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Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that often emerges in childhood and manifests through persistent patterns of inattention, hyperactivity, and impulsivity that are inappropriate for the child's developmental level. The disorder can significantly disrupt academic performance, social interactions, and family dynamics, with symptoms often continuing into adulthood. ADHD affects approximately 3% to 7% of schoolage children globally, with a higher prevalence in boys, and is frequently observed across all cultural, racial, and socioeconomic groups. The etiology of ADHD is multifaceted, involving genetic, neurobiological, and environmental factors. Potential causes include neuromaturational delays, neurotransmitter imbalances, and structural or functional abnormalities in brain regions, particularly the frontal lobes. Additionally, prenatal factors such as tobacco or alcohol exposure and environmental toxins are associated with increased ADHD risk. Symptoms of inattention include difficulties sustaining focus, disorganization, and forgetfulness, while hyperactivity is characterized by excessive movement and restlessness. Impulsivity in children with ADHD can lead to hasty actions without consideration of consequences. Early diagnosis and intervention are crucial for managing ADHD, as untreated symptoms can impair educational and social development. Understanding the diverse presentations and underlying causes of ADHD is essential for effective treatment and support strategies, highlighting the need for continued research and awareness. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Methamphetamine use disorders (MUDs) cause widespread disruptions in metabolomic and immunologic processes, highlighting the need for new therapeutic approaches. The purpose of this study was to find molecular and neuroimaging biomarkers for methamphetamine addiction.In this study, we recruited 231 patients with MUD at varying stages of withdrawal and 40 healthy controls to quantify the blood levels of 52 molecules using enzyme‐linked immunosorbent assay.The overall molecular disruption caused by methamphetamine was inversely related to withdrawal time (P = 0.0008), with partial recovery observed after 1 year of follow‐up (P = 2.20 × 10−5). Molecules related to stress, immune activation, oxidative products, and cardiac injury were significantly elevated in all MUD groups, while antioxidation enzymes were downregulated. Additionally, the blood level of brain‐derived neurotrophic factor was significantly correlated with gray matter volumes in nine brain regions (fusiform gyrus, orbitofrontal cortex, temporal pole, caudate, cerebellum crus, and vermis, adjusted P < 0.05) among patients with MUD.These findings suggest that patients with MUD exhibit elevated levels of immune response, stress, and oxidative stress, which are associated with brain structural abnormalities. [ABSTRACT FROM AUTHOR]

Since epilepsy is often complicated by psychiatric symptoms, the contributions of psychiatry are indispensable for the care and improvement of the quality of life of individuals with epilepsy. Moreover, the existence of a bidirectional relationship between epilepsy and psychiatric symptoms was recently proposed, based on the evidence that not only are some psychiatric symptoms more likely than others to follow epilepsy, but also that psychiatric symptoms may precede the onset of epilepsy and the presence of psychiatric symptoms may influence the outcome of treatment for seizures. There has also been a gradual accumulation of neurobiological findings related to psychosis, depressive, and anxiety symptoms that are associated with epilepsy with respect to abnormalities in brain networks and neurotransmission. This mini-review focuses on the neuropsychiatric aspects of epilepsy and proposes that a reconsideration of neuropsychiatry in light of epilepsy findings could serve as a bridge between psychiatry and neurology. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify predictors of brain CT abnormalities in patients who sustained a mild traumatic brain injury (mTBI). Methods: Retrospective observational cohort of adult patients with mTBI (Glasgow Coma Score 13–15) that occurred within the preceding 24 h. Results: 2548 (91%) of the cohort had a brain CT and 698 (27%) demonstrated abnormal findings. The most frequently observed CT abnormalities were bleeding (638, 25%) and fractures (190, 7.4%). Multivariate logistic regression analysis revealed several significant predictors associated with the presence of brain CT abnormalities including older age [P < 0.0001], male sex [P < 0.0001], loss of consciousness [P = 0.0041], associated vomiting [P = 0.0011], alteration of consciousness (AOC) [P = 0102], and GCS score [P < 0.0001]. This was a robust model with an R² of 14.2%. Conclusion: In this retrospective analysis, older age, male sex, the presence of loss of consciousness or alteration in consciousness, lower GCS score, and associated vomiting were found to be significant predictors of having an abnormal brain CT. These findings highlight the importance of considering these factors when determining the necessity of brain CT scans in patients with mTBI and suggest that existing clinical decision rules may be limited. These findings may also help to inform clinical decision rules. Early identification of individuals at a higher risk of CT abnormalities may assist in appropriate management and allocation of healthcare resources. [ABSTRACT FROM AUTHOR]

Emotional disorders inflict an enormous burden on society. Research on brain abnormalities implicated in emotional disorders has witnessed great progress over the past decades. Using cross‐sectional and longitudinal designs, resting state functional magnetic resonance imaging (rs‐fMRI) and its analytic approaches have been applied to characterize the local properties of patients with emotional disorders. Additionally, brain activity alterations of emotional disorders have shown frequency‐specific. Despite the gains in understanding the roles of brain abnormalities in emotional disorders, the limitation of the small sample size needs to be highlighted. Lastly, we proposed that evidence from the positive psychology research stream presents it as a viable discipline, whose suggestions could be developed in future emotional disorders research. Such interdisciplinary research may produce novel treatments and intervention options. This article is categorized under:Psychology > Brain Function and Dysfunction [ABSTRACT FROM AUTHOR]

Background and aims: Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria. Methods: Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18 years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st – Nov. 15th, 2021). Results: We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42–24.11; p = 0.014). Conclusions: Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that follows exposure to a traumatic stressor. Though previous in vivo proton (1H) MRS) research conducted at 4 T or lower has identified alterations in glutamate metabolism associated with PTSD predisposition and/or progression, no prior investigations have been conducted at higher field strength. In addition, earlier studies have not extensively addressed the impact of psychiatric comorbidities such as major depressive disorder (MDD) on PTSD‐associated 1H‐MRS‐visible brain metabolite abnormalities. Here we employ 7 T 1H MRS to examine concentrations of glutamate, glutamine, GABA, and glutathione in the medial prefrontal cortex (mPFC) of PTSD patients with MDD (PTSD+MDD+; N = 6) or without MDD (PTSD+MDD−; N = 5), as well as trauma‐unmatched controls without PTSD but with MDD (PTSD−MDD+; N = 9) or without MDD (PTSD−MDD−; N = 18). Participants with PTSD demonstrated decreased ratios of GABA to glutamine relative to healthy PTSD−MDD− controls but no single‐metabolite abnormalities. When comorbid MDD was considered, however, MDD but not PTSD diagnosis was significantly associated with increased mPFC glutamine concentration and decreased glutamate:glutamine ratio. In addition, all participants with PTSD and/or MDD collectively demonstrated decreased glutathione relative to healthy PTSD−MDD− controls. Despite limited findings in single metabolites, patterns of abnormality in prefrontal metabolite concentrations among individuals with PTSD and/or MDD enabled supervised classification to separate them from healthy controls with 80+% sensitivity and specificity, with glutathione, glutamine, and myoinositol consistently among the most informative metabolites for this classification. Our findings indicate that MDD can be an important factor in mPFC glutamate metabolism abnormalities observed using 1H MRS in cohorts with PTSD. [ABSTRACT FROM AUTHOR]

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by increasing prevalence, diverse impairments, and unclear origins and mechanisms. To gain a better grasp of the origins of ASD, it is essential to identify the most distinctive structural brain abnormalities in individuals with ASD. Methods: A Multi-Stage Progressive Feature Refinement Approach was employed to identify the most pivotal structural magnetic resonance imaging (MRI) features that distinguish individuals with ASD from typically developing (TD) individuals. The study included 175 individuals with ASD and 69 TD individuals, all aged between 7 and 18 years, matched in terms of age and gender. Both cortical and subcortical features were integrated, with a particular focus on hippocampal subfields. Results: Out of 317 features, 9 had the most significant impact on distinguishing ASD from TD individuals. These structural features, which include a specific hippocampal subfield, are closely related to the brain areas associated with the reward system. Conclusion: Structural irregularities in the reward system may play a crucial role in the pathophysiology of ASD, and specific hippocampal subfields may also contribute uniquely, warranting further investigation. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To determine the pattern, degree and prevalence of optic disc optical coherence tomography (OCT) alterations in adults born preterm with very low birth weight (VLBW; birth weight < 1500 g).Optic disc OCT was assessed in 98 VLBW participants and 139 term‐born controls from birth cohorts in Finland and Norway at the mean age of 36 years. The participants had not been treated for retinopathy of prematurity and had no diagnosed brain abnormality. OCT assessment included parameters for optic disc size, neural rim and peripapillary retinal nerve fibre layer thickness (pRNFLT), and for the foveal developmental stage. Background data, visual acuity, refractive error and intraocular pressure were recorded.In the VLBW group, optic disc neural rim and pRNFLT were significantly decreased, most frequently in the nasal and inferior sectors. In 40% (95% CI: 33–47) of the VLBW eyes, nerve fibre thickness of at least one optic disc sector was below the fifth percentile of the control group, including 9% (95% CI: 6–14) subgroup falling below the first percentile, that is, clinically below normal limits. VLBW participants with nerve fibre thickness below the fifth percentile did not differ by perinatal data or foveal developmental stage from the other VLBW participants. All participants had normal visual acuity.A moderate decrease of the optic disc neural rim and pRNFLT is frequently seen in clinically healthy adults born preterm with VLBW. Awareness of the VLBW‐related optic disc nerve fibre shallowness especially in the inferior and nasal sectors is important while evaluating acquired optic disc pathology in adulthood. [ABSTRACT FROM AUTHOR]

[Display omitted] • Schizophrenia arises from a mix of genetic and environmental factors. • Schizophrenia symptoms link to myelination alterations in brain structures. • Undernutrition disrupts early neurodevelopment and the myelination process. • The myelin dysfunction hypothesis adds to understanding schizophrenia triggers. Schizophrenia (SZ) is a complex mental illness characterized by disturbances in thinking, emotionality, and behavior, significantly impacting the quality of life for individuals affected and those around them. The etiology of SZ involves intricate interactions between genetic and environmental factors, although the precise mechanisms remain incompletely understood. Genetic predisposition, neurotransmitter dysregulation (particularly involving dopamine and serotonin), and structural brain abnormalities, including impaired prefrontal cortex function, have been implicated in SZ development. However, increasing evidence reveals the role of environmental factors, such as nutrition, during critical periods like pregnancy and lactation. Epidemiological studies suggest that early malnutrition significantly increases the risk of SZ symptoms manifesting in late adolescence, a crucial period coinciding with peak myelination and brain maturation. Prenatal undernutrition may disrupt myelin formation, rendering individuals more susceptible to SZ pathology. This review explores the potential relationship between prenatal undernutrition, myelin alterations, and susceptibility to SZ. By delineating the etiopathogenesis, examining genetic and environmental factors associated with SZ, and reviewing the relationship between SZ and myelination disorders, alongside the impact of malnutrition on myelination, we aim to examine how malnutrition might be linked to SZ by altering myelination processes, which contribute to increasing the understanding of SZ etiology and help identify targets for intervention and management. [ABSTRACT FROM AUTHOR]

To provide objective diagnostic markers for fibromyalgia symptoms (FMS) diagnosis, we have created interpretable extreme gradient boosting (XGBoost) models using radiomics to aid in the diagnosis of chronic pain (CP) and to develop nomogram models for diagnosing subgroups of FMS. A group of 54 patients with CP and 71 healthy controls was randomly separated into training and validation groups, using a 7:3 ratio. Radiomics features were extracted from grey-matter and white-matter in the filtered mwp0* image. The Mann-Whitney U test, Spearman's rank correlation test, and least absolute shrinkage and selection operator (LASSO) were utilized to select features. An XGBoost model was created based on these features, and Shapley Additive exPlanations (SHAP) was used for personalization and visual interpretation. A nomogram was developed for the diagnosis of FMS subgroups, utilizing radiomics scores and clinical predictors. The efficacy of the nomogram was evaluated using the area under the receiver operating characteristic curve, while decision curve analysis was employed to evaluate its clinical efficacy. The XGBoost model displays stability in the training validation group, indicating lower overfitting of CP model. The nomogram model combined with the rad-score has a greater ability to distinguish between typical and sub-clinical than the clinical factor model alone. We developed and validated a CP diagnosis model by XGBoost and realized model visualization through SHAP. The rad-score obtained by machine learning was used to build a nomogram model that combines clinical scales to distinguish patients with typical and sub-clinical fibromyalgia. [ABSTRACT FROM AUTHOR]

Since epilepsy is often complicated by psychiatric symptoms, the contributions of psychiatry are indispensable for the care and improvement of the quality of life of individuals with epilepsy. Moreover, the existence of a bidirectional relationship between epilepsy and psychiatric symptoms was recently proposed, based on the evidence that not only are some psychiatric symptoms more likely than others to follow epilepsy, but also that psychiatric symptoms may precede the onset of epilepsy and the presence of psychiatric symptoms may influence the outcome of treatment for seizures. There has also been a gradual accumulation of neurobiological findings related to psychosis, depressive, and anxiety symptoms that are associated with epilepsy with respect to abnormalities in brain networks and neurotransmission. This mini-review focuses on the neuropsychiatric aspects of epilepsy and proposes that a reconsideration of neuropsychiatry in light of epilepsy findings could serve as a bridge between psychiatry and neurology. [ABSTRACT FROM AUTHOR]

The intricate spatial configurations of brain networks offer essential insights into understanding the specific patterns of brain abnormalities and the underlying biological mechanisms associated with Alzheimer's disease (AD), normal aging, and other neurodegenerative disorders. This study investigated alterations in the topographical structure of the brain related to aging and neurodegenerative diseases by analyzing brain gradients derived from structural MRI data across multiple cohorts (n = 7323). The analysis identified distinct gradient patterns in AD, aging, and other neurodegenerative conditions. Gene enrichment analysis indicated that inorganic ion transmembrane transport was the most significant term in normal aging, while chemical synaptic transmission is a common enrichment term across various neurodegenerative diseases. Moreover, the findings show that each disorder exhibits unique dysfunctional neurophysiological characteristics. These insights are pivotal for elucidating the distinct biological mechanisms underlying AD, thereby enhancing our understanding of its unique clinical phenotypes in contrast to normal aging and other neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Background: Aquaporin‐4 (AQP4), predominantly expressed in astrocytes, has been implicated in the development of brain edema following ischemic events. However, its role in post‐stroke neuroinflammation is not fully understood. Methods: Using a middle cerebral artery occlusion (MCAO) mouse model, we assessed AQP4's role in post‐stroke inflammation. Brain tissue slices from male C57BL/6 mice were subjected to immunohistochemistry and western blot post‐MCAO. Additionally, primary astrocytes were isolated for quantitative real‐time PCR and immunofluorescence assays to evaluate the expression of inflammatory markers glial fibrillary acidic protein (GFAP) and AQP4. AQP4 modulation was achieved using viral knockdown and overexpression methods. Neuronal damage was assessed using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests in co‐culture studies. Results: MCAO mice exhibited a significant upregulation in GFAP. This reactive astrogliosis corresponded with an elevation in inflammatory markers. AQP4 expression responded to this inflammatory trend, peaking at 6 h after OGD and returning to baseline levels at 24 and 48 h. Co‐culture experiments revealed that AQP4(+) astrocytes exacerbated injury in OGD‐treated neurons, as evidenced by increased TUNEL positivity and apoptotic events. Conversely, AQP4(−) astrocytes appeared to have a protective effect. Knockdown of AQP4 resulted in reduced post‐OGD inflammatory response, whereas AQP4 overexpression intensified the injury to neurons post‐OGD. In vivo experiments also confirmed that AQP4 inhibitor TGN‐020 reduced and overexpression of AQP4 increased behavioral abnormalities and brain infarcts. Conclusion: Our findings underscore AQP4's pivotal role in modulating post‐stroke neuroinflammation. Targeting AQP4 may present a novel therapeutic avenue for mitigating ischemia‐induced neuronal damage. [ABSTRACT FROM AUTHOR]

Spina bifida (SB) is a developmental disorder of the central nerve system. Due to incomplete closure of the neural tube, there is a congenital spinal cord lesion, which can be accompanied by cerebral anomalies. Due to folic acid suppletion and antenatal screening, the incidence of SB has decreased. Improvements in urological and specialized health care have led to a longer life expectancy and better quality of life. Lifelong care should take place in a multidisciplinary team, including a urologist experienced in the diagnosis and treatment of neurogenic bladder disorders and concomitant problems, such as urinary tract infections, urolithiasis and malignancies. [ABSTRACT FROM AUTHOR]

Introduction: Canavan disease (CD) is a rare autosomal recessive neurodegenerative disorder caused by a deficiency of aspartoacylase A, an enzyme that degrades N-acetylaspartate (NAA). The disease is characterized by progressive white matter degeneration, leading to intellectual disability, seizures, and death. This retrospective study aims to describe the full spectrum of magnetic resonance imaging (MRI) findings in a large case series of CD patients. Materials and methods: MRI findings in 18 patients with confirmed CD were investigated, and the full spectrum of brain abnormalities was compared with the existing literature to provide new insights regarding the brain MRI findings in these patients. All the cases were proven based on genetic study or NAA evaluation in urine or brain. Results: Imaging analysis showed involvement of the deep and subcortical white matter as well as the globus pallidus in all cases, with sparing of the putamen, caudate, and claustrum. The study provides updates on the imaging characteristics of CD and validates some underreported findings such as the involvement of the lateral thalamus with sparing of the pulvinar, involvement of the internal capsules and corpus callosum, and cystic formation during disease progression. Conclusion: To our knowledge, this is one of the largest case series of patients with CD which includes a detailed description of the brain MRI findings. The study confirmed many of the previously reported MRI findings but also identified abnormalities that were previously rarely or not described. We speculate that areas of ongoing myelination are particularly vulnerable to changes in CD. [ABSTRACT FROM AUTHOR]

Background: Juvenile myoclonic epilepsy (JME) is characterized by altered patterns of brain functional connectivity (FC). However, the nature and extent of alterations in the spatiotemporal characteristics of dynamic FC in JME patients remain elusive. Dynamic networks effectively encapsulate temporal variations in brain imaging data, offering insights into brain network abnormalities and contributing to our understanding of the seizure mechanisms and origins. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were procured from 37 JME patients and 37 healthy counterparts. Forty-seven network nodes were identified by group-independent component analysis (ICA) to construct the dynamic network. Ultimately, patients' and controls' spatiotemporal characteristics, encompassing temporal clustering and variability, were contrasted at the whole-brain, large-scale network, and regional levels. Results: Our findings reveal a marked reduction in temporal clustering and an elevation in temporal variability in JME patients at the whole-brain echelon. Perturbations were notably pronounced in the default mode network (DMN) and visual network (VN) at the large-scale level. Nodes exhibiting anomalous were predominantly situated within the DMN and VN. Additionally, there was a significant correlation between the severity of JME symptoms and the temporal clustering of the VN. Conclusions: Our findings suggest that excessive temporal changes in brain FC may affect the temporal structure of dynamic brain networks, leading to disturbances in brain function in patients with JME. The DMN and VN play an important role in the dynamics of brain networks in patients, and their abnormal spatiotemporal properties may underlie abnormal brain function in patients with JME in the early stages of the disease. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) in pregnancy could be a disastrous event with increased maternal and perinatal morbidity and mortality. DKA can occur with a normal blood glucose level, known as euglycemic DKA. It particularly affects pregnant women with type I diabetes. Here, we report the case of a 28 year‐old primigravid patient, with a diagnosis of type 1 diabetes for 8 years. This patient consulted our department at 29 weeks of gestation with a previous history of headaches, vomiting and diarrhea for 9 h. Blood glucose level was 8.8 mmol/L with a ketone test positive (>15 mg/dL). Blood test showed high anion gap (17.9 mmol/L) with low serum bicarbonate rate (21 mmol/L). Systemic examination and fetal heart rate (FHR) was reassuring. The patient was subsequently discharged. She returned to the clinic 19 h later with further symptoms of nausea, polyuria‐polydipsia, asthenia and a weight loss of 4 kg since the day before. Blood sugar was 14.3 mmol/L and a ketone test was strongly positive. Cardiotocography showed fetal tachycardia and repeated late decelerations. A diagnosis of DKA was made and emergency cesarean was performed for fetal distress. At delivery, pH was acidosis (pH: 7.02, lactates: 6.2). The patient was successfully treated with intravenous hydration and insulin. Neonatal evolution was favorable. Pregnant women with type I diabetes can develop euglycemic DKA. Early recognition and prompt treatment could help prevent severe maternal and fetal adverse outcomes. DKA in pregnant women can induce fetal acidosis with abnormal FHR. In this situation, a cesarean can be performed to improve neonatal outcome even inducing a premature delivery. Prolonged pregnancy can lead to irreversible neonatal brain abnormalities. Synopsis: Diabetic ketoacidosis in pregnant women can induce fetal acidosis with abnormal fetal heart rate, which can lead to irreversible neonatal brain abnormalities. [ABSTRACT FROM AUTHOR]

There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment. [ABSTRACT FROM AUTHOR]

Luteolin is an essential natural polyphenol found in a variety of plants. Numerous studies have supported its protective role in neurodegenerative diseases, yet the research for its therapeutic utility in D-galactose (D-gal)-induced brain ageing is still lacking. In this study, the potential neuroprotective impact of luteolin against D-gal-induced brain ageing was explored. Forty rats were randomly divided into four groups: control, luteolin, D-gal, and luteolin-administered D-gal groups. All groups were subjected to behavioural, cholinergic function, and hippocampal mitochondrial respiration assessments. Hippocampal oxidative, neuro-inflammatory, senescence and apoptotic indicators were detected. Gene expressions of SIRT1, BDNF, and RAGE were assessed. Hippocampal histopathological studies, along with GFAP and Ki67 immunoreactivity, were performed. Our results demonstrated that luteolin effectively alleviated D-gal-induced cognitive impairment and reversed cholinergic abnormalities. Furthermore, luteolin administration substantially mitigated hippocampus oxidative stress, mitochondrial dysfunction, neuro-inflammation, and senescence triggered by D-gal. Additionally, luteolin treatment considerably attenuated neuronal apoptosis and upregulated hippocampal SIRT1 mRNA expression. In conclusion, our findings revealed that luteolin administration attenuated D-gal-evoked brain senescence, improving mitochondrial function and enhancing hippocampal neuroregeneration in an ageing rat model through its antioxidant, senolytic, anti-inflammatory, and anti-apoptotic impacts, possibly due to upregulation of SIRT1. Luteolin could be a promising therapeutic modality for brain aging-associated abnormalities. [ABSTRACT FROM AUTHOR]

Objective: To establish a multi-dimensional representation solely on structural MRI (sMRI) for early diagnosis of AD. Methods: A total of 3377 participants' sMRI from four independent databases were retrospectively identified to construct an interpretable deep learning model that integrated multi-dimensional representations of AD solely on sMRI (called s2MRI-ADNet) by a dual-channel learning strategy of gray matter volume (GMV) from Euclidean space and the regional radiomics similarity network (R2SN) from graph space. Specifically, the GMV feature map learning channel (called GMV-Channel) was to take into consideration spatial information of both long-range spatial relations and detailed localization information, while the node feature and connectivity strength learning channel (called NFCS-Channel) was to characterize the graph-structured R2SN network by a separable learning strategy. Results: The s2MRI-ADNet achieved a superior classification accuracy of 92.1% and 91.4% under intra-database and inter-database cross-validation. The GMV-Channel and NFCS-Channel captured complementary group-discriminative brain regions, revealing a complementary interpretation of the multi-dimensional representation of brain structure in Euclidean and graph spaces respectively. Besides, the generalizable and reproducible interpretation of the multi-dimensional representation in capturing complementary group-discriminative brain regions revealed a significant correlation between the four independent databases (p < 0.05). Significant associations (p < 0.05) between attention scores and brain abnormality, between classification scores and clinical measure of cognitive ability, CSF biomarker, metabolism, and genetic risk score also provided solid neurobiological interpretation. Conclusion: The s2MRI-ADNet solely on sMRI could leverage the complementary multi-dimensional representations of AD in Euclidean and graph spaces, and achieved superior performance in the early diagnosis of AD, facilitating its potential in both clinical translation and popularization. [ABSTRACT FROM AUTHOR]

Purpose: To achieve high‐resolution fetal brain anatomical imaging without introducing image artifacts by reducing the FOV, and to demonstrate improved image quality compared to conventional full‐FOV fetal brain imaging. Methods: Reduced FOV was achieved by applying outer volume suppression (OVS) pulses immediately prior to standard single‐shot fast spin echo (SSFSE) imaging. In the OVS preparation, a saturation RF pulse followed by a gradient spoiler was repeated three times with optimized flip‐angle weightings and a variable spoiler scheme to enhance signal suppression. Simulations and phantom and in‐vivo experiments were performed to evaluate OVS performance. In‐vivo high‐resolution SSFSE images acquired using the proposed approach were compared with conventional and high‐resolution SSFSE images with a full FOV, using image quality scores assessed by neuroradiologists and calculated image metrics. Results: Excellent signal suppression in the saturation bands was confirmed in phantom and in‐vivo experiments. High‐resolution SSFSE images with a reduced FOV acquired using OVS demonstrated the improved depiction of brain structures without significant motion and blurring artifacts. The proposed method showed the highest image quality scores in the criteria of sharpness, contrast, and artifact and was selected as the best method based on overall image quality. The calculated image sharpness and tissue contrast ratio were also the highest with the proposed method. Conclusion: High‐resolution fetal brain anatomical images acquired using a reduced FOV with OVS demonstrated improved image quality both qualitatively and quantitatively, suggesting the potential for enhanced diagnostic accuracy in detecting fetal brain abnormalities in utero. [ABSTRACT FROM AUTHOR]

Background The past decade has witnessed a surge of articles describing the neurocognitive sequelae and associated structural and functional brain abnormalities of patients with overt hypothyroidism (OH) and subclinical hypothyroidism (SCH). Findings show effects primarily within the frontal lobes with usually worse outcomes for OH than SCH. Several recent studies have also indicated hypothyroid patients may have smaller hippocampi, a key structure for memory. Context The JCEM paper by Zhang and colleagues applies 2 novel approaches for analyzing hippocampal structure and function. One uses an automated processing tool that segments the hippocampus into distinct subregions, and the other performs connectivity analysis to assess the relationships between specific hippocampal subregions and cortical areas. Relatively large samples of OH and SCH patients and healthy controls received a test of global cognitive functioning and underwent structural and functional magnetic resonance imaging. Results showed hypothyroid groups scored significantly below controls on the memory scale and also had smaller hippocampal volumes in selective subregions. Effects were stronger for SCH than OH groups, who also showed different patterns of interconnectivity between hippocampal subregions and specific frontal lobe areas. Interpretation To make sense of these findings, I explored the rodent and human literatures on thyroid hormone's role in hippocampal functioning and on hippocampal subfields and their purported functions and interconnections. Because current results suggest SCH may represent a distinct clinical entity with unique brain manifestations, I hypothesized 2 explanations for these findings, one involving transporter defects in the brain barriers and the other, differential neurodegeneration of the blood-brain barrier vascular unit. [ABSTRACT FROM AUTHOR]

Background: The Coiled-Coil Domain-Containing Protein 88 A (CCDC88A) gene encodes the actin-binding protein Girdin, which plays important roles in maintaining the actin cytoskeleton and in cell migration and was recently associated with a specific form of epileptic encephalopathy. Biallelic protein-truncating variants of CCDC88A have been considered responsible for progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO)-like syndrome. To date, only three consanguineous families with loss-of-function homozygous variants in the CCDC88A gene have been reported. The described patients share many clinical features, such as microcephaly, neonatal hypotonia, seizures, profound developmental delay, face and limb edema, and dysmorphic features, with a similar appearance of the eyes, nose, mouth, and fingers. Case presentation: We report on a child from a nonconsanguineous family who presented with profound global developmental delay, severe epilepsy, and brain malformations, including subcortical band heterotopia. The patient harbored two heterozygous pathogenic variants in the trans configuration in the CCDC88A gene, which affected the coiled-coil and C-terminal domains. Conclusions: We detail the clinical and cerebral imaging data of our patient in the context of previously reported patients with disease-causing variants in the CCDC88A gene, emphasizing the common phenotypes, including cortical malformations, that warrant screening for sequence variants in this gene. [ABSTRACT FROM AUTHOR]

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Autism Spectrum Disorder (ASD) is a developmental condition resulting from abnormalities in brain structure and function, which can manifest as communication and social interaction difficulties. Conventional methods for diagnosing ASD may not be effective in the early stages of the disorder. Hence, early diagnosis is crucial to improving the patient's overall health and well-being. One alternative and effective method for early autism diagnosis is facial expression recognition since autistic children typically exhibit distinct facial expressions that can aid in distinguishing them from other children. This paper provides a deep convolutional neural network (DCNN)-based real-time emotion recognition system for autistic kids. The proposed system is designed to identify six facial emotions, including surprise, delight, sadness, fear, joy, and natural, and to assist medical professionals and families in recognizing facial expressions in autistic children for early diagnosis and intervention. In this study, an attention-based YOLOv8 (AutYOLO-ATT) algorithm for facial expression recognition is proposed, which enhances the YOLOv8 model's performance by integrating an attention mechanism. The proposed method (AutYOLO-ATT) outperforms all other classifiers in all metrics, achieving a precision of 93.97%, recall of 97.5%, F1-score of 92.99%, and accuracy of 97.2%. These results highlight the potential of the proposed method for real-world applications, particularly in fields where high accuracy is essential. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. Methods: The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. Results: In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. Conclusions: Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To evaluate the role of parental magnetic resonance imaging (MRI) in assessing fetuses with suspected brain anomalies and its use in prenatal counselling.A retrospective, multicentre chart review was conducted on fetuses who underwent brain MRI because of suspected brain abnormalities between January 2008 and December 2022, with one or both parents who underwent brain MRI (MRI‐Trio) as part of prenatal counselling. Clinical and demographic data were collected, including fetal and parental MRI findings, prenatal counselling outcomes, genetic testing results, family and previous pregnancy history, neurological examinations of the born children up to 24 months of age, and autopsy reports of fetuses from terminated pregnancies. MRI‐Trio concordance was defined as at least one abnormal brain feature identified with similarity in the fetus and the parents. The live‐born children were assessed postnatally through either neurodevelopmental evaluations or telephone interviews.Sixty pregnancies were included (41.7% with concordant and 58.3% with discordant MRI‐Trio). Forty‐two children were born (70%) and 17 pregnancies were terminated (28.3%). One case of in utero fetal death (1.7%) was reported. The most common brain findings were multiple anomalies (n = 26, 43.3%), isolated disorders of the corpus callosum (n = 17, 28.3%), atypical periventricular pseudocysts (n = 6, 10%), and anomalies of the anterior complex (n = 4, 6.7%). MRI‐Trio enabled better prognostication. When MRI‐Trio was concordant, counselling was more favourable (n = 22, 36.6%) and the majority of live‐born children exhibited typical development (p < 0.001).MRI‐Trio is a valuable tool for identifying dominantly inherited brain anomalies that may not hold developmental significance or are associated with favourable outcomes, acknowledging the potential for variable penetrance, which may result in more severe presentations. Concordant MRI‐Trio findings can enhance the accuracy of prenatal counselling, potentially reducing the incidence of termination of pregnancy. [ABSTRACT FROM AUTHOR]

Background: Previous studies based on resting-state functional magnetic resonance imaging(rs-fMRI) and voxel-based morphometry (VBM) have demonstrated significant abnormalities in brain structure and resting-state functional brain activity in patients with early-onset schizophrenia (EOS), compared with healthy controls (HCs), and these alterations were closely related to the pathogenesis of EOS. However, previous studies suffer from the limitations of small sample sizes and high heterogeneity of results. Therefore, the present study aimed to effectively integrate previous studies to identify common and specific brain functional and structural abnormalities in patients with EOS. Methods: The PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were systematically searched to identify publications on abnormalities in resting-state regional functional brain activity and gray matter volume (GMV) in patients with EOS. Then, we utilized the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software to conduct a whole-brain voxel meta-analysis of VBM and rs-fMRI studies, respectively, and followed by multimodal overlapping on this basis to comprehensively identify brain structural and functional abnormalities in patients with EOS. Results: A total of 27 original studies (28 datasets) were included in the present meta-analysis, including 12 studies (13 datasets) related to resting-state functional brain activity (496 EOS patients, 395 HCs) and 15 studies (15 datasets) related to GMV (458 EOS patients, 531 HCs). Overall, in the functional meta-analysis, patients with EOS showed significantly increased resting-state functional brain activity in the left middle frontal gyrus (extending to the triangular part of the left inferior frontal gyrus) and the right caudate nucleus. On the other hand, in the structural meta-analysis, patients with EOS showed significantly decreased GMV in the right superior temporal gyrus (extending to the right rolandic operculum), the right middle temporal gyrus, and the temporal pole (superior temporal gyrus). Conclusion: This meta-analysis revealed that some regions in the EOS exhibited significant structural or functional abnormalities, such as the temporal gyri, prefrontal cortex, and striatum. These findings may help deepen our understanding of the underlying pathophysiological mechanisms of EOS and provide potential biomarkers for the diagnosis or treatment of EOS. [ABSTRACT FROM AUTHOR]

It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies. [ABSTRACT FROM AUTHOR]

Early detection of brain abnormalities is vital for enhancing patient outcomes and survival rates. However, accurately identifying and segmenting these abnormalities from MRI images remains a persistent challenge. This study assesses the efficacy of the Selective Local Image Fitting (SLIF) model in segmenting brain abnormalities from colour MRI images and compares its performance with converted greyscale counterparts. The rationale behind this comparison stems from standard practice in image segmentation, where colour images are often converted to greyscale before the segmentation task. Converting the image might degrade data by diminishing its dimensions, potentially affecting segmentation computations. This study intends to evaluate the influence of colour information on segmentation accuracy and efficiency by directly assessing the SLIF model on both colour and converted greyscale images. Segmentation accuracy was evaluated using metrics such as the Dice Similarity Coefficient (DSC), Matthews Correlation Coefficient (MCC), and Intersection-over-Union (IoU). Efficiency was determined by measuring the average elapsed processing time. Experimental results demonstrate that colour MRI brain images outperform their converted greyscale counterparts in segmentation accuracy, as colour providing essential supplementary information for precise abnormality delineation. Despite a slight increase in average elapsed processing time for colour images, the enhanced accuracy justifies this trade-off. These findings emphasize the importance of colour MRI in enhancing diagnostic accuracy, especially in detecting brain abnormalities. This study can be extended in future work to evaluate the segmentation accuracy and efficiency of brain abnormalities in 3D colour and greyscale MRI images. [ABSTRACT FROM AUTHOR]

Background: Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG‐1 syndromes, most of which are inherited as autosomal recessive traits, although X‐linked inheritance has also been reported. Pathogenic variants in the asparagine‐linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date. Methods: We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant. Results: All three males have a de novo mutation, infantile spasms, DEE, drug‐resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13. Conclusion: The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV), transmitted by Aedes mosquitoes, has been a global health concern since 2007. It primarily causes fetal microcephaly and neuronal defects through maternal transmission and induces neurological complications in adults. Recent studies report elevated proinflammatory cytokines and persistent neurological alterations post recovery, but the in vivo mechanisms remain unclear. In our study, viral RNA loads in the brains of mice infected with ZIKV peaked at 7 days post infection and returned to baseline by day 21, indicating recovery. RNA sequencing of the cerebral cortex at 7 and 21 days revealed upregulated genes related to neuroinflammation and microglial activation. Histological analyses indicated neuronal cell death and altered neurite morphology owing to severe neuroinflammation. Additionally, sustained microglial activation was associated with increased phospho-Tau levels, constituting a marker of neurodegeneration. These findings highlight how persistent microglial activation leads to neuronal dysfunction post ZIKV recovery, providing insights into the molecular pathogenesis of ZIKV-induced brain abnormalities. [ABSTRACT FROM AUTHOR]

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches. [ABSTRACT FROM AUTHOR]

The development of structural and functional magnetic resonance imaging (MRI) techniques over the decades has led to many studies seeking to identify cerebral abnormalities in amblyopia. The cause of reduced visual acuity and other visual characteristics of this common visual disorder cannot be identified by standard ophthalmological examination. As there are several variants of this disease, with fundamental differences in etiology, it is natural to suggest that there are different types of corresponding abnormalities in the brain. Thus, until a general picture of the pathogenesis of amblyopia is obtained, studies on groups of specially selected patients with similar symptomatologies are very important. The present paper presents a study of school-age children with left-sided anisometropic amblyopia. Structural MRI revealed interhemisphere differences in the thickness of the lateral occipital cortex in these patients, while resting-state functional MRI revealed interhemisphere differences in local hemodynamic signal coherence in Brodmann area 17 and in the functional connectivity of area 17 with areas 18 and 19. The results contribute to the creation of a general MRI database on the pathophysiology of amblyopia, clarify some controversial issues, and indicate the feasibility of using resting-state functional MRI in ophthalmology. [ABSTRACT FROM AUTHOR]

Schizencephaly arises from irregular neuronal migration leading to clefts development in the cerebral cortex. The condition is often detected in childhood and it is extremely rare to go unnoticed. This case highlights a 45-year-old male with no previous medical history who presented with a seizure for the first time in the emergency department after which an MRI was done and detected schizcenphaly which at this point was the first time for the patient to be diagnosed with this condition. The available data on schizcencphaly in the literature is very little and the data on the condition when diagnosed in adulthood is even less, hence our case report aims to shed light on this unthought etiology of adult-onset seizures which could have major potential risks if not detected. Adults who receive a diagnoses later in life may face prognosis issues hence imaging should be encouraged to be a part of seizure workup to avoid underdiagnoses of brain abnormalities that may go unnoticed in childhood.

Numerous studies have underscored the presence of abnormal intrinsic neural activity (INA) in individuals with depression. However, recognizing that the age stage may influence the pathophysiology of depression, our study sought to delve into the interplay of depression and age on INA and molecular architecture. One hundred and thirty-eight first-episode depression patients and 120 healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging. The participants were stratified into four groups based on age. Utilizing amplitude of low-frequency fluctuation (ALFF) analyses, we employed an ANCOVA to compare INA patterns in four groups. Additionally, we conducted correlation analyses between ALFF and neurotransmitter maps to elucidate molecular underpinnings of INA abnormalities. In comparison to adolescents with early-onset depression and adult HC, adult-onset depression exhibited increased ALFF in the right paracentral lobule. Conversely, early-onset depression, when contrasted with adolescent HC, displayed reduced ALFF in the right paracentral lobule. The interactive brain regions affected by ALFF alterations were associated with serotonergic, GABAergic, and opioid neurotransmitter systems. The present study was limited to its cross-sectional design. This study illuminates an antagonistic effect of depression and age on brain activity in paracentral lobule and provides molecular underpinnings of the corresponding INA abnormalities related to key neurotransmitter systems. These insights may prove valuable in the development of neuromarkers for clinical intervention and treatment of depression. • Our study underscores the significance of age status in depression and reveals an antagonistic effect induced by depression and age on brain activity. • The molecular underpinnings of these brain activity abnormalities are associated with key neurotransmitter systems. • These insights may prove valuable in the development of neuromarkers for clinical intervention and treatment of depression. [ABSTRACT FROM AUTHOR]

Cerebral/cortical visual impairment (CVI), a brain-based condition, has emerged as a leading cause of pediatric visual impairment in the United States and other industrialized nations. The National Eye Institute (NEI) recognized CVI as a priority area for research as part of their 2021 NEI Vision for the Future Strategic Plan and partnered with the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurologic Disorders and Stroke within the National Institutes of Health (NIH) to sponsor a CVI Workshop in November 2023. A panel consisting of a group of clinicians with expertise in diagnosing CVI convened to draft a working definition for this condition. Five key elements were identified: (1) CVI encompasses a spectrum of visual impairments caused by an underlying brain abnormality that affects the development of visual processing pathways and is characterized by deficits in visual function and functional vision; (2) the visual dysfunction in CVI is greater than expected by any comorbid ocular conditions alone; (3) the visual dysfunction in CVI may manifest as lower-order or higher-order afferent visual deficits, or both, leading to characteristic behaviors in affected individuals; (4) although CVI may be comorbid with other neurodevelopmental disorders, CVI is not primarily a disorder of language, learning, or social communication; and (5) the underlying neurologic insult of the developing brain may go unrecognized or undiagnosed until later in life. Future work is needed to achieve consensus on nomenclature, diagnostic criteria, and strategies for early identification and intervention. The NIH is developing a CVI registry to collect relevant demographic and clinical data prospectively and longitudinally to help inform future research questions and to provide insight into considerations for future clinical trials in the field of CVI. [ABSTRACT FROM AUTHOR]

Backgroud: Neurological disorders are common in preterm (PT) born individuals. Diffusion tensor imaging (DTI) studies using tract-based spatial statistics (TBSS) effectively detect microstructural white matter (WM) abnormalities in the brain. We conducted this systematic review to integrate the findings of TBSS studies to determine the most consistent WM alterations in PT born individuals. Methods: PubMed, embase, Web of Science and Science Direct were searched. DTI studies using TBSS in PT born individuals were screened up to October 2022. The systematic review included studies reporting alterations in FA values for the entire brain in a stereotactic space, with three coordinates (x, y, z), according to the seed-based d mapping method. Results: The search strategy identified seventeen studies that fulfilled our inclusion criteria, with a total of 911 PT-born individuals and 563 matched controls were analysed. Of the seventeen studies, eight were dedicated to 650 adults, five to 411 children and four to 413 infants. Ten studies recruited 812 individuals born very prematurely (GA <29 weeks), six studies recruited 386 moderately premature individuals (GA = 29-32 weeks) and one study recruited 276 individuals born late prematurely (GA >32 weeks). This meta-analysis of six studies including 388 individuals highlighted four brain regions in which fractional anisotropy (FA) was lower in PT group than in people born at term. The quantitative meta-analysis found that the most robust WM alterations were located in the corpus callosum (CC), the bilateral thalamus and the left superior longitudinal fasciculus (SLF) II. Significant changes in FA reflect WM abnormalities in PT born individuals from infant to young adulthood. Conclusions: Significant changes in FA reflect WM abnormalities in individuals born PT from infancy to young adulthood. The abnormal development of the CC, bilateral thalamus and left SLF may play a vital role in the neurodevelopment of PT individuals. [ABSTRACT FROM AUTHOR]

Maternal immune activation (MIA) induces a variety of behavioral and brain abnormalities in offspring of rodent models, compatible with neurodevelopmental disorders, such as schizophrenia or autism. However, it remains controversial whether MIA impairs reversal learning, a basic expression of cognitive flexibility that seems to be altered in schizophrenia. In the present study, MIA was induced by administration of a single dose of polyriboinosinic‐polyribocytidylic acid (Poly (I:C) (5 mg/kg i.p.)) or saline to mouse pregnant dams in gestational day (GD) 9.5. Immune activation was monitored through changes in weight and temperature. The offspring were evaluated when they reached adulthood (8 weeks) using a touchscreen‐based system to investigate the effects of Poly (I:C) on discrimination and reversal learning performance. After an initial pre‐training, mice were trained to discriminate between two different stimuli, of which only one was rewarded (acquisition phase). When the correct response reached above 80% values for two consecutive days, the images were reversed (reversal phase) to assess the adaptation capacity to a changing environment. Maternal Poly (I:C) treatment did not interfere with the learning process but induced deficits in reversal learning compared to control saline animals. Thus, the accuracy in the reversal phase was lower, and Poly (I:C) animals required more sessions to complete it, suggesting impairments in cognitive flexibility. This study advances the knowledge of how MIA affects behavior, especially cognitive domains that are impaired in schizophrenia. The findings support the validity of the Poly (I:C)‐based MIA model as a tool to develop pharmacological treatments targeting cognitive deficits associated with neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Background: The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain restingstate (rs)-activity with disease-related features. Methods: Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables. Results: Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity. Conclusion: Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes. [ABSTRACT FROM AUTHOR]

• Use multimodal functional imaging data. • Explore abnormalities in goal-directed and habitual-learning in patients with OCD. • Abnormal brain regions of goal-directed is associated with duration of illness. • Abnormal brain regions of goal-directed can distinguish the duration of illness. It is increasingly evident that structural and functional changes in brain regions associated with obsessive–compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate whether idiopathic cuneate gyrus herniation (ICH) is an anomaly or a normal variant, its prevalence, whether there is a coexisting finding or pathology, as well as to characterize it with magnetic resonance imaging (MRI) findings. Method: We evaluated 0-17-year-olds’ brain MR images from January 2021-August 2023 at our clinic. Standard brain protocols utilize 1.5 Tesla MRI scanners. ICH and congenital brain abnormalities were evaluated in optimal brain MRIs. Malformations were classified as posterior fossa anomalies (PFA), commissural and cortical developmental anomalies (CCDA), and midline malformations. Results: Our study comprised 691 pediatric brain MRIs with a mean age of 5.93±3.4 years, with 48.77% male and 51.23% female. The mean age of 32 ICH (+) patients was 6.19±4.02 years, with 40.63% male and 59.37% female. The prevalence of ICH was 32/691 (4.6%). In 63 (9.11%) congenital brain malformation patients, ICH presence differed (p=0.005). Congenital brain malformation patients with ICH showed a significantly higher PFA rate (n=8) than without ICH. The frequency of CCDA (n=23) and the association of PFA and CCDA (n=12) were significantly higher in ICH patients with congenital brain malformation. The frequency of congenital brain malformation was higher in 32 ICH (+) patients, with a rate of 50% (p<0.001). Conclusion: We found that ICH is more frequent than reported and may be associated with congenital brain malformations. ICH must be differentiated from pathology to avoid unnecessary procedures. Congenital brain abnormalities may accompany ICH and should be carefully screened. [ABSTRACT FROM AUTHOR]

Background: Upon learning that a mental disorder has a biological etiology (e.g., multiple gene interactions, brain abnormalities), people tend to doubt the effectiveness of psychotherapy even though psychotherapy combined with pharmacotherapy is often considered optimal. The aim of this study was to empirically identify reasons for this lessened perceived effectiveness of psychotherapy. Methods: Participants (N = 278 U.S. adults) indicated their endorsement of three beliefs hypothesized to explain the reduced perceived effectiveness of psychotherapy for a mental disorder with a biological etiology; (1) the belief that mental activities affect the brain less than they affect the mind, (2) the belief that biological processes are less controllable than psychological processes, and (3) the belief that psychosocial causes are less likely to be present when biological causes are present. Additionally, participants judged the effectiveness of psychotherapy for a hypothetical case of depression before and after learning about its biological etiology. Results: Participants endorsed each of the proposed beliefs. Furthermore, the extent of holding these beliefs correlated with the extent to which psychotherapy was undermined after learning that a hypothetical patient's depression was biologically caused. Conclusions: By identifying these beliefs, the current findings offer specific strategies to mitigate the lessened perceived effectiveness of psychotherapy for mental disorders with biological etiologies. [ABSTRACT FROM AUTHOR]

The aim of our study is to define the most frequent etiology, clinical presentation, and predictive factors of outcome in children with acute ataxia (AA) and to determine "the red flags" in the diagnostic approach to children with AA. The retrospective study included the patients with AA treated in the institute from 2015 to 2021. The inclusion criteria were children aged 1–18 years, evolution time of ataxia within 72 h, and diagnosis made by a physician. The exclusion criteria were anamnestic data about ataxia without confirmation by any physician, chronic/persistent ataxia, and psychogenic or postictal ataxia. Clinical presentation was divided into two categories: (1) isolated cerebellar signs (CS): ataxic gait, dysmetria, dysdiadochokinesia, intention tremor, dysarthria, and nystagmus; (2) CS-plus symptoms which included CS associated with any of other symptoms such as encephalopathy (GCS < 15), awareness disturbances, vomiting, headache, a new onset limb or facial paresis, torticollis, hypotonia, and opsoclonus. The outcome was assessed at the end of hospitalization and was defined as complete or incomplete recovery. The study included 76 children, with a mean age of 5.7 years (IQR 2.1–8.3). The most frequent causes of AA were immune-mediated/infective cerebellar ataxia in 27 (35.5%), and intoxication in 24 (31.6%) cases, followed by vestibular ataxia, opsoclonus-myoclonus-ataxia syndrome, and intracranial expansive process. Forty-two (56%) cases experienced isolated CS, and 35 (46%) cases had CS-plus. Complete recovery was experienced by 62 (81.6%) patients. Analysis of some risk factors (sex, age, presence of previous infection, "cerebellar plus symptoms," and structural abnormalities/neuroimaging abnormalities) and their relation to outcome was performed. Analysis showed that presence of additional symptoms to ataxia, so called "cerebellar plus symptoms" (p = 0.002) and structural abnormalities (p < 0.001), had statistically higher frequency of poor outcome. Statistical significance remained in the univariate analysis. Significant data was included in multivariate logistic regression analysis which also showed that presence of "cerebellar plus symptoms" (p = 0.021) and structural abnormalities (p = 0.002) is related to a poor outcome. Most of the children with AA have "benign" etiology such as intoxication and post/parainfectious cerebellar ataxia with favorable outcomes. On the other hand, AA might be the first manifestation of CNS neoplasm or paraneoplastic phenomena. "The red flags" associated with cerebellar signs are limbs or facial palsy, hypotonia, GCS < 15, vomiting, opsoclonus, headache, myoclonus, visual impairment, torticollis, and vertigo. The presence of those signs and/or structural brain abnormalities was related to poor outcomes in children with AA. [ABSTRACT FROM AUTHOR]

Objective: Infantile seizures cause great concern for both doctors and parents. In addition to modern neuroimaging and genetics, clinical tools helpful in predicting the course of the disease are needed. We prospectively studied the incidence, electroclinical characteristics and etiologies of epilepsy syndromes with onset before the age of 12 months and looked for prognostic determinants of outcome by age 24 months. Methods: From February 2017 through May 2019, we recruited all eligible infants diagnosed with epilepsy at our unit. Data on electroclinical studies, genetic investigations and drug response were gathered prospectively. The infants were given a structured neurological examination (Hammersmith Infantile Neurological examination [HINE] and Griffiths scales) at predetermined intervals until age 24 months at which age neurocognitive evaluation with Bayley scales was performed. Results: Included were 60 infants (27 female). The mean onset age of epilepsy was 5.3 (±2.5 standard deviation) months. The incidence of epilepsy in the population‐based cohort was 131 (95% confidence interval 99–172)/100 000. Epilepsy syndrome was identified in 80% and etiology in 58% of infants. Self‐limited infantile epilepsy was the second most common syndrome (incidence 18/100 000) after infantile epileptic spasms syndrome. PRRT2 was the most common monogenic cause. At age 24 months, 37% of the infants had drug‐resistant epilepsy (DRE) and half had a global developmental delay (GDD). Abnormal first HINE was the strongest predictor of GDD, followed by DRE and identified etiology. DRE was associated with structural etiology and GDD. Those with normal first HINE and good response to treatment had favorable outcomes, irrespective of the identified etiology. Significance: Our results support a high incidence of self‐limited epilepsy in infancy and PRRT2 as the genetic cause in the first year of life. Notwithstanding the advances in etiological discovery, we want to highlight the importance of clinical evaluation as standardized neurological examination with HINE proved a valuable tool in prognostication. Plain Language Summary: One in every 700–800 babies develop epilepsy within the first year after birth. Our study identified an epilepsy syndrome in 80% and the cause of epilepsy in 60% of the participants. By age 2 years, over one‐third of the children still experienced seizures, and almost half faced significant developmental delay. Structural brain abnormalities increased the likelihood of difficult epilepsy and developmental challenges. Babies whose epilepsy was caused by a gene defect varied widely in development and response to medications. Babies with normal neurological examination at first visit, especially if their seizures stopped quickly, had favorable development. [ABSTRACT FROM AUTHOR]

Mania is associated with disturbed dopaminergic transmission in frontotemporal regions. D-amphetamine (AMPH) causes increased extracellular DA levels, considered an acknowledged mania model in rodents. Doxycycline (DOXY) is a second-generation tetracycline with promising neuroprotective properties. Here, we tested the hypothesis that DOXY alone or combined with Lithium (Li) could reverse AMPH-induced mania-like behavioral alterations in mice by the modulation of monoamine levels in brain areas related to mood regulation, as well as cytoprotective and antioxidant effects in hippocampal neurons. Male Swiss mice received AMPH or saline intraperitoneal (IP) injections for 14 days. Between days 8–14, mice receive further IP doses of DOXY, Li, or their combination. For in vitro studies, we exposed hippocampal neurons to DOXY in the presence or absence of AMPH. DOXY alone or combined with Li reversed AMPH-induced risk-taking behavior and hyperlocomotion. DOXY also reversed AMPH-induced hippocampal and striatal hyperdopaminergia. In AMPH-exposed hippocampal neurons, DOXY alone and combined with Li presented cytoprotective and antioxidant effects, while DOXY+Li also increased the expression of phospho-Ser133-CREB. Our results add novel evidence for DOXY's ability to reverse mania-like features while revealing that antidopaminergic activity in some brain areas, such as the hippocampus and striatum, as well as hippocampal cytoprotective effects may account for this drug's antimanic action. This study provides additional rationale for designing clinical trials investigating its potential as a mood stabilizer agent. Doxycycline combined with Lithium reversed mania-like features induced by D-amphetamine (AMPH), notably risk-taking and vigor-like behaviors and hyperdopaminergic state in mice brain. This combination protected hippocampal neurons in vitro from increased oxidative damage and cytotoxicity. An increase in dopamine transporter (DAT) expression and CREB phospho-activation are potential underlying mechanisms. Abbreviations: AMH: amphetamine; CREB: cAMP response element binding protein; DA: dopamine: DAT: dopamine transporter; NE: noradrenaline. Created with BioRender.com [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TMA) in association with RNA exosome encoding mutations has only recently been recognized. Here, we present an infant (female) with an EXOSC5 mutation (c.230_232del p.Glu77del) associated with the clinical phenotype known as CABAC syndrome (cerebellar ataxia, brain abnormalities, and cardiac conduction defects), including pontocerebellar hypoplasia, who developed renal TMA. At the age of four months, she presented with signs of septic illness, after which she developed TMA. A stool culture showed rotavirus as a potential trigger. The patient received eculizumab once, alongside supportive treatment, while awaiting diagnostic analysis of TMA, including genetic complement analysis, all of which were negative. Eculizumab was withdrawn and the patient's TMA recovered quickly. A review of the literature identified an additional four patients (age < 1 year) who developed TMA after a viral trigger in the presence of mutations in EXOSC3. The recurrence of TMA in one of these patients with an EXOSC3 mutation while on eculizumab treatment underscores the apparent lack of responsiveness to C5 inhibition. In conclusion, mutations in genes influencing the RNA exosome, like EXOSC3 and EXOSC5, characterized by neurodevelopment and neurodegenerative disorders could potentially lead to TMA in the absence of complement dysregulation. Hence, these patients were likely non-responsive to eculizumab. [ABSTRACT FROM AUTHOR]

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy are starting to be unraveled, namely in the supraspinal pain modulatory system. Based on our interests and experience in the field, we undertook a review of the brain-centered alterations that may underpin pain in CIPN. The changes in the descending pain modulation in CIPN models along with the functional and connectivity abnormalities in the brain of CIPN patients are analyzed. A translational analysis of preclinical findings about descending pain regulation during CIPN is reviewed considering the main neurochemical systems (serotoninergic and noradrenergic) targeted in CIPN management in patients, namely by antidepressants. In conclusion, this review highlights the importance of studying supraspinal areas involved in descending pain modulation to understand the pathophysiology of CIPN, which will probably allow a more personalized and effective CIPN treatment in the future. [ABSTRACT FROM AUTHOR]