Brain Integrity Research Articles

Effects of Anesthesia and Surgery on the Morphologic and Functional Development of the Premature Neonatal Brain: A Systematic Review and Meta-Analysis

Background: The percentage of preterm infants requiring surgery before 44 weeks of postmenstrual age (PMA) varies between 19% and 36%. The potential impact of general anesthesia on the vulnerable developing brain of preterm infants remains unknown. Methods: A systematic review and meta-analysis on the impact of general anesthesia on brain integrity and neurodevelopmental outcomes in preterm infants undergoing surgery before 44 weeks PMA was conducted. Studies were identified via a PubMed, EMBASE (Ovid), and Cochrane CENTRAL search conducted from inception until 8 March 2023, following PRISMA guidelines. Brain abnormality was assessed using MRI-based brain volume and abnormality scores. Neurodevelopment was evaluated through Bayley Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) tests. Quality was assessed via the Cochrane ROBINS-I tool and GRADE. Results: Our systematic search identified 2883 records, leading to the inclusion of 12 observational studies. Very low-quality evidence suggests that preterm infants exposed to anesthesia were more likely to show postoperative brain abnormalities on MRI (OR 2.01, 95%CI 1.24–3.25, p = 0.005). They had lower neurodevelopmental scores on the BSID II and III (psychomotor developmental index: mean difference (MD) −10.98; 95%CI −12.04 to −9.91; p < 0.001 and cognitive composite score: (MD) −10.11; 95%CI −11.06 to −9.16; p < 0.001 at two years of age compared to preterm infants not exposed to anesthesia. Conclusion: Exposure to surgery and anesthesia before term age is associated with brain abnormalities and neurodevelopmental delay at two years, but conclusions are limited by low evidence quality, uncontrolled confounders, and the methodological biases of the included studies; thus further robust studies are required (PROSPERO:CRD42021255907).

Repetition Suppression and Related Effects

We present an extensive review of the repetition effect aiming to understand a simple experimental fact: why the repetition of a stimulus leads to reduced neural activity as compared to unrepeated stimuli. Previous attempts to understand this fact were connected mainly with the application of the mechanisms of local models (synchrony, facilitation and sharpening). We show that the Neurolocator model earlier proposed for the explanation of neural memory, focused attention, and Pavlovian conditioning can also successfully explain most difficult cases of repetition effects. The Supplement Material includes wide range of related effects such as habituation and sensitization, negative priming, inhibition of return, whole brain segregation and integration. All of them need an additional works to build specific models in each case, but we believe that their successful modeling will be closely connected with the Neurolocator model.

MgSO4 as a novel hypothermia infusion solution promotes ischemic stroke recovery through Ca2+ regulation of neurovascular units.

The neuroprotection of acute ischemic stroke (AIS) patients to alleviate the reperfusion injury is a long-standing problem. Although the intra-arterial selective cooling saline infusion (IA-SCSI) is a promising technique to improve the outcome of AIS, the clinical results are not sufficiently satisfactory. Magnesium-containing solutions such as magnesium sulfate (MgSO4) can protect cells by modulating the intracellular Ca2+ content in damaged cells, suggesting that they could be hypothermia infusion solution. In this study, we hypothesized that MgSO4, as a novel hypothermia infusion solution (IA-SCMI), can promote AIS recovery. Methods: First, IA-SCMI was performed in rats subjected to the middle cerebral artery occlusion. The effect of combined hypothermia and MgSO4 treatment on different neurovascular (NVU) cells after oxygen-glucose deprivation/reoxygenation (OGD/R) injury was examined. Results: Compared with the IA-SCSI or IA-MgSO4 infusion alone, IA-SCMI offered the best protective effect by improving neurological defects, and alleviating brain integrity damage and CBF reduction. Meanwhile, in vitro results revealed that the combination of hypothermia and MgSO4 provided maximum protection to the NVU cells, and this protective effect was mainly achieved through the regulation of Ca2+ homeostasis in different cells. Conclusion: MgSO4 may be a promising hypothermia infusion solution to facilitate the recovery of neurological function in AIS patients.

Developmental Trajectories and Differences in Functional Brain Network Properties of Preterm and At-Term Neonates.

Premature infants, born before 37 weeks of gestation can have alterations in neurodevelopment and cognition, even when no anatomical lesions are evident. Resting-state functional neuroimaging of naturally sleeping babies has shown altered connectivity patterns, but there is limited evidence on the developmental trajectories of functional organization in preterm neonates. By using a large dataset from the developing Human Connectome Project, we explored the differences in graph theory properties between at-term (n = 332) and preterm (n = 115) neonates at term-equivalent age, considering the age subgroups proposed by the World Health Organization for premature birth. Leveraging the longitudinal follow-up for some preterm participants, we characterized the developmental trajectories for preterm and at-term neonates, for this purpose linear, quadratic, and log-linear mixed models were constructed with gestational age at scan as an independent fixed-effect variable and random effects were added for the intercept and subject ID. Significance was defined at p < 0.05, and the model with the lowest Akaike Information Criterion (AIC) was selected as the best model. We found significant differences between groups in connectivity strength, clustering coefficient, characteristic path length and global efficiency. Specifically, at term-equivalent ages, higher connectivity, clustering coefficient and efficiency are identified for neonates born at later postmenstrual ages. Similarly, the characteristic path length showed the inverse pattern. These results were consistent for a variety of connectivity thresholds at both the global (whole brain) and local level (brain regions). The brain regions with the greatest differences between groups include primary sensory and motor regions and the precuneus which may relate to the risk factors for sensorimotor and behavioral deficits associated with premature birth. Our results also show non-linear developmental trajectories for premature neonates, but decreased integration and segregation even at term-equivalent age. Overall, our results confirm altered functional connectivity, integration and segregation properties of the premature brain despite showing rapid maturation after birth.

Copper nanoparticles induced oxidative stress and tissue integrity in gills and brain of Cyprinus carpio

Copper nanoparticles are widely used in various commercial and industrial products and have potential toxicity. This study assessed the effects of copper nanoparticles on gills and the brain of Cyprinus carpio. This study investigated the sub-lethal effects of waterborne copper nanoparticles by involving Cyprinus carpio (n=120) of 40±5g weight distributed into four groups with 3 replicates having 10 fish in each group. For this purpose Cyprinus carpio were exposed to either 0.6 or 1.04 or 1.6 mg/L of waterborne copper nanoparticles for 14 days. Histopathological and enzymatic studies were carried out. Control fish showed normal histology while in treated groups; gill tissues showed alterations such as necrosis, filament fusion, congestion, the curvature of filaments, gills edema and thickening of the primary and secondary lamella. Enlarged primordial cells, necrosis, and hemorrhage were the changes reported in the brain. These changes were dose-dependent and increased with increasing dose. In this study activity of catalase enzymes decreased as compared to control while activities of lipid peroxide and reduced glutathione increased significantly when compared with control group activities. Study revealed that Copper nanoparticles exposure induced significant toxicological impacts on gills and brain

Intermodulation frequencies reveal common neural assemblies integrating facial and vocal fearful expressions.

Effective social communication depends on the integration of emotional expressions coming from the face and the voice. Although there are consistent reports on how seeing and hearing emotion expressions can be automatically integrated, direct signatures of multisensory integration in the human brain remain elusive. Here we implemented a multi-input electroencephalographic (EEG) frequency tagging paradigm to investigate neural populations integrating facial and vocal fearful expressions. High-density EEG was acquired in participants attending to dynamic fearful facial and vocal expressions tagged at different frequencies (fvis, faud). Beyond EEG activity at the specific unimodal facial and vocal emotion presentation frequencies, activity at intermodulation frequencies (IM) arising at the sums and differences of the harmonics of the stimulation frequencies (mfvis±nfaud) were observed, suggesting non-linear integration of the visual and auditory emotion information into a unified representation. These IM provide evidence that common neural populations integrate signal from the two sensory streams. Importantly, IMs were absent in a control condition with mismatched facial and vocal emotion expressions. Our results provide direct evidence from non-invasive recordings in humans for common neural populations that integrate fearful facial and vocal emotional expressions.

Brain Resilience to Targeted Attack of Resting BOLD Networks as a Measure of Cognitive Reserve.

Recent advancements in connectome analyses have enabled more precise measurements of brain network integrity. Identifying neural measures that can operate as mechanisms of cognitive reserve (CR) is integral for the study of individual variability in age-related cognitive changes. In the present study, we tested the hypothesis that network resilience, or the network's ability to maintain functionality when facing internal or external perturbations that cause damage or error, can function as a CR candidate, modifying the relationship between cognitive and brain changes in a lifespan cohort of cognitively healthy adults. One hundred cognitively healthy older adults from the Reference Ability Neural Network (RANN) longitudinal lifespan cohort (50-80 years) underwent resting-state fMRI and neuropsychological testing at baseline and five-year follow-up. Using undirected weighted adjacency matrices created from the Schaefer et al. (2018) 400-parcellation atlas and 19 additional subcortical regions (419 nodes in total), whole-brain network resilience was assessed through a targeted attack approach, where nodes were sequentially removed by nodal strength and resilience defined as the iteration of the steepest slope in the largest connected component (LCC) decay. We observed that brain resilience (BR) moderated the effect of cortical thickness (CT) changes on longitudinal changes in Fluid Reasoning performance, even after adjusting for baseline differences, demographic factors, and the initial LCC of the unlesioned matrix, indicating that individuals with greater resilience were less sensitive to the effect of cortical thickness changes on changes in cognition. These findings support the use of targeted attack as a measure of cognitive reserve, suggesting that higher brain network resilience may allow individuals with reduced brain integrity to better cope with structural loss and maintain cognitive function.

Novel Diagnostic Tool for Detecting Cognitive Impairment by Integrating Functional Near‐infrared Spectroscopy and Plasma Biomarkers in a Large Chinese Cohort

AbstractBackgroundAn objective and effective screening tool for cognitive impairment (CI) is needed in the Chinese population. However, whether the integration of brain resting‐state functional connectivity (rs‐FC) and neurodegenerative plasma biomarkers can distinguish CI from cognitively normal (CN) individuals remains unclear.MethodA total of 1077 participants from a longitudinal Liuyang community cohort were enrolled. The rs‐FC was collected using functional near‐infrared spectroscopy (fNIRS). Plasma biomarkers, including p‐tau181, p‐tau217, p‐tau231, Aβ40, Aβ42, NfL, and GFAP were detected using single molecule assay method.ResultThe average FC of the CI group was significantly lower than that of the CN group (p &lt; 0.0001). The CI detection model based on the combined altered FCs, achieved an area under the curve (AUC) of 0.785, which showed better diagnostic performance than that of single plasma biomarker with AUC of 0.592‐0.631. However, the integration of altered FC and plasma biomarker presented the best accuracy with AUC of 0.887‐0.933. Totally, 27 FCs were correlated with plasma biomarkers, and among them, the strength of right part of Brodmann's area 6 vs. right part of Brodmann's area 1+2 (BA6R.vs.BA1+2R) was negatively associated with p‐tau231, p‐tau217 and GFAP. Additionally, 13 FCs could mediate the effects of three plasma biomarkers on cognition, including p‐tau217 (n = 3), NfL (n = 10), and GFAP (n = 1).ConclusionRs‐FC based on fNIRS combined with plasma biomarkers is feasible and effective for non‐invasive CI screening.

Brain Resilience to Targeted Attack of Resting BOLD Networks as a Measure of Cognitive Reserve

AbstractBackgroundRecent advancements in connectome analyses allow for more fine‐grained measurements of brain network integrity. One measure of integrity is resilience, or the capacity of the network to retain functionality when confronted with endogenous or exogenous perturbations that result in damage or error. We assessed the impact of individual differences in the resilience of resting BOLD connectivity on the relationship between cognitive and brain changes in a lifespan cohort of cognitively healthy adults over a 5‐year period.MethodOne hundred twenty‐six cognitively healthy participants from the Reference Ability Neural Network (RANN) longitudinal lifespan cohort (age 20‐80 years) underwent resting‐state fMRI to measure functional connectivity and an out‐of‐scanner neuropsychological battery at baseline and five‐year follow‐up. Undirected weighted adjacency matrices were generated from Schaefer et al. (2018) 400 parcellation atlas. As a measure of whole‐brain network resilience, we adopted a targeted attack approach, whereby nodes are sequentially removed from the connectome in order of nodal strength. At each iteration of attack, nodal strength is recalculated based on the effect of prior lesioning and the largest connected component (LCC) is measured. We inferred that more resilient individuals will sustain larger LCCs over longer iterations of lesioning before decay in LCC becomes evident, with resilience operationalized as the iteration of steepest slope in LCC.ResultWe tested whether our operationalization of brain resilience (BR) moderated the effect of brain integrity (i.e., cortical thickness; CT) on out‐of‐scanner neuropsychological test performance across four domains of cognition in the context of longitudinal change (∆) over time. After accounting for baseline differences in change variables and adjusting for the demographic factors of Age, Sex, NART IQ, and Education, we observed a significant negative interaction between ∆CT and ∆BR on ΔCognition for the Fluid Reasoning domain. That is, individuals with increased brain resilience over time were less sensitive to the effect of changes in cortical thickness on changes in cognition.ConclusionOur finding supports evidence for targeted attack as a measure of cognitive reserve, where higher brain network resilience may have permitted individuals with reduced brain integrity to better cope with structural loss and enhance preservation of cognitive function.

Social determinants in early midlife and trajectories in cognition and brain integrity in midlife

Social determinants in early midlife and trajectories in cognition and brain integrity in midlife

Application of High‐Resolution Diffusion‐MRI in Neurotrauma Accelerated Alzheimer's Disease

AbstractBackgroundTraumatic brain injury (TBI) is a risk factor for earlier onset of Alzheimer’s disease (AD)( Graves AB, et al., 1990), and the more severe the injury, the greater the risk of developing AD(Johnson VE, et al.,2010). Given the prevalence of AD in modern society, the possibility that TBI may predispose individuals to develop AD has significant social and economic implications. Therefore, it is important to understand how TBI triggers accelerated AD progression. In this study, we explored how neurotrauma accelerated white matter degeneration in a transgenic mouse model of AD using high‐resolution (60mm3) ex vivo diffusion MRI.Method3xTg‐AD mice were pretreated with a non‐sedating dose of the analgesic buprenorphine (0.2mg/kg, i.p.) prior to TBI. 3xTg‐AD mice were subjected to left‐lateral closed‐head impact injury at 10‐12 weeks of age (Tagge CA, et al.,2018). At six months post‐TBI, mice were sacrificed using transcardial perfusion. The harvested brains were submerged in 10% formalin for 24 hours and stored in Gadavist‐doped PBS (1:400 dilution) until MRI. MRI data were acquired using a 9.4T Bruker scanner and a 2‐element cryoprobe. Key parameters are TR=300ms, TE=27.7ms, b=3000 and 5000 s/mm2 (64 directions), FOV=13.92x10.20x7.20mm3, Matrix=232x170x120, resolution=60mm3. Diffusion MRI was analyzed in DSI Studio (http://dsistudio.labsolver.org). Age‐ and gender‐matched 3xTg‐AD mice without TBI were used as controls.ResultFigure 1 shows the representative quantitative anisotropy (QA) maps obtained from a mouse with TBI. At 6 months post‐TBI, decreased QA values were observed in the brain regions ipsilateral to the injury (arrows) compared to the corresponding contralateral regions. Figure 2 shows the representative QA maps of the regions around the hippocampus in mice with and without TBI. Compared to the control mouse, the mouse with neurotrauma showed decreased QA values in the corpus callosum and bilateral hippocampus, especially in the CA1 subregion.ConclusionOur results demonstrated that ultra‐high resolution diffusion MRI can capture subtle alterations of white matter integrity in different brain sub‐regions. Using this technique, we were able to detect subtle white matter degeneration in a mouse model of Alzheimer’s disease. The observed white matter deterioration may contribute to the worsening of Alzheimer’s disease after neurotrauma.

Allostasis links white matter hyperintensities with age‐related human brain structure and function: evidence from EEG and structural MRI

AbstractBackgroundThe human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure. While the strong association between vascular/metabolic systems and brain structure/function is established, the precise mechanisms linking allostasis to WMH remain elusive. We hypothesized that allostasis influences white matter through neuroinflammatory mechanisms, and WMH mediate neuroinflammatory effects on EEG measures.MethodTo test this hypothesis we conducted a comprehensive analysis on MRI, EEG, and multisystemic data from 196 subjects (20 to 75 years, 69 females) sourced from the LEMON database in Leipzig, Germany. Using the lesion segmentation tool (LST) on SPM12, we automatically identified WMH in fluid‐attenuated inversion recovery (FLAIR) images. FastSurfer was employed to determine the volumes of the bilateral hippocampus (HV) and lateral ventricles (VV), representing proxies for neurodegenerative and neuroinflammatory processes, respectively. Volumetric corrections were applied using total intracranial volume. Furthermore, a regression analysis was conducted to discern and subtract the shared contributions of VH and VV on each other. EEG data underwent spectral analysis for oscillatory (alpha waves) and aperiodic (1/f) components using NeuroDSP and FOOOF, respectively. An allostatic load index (ALI), incorporating lipid profile, inflammation, metabolic factors, and blood pressure, was computed. All measures were age, sex, and education level‐corrected.ResultWe found age differences in every metric of interest, but importantly just ALI, VV and 1/f correlated with WMH number and those effects survived age correction (Figure 1 A and B). VV, but not HV mediates the relationship between ALI and WMH. Also, WMH completely mediate the effects of neuroinflammation over the 1/f (Figure 1 C).ConclusionOur findings reveal that allostasis affects white matter through neuroinflammatory pathways, with WMH serving as crucial mediators of neuroinflammatory impact on EEG measures. This research provides key insights into the intricate interplay of vascular and metabolic factors with brain structure. Identified relationships and mediators open avenues for targeted interventions and personalized treatments in neurodegenerative and neuroinflammatory conditions.

Psoas Muscle Sarcopenia Predicts Brain Volume Loss on MRI in 7,149 Individuals

AbstractBackgroundSarcopenia has been linked to brain atrophy and there is lack of information on specific muscle groups that may contribute to this link. The psoas muscles are sensitive to sarcopenia and thus may sensitively relate to brain aging and Alzheimer disease risk.MethodThis study utilized 7,149 healthy individuals across four sites (Mean age 53.06 ± 12.95 years, age range 18‐97 years; 48% women; 52% men; 38% non‐white) were scanned on 1.5T MR machines with a whole‐body protocol. Whole body sequences included coronal T1 for segmentation of psoas muscle volumes. Deep learning with FastSurfer on 3D T1 volumetric MPRAGE trained on 134 participants aged 27‐66 segmented 96 brain regions. Partial correlation analysis was done on psoas muscle volumes and brain regions controlling for sex and total intracranial volume to determine if lower psoas muscle volumes correlated to brain atrophy. Multiple comparisons were accounted for using the Bonferroni Method.ResultLower psoas muscle volumes demonstrated a statistically partial correlation to lower gray matter (rp = ‐0.164, p = 2.66×10−43) and white matter volumes (rp = ‐0.171, p = 4.39×10−47). The frontal lobe exhibited a negative correlation (rp = ‐0.172, p = 1.30×10−47), identical to the temporal lobe (rp = ‐0.172, p = 1.21×10−47). Negative correlations were also noted in the parietal lobe (rp = ‐0.119, p = 8.72×10−23), and occipital lobe (rp = ‐0.139; p = 2.89×10−31). The hippocampus also showed a statistically significant negative correlation (rp = ‐0.145, p = 7.65×10−34), as did the posterior cingulate (rp = ‐0.162, p = 5.20×10−42) and the precuneus (rp = ‐0.101, p = 1.34×10−16). The cerebral ventricles showed a non‐significant negative correlation (rp = ‐0.025, p = 0.345).ConclusionWe demonstrate a significant correlation between lower psoas muscle volume and brain volume loss, including AD risk regions such as the hippocampus and precuneus. These MRI findings underscore the importance of muscle health in relation to brain integrity. The volume of the psoas, which is involved in basic leg flexion activities such as walking, could be a crucial indicator of brain health and Alzheimer risk.

Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [11C]Leucine PET

PurposeProtein synthesis is essential to maintain integrity and function of the human brain, and protein synthesis is associated specifically with the formation of long-term memory. Experimental and clinical observations indicate that this process is disturbed in Alzheimer’s dementia and other neurodegenerative diseases. In-vivo investigation with positron emission tomography (PET) using [11C]leucine provides a unique possibility to measure regional cerebral protein synthesis (rCPS) rates in human brain and to determine whether it is altered in Alzheimer’s disease (AD), and thus may provide a target for future therapeutic interventions.ProceduresIn this first human study, we measured rCPS by [11C]leucine PET in four patients with AD (age 57–73 years) and compared the results with six healthy controls (three of whom were age matched and the other three were young controls). Quantification of rCPS also required measurement of amino acid (AA) levels and of free and protein-bound [11C]leucine in plasma during the 90 min PET scans conducted following at least six hours of fasting.ResultsRates of rCPS measured in absolute units of nmol/g/min ranged between 1.81 and 2.53 in AD patients, 2.10 and 2.54 in matched controls, and 2.21 to 2.35 in the young controls. Mean and median values did not show significant differences between the groups. Rates of rCPS also depended upon whether corrections for plasma AA levels were included in the calculations. When considering regional values relative to the corpus callosum as a reference region, there was a tendency towards impairment of rCPS in patients, which was most prominent in the parietal cortex, but did not reach significance. Similar findings were observed with normalisation of rCPS to global cortical mean.ConclusionsIn summary, this first human study assessing regional protein synthesis with [11C]leucine in AD has demonstrated where the sources of variance in measurements of cerebral protein synthesis may arise, along with the potential magnitude of this variance. This study also indicates that there is a tendency towards impairment of rCPS in patients with Alzheimer’s disease, which requires further investigation including possible partial volume effects due to atrophy.

MRI-based whole-brain elastography and volumetric measurements to predict brain age.

Brain age, as a correlate of an individual's chronological age obtained from structural and functional neuroimaging data, enables assessing developmental or neurodegenerative pathology relative to the overall population. Accurately inferring brain age from brain magnetic resonance imaging (MRI) data requires imaging methods sensitive to tissue health and sophisticated statistical models to identify the underlying age-related brain changes. Magnetic resonance elastography (MRE) is a specialized MRI technique which has emerged as a reliable, non-invasive method to measure the brain's mechanical properties, such as the viscoelastic shear stiffness and damping ratio. These mechanical properties have been shown to change across the life span, reflect neurodegenerative diseases, and are associated with individual differences in cognitive function. Here, we aim to develop a machine learning framework to accurately predict a healthy individual's chronological age from maps of brain mechanical properties. This framework can later be applied to understand neurostructural deviations from normal in individuals with neurodevelopmental or neurodegenerative conditions. Using 3D convolutional networks as deep learning models and more traditional statistical models, we relate chronological age as a function of multiple modalities of whole-brain measurements: stiffness, damping ratio, and volume. Evaluations on held-out subjects show that combining stiffness and volume in a multimodal approach achieves the most accurate predictions. Interpretation of the different models highlights important regions that are distinct between the modalities. The results demonstrate the complementary value of MRE measurements in brain age models, which, in future studies, could improve model sensitivity to brain integrity differences in individuals with neuropathology.

Single-cell RNA sequencing reveals S100A8/A9hi neutrophils-induced endothelial cell death and lymphocyte infiltration after ischemic stroke

Stroke is a major global cause of death and disability, with ischemic stroke being the most common type. The disruption of the blood-brain barrier (BBB) is a key factor in the pathophysiology of ischemic stroke, allowing immune cells to infiltrate and worsening neuroinflammation. This study uses single-cell RNA sequencing (scRNA-seq) to examine the transcriptional changes in neutrophils, endothelial cells, and T cells during ischemic stroke. Our findings indicate a significant increase in neutrophil and lymphocyte infiltration, along with a notable decrease in endothelial cell populations, demonstrating severe BBB disruption. Differential gene expression analysis shows that endothelial cells lose important characteristics post-stroke, while lymphocytes activate cytotoxic pathways that may lead to neuronal damage. Additionally, we reveal the contrasting roles of CXCR2 and CXCR4 in neutrophil movement and identify neutrophil-derived damage-associated molecular patterns (DAMPs) and matrix metalloproteinases (MMPs) as key drivers of endothelial cell apoptosis. Notably, the S100A8/A9 inhibitor paquinimod significantly protects neurons and reduces lymphocyte infiltration, suggesting that targeting S100A8/A9 could be a promising therapeutic strategy for reducing neurological deficits after ischemic stroke. Overall, these results enhance our understanding of the complex interactions between immune cells and the BBB in ischemic stroke, paving the way for innovative therapeutic approaches aimed at maintaining brain integrity and improving patient outcomes.

Diffusion tensor imaging of spinal cord in healthy children

Introduction. Diffusion tensor imaging (DTI) is a technique that allows evaluating diffusion of water molecules along the myelin sheath of nerve fibers and obtaining information about the integrity of brain and spinal cord pathways. Obtaining reproducible values of diffusion parameters is an urgent and feasible task. The aim of this study was to establish the values of DTI parameters along the entire length of the spinal cord in healthy children for further use in the assessment of acute injury, its consequences and other spinal cord diseases. Materials and methods. The study included fifteen healthy patients of 13 to 18 years, including 6 girls and 8 boys, average age was 15.2 ± 1.2 years. The study was performed on a Philips Achieva dStream 3T MRI scanner (Netherlands). As part of this study, a spine MRI protocol was developed to cover the entire volume of spinal cord with separate visualization of cervical and thoracic spine (duration: 9 min 48 sec). The IRIS ZOOM sequence (Philips) was used to obtain DTI images. Spinal Cord Toolbox software package was used to process the data. Statistical analysis was performed using GraphPad Prism software, and significance was determined at p &lt; 0.05. Results. Mapping and calculation of the following diffusion parameters: fractional anisotropy (FA), medial (MD), longitudinal or axial (AD) and transverse (RD) diffusion showed the average values of the parameters FA, AD, MD, RD of the spinal cord of children to be: FA, AD, MD, RD of spinal cord were: FA = 0.63 ± 0.06, AD = 2.1 ± 0.3 × 10−3 mm2/s, MD = 1.15 ± 0.16 × 10−3 mm2/s, RD = 0.68 ± 0.12 × 10−3 mm2/s. An increase in FA was detected at the Th2–Th9 level compared to the values at the C6–Th1 and Th10–Th12 levels. The AD coefficient at the Th2–Th9 level is increased relative to the C2–C5 and C6–Th1 levels. MD values in spinal cord areas at the Th2–Th9 and Th10–Th12 levels are statistically higher relative to higher levels of the spinal cord. RD values in the zone at the Th10–Th12 level are increased relative to all other areas. Conclusion. The study established the diffusion indices of FA, MD, AD, RD of spinal cord in children aged 12 to 18 years and showed small differences between the spinal cord regions. The data obtained can be used as reference values for assessing spinal cord condition in various pathological processes (trauma, demyelinating and tumor diseases) in children for the corresponding age group.

Childhood Community Disadvantage and MRI-Derived Structural Brain Integrity After Age 65 Years

Prior studies associate late-life community disadvantage with worse brain health. It is relatively unknown if childhood community disadvantage associates with late-life brain health. To test associations between childhood residence in an economically disadvantaged community, individual income and education, and late-life cortical brain volumes and white matter integrity. This cohort study was conducted in the ongoing harmonized cohorts KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences Study; initiated 2017) and STAR (Study of Healthy Aging in African Americans; initiated 2018) using all available data collected out of a regional integrated health care delivery network in California between cohort initiation and analysis initiation in June 2023. Eligible participants were Kaiser Permanente Northern California member ages 65 years or older. Data were analyzed between June and November 2023. Residence at birth was geocoded and linked to historical Area Deprivation Indices (ADI). ADI is a nationally ranked percentile; community disadvantage was defined as ADI of 80 or higher. Regional brain volumes and white matter integrity measures were derived from a random subset of participants who underwent 3T magnetic resonance imaging. Models adjusted for race and ethnicity, sex, and parental education. Of a total 2161 individuals in the combined cohort, 443 individuals were eligible for imaging (mean [SD] age, 76.3 [6.5] years; 253 female [57.1%]; 56 Asian [12.6%], 212 Black [47.9%], 67 Latino [15.1%], 109 White [24.6%]). Imaging participants had a mean (SD) 15.0 (2.5) years of education, and 183 (41.3%) earned $55 000 to $99 999 annually. Fifty-four participants (12.2%) resided in a disadvantaged childhood community. Childhood community disadvantage was associated with smaller gray matter volumes overall (-0.39 cm3; 95% CI, -0.65 to -0.10 cm3) and in the cerebellum (-0.39 cm3; 95% CI, -0.66 to -0.09 cm3), hippocampus (-0.37 cm3; 95% CI, -0.68 to -0.04 cm3), and parietal cortex (-0.25 cm3; 95% CI, -0.46 to -0.04 cm3) and larger mean lateral ventricle (0.44 cm3; 95% CI, 0.12 to 0.74 cm3), third ventricle (0.28 cm3; 95% CI, 0.03 to 0.55 cm3), and white matter hyperintensity volume (0.31 cm3; 95% CI, 0.06 to 0.56 cm3). Educational attainment and late-life income did not mediate these associations. In this cohort study of racially and ethnically diverse health plan members, childhood community disadvantage was associated with worse late-life brain health independent of individual socioeconomic status. Future work should explore alternative pathways (eg, cardiovascular health) that may explain observed associations.

Sleep quality and the integrity of ascending reticular activating system – A multimodal MRI study

Sleep is crucial for maintaining brain homeostasis and individuals with insufficient sleep are prone to more pronounced brain atrophy as compared to sufficiently sleeping peers. Moreover, sleep quality deteriorates with ageing and ageing is also associated with cerebral structural and functional changes, pointing to their mutual bidirectional interrelationship. This study aimed at determining whether sleep quality and age, separately, affect brain integrity and subsequently, whether sleep significantly modulates the effect of age on brain structural and functional integrity. 113 healthy volunteers underwent a multi-modal MRI imaging to extract information about the microstructure and function of major nodes of the ascending reticular activating system. Sleep quality was assessed by self-administered Pittsburgh's sleep quality index (PSQI) questionnaire. Subject were divided into good (global PSQI score <5) and poor (global PSQI score ≥5) sleep quality group. Whereas only borderline correlations were found between sleep quality and MRI metrics, age exhibited widespread correlations with both functional and microstructural MRI metrics. The latter effect was significantly modulated by sleep quality in ascending reticular activating system, hypothalamus, thalamus and also hippocampus in MRI metrics associated with iron load, cellularity and connectivity, mainly in the subgroup with poor sleep quality. Ergo, our results indicate sleep quality as a substantial contributor to both microstructural and functional brain changes in ageing and call for further research in this emerging topic.

Brain age in genetic and idiopathic Parkinson's disease.

The brain-age gap, i.e. the difference between the brain age estimated from structural MRI data and the chronological age of an individual, has been proposed as a summary measure of brain integrity in neurodegenerative diseases. Here, we aimed to determine the brain-age gap in genetic and idiopathic Parkinson's disease and its association with surrogate markers of Alzheimer's disease and Parkinson's disease pathology and with rates of cognitive and motor function decline. We studied 1200 cases from the Parkinson's Progression Markers Initiative cohort, including idiopathic Parkinson's disease, asymptomatic and clinical mutation carriers in the leucine-rich repeat kinase 2 gene (LRRK2) and the glucocerebrosidase gene (GBA), and normal controls using a cohort study design. For comparison, we studied 187 Alzheimer's disease dementia cases and 254 controls from the Alzheimer's Disease Neuroimaging Initiative cohort. We used Bayesian ANOVA to determine associations of the brain-age gap with diagnosis, and baseline measures of motor and cognitive function, dopamine transporter activity and CSF markers of Alzheimer's disease type amyloid-β42 and phosphotau pathology. Associations of brain-age gap with rates of cognitive and motor function decline were determined using Bayesian generalized mixed effect models. The brain-age gap in idiopathic Parkinson's disease patients was 0.7 years compared to controls, but 5.9 years in Alzheimer's disease dementia cases. In contrast, asymptomatic LRRK2 individuals had a 1.1. year younger brain age than controls. Across all cases, the brain-age gap was associated with motor impairment and (in the clinically manifest PD cases) reduced dopamine transporter activity, but less with CSF amyloid-β42 and phosphotau. In idiopathic Parkinson's disease cases, however, the brain-age gap was associated with lower CSF amyloid-β42 levels. In sporadic and genetic Parkinson's disease cases, a higher brain-age gap was associated with faster decline in episodic memory, and executive and motor function, whereas in asymptomatic LRRK2 cases, a smaller brain-age gap was associated with faster cognitive decline. In conclusion, brain age was sensitive to Alzheimer's disease like rather than Parkinson's disease like brain atrophy. Once an individual had idiopathic Parkinson's disease, their brain age was associated with markers of Alzheimer's disease rather than Parkinson's disease. Asymptomatic LRRK2 cases had seemingly younger brains than controls, and in these cases, younger brain age was associated with poorer cognitive outcome. This suggests that the term brain age is misleading when applied to disease stages where reactive brain changes with apparent volume increases rather than atrophy may drive the calculation of the brain age.