Pub Date : 2024-11-14eCollection Date: 2024-01-01DOI: 10.1093/oons/kvae011
Ahmad Abujaber, Said Yaseen, Yahia Imam, Abdulqadir Nashwan, Naveed Akhtar
Background: Accurate prediction of mortality following an ischemic stroke is essential for tailoring personalized treatment strategies. This study evaluates the effectiveness of machine learning models in predicting one-year mortality after an ischemic stroke.
Methods: Five machine learning models were trained using data from a national stroke registry, with logistic regression demonstrating the highest performance. The SHapley Additive exPlanations (SHAP) analysis explained the model's outcomes and defined the influential predictive factors.
Results: Analyzing 8183 ischemic stroke patients, logistic regression achieved 83% accuracy, 0.89 AUC, and an F1 score of 0.83. Significant predictors included stroke severity, pre-stroke functional status, age, hospital-acquired pneumonia, ischemic stroke subtype, tobacco use, and co-existing diabetes mellitus (DM).
Discussion: The model highlights the importance of predicting mortality in enhancing personalized stroke care. Apart from pneumonia, all predictors can serve the early prediction of mortality risk which supports the initiation of early preventive measures and in setting realistic expectations of disease outcomes for all stakeholders. The identified tobacco paradox warrants further investigation.
Conclusion: This study offers a promising tool for early prediction of stroke mortality and for advancing personalized stroke care. It emphasizes the need for prospective studies to validate these findings in diverse clinical settings.
{"title":"Machine learning-based prediction of one-year mortality in ischemic stroke patients.","authors":"Ahmad Abujaber, Said Yaseen, Yahia Imam, Abdulqadir Nashwan, Naveed Akhtar","doi":"10.1093/oons/kvae011","DOIUrl":"10.1093/oons/kvae011","url":null,"abstract":"<p><strong>Background: </strong>Accurate prediction of mortality following an ischemic stroke is essential for tailoring personalized treatment strategies. This study evaluates the effectiveness of machine learning models in predicting one-year mortality after an ischemic stroke.</p><p><strong>Methods: </strong>Five machine learning models were trained using data from a national stroke registry, with logistic regression demonstrating the highest performance. The SHapley Additive exPlanations (SHAP) analysis explained the model's outcomes and defined the influential predictive factors.</p><p><strong>Results: </strong>Analyzing 8183 ischemic stroke patients, logistic regression achieved 83% accuracy, 0.89 AUC, and an F1 score of 0.83. Significant predictors included stroke severity, pre-stroke functional status, age, hospital-acquired pneumonia, ischemic stroke subtype, tobacco use, and co-existing diabetes mellitus (DM).</p><p><strong>Discussion: </strong>The model highlights the importance of predicting mortality in enhancing personalized stroke care. Apart from pneumonia, all predictors can serve the early prediction of mortality risk which supports the initiation of early preventive measures and in setting realistic expectations of disease outcomes for all stakeholders. The identified tobacco paradox warrants further investigation.</p><p><strong>Conclusion: </strong>This study offers a promising tool for early prediction of stroke mortality and for advancing personalized stroke care. It emphasizes the need for prospective studies to validate these findings in diverse clinical settings.</p>","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"3 ","pages":"kvae011"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-22eCollection Date: 2024-01-01DOI: 10.1093/oons/kvae010
Mastura Akter, Zhongqi Fu, Xianlin Zheng, Zafar Iqbal, Na Zhang, Anwarul Karim, Ying Li
Decision making is a process of selecting a course of action by assessing the worth or value of the potential consequences. Rat Gambling Task (RGT) is a well-established behavioral paradigm that allows for assessment of the decision-making performance of rats. Astrocytes are emerging as key players in modulating cognitive functions. Using repeated RGTs with short intersession time intervals (48 h), the current study demonstrates that Gi pathway activation of astrocytes in the anterior cingulate cortex (ACC) leads to impaired decision-making in consistently good decision-making rats. On the other hand, ACC astrocytic Gq pathway activation improves decision-making in a subset of rats who are not consistently good decision-makers. Furthermore, we show that astrocytic Gq activation is associated with an increase in the L-lactate level in the extracellular fluid of the ACC. Together, these results expand our knowledge of the role of astrocytic GPCR signaling in modulating cognitive functions.
{"title":"Astrocytic GPCR signaling in the anterior cingulate cortex modulates decision making in rats.","authors":"Mastura Akter, Zhongqi Fu, Xianlin Zheng, Zafar Iqbal, Na Zhang, Anwarul Karim, Ying Li","doi":"10.1093/oons/kvae010","DOIUrl":"10.1093/oons/kvae010","url":null,"abstract":"<p><p>Decision making is a process of selecting a course of action by assessing the worth or value of the potential consequences. Rat Gambling Task (RGT) is a well-established behavioral paradigm that allows for assessment of the decision-making performance of rats. Astrocytes are emerging as key players in modulating cognitive functions. Using repeated RGTs with short intersession time intervals (48 h), the current study demonstrates that G<sub>i</sub> pathway activation of astrocytes in the anterior cingulate cortex (ACC) leads to impaired decision-making in consistently good decision-making rats. On the other hand, ACC astrocytic G<sub>q</sub> pathway activation improves decision-making in a subset of rats who are not consistently good decision-makers. Furthermore, we show that astrocytic G<sub>q</sub> activation is associated with an increase in the L-lactate level in the extracellular fluid of the ACC. Together, these results expand our knowledge of the role of astrocytic GPCR signaling in modulating cognitive functions.</p>","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"3 ","pages":"kvae010"},"PeriodicalIF":0.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The marble-burying test is a pharmacologically validated paradigm used to study anxiety-like behaviors in laboratory rodents. Our laboratory has employed this assay as part of a behavioral screen to examine drug-induced negative affective states. Historically, the majority of our prior binge alcohol-drinking studies employed male subjects exclusively and reliably detected adolescent-adult differences in both basal and alcohol withdrawal-induced negative affect. However, age-related differences in marble-burying behavior were either absent or opposite those observed in our prior work when female subjects were included in the experimental design. As chemosensory cues from females are reported to be anxiolytic in males, the present study examined how odors from adult members of the opposite and same sex (obtained from soiled bedding) influence marble-burying behavior in adult, as well as adolescent, mice. Control studies examined the responsiveness of mice in the presence of novel neutral (vanilla) and aversive (tea tree) odors. Adult males exhibited reduced signs of anxiety-like behavior in the presence of female-soiled bedding, while adult females and adolescent mice of both sexes increased marble-burying behavior in the presence of both male- and female-soiled bedding. All mice exhibited increased burying in the presence of an aversive odor, while only adolescents increased marble-burying in response to the novel neutral odor. These data indicate sex by age interactions in the effects of volatile and nonvolatile odors from sexually-naive adult conspecifics on indices of anxiety-like behavior in the marble-burying test of relevance to the experimental design and procedural timing of experiments including sex as a biological variable.
{"title":"Modulation of marble-burying behavior in adult versus adolescent C57BL/6J mice of both sexes by ethologically relevant chemosensory stimuli","authors":"C. L. J. Chavez, K. Szumlinski","doi":"10.1093/oons/kvae009","DOIUrl":"https://doi.org/10.1093/oons/kvae009","url":null,"abstract":"\u0000 The marble-burying test is a pharmacologically validated paradigm used to study anxiety-like behaviors in laboratory rodents. Our laboratory has employed this assay as part of a behavioral screen to examine drug-induced negative affective states. Historically, the majority of our prior binge alcohol-drinking studies employed male subjects exclusively and reliably detected adolescent-adult differences in both basal and alcohol withdrawal-induced negative affect. However, age-related differences in marble-burying behavior were either absent or opposite those observed in our prior work when female subjects were included in the experimental design. As chemosensory cues from females are reported to be anxiolytic in males, the present study examined how odors from adult members of the opposite and same sex (obtained from soiled bedding) influence marble-burying behavior in adult, as well as adolescent, mice. Control studies examined the responsiveness of mice in the presence of novel neutral (vanilla) and aversive (tea tree) odors. Adult males exhibited reduced signs of anxiety-like behavior in the presence of female-soiled bedding, while adult females and adolescent mice of both sexes increased marble-burying behavior in the presence of both male- and female-soiled bedding. All mice exhibited increased burying in the presence of an aversive odor, while only adolescents increased marble-burying in response to the novel neutral odor. These data indicate sex by age interactions in the effects of volatile and nonvolatile odors from sexually-naive adult conspecifics on indices of anxiety-like behavior in the marble-burying test of relevance to the experimental design and procedural timing of experiments including sex as a biological variable.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"13 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Retina regeneration: lessons from vertebrates","authors":"","doi":"10.1093/oons/kvae008","DOIUrl":"https://doi.org/10.1093/oons/kvae008","url":null,"abstract":"","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"142 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141114727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kruttika Phalnikar, M. Srividya, S. Mythri, N. S. Vasavi, Archisha Ganguly, Aparajita Kumar, Padmaja S, Kishan Kalia, Srishti S Mishra, S. Dhanya, P. Paul, B. Holla, Suhas Ganesh, Puli Chandramouli Reddy, R. Sud, B. Viswanath, Bhavana Muralidharan
Abstract Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects. The BD organoids show a reduction in both the number of neuroepithelial buds/cortical rosettes and the ventricular zone size. Additionally, patient organoids show a lower number of SOX2-positive and EdU-positive cycling progenitors, suggesting a progenitor proliferation defect. Further, the patient neurons show abnormal positioning in the ventricular/intermediate zone of the neuroepithelial bud. Transcriptomic analysis of control and patient organoids supports our cellular topology data and reveals dysregulation of genes crucial for progenitor proliferation and neuronal migration. Lastly, time-lapse imaging of neural stem cells in 2D in vitro cultures reveals abnormal cellular migration in BD samples. Overall, our study pinpoints a cellular and molecular deficit in BD patient-derived organoids and neural stem cell cultures.
摘要 双相情感障碍（BD）是一种严重的精神疾病，可由神经发育异常导致，尤其是在家族性双相情感障碍中，可能包括致病基因变异。在本研究中，我们从躁狂症患者和健康（对照）个体中提取了皮质器官组织，这些患者来自印度人口中的一个临床密集型家族。我们的数据显示，患者的器官组织显示出神经发育异常，包括组织、增殖和迁移缺陷。BD患者的器官组织显示神经上皮芽/皮质花环的数量和脑室区的大小均有所减少。此外，患者器官组织显示 SOX2 阳性和 EdU 阳性的循环祖细胞数量较少，这表明祖细胞增殖存在缺陷。此外，患者的神经元在神经上皮芽的室间/中间区定位异常。对照组和患者器官组织的转录组分析支持了我们的细胞拓扑数据，并揭示了对祖细胞增殖和神经元迁移至关重要的基因失调。最后，二维体外培养神经干细胞的延时成像显示，BD样本中的细胞迁移异常。总之，我们的研究指出了BD患者衍生的器官组织和神经干细胞培养物的细胞和分子缺陷。
{"title":"Altered neuroepithelial morphogenesis and migration defects in iPSC-derived cerebral organoids and 2D neural stem cells in familial bipolar disorder","authors":"Kruttika Phalnikar, M. Srividya, S. Mythri, N. S. Vasavi, Archisha Ganguly, Aparajita Kumar, Padmaja S, Kishan Kalia, Srishti S Mishra, S. Dhanya, P. Paul, B. Holla, Suhas Ganesh, Puli Chandramouli Reddy, R. Sud, B. Viswanath, Bhavana Muralidharan","doi":"10.1093/oons/kvae007","DOIUrl":"https://doi.org/10.1093/oons/kvae007","url":null,"abstract":"Abstract Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects. The BD organoids show a reduction in both the number of neuroepithelial buds/cortical rosettes and the ventricular zone size. Additionally, patient organoids show a lower number of SOX2-positive and EdU-positive cycling progenitors, suggesting a progenitor proliferation defect. Further, the patient neurons show abnormal positioning in the ventricular/intermediate zone of the neuroepithelial bud. Transcriptomic analysis of control and patient organoids supports our cellular topology data and reveals dysregulation of genes crucial for progenitor proliferation and neuronal migration. Lastly, time-lapse imaging of neural stem cells in 2D in vitro cultures reveals abnormal cellular migration in BD samples. Overall, our study pinpoints a cellular and molecular deficit in BD patient-derived organoids and neural stem cell cultures.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"103 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140747022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Monfils, Michael Pasala, Cassidy A. Malone, L. Agee, R. Roquet, Lawrence Cormack
Abstract Environment is a determining factor that can facilitate or hinder social interactions. A precursor to meaningfully engaging with conspecifics is being exposed to opportunistic encounters with others. Increasing the number of individuals in a given space (thus increasing density) would, statistically speaking, increase the likelihood of accidental encounters. This might have consequences on the formation of social networks—an idea that has not reliably been explored. If true, we would expect that increasing density would lead to an increase in the number and the duration of ‘clusters’ of animals. Here, we examined whether varying the number of rats in an open field environment differentially affected their movement dynamics or their propensity to aggregate into clusters and, if so, whether such effects are dependent solely on statistical factors due to increases in density, the potential for actively-sought social interactions, or both. We found that the number of rats in an environment impacts ambulation speed, distance traveled, cluster formation and approaches, and that number and duration of clusters are highly dependent on the propensity for the rats to engage in social interactions.
{"title":"Effects of group size on movement patterns and clustering dynamics in rats","authors":"M. Monfils, Michael Pasala, Cassidy A. Malone, L. Agee, R. Roquet, Lawrence Cormack","doi":"10.1093/oons/kvae005","DOIUrl":"https://doi.org/10.1093/oons/kvae005","url":null,"abstract":"Abstract Environment is a determining factor that can facilitate or hinder social interactions. A precursor to meaningfully engaging with conspecifics is being exposed to opportunistic encounters with others. Increasing the number of individuals in a given space (thus increasing density) would, statistically speaking, increase the likelihood of accidental encounters. This might have consequences on the formation of social networks—an idea that has not reliably been explored. If true, we would expect that increasing density would lead to an increase in the number and the duration of ‘clusters’ of animals. Here, we examined whether varying the number of rats in an open field environment differentially affected their movement dynamics or their propensity to aggregate into clusters and, if so, whether such effects are dependent solely on statistical factors due to increases in density, the potential for actively-sought social interactions, or both. We found that the number of rats in an environment impacts ambulation speed, distance traveled, cluster formation and approaches, and that number and duration of clusters are highly dependent on the propensity for the rats to engage in social interactions.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"178 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140755106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. De Felice, U. Hakim, N. Gunasekara, P. Pinti, I. Tachtsidis, A. Hamilton
How does co-presence change our neural experience of the world? Can a conversation change how we synchronise with our partner during later events? Using fNIRS hyperscanning, we measured brain activity from 27 pairs of familiar adults simultaneously over frontal, temporal and parietal regions bilaterally, as they co-watched two different episodes of a short cartoon. In-between the two episodes, each pair engaged in a face-to-face conversation on topics unrelated to the cartoon episodes. Brain synchrony was calculated using wavelet transform coherence and computed separately for real pairs and shuffled (pseudo) pairs. Findings reveal that real pairs showed increased brain synchrony over right Dorso-Lateral Pre-Frontal cortex (DLPFC) and right Superior Parietal Lobe (SPL), compared to pseudo pairs (who had never seen each other and watched the same movie at different times; uncorrected for multiple comparisons). In addition, co-watching after a conversation was associated with greater synchrony over right TPJ compared to co-watching before a conversation, and this effect was significantly higher in real pairs (who engaged in conversation with each other) compared to pseudo pairs (who had a conversation with someone else; uncorrected for multiple comparisons). The present study has shed the light on the role of social interaction in modulating brain synchrony across people not just during social interaction, but even for subsequent non-social activities. These results have implications in the growing domain of naturalistic neuroimaging and interactive neuroscience.
{"title":"Having a chat and then watching a movie: how social interaction synchronises our brains during co-watching","authors":"S. De Felice, U. Hakim, N. Gunasekara, P. Pinti, I. Tachtsidis, A. Hamilton","doi":"10.1093/oons/kvae006","DOIUrl":"https://doi.org/10.1093/oons/kvae006","url":null,"abstract":"\u0000 How does co-presence change our neural experience of the world? Can a conversation change how we synchronise with our partner during later events? Using fNIRS hyperscanning, we measured brain activity from 27 pairs of familiar adults simultaneously over frontal, temporal and parietal regions bilaterally, as they co-watched two different episodes of a short cartoon. In-between the two episodes, each pair engaged in a face-to-face conversation on topics unrelated to the cartoon episodes. Brain synchrony was calculated using wavelet transform coherence and computed separately for real pairs and shuffled (pseudo) pairs. Findings reveal that real pairs showed increased brain synchrony over right Dorso-Lateral Pre-Frontal cortex (DLPFC) and right Superior Parietal Lobe (SPL), compared to pseudo pairs (who had never seen each other and watched the same movie at different times; uncorrected for multiple comparisons). In addition, co-watching after a conversation was associated with greater synchrony over right TPJ compared to co-watching before a conversation, and this effect was significantly higher in real pairs (who engaged in conversation with each other) compared to pseudo pairs (who had a conversation with someone else; uncorrected for multiple comparisons). The present study has shed the light on the role of social interaction in modulating brain synchrony across people not just during social interaction, but even for subsequent non-social activities. These results have implications in the growing domain of naturalistic neuroimaging and interactive neuroscience.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"112 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human brain organoids equipped with complex cytoarchitecture and closed-loop feedback from virtual environments could provide insights into neural mechanisms underlying cognition. Yet organoids with certain cognitive capacities might also merit moral consideration. A precautionary approach has been proposed to address these ethical concerns by focusing on the epistemological question of whether organoids possess neural structures for morally-relevant capacities that bear resemblance to those found in human brains. Critics challenge this similarity approach on philosophical, scientific, and practical grounds but do so without a suitable alternative. Here, I introduce an architectural approach that infers the potential for cognitive-like processing in brain organoids based on the pattern of information flow through the system. The kind of computational architecture acquired by an organoid then informs the kind of cognitive capacities that could, theoretically, be supported and empirically investigated. The implications of this approach for the moral considerability of brain organoids are discussed.
{"title":"Moral considerability of brain organoids from the perspective of computational architecture","authors":"J. Lomax Boyd","doi":"10.1093/oons/kvae004","DOIUrl":"https://doi.org/10.1093/oons/kvae004","url":null,"abstract":"\u0000 Human brain organoids equipped with complex cytoarchitecture and closed-loop feedback from virtual environments could provide insights into neural mechanisms underlying cognition. Yet organoids with certain cognitive capacities might also merit moral consideration. A precautionary approach has been proposed to address these ethical concerns by focusing on the epistemological question of whether organoids possess neural structures for morally-relevant capacities that bear resemblance to those found in human brains. Critics challenge this similarity approach on philosophical, scientific, and practical grounds but do so without a suitable alternative. Here, I introduce an architectural approach that infers the potential for cognitive-like processing in brain organoids based on the pattern of information flow through the system. The kind of computational architecture acquired by an organoid then informs the kind of cognitive capacities that could, theoretically, be supported and empirically investigated. The implications of this approach for the moral considerability of brain organoids are discussed.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"46 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140250135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Janay M. Vacharasin, Joseph A Ward, Mikayla M. McCord, Kaitlin Cox, Jaime Imitola, Sofia B Lizarraga
Autism spectrum disorders (ASD) affect 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.
{"title":"Neuroimmune Mechanisms in Autism Etiology - Untangling A Complex Problem using Human Cellular Models","authors":"Janay M. Vacharasin, Joseph A Ward, Mikayla M. McCord, Kaitlin Cox, Jaime Imitola, Sofia B Lizarraga","doi":"10.1093/oons/kvae003","DOIUrl":"https://doi.org/10.1093/oons/kvae003","url":null,"abstract":"\u0000 Autism spectrum disorders (ASD) affect 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.","PeriodicalId":74386,"journal":{"name":"Oxford open neuroscience","volume":"27 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140441263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08eCollection Date: 2024-01-01DOI: 10.1093/oons/kvae002
Ana S Cruz, Sara Cruz, Miguel Remondes
Working memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the anterior cingulate cortex (CG). Functionally and anatomically connected to the medial prefrontal, retrosplenial, midcingulate and hippocampus, as well as motor cortices, CG has been implicated in retrieving appropriate information when needed to select and control appropriate behavior. The role of cingulate cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with its activity during specific epochs of working memory. We used eNpHR3.0 to silence cingulate neurons while animals perform a standard delayed non-match to trajectory task, and found that, while not causing an absolute impairment in working memory, silencing cingulate neurons during retrieval decreases the mean performance if compared to silencing during encoding. Such retrieval-associated changes are accompanied by longer delays observed when light is delivered to control animals, when compared to eNpHR3.0+ ones, consistent with an adaptive recruitment of additional cognitive resources.
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