA), we categorized patients with “improved postoperative function” and “non-improved postoperative function” based on subjective assessment and neuropsychological tests. The results showed that 11% of the patients showed an improvement in postoperative function. Through single-photon emission computerized tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), etc., it was found that improvement of cerebral blood flow by carcinoembryonic antigen (CEA) → improvement of cerebral metabolism → improvement of cerebral cortical neuroreceptor function and cerebral white matter microstructure → improvement of cognitive function. The degree of preoperative cerebral hemispheric white matter lesions was the rate-limiting factor for improvement in cognitive function.

Investigation of the association between central arterial stiffness and aggregate g-ratio in cognitively unimpaired adults.

Stiffness of the large arteries has been shown to impact cerebral white matter (WM) microstructure in both younger and older adults. However, no study has yet demonstrated an association between arterial stiffness and aggregate g-ratio, a specific magnetic resonance imaging (MRI) measure of axonal myelination that is highly correlated with neuronal signal conduction speed. In a cohort of 38 well-documented cognitively unimpaired adults spanning a wide age range, we investigated the association between central arterial stiffness, measured using pulse wave velocity (PWV), and aggregate g-ratio, measured using our recent advanced quantitative MRI methodology, in several cerebral WM structures. After adjusting for age, sex, smoking status, and systolic blood pressure, our results indicate that higher PWV values, that is, elevated arterial stiffness, were associated with lower aggregate g-ratio values, that is, lower microstructural integrity of WM. Compared to other brain regions, these associations were stronger and highly significant in the splenium of the corpus callosum and the internal capsules, which have been consistently documented as very sensitive to elevated arterial stiffness. Moreover, our detailed analysis indicates that these associations were mainly driven by differences in myelination, measured using myelin volume fraction, rather than axonal density, measured using axonal volume fraction. Our findings suggest that arterial stiffness is associated with myelin degeneration, and encourages further longitudinal studies in larger study cohorts. Controlling arterial stiffness may represent a therapeutic target in maintaining the health of WM tissue in cerebral normative aging.

Disparate Radiation-Induced Microstructural Injuries in Whole-Brain White Matter of Patients With Nasopharyngeal Carcinoma: A Longitudinal Study Using Multishell Diffusion MRI.

Evidence for prevention strategies of radiotherapy (RT)-related injury in patients with nasopharyngeal carcinoma (NPC) was lacking. Understanding the dynamic alterations in the cerebral white matter (WM) microstructure after RT may be helpful. To investigate the dynamic alterations in the whole brain WM microstructure in patients with NPC in the 12months after RT using multishell diffusion MRI (MS-dMRI). Single-center longitudinal study. A total of 28 treatment-naïve patients with pathologically confirmed NPC (age: 39.68 ± 8.93 years, 11 female) and 20 healthy controls (age: 40.65 ± 9.76 years, 7 female). A 3 T, MS-dMRI using a single-shot echo planar imaging sequence. MS-dMRI was acquired at baseline for the NPC patients and healthy controls, at 0-3 (acute, AC), 6 (early delayed, ED) and 12months (late delayed, LD) after RT for the NPC patients. The mean and maximum radiation doses to the temporal lobe were acquired. The quality of images was reviewed. MS-dMRI was analyzed using tract-based spatial statistics (TBSS). The presentations of injury were defined by the findings of TBSS. Chi-square, t tests, repeated ANOVA, and Spearman-rank correlation analysis were used. P < 0.05 was considered to be statistically significant. TBSS showed two WM injuries (injuries 1 and 2). Injury 1 emerged in the ED phase in the bilateral temporal poles and persisted throughout the ED and LD phases. Injury 2 developed from the AC to ED phase in the bilateral hemisphere and partially recovered in the LD phase. In the ED and LD phases, the multiple diffusion metrics were well correlated (r > 0.5 or <-0.5) with the RT dose, especially in the WM tracts in the temporal lobes. Disparate WM injuries were observed in NPC patients after RT. The injuries may be primarily or secondarily induced by radiation. Injury 1 may be irreversible, while injury 2 seems to partially recover. 2. Stage 4.

White matter microstructure and executive functions in congenital heart disease from childhood to adulthood: A pooled case–control study

ABSTRACT Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population.

Cerebral Microbleeds and Structural White Matter Integrity in Patients With Traumatic Brain Injury-A Diffusion Tensor Imaging Study.

Diffuse axonal injury (DAI) is a common neuropathological manifestation of traumatic brain injury (TBI), presenting as traumatic alterations in the cerebral white matter (WM) microstructure and often leading to long-term neurocognitive impairment. These WM alterations can be assessed using diffusion tensor imaging (DTI). Cerebral microbleeds (CMBs) are a common finding on head imaging in TBI and are often considered a visible sign of DAI, although they represent diffuse vascular injury. It is poorly known how they associate with long-term white matter integrity. This study included 20 patients with TBI and CMBs, 34 patients with TBI without CMBs, and 11 controls with orthopedic injuries. DTI was used to assess microstructural WM alterations. CMBs were detected using susceptibility-weighted imaging (SWI) and graded according to their location in the WM and total lesion load was counted. Patients underwent SWI within 2 months after injury. DTI and clinical outcome assessment were performed at an average of eight months after injury. Outcome was assessed using the extended Glasgow Outcome Scale (GOSe). The Glasgow Coma Scale (GCS) and length of post-traumatic amnesia (PTA) were used to assess clinical severity of the injury. We found that CMB grading and total lesion load were negatively associated with fractional anisotropy (FA) and positively associated with mean diffusivity (MD). Patients with TBI and CMBs had decreased FA and increased MD compared with patients with TBI without CMBs. CMBs were also associated with worse clinical outcome. When adjusting for the clinical severity of the injury, none of the mentioned associations were found. Thus, the difference in FA and MD is explained by patients with TBI and CMBs having more severe injuries. Our results suggest that CMBs are not associated with greater WM alterations when adjusting for the clinical severity of TBI. Thus, CMBs and WM alterations may not be strongly associated pathologies in TBI.

Role of White Matter Microstructure in Impulsive Behavior.

Increased impulsivity is a hallmark trait of some neuropsychiatric illnesses, including addiction, traumatic brain injury, and externalizing disorders. The authors hypothesized that altered cerebral white matter microstructure may also underwrite normal individual variability in impulsive behaviors and tested this among healthy individuals. Impulsivity and diffusion tensor imaging (DTI) data were collected from 74 healthy adults (32 women; mean age=36.6 years [SD=13.6]). Impulsivity was evaluated using the Barratt Impulsiveness Scale-11, which provides a total score and scores for three subdomains: attentional, motor, and nonplanning impulsiveness. DTI was processed using the Enhancing Neuro Imaging Genetics Through Meta Analysis-DTI analysis pipeline to measure whole-brain and regional white matter fractional anisotropy (FA) values in 24 tracts. Whole-brain total average FA was inversely correlated with motor impulsiveness (r=-0.32, p=0.007) and positively correlated with nonplanning impulsiveness (r=0.29, p=0.02); these correlations were significant after correction for multiple comparisons. Additional significant correlations were observed for motor impulsiveness and regional FA values for the corticospinal tract (r=-0.29, p=0.01) and for nonplanning impulsiveness and regional FA values for the superior fronto-occipital fasciculus (r=0.32, p=0.008). These results provide initial evidence that the motor and nonplanning subdomains of impulsive behavior are linked to specific white matter microstructural connectivity, supporting the notion that impulsivity is in part a network-based construct involving white matter microstructural integrity among otherwise healthy populations.

Potential Pitfalls of Using Fractional Anisotropy, Axial Diffusivity, and Radial Diffusivity as Biomarkers of Cerebral White Matter Microstructure.

Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) are commonly used as MRI biomarkers of white matter microstructure in diffusion MRI studies of neurodevelopment, brain aging, and neurologic injury/disease. Some of the more frequent practices include performing voxel-wise or region-based analyses of these measures to cross-sectionally compare individuals or groups, longitudinally assess individuals or groups, and/or correlate with demographic, behavioral or clinical variables. However, it is now widely recognized that the majority of cerebral white matter voxels contain multiple fiber populations with different trajectories, which renders these metrics highly sensitive to the relative volume fractions of the various fiber populations, the microstructural integrity of each constituent fiber population, and the interaction between these factors. Many diffusion imaging experts are aware of these limitations and now generally avoid using FA, AD or RD (at least in isolation) to draw strong reverse inferences about white matter microstructure, but based on the continued application and interpretation of these metrics in the broader biomedical/neuroscience literature, it appears that this has perhaps not yet become common knowledge among diffusion imaging end-users. Therefore, this paper will briefly discuss the complex biophysical underpinnings of these measures in the context of crossing fibers, provide some intuitive “thought experiments” to highlight how conventional interpretations can lead to incorrect conclusions, and suggest that future studies refrain from using (over-interpreting) FA, AD, and RD values as standalone biomarkers of cerebral white matter microstructure.

Cerebral white matter microstructure in superagers: A diffusion MRI study of a population over the age of 80 with youthful episodic memory

AbstractBackgroundSuperagers are people over the age of 80 who possess the episodic memory function of a person 20‐30 years younger. We have recently identified the grey matter signature of this population, with preserved volume in episodic memory‐related areas and motor thalamus. Here we extend these observations by characterising superagers’ cerebral white matter microstructure using diffusion MR imaging.MethodA sample of 64 superagers (mean age 81.9 years ± 1.9 std, 59.4% women) and 55 age‐matched controls (mean age 82.4 years ± 1.9 std, 63.6% women) from the Vallecas Project cohort in Madrid, Spain, were selected according to their episodic memory score in the Free and Cued Selective Reminding Test. Superagers scored at or above the mean value of a 50‐56yo person, whereas controls scored within one standard deviation for their age. Differences across groups in two measures derived from DTI data were tested, comprising fractional anisotropy (FA), and mean diffusivity (MD). Voxelwise analyses were carried out using TBSS (Tract‐Based Spatial Statistics, [Smith 2006]), in FSL software.ResultSuperagers showed higher FA than controls in bilateral frontal tracts and the anterior thalamic radiation (p &lt; 0.05, FWE‐corrected). Lower MD were found in superagers compared to controls in an extensive network comprising the forceps major and minor, superior and inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, anterior thalamic radiation, corticospinal tracts and cingulum bundle (p &lt; 0.05, FWE‐corrected).ConclusionHigher FA and lower MD can be indicative of preserved white matter microstructure. Superagers exhibit higher FA in frontal tracts and lower MD across the main cerebral white matter tracts relative to healthy controls with normal‐memory‐for‐age. These results suggest an association between preservation of white matter microstructure and extraordinary memory function in old age.

Cardiometabolic disorders are associated with reduced cerebral perfusion and white matter microstructure

AbstractBackgroundCardiometabolic disorders (hypertension and diabetes) often co‐occur and are considered key modifiable risk factors for Alzheimer’s disease and related disorders; yet, the extent to which they each affect brain structure and function is unclear. We examined their associations with neuroimaging biomarkers of white matter microstructure, cerebral perfusion, and cognitive function in a diverse cohort of older adults.MethodParticipants aged 50‐85 years enrolled in Wake Forest Alzheimer’s Disease Research Center’s Clinical Core between 2016‐2020 received clinical evaluation, oral glucose tolerance testing (OGTT), neuroimaging, cognitive testing, and adjudication for mild cognitive impairment (MCI) and dementia. 3T brain MRI included T1 (for gray/white matter segmentation, regional volumes/thicknesses); FLAIR for white matter hyperintensity volume (WMHv); arterial spin labeling for cerebral blood flow (CBF); diffusion tensor imaging (DTI) for fractional anisotropy (FA); and neurite orientation dispersion and density imaging (NODDI) for Free Water. Hypertension (HTN) was staged using seated blood pressure (BP) and medications. Hyperglycemia was staged using OGTT 120 minute glucose levels (OGTT120), hemoglobin A1c, and fasting glucose as available. Cardiometabolic status was categorized (HTN only, hyperglycemia only, hyperglycemia+HTN, neither). Multivariable linear regression modeled associations with neuroimaging measures adjusted for age, gender, and race.ResultMRI was available on 478 participants (35% MCI and 10% dementia) with mean age of 70±8 years, 74% with HTN, 61% with hyperglycemia (4% with non‐insulin treated diabetes), and 15% African‐Americans. The combination of hyperglycemia+HTN was associated with significantly higher NODDI Free Water and WMHv, lower FA, and lower gray matter perfusion, compared to neither factor (Table). Continuous levels of systolic BP and OGTT120 broadly correlated with WM microstructure, WMHv, and gray matter CBF (Figure). In adjusted models, systolic BP remained significantly associated with higher NODDI Free Water and WMHv, and CBF in gray and white matter. OGTT120 and WMHv remained significant in adjusted models. Cardiometabolic factors were not associated with gray matter macrostructure (e.g. volumes, temporal lobe cortical thickness) or cognitive status in this sample.ConclusionIn this deeply phenotyped and racially diverse sample, individual cardiometabolic factors and the co‐occurrence of disorders was associated with reduced cerebral gray matter perfusion and reduced white matter microstructure.

Abnormalities of Cerebral White Matter Microstructure in Children With New-Onset, Untreated Idiopathic-Generalized Epilepsy.

Despite evidence for microstructural brain alterations in epilepsy patients, little is known about how these develop with age and the progress of the disease. The aim of this study was to investigate microstructural abnormalities of the white matter (WM) in children with new-onset, untreated idiopathic-generalized epilepsy (IGE) using the MRI technique of diffusion tensor imaging (DTI). The study was approved by the institutional review board, and all individuals or their parents gave signed informed consent. In total, 45 patients with IGE (age 5–18 years, male: female 26:19) and 32 healthy controls (HCs; age 5–18 years, male: female 21:11) were included. Voxel-based analysis (VBA) was used to compare patients and controls, and Pearson correlation analysis was used to investigate relationships between altered DTI metrics and clinical parameters. Compared with controls, patients with IGE showed increased mean diffusivity (MD) in the left splenium of the corpus callosum, increased fractional anisotropy (FA) in the right WM of the superior and middle frontal gyri, increased axial diffusivity (AD) in the WM of right corona radiata and left occipital lobe, and decreased AD in the WM of the left thalamus and the right middle cerebellar peduncle. There was no correlation between the altered diffusion parameters and clinical measures. Our study demonstrated several distinct microstructural impairments in children with new-onset, untreated IGE, of which altered AD might be the most sensitive marker of dysmyelination. The increased FA in the IGE group might suggest an initiating or compensatory mechanism that is activated prior to cognitive decline in these children.

Acute and Chronic Effects of Multiple Concussions on Midline Brain Structures.

To test the hypothesis that a history of concussion (HOC) causes greater disturbances in cerebral blood flow (CBF) and white matter microstructure of midline brain structures after subsequent concussions, during the acute and chronic phases of recovery. In this longitudinal MRI study, 61 athletes with uncomplicated concussion (36 with HOC) were imaged at the acute phase of injury (1-7 days after injury), the subacute phase (8-14 days), medical clearance to return to play (RTP), 1 month after RTP, and 1 year after RTP. A normative group of 167 controls (73 with HOC) were also imaged. Each session assessed CBF of the cingulate cortex, along with fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum. Linear mixed models tested for interactions of HOC with time since injury. The Sport Concussion Assessment Tool (SCAT) was also used to evaluate effects of HOC on symptoms, cognition, and balance. Athletes with HOC had significantly greater declines in midcingulate CBF subacutely (z = -3.29, p = 0.002) and greater declines in posterior cingulate CBF at 1 year after RTP (z = -2.42, p = 0.007). No significant effects of HOC were seen for FA, whereas athletes with HOC had higher MD of the splenium at RTP (z = 2.54, p = 0.008). These effects were seen in the absence of significant differences in SCAT domains (|z| ≤ 1.14, p ≥ 0.256) or time to RTP (z = 0.23, p = 0.818). Results indicate subacute and chronic effects of HOC on cingulate CBF and callosal microstructure in the absence of differences in clinical indices. These findings provide new insights into physiologic brain recovery after concussion, with cumulative effects of repeated injury detected among young, healthy athletes.

Brain Health in Children with Type 1 Diabetes: Risk and Protective Factors.

To synthesize findings from studies of neurocognitive complications in children with type 1 diabetes (T1D) and highlight potential risk and protective factors. Emerging evidence suggests that hyperglycemia and time in range may be more important for brain development than episodes of hypoglycemia. Further, diabetic ketoacidosis (DKA) at the time of T1D diagnosis appears to be a particular risk factor for neurocognitive complications, particularly deficits in executive function skills and memory, with differences in cerebral white matter microstructure seen via advanced magnetic resonance imaging methods, and lower scores on measures of attention and memory observed among children who were diagnosed in DKA. Other factors that may influence neurocognitive development include child sleep, caregiver distress, and diabetes device use, presumably due to improved glycemic control. We highlight neurocognitive risk and protective factors for children with T1D and priorities for future research in this high-risk population.

Longitudinal changes in cerebral white matter microstructure in newly diagnosed systemic lupus erythematosus patients

ObjectivesTo evaluate longitudinal variations in diffusion tensor imaging (DTI) metrics of different white matter (WM) tracts of newly diagnosed SLE patients, and to assess whether DTI changes relate to changes in clinical characteristics over time.MethodsA total of 17 newly diagnosed SLE patients (19–55 years) were assessed within 24 months from diagnosis with brain MRI (1.5 T Philips Achieva) at baseline, and after at least 12 months. Fractional anisotropy, mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity values were calculated in several normal-appearing WM tracts. Longitudinal variations in DTI metrics were analysed by repeated measures analysis of variance. DTI changes were separately assessed for 21 WM tracts. Associations between longitudinal alterations of DTI metrics and clinical variables (SLEDAI-2K, complement levels, glucocorticoid dosage) were evaluated using adjusted Spearman correlation analysis.ResultsMean MD and RD values from the normal-appearing WM significantly increased over time (P = 0.019 and P = 0.021, respectively). A significant increase in RD (P = 0.005) and MD (P = 0.012) was found in the left posterior limb of the internal capsule; RD significantly increased in the left retro-lenticular part of the internal capsule (P = 0.013), and fractional anisotropy significantly decreased in the left corticospinal tract (P = 0.029). No significant correlation was found between the longitudinal change in DTI metrics and the change in clinical measures.ConclusionIncrease in diffusivity, reflecting a compromised WM tissue microstructure, starts in initial phases of the SLE disease course, even in the absence of overt neuropsychiatric (NP) symptoms. These results indicate the importance of monitoring NP involvement in SLE, even shortly after diagnosis.

Association of Poorer Hearing With Longitudinal Change in Cerebral White Matter Microstructure

There is a dearth of studies that examine the association between poorer hearing and change in cerebral white matter (WM) microstructure. To examine the association of poorer hearing with baseline and change in WM microstructure among older adults. This was a prospective cohort study that evaluated speech-in-noise, pure-tone audiometry, and WM microstructure, as measured by mean diffusivity (MD) and fractional anisotropy (FA), both of which were evaluated by diffusion tensor imaging (DTI) in 17 WM regions. Data were collected between October 2012 and December 2018 and analyzed between March 2019 and August 2019 with a mean follow-up time of 1.7 years. The study evaluated responses to the Baltimore Longitudinal Study of Aging among 356 cognitively normal adults who had at least 1 hearing assessment and DTI session. Excluded were those with baseline cognitive impairment, stroke, head injuries, Parkinson disease, and/or bipolar disorder. Peripheral auditory function was measured by pure-tone average in the better-hearing ear. Central auditory function was measured by signal-to-noise ratio score from a speech-in-noise task and adjusted by pure-tone average. Linear mixed-effects models with random intercepts and slopes were used to examine the association of poorer peripheral and central auditory function with baseline and longitudinal DTI metrics in 17 WM regions, adjusting for baseline characteristics (age, sex, race, hypertension, elevated total cholesterol, and obesity). Of 356 cognitively normal adults included in the study, the mean (SD) age was 73.5 (8.8) years, and 204 (57.3%) were women. There were no baseline associations between hearing and DTI measures. Longitudinally, poorer peripheral hearing was associated with increases in MD in the inferior fronto-occipital fasciculus (β = 0.025; 95% CI, 0.008-0.042) and the body (β = 0.050; 95% CI, 0.015-0.085) of the corpus callosum, but there were no associations of peripheral hearing with FA changes in these tracts. Poorer central auditory function was associated with longitudinal MD increases (β = 0.031; 95% CI, 0.010-0.052) and FA declines (β = -1.624; 95% CI, -2.511 to -0.738) in the uncinate fasciculus. Findings of this cohort study suggest that poorer hearing is related to change in integrity of specific WM regions involved with auditory processing.

The assessment of cerebral white matter microstructure in cerebral small vessel disease based on the diffusion-weighted magnetic resonance imaging

Introduction. Multidimensional or biophysical modelling approaches are actively used to examine the complex microstructure of brain matter in diffusion-weighted MRI, where tissue structures are schematically simplified and divided into separate regions to calculate the diffusion values. This approach demonstrates greater specificity when compared with the widely used diffusion tensor MRI (DT-MRI) and its metrics. The aim of the study was to compare DT-MRI and the biophysical diffusion models, and to evaluate their possible use in a more precise studying of the affected white matter in cerebral small vessel disease (CSVD). Materials and methods. We examined 96 patients (including 65 women; mean age 61.0±6.6 years) with CSVD and 23 healthy volunteers, comparable in age and gender (including 15 women; mean age 58±6 years). The patients were divided into 3 groups according to the severity of white matter disease as measured using the Fazekas scale. All study subjects underwent a brain MRI (3 T) with diffusion-weighted MRI (b = 0, 1000 and 2500 sec/mm 2 , 64 gradient directions) followed by the data processing; we obtained DT-MRI metric maps, as well as white matter tract integrity model and model using the spherical mean technique. Results. Significant differences were found between the study groups (except groups F0 and F1) in all metrics when the overall value of the white matter skeleton was examined ( p £ 0.05): there was a decrease in tissue anisotropy and axonal density in the white matter, as well as increased intra- and extra-axonal coefficients with more severe white matter disease. Analysis of individual white matter regions showed that the radial diffusion values had greater intergroup differences than the axial diffusion values in the corpus callosum (particularly, in the body and splenium). Conclusion. Biophysical models allow us to evaluate white matter disease in patients with CSVD using structural tissue features and indirect measures of intra- and extracellular diffusion. To clarify and increase the statistical significance of the obtained results, it is necessary to analyse the diffusion metrics using data from a larger patient sample.