Pub Date : 2024-06-10DOI: 10.3389/fnins.2024.1404816
Yan Jin, Jing Li, Zhuyao Fan, Xian Hua, Ting Wang, Shunlan Du, Xugang Xi, Lihua Li
Nowadays, increasingly studies are attempting to analyze strokes in advance. The identification of brain damage areas is essential for stroke rehabilitation.We proposed Electroencephalogram (EEG) multi-modal frequency features to classify the regions of stroke injury. The EEG signals were obtained from stroke patients and healthy subjects, who were divided into right-sided brain injury group, left-sided brain injury group, bilateral brain injury group, and healthy controls. First, the wavelet packet transform was used to perform a time-frequency analysis of the EEG signal and extracted a set of features (denoted as WPT features). Then, to explore the nonlinear phase coupling information of the EEG signal, phase-locked values (PLV) and partial directed correlations (PDC) were extracted from the brain network, and the brain network produced a second set of features noted as functional connectivity (FC) features. Furthermore, we fused the extracted multiple features and used the resnet50 convolutional neural network to classify the fused multi-modal (WPT + FC) features.The classification accuracy of our proposed methods was up to 99.75%.The proposed multi-modal frequency features can be used as a potential indicator to distinguish regions of brain injury in stroke patients, and are potentially useful for the optimization of decoding algorithms for brain-computer interfaces.
{"title":"Recognition of regions of stroke injury using multi-modal frequency features of electroencephalogram","authors":"Yan Jin, Jing Li, Zhuyao Fan, Xian Hua, Ting Wang, Shunlan Du, Xugang Xi, Lihua Li","doi":"10.3389/fnins.2024.1404816","DOIUrl":"https://doi.org/10.3389/fnins.2024.1404816","url":null,"abstract":"Nowadays, increasingly studies are attempting to analyze strokes in advance. The identification of brain damage areas is essential for stroke rehabilitation.We proposed Electroencephalogram (EEG) multi-modal frequency features to classify the regions of stroke injury. The EEG signals were obtained from stroke patients and healthy subjects, who were divided into right-sided brain injury group, left-sided brain injury group, bilateral brain injury group, and healthy controls. First, the wavelet packet transform was used to perform a time-frequency analysis of the EEG signal and extracted a set of features (denoted as WPT features). Then, to explore the nonlinear phase coupling information of the EEG signal, phase-locked values (PLV) and partial directed correlations (PDC) were extracted from the brain network, and the brain network produced a second set of features noted as functional connectivity (FC) features. Furthermore, we fused the extracted multiple features and used the resnet50 convolutional neural network to classify the fused multi-modal (WPT + FC) features.The classification accuracy of our proposed methods was up to 99.75%.The proposed multi-modal frequency features can be used as a potential indicator to distinguish regions of brain injury in stroke patients, and are potentially useful for the optimization of decoding algorithms for brain-computer interfaces.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 69","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141365296","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 : 2024-06-10DOI: 10.3389/fnins.2024.1426180
Sierra Jaye, U. Sandau, Trevor J. McFarland, Randy L. Woltjer, J. Saugstad
Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary Tau tangles in the brain. We previously identified a set of candidate AD microRNAs (miRNAs) in human cerebrospinal fluid (CSF) and used a target prediction pipeline to identify mRNAs and pathways that could potentially be regulated by the miRNAs. Of these pathways, clathrin mediated endocytosis (CME) was selected for further investigation. CME is altered in multiple brain cell types in AD and is implicated in early cellular phenotypes such as enlarged early endosomes and pathogenic processing of Aβ. However, a comprehensive evaluation of major CME hub proteins in humans with AD across multiple brain regions is lacking. Thus, we used immunoblots to evaluate human post-mortem AD and control (CTL) frontal cortex (FC; AD n = 22, CTL n = 23) and hippocampus (HP; AD n = 34, CTL n = 22) for changes in Intersectin 1 (ITSN1), Phosphatidylinositol Binding Clathrin Assembly Protein gene (PICALM), Clathrin Light Chain (CLT), FCH and Mu Domain Containing Endocytic Adaptor 1 (FCHO1), Adaptor Related Protein Complex 2 (AP2) Subunit Alpha 1 (AP2A1), and Dynamin 2 (DNM2). Of these, we found that in AD, ITSN1-long (ITSN1-L) was decreased in the FC of males and HP of females, while ITSN1-short was increased in the HP of both males and females. We further evaluated ITSN1-L levels in cortex (CTX) and HP of the 5xFAD mouse model of Aβ pathology at different timepoints during aging and disease progression by immunoblot (n = 5–8 per group). At 3 months, female 5xFAD exhibited an increase of ITSN1-L in CTX but a decrease at 6 and 9 months. Additionally, immunofluorescent staining of 5xFAD primary HP neurons showed an increase of ITSN1-L in matured 5xFAD neurons at 21 and 28 days in vitro. Together, our studies show that in AD, isoforms of ITSN1 change in a brain region-and sex-dependent manner. Further, changes in ITSN1-L are transient with levels increasing during early Aβ accumulation and decreasing during later progression. These findings suggest that ITSN1 expression, and consequently CME activity, may change depending on the stage of disease progression.
阿尔茨海默病（AD）是最常见的痴呆症，其特征是大脑中淀粉样β（Aβ）斑块和神经纤维Tau缠结的积累。我们先前在人类脑脊液（CSF）中发现了一组候选的AD microRNA（miRNA），并利用目标预测管道确定了可能受miRNA调控的mRNA和通路。在这些通路中，选择了凝集素介导的内吞（CME）进行进一步研究。CME在AD患者的多种脑细胞类型中发生改变，并与早期细胞表型有关，如早期内体增大和Aβ的致病处理。然而，目前还缺乏对AD患者多个脑区主要CME中枢蛋白的全面评估。因此，我们使用免疫印迹法评估了人类死后AD和对照组（CTL）的额叶皮层（FC；AD n = 22，CTL n = 23）和海马（HP；AD n = 34，CTL n = 22）中交联蛋白 1 (ITSN1)、磷脂酰肌醇结合鞘磷脂组装蛋白基因 (PICALM)、鞘磷脂轻链 (CLT)、FCH 和 Mu 域包含内吞适配体 1 (FCHO1)、适配体相关蛋白复合物 2 (AP2) 亚基 Alpha 1 (AP2A1) 和 Dynamin 2 (DNM2) 的变化。其中，我们发现在 AD 中，男性 FC 和女性 HP 中的 ITSN1-长（ITSN1-L）减少，而男性和女性 HP 中的 ITSN1-短增加。我们通过免疫印迹进一步评估了5xFAD小鼠Aβ病理模型在衰老和疾病进展过程中不同时间点皮层（CTX）和HP中的ITSN1-L水平（n = 5-8/组）。3 个月时，雌性 5xFAD CTX 中的 ITSN1-L 有所增加，但在 6 个月和 9 个月时有所减少。此外，对 5xFAD 初级 HP 神经元的免疫荧光染色显示，在体外 21 天和 28 天时，成熟的 5xFAD 神经元中的 ITSN1-L 有所增加。总之，我们的研究表明，在 AD 中，ITSN1 的同工型以脑区和性别依赖的方式发生变化。此外，ITSN1-L的变化是短暂的，其水平在早期Aβ积累时升高，而在后期发展时降低。这些研究结果表明，ITSN1的表达以及由此产生的CME活性可能会随着疾病的进展阶段而发生变化。
{"title":"A clathrin mediated endocytosis scaffolding protein, Intersectin 1, changes in an isoform, brain region, and sex specific manner in Alzheimer’s disease","authors":"Sierra Jaye, U. Sandau, Trevor J. McFarland, Randy L. Woltjer, J. Saugstad","doi":"10.3389/fnins.2024.1426180","DOIUrl":"https://doi.org/10.3389/fnins.2024.1426180","url":null,"abstract":"Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary Tau tangles in the brain. We previously identified a set of candidate AD microRNAs (miRNAs) in human cerebrospinal fluid (CSF) and used a target prediction pipeline to identify mRNAs and pathways that could potentially be regulated by the miRNAs. Of these pathways, clathrin mediated endocytosis (CME) was selected for further investigation. CME is altered in multiple brain cell types in AD and is implicated in early cellular phenotypes such as enlarged early endosomes and pathogenic processing of Aβ. However, a comprehensive evaluation of major CME hub proteins in humans with AD across multiple brain regions is lacking. Thus, we used immunoblots to evaluate human post-mortem AD and control (CTL) frontal cortex (FC; AD n = 22, CTL n = 23) and hippocampus (HP; AD n = 34, CTL n = 22) for changes in Intersectin 1 (ITSN1), Phosphatidylinositol Binding Clathrin Assembly Protein gene (PICALM), Clathrin Light Chain (CLT), FCH and Mu Domain Containing Endocytic Adaptor 1 (FCHO1), Adaptor Related Protein Complex 2 (AP2) Subunit Alpha 1 (AP2A1), and Dynamin 2 (DNM2). Of these, we found that in AD, ITSN1-long (ITSN1-L) was decreased in the FC of males and HP of females, while ITSN1-short was increased in the HP of both males and females. We further evaluated ITSN1-L levels in cortex (CTX) and HP of the 5xFAD mouse model of Aβ pathology at different timepoints during aging and disease progression by immunoblot (n = 5–8 per group). At 3 months, female 5xFAD exhibited an increase of ITSN1-L in CTX but a decrease at 6 and 9 months. Additionally, immunofluorescent staining of 5xFAD primary HP neurons showed an increase of ITSN1-L in matured 5xFAD neurons at 21 and 28 days in vitro. Together, our studies show that in AD, isoforms of ITSN1 change in a brain region-and sex-dependent manner. Further, changes in ITSN1-L are transient with levels increasing during early Aβ accumulation and decreasing during later progression. These findings suggest that ITSN1 expression, and consequently CME activity, may change depending on the stage of disease progression.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 426","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141364577","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 : 2024-06-07DOI: 10.3389/fnins.2024.1375299
D. Galatolo, S. Rocchiccioli, N. Di Giorgi, Flavio Dal Canto, Giovanni Signore, Federica Morani, Elisa Ceccherini, S. Doccini, Filippo M. Santorelli
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare incurable neurodegenerative disease caused by mutations in the SACS gene, which codes for sacsin, a large protein involved in protein homeostasis, mitochondrial function, cytoskeletal dynamics, autophagy, cell adhesion and vesicle trafficking. However, the pathogenic mechanisms underlying sacsin dysfunction are still largely uncharacterized, and so attempts to develop therapies are still in the early stages.To achieve further understanding of how processes are altered by loss of sacsin, we used untargeted proteomics to compare protein profiles in ARSACS fibroblasts versus controls.Our analyses confirmed the involvement of known biological pathways and also implicated calcium and lipid homeostasis in ARSACS skin fibroblasts, a finding further verified in SH-SY5Y SACS–/– cells. Validation through mass spectrometry-based analysis and comparative quantification of lipids by LC-MS in fibroblasts revealed increased levels of ceramides coupled with a reduction of diacylglycerols.In addition to confirming aberrant Ca2+ homeostasis in ARSACS, this study described abnormal lipid levels associated with loss of sacsin.
{"title":"Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin","authors":"D. Galatolo, S. Rocchiccioli, N. Di Giorgi, Flavio Dal Canto, Giovanni Signore, Federica Morani, Elisa Ceccherini, S. Doccini, Filippo M. Santorelli","doi":"10.3389/fnins.2024.1375299","DOIUrl":"https://doi.org/10.3389/fnins.2024.1375299","url":null,"abstract":"Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare incurable neurodegenerative disease caused by mutations in the SACS gene, which codes for sacsin, a large protein involved in protein homeostasis, mitochondrial function, cytoskeletal dynamics, autophagy, cell adhesion and vesicle trafficking. However, the pathogenic mechanisms underlying sacsin dysfunction are still largely uncharacterized, and so attempts to develop therapies are still in the early stages.To achieve further understanding of how processes are altered by loss of sacsin, we used untargeted proteomics to compare protein profiles in ARSACS fibroblasts versus controls.Our analyses confirmed the involvement of known biological pathways and also implicated calcium and lipid homeostasis in ARSACS skin fibroblasts, a finding further verified in SH-SY5Y SACS–/– cells. Validation through mass spectrometry-based analysis and comparative quantification of lipids by LC-MS in fibroblasts revealed increased levels of ceramides coupled with a reduction of diacylglycerols.In addition to confirming aberrant Ca2+ homeostasis in ARSACS, this study described abnormal lipid levels associated with loss of sacsin.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141371651","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 : 2024-06-07DOI: 10.3389/fnins.2024.1389111
Rong Guo, Shaolin Yang, H. Wiesner, Yudu Li, Yibo Zhao, Zhi-Pei Liang, Wei Chen, Xiao-Hong Zhu
Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.
烟酰胺腺嘌呤二核苷酸（NAD）是细胞新陈代谢和信号传导的关键分子。绘制人脑细胞内 NAD 含量图一直是人们关注的问题。在这项研究中，我们在超高场（7 特斯拉）下采用了基于磷-31 磁共振光谱成像（31P-MRSI）的 NAD 检测方法，并结合基于概率子空间的处理方法，证明了无创绘制整个人脑中 NAD 含量图的可行性。与原始测量相比，该处理方法可将噪声降低约 10 倍，从而显著减少了 NAD 的估计误差。量化的 NAD 含量约为 0.4 mM，在同一受试者的重复扫描中表现出良好的重现性，在不同受试者的组数据（2.3 毫升标称分辨率）中表现出良好的一致性。一组更高分辨率的数据（1.0 毫升标称分辨率）显示出评估组织代谢异质性的潜力，在白质和灰质中显示出相似的 NAD 分布。这些结果表明，我们首次尝试使用超高场 31P-MRSI 和先进的处理技术生成人脑低浓度细胞内 NAD 含量的全脑图谱，取得了良好的效果。
{"title":"Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla","authors":"Rong Guo, Shaolin Yang, H. Wiesner, Yudu Li, Yibo Zhao, Zhi-Pei Liang, Wei Chen, Xiao-Hong Zhu","doi":"10.3389/fnins.2024.1389111","DOIUrl":"https://doi.org/10.3389/fnins.2024.1389111","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141373053","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 : 2024-06-07DOI: 10.3389/fnins.2024.1420322
Alexandra Strohm, A. Majewska
There is a well-established link between physical activity and brain health. As such, the effectiveness of physical exercise as a therapeutic strategy has been explored in a variety of neurological contexts. To determine the extent to which physical exercise could be most beneficial under different circumstances, studies are needed to uncover the underlying mechanisms behind the benefits of physical activity. Interest has grown in understanding how physical activity can regulate microglia, the resident immune cells of the central nervous system. Microglia are key mediators of neuroinflammatory processes and play a role in maintaining brain homeostasis in healthy and pathological settings. Here, we explore the evidence suggesting that physical activity has the potential to regulate microglia activity in various animal models. We emphasize key areas where future research could contribute to uncovering the therapeutic benefits of engaging in physical exercise.
{"title":"Physical exercise regulates microglia in health and disease","authors":"Alexandra Strohm, A. Majewska","doi":"10.3389/fnins.2024.1420322","DOIUrl":"https://doi.org/10.3389/fnins.2024.1420322","url":null,"abstract":"There is a well-established link between physical activity and brain health. As such, the effectiveness of physical exercise as a therapeutic strategy has been explored in a variety of neurological contexts. To determine the extent to which physical exercise could be most beneficial under different circumstances, studies are needed to uncover the underlying mechanisms behind the benefits of physical activity. Interest has grown in understanding how physical activity can regulate microglia, the resident immune cells of the central nervous system. Microglia are key mediators of neuroinflammatory processes and play a role in maintaining brain homeostasis in healthy and pathological settings. Here, we explore the evidence suggesting that physical activity has the potential to regulate microglia activity in various animal models. We emphasize key areas where future research could contribute to uncovering the therapeutic benefits of engaging in physical exercise.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141372233","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 : 2024-06-07DOI: 10.3389/fnins.2024.1401068
C. Porcaro, Dario Seppi, Giovanni Pellegrino, Filippo Dainese, B. Kassabian, Luciano Pellegrino, Gianluigi De Nardi, Alberto Grego, Maurizio Corbetta, Florinda Ferreri
An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods.Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC).EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups.The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ.FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes.Our work suggests that FD is a promising measure to monitor the response to ASMs in FE.
{"title":"Characterization of antiseizure medications effects on the EEG neurodynamic by fractal dimension","authors":"C. Porcaro, Dario Seppi, Giovanni Pellegrino, Filippo Dainese, B. Kassabian, Luciano Pellegrino, Gianluigi De Nardi, Alberto Grego, Maurizio Corbetta, Florinda Ferreri","doi":"10.3389/fnins.2024.1401068","DOIUrl":"https://doi.org/10.3389/fnins.2024.1401068","url":null,"abstract":"An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods.Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC).EEG data were investigated from two different angles: frequency domain—spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain—FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups.The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The θ power differed between DR-t1 and DR-t2 (p = 0.015) and between DR-t1 and HC (p = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, p < 0.01 and DR-t2 vs. HC, p < 0.01). The IAF value was lower for DR-t1 than DR-t2 (p = 0.048) and HC (p = 0.042). The FD value was lower in DR-t1 than in DR-t2 (p = 0.015) and HC (p = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ.FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes.Our work suggests that FD is a promising measure to monitor the response to ASMs in FE.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141371017","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 : 2024-06-06DOI: 10.3389/fnins.2024.1426177
Daniel Bauersachs, Louise Bomholtz, Sara del Rey Mateos, Ralf Kühn, Pawel Lisowski
Recently a broad range of phenotypic abnormalities related to the neurodevelopmental and neurodegenerative disorder NEDAMSS (Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures) have been associated with rare single-nucleotide polymorphisms (SNPs) or insertion and deletion variants (Indel) in the intron-less gene IRF2BPL. Up to now, 34 patients have been identified through whole exome sequencing carrying different heterozygous pathogenic variants spanning the intron-less gene from the first polyglutamine tract at the N-terminus to the C3HC4 RING domain of the C-terminus of the protein. As a result, the phenotypic spectrum of the patients is highly heterogeneous and ranges from abnormal neurocognitive development to severe neurodegenerative courses with developmental and seizure-related encephalopathies. While the treatment of IRF2BPL-related disorders has focused on alleviating the patient’s symptoms by symptomatic multidisciplinary management, there has been no prospect of entirely relieving the symptoms of the individual patients. Yet, the recent advancement of CRISPR-Cas9-derived gene editing tools, leading to the generation of base editors (BEs) and prime editors (PEs), provide an encouraging new therapeutic avenue for treating NEDAMSS and other neurodevelopmental and neurodegenerative diseases, which contain SNPs or smaller Indels in post-mitotic cell populations of the central nervous system, due to its ability to generate site-specific DNA sequence modifications without creating double-stranded breaks, and recruiting the non-homologous DNA end joining repair mechanism.
最近，与神经发育和神经退行性疾病 NEDAMSS（神经发育障碍性疾病，伴有退行、异常运动、失语和癫痫发作）相关的一系列表型异常与无内含子基因 IRF2BPL 中的罕见单核苷酸多态性（SNP）或插入和缺失变异（Indel）有关。迄今为止，通过全外显子组测序，已发现 34 名患者携带不同的杂合致病变体，这些变体横跨无内含子基因，从蛋白 N 端第一个多聚谷氨酰胺束到 C 端 C3HC4 RING 结构域。因此，患者的表型谱具有高度异质性，从神经认知发育异常到严重的神经退行性病程，以及发育和癫痫相关性脑病不等。虽然 IRF2BPL 相关疾病的治疗侧重于通过多学科对症治疗来缓解患者的症状，但一直没有完全缓解患者症状的前景。然而，最近 CRISPR-Cas9 衍生基因编辑工具的发展，导致碱基编辑器（BE）和质粒编辑器（PE）的产生，为治疗 NEDAMSS 及其他神经发育性疾病和神经退行性疾病提供了令人鼓舞的新疗法途径，这些疾病在中枢神经系统的有丝分裂后细胞群中含有 SNP 或较小的 Indels，这是因为 CRISPR-Cas9 能够在不产生双链断裂的情况下产生位点特异性 DNA 序列修饰，并招募非同源 DNA 端接修复机制。
{"title":"Novel human neurodevelopmental and neurodegenerative disease associated with IRF2BPL gene variants—mechanisms and therapeutic avenues","authors":"Daniel Bauersachs, Louise Bomholtz, Sara del Rey Mateos, Ralf Kühn, Pawel Lisowski","doi":"10.3389/fnins.2024.1426177","DOIUrl":"https://doi.org/10.3389/fnins.2024.1426177","url":null,"abstract":"Recently a broad range of phenotypic abnormalities related to the neurodevelopmental and neurodegenerative disorder NEDAMSS (Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures) have been associated with rare single-nucleotide polymorphisms (SNPs) or insertion and deletion variants (Indel) in the intron-less gene IRF2BPL. Up to now, 34 patients have been identified through whole exome sequencing carrying different heterozygous pathogenic variants spanning the intron-less gene from the first polyglutamine tract at the N-terminus to the C3HC4 RING domain of the C-terminus of the protein. As a result, the phenotypic spectrum of the patients is highly heterogeneous and ranges from abnormal neurocognitive development to severe neurodegenerative courses with developmental and seizure-related encephalopathies. While the treatment of IRF2BPL-related disorders has focused on alleviating the patient’s symptoms by symptomatic multidisciplinary management, there has been no prospect of entirely relieving the symptoms of the individual patients. Yet, the recent advancement of CRISPR-Cas9-derived gene editing tools, leading to the generation of base editors (BEs) and prime editors (PEs), provide an encouraging new therapeutic avenue for treating NEDAMSS and other neurodevelopmental and neurodegenerative diseases, which contain SNPs or smaller Indels in post-mitotic cell populations of the central nervous system, due to its ability to generate site-specific DNA sequence modifications without creating double-stranded breaks, and recruiting the non-homologous DNA end joining repair mechanism.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"132 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141376122","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 : 2024-05-17DOI: 10.3389/fnins.2024.1374112
Matin Ramzani Shahrestani, Sara Motamed, Mohammadreza Yamaghani
Expressing emotions play a special role in daily communication, and one of the most essential methods in detecting emotions is to detect facial emotional states. Therefore, one of the crucial aspects of the natural human–machine interaction is the recognition of facial expressions and the creation of feedback, according to the perceived emotion.To implement each part of this model, two main steps have been introduced. The first step is reading the video and converting it to images and preprocessing on them. The next step is to use the combination of 3D convolutional neural network (3DCNN) and learning automata (LA) to classify and detect the rate of facial emotional recognition. The reason for choosing 3DCNN in our model is that no dimension is removed from the images, and considering the temporal information in dynamic images leads to more efficient and better classification. In addition, the training of the 3DCNN network in calculating the backpropagation error is adjusted by LA so that both the efficiency of the proposed model is increased, and the working memory part of the SOAR model can be implemented.Due to the importance of the topic, this article presents an efficient method for recognizing emotional states from facial images based on a mixed deep learning and cognitive model called SOAR. Among the objectives of the proposed model, it is possible to mention providing a model for learning the time order of frames in the movie and providing a model for better display of visual features, increasing the recognition rate. The accuracy of recognition rate of facial emotional states in the proposed model is 85.3%. To compare the effectiveness of the proposed model with other models, this model has been compared with competing models. By examining the results, we found that the proposed model has a better performance than other models.
{"title":"Recognition of facial emotion based on SOAR model","authors":"Matin Ramzani Shahrestani, Sara Motamed, Mohammadreza Yamaghani","doi":"10.3389/fnins.2024.1374112","DOIUrl":"https://doi.org/10.3389/fnins.2024.1374112","url":null,"abstract":"Expressing emotions play a special role in daily communication, and one of the most essential methods in detecting emotions is to detect facial emotional states. Therefore, one of the crucial aspects of the natural human–machine interaction is the recognition of facial expressions and the creation of feedback, according to the perceived emotion.To implement each part of this model, two main steps have been introduced. The first step is reading the video and converting it to images and preprocessing on them. The next step is to use the combination of 3D convolutional neural network (3DCNN) and learning automata (LA) to classify and detect the rate of facial emotional recognition. The reason for choosing 3DCNN in our model is that no dimension is removed from the images, and considering the temporal information in dynamic images leads to more efficient and better classification. In addition, the training of the 3DCNN network in calculating the backpropagation error is adjusted by LA so that both the efficiency of the proposed model is increased, and the working memory part of the SOAR model can be implemented.Due to the importance of the topic, this article presents an efficient method for recognizing emotional states from facial images based on a mixed deep learning and cognitive model called SOAR. Among the objectives of the proposed model, it is possible to mention providing a model for learning the time order of frames in the movie and providing a model for better display of visual features, increasing the recognition rate. The accuracy of recognition rate of facial emotional states in the proposed model is 85.3%. To compare the effectiveness of the proposed model with other models, this model has been compared with competing models. By examining the results, we found that the proposed model has a better performance than other models.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"10 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140962686","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 : 2024-05-17DOI: 10.3389/fnins.2024.1380467
Xiaolei Chu, Shuaiyi Liu, Xiaoxuan Zhao, Tao Liu, Zheng Xing, Qingwen Li, Qi Li
Spinal cord injury is a condition affecting the central nervous system, causing different levels of dysfunction below the point of nerve damage. A 50-year-old woman suffered a neck injury as a result of a car accident. After undergoing posterior cervical C3–C6 internal fixation with titanium plates on one side and C7 lamina decompression, the patient, who had been diagnosed with C3–C7 cervical disk herniation and spinal stenosis causing persistent compression of the spinal cord, was transferred to the rehabilitation department. After implementing the combined therapy of Virtual Reality-based arm and leg cycling along with transcutaneous electrical stimulation of the spinal cord, the patients experienced a notable enhancement in both sensory and motor abilities as per the ASIA scores. The patient’s anxiety and depression were reduced as measured by the Hamilton Anxiety and Hamilton Depression Tests. As evaluated by the SCIM-III, the patient’s self-reliance and capacity to carry out everyday tasks showed ongoing enhancement, leading to the restoration of their functionality. Hence, the use of Virtual Reality-based arm and leg cycling along with transcutaneous electrical spinal cord stimulation has potential to positively impact function in patients with spinal cord injury. However, as this is a case report, the small number of patients and the fact that the intervention was initiated early after the injury, we were unable to separate the recovery due to the intervention from the natural recovery that is known to occur in the initial weeks and months after SCI. Therefore, further randomized controlled trials with a large sample size is necessary.
{"title":"Case report: Virtual reality-based arm and leg cycling combined with transcutaneous electrical spinal cord stimulation for early treatment of a cervical spinal cord injured patient","authors":"Xiaolei Chu, Shuaiyi Liu, Xiaoxuan Zhao, Tao Liu, Zheng Xing, Qingwen Li, Qi Li","doi":"10.3389/fnins.2024.1380467","DOIUrl":"https://doi.org/10.3389/fnins.2024.1380467","url":null,"abstract":"Spinal cord injury is a condition affecting the central nervous system, causing different levels of dysfunction below the point of nerve damage. A 50-year-old woman suffered a neck injury as a result of a car accident. After undergoing posterior cervical C3–C6 internal fixation with titanium plates on one side and C7 lamina decompression, the patient, who had been diagnosed with C3–C7 cervical disk herniation and spinal stenosis causing persistent compression of the spinal cord, was transferred to the rehabilitation department. After implementing the combined therapy of Virtual Reality-based arm and leg cycling along with transcutaneous electrical stimulation of the spinal cord, the patients experienced a notable enhancement in both sensory and motor abilities as per the ASIA scores. The patient’s anxiety and depression were reduced as measured by the Hamilton Anxiety and Hamilton Depression Tests. As evaluated by the SCIM-III, the patient’s self-reliance and capacity to carry out everyday tasks showed ongoing enhancement, leading to the restoration of their functionality. Hence, the use of Virtual Reality-based arm and leg cycling along with transcutaneous electrical spinal cord stimulation has potential to positively impact function in patients with spinal cord injury. However, as this is a case report, the small number of patients and the fact that the intervention was initiated early after the injury, we were unable to separate the recovery due to the intervention from the natural recovery that is known to occur in the initial weeks and months after SCI. Therefore, further randomized controlled trials with a large sample size is necessary.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"2 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140963306","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 : 2024-05-17DOI: 10.3389/fnins.2024.1375225
Shehzaib Shafique, Walter Setti, Claudio Campus, Silvia Zanchi, Alessio Del Bue, Monica Gori
For animals to locate resources and stay safe, navigation is an essential cognitive skill. Blind people use different navigational strategies to encode the environment. Path integration significantly influences spatial navigation, which is the ongoing update of position and orientation during self-motion. This study examines two separate things: (i) how guided and non-guided strategies affect blind individuals in encoding and mentally representing a trajectory and (ii) the sensory preferences for potential navigational aids through questionnaire-based research. This study first highlights the significant role that the absence of vision plays in understanding body centered and proprioceptive cues. Furthermore, it also underscores the urgent need to develop navigation-assistive technologies customized to meet the specific needs of users.
{"title":"How path integration abilities of blind people change in different exploration conditions","authors":"Shehzaib Shafique, Walter Setti, Claudio Campus, Silvia Zanchi, Alessio Del Bue, Monica Gori","doi":"10.3389/fnins.2024.1375225","DOIUrl":"https://doi.org/10.3389/fnins.2024.1375225","url":null,"abstract":"For animals to locate resources and stay safe, navigation is an essential cognitive skill. Blind people use different navigational strategies to encode the environment. Path integration significantly influences spatial navigation, which is the ongoing update of position and orientation during self-motion. This study examines two separate things: (i) how guided and non-guided strategies affect blind individuals in encoding and mentally representing a trajectory and (ii) the sensory preferences for potential navigational aids through questionnaire-based research. This study first highlights the significant role that the absence of vision plays in understanding body centered and proprioceptive cues. Furthermore, it also underscores the urgent need to develop navigation-assistive technologies customized to meet the specific needs of users.","PeriodicalId":509131,"journal":{"name":"Frontiers in Neuroscience","volume":"38 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140966279","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}
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