Cortical Morphology Research Articles

Cortical Morphology in Cannabis Use Disorder: Implications for Transcranial Direct Current Stimulation Treatment.

Transcranial direct current stimulation (tDCS) has been studied as an adjunctive treatment option for substance use disorders (SUDs). Alterations in brain structure following SUD may change tDCS-induced electric field (EF) and subsequent responses; however, group-level differences between healthy controls (HC) and participants with SUDs in terms of EF and its association with cortical architecture have not yet been modeled quantitatively. This study provides a methodology for group-level analysis of computational head models to investigate the influence of cortical morphology metrics on EFs. Whole-brain surface-based morphology was conducted, and cortical thickness, volume, and surface area were compared between participants with cannabis use disorders (CUD) (n=20) and age-matched HC (n=22). Meanwhile, EFs were simulated for bilateral tDCS over the dorsolateral prefrontal cortex. The effects of structural alterations on EF distribution were investigated based on individualized computational head models. Regarding EF, no significant difference was found within the prefrontal cortex; however, EFs were significantly different in left-postcentral and right-superior temporal gyrus (P<0.05) with higher levels of variance in CUD compared to HC [F(39, 43)=5.31, P<0.0001, C=0.95]. Significant differences were observed in cortical area (caudal anterior cingulate and rostral middle frontal), thickness (lateral orbitofrontal), and volume (paracentral and fusiform) between the two groups. Brain morphology and tDCS-induced EFs may be changed following CUD; however, differences between CUD and HCs in EFs do not always overlap with brain areas that show structural alterations. To sufficiently modulate stimulation targets, whether individuals with CUD need different stimulation doses based on tDCS target location should be checked.

Post-Concussion Symptom Burden Is Associated With Abnormal Cortical Morphology In Brain Areas Characterized By Inhibitory Interneuron Expression: An Imaging Transcriptomics Analysis Of CARE 1.0 Data

Post-Concussion Symptom Burden Is Associated With Abnormal Cortical Morphology In Brain Areas Characterized By Inhibitory Interneuron Expression: An Imaging Transcriptomics Analysis Of CARE 1.0 Data

Genetic risks of Alzheimer's by APOE and MAPT on cortical morphology in young healthy adults.

Genetic risk factors such as APOE ε4 and MAPT (rs242557) A allele are associated with amyloid and tau pathways and grey matter changes at both early and established stages of Alzheimer's disease, but their effects on cortical morphology in young healthy adults remain unclear. A total of 144 participants aged from 18 to 24 underwent 3T MRI and genotyping for APOE and MAPT to investigate unique impacts of these genetic risk factors in a cohort without significant comorbid conditions such as metabolic and cardiovascular diseases. We segmented the cerebral cortex into 68 regions and calculated the cortical area, thickness, curvature and folding index for each region. Then, we trained machine learning models to classify APOE and MAPT genotypes using these morphological features. In addition, we applied a growing hierarchical self-organizing maps algorithm, which clustered the 68 regions into 4 subgroups representing different morphological patterns. Then, we performed general linear model analyses to estimate the interaction between APOE and MAPT on cortical patterns. We found that the classifiers using all cortical features could accurately classify individuals carrying genetic risks of dementia outperforming each individual feature alone. APOE ε4 carriers had a more convoluted and thinner cortex across the cerebral cortex. A similar pattern was found in MAPT A allele carriers only in the regions that are vulnerable for early tau pathology. With the clustering analysis, we found a synergetic effect between APOE ε4 and MAPT A allele, i.e. carriers of both risk factors showed the most deviation of cortical pattern from the typical pattern of that cluster. Genetic risk factors of dementia by APOE ε4 and MAPT (rs242557) A allele were associated with variations of cortical morphology, which can be observed in young healthy adults more than 30 years before Alzheimer's pathology is likely to occur and 50 years before dementia symptoms may begin.

Cortical morphology in patients with the deficit and non-deficit syndrome of schizophrenia: a worldwide meta- and mega-analyses

Converging evidence suggests that schizophrenia (SZ) with primary, enduring negative symptoms (i.e., Deficit SZ (DSZ)) represents a distinct entity within the SZ spectrum while the neurobiological underpinnings remain undetermined. In the largest dataset of DSZ and Non-Deficit (NDSZ), we conducted a meta-analysis of data from 1560 individuals (168 DSZ, 373 NDSZ, 1019 Healthy Controls (HC)) and a mega-analysis of a subsampled data from 944 individuals (115 DSZ, 254 NDSZ, 575 HC) collected across 9 worldwide research centers of the ENIGMA SZ Working Group (8 in the mega-analysis), to clarify whether they differ in terms of cortical morphology. In the meta-analysis, sites computed effect sizes for differences in cortical thickness and surface area between SZ and control groups using a harmonized pipeline. In the mega-analysis, cortical values of individuals with schizophrenia and control participants were analyzed across sites using mixed-model ANCOVAs. The meta-analysis of cortical thickness showed a converging pattern of widespread thinner cortex in fronto-parietal regions of the left hemisphere in both DSZ and NDSZ, when compared to HC. However, DSZ have more pronounced thickness abnormalities than NDSZ, mostly involving the right fronto-parietal cortices. As for surface area, NDSZ showed differences in fronto-parietal-temporo-occipital cortices as compared to HC, and in temporo-occipital cortices as compared to DSZ. Although DSZ and NDSZ show widespread overlapping regions of thinner cortex as compared to HC, cortical thinning seems to better typify DSZ, being more extensive and bilateral, while surface area alterations are more evident in NDSZ. Our findings demonstrate for the first time that DSZ and NDSZ are characterized by different neuroimaging phenotypes, supporting a nosological distinction between DSZ and NDSZ and point toward the separate disease hypothesis.

Single-subject cortical morphological brain networks across the adult lifespan.

Age-related changes in focal cortical morphology have been well documented in previous literature; however, how interregional coordination patterns of the focal cortical morphology reorganize with advancing age is not well established. In this study, we performed a comprehensive analysis of the topological changes in single-subject morphological brain networks across the adult lifespan. Specifically, we constructed four types of single-subject morphological brain networks for 650 participants (aged from 18 to 88 years old), and characterized their topological organization using graph-based network measures. Age-related changes in the network measures were examined via linear, quadratic, and cubic models. We found profound age-related changes in global small-world attributes and efficiency, local nodal centralities, and interregional similarities of the single-subject morphological brain networks. The age-related changes were mainly embodied in cortical thickness networks, involved in frontal regions and highly connected hubs, concentrated on short-range connections, characterized by linear changes, and susceptible to connections between limbic, frontoparietal, and ventral attention networks. Intriguingly, nonlinear (i.e., quadratic or cubic) age-related changes were frequently found in the insula and limbic regions, and age-related cubic changes preferred long-range morphological connections. Finally, we demonstrated that the morphological similarity in cortical thickness between two frontal regions mediated the relationship between age and cognition measured by Cattell scores. Taken together, these findings deepen our understanding of adaptive changes of the human brain with advancing age, which may account for interindividual variations in behaviors and cognition.

Quantitative analysis of mandibular cortical morphology using artificial intelligence-based computer assisted diagnosis for panoramic radiography on underlying diseases and dental status in women over 20 years of age

Background/purposeRecently, an artificial intelligence-based computer-assisted diagnosis (AI-CAD) for panoramic radiography was developed to scan the inferior margin of the mandible and automatically evaluate mandibular cortical morphology. The aim of this study was to analyze quantitatively the mandibular cortical morphology using the AI-CAD, especially focusing on underlying diseases and dental status in women over 20 years of age. Materials and methods419 patients in women over 20 years of age who underwent panoramic radiography were included in this study. The mandibular cortical morphology was analyzed with an AI-CAD that evaluated the degree of deformation of the mandibular inferior cortex (MIC) and mandibular cortical index (MCI) automatically. Those were analyzed in relation to underlying diseases, such as diabetes, hypertension, dyslipidemia, rheumatism and osteoporosis, and dental status, such as the number of teeth present in the maxilla and mandible. ResultsThe degree of deformation of MIC in women under 51 years of age (21–50 years; n = 229, 16.0 ± 12.7) was significantly lower than those of over 50 years of age (51–90 years; n = 190, 45.1 ± 23.0), and the MCI was a significant difference for the different age group. Regarding the degree of deformation of MIC and MCI in women over 50 years of age, osteoporosis and number of total teeth present in the maxilla and mandible were significant differences. ConclusionThe results of this study indicated that the mandibular cortical morphology using the AI-CAD is significantly related to osteoporosis and dental status in women over 50 years of age.

Altered functional connectivity and network excitability in a model of cortical dysplasia

Focal cortical dysplasias (FCDs) are malformations of cortical development that often result in medically refractory epilepsy, with a greater incidence in the pediatric population. The relationship between the disturbed cortical morphology and epileptogenic activity of FCDs remains unclear. We used the BCNU (carmustine 1-3-bis-chloroethyl-nitrosourea) animal model of cortical dysplasia to evaluate neuronal and laminar alterations and how these result in altered activity of intracortical networks in early life. We corroborated the previously reported morphological anomalies characteristic of the BCNU model, comprising slightly larger and rounder neurons and abnormal cortical lamination. Next, the neuronal activity of live cortical slices was evaluated through large field-of-view calcium imaging as well as the neuronal response to a stimulus that leads to cortical hyperexcitability (pilocarpine). Examination of the joint activity of neuronal calcium time series allowed us to identify intracortical communication patterns and their response to pilocarpine. The baseline power density distribution of neurons in the cortex of BCNU-treated animals was different from that of control animals, with the former showing no modulation after stimulus. Moreover, the intracortical communication pattern differed between the two groups, with cortexes from BCNU-treated animals displaying decreased inter-layer connectivity as compared to control animals. Our results indicate that the altered anatomical organization of the cortex of BCNU-treated rats translates into altered functional networks that respond abnormally to a hyperexcitable stimulus and highlight the role of network dysfunction in the pathophysiology of cortical dysplasia.

Chromosomal inversion polymorphisms shape human brain morphology

The impact of chromosomal inversions on human brain morphology remains underexplored. We studied 35 common inversions classified from genotypes of 33,018 adults with European ancestry. The inversions at 2p22.3, 16p11.2, and 17q21.31 reach genome-wide significance, followed by 8p23.1 and 6p21.33, in their association with cortical and subcortical morphology. The 17q21.31, 8p23.1, and 16p11.2 regions comprise the LRRC37, OR7E, and NPIP duplicated gene families. We find the 17q21.31 MAPT inversion region, known for harboring neurological risk, to be the most salient locus among common variants for shaping and patterning the cortex. Overall, we observe the inverted orientations decreasing brain size, with the exception that the 2p22.3 inversion is associated with increased subcortical volume and the 8p23.1 inversion is associated with increased motor cortex. These significant inversions are in the genomic hotspots of neuropsychiatric loci. Our findings are generalizable to 3,472 children and demonstrate inversions as essential genetic variation to understand human brain phenotypes.

Causality between inflammatory bowel disease and the cerebral cortex: insights from Mendelian randomization and integrated bioinformatics analysis.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, progressive, and recurrent intestinal condition that poses a significant global health burden. The high prevalence of neuropsychiatric comorbidities in IBD necessitates the development of targeted management strategies. Leveraging genetic data from genome-wide association studies and Immunochip genotype analyses of nearly 150,000 individuals, we conducted a two-sample Mendelian randomization study to elucidate the driving force of IBD, UC, and CD on cortical reshaping. Genetic variants mediating the causality were collected to disclose the biological pathways linking intestinal inflammation to brain dysfunction. Here, 115, 69, and 98 instrumental variables genetically predicted IBD, UC, and CD. We found that CD significantly decreased the surface area of the temporal pole gyrus (β = -0.946 mm2, P = 0.005, false discovery rate-P = 0.085). Additionally, we identified suggestive variations in cortical surface area and thickness induced by exposure across eight functional gyri. The top 10 variant-matched genes were STAT3, FOS, NFKB1, JAK2, STAT4, TYK2, SMAD3, IL12B, MYC, and CCL2, which are interconnected in the interaction network and play a role in inflammatory and immune processes. We explore the causality between intestinal inflammation and altered cortical morphology. It is likely that neuroinflammation-induced damage, impaired neurological function, and persistent nociceptive input lead to morphological changes in the cerebral cortex, which may trigger neuropsychiatric disorders.

Structural brain morphology in young adult women who have been choked/strangled during sex: A whole-brain surface morphometry study.

Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18-30 years old) who were exposed to frequent sexual choking and their choking naïve controls. This cross-sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs. choking-naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High-resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth). Forty-one participants (choking n=20; choking-naïve n=21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking-naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking-naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi-directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex. These data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.

Heroin Self-Administration and Extinction Increase Prelimbic Cortical Astrocyte-Synapse Proximity and Alter Dendritic Spine Morphometrics That Are Reversed by N-Acetylcysteine.

Clinical and preclinical studies indicate that adaptations in corticostriatal neurotransmission significantly contribute to heroin relapse vulnerability. In animal models, heroin self-administration and extinction produce cellular adaptations in both neurons and astrocytes within the nucleus accumbens (NA) core that are required for cue-induced heroin seeking. Specifically, decreased glutamate clearance and reduced association of perisynaptic astrocytic processes with NAcore synapses allow glutamate release from prelimbic (PrL) cortical terminals to engage synaptic and structural plasticity in NAcore medium spiny neurons. Normalizing astrocyte glutamate homeostasis with drugs like the antioxidant N-acetylcysteine (NAC) prevents cue-induced heroin seeking. Surprisingly, little is known about heroin-induced alterations in astrocytes or pyramidal neurons projecting to the NAcore in the PrL cortex (PrL-NAcore). Here, we observe functional adaptations in the PrL cortical astrocyte following heroin self-administration (SA) and extinction as measured by the electrophysiologically evoked plasmalemmal glutamate transporter 1 (GLT-1)-dependent current. We likewise observed the increased complexity of the glial fibrillary acidic protein (GFAP) cytoskeletal arbor and increased association of the astrocytic plasma membrane with synaptic markers following heroin SA and extinction training in the PrL cortex. Repeated treatment with NAC during extinction reversed both the enhanced astrocytic complexity and synaptic association. In PrL-NAcore neurons, heroin SA and extinction decreased the apical tuft dendritic spine density and enlarged dendritic spine head diameter in male Sprague-Dawley rats. Repeated NAC treatment during extinction prevented decreases in spine density but not dendritic spine head expansion. Moreover, heroin SA and extinction increased the co-registry of the GluA1 subunit of AMPA receptors in both the dendrite shaft and spine heads of PrL-NAcore neurons. Interestingly, the accumulation of GluA1 immunoreactivity in spine heads was further potentiated by NAC treatment during extinction. Finally, we show that the NAC treatment and elimination of thrombospondin 2 (TSP-2) block cue-induced heroin relapse. Taken together, our data reveal circuit-level adaptations in cortical dendritic spine morphology potentially linked to heroin-induced alterations in astrocyte complexity and association at the synapses. Additionally, these data demonstrate that NAC reverses PrL cortical heroin SA-and-extinction-induced adaptations in both astrocytes and corticostriatal neurons.

Transcriptional expression of radiation-induced early cortical morphological alterations and its association with radiation necrosis in patients with nasopharyngeal carcinoma

PurposeTo explore the effects of standard radiotherapy on cortical morphology and its potential transcriptional expression, and to determine the predictive power of cortical morphological measurement at the early stage for radiation necrosis (RN) occurrence within 3 years post-radiotherapy in patients with nasopharyngeal carcinoma (NPC). Methods185 NPC patients participated. Pre-treatment and post-radiotherapy (1–3 months) structural MRI were collected longitudinally and prospectively. Multiple cortical morphological indices were compared between pre-treatment and post-radiotherapy. Brain-wide gene expression was used to assess the transcriptional profiles associated with radiation-induced cortical morphological changes. Machine learning was used to construct predictive models for RN with cortical morphological alterations at the early stage. ResultsRelative to pre-treatment, NPC patients exhibited a widespread reduction in cortical volume (CV) and cortical thickness (CT) post-radiotherapy (p < 0.001). Partial least squares regression analysis revealed that radiotherapy-related cortical atrophy was closely related to transcriptional profiles (p < 0.001), with the most correlated genes enriched in ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Furthermore, models constructed with cortical morphological features at 1–3 months post-radiotherapy had favorable predictive power for RN occurrence in NPC patients within 3-year follow-up, the area under the curve was 0.854 and 0.843 for CV and CT, respectively. ConclusionsNPC patients exhibited widespread cortical atrophy at 1–3 months post-radiotherapy, which was closely correlated with dysfunction of the ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Cortical morphology at 1–3 months post-radiotherapy may serve as an early biomarker for identifying RN.

The hierarchical organization of the precuneus captured by functional gradients

The precuneus shows considerable heterogeneity in multiple dimensions including anatomy, function, and involvement in brain disorders. Leveraging the state-of-the-art functional gradient approach, we aimed to investigate the hierarchical organization of the precuneus, which may hold promise for a unified understanding of precuneus heterogeneity. Resting-state functional MRI data from 793 healthy individuals were used to discover and validate functional gradients of the precuneus, which were calculated based on the voxel-wise precuneus-to-cerebrum functional connectivity patterns. Then, we further explored the potential relationships of the precuneus functional gradients with cortical morphology, intrinsic geometry, canonical functional networks, and behavioral domains. We found that the precuneus principal and secondary gradients showed dorsoanterior-ventral and ventroposterior-dorsal organizations, respectively. Concurrently, the principal gradient was associated with cortical morphology, and both the principal and secondary gradients showed geometric distance dependence. Importantly, precuneus functional subdivisions corresponding to canonical functional networks (behavioral domains) were distributed along both gradients in a hierarchical manner, i.e., from the sensorimotor network (somatic movement and sensation) at one extreme to the default mode network (abstract cognitive functions) at the other extreme for the principal gradient and from the visual network (vision) at one end to the dorsal attention network (top-down control of attention) at the other end for the secondary gradient. These findings suggest that the precuneus functional gradients may provide mechanistic insights into the multifaceted nature of precuneus heterogeneity.

Functional connectivity gradients of the cingulate cortex

Heterogeneity of the cingulate cortex is evident in multiple dimensions including anatomy, function, connectivity, and involvement in networks and diseases. Using the recently developed functional connectivity gradient approach and resting-state functional MRI data, we found three functional connectivity gradients that captured distinct dimensions of cingulate hierarchical organization. The principal gradient exhibited a radiating organization with transitions from the middle toward both anterior and posterior parts of the cingulate cortex and was related to canonical functional networks and corresponding behavioral domains. The second gradient showed an anterior–posterior axis across the cingulate cortex and had prominent geometric distance dependence. The third gradient displayed a marked differentiation of subgenual and caudal middle with other parts of the cingulate cortex and was associated with cortical morphology. Aside from providing an updated framework for understanding the multifaceted nature of cingulate heterogeneity, the observed hierarchical organization of the cingulate cortex may constitute a novel research agenda with potential applications in basic and clinical neuroscience.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis

BackgroundChoosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment.MethodsParticipants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R2 for regression, and decision curve analysis.ResultsSix risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867–0.881), R2 = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841–0.861), R2 = 0.507].ConclusionsThis study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry (https://www.chictr.org.cn/), 18. Aug 2009 retrospectively registered: CAPOC—ChiCTR-RNC-09000521 (https://www.chictr.org.cn/showproj.aspx?proj=9014), CAPEC—ChiCTR-RNC-09000522 (https://www.chictr.org.cn/showproj.aspx?proj=9013).

Evaluation of mandibular cortical and trabecular radiomorphometry in familial Mediterranean fever patients

The objective of this retrospective study was to evaluate the mandibular cortical and trabecular morphology and microarchitecture of patients with familial Mediterranean fever (FMF) and compare them to those of healthy individuals by examining radiomorphometric indices on panoramic radiographs. We examined a group of 56 FMF patients aged 5 to 71 years and an age- and sex-matched control group of individuals with no systemic diseases. We classified the FMF and control groups according to age and sex and the FMF group according to colchicine use. We evaluated the quantitative radiomorphometic indices of gonial index, antegonial index, molar cortical thickness, mental index, panoramic mandibular index, and lacunarity, and the qualitative mandibular cortical index on all panoramic radiographs and performed between and within group analysis. Mean gonial index, antegonial index, and molar cortical thickness values of the FMF group were significantly smaller than those of the control group. Significantly fewer patients in the FMF group were classified as mandibular cortical index type 1 compared to the control group. There were no significant differences in quantitative index values according to colchicine use in the FMF group or regarding the categorical parameters of age, sex, and mandibular cortical index classification. Radiomorphometric values of the mandibular basal cortex posterior to the mental foramen differ significantly in FMF patients compared to healthy counterparts. Dentists should note mandibular morphologic changes indicative of low bone density when examining panoramic images of patients with this disease.

Corneal Edema in Inducible Slc4a11 Knockout Is Initiated by Mitochondrial Superoxide Induced Src Kinase Activation.

Inducible Slc4a11 KO leads to corneal edema by disruption of the pump and barrier functions of the corneal endothelium (CE). The loss of Slc4a11 NH3-activated mitochondrial uncoupling leads to mitochondrial membrane potential hyperpolarization-induced oxidative stress. The goal of this study was to investigate the link between oxidative stress and the failure of pump and barrier functions and to test different approaches to revert the process. Mice which were homozygous for Slc4a11 Flox and Estrogen receptor -Cre Recombinase fusion protein alleles at 8 weeks of age were fed Tamoxifen (Tm)-enriched chow (0.4 g/Kg) for 2 weeks, and controls were fed normal chow. During the initial 14 days, Slc4a11 expression, corneal thickness (CT), stromal [lactate], Na+-K+ ATPase activity, mitochondrial superoxide levels, expression of lactate transporters, and activity of key kinases were assessed. In addition, barrier function was assessed by fluorescein permeability, ZO-1 tight junction integrity, and cortical cytoskeleton F-actin morphology. Tm induced a rapid decay in Slc4a11 expression that was 84% complete at 7 days and 96% complete at 14 days of treatment. Superoxide levels increased significantly by day 7; CT and fluorescein permeability by day 14. Tight junction ZO-1 distribution and the cortical cytoskeleton were disrupted at day 14, concomitant with decreased expression of Cldn1, yet with increased tyrosine phosphorylation. Stromal lactate increased by 60%, Na+-K+ ATPase activity decreased by 40%, and expression of lactate transporters MCT2 and MCT4 significantly decreased, but MCT1 was unchanged at 14 days. Src kinase was activated, but not Rock, PKCα, JNK, or P38Mapk. Mitochondrial antioxidant Visomitin (SkQ1, mitochondrial targeted antioxidant) and Src kinase inhibitor eCF506 significantly slowed the increase in CT, with concomitant decreased stromal lactate retention, improved barrier function, reduced Src activation and Cldn1 phosphorylation, and rescued MCT2 and MCT4 expression. Slc4a11 KO-induced CE oxidative stress triggered increased Src kinase activity that resulted in perturbation of the pump components and barrier function of the CE.

Association of Preterm Birth and Socioeconomic Status With Neonatal Brain Structure

Preterm birth and socioeconomic status (SES) are associated with brain structure in childhood, but the relative contributions of each during the neonatal period are unknown. To investigate associations of birth gestational age (GA) and SES with neonatal brain morphology by testing 3 hypotheses: GA and SES are associated with brain morphology; associations between SES and brain morphology vary with GA; and associations between SES and brain structure and morphology depend on how SES is operationalized. This cohort study recruited participants from November 2016 to September 2021 at a single center in the United Kingdom. Participants were 170 extremely and very preterm infants and 91 full-term or near-term infants. Exclusion criteria were major congenital malformation, chromosomal abnormality, congenital infection, cystic periventricular leukomalacia, hemorrhagic parenchymal infarction, and posthemorrhagic ventricular dilatation. Birth GA and SES, operationalized at the neighborhood level (using the Scottish Index of Multiple Deprivation), the family level (using parental education and occupation), and subjectively (World Health Organization Quality of Life measure). Brain volume (85 parcels) and 5 whole-brain cortical morphology measures (gyrification index, thickness, sulcal depth, curvature, surface area) at term-equivalent age (median [range] age, 40 weeks, 5 days [36 weeks, 2 days to 45 weeks, 6 days] and 42 weeks [38 weeks, 2 days to 46 weeks, 1 day] for preterm and full-term infants, respectively). Participants were 170 extremely and very preterm infants (95 [55.9%] male; 4 of 166 [2.4%] Asian, 145 of 166 [87.3%] White) and 91 full-term or near-term infants (50 [54.9%] male; 3 of 86 [3.5%] Asian, 78 of 86 [90.7%] White infants) with median (range) birth GAs of 30 weeks, 0 days (22 weeks, 1 day, to 32 weeks, 6 days) and 39 weeks, 4 days (36 weeks, 3 days, to 42 weeks, 1 day), respectively. In fully adjusted models, birth GA was associated with a higher proportion of brain volumes (27 of 85 parcels [31.8%]; β range, -0.20 to 0.24) than neighborhood-level SES (1 of 85 parcels [1.2%]; β = 0.17 [95% CI, -0.16 to 0.50]) or family-level SES (maternal education: 4 of 85 parcels [4.7%]; β range, 0.09 to 0.15; maternal occupation: 1 of 85 parcels [1.2%]; β = 0.06 [95% CI, 0.02 to 0.11] respectively). There were interactions between GA and both family-level and subjective SES measures on regional brain volumes. Birth GA was associated with cortical surface area (β = 0.10 [95% CI, 0.02 to 0.18]) and gyrification index (β = 0.16 [95% CI, 0.07 to 0.25]); no SES measure was associated with cortical measures. In this cohort study of UK infants, birth GA and SES were associated with neonatal brain morphology, but low GA had more widely distributed associations with neonatal brain structure than SES. Further work is warranted to elucidate the mechanisms underlying the association of both GA and SES with early brain development.

HISTOLOGICAL AND MORPHOMETRIC STUDIES OF BONE TISSUE AUTOGRAFTS FROM INTRAORAL AND EXTRAORAL DONOR ZONES

Major research carried out in modern dentistry and maxillofacial surgery is commonly focused on long-term and stable results for implant rehabilitation of jaw defects and deformities in patients with bone and soft tissue losses at the site of planned implantation. Various osteoplastic materials, donor or the patient’s own bone, tissue-engineering and cellular products are common in clinical medicine, since guided regeneration can help not only recover the volume of bone tissue once lost, yet also ensure an outcome acceptable from both functional and aesthetic view. Guided bone regeneration employs methods of regenerative medicine and tissue engineering, with transplantation of native bone tissue and cell transplants, as well as various osteoplastic materials with osteoinductive and osteoconductive properties. In order to compare the structure of intact bone tissue obtained from intraoral and extraoral donor zones, histological and morphometric studies of bone autografts in 4 certified male cadavers with intact dentition were carried out. The results of histological studies in bone tissue autografts from intraoral and extraoral donor zones revealed that the highest density of bone rods could be observed in biopsies taken from the mandible outer oblique line area and chin symphysis. Whereas the lowest rate of the said factor we observed in the biopsies obtained from the iliac crest area. The highest rate of the inter-rod girder space was found in the area of the iliac crest, and the minimal – in biopsies from the parietal bone. The highest bone vascularization level was identified at the iliac crest and the parietal bone, while its lowest levels were seen in biopsies taken from the area of the mandible outer oblique line. The density of cellular elements was found to be highest at the iliac crest. The lowest density level was registered in biopsies from the area of the mandible outer oblique line. The high rates of cellular elements in autografts from the iliac crest area can be accounted for by the predominance of spongy substance over cortical, while in bone biopsies taken from the mandible outer oblique line, chin symphysis, maxillary tuberosity and parietal bone, the share of cellular elements failed to exceed 27% within the total data set. This points at the predominance of cortical rather than spongy substance. In reconstructive bone plastic surgery for augmentation of the maxillary alveolar process and the mandible alveolar part with significant atrophy, it is reasonable to use autogenous transplants taken from intraoral donor zones. The autogenous transplants have cortical morphology and embryological origin similar to the jaw bones. Bone blocks from the donor zones of the mandible outer oblique line, the chin symphysis and the maxillary tuberosity have the highest density of the bone cortical substance and the duly sufficient amount of spongy substance.

Traumatic brain injury alters the relationship between brain structure and episodic memory.

Focal and diffuse pathology resulting from traumatic brain injury (TBI) often disrupts brain circuitry that is critical for episodic memory, including medial temporal lobe and prefrontal regions. Prior studies have focused on unitary accounts of temporal lobe function, associating verbally learned material and brain morphology. Medial temporal lobe structures, however, are domain-sensitive, preferentially supporting different visual stimuli. There has been little consideration of whether TBI preferentially disrupts the type of visually learned material and its association with cortical morphology following injury. Here, we investigated whether (1) episodic memory deficits differ according to the stimulus type, and (2) the pattern in memory performance can be linked to changes in cortical thickness. Forty-three individuals with moderate-severe TBI and 38 demographically similar healthy controls completed a recognition task in which memory was assessed for three categories of stimuli: faces, scenes, and animals. The association between episodic memory accuracy on this task and cortical thickness was subsequently examined within and between groups. Our behavioral results support the notion of category-specific impairments: the TBI group had significantly impaired accuracy for memory for faces and scenes, but not animals. Moreover, the association between cortical thickness and behavioral performance was only significant for faces between groups. Taken together, these behavioral and structural findings provide support for an emergent memory account, and highlight that cortical thickness differentially affects episodic memory for specific categories of stimuli.