Urine-derived cells from the aged donor for the 2D/3D modeling of neural cells via iPSCs.

Human neural cell models derived from induced pluripotent stem cells (iPSCs) have been widely accepted to model various neurodegenerative diseases such as Alzheimer's disease (AD) in vitro. Although the most common sources of iPSCs are fibroblasts and peripheral blood mononuclear cells, the collection of these cells is invasive. To reduce the donor's burden, we propose the use of urine-derived cells (UDCs), which can be obtained non-invasively from a urine sample. However, the collection of UDCs from elderly donors suffering from age-related diseases such as AD has not been reported, and it is unknown whether these UDCs from the donor aged over 80 years old can be converted into iPSCs and differentiated into neural cells. In this study, we reported a case of using the UDCs from the urine sample of an 89-year-old AD patient, and the UDCs were successfully reprogrammed into iPSCs and differentiated into neural cells in four different ways: (i) the dual SMAD inhibition with small-molecules via the neural progenitor precursor stage, (ii) the rapid induction method using transient expression of Ngn2 and microRNAs without going through the neural progenitor stage, (iii) the cortical brain organoids for 3D culture, and (iv) the human astrocytes. The accumulation of phosphorylated Tau proteins, which is a pathological hallmark of AD, was examined in the neuronal models generated from the UDCs of the aged donor. The application of this cell source will broaden the target population for disease modeling using iPS technology.

A novel organotypic cortical slice culture model for traumatic brain injury: molecular changes induced by injury and mesenchymal stromal cell secretome treatment.

Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a screening platform for drug testing are lacking. Here we developed a new in vitro model of brain contusion on organotypic cortical brain slices and tested its responsiveness to mesenchymal stromal cell (MSC) derived secretome. A focal TBI was induced on organotypic slices by an electromagnetic impactor. Compared to control condition, a temporal increase in cell death was observed after TBI by propidium iodide incorporation and lactate dehydrogenase release assays up to 48 h post-injury. TBI induced gross neuronal loss in the lesion core, with disruption of neuronal arborizations measured by microtubule-associated protein-2 (MAP-2) immunostaining and associated with MAP-2 gene down-regulation. Neuronal damage was confirmed by increased levels of neurofilament light chain (NfL), microtubule associated protein (Tau) and ubiquitin C-terminal hydrolase L1 (UCH-L1) released into the culture medium 48 h after TBI. We detected glial activation with microglia cells acquiring an amoeboid shape with less ramified morphology in the contusion core. MSC-secretome treatment, delivered 1 h post-injury, reduced cell death in the contusion core, decreased NfL release in the culture media, promoted neuronal reorganization and improved microglia survival/activation. Our 3D in vitro model of brain contusion recapitulates key features of TBI pathology. We showed protective effects of MSC-secretome, suggesting the model stands as a tractable medium/high throughput, ethically viable, and pathomimetic biological asset for testing new cell-based therapies.

A simplified protocol for the generation of cortical brain organoids.

Human brain organoid technology has the potential to generate unprecedented insight into normal and aberrant brain development. It opens up a developmental time window in which the effects of gene or environmental perturbations can be experimentally tested. However, detection sensitivity and correct interpretation of phenotypes are hampered by notable batch-to-batch variability and low reproducibility of cell and regional identities. Here, we describe a detailed, simplified protocol for the robust and reproducible generation of brain organoids with cortical identity from feeder-independent induced pluripotent stem cells (iPSCs). This self-patterning approach minimizes media supplements and handling steps, resulting in cortical brain organoids that can be maintained over prolonged periods and that contain radial glial and intermediate progenitors, deep and upper layer neurons, and astrocytes.

Structural polymorphism and cytotoxicity of brain-derived ß-amyloid extracts.

To date, more than 37 amyloidogenic proteins have been found to form toxic aggregates that are implicated in the progression of numerous debilitating protein misfolding diseases including Alzheimer's disease (AD). Extensive literature highlights the role of ß-amyloid (Aß) aggregates in causing excessive neuronal cell loss in the brains of AD patients. In fact, major advances in our understanding of Aß aggregation process, including kinetics, toxicity, and structures of fibrillar aggregates have been revealed by examining in vitro preparations of synthetic Aß peptides. However, ongoing research shows that brain-derived Aß aggregates have specific characteristics that distinguish them from in vitro prepared species. Notably, the molecular structures of amyloid fibrils grown in the human brain were found to be markedly different than synthetic Aß fibrils. In addition, recent findings report the existence of heterogeneous Aß proteoforms in AD brain tissue in contrast to synthetically produced full-length aggregates. Despite their high relevance to AD progression, brain-derived Aß species are less well-characterized compared with synthetic aggregates. The aim of this review is to provide an overview of the literature on brain-derived Aß aggregates with particular focus on recent studies that report their structures as well as pathological roles in AD progression. The main motivation of this review is to highlight the importance of utilizing brain-derived amyloids for characterizing the structural and toxic effects of amyloid species. With this knowledge, brain-derived aggregates can be adopted to identify more relevant drug targets and validate potent aggregation inhibitors toward designing highly effective therapeutic strategies against AD.

To Study the Effect of Anterior Palatal Surface Modifications of Complete Denture on Speech Intelligibility Oral Perception and Cortical Brain Function Activity: An In Vivo Study.

BACKGROUND:  The classic maxillary full denture covers the whole palate, preventing the tongue from touching the denture base tissues itself. Thus, it has deleterious effects on cortical brain function and the ability to understand spoken language. AIM:  This study aimed to determine the effect of anterior palatal surface modifications of the complete denture on speech intelligibility oral perception and cortical brain function activity. METHODS AND MATERIALS:  This study compared the speech clarity, oral discernment, and cortical mind capability activity of complete denture wearers in three study groups: a) complete denture wearers with a small opening (SO) in the maxillary front palatal base; b) complete denture patients who wear regular complete denture; c) complete denture patients who did not wear complete denture; and d) complete denture patients who wear a functionally contoured modified palate (FCMP). Patients with no teeth at all underwent four phases of testing to assess their cognitive abilities and speech quality (pitch and volume). In the first phase, partial dentures were used. During phase 2, a conventional full denture was inserted. In the third phase, a palatal base denture was functionally altered. In phase 4, dentures with a little aperture at the front of the palatal base were used.  Results: The values of pitch and intensity of sound in category A with FCMP modification I were 180.76 ± 24.12 and 73.27 ± 9.74, respectively. On the other hand, the values of pitch and intensity of sound in category B with FCMP modification I were 185.41 ± 27.29 and 73.91 ± 8.31, respectively. The values of pitch and intensity of sound in category A with SO modification II were 188.52 ± 21.11 and 76.13 ± 5.21, respectively. On the other hand, the values of pitch and intensity of sound in category B with SO modification II were 194.59 ± 24.02 and 75.21 ± 6.12, respectively. The findings for values of pitch and intensity were statistically significant among the four phases (p < 0.001). The highest speech intelligibility and cortical brain function were observed in phase 4 in both categories A and B, with the highest scores by experts of 3.21 and 3.42, respectively. Conclusion: Based on the findings of this in vivo investigation, it can be concluded that using modified dentures (modification types I and II) following denture installation improves speech intelligibility, oral perception, and cortical brain function activity.

Transient receptor potential Ankyrin-1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices.

Oligodendrocytes are highly specialized glial cells characterized by their production of multilayer myelin sheaths that wrap axons to speed up action potential propagation. It is due to their specific role in supporting axons that impairment of myelin structure and function leads to debilitating symptoms in a wide range of degenerative diseases, including Multiple Sclerosis and Leukodystrophies. It is known that myelin damage can be receptor-mediated and recently oligodendrocytes have been shown to express Ca2+ -permeable Transient Receptor Potential Ankyrin-1 (TRPA1) channels, whose activation can result in myelin damage in ischemia. Here, we show, using organotypic cortical slice cultures, that TRPA1 activation, by TRPA1 agonists JT010 and Carvacrol for varying lengths of time, induces myelin damage. Although TRPA1 activation does not appear to affect oligodendrocyte progenitor cell number or proliferation, it prevents myelin formation and after myelination causes internodal shrinking and significant myelin degradation. This does not occur when the TRPA1 antagonist, A967079, is also applied. Of note is that when TRPA1 agonists are applied for either 24 h, 3 days or 7 days, axon integrity appears to be preserved while mature myelinated oligodendrocytes remain but with significantly shortened internodes. These results provide further evidence that TRPA1 inhibition could be protective in demyelination diseases and a promising therapy to prevent demyelination and promote remyelination.

Motor symptoms in Parkinson's disease are related to the interplay between cortical curvature and thickness.

INTRODUCTION: Brain atrophy in Parkinson's disease occurs to varying degrees in different brain regions, even at the early stage of the disease. While cortical morphological features are often considered independently in structural brain imaging studies, research on the co-progression of different cortical morphological measurements could provide new insights regarding the progression of PD. This study's aim was to examine the interplay between cortical curvature and thickness as a function of PD diagnosis, motor symptoms, and cognitive performance. METHODS: A total of 359 de novo PD patients and 159 healthy controls (HC) from the Parkinson's Progression Markers Initiative (PPMI) database were included in this study. Additionally, an independent cohort from four databases (182 PD, 132 HC) with longer disease durations was included to assess the effects of PD diagnosis in more advanced cases. Pearson correlation was used to determine subject-specific associations between cortical curvature and thickness estimated from T1-weighted MRI images. General linear modeling (GLM) was then used to assess the effect of PD diagnosis, motor symptoms, and cognitive performance on the curvature-thickness association. Next, longitudinal changes in the curvature-thickness correlation as well as the predictive effect of the cortical curvature-thickness association on changes in motor symptoms and cognitive performance across four years were investigated. Finally, Akaike information criterion (AIC) was used to build a GLM to model PD motor symptom severity cross-sectionally. RESULTS: A significant interaction effect between PD motor symptoms and age on the curvature-thickness correlation was found (ßstandardized = 0.11; t(350) = 2.12; p = 0.03). This interaction effect showed that motor symptoms in older patients were related to an attenuated curvature-thickness association. No significant effect of PD diagnosis was observed for the PPMI database (ß = 0.03; t(510) = 0.35; p = 0.72). However, in patients with a longer disease duration, a significant effect of diagnosis on the curvature-thickness association was found (ßstandardized = 0.31; t(306.7) = 3.49; p = 0.0006). Moreover, rigidity, but not tremor, in PD was significantly related to the curvature-thickness correlation (ßstandardized = 0.11, t(350) = 2.24, p = 0.03; ßstandardized = -0.03, t(350) = -0.58, p = 0.56, respectively). The curvature-thickness association was attenuated over time in both PD and HC, but the two groups did not show a significantly different effect (ßstandardized = 0.03, t(184.7) = 0.78, p = 0.44). No predictive effects of the CC-CT correlation on longitudinal changes in cognitive performance or motor symptoms were observed (all p-values > 0.05). The best cross-sectional model for PD motor symptoms included the curvature-thickness correlation, cognitive performance, and putamen dopamine transporter (DAT) binding, which together explained 14 % of variance. CONCLUSION: The association between cortical curvature and thickness is related to PD motor symptoms and age. This research shows the potential of modeling the curvature-thickness interplay in PD.

Practical aspects of functional mri in clinical examinations / Aspectos práticos de rm funcional em exames clínicos / Aspectos prácticos de la rm funcional en los exámenes clínicos

The eloquent cerebral cortices are involved in movement, sensation, speech, vision, and higher cortical functions. Functional magnetic resonance imaging (fMRI) allows the evaluation of brain function, aiding in neurosurgical planning by mapping eloquent cortical areas. Considering the high cost of the hardware involved, the purpose of this work is to present a more affordable, in-house alternative for these studies that can provide adequate results in a clinical setting. We also present some practical information on how to perform these exams. We describe an affordable in-house hardware solution used by an imaging center, and examples of fMRI paradigms used to evaluate motor and language tasks. The fMRI studies show robust activations in eloquent areas consistent with the tasks performed on the exam. Images of post-processed studies illustrate clinical cases. The fMRI have well-established applications, mapping eloquent cortical areas in patients with brain lesions. In the case of surgical planning, it allows the surgeon to maximize the resection area while minimizing sequelae. More affordable hardware can reduce the cost of these exams, making them more accessible to the general public.

O córtex cerebral eloquente está envolvido nas atividades motora, sensação, fala, visão e funções corticais superiores. A ressonância magnética funcional (RMf) permite a avaliação da função cerebral, ajudando no planejamento neurocirúrgico através do mapeamento de áreas corticais eloquentes. Considerando o elevado custo do hardware envolvido, o objetivo deste trabalho é apresentar uma alternativa mais acessível para estes estudos, que possa fornecer resultados adequados em um ambiente clínico. Também apresentamos algumas informações práticas sobre a realização destes exames. Descrevemos uma solução de hardware acessível utilizada por um centro de imagens, e exemplos de paradigmas de RMf usados para avaliar tarefas motoras e relacionadas à fala. Os estudos de RMf mostram ativações em áreas eloquentes, consistentes com as tarefas realizadas no exame com imagens de estudos pós-processados ilustrando casos clínicos. A RMf tem aplicações bem estabelecidas, mapeando áreas corticais eloquentes em pacientes com lesões cerebrais. No caso do planejamento cirúrgico, permite que o cirurgião maximize a área de ressecção enquanto minimiza potenciais sequelas. Equipamentos mais acessíveis podem reduzir o custo destes exames, podendo aumentar a disponibilização ao público em geral.

La corteza cerebral elocuente está implicada en las actividades motoras, la sensibilidad, el habla, la visión y las funciones corticales superiores. La resonancia magnética funcional (RMf) permite la evaluación de la función cerebral, ayudando en la planificación neuroquirúrgica mediante el mapeo de las áreas corticales elocuentes. Teniendo en cuenta el elevado coste del hardware implicado, el objetivo de este artículo es presentar una alternativa más asequible para estos estudios que pueda proporcionar resultados adecuados en un entorno clínico. También presentamos información práctica sobre cómo realizar estos exámenes. Describimos una solución de hardware asequible utilizada por un centro de diagnóstico por imagen, y ejemplos de paradigmas de RMf utilizados para evaluar tareas motoras y relacionadas con el habla. Los estudios de RMf muestran activaciones en áreas elocuentes, coherentes con las tareas realizadas en el examen, con imágenes de estudios postprocesados que ilustran casos clínicos. La RMf tiene aplicaciones bien establecidas en el mapeo de áreas corticales elocuentes en pacientes con lesiones cerebrales. En el caso de la planificación quirúrgica, permite al cirujano maximizar el área de resección minimizando las posibles secuelas. Un equipo más asequible puede reducir el coste de estas exploraciones, aumentando potencialmente su disponibilidad para el público en general.

Structural, Functional and Neurochemical Cortical Brain Changes Associated with Chronic Low Back Pain.

Chronic low back pain (CLBP) is one of the most prevalent musculoskeletal disorders, being one of the leading contributors to disability worldwide and involving an important economic and social burden. Up to 90% of CLBP is non-specific (not associated with specific injuries), with a chronicity expectation estimated at 10%. Currently, motivational and emotional central circuits are being investigated due to their role in CLBP persistency and chronification. Therefore, this narrative review aimed to summarize the evidence regarding the cortical brain changes described for proposing novel multidisciplinary approaches. Novel advances in neuroimaging techniques demonstrated structural (e.g., decrease in the grey matter located at the dorsolateral prefrontal cortex), functional (e.g., connectivity impairments in those areas involved in pain processing), and neurochemical changes (e.g., decrease in cerebral metabolites). In addition, significant changes were found in the primary somatosensory and motor cortex, contributing to the alteration of low back muscles activation and function.

Severe cortical damage associated with COVID-19 case report.

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Moringa oleifera Lam. extract rescues lead-induced oxidative stress, inflammation, and apoptosis in the rat cerebral cortex.

In this study, we investigate the potential protective effect of Moringa oleifera Lam. extract (MOE) against lead-induced neurotoxicity. Wistar rats were allocated equally into (a) a control group, (b) a lead acetate (PbAc) group intraperitoneally injected with 20 mg/kg PbAc, (c) a MOE group orally gavaged with MOE (250 mg/kg), and (d) a MOE + PbAc group orally gavaged with MOE 3 hr before receiving intraperitoneal injections of PbAc. All rats were treated for 14 days. Our results revealed that PbAc-induced brain injury, accompanied by increased levels of oxidative stress markers. Moreover, Pb enhanced the inflammatory response and triggered neuronal apoptosis, as well as significantly depleted glutathione content and inhibited antioxidant enzyme activity. Interestingly, concurrent treatment with MOE ameliorated oxidative stress, inflammation, and apoptosis in the brain cortex. The current study provides evidence that MOE has the potential to protect neuronal tissues in PbAc-exposed rats via attenuation of nuclear factor-kappa B (NF-κB) signaling. PRACTICAL APPLICATIONS: This study reports the potential neuroprotective effect of Moringa oleifera Lam. (MOE) against lead-induced cortical brain toxicity. Our data reveal that PbAc-induced oxidative stress, neuroinflammation, and apoptosis in cortical tissues. However, simultaneous treatment of rats with MOE abrogated cortical brain inflammatory biomarkers, mitigated cortical tissue damage, and restrained oxidative stress, programmed cell death, and nuclear factor-kappa B (NF-κB) translocation. In addition, MOE stimulated detoxifying enzymes in PbAc-treated rats. These findings provide evidence that simultaneous treatment with MOE has the potential to attenuate PbAc-induced brain damage in rats by restraining oxidative stress, neuroinflammation, and apoptosis via attenuation of NF-κB signaling.

Subacute phase of subarachnoid haemorrhage in female rats: Increased intracranial pressure, vascular changes and impaired sensorimotor function.

OBJECTIVE: Early brain injury (EBI) and delayed cerebral ischemia (DCI) after subarachnoid haemorrhage (SAH) has devastating consequences but therapeutic options and the underlying pathogenesis remain poorly understood despite extensive preclinical and clinical research. One of the drawbacks of most preclinical studies to date is that the mechanisms behind DCI after SAH are studied only in male animals. In this study we therefore established a female rat model of SAH in order to determine subacute pathophysiological changes that may contribute to DCI in females. METHODS: Experimental SAH was induced in female rats by intracisternal injection of 300 µL of autologous blood. Sham operation served as a control. Neurological deficits and intracranial pressure measurements were evaluated at both 1 and 2 days after surgery. Additionally, changes in cerebral vascular contractility were evaluated 2 days after surgery using wire myography. RESULTS: SAH in female rats resulted in sensorimotor deficits and decreased general wellbeing on both day 1 and day 2 after SAH. Intracranial pressure uniformly increased in all rats subjected to SAH on day 1. On day 2 the intracranial pressure had increased further, decreased slightly or remained at the level seen on day 1. Furthermore, female rats subjected to SAH developed cortical brain edema. Cerebral arteries, isolated 2 days after SAH, exhibited increased vascular contractions to endothelin-1 and 5-carboxamidotryptamine. CONCLUSION: In the subacute phase after SAH in female rats, we observed increased intracranial pressure, decreased wellbeing, sensorimotor deficits, increased vascular contractility and cortical brain edema. Collectively, these pathophysiological changes may contribute to DCI after SAH in females. Previous studies reported similar pathophysiological changes for male rats in the subacute phase after SAH. Thus, prevention of these gender-independent mechanisms may provide the basis for a universal treatment strategy for DCI after SAH. Nevertheless, preclinical studies of potential therapies should employ both male and female SAH models.

[Research on the effect of background music on spatial cognitive working memory based on cortical brain network].

Background music has been increasingly affecting people's lives. The research on the influence of background music on working memory has become a hot topic in brain science. In this paper, an improved electroencephalography (EEG) experiment based on n-back paradigm was designed. Fifteen university students without musical training were randomly selected to participate in the experiment, and their behavioral data and the EEG data were collected synchronously in order to explore the influence of different types of background music on spatial positioning cognition working memory. The exact low-resolution brain tomography algorithm (eLORETA) was applied to localize the EEG sources and the cross-correlation method was used to construct the cortical brain function networks based on the EEG source signals. Then the characteristics of the networks under different conditions were analyzed and compared to study the effects of background music on people's working memory. The results showed that the difference of peak periods after stimulated by different types of background music were mainly distributed in the signals of occipital lobe and temporal lobe ( P < 0.05). The analysis results showed that the brain connectivity under the condition with background music were stronger than those under the condition without music. The connectivities in the right occipital and temporal lobes under the condition of rock music were significantly higher than those under the condition of classical music. The node degrees, the betweenness centrality and the clustering coefficients under the condition without music were lower than those under the condition with background music. The node degrees and clustering coefficients under the condition of classical music were lower than those under the condition of rock music. It indicates that music stimulation increases the brain activity and has an impact on the working memory, and the effect of rock music is more remarkable than that of classical music. The behavioral data showed that the response accuracy in the state of no music, classical music and rock music were 86.09% ± 0.090%, 80.96% ± 0.960% and 79.36% ± 0.360%, respectively. We conclude that background music has a negative impact on the working memory, for it takes up the cognitive resources and reduces the cognitive ability of spatial location.

Epigenetically Upregulated T-Type Calcium Channels Contribute to Abnormal Proliferation of Embryonic Neural Progenitor Cells Exposed to Valproic Acid.

Valproic acid is a clinically used mood stabilizer and antiepileptic drug. Valproic acid has been suggested as a teratogen associated with the manifestation of neurodevelopmental disorders, such as fetal valproate syndrome and autism spectrum disorders, when taken during specific time window of pregnancy. Previous studies proposed that prenatal exposure to valproic acid induces abnormal proliferation and differentiation of neural progenitor cells, presumably by inhibiting histone deacetylase and releasing the condensed chromatin structure. Here, we found valproic acid up-regulates the transcription of T-type calcium channels by inhibiting histone deacetylase in neural progenitor cells. The pharmacological blockade of T-type calcium channels prevented the increased proliferation of neural progenitor cells induced by valproic acid. Differentiated neural cells from neural progenitor cells treated with valproic acid displayed increased levels of calcium influx in response to potassium chloride-induced depolarization. These results suggest that prenatal exposure to valproic acid up-regulates T-type calcium channels, which may contribute to increased proliferation of neural progenitor cells by inducing an abnormal calcium response and underlie the pathogenesis of neurodevelopmental disorders.

Cortical Brain Age from Pre-treatment to Post-chemotherapy in Patients with Breast Cancer.

Chemotherapy-related cognitive impairment and associated brain changes may reflect accelerated brain aging; however, empirical evidence for this theory is limited. The purpose of this study was to measure brain aging in newly diagnosed patients with breast cancer treated with chemotherapy (n = 43) and compare its longitudinal change to that of controls (n = 50). Brain age indices, derived from cortical measures, were compared between women with breast cancer and matched healthy controls across 3 timepoints (time 1: pre-surgery, time 2: 1 month following chemotherapy completion, and time 3: 1-year post-chemotherapy). The breast cancer group showed a significant decrease in cortical thickness across the 3 timepoints (p < .001) and a trend towards significant increase in predicted brain age especially from pre-treatment (time 1) to post-chemotherapy (time 2) compared to controls (p = 0.08). Greater increase in predicted brain age was related to several clinical factors (HER-2 status, surgery type, and history of neoadjuvant chemotherapy) and greater decrease in cortical thickness was associated with greater decrease in performance on a verbal learning task from time 1 to time 3 (r = - 0.48, p < .01). This study demonstrated evidence of increased cortical brain aging in middle-aged patients with breast cancer following chemotherapy treatment that was associated with decreased verbal memory performance.

Research on the effect of background music on spatial cognitive working memory based on cortical brain network / 生物医学工程学杂志

Background music has been increasingly affecting people's lives. The research on the influence of background music on working memory has become a hot topic in brain science. In this paper, an improved electroencephalography (EEG) experiment based on n-back paradigm was designed. Fifteen university students without musical training were randomly selected to participate in the experiment, and their behavioral data and the EEG data were collected synchronously in order to explore the influence of different types of background music on spatial positioning cognition working memory. The exact low-resolution brain tomography algorithm (eLORETA) was applied to localize the EEG sources and the cross-correlation method was used to construct the cortical brain function networks based on the EEG source signals. Then the characteristics of the networks under different conditions were analyzed and compared to study the effects of background music on people's working memory. The results showed that the difference of peak periods after stimulated by different types of background music were mainly distributed in the signals of occipital lobe and temporal lobe ( < 0.05). The analysis results showed that the brain connectivity under the condition with background music were stronger than those under the condition without music. The connectivities in the right occipital and temporal lobes under the condition of rock music were significantly higher than those under the condition of classical music. The node degrees, the betweenness centrality and the clustering coefficients under the condition without music were lower than those under the condition with background music. The node degrees and clustering coefficients under the condition of classical music were lower than those under the condition of rock music. It indicates that music stimulation increases the brain activity and has an impact on the working memory, and the effect of rock music is more remarkable than that of classical music. The behavioral data showed that the response accuracy in the state of no music, classical music and rock music were 86.09% ± 0.090%, 80.96% ± 0.960% and 79.36% ± 0.360%, respectively. We conclude that background music has a negative impact on the working memory, for it takes up the cognitive resources and reduces the cognitive ability of spatial location.

Patterns of Cortical Structures and Cognition in Antipsychotic-Naïve Patients With First-Episode Schizophrenia: A Partial Least Squares Correlation Analysis.

BACKGROUND: Schizophrenia is associated with alterations in cortical structures and cognitive impairments, but antipsychotic medication may affect these measures. We investigated patterns of relationships between cortical structures and cognitive domains in antipsychotic-naïve patients with first-episode schizophrenia. METHODS: T1-weighted 3T magnetic resonance imaging was performed in 105 patients and 136 healthy control subjects. Using FreeSurfer, we obtained measurements of cortical thickness, surface area, and mean curvature. Using an extensive neurocognitive battery including the Danish Adult Reading Test and subtests from the Cambridge Neuropsychological Test Automated Battery, we obtained estimates of premorbid intelligence, spatial working memory, spatial planning, intra-extradimensional set shifting, and reaction and movement times. With univariate analyses, we tested group differences between cortical structures and cognition. With partial least squares correlation analyses, we investigated patterns of associations between cortical structures and cognition. RESULTS: Patients had significantly higher mean curvature and were impaired on 7 of 11 cognitive parameters. The between-group partial least squares correlation analysis revealed two cortical thickness/cognition patterns that differentiated patients and healthy control subjects (omnibus test, p = .011). Most cortical regions contributed reliably to these patterns. In patients, spatial working memory, spatial planning, reaction and movement times, and premorbid intelligence contributed reliably to the pattern; in healthy control subjects, spatial planning and intra-extradimensional set shifting contributed reliably. CONCLUSIONS: Antipsychotic-naïve patients with first-episode schizophrenia displayed a higher mean curvature, but no significant difference in other gray matter indices was found. Nevertheless, the pattern of associations between global cortical thickness and cognitive functions was markedly different between groups. These multivariate analyses reveal a novel linkage between regional cortical brain structure and cognitive deficits at the earliest, never-medicated illness stage.

Ultrastructural morphological alterations during hyperoxia exposure in relation to glutathione peroxidase activity and free radicals productions in the mitochondria of the cortical brain / Alteraciones morfológicas ultraestructurales durante la exposición a la hiperoxia en relación con la actividad de la glutatión peroxidasa y la producción de radicales libres en las mitocondrias de la corteza cerebral

Exposure to normobaric hyperoxia (NH) is known to increase the production of reactive oxygen species (ROS) by mitochondria. The present study was designed to examine mitochondrial ultrastructure morphological changes in the cortical brainin relation to glutathione peroxidase (GPX) activity and free radicals (FR) productions in brain tissue during hyperoxia exposure. The experimental groups were exposed to NH for 24 and 48 h continuously. Following the exposure periods, animals were sacrificed and cortical tissues were divided randomly into two parts; the first part was processed for the ultrastructural examination and the second was homogenized for GPX and FR determinations. Analysis of variance (ANOVA) showed that the main effects of O2 exposure periods were significant (p<0.05) for GPX and FR. Pair-wise means comparisons showed that NH elevated the average (+SE) GPX activity significantly (p<0.05) from the baseline control value of 5670.99+556.34 to13748.42+283.04 and 15134.19+1529.26 U/L with increasing length of NH exposure period from 24 to 48 h, respectively. Similarly, FR production was increased significantly (p<0.05) to 169.73+10.31 and 185.33+21.87, above baseline control of 105.27+5.25 Unit. Ultrastructure examination showed that O2 breathing for 48 h resulted in giant and swelled mitochondria associated with diluted inner membrane and damaged cristae. These mitochondria pathological alterations were associated with damages of myelin, axonal and cellular organelles. Normobaric-hyperoxia inducts mitochondria oxidative stress (MOS) and the subsequent rise of ROS causes variety of ultrastructure morphological pathological alterations in the organelles of cortical brain cells.

Se sabe que la exposición a la hiperoxia normobárica (HN) aumenta la producción de especies reactivas de oxígeno (ERO) por parte de las mitocondrias. El estudio se diseñó para examinar los cambios morfológicos de la ultraestructura mitocondrial en la corteza cerebral con la actividad de la glutatión peroxidasa (GPX) y la producción de radicales libres (RL) en el tejido cerebral durante la exposición a la hiperoxia. Los grupos experimentales fueron expuestos a HN durante 24 y 48 h continuamente. Tras los períodos de exposición, los animales se sacrificaron y los tejidos corticales se dividieron aleatoriamente en dos partes; la primera parte se procesó para el examen ultraestructural y la segunda se homogeneizó para las determinaciones de GPX y RL. El análisis de varianza (ANOVA) mostró que los efectos principales de los períodos de exposición al O2 fueron significativos (p <0,05) para GPX y RL. Las comparaciones de medias por pares mostraron que la HN elevó la actividad promedio de GPX (+ SE) significativamente (p <0,05) desde el valor de control de línea base de 5670,99 + 556,34 a 13748,42 + 283,04 y 15134,19 + 1529,26 U / L con una mayor duración del período de exposición a HN de 24 a 48 h, respectivamente. De manera similar, la producción de RL se incrementó significativamente (p <0,05) a 169,73 + 10,31 y 185,33 + 21,87, por encima del control de referencia de 105,27 + 5,25 unidades. El examen de la ultraestructura mostró que la respiración de O2 durante 48 h dio lugar a mitocondrias gigantes e hinchadas asociadas con la membrana interna diluida y las crestas dañadas. Estas alteraciones patológicas de las mitocondrias se asociaron con daños de mielina, axones y organelos celulares. La hiperoxia normobárica induce el estrés oxidativo mitocondrial (MOS) y el posterior aumento de las ERO provoca una variedad de alteraciones patológicas y morfológicas en los organelos de las células cerebrales corticales.

Neurosphere Development from Hippocampal and Cortical Embryonic Mixed Primary Neuron Culture: A Potential Platform for Screening Neurochemical Modulator.

Reconstitution of a complex biological structure or system following a simple and facile strategy using minimum physiochemical cues is challenging for an in-depth understanding of the system. In particular, the brain is a highly sophisticated and complex network of trillions of neurons and glial cells that controls function of our body. Understanding this complex machinery requires an innovative and simple bottom-up approach. In this venture, we report an easy and efficient strategy to culture cortical and hippocampal primary neurons from the E14-E16 embryo of Sprague-Dawley rat. This generates spontaneous neurospheres within 6-7 days of primary neuron culture of E14-E16 embryo. It further proliferates and forms radial glia-like structures, which are known to be the primary neural progenitor cells that differentiate into neurons, astrocytes, and oligodendrocytes. Interestingly, neurospheres lead to the formation of large projection neurons and radial glia, which mimic the early stage of cortical development in an in vivo system. Overall, this new, facile, strategic mixed primary neuron culture method offers a potential platform for understanding the effect of neurochemical modulators, which has tremendous future implications in the screening of neurotherapeutics.

Impaired short-term plasticity in restless legs syndrome: a pilot rTMS study.

BACKGROUND: Previous studies showed an impairment of the LTP-like plasticity to TMS in restless legs syndrome (RLS). Clinically, repetitive TMS (rTMS) was effective in alleviating the sensory-motor complaints of patients, although the effects induced by low-frequency (inhibitory) rTMS have not yet been investigated. An impaired LTD-like mechanism of cortical plasticity has been hypothesized, which we have directly assessed in this pilot study. METHODS: Motor evoked potentials (MEPs) from the right first dorsal interosseus muscle were recorded at the stimulus intensity of 110% of the resting motor threshold (rMT) from 13 right-handed patients and ten age-matched right-handed healthy controls. Median peak-to-peak amplitudes were calculated in all participants at baseline (T0), after the first train of a single evening session of low-frequency (1 Hz) rTMS over the left primary motor cortex (T1), and after the whole rTMS procedure (T2), which consists of 20 trains with 50 stimuli per train and intertrain interval of 30 s (1000 stimuli in total). RESULTS: No differences were found for rMT and MEPs size between the two groups at T0. Smaller MEPs amplitudes at both T1 and T2 were observed in all subjects, although this was significantly more pronounced in controls than in patients. CONCLUSIONS: Compared to normal individuals, patients exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus adding support to the involvement of GABA in RLS pathophysiology. Although future studies with a larger population are needed, TMS is confirmed to be effective in noninvasive probing of the neurophysiology and neurochemistry of RLS.