Reduction In Cortical Thickness Research Articles

Focal Cortical Dysplasia: Diagnosis, Classification, and Treatment Options

AbstractFocal cortical dysplasias (FCDs) include a spectrum of anomalies of cortical development that consist in one or more areas with altered lamination and in some cases, neurons of abnormal morphology. Clinically, these structural anomalies led to arise of epilepsy, which is more often a focal, drug-resistant type with onset in pediatric or adolescent age. Occasionally, other symptoms have been reported in patients with FCDs, such as headache, movement disorders, and cognitive impairment. According to International League against Epilepsy scheme of 2011, three main subtypes of FCD can be distinguished, based of anatomopathological feature, radiological signs, and clinical expression. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography, and neurophysiology are the cornerstones of diagnosis, although their negativity cannot exclude FCD in symptomatic patients, especially in FCD type I which often is elusive. In MRI, the main finding is the irregularity of the cortical–subcortical signal, specifically reduction of cortical thickness and absence of clear demarcation between gray and white matters, which is strongly diagnostic for FCD. Epilepsy related to FCD is difficult to manage and until now there is not a clear direction for treatment's rules. FCD shows poor response to antiepileptic drugs (AEDs), and there is no evidence of some AED that has proved more efficacy than others in patients with FCDs. Considering genetical and pathophysiological recent acquisitions, mammalian target of rapamycin inhibitors may play a fundamental role in future treatment of FCDs, but nowadays, surgery still remains the main weapon, with 50% of patients who undergo neurosurgery.

Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study

BackgroundStimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood.PurposeInvestigate the long-term age-dependent effects of stimulant medication use on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD.MethodsThis prospective study included the baseline and 4-year follow-up assessment of the “effects of Psychotropic drugs On the Developing brain-MPH” (“ePOD-MPH”) project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness.ResultsA total of 32 male adolescents (aged mean ± SD, 11.2 ± 0.9 years at baseline) and 24 men (aged mean ± SD, 29.9 ± 5.0 years at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and more improvement of ADHD symptoms was associated with higher medication use in adults (P=0.001).ConclusionWe found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development.

Longitudinal study investigating the influence of COMT gene polymorphism on cortical thickness changes in Parkinson's disease over four years.

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting over 3% of those over 65. It's caused by reduced dopaminergic neurons and Lewy bodies, leading to motor and non-motor symptoms. The relationship between COMT gene polymorphisms and PD is complex and not fully elucidated. Some studies have reported associations between certain COMT gene variants and PD risk, while others have not found significant associations. This study investigates how COMT gene variations impact cortical thickness changes in PD patients over time, aiming to link genetic factors, especially COMT gene variations, with PD progression. This study analyzed data from 44 PD patients with complete 4-year imaging follow-up from the Parkinson Progression Marker Initiative (PPMI) database. Magnetic resonance imaging (MRI) scans were acquired using consistent methods across 9 different MRI scanners. COMT single-nucleotide polymorphisms (SNPs) were assessed based on whole genome sequencing data. Longitudinal image analysis was conducted using FreeSurfer's processing pipeline. Linear mixed-effect models were employed to examine the interaction effect of genetic variations and time on cortical thickness, while controlling for covariates and subject-specific variations. The rs165599 SNP stands out as a potential contributor to alterations in cortical thickness, showing a significant reduction in overall mean cortical thickness in both hemispheres in homozygotes (Left: P = 0.023, Right: P = 0.028). The supramarginal, precentral, and superior frontal regions demonstrated significant bilateral alterations linked to rs165599. Our findings suggest that the rs165599 variant leads to earlier manifestation of cortical thinning during the course of the disease. However, it does not result in more severe cortical thinning outcomes over time. There is a need for larger cohorts and control groups to validate these findings and consider genetic variant interactions and clinical features to elucidate the specific mechanisms underlying COMT-related neurodegenerative processes in PD.

Correlation Between Cortical Thickness Abnormalities of the Olfactory Sulcus and Olfactory Identification Disorder and Persistent Auditory Verbal Hallucinations in Chinese Patients With Chronic Schizophrenia.

Persistent auditory verbal hallucinations (pAVHs) and olfactory identification impairment are common in schizophrenia (SCZ), but the neuroimaging mechanisms underlying both pAVHs and olfactory identification impairment are unclear. This study aimed to investigate whether pAVHs and olfactory identification impairment in SCZ patients are associated with changes in cortical thickness. In this study, cortical thickness was investigated in 78 SCZ patients with pAVHs (pAVH group), 58 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) using 3T magnetic resonance imaging. The severity of pAVHs was assessed by the Auditory Hallucination Rating Scale. Olfactory identification deficits were assessed using the Odor Stick Identification Test for Japanese (OSIT-J). In addition, the relationship between the severity of pAVHs and olfactory identification disorder and cortical thickness abnormalities was determined. Significant reductions in cortical thickness were observed in the right medial orbital sulcus (olfactory sulcus) and right orbital sulcus (H-shaped sulcus) in the pAVH group compared to both the non-AVH and HC groups (P < .003, Bonferroni correction). Furthermore, the severity of pAVHs was found to be negatively correlated with the reduction in cortical thickness in the olfactory sulcus and H-shaped sulcus. Additionally, a decrease in cortical thickness in the olfactory sulcus showed a positive correlation with the OSIT-J scores (P < .05, false discovery rate correction). Cortical thickness abnormalities in the olfactory sulcus may be a common neuroimaging mechanism for pAVHs and olfactory identification deficits in SCZ patients.

Brain morphometry in former American football players: Findings from the DIAGNOSE CTE research project.

Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.

Alveolar Bone and Gingival Changes in Mandibular Anterior Region Following Herbst Appliance Therapy: A Systematic Review and Meta-analysis.

To assess the alveolar bone changes and gingival recession following Herbst appliance therapy. Electronic databases such as PubMed, Ovid, Cochrane Library, Lilacs, Scopus, Web of Science, and Embase were searched until August 2022. Hand-searching of major orthodontic journals was performed to identify all peer-reviewed articles potentially relevant to the review. The quality of the selected studies was ranked using the revised Cochrane risk of bias tool for nonrandomized trials-Risk of Bias In Nonrandomized Studies (ROBINS) 1. Five relevant articles (all nonrandomized studies) were considered for qualitative analysis. The risk of bias was low for four studies and moderate for one. The reduction in the vertical alveolar bone height was 0.13 ± 0.07 mm, with the Herbst appliance. The mean difference in the loss of buccal cortical thickness between the Herbst appliance and untreated control group was 0.22 mm [95% confidence interval (CI) of -0.62-0.18]. Subsequent to Herbst appliance therapy, in the mandibular anterior region 0.1 ± 0.5 mm of gingival recession was observed. Herbst appliance treatment produces a negligible reduction in the buccal cortical thickness, vertical alveolar bone height, and gingival recession. Though the changes produced by the Herbst appliance were minimal, they are clinically important considering the young age of the patients warranting periodic periodontal assessment. Kumar MV, Kannan A, Kailasam V. Alveolar Bone and Gingival Changes in Mandibular Anterior Region Following Herbst Appliance Therapy: A Systematic Review and Meta-analysis. Int J Clin Pediatr Dent 2024;17(1):114-120.

Correlation between frailty and reduction in cortical thickness in patients with chronic obstructive pulmonary disease

Physical inactivity and cognitive impairment in patients with chronic obstructive pulmonary disease (COPD) can lead to frailty and poor prognoses. However, little is known regarding the association between frailty and the human brain. We hypothesized that the brain structure could change according to frailty in patients with COPD and focused on cortical thickness. Cortical thickness measured by magnetic resonance imaging and frailty scores using the Kihon Checklist (KCL) were assessed in 40 patients with stable COPD and 20 healthy controls. Among the 34 regions assessed, multiple regions were thinner in patients with COPD than in healthy individuals (p < 0.05). We found significant negative correlations between the eight regions and the KCL scores only in patients with COPD. After adjusting for age and cognitive impairment, the association between the left and six right regions remained statistically significant. The correlation coefficient was the strongest in the bilateral superior frontal gyrus (left: ρ = − 0.5319, p = 0.0006) (right: ρ = − 0.5361, p = 0.0005). Interestingly, among the KCL scores, the daily activity domain showed the strongest correlation (sensitivity, 90%; specificity, 73%) with the bottom quartile of the reduction in the superior frontal gyrus. Frailty in patients with COPD is associated with a thickness reduction in the cortical regions, reflecting social vulnerability.

May anti-seizure medications alter brain structure in temporal lobe epilepsy? A prospective study.

Mild mesial temporal lobe epilepsy (MTLE) patients may remain untreated for a considerable time after disease onset or achieve seizure control with a single anti-seizures medication (ASM). Thus, they represent an optimal population to investigate whether ASMs might have influence on brain structure. We consecutively enrolled 56 mild MTLE patients (22/56 untreated, 34/56 on-monotherapy) and 58 healthy controls, matched for age and gender. All subjects underwent 3T-brain MRI, using FreeSurfer for automated morphometry. Differences in gray matter were assessed using one-way Analysis of Covariance (ANCOVA), adjusting for age, disease duration and intracranial volume. No significant change was observed between treated and untreated patients. We observed a significant reduction in cortical thickness of left inferior parietal, inferior temporal, middle temporal gyri, and right inferior parietal gyrus, temporal pole in monotherapy patients compared to healthy controls, as well as an increase in left isthmus of cingulate gyrus in untreated MTLE subjects compared to controls. Surface and subcortical volumes analysis revealed no differences among groups. Our study demonstrated no substantial morphological abnormalities between untreated mild MTLE patients and those undergoing monotherapy. Although exploratory, these results may reassure about safety of commonly used drugs and their marginal role in influencing neuroimaging results. PLAIN LANGUAGE SUMMARY: This study investigated the following question: can medications against epileptic seizures have an effect on brain structure in mild mesial temporal lobe? Preliminary results from our analyses suggest not, as we did not find any difference in brain gray matter between untreated patients and those treated with a single anti-seizures medication. On the other hand, epilepsy patients presented cortical thinning compared to healthy controls in several regions of the temporal and parietal lobes, in line with previous studies investigating the disease.

Facial emotion recognition deficits are associated with hypomimia and related brain correlates in Parkinson's disease.

Hypomimia is a frequent manifestation in Parkinson's disease (PD) that can affect interpersonal relationships and quality of life. Recent studies have suggested that hypomimia is not only related to motor dysfunction but also to impairment in emotional processing networks. Therefore, we hypothesized that the severity of hypomimia could be associated with performance on a task aimed at assessing facial emotion recognition. In this study, we explored the association between hypomimia, recognition of facial expressions of basic emotions using the Ekman 60 Faces Test (EF), and brain correlates of both hypomimia and performance on the EF. A total of 94 subjects underwent clinical assessments (neurological and neuropsychological examinations), and 56 of them participated in the neuroimaging study. We found significant correlation between hypomimia, EF Disgust (r = -0.242, p = 0.022) and EF Happiness (r = -0.264, p = 0.012); an independent reduction in Cortical Thickness (Cth) in the postcentral gyrus, insula, middle and superior temporal gyri, supramarginal gyrus, banks of the superior temporal sulcus, bilateral fusiform gyri, entorhinal cortex, parahippocampal gyrus, inferior and superior parietal cortex, and right cuneus and precuneus; and multiple correlations between negative emotions such as EF Disgust or EF Anger and a reduced Cth in fronto-temporo-parietal regions. In conclusion, these results suggest that the association between hypomimia and emotion recognition deficits in individuals with PD might be mediated by shared circuits, supporting the concept that hypomimia is not only the result of the dysfunction of motor circuits, but also of higher cognitive functions.

Meta-analysis of cortical thickness reduction in adult schizophrenia.

Numerous neuroimaging studies using surface-based morphometry analyses have reported altered cortical thickness among patients with schizophrenia, but the results have been inconsistent. We sought to provide a whole-brain meta-analysis, which may help enhance the spatial accuracy of identification. We conducted a meta-analysis of whole-brain studies that explored cortical thickness alteration among adult patients with schizophrenia, including first-episode patients with schizophrenia, and patients with chronic schizophrenia, compared with healthy controls by using the seed-based d mapping with permutation of subject images (SDM-PSI) software. A systematic literature search identified 25 studies (33 data sets) of cortical thickness, including 2008 patients with schizophrenia and 2004 healthy controls. Overall, patients with schizophrenia showed decreased cortical thickness in the right inferior frontal gyrus (IFG) and bilateral insula extending to the superior temporal gyrus (STG). Subgroup meta-analysis reported that patients with chronic schizophrenia showed decreased cortical thickness in the right insula extending to the right IFG. There was no significant cortical thickness difference between first-episode patients with schizophrenia and healthy controls. The results of meta-regression analyses should be viewed cautiously since they were driven by a small number of studies or did not overlap with the between-group differences found in the primary analyses. The meta-analysis suggested robust cortical thickness reduction in the IFG, insula and STG among adult patients with schizophrenia, particularly in those with chronic schizophrenia. The results provide useful insights to understanding the underlying pathophysiology of schizophrenia.

Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.

Previous studies revealed innate immune system activation in people with schizophrenia (SZ), potentially mediated by endogenous pathogen recognition receptors, notably Toll-like receptors (TLR). TLRs are activated by pathogenic molecules like bacterial lipopolysaccharides (TLR1 and TLR4), viral RNA (TLR3), or both (TLR8). Furthermore, the complement system, another key component of innate immunity, has previously been linked to SZ. Peripheral mRNA levels of TLR1, TLR3, TLR4, and TLR8 were compared between SZ and healthy controls (HC). We investigated their relationship with immune activation through complement expression and cortical thickness of the cingulate gyrus, a region susceptible to immunological hits. TLR mRNA levels and peripheral complement receptor mRNA were extracted from 86 SZ and 77 HC white blood cells; structural MRI scans were conducted on a subset. We found significantly higher TLR4 and TLR8 mRNA levels and lower TLR3 mRNA levels in SZ compared to HC. TLRs and complemental factors were significantly associated in SZ and HC, with the strongest deviations of TLR mRNA levels in the SZ subgroup having elevated complement expression. Cortical thickness of the cingulate gyrus was inversely associated with TLR8 mRNA levels in SZ, and with TLR4 and TLR8 levels in HC. The study underscores the role of innate immune activation in schizophrenia, indicating a coordinated immune response of TLRs and the complement system. Our results suggest there could be more bacterial influence (based on TLR 4 levels) as opposed to viral influence (based on TLR3 levels) in schizophrenia. Specific TLRs were associated with brain cortical thickness reductions of limbic brain structures.

Cortical thickness reductions associate with brain network architecture in major depressive disorder

BackgroundCortical thickness reductions in major depressive disorder are distributed across multiple regions. Research has indicated that cortical atrophy is influenced by connectome architecture on a range of neurological and psychiatric diseases. However, whether connectome architecture contributes to changes in cortical thickness in the same manner as it does in depression is unclear. This study aims to explain the distribution of cortical thickness reductions across the cortex in depression by brain connectome architecture. MethodsHere, we calculated a differential map of cortical thickness between 110 depression patients and 88 age-, gender-, and education level-matched healthy controls by using T1-weighted images and a structural network reconstructed through the diffusion tensor imaging of control group. We then used a neighborhood deformation model to explore how cortical thickness change in an area is influenced by areas structurally connected to it. ResultsWe found that cortical thickness in the frontoparietal and default networks decreased in depression, regional cortical thickness changes were related to reductions in their neighbors and were mainly limited by the frontoparietal and default networks, and the epicenter was in the prefrontal lobe. ConclusionCurrent findings suggest that connectome architecture contributes to the irregular topographic distribution of cortical thickness reductions in depression and cortical atrophy is restricted by and dependent on structural foundation.

42 Cognitive and Neuroanatomic Correlates of Olfactory Function in Cognitively Unimpaired and Impaired Older Adults

Objective:Olfactory function declines during normal aging; however, accelerated olfactory decline is observed in neurodegenerative diseases, such as Alzheimer’s disease (AD). Moreover, olfactory deficits in pre-clinical AD are associated with future cognitive decline. Odor identification and memory deficits have been consistently reported in early stage AD indicating its potential sensitivity to AD pathophysiology in olfactory and limbic structures, yet few studies of olfaction have incorporated structural measures in a well-characterized cohort of older adults. In the current study we examined the association between odor identification impairment, cognition, and medial temporal lobe (MTL) sub-regions in cognitively unimpaired and impaired older adults.Participants and Methods:We enrolled 140 participants (age=72.25±6.54, 56% female, years of education=16.30±2.63, 82% Caucasian, 15% Black/AA, 3% Multiracial) from the Penn Alzheimer’s Disease Research Center Clinical Cohort. Participants completed the Sniffin’ Sticks Odor Identification Test (SS-OIT), cognitive testing (NACC UDS2 or UDS3 and additional cognitive tests), and MRI scans (3T Siemens MAGNETOM Prisma MRI scanner). For the SS-OIT, participants were presented with 16 odorants using felt-tipped pen dispensers and asked to identify each odor from four multiple-choice options. Scores range from 0 to 16. Additionally, cognitive domains were created by averaging z-scores from tests within each domain: attention, memory, language, executive function, and visuospatial. This cohort was divided into participants with unimpaired cognition (n=96) and impaired cognition (MCI, dementia; n=44) using established normative data and consensus diagnosis. Linear regressions were performed to examine the association between SS-OIT score, each cognitive domain, and MTL measurements for unimpaired and impaired groups. For all analyses, we controlled for age, race, sex, education, smoking status, and hypertension and additionally for MOCA score and intracranial volume with MTL measurements.Results:In the unimpaired group, SS-OIT significantly associated with language (p&lt;.05). In the impaired group, SS-OIT significantly associated with language and memory (p&lt;.05). In the unimpaired group, SS-OIT significantly associated with right anterior hippocampal volume (p&lt;.05). In the impaired group, significant associations were found between SS-OIT and right anterior hippocampal volume (p&lt;.05) and left hippocampal mean thickness (p&lt;.05). Additionally, SS-OIT significantly associated with left and right entorhinal cortex volume (p&lt;.05) and mean thickness (p&lt;.05).Conclusions:This study reveals that lower odor identification performance is related to lower performance on measures of cognition and atrophy in MTL sub-regions in unimpaired and impaired older adults. Our findings support prior results demonstrating relationships between olfactory function, cognition, and MTL sub-regions. Specifically, olfactory function and episodic memory have been shown to follow similar patterns of decline in the course of AD, potentially reflecting AD pathology in shared regions of the MTL subserving episodic memory and olfactory function. Our findings demonstrate that reductions in both cortical thickness and grey matter volume of MTL regions are linked to olfactory deficits in individuals at risk for Alzheimer’s dementia. Future steps will include the analysis of longitudinal cognitive and imaging indices and the incorporation of fluid biomarker data.

Cortical growth from infancy to adolescence in preterm and term-born children.

Early life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks. Our aims were to: chart typical longitudinal cortical development and sex differences in cortical development from birth to adolescence in healthy term-born children; estimate differences in cortical development between children born at term and very preterm; and estimate differences in cortical development between children with normal and impaired cognition in adolescence. This longitudinal cohort study included children born at term (≥37 weeks' gestation) and very preterm (<30 weeks' gestation) with MRI scans at ages 0, 7 and 13 years (n = 66 term-born participants comprising 34 with one scan, 18 with two scans and 14 with three scans; n = 201 very preterm participants comprising 56 with one scan, 88 with two scans and 57 with three scans). Cognitive assessments were performed at age 13 years. Cortical surface reconstruction and parcellation were performed with state-of-the-art, equivalent MRI analysis pipelines for all time points, resulting in longitudinal cortical volume, surface area and thickness measurements for 62 cortical regions. Developmental trajectories for each region were modelled in term-born children, contrasted between children born at term and very preterm, and contrasted between all children with normal and impaired cognition. In typically developing term-born children, we documented anticipated patterns of rapidly increasing cortical volume, area and thickness in early childhood, followed by more subtle changes in later childhood, with smaller cortical size in females than males. In contrast, children born very preterm exhibited increasingly reduced cortical volumes, relative to term-born children, particularly during ages 0-7 years in temporal cortical regions. This reduction in cortical volume in children born very preterm was largely driven by increasingly reduced cortical thickness rather than area. This resulted in amplified cortical volume and thickness reductions by age 13 years in individuals born very preterm. Alterations in cortical thickness development were found in children with impaired language and memory. This study shows that the neurobiological impact of very preterm birth on cortical growth is amplified from infancy to adolescence. These data further inform the long-lasting impact on cortical development from very preterm birth, providing broader insights into neurodevelopmental consequences of early life experiences.

Language deficits in primary lateral sclerosis: cortical atrophy, white matter degeneration and functional disconnection between cerebral regions.

Primary lateral sclerosis (PLS) is traditionally regarded as a pure upper motor neuron disorder, but recent cases series have highlighted cognitive deficits in executive and language domains. A single-centre, prospective neuroimaging study was conducted with comprehensive clinical and genetic profiling. The structural and functional integrity of language-associated brain regions and networks were systematically evaluated in 40 patients with PLS in comparison to 111 healthy controls. The structural integrity of the arcuate fascicle, frontal aslant tract, inferior occipito-frontal fascicle, inferior longitudinal fascicle, superior longitudinal fascicle and uncinate fascicle was evaluated. Functional connectivity between the supplementary motor region and the inferior frontal gyrus and connectivitybetween Wernicke's and Broca's areas was also assessed. Cortical thickness reductions were observed in both Wernicke's and Broca's areas. Fractional anisotropy reduction was noted in the aslant tract and increased radical diffusivity (RD) identifiedin the aslanttract, arcuate fascicle and superior longitudinal fascicle in the left hemisphere. Functional connectivity was reduced along the aslant track, i.e. between the supplementary motor region and the inferior frontal gyrus, but unaffected between Wernicke's and Broca's areas. Cortical thickness alterations, structural and functional connectivity changes were also noted in the right hemisphere. Disease-burden in PLS is not confined to motor regions, but there is also a marked involvement of language-associated tracts, networks and cortical regions. Given the considerably longer survival in PLS compared to ALS, the impact of language impairment on the management of PLS needs to be carefully considered.

Structural brain networks in schizophrenia based on nonnegative matrix factorization.

Schizophrenia is a severe mental disease with significant morphometric reductions in gray matter volume and cortical thickness in a variety of brain regions. However, most studies only focused on the voxel level alterations in specific cerebral regions and ignored the spatial relationship between voxels. In the present study, we used a novel, data-driven technique-nonnegative matrix factorization (NMF) to group voxels with similar information into a network, and studied the structural covariance at the network level in schizophrenia. Our sample included 36 patients with schizophrenia and 21 healthy controls. Compared with healthy controls, patients with schizophrenia showed significant gray matter volume reductions in six structural covariance networks (dorsal striatum, thalamus, hippocampus-parahippocampus, supplementary motor area-fusiform, middle/inferior temporal network, frontal-parietal-occipital network). Our findings confirmed the assumption of a disturbance in the cortical-subcortical circuit in schizophrenia and suggested that NMF is a useful multivariate method to identify brain networks, which provides a new perspective to study the neural mechanism in schizophrenia.

Buccal Alveolar Bone changes and upper first molar displacement after maxillary expansion with RME, Ni-Ti leaf springs expander and Tooth- Bone-borne Expander. A CBCT based analysis.

To evaluate the buccal alveolar bone changes and the upper first molar displacement in subjects treated with conventional rapid maxillary expansion (RME), Ni-Ti leaf springs expander (Leaf Expander) and Tooth-Bone-borne Expander (Hybrid Expander) using CBCT scans. The sample consisted of 52 children treated with RME (n=18), Leaf Expander (n= 17) and Hybrid Expander (n= 17). CBCTs were taken before and after maxillary expansion and the Horos software was used for the analysis. Descriptive statistics and paired t-test were used to assess changes between the pre-treatment and post-treatment measurements. ANOVA test and Tukey's post hoc test with Bonferroni correction was used for between groups comparison. The Hybrid Expander during preadolescence showed few advantages over the use of tooth-anchored expanders. An expansion approach with mini-screws is not preferable during early mixed dentition to a conventional approach. The differences in dental tipping values were clinically insignificant and the reduction in cortical bone thickness remained less than 1 mm. When possible, the use of second primary molars as anchorage should be preferred.

A prospective 5-year longitudinal study detects neurocognitive and imaging correlates of seizure remission in self-limiting Rolandic epilepsy

ObjectiveSelf-limiting Rolandic epilepsy (RE) is the most common epilepsy in school-age children. Seizures are generally infrequent, but cognitive, language, and motor coordination problems can significantly impact the child’s life. To better understand brain structure and function changes in RE, we longitudinally assessed neurocognition, cortical thickness, and subcortical volumes. MethodsAt baseline, we recruited 30 participants diagnosed with RE and 24-healthy controls and followed up for 4.94 ± 0.8 years when the participants with RE were in seizure remission. Measures included were as follows: T1-weighted magnetic resonance brain imaging (MRI) with FreeSurfer analysis and detailed neuropsychological assessments. MRI and neuropsychological data were compared between baseline and follow-up in seizure remission. ResultsLongitudinal MRI revealed excess cortical thinning in the left-orbitofrontal (p = 0.0001) and pre-central gyrus (p = 0.044).There is a significant association (p = 0.003) between a reduction in cortical thickness in the left-orbitofrontal cluster and improved processing of filtered words.Longitudinal neuropsychology revealed significant improvements in the symptoms of developmental coordination disorder (DCD, p = 0.005) in seizure remission. ConclusionsThere is evidence for altered development of neocortical regions between active seizure state and seizure remission in RE within two clusters maximal in the left-orbitofrontal and pre-central gyrus. There is significant evidence for improvement in motor coordination between active seizures and seizure remission and suggestive evidence for a decline in fluid intelligence and gains in auditory processing.

Histological analysis of early gonadal development in three bird species reveals gonad asymmetry from the beginning of gonadal ridge formation and a similar course of sex differentiation

The developing gonads constitute a valuable model for studying developmental mechanisms because the testes and ovaries, while originating from the same primordia, undergo two different patterns of development. So far, gonadal development among birds has been described in detail in chickens, but literature on the earliest stages of gonadogenesis is scarce. This study presents changes in the structure of the gonads in three species of breeding birds (chicken, duck, and pigeon), starting from the first signs of gonadal ridge formation, that is, the thickenings of the coelomic epithelium. It appears that both gonads show asymmetry from the very beginning of gonadal ridge formation in both genetic sexes. The left gonadal ridge is thicker than the right one, and it is invaded by a higher number of primordial germ cells. Undifferentiated gonads, both left and right, consist of the primitive cortex and the medulla. The primitive cortex develops from the thickened coelomic epithelium, while the primitive medulla – by the aggregation of mesenchymal cells. This study also describes the process of sex differentiation of the testes and ovaries, which is initiated at the same embryonic stage in all three studied species. The first sign of gonadal sex differentiation is the decrease in the number of cortical germ cells and a reduction in cortical thickness in the differentiating testes. This is followed by an increase in the number of germ cells in the medulla. The cortical asymmetry and difference in size between the left and right testes diminishes during later development. However, the differentiating left ovary shows an increase in the number of cortical germ cells and cortical thickness. No regression is seen in the right ovary, although its development is slower. The right ovarian cortex undergoes testis-specific reduction, while the medulla undergoes ovary-specific development. The process of gonadogenesis is similar in the three studied species, with only slight differences in gonadal structure.

Lactobacillus Reuteri 6475 Prevents Bone Loss in a Clinically Relevant Oral Model of Glucocorticoid-Induced Osteoporosis in Male CD-1 Mice.

Glucocorticoids (GCs) are commonly used anti-inflammatory medications with significant side effects, including glucocorticoid-induced osteoporosis (GIO). We have previously demonstrated that chronic subcutaneous GC treatment in mice leads to gut barrier dysfunction and trabecular bone loss. We further showed that treating with probiotics or barrier enhancers improves gut barrier function and prevents GIO. The overall goal of this study was to test if probiotics could prevent GC-induced gut barrier dysfunction and bone loss in a clinically relevant oral-GC model of GIO. Eight-week-old male CD-1 mice were treated with vehicle or corticosterone in the drinking water for 4 weeks and administered probiotics Lactobacillus reuteri ATCC 6475 (LR 6475) or VSL#3 thrice weekly via oral gavage. As expected, GC treatment led to significant gut barrier dysfunction (assessed by measuring serum endotoxin levels) and bone loss after 4 weeks. Serum endotoxin levels significantly and negatively correlated with bone volume. Importantly, LR 6475 treatment effectively prevented both GC-induced increase in serum endotoxin and trabecular bone loss. VSL#3 had intermediate results, not differing from either control or GC-treated animals. GC-induced reductions in femur length, cortical thickness, and cortical area were not affected by probiotic treatment. Taken together, these results are the first to demonstrate that LR 6475 effectively prevents the detrimental effects of GC treatment on gut barrier, which correlates with enhanced trabecular bone health in an oral mouse model of GIO. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.