Cortical Morphology Research Articles

Automatic segmentation of cortical bone microstructure: Application and analysis of three proximal femur sites.

Osteoporosis is the most common bone metabolic unbalance, leading to fragility fractures, which are known to be associated with structural changes in the bone. Cortical bone accounts for 80 % of the skeleton mass and undergoes remodeling throughout life, leading to changes in its thickness and microstructure. Although many studies quantified the different cortical bone structures using CT techniques (3D), they are often realised on a small number of samples. Therefore, the work presented here proposes a method to quantify cortical bone microstructure using 2D histology, shows its application on a set of 94 samples and compares to 3D methods. Fresh frozen human femur pairs from 47 donors aged between 57 and 96 years were obtained from the Medical University of Vienna. Bone samples were cut from 3 sites: proximal part of the diaphysis, inferior and superior segments of the neck. The samples were stained with toluidine blue and imaged under light microscopy. After manual segmentation of a few regions of interest by multiple operators, a convolutional neural network was trained in combination with a random forest for automatic segmentation. The segmentation analysis compares morphology and structure distribution of Haversian canals, osteocyte lacunae, and cement lines with literature, between anatomical sites, sex, left and right sides, and relation to ageing. Morphological analysis of the segmentation gives results similar to the literature. Comparison between male and female donors shows no significant differences. There is no significant difference between left and right femur on paired samples but significant differences are observed between anatomical locations. The structures' relative amounts do not present significant changes with age but only weak tendencies. Nevertheless, a strong correlation was observed between osteocyte lacunae density and bone areal fraction. This study presents a full process to stain and automatically segment digital cortical bone images. Its application to a large sample set of proximal femora provides strong statistics on the cortical bone structures morphology and distribution. Similarities observed between sides and sexes together with differences observed between sites could indicate that mechanical loading might be a main driver for bone microstructure. Additionally, the relationship between osteocyte lacunae density and bone areal fraction could suggest that bone porosity is regulated by osteocyte survival.

Three-Dimensional Morphological Characterisation of Human Cortical Organoids Using a Customised Image Analysis Workflow

Summary Statement: A tailored image analysis workflow was applied to quantify cortical organoid health, development, morphology and cellular composition over time. The assessment of cellular composition and viability of stem cell-derived organoid models is a complex but essential approach to understanding the mechanisms of human development and disease. Aim: Our study was motivated by the need for an image-analysis workflow, including high-cell content, high-throughput methods, to measure the architectural features of developing organoids. We assessed stem cell-derived cortical organoids at 4 and 6 months post-induction using immunohistochemistry-labelled sections as the analysis testbed. The workflow leveraged fluorescence imaging tailored to classify cells as viable and dying or non-viable and assign neuronal and astrocytic perinuclear markers to count cells. Results/Outcomes: Image acquisition was accelerated by capturing the organoid slice in 3D using widefield-fluorescence microscopy. This method used computational clearing to resolve nuclear and perinuclear markers and retain their spatial information within the organoid’s heterogeneous structure. The customised workflow analysed over 1.5 million cells using DAPI-stained nuclei, filtering and quantifying viable and non-viable cells and the necrotic-core regions. Temporal analyses of neuronal cell number derived from perinuclear labelling were consistent with organoid maturation from 4 to 6 months of in vitro differentiation. Overall: We have provided a comprehensive and enhanced image analysis workflow for organoid structural evaluation, creating the ability to gather cellular-level statistics in control and disease models.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex. Instead of considering a complex one-to-one mapping between genetic coding and interareal connectivity, we hypothesized the existence of a more efficient way that the organizing principles are embedded in genetic profiles to underpin the cortical wiring space. Leveraging vertex-wise tractography in diffusion-weighted MRI, we derived the global connectopies in both female and male to reliably index the organizing principles of interareal connectivity variation in a low-dimensional space, which captured three dominant topographic patterns along the dorsoventral, rostrocaudal, and mediolateral axes of the cortex. More importantly, we demonstrated that the global connectopies converge with the gradients of a vertex-by-vertex genetic correlation matrix on the phenotype of cortical morphology and the cortex-wide spatiomolecular gradients. By diving into the genetic profiles, we found that the critical role of genes scaffolding the global connectopies was related to brain morphogenesis and enriched in radial glial cells before birth and excitatory neurons after birth. Taken together, our findings demonstrated the existence of a genetically determined space that encodes the interareal connectivity variation, which may give new insights into the links between cortical connections and arealization.Significance Statement Genetic factors have involved the gradual emergence of cortical areas since the neural tube begins to form, shaping the specialization of neural circuitry in the human brain. However, the mechanisms through which genetics encode the complex interareal connectivity remain a pivotal and unanswered question in the field of neuroscience. Here, we hypothesized that a genetically determined space encoding the interareal connectivity variation exists, which may give new insights into the links between cortical connections and arealization. We combined diffusion tractography with a dimension reduction framework to unravel the underlying global topographic principle revealed by the anatomical connections.

Decreased Cortical Sulcus Depth in Parkinson's Disease with Excessive Daytime Sleepiness.

Excessive daytime sleepiness (EDS), aprevalent non-motor symptom in Parkinson's disease (PD), significantly impacts the quality of life for PD patients and elevates the risks of injury. Our study is to investigate the altered cortical surface morphology characteristics in PD patients with EDS (PD-EDS). Clinical data and magnetic resonance imaging were obtained from the Parkinson's Progression Marker Initiative database, comprising 36PD-EDS and 98PD patients without EDS (PD-nEDS). The computational anatomy toolbox was utilized to derive sulcus depth (SD) and deep grey matter (GM) nuclei volumes. PD-EDS patients exhibited significantly decreased SD values in the right caudal middle frontal gyrus, pars opercularis, and superior temporal cortex relative to PD-nEDS patients. However, no significant differences in deep GM nuclei volumes were identified. Receiver operating characteristic (ROC) curve analyses further revealed that these cortical SD values could potentially serve as ascreening index for distinguishing PD-EDS from PD-nEDS. Additionally, although PD-EDS patients had a longer disease duration and poorer performance in motor function and depression compared to PD-nEDS patients, these factors were included as covariates in the neuroimaging analyses. Our study findings demonstrated that decreased cortical SD values might induce sleep-wake state instability and contribute to the pathophysiological mechanisms of EDS in early-stage PD.

Cortical complexity alterations in motor subtypes of Parkinson's disease: A surface-based morphometry analysis of fractal dimension.

Based on motor symptoms, Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability gait difficulty (PIGD) subtypes. Few studies have examined cortical complexity differences in PD motor subtypes. This study aimed to investigate differences in cortical complexity and grey matter volume (GMV) between TD and PIGD. We enrolled 36 TD patients, 27 PIGD patients and 66 healthy controls (HC) from the PPMI (Parkinson's Progression Markers Initiative) database. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were utilized to assess differences in GMV, cortical thickness and cortical complexity. The structural MRI data of participants was analysed using CAT12/SPM12 (p < 0.05, FDR corrected). Additionally, correlations between clinical data and structural changes were examined (p < 0.05, Holm-Bonferroni corrected). In comparison to both HC and TD groups, PIGD patients exhibited a significant fractal dimension (FD) decrease in many cortical regions. A significant negative correlation between age and FD was observed in the left insula for the PIGD patients and in the bilateral insula for the TD patients. However, no significant differences were found in GMV, cortical thickness or other complexity indices. Altered FD in the bilateral insula indicates that postural instability and gait disturbances may result from a failure to integrate information from various structures, whereas parkinsonian rest tremor is not associated with this integration. Also, widespread decreases in cortical FD demonstrate that FD is more sensitive than other complexity measures and can serve as a novel biomarker for identifying subtle changes in cortical morphology in the PIGD subtype.

Correlation analysis of ApoB, ApoA1 and ApoB/ApoA1 with cortical morphology in patients with memory complaints

Correlation analysis of ApoB, ApoA1 and ApoB/ApoA1 with cortical morphology in patients with memory complaints

Genotype and corticosteroid treatment are distinctively associated with gray matter characteristics in patients with Duchenne muscular dystrophy

This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes.The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (n=40; 9-18 years) and age-matched controls (n=40). Comparisons were made between DMD vs. controls, daily vs. intermittent corticosteroid treatment (n=20 each), and Dp140+ vs. Dp140- gene mutations (n=15 vs. 25). MANCOVA, CAT12 3D statistics and Pearson correlations were conducted.DMD patients showed differences in volumes of distinct subcortical structures, left hemisphere cortical thickness, and gyrification in multiple brain areas compared with healthy controls. The daily treated DMD group exhibited differences in subcortical volumes and different patterns of cortical thickness, sulci depth, and gyrification compared to the intermittent treated DMD group. DMD Dp140+ patients displayed altered gyrification and sulci depth compared to DMD Dp140- patients. Finally, we found correlations between neurobehavioral outcomes and brain areas that showed differences in cortical morphology associated with corticosteroid treatment.Both genotype and corticosteroid treatment are associated with variations in subcortical volumes and cortical morphology, albeit in different ways. Corticosteroid treatment appears to have a more profound association with differences in gray matter characteristics of brain regions that are associated with functional outcomes.

Mandibular cortical morphology in patients with osteoporosis using computer‐aided detection with dental panoramic imaging: A pilot study of the relation to age and bone‐modifying agents

AbstractAimMandibular cortical morphology with panoramic radiography is considered to be a useful technique for identifying at risk of osteoporosis. The aim of the study was to investigate the mandibular cortical morphology in patients with osteoporosis using computer‐aided detection (CAD) with dental panoramic imaging, especially the relation to age and bone‐modifying agents.MethodsOne hundred and thirteen patients with osteoporosis were underwent panoramic radiography. The mandibular cortical morphology, such as mandibular cortical index (MCI) and degree of deformation of mandibular inferior cortex, was analyzed automatically with a CAD with dental panoramic imaging “PanoSCOPE.” Those were analyzed in relation to age and bone‐modifying agents.ResultsRegarding Class 3 (severely eroded) of the MCI classifications, the frequency in 61–70, 71–80, and 81–90 years were 22.2%, 38.6%, and 26.3%, respectively, and the MCI in bisphosphonate and denosumab were 29.8% and 42.1%, respectively. The degree of deformation in 61–70, 71–80, and 81–90 years were 45.9 ± 22.6, 58.8 ± 20.0, and 52.6 ± 21.5, respectively, and those in bisphosphonate and denosumab were 54.1 ± 20.6 and 57.5 ± 25.0, respectively. The MCI and degree of deformation in patients with osteoporosis were not significant differences for age and bone‐modifying agents.ConclusionThis study suggests that the CAD using PanoSCOPE can perform a quantitative analysis of mandibular cortical morphology in patients with osteoporosis.

Sex-specific associations between maternal prenatal inflammation and offspring cortical morphology in youth: A harmonised study across four birth cohorts

Maternal immune activation (MIA) during pregnancy is implicated in offspring psychiatric disorders. However, it is unknown to what extent MIA affects neurodevelopment, particularly cerebrocortical anatomy, in the general population, and whether effects differ by sex. The current study used vertex-wise statistics to examine the association between maternal prenatal CRP, an archetypal systemic inflammatory marker, and offspring cortical thickness, surface area, and volume, in 2635 mother–child dyads (5.4–26.5 years) from three population-based cohorts, and one clinical cohort enriched for presence of inflammation markers.Maternal CRP within a normal physiological range (<10 mg/L) exhibited sex-specific quadratic associations with cortical morphological measures in 2 regions in males and 1 region in females at childhood. Elevated (>10 mg/L) CRP was associated with regional cortical morphology in females and in a pooled sample of sexes. Overall, MIA is associated with cortical development in a regional and sex-specific manner in studies spanning childhood to adulthood.

Exploring cognitive functions and brain structure in Hereditary Transthyretin amyloidosis using brain MRI and neuropsychological assessment.

Central nervous system symptoms, such as cognitive dysfunction, have been reported in Hereditary Transthyretin Amyloidosis (ATTRv). However, there is a lack of neuroimaging studies investigating structural alterations in the brain related to cognition in ATTRv amyloidosis. This study aimed to investigate cognition and cortical morphology in a cohort of ATTRv patients. 29 ATTRv patients and 26 healthy controls completed neuropsychological assessment. 21 of these patients underwent 3T brain MRI, and 23 healthy subjects constituted the control group for MRI. Cortical measures of volume, thickness, fractional anisotropy (FA), and mean diffusivity (MD) were obtained for both groups. Correlation analyses between brain and cognitive measurements were performed. Patients displayed worse performance than controls in executive functions, verbal and visual memory, visuospatial domains, and language tests. Our study indicated cortical thinning in ATTRv patients in the temporal, occipital, frontal, and parietal areas. The inferior temporal gyrus correlated with verbal memory. Insula and, pars opercularis correlated with both verbal memory and executive function. Cortical thickness in the inferior temporal gyrus, pars opercularis, and insula were linked to memory and executive function. We observed no correlations between cortical volume measures and cognition. Further investigations are imperative to confirm these findings across different populations.

Brain functional gradients are related to cortical folding gradient.

Cortical folding is closely linked to brain functions, with gyri acting more like local functional "hubs" to integrate information than sulci do. However, understanding how anatomical constraints relate to complex functions remains fragmented. One possible reason is that the relationship is estimated on brain mosaics divided by brain functions and cortical folding patterns. The boundaries of these hypothetical hard-segmented mosaics could be subject to the selection of functional/morphological features and as well as the thresholds. In contrast, functional gradient and folding gradient could provide a more feasible and unitless platform to mitigate the uncertainty introduced by boundary definition. Based on the MRI datasets, we used cortical surface curvature as the folding gradient and related it to the functional connectivity transition gradient. We found that, at the local scale, the functional gradient exhibits different function transition patterns between convex/concave cortices, with positive/negative curvatures, respectively. At the global scale, a cortex with more positive curvature could provide more function transition efficiency and play a more dominant role in more abstractive functional networks. These results reveal a novel relation between cortical morphology and brain functions, providing new clues to how anatomical constraint is related to the rise of an efficient brain function architecture.

Neuroanatomical correlates of subjective tinnitus: insights from advanced cortical morphology analysis.

Subjective tinnitus, characterized by the perception of phantom sounds in the absence of external stimuli, presents significant challenges in both audiology and neurology. Once thought to primarily involve aberrant neural activity within auditory pathways, it is now understood to engage a broader array of neuroanatomical structures. This study investigated the connections between auditory, cognitive, and sensory processing regions, which are crucial for unraveling the complex neurobiological basis of tinnitus. Using high-resolution T1-weighted magnetic resonance imaging, we compared 52 individuals with subjective tinnitus with 52 age-matched healthy controls, focusing on cerebral cortex features, including fractal dimensionality, gyrification, and sulcal depth. Covariate analyses were conducted to explore the relationships between tinnitus duration, Tinnitus Handicap Inventory scores, anxiety score, and neuroanatomical changes. We found significant alterations in key brain regions involved in sensory processing, cognition, and emotional regulation, including the insula, lateral occipital cortex, middle frontal gyrus, and superior parietal lobule. These neuroanatomical changes were strongly correlated with the severity and chronicity of tinnitus symptoms. Our findings reveal profound structural changes in the brain associated with subjective tinnitus, offering valuable insights into the condition's underlying mechanisms and providing a potential framework for guiding future research and therapeutic interventions.

Correlation Analysis of ApoB, ApoA1, and ApoB/ApoA1 with Cortical Morphology in Patients with Memory Complaints.

Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease. To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints. Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People's Hospital of Chengdu (FPHC). The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient's cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed. Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth. ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints.

Shared and distinct alterations in brain morphology in children with ADHD and obesity: Reduced cortical surface area in ADHD and thickness in overweight/obesity

ObjectiveTo investigate shared versus distinct differences in brain structure among children with ADHD and obesity, we examined the morphology of regions implicated in cognitive control and reward function in a single cross-sectional cohort of children with and without ADHD and overweight/obesity (OV/OB). MethodParticipants included 471 children ages 8–12 years with ADHD (n = 244; 58 OV/OB) and neurotypical (NT) controls (n = 227; 81 OV/OB) classified as healthy-weight (HW; BMI %ile 5th to <85th) vs. having OV/OB (BMI %ile≥85th). Structural MRI was performed to obtain measures of cortical and subcortical morphology and compared across ADHD × BMI groups. ResultsSurface area was generally lower in ADHD vs. NT including in anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), medial (m)PFC, and primary motor (M1) cortex. In contrast, cortical thickness was generally lower in OV/OB vs. HW for ACC, dlPFC, orbitofrontal cortex (OFC), mPFC, and supplementary motor cortex (SMC). Furthermore, ADHD × OV/OB interactions were observed for the ACC and OFC, with the lowest ACC volume in the ADHD + OV/OB group and the highest OFC surface area in the NT + OV/OB group. Subcortical volumes did not differ between groups. ConclusionsOur findings reveal distinct alterations in cortical morphology in association with ADHD and overweight, with cortical surface area reduced in ADHD vs. thickness reduced in OV/OB. Additionally, the findings provide evidence of combined effects of ADHD × OV/OB in brain regions integral to cognition and motivation. Our results support further investigation of causes and correlates of shared and distinct ADHD- and OV/OB-associated differences in developing frontocingulate morphology.

7943 In Obese C57Bl6 Male Mice, Weight Loss due to Caloric Restriction Reduced Bone Morphology but Improved Components of Systemic Metabolism

Abstract Disclosure: C. Chlebek: None. C. McAndrews: None. S.N. Costa: None. C.J. Rosen: None. Obesity and calorie restriction individually alter systemic cellular metabolism and affect musculoskeletal tissue health. Obesity reduces trabecular and cortical bone quality. Clinically, obese patients are advised to lose weight, despite the negative effects of calorie restriction on bone in nonobese preclinical models. Little is known about bone quality following weight loss in obese preclinical models. We hypothesized that in obese models, caloric restriction would further worsen bone quality. To induce obesity, male C57Bl6 mice (8 weeks old) received 60% high fat diet for 12 weeks (high fat feeding phase). Following obesity induction, the HFD-CR group was acclimated to control low fat diet for 2 wks and then underwent 30% caloric restriction for 8 wks (caloric restriction feeding phase). The HFD group received 60% kcal high fat diet from ages 8 to 30 wks. LFD mice received control low fat 10% kcal diet for the study duration. Mice were euthanized at 30 wks of age. Body weight, body composition, and bone mineral density were recorded at baseline and at the end of each diet. Glucose and insulin tolerance were recorded at the end of the high fat and caloric restriction feeding phases. At euthanasia, cortical and trabecular bone morphology (µCT) were assessed.Adverse metabolic parameters worsened with high fat feeding but improved by caloric restriction. Compared to LFD animals, HFD and HFD-CR mice gained body weight, fat mass, and lean mass during the high fat feeding phase. After the caloric restriction feeding phase, body weight, fat mass, and lean mass were reduced in HFD-CR compared to both HFD and LFD controls (p &amp;lt; 0.0001). After 12 weeks of high fat feeding, glucose and insulin tolerance were reduced in HFD and HFD-CR mice compared to LFD (p &amp;lt; 0.0001). Caloric restriction improved both glucose and insulin tolerance in HFD-CR mice compared to both HFD and LFD animals (p &amp;lt; 0.0001). Caloric restriction improved areal bone mineral density, but at euthanasia, HFD-CR mice had worse bone morphology compared to LFD or HFD animals. Although areal bone mineral density (aBMD) was reduced by the high fat feeding phase, HFD-CR and LFD aBMD was not different at the end of the study (p &amp;lt; 0.0001). At euthanasia, HFD-CR mice had reduced cortical area and cortical thickness (p &amp;lt; 0.05). Marrow area and moment of inertia were not different between diets. Compared to LFD, both HFD and HFD-CR mice had reduced tibial bone volume fraction (p &amp;lt; 0.05). HFD-CR animals had smaller trabecular thickness (p &amp;lt; 0.05) and greater trabecular number (p &amp;lt; 0.01) compared to HFD mice. Despite improvements in components of systemic metabolism, caloric restriction in obese preclinical models reduced bone morphology in both trabecular and cortical compartments. This work will improve our understanding of the musculoskeletal system following caloric restriction in obese models and will aid in nutritional counseling for obese patients. Presentation: 6/1/2024

Exploring cortical morphology biomarkers of amnesic mild cognitive impairment using novel fractal dimension-based structural MRI analysis.

Amnestic mild cognitive impairment (aMCI) is considered as an intermediate stage of Alzheimer's disease, but no MRI biomarkers currently distinguish aMCI from healthy individuals effectively. Fractal dimension, a quantitative parameter, provides superior morphological information compared to conventional cortical thickness methods. Few studies have used cortical fractal dimension values to differentiate aMCI from healthy controls. In this study, we aim to build an automated discriminator for accurately distinguishing aMCI using fractal dimension measures of the cerebral cortex. Thirty aMCI patients and 30 health controls underwent structural MRI of the brain. First, the atrophy of participants' cortical sub-regions of Desikan-Killiany cortical atlas was assessed using fractal dimension and cortical thickness. The fractal dimension is more sensitive than cortical thickness in reducing dimensional effects and may accurately reflect morphological changes of the cortex in aMCI. The aMCI group had significantly lower fractal dimension values in the bilateral temporal lobes, right limbic lobe and right parietal lobe, whereas they showed significantly lower cortical thickness values only in the bilateral temporal lobes. Fractal dimension analysis was able to depict most of the significantly different focal regions detected by cortical thickness, but additionally with more regions. Second, applying the measured fractal dimensions (and cortical thickness) of both cerebral hemispheres, an unsupervised discriminator was built for the aMCI and healthy controls. The proposed fractal dimension-based method achieves 80.54% accuracy in discriminating aMCI from healthy controls. The fractal dimension appears to be a promising biomarker for cortical morphology changes that can discriminate patients with aMCI from healthy controls.

The cross-sectional morphology of the proximal femoral diaphysis is defined by the anteversion angle.

Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long-term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross-section to the external and internal borders based on CT images. Using this method, 44 sides of a female femoral skeleton specimen were examined and areas of protrusion and thickening in the medial anterior and lateral posterior regions just below the lesser trochanter were identified. These positions strongly correlated with the anteversion angle, suggesting the involvement of the distribution of the load received from body weight defined by the angle. The finite element method was used to examine the relationships between the positions of these areas with compressive and tensile stress distribution areas in the one-legged standing condition. The medial anterior region and lateral posterior region protruded and thickened in response to compressive and tensile stress, respectively. In addition, a hierarchical relationship was observed between the anteversion angle, tensile stress distribution, protrusion, and thickening in femurs with thinning of cortical bone, indicating that morphogenesis occurs adaptively to loading. The present results demonstrate the usefulness of this method in considering the formation mechanism and function of the femoral diaphysis and suggest that bone remodeling is necessary to maintain adaptability.

Association of cortical morphology, white matter hyperintensity, and glymphatic function in frontotemporal dementia variants.

Frontotemporal dementia (FTD) can be phenotypically divided into behavioral variant FTD (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). However, the neural underpinnings of this phenotypic heterogeneity remain elusive. Cortical morphology, white matter hyperintensities (WMH), diffusion tensor image analysis along the perivascular space (DTI-ALPS), and their interrelationships were assessed in subtypes of FTD. Neuroimaging-transcriptional analyses on the regional cortical morphological deviances among subtypes were also performed. Changes in cortical thickness, surface area, gyrification, WMH, and DTI-ALPS were subtype-specific in FTD. The three morphologic indices are related to whole-brain WMH volume and cognitive performance, while cortical thickness is related to DTI-ALPS. Neuroimaging-transcriptional analyses identified key biological pathways linked to the formation and/or spread of TDP-43/tau pathologies. We found subtype-specific changes in cortical morphology, WMH, and glymphatic function in FTD. Our findings have the potential to contribute to the development of personalized predictions and treatment strategies for this disorder. Cortical morphologic changes, white matter hyperintensities (WMH), and glymphatic dysfunction are subtype-specific. Cortical morphologic changes, WMH, and glymphatic dysfunction are inter-correlated. Cortical morphologic changes and WMH burden contribute to cognitive impairments.

Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples.

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals. CNV associations were assessed for replication in 235 SSD relatives and 583 controls, and 9,930 youth from the Adolescent Brain Cognitive Development (ABCD) Study. Known SSD- and neurodevelopmental disorder (NDD)-risk CNVs were associated with borderline intellectual functioning in SSD cases (odds ratios (OR) = 7.09 and 4.57, respectively); NDD-risk deletions were nominally associated with childhood-onset psychosis (OR = 4.34). Furthermore, deletion of genes involved in regulating gene expression during fetal brain development was associated with borderline intellectual functioning across SSD cases and non-cases (OR = 2.58), with partial replication in the ABCD cohort. Exploratory analyses of cortical morphology showed associations between fetal gene regulatory gene deletions and altered gray matter volume and cortical thickness across cohorts. Results highlight contributions of known risk CNVs to phenotypic variability in SSD and the utility of a neurodevelopmental framework for identifying mechanisms that influence phenotypic variability in SSDs, as well as the broader population, with implications for personalized medicine approaches to care.

The potential protective effect of propolis on diabetic nephropathy induced by streptozotocin in adult albino rats

ABSTRACT Diabetes mellitus is a common metabolic disorder. It is associated with serious life-threatening complications if not properly managed. The current study aimed at investigating the possible protective role of propolis on streptozotocin-induced diabetic nephropathy. A diabetic rat model was induced by a single intraperitoneal injection of 55 mg/kg streptozotocin. After 4 days, the diabetic rats received oral propolis (300 mg/kg/day) via gastric gavage for 28 days. Biochemical, histopathological and ultrastructural evaluations were performed. The results showed that: streptozotocin-induced diabetes was associated with a marked decrease in the serum high-density lipoproteins and antioxidant enzymes. However, a significant elevation in the levels of serum creatinine, blood urea nitrogen, uric acid, cholesterol, triglycerides and low-density lipoproteins was detected. Furthermore, streptozotocin treatment induced histopathological alterations of the renal cortex; in the form of distorted glomerular capillaries, widened Bowman’s space and signs of epithelial tubular degeneration. Ultra-structurally, thickening and irregularity of the glomerular basement membrane and podocytes foot processes effacement were observed. The tubular epithelial cells showed swollen vacuolated mitochondria, scarce basal infoldings and loss of microvilli. Conversely, propolis partially restored the normal lipid profile, antioxidant biomarkers and renal cortical morphology. Propolis exhibited a sort of renoprotection through hypoglycemic, anti-hyperlipidemic and antioxidant effects.