Serum albumin and white matter hyperintensities.

People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)-a neuroimaging feature of cerebral small vessel disease-are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.

Human post-mortem organotypic brain slice cultures: a tool to study pathomechanisms and test therapies.

Human brain experimental models recapitulating age- and disease-related characteristics are lacking. There is urgent need for human-specific tools that model the complex molecular and cellular interplay between different cell types to assess underlying disease mechanisms and test therapies. Here we present an adapted ex vivo organotypic slice culture method using human post-mortem brain tissue cultured at an air-liquid interface to also study brain white matter. We assessed whether these human post-mortem brain slices recapitulate the in vivo neuropathology and if they are suitable for pathophysiological, experimental and pre-clinical treatment development purposes, specifically regarding leukodystrophies. Human post-mortem brain tissue and cerebrospinal fluid were obtained from control, psychiatric and leukodystrophy donors. Slices were cultured up to six weeks, in culture medium with or without human cerebrospinal fluid. Human post-mortem organotypic brain slice cultures remained viable for at least six weeks ex vivo and maintained tissue structure and diversity of (neural) cell types. Supplementation with cerebrospinal fluid could improve slice recovery. Patient-derived organotypic slice cultures recapitulated and maintained known in vivo neuropathology. The cultures also showed physiologic multicellular responses to lysolecithin-induced demyelination ex vivo, indicating their suitability to study intrinsic repair mechanisms upon injury. The slice cultures were applicable for various experimental studies, as multi-electrode neuronal recordings. Finally, the cultures showed successful cell-type dependent transduction with gene therapy vectors. These human post-mortem organotypic brain slice cultures represent an adapted ex vivo model suitable for multifaceted studies of brain disease mechanisms, boosting translation from human ex vivo to in vivo. This model also allows for assessing potential treatment options, including gene therapy applications. Human post-mortem brain slice cultures are thus a valuable tool in preclinical research to study the pathomechanisms of a wide variety of brain diseases in living human tissue.

[Correlation study between brain damage and anxiety, depression, and cognitive impairment in patients with moderate to severe obstructive sleep apnea hypopnea syndrome using diffusional kurtosis imaging].

Objective: To explore the brain white matter damage in patients with moderate to severe obstructive sleep apnea hypopnea syndrome(OSAHS) using diffusional kurtosis imaging(DKI), and to analyze its relationship with anxiety, depression and cognitive impairment in patients. Methods: This was a retrospective case-control study. Fifty confirmed cases (47 males and 3 females) of moderate to severe OSAHS diagnosed by polysomnography(PSG) from November 2017 to December 2022 were selected as OSAHS group(age range from 22 to 65 years old, with median age of 40 years old), and 32 healthy controls(27 males and 5 females) of non-OSAHS diagnosed by PSG were selected as control group(age range from 19 to 56 years old, with median age of 34 years old). DKI scanning, Beck Anxiety Inventory(BAI), Beck Depression Inventory-Ⅱ(BDI-Ⅱ), and Montreal cognitive assessment(MoCA) scores were performed in all subjects. Differences in kurtosis fractional anisotropy(KFA) of various brain regions were compared between the two groups to identify differential brain regions. Correlations were analyzed between KFA reduction and anxiety, depression, and cognitive impairment in OSAHS patients. To study the correlation between brain injury and anxiety, depressive mood, and cognitive dysfunction, statistical methods such as non-parametric tests for two independent samples, chi-square tests, and partial correlation analysis, were used to analyze the evaluation indicators of the two groups. Results: The KFA values in right external capsule, left anterior corona radiata, right anterior corona radiata, left posterior corona radiata, right posterior corona radiata, left superior corona radiata, right superior corona radiata, left superior longitudinal fasciculus, right superior longitudinal fasciculus, genu of corpus callosum, splenium of corpus callosum, body of corpus callosum, posterior cingulate gyrus of moderate to severe OSAHS group were all lower than those in the control group(t=-2.247, -3.028, -3.955, -4.871, -2.632, -2.594, -2.121, -2.167, -3.129, -2.015, -2.317, -2.313, -2.152,P<0.05). For the moderate to severe OSAHS group, the correlation between AHI and KFA values of right posterior corona radiata, right superior corona radiata, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.378, -0.307, -0.337, -0.343, -0.341, -0.613, -0.390, -0.384, -0.396, P<0.05). The correlation between LSO2 and KFA values of right anterior corona radiata, right posterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left posterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum, posterior cingulate gyrus were all positive(r=0.330, 0.338, 0.425, 0.312, 0.433, 0.358, 0.410, 0.459, 0.473, 0.659, 0.489, 0.356, P<0.05). The correlation between BAI scores and KFA values of right external capsule, right anterior corona radiata, left posterior corona radiata, left superior corona radiata, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.306, -0.372, -0.296, -0.346, -0.318, -0.386, P<0.05). The correlation between BDI-Ⅱ scores and KFA values of right superior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all negative(r=-0.334, -0.289, -0.309, -0.310, -0.503, -0.469, P<0.05). The correlation between MoCA scores and KFA values of right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, left superior corona radiata, left superior longitudinal fasciculus, genu of corpus callosum, body of corpus callosum, splenium of corpus callosum were all positive(r=0.368, 0.431, 0.324, 0.410, 0.469, 0.384, 0.369, 0.309, P<0.05). Conclusions: With the aggravation of OSAHS, the damage to some brain regions becomes more pronounced in moderate to severe OSAHS patients. These damage brain functional areas are closely related to the anxiety, depression, and cognitive impairment of patients.

Characteristic BOLD signals are detectable in white matter of the spinal cord at rest and after a stimulus.

We report the reliable detection of reproducible patterns of blood-oxygenation-level-dependent (BOLD) MRI signals within the white matter (WM) of the spinal cord during a task and in a resting state. Previous functional MRI studies have shown that BOLD signals are robustly detectable not only in gray matter (GM) in the brain but also in cerebral WM as well as the GM within the spinal cord, but similar signals in WM of the spinal cord have been overlooked. In this study, we detected BOLD signals in the WM of the spinal cord in squirrel monkeys and studied their relationships with the locations and functions of ascending and descending WM tracts. Tactile sensory stimulus -evoked BOLD signal changes were detected in the ascending tracts of the spinal cord using a general-linear model. Power spectral analysis confirmed that the amplitude at the fundamental frequency of the response to a periodic stimulus was significantly higher in the ascending tracts than the descending ones. Independent component analysis of resting-state signals identified coherent fluctuations from eight WM hubs which correspond closely to the known anatomical locations of the major WM tracts. Resting-state analyses showed that the WM hubs exhibited correlated signal fluctuations across spinal cord segments in reproducible patterns that correspond well with the known neurobiological functions of WM tracts in the spinal cord. Overall, these findings provide evidence of a functional organization of intraspinal WM tracts and confirm that they produce hemodynamic responses similar to GM both at baseline and under stimulus conditions.

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. METHODS: Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. RESULTS: Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. DISCUSSION: Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

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

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: 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 (ß=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). CONCLUSIONS: 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.

Diffusion-tensor-imaging 1-year-old and 2-year-old infant brain atlases with comprehensive gray and white matter labels.

Human infancy is marked by fastest postnatal brain structural changes. It also coincides with the onset of many neurodevelopmental disorders. Atlas-based automated structure labeling has been widely used for analyzing various neuroimaging data. However, the relatively large and nonlinear neuroanatomical differences between infant and adult brains can lead to significant offsets of the labeled structures in infant brains when adult brain atlas is used. Age-specific 1- and 2-year-old brain atlases covering all major gray and white matter (GM and WM) structures with diffusion tensor imaging (DTI) and structural MRI are critical for precision medicine for infant population yet have not been established. In this study, high-quality DTI and structural MRI data were obtained from 50 healthy children to build up three-dimensional age-specific 1- and 2-year-old brain templates and atlases. Age-specific templates include a single-subject template as well as two population-averaged templates from linear and nonlinear transformation, respectively. Each age-specific atlas consists of 124 comprehensively labeled major GM and WM structures, including 52 cerebral cortical, 10 deep GM, 40 WM, and 22 brainstem and cerebellar structures. When combined with appropriate registration methods, the established atlases can be used for highly accurate automatic labeling of any given infant brain MRI. We demonstrated that one can automatically and effectively delineate deep WM microstructural development from 3 to 38 months by using these age-specific atlases. These established 1- and 2-year-old infant brain DTI atlases can advance our understanding of typical brain development and serve as clinical anatomical references for brain disorders during infancy.

Artificial intelligence for volumetric measurement of cerebral white matter hyperintensities on thick-slice fluid-attenuated inversion recovery (FLAIR) magnetic resonance images from multiple centers.

We aimed to develop a new artificial intelligence software that can automatically extract and measure the volume of white matter hyperintensities (WMHs) in head magnetic resonance imaging (MRI) using only thick-slice fluid-attenuated inversion recovery (FLAIR) sequences from multiple centers. We enrolled 1092 participants in Japan, comprising the thick-slice Private Dataset. Based on 207 randomly selected participants, neuroradiologists annotated WMHs using predefined guidelines. The annotated images of participants were divided into training (n = 138) and test (n = 69) datasets. The WMH segmentation model comprised a U-Net ensemble and was trained using the Private Dataset. Two other models were trained for validation using either both thin- and thick-slice MRI datasets or the thin-slice dataset alone. The voxel-wise Dice similarity coefficient (DSC) was used as the evaluation metric. The model trained using only thick-slice MRI showed a DSC of 0.820 for the test dataset, which is comparable to the accuracy of human readers. The model trained with the additional thin-slice dataset showed only a slightly improved DSC of 0.822. This automatic WMH segmentation model comprising a U-Net ensemble trained on a thick-slice FLAIR MRI dataset is a promising new method. Despite some limitations, this model may be applicable in clinical practice.

Anatomical analysis of white fiber tracts in SMA and its implications related to en-masse tumor resection technique.

OBJECTIVE: Anatomy and connections of the supplementary motor area (SMA) are studied essentially to analyze the SMA syndrome. Experience with surgical treatment of 19 tumors located in SMA is analyzed. MATERIAL AND METHODS: The cortical anatomy and subcortical connectivity of the SMA was studied on ten previously frozen and formalin fixed human cadaveric brain specimens. The white fiber dissection was performed using Klingler's method. Nineteen patients with low grade gliomas in the region of the SMA treated surgically were clinically analyzed. RESULTS: The white fiber connections of the SMA include short arcuate connections with the pre-central, middle and inferior frontal gyri, the medial part of the SLF, the cingulum, the frontal aslant tract (FAT), the claustro-cortical fibers, the fronto-striatal tract and the crossed frontal aslant tract. All tumors were operated using en-masse surgical technique described by us and its subsequent modifications that focused on attempts towards preservation of related critical fiber tracts namely FAT, cingulum and corpus callosum presumed to be responsible for postoperative SMA syndrome. Eight patients developed an SMA syndrome in the immediate post-operative period. Eleven patients did not develop any post-operative neurological deficits. In all these 11 patients it was apparent that the cingulum, FAT and the corpus callosal fibers were preserved during surgery by modifying the tumor resection technique. CONCLUSIONS: SMA syndrome is a frequent occurrence following surgery in patients with tumors in the region of the SMA complex. Surgical strategy that preserves the cingulum and the FAT can prevent the occurrence of the SMA syndrome.

Migraine or any headaches and white matter hyperintensities and their progression in women and men.

BACKGROUND: Cross-sectional and longitudinal studies have been conducted to investigate the association between migraine and any headache and white matter hyperintensities (WMH). However, studies are inconsistent regarding the strength of the association and its clinical significance. The aim of our study was to investigate the association between headache and its subtypes (migraine with aura (MigA+), migraine without aura (MigA-), non-migraine headache (nonMigHA)) and WMH and its course in the population-based 1000BRAINS study using state-of-the-art imaging techniques and migraine classification according to modified international classification of headache disorders. METHODS: Data from 1062 participants (45% women, 60.9 ± 13.0 years) with ever or never headache (neverHA) and complete quantitative (WMH volume) and qualitative (Fazekas classification) WMH data at first imaging and after 3.7 ± 0.7 years (393 participants) were analyzed. The sex-specific association between headache and its subtypes and WMH volume and its change was evaluated by linear regression, between headache and its subtypes and Fazekas score high vs. low (2-3 vs. 0-1) by log-binomial regression, adjusted for confounders. RESULTS: The lifetime prevalence of headache was 77.5% (10.5% MigA+, 26.9% MigA-, 40.1% nonMigHA). The median WMH volume was 4005 (IQR: 2454-6880) mm3 in women and 4812 (2842-8445) mm3 in men. Women with any headaches (all headache types combined) had a 1.23 [1.04; 1.45]-fold higher WMH volume than women who reported never having had a headache. There was no indication of higher Fazekas grading or more WMH progression in women with migraine or any headaches. Men with migraine or any headaches did not have more WMH or WMH progression compared to men without migraine or men who never had headache. CONCLUSIONS: Our study demonstrated no increased occurrence or progression of WMH in participants with mgiraine. But, our results provide some evidence of greater WMH volume in women with headache of any type including migraine. The underlying pathomechanisms and the reasons why this was not shown in men are unclear and require further research.

White matter hyperintensity, parent artery steno-occlusion, and neurological deterioration in anterior circulation single subcortical infarction patients.

BACKGROUND: The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. METHODS: In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24 h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. RESULTS: PAS modified the association between WMH severity and ND among patients with SSI (pinteraction = .029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend = .428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend = .043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p = .005; integrated discrimination index: 2.5%, p = .004) but not in those with PAS. CONCLUSION: There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.

Decreased brain iron deposition based on quantitative susceptibility mapping correlates with reduced neurodevelopmental status in children with autism spectrum disorder.

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children.

Diabetes-related clinical and microstructural white matter changes in patients with Alzheimer's disease.

AIM: Although there exists substantial epidemiological evidence indicating an elevated risk of dementia in individuals with diabetes, our understanding of the neuropathological underpinnings of the association between Type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) remains unclear. This study aims to unveil the microstructural brain changes associated with T2DM in AD and identify the clinical variables contributing to these changes. METHODS: In this retrospective study involving 64 patients with AD, 31 individuals had concurrent T2DM. The study involved a comparative analysis of diffusion tensor imaging (DTI) images and clinical features between patients with and without T2DM. The FSL FMRIB software library was used for comprehensive preprocessing and tractography analysis of DTI data. After eddy current correction, the "bedpost" model was utilized to model diffusion parameters. Linear regression analysis with a stepwise method was used to predict the clinical variables that could lead to microstructural white matter changes. RESULTS: We observed a significant impairment in the left superior longitudinal fasciculus (SLF) among patients with AD who also had T2DM. This impairment in patients with AD and T2DM was associated with an elevation in creatine levels. CONCLUSION: The white matter microstructure in the left SLF appears to be sensitive to the impairment of kidney function associated with T2DM in patients with AD. The emergence of AD in association with T2DM may be driven by mechanisms distinct from the typical AD pathology. Compromised renal function in AD could potentially contribute to impaired white matter integrity.

Choir singing is associated with enhanced structural connectivity across the adult lifespan.

The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.

The impact of sunlight exposure on brain structural markers in the UK Biobank.

Sunlight is closely intertwined with daily life. It remains unclear whether there are associations between sunlight exposure and brain structural markers. General linear regression analysis was used to compare the differences in brain structural markers among different sunlight exposure time groups. Stratification analyses were performed based on sex, age, and diseases (hypertension, stroke, diabetes). Restricted cubic spline was performed to examine the dose-response relationship between natural sunlight exposure and brain structural markers, with further stratification by season. A negative association of sunlight exposure time with brain structural markers was found in the upper tertile compared to the lower tertile. Prolonged natural sunlight exposure was associated with the volumes of total brain (ß: - 0.051, P < 0.001), white matter (ß: - 0.031, P = 0.023), gray matter (ß: - 0.067, P < 0.001), and white matter hyperintensities (ß: 0.059, P < 0.001). These associations were more pronounced in males and individuals under the age of 60. The results of the restricted cubic spline analysis showed a nonlinear relationship between sunlight exposure and brain structural markers, with the direction changing around 2 h of sunlight exposure. This study demonstrates that prolonged exposure to natural sunlight is associated with brain structural markers change.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Human intraparietal sulcal morphology relates to individual differences in language and memory performance.

The sulco-gyral pattern is a qualitative feature of the cortical anatomy that is determined in utero, stable throughout lifespan and linked to brain function. The intraparietal sulcus (IPS) is a nodal associative brain area, but the relation between its morphology and cognition is largely unknown. By labelling the left and right IPS of 390 healthy participants into two patterns, according to the presence or absence of a sulcus interruption, here we demonstrate a strong association between the morphology of the right IPS and performance on memory and language tasks. We interpret the results as a morphological advantage of a sulcus interruption, probably due to the underlying white matter organization. The right-hemisphere specificity of this effect emphasizes the neurodevelopmental and plastic role of sulcus morphology in cognition prior to lateralisation processes. The results highlight a promising area of investigation on the relationship between cognitive performance, sulco-gyral pattern and white matter bundles.

Predicting Alzheimer's progression in MCI: a DTI-based white matter network model.

OBJECTIVE: This study aimed to identify features of white matter network attributes based on diffusion tensor imaging (DTI) that might lead to progression from mild cognitive impairment (MCI) and construct a comprehensive model based on these features for predicting the population at high risk of progression to Alzheimer's disease (AD) in MCI patients. METHODS: This study enrolled 121 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among them, 36 progressed to AD after four years of follow-up. A brain network was constructed for each patient based on white matter fiber tracts, and network attribute features were extracted. White matter network features were downscaled, and white matter markers were constructed using an integrated downscaling approach, followed by forming an integrated model with clinical features and performance evaluation. RESULTS: APOE4 and ADAS scores were used as independent predictors and combined with white matter network markers to construct a comprehensive model. The diagnostic efficacy of the comprehensive model was 0.924 and 0.919, sensitivity was 0.864 and 0.900, and specificity was 0.871 and 0.815 in the training and test groups, respectively. The Delong test showed significant differences (P < 0.05) in the diagnostic efficacy of the combined model and APOE4 and ADAS scores, while there was no significant difference (P > 0.05) between the combined model and white matter network biomarkers. CONCLUSIONS: A comprehensive model constructed based on white matter network markers can identify MCI patients at high risk of progression to AD and provide an adjunct biomarker helpful in early AD detection.

Proteomic dissection of vanishing white matter pathogenesis.

Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear which factors contribute to VWM pathogenesis. Here, we investigated the basis of VWM pathogenesis using the 2b5ho mouse model. We first mapped the temporal proteome in the cerebellum, corpus callosum, cortex, and brainstem of 2b5ho and wild-type (WT) mice. Protein changes observed in 2b5ho mice were then cross-referenced with published proteomic datasets from VWM patient brain tissue to define alterations relevant to the human disease. By comparing 2b5ho mice with their region- and age-matched WT counterparts, we showed that the proteome in the cerebellum and cortex of 2b5ho mice was already dysregulated prior to pathology development, whereas proteome changes in the corpus callosum only occurred after pathology onset. Remarkably, protein changes in the brainstem were transient, indicating that a compensatory mechanism might occur in this region. Importantly, 2b5ho mouse brain proteome changes reflect features well-known in VWM. Comparison of the 2b5ho mouse and VWM patient brain proteomes revealed shared changes. These could represent changes that contribute to the disease or even drive its progression in patients. Taken together, we show that the 2b5ho mouse brain proteome is affected in a region- and time-dependent manner. We found that the 2b5ho mouse model partly replicates the human disease at the protein level, providing a resource to study aspects of VWM pathogenesis by highlighting alterations from early to late disease stages, and those that possibly drive disease progression.

Visual training after central retinal loss limits structural white matter degradation: an MRI study.

BACKGROUND: Macular degeneration of the eye is a common cause of blindness and affects 8% of the worldwide human population. In adult cats with bilateral lesions of the central retina, we explored the possibility that motion perception training can limit the associated degradation of the visual system. We evaluated how visual training affects behavioral performance and white matter structure. Recently, we proposed (Kozak et al. in Transl Vis Sci Technol 10:9, 2021) a new motion-acuity test for low vision patients, enabling full visual field functional assessment through simultaneous perception of shape and motion. Here, we integrated this test as the last step of a 10-week motion-perception training. RESULTS: Cats were divided into three groups: retinal-lesioned only and two trained groups, retinal-lesioned trained and control trained. The behavioral data revealed that trained cats with retinal lesions were superior in motion tasks, even when the difficulty relied only on acuity. 7 T-MRI scanning was done before and after lesioning at 5 different timepoints, followed by Fixel-Based and Fractional Anisotropy Analysis. In cats with retinal lesions, training resulted in a more localized and reduced percentage decrease in Fixel-Based Analysis metrics in the dLGN, caudate nucleus and hippocampus compared to untrained cats. In motion-sensitive area V5/PMLS, the significant decreases in fiber density were equally strong in retinal-lesioned untrained and trained cats, up to 40% in both groups. The only cortical area with Fractional Anisotropy values not affected by central retinal loss was area V5/PMLS. In other visual ROIs, the Fractional Anisotropy values increased over time in the untrained retinal lesioned group, whereas they decreased in the retinal lesioned trained group and remained at a similar level as in trained controls. CONCLUSIONS: Overall, our MRI results showed a stabilizing effect of motion training applied soon after central retinal loss induction on white matter structure. We propose that introducing early motion-acuity training for low vision patients, aimed at the intact and active retinal peripheries, may facilitate brain plasticity processes toward better vision.