middle temporal gyrus

颞中回
  • 文章类型: Journal Article
    很少有研究调查与可卡因使用障碍(CUD)恢复相关的大脑结构和功能的变化,很少有人发现与特定CUD治疗相关的大脑变化,这可以为治疗的发展和优化提供信息。
    在这项纵向研究中,在门诊治疗开始和12周后,从41名美沙酮维持的CUD患者(15名女性)获得了T1加权磁共振成像扫描。作为一项更大的随机对照试验的一部分,这些参与者被随机分配接受(或不接受)基于计算机的认知行为疗法(CBT4CBT)训练,和加兰他敏(或安慰剂)。
    无论治疗情况如何,基于全脑体素的形态计量学分析显示右尾状体显著减少,双侧小脑,治疗后相对于治疗开始时的右侧颞中回灰质体积(GMV)。随后的感兴趣区域分析发现,右尾状核和双侧小脑GMV的减少与治疗期间可卡因使用的相对和绝对水平较高有关。分别。完成更多CBT4CBT模块的参与者右颞中回GMV减少更大。
    这些结果扩展了先前关于尾状和小脑GMV变化作为可卡因使用功能的发现,并提供了大脑结构变化作为参与数字CBT成瘾功能的第一个证据。这些数据表明了一种新的潜在机制,即CBT4CBT和CBT如何更广泛地通过涉及语义知识的大脑区域对物质使用相关行为发挥治疗作用。
    UNASSIGNED: Few studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization.
    UNASSIGNED: In this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo).
    UNASSIGNED: Irrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV.
    UNASSIGNED: These results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.
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  • 文章类型: Journal Article
    亨廷顿氏病(HD)是一种严重影响基底神经节和大脑皮层区域的神经退行性疾病。虽然星形细胞增多和小胶质细胞增多都有助于基底神经节病理,神经胶质增生和驱动人类HD大脑皮层神经胶质活动的潜在因素的贡献尚不清楚。我们的研究旨在确定HD中神经胶质增生的细微差别指标,这在严重退化的基底神经节中具有挑战性。通过调查颞中回(MTG),先前记录的皮质区域显示较温和的神经元丢失。在包含29例HD和35例神经系统正常病例的MTG石蜡包埋组织微阵列(TMAs)上进行免疫组织化学,以比较关键星形细胞蛋白(胶质原纤维酸性蛋白,GFAP;向内整流钾通道4.1,Kir4.1;谷氨酸转运蛋白1,GLT-1;水通道蛋白4,AQP4),关键的小胶质蛋白(离子化钙结合衔接分子-1,IBA-1;人白细胞抗原(HLA)-DR;跨膜蛋白119,TMEM119;嘌呤受体P2RY12,P2RY12),和增殖指标(Ki-67;增殖细胞核抗原,PCNA)。我们的发现表明GFAP+蛋白表达上调归因于HD中更多GFAP+表达细胞的存在。与更大的皮质突变体亨廷顿(mHTT)沉积相关。相比之下,在HD中,Kir4.1、GLT-1和AQP4免疫反应性水平没有变化。我们还证明IBA-1+和TMEM119+小胶质细胞的数量增加,并伴有小体增大。IBA-1+,TMEM119+,和P2RY12+反应性小胶质细胞免疫表型也在HD中鉴定,杆状的存在证明了这一点,肥大,营养不良的小胶质细胞.在HD病例中,IBA-1+细胞含有Ki-67或PCNA,而GFAP+星形胶质细胞缺乏增殖核。这些发现表明皮质小胶质细胞增生可能是由HD的增殖驱动的,支持小胶质细胞增殖作为HD病理生理学特征的假设。相比之下,HD中的星形胶质细胞显示与mHTT沉积程度相关的GFAP表达谱改变.
    Huntington\'s disease (HD) is a neurodegenerative disorder that severely affects the basal ganglia and regions of the cerebral cortex. While astrocytosis and microgliosis both contribute to basal ganglia pathology, the contribution of gliosis and potential factors driving glial activity in the human HD cerebral cortex is less understood. Our study aims to identify nuanced indicators of gliosis in HD which is challenging to identify in the severely degenerated basal ganglia, by investigating the middle temporal gyrus (MTG), a cortical region previously documented to demonstrate milder neuronal loss. Immunohistochemistry was conducted on MTG paraffin-embedded tissue microarrays (TMAs) comprising 29 HD and 35 neurologically normal cases to compare the immunoreactivity patterns of key astrocytic proteins (glial fibrillary acidic protein, GFAP; inwardly rectifying potassium channel 4.1, Kir4.1; glutamate transporter-1, GLT-1; aquaporin-4, AQP4), key microglial proteins (ionised calcium-binding adapter molecule-1, IBA-1; human leukocyte antigen (HLA)-DR; transmembrane protein 119, TMEM119; purinergic receptor P2RY12, P2RY12), and indicators of proliferation (Ki-67; proliferative cell nuclear antigen, PCNA). Our findings demonstrate an upregulation of GFAP+ protein expression attributed to the presence of more GFAP+ expressing cells in HD, which correlated with greater cortical mutant huntingtin (mHTT) deposition. In contrast, Kir4.1, GLT-1, and AQP4 immunoreactivity levels were unchanged in HD. We also demonstrate an increased number of IBA-1+ and TMEM119+ microglia with somal enlargement. IBA-1+, TMEM119+, and P2RY12+ reactive microglia immunophenotypes were also identified in HD, evidenced by the presence of rod-shaped, hypertrophic, and dystrophic microglia. In HD cases, IBA-1+ cells contained either Ki-67 or PCNA, whereas GFAP+ astrocytes were devoid of proliferative nuclei. These findings suggest cortical microgliosis may be driven by proliferation in HD, supporting the hypothesis of microglial proliferation as a feature of HD pathophysiology. In contrast, astrocytes in HD demonstrate an altered GFAP expression profile that is associated with the degree of mHTT deposition.
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  • 文章类型: Journal Article
    先前的研究表明,传统的经颅直流电刺激(tDCS)可以增强新词学习。然而,由于这些设置引起的大电流和缺乏适当的控制条件,对潜在的神经机制知之甚少。在目前的双盲和假tDCS对照研究中,我们首次调查了在不同时间点针对新词学习网络的两个关键节点的区域精确局灶性tDCS是否会导致区域和时间上不同的影响。156名参与者完成了上下文小说单词学习范式,并在习得期后和30分钟后立即探究了学习成功。参与者被随机分配到六个刺激条件:主动tDCS(1.5mA)被给予左下额叶(IFG)或颞中回(MTG),无论是在收购还是延迟召回。对照组在采集或延迟召回期间接受假tDCS(50%IFG/MTG)。在贝叶斯框架中使用具有二项链接函数的广义线性混合模型分析数据。我们的结果表明,正面tDCS选择性地增加了从即时到延迟召回的准确性增益,不管刺激的时间。没有证据表明颞中回tDCS具有有益作用。我们的发现证实,IFGtDCS可以增强区域内的新词学习,但不是具体的时间。暂时,这可以通过增强语义选择过程来解释,从而导致更有效的整合和/或检索。需要在评估之间使用更长的时间间隔进行未来的研究,以阐明在采集期间施用IFGtDCS的神经生理学后效应对增强巩固的潜在贡献。
    Previous studies have demonstrated that conventional transcranial direct current stimulation (tDCS) can enhance novel-word learning. However, because of the widespread current that is induced by these setups and lack of appropriate control conditions, little is known about the underlying neural mechanisms. In the present double-blinded and sham-tDCS controlled study, we investigated for the first time if regionally precise focal tDCS targeting two key nodes of the novel-word learning network at different time points would result in regionally and temporally distinct effects. 156 participants completed a contextual novel-word-learning paradigm and learning success was probed immediately after the acquisition period and 30-min later. Participants were randomly assigned to six stimulation conditions: Active tDCS (1.5 mA) was administered to left inferior frontal (IFG) or middle temporal gyrus (MTG), either during acquisition or delayed recall. Control groups received sham-tDCS either during acquisition or delayed recall (50% IFG/MTG). Data were analyzed with a generalized linear mixed model with a binomial link function in a Bayesian framework. Our results showed that frontal tDCS selectively increased accuracy gains from immediate to delayed recall, irrespective of timing of the stimulation. There was no evidence for beneficial effects of middle temporal gyrus tDCS. Our findings confirm that IFG tDCS can enhance novel-word learning in a regionally, but not timing specific way. Tentatively, this may be explained by enhancement of semantic selection processes resulting in more effective consolidation and/or retrieval. Future studies using longer time intervals between assessments are required to clarify the potential contribution of neurophysiological after-effects of IFG tDCS administered during acquisition to enhanced consolidation.
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  • 文章类型: Journal Article
    社会认知(SC)的缺陷会干扰精神分裂症(SZ)的恢复,并且可能与静息状态的大脑连接有关。这项研究旨在评估与健康受试者相比,SZ患者的静息状态功能连接与社会认知能力之间关系的改变。我们根据人类健康志愿者大脑图集将大脑分为246个感兴趣的区域(ROI)。对于每个参与者,我们根据度中心性(DC)计算了静息状态功能连通性(rsFC),它评估休息期间每个ROI与所有其他ROI最强大的协同作用的总强度。ROI的rs-DC与SC评估45名健康志愿者(HVs)作为规范样本的情绪处理和心理的五种指标相关。然后,控制症状的严重程度,我们验证了这些重要的关联是否被改变了,即,不存在或相反的符号,在55例SZ患者中。我们发现SZ患者和HV之间存在五个显着差异:在患者组中,情绪识别任务与右内嗅皮层(R-EC)rsFC的相关性,左顶叶上小叶(L-SPL),右尾海马(R-c-Hipp),右尾(R-c)和左首(L-r)颞中回(MTG)丢失。L-SPL的静息状态功能连通性改变,R-EC,R-c-Hipp,SZ患者的双侧MTG可能与情绪识别受损有关。如果确认,这些结果可能会促进针对这些大脑区域的非侵入性脑刺激干预措施的发展,以减少SZ的SC缺陷。
    Deficits in social cognition (SC) interfere with recovery in schizophrenia (SZ) and may be related to resting state brain connectivity. This study aimed at assessing the alterations in the relationship between resting state functional connectivity and the social-cognitive abilities of patients with SZ compared to healthy subjects. We divided the brain into 246 regions of interest (ROI) following the Human Healthy Volunteers Brainnetome Atlas. For each participant, we calculated the resting-state functional connectivity (rsFC) in terms of degree centrality (DC), which evaluates the total strength of the most powerful coactivations of every ROI with all other ROIs during rest. The rs-DC of the ROIs was correlated with five measures of SC assessing emotion processing and mentalizing in 45 healthy volunteers (HVs) chosen as a normative sample. Then, controlling for symptoms severity, we verified whether these significant associations were altered, i.e., absent or of opposite sign, in 55 patients with SZ. We found five significant differences between SZ patients and HVs: in the patients\' group, the correlations between emotion recognition tasks and rsFC of the right entorhinal cortex (R-EC), left superior parietal lobule (L-SPL), right caudal hippocampus (R-c-Hipp), and the right caudal (R-c) and left rostral (L-r) middle temporal gyri (MTG) were lost. An altered resting state functional connectivity of the L-SPL, R-EC, R-c-Hipp, and bilateral MTG in patients with SZ may be associated with impaired emotion recognition. If confirmed, these results may enhance the development of non-invasive brain stimulation interventions targeting those cerebral regions to reduce SC deficit in SZ.
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  • 文章类型: Journal Article
    联想记忆可以说是最基本的记忆功能,其中构成了所有情节和语义记忆过程的基础。同时,联想记忆的下降代表了两者与年龄相关的认知能力下降的核心特征,健康和病理(即,与痴呆症相关的)衰老。与年龄相关的联想记忆损伤的潜在神经机制仍未完全理解,特别是关于附带的(即,非故意)学习。
    我们调查了46名年轻人(N=23;平均年龄=23.39岁)和老年人(N=22,平均年龄=69.05岁)参与者的年龄对面部名称组合的附带学习和记忆检索的影响。更具体地说,特别感兴趣的是编码/检索(E/R)翻转中与年龄相关的变化,这表示在记忆编码和检索过程中,同一大脑区域的相反激活模式的神经拮抗作用,使用fMRI进行评估。
    根据我们的假设,结果显示,老年组的检索性能显著下降.此外,在神经层面,我们发现,在老年受试者中,右前脑岛和关节的E/R翻转已消除,但在后中扣带皮质的E/R翻转激活幅度降低。
    总而言之,本研究结果表明,右侧aIC中E/R翻转的神经调节受损可能是早期检测神经衰老的敏感标志物。
    UNASSIGNED: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning.
    UNASSIGNED: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI.
    UNASSIGNED: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects.
    UNASSIGNED: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.
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  • 文章类型: Journal Article
    目的:评估中颞叶回(MTG)方法治疗中颞叶(MTL)肿瘤是否是治疗儿童癫痫的有效方法。
    目的:MTL肿瘤是儿童耐药性癫痫的常见原因。目前尚未就其治疗达成共识。一种可能性是通过MTG方法切除。
    方法:我们评估了神经外科患者的医疗记录,儿童纪念健康研究所,华沙,波兰在2002年至2020年之间。前瞻性维护的数据库,包括临床,实验室,和射线照相显示,以及手术前和手术后的过程,进行了分析。包括至少一年随访的患者。
    结果:有14名年龄在4-18岁之间的患者接受了MTG方法治疗MTL肿瘤。都出现了癫痫发作,入院时没有神经缺损。中位随访时间为2.5年。神经导航被用来调整方法,定位颞角,并实现肿瘤和海马的根治性切除。所有病例均进行了大体全切除。在大多数患者中,组织病理学检查显示神经节胶质瘤。1例患者出现短暂性失语。两名患者在手术后出现偏瘫,后来改进了。其中一人还经历了视觉障碍。急性并发症在年轻患者中更为常见(p=0.024)。在所有情况下,MRI证实完全切除,随访期间无肿瘤复发。13/14患者仍无癫痫发作(EngelI类)。
    结论:MTG治疗MTL肿瘤是治疗儿童癫痫的有效方法。它避免了颞叶外侧的去除,并且仅造成永久性神经系统并发症的微小风险。
    OBJECTIVE: To assess whether the middle temporal gyrus (MTG) approach to mesial temporal lobe (MTL) tumours is an effective procedure for the treatment of epilepsy in children.
    OBJECTIVE: MTL tumours are a common cause of drug-resistant epilepsy in children. There is as yet no consensus regarding their treatment. One possibility is resection via a MTG approach.
    METHODS: We assessed the medical records of patients treated at the Department of Neurosurgery, Children\'s Memorial Health Institute,Warsaw, Poland between 2002 and 2020. A prospectively maintained database including clinical, laboratory, and radiographic presentation, as well as pre- and post-operative course, was analysed. Patients with at least a one- -year follow-up were included.
    RESULTS: There were 14 patients aged 4-18 years who underwent a MTG approach for a MTL tumour. All presented with epileptic seizure, and none had neurological deficit on admission to hospital. Median follow-up was 2.5 years. Neuronavigation was used to adjust the approach, localise the temporal horn, and achieve radical resection of the tumour and the hippocampus. Gross total resection was performed in all cases. In most patients, histopathological examination revealed ganglioglioma. One patient had transient aphasia. Two patients developed hemiparesis after surgery, which later improved. One of them also experienced visual disturbances. Acute complications were more frequent in younger patients (p = 0.024). In all cases, MRI confirmed complete resection and there was no tumour recurrence during the follow-up period. 13/14 patients remained seizure-free (Engel class I).
    CONCLUSIONS: The MTG approach to MTL tumours is an effective procedure for the treatment of epilepsy in children. It avoids removal of the lateral temporal lobe and poses only a minor risk of permanent neurological complications.
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  • 文章类型: Journal Article
    感知的社会支持被认为在促进个人健康和福祉方面发挥着重要作用,然而,感知社会支持的神经相关性尚未完全理解。探索SPS中个体差异的神经相关性可以帮助我们更全面地了解感知社会支持的神经相关性。更重要的是,我们的研究将探讨感知社会支持之间的关系,大脑区域,和心理健康,从认知神经科学的角度来看,这可能为感知社会支持与心理健康之间的关系提供新的神经关联。
    这里,我们使用社会规定量表来评估个人感知的社会支持,磁共振成像用于测量整个大脑的灰质(GM)体积。更重要的是,我们还使用心理健康量表来衡量心理健康,并运用中介分析探讨感知社会支持与感知社会支持之间的关系,大脑区域,和心理健康。
    对全脑的基于体素的形态计量学分析显示,感知的社会支持与左颞中回(MTG)的GM体积呈正相关。该发现表明,在左侧MTG中,转基因数量较大的人感受到了更多的社会支持。更重要的是,上面观察到的左侧MTGGM体积也与心理健康有关,两者之间的联系是由感知到的社会支持介导的。
    这些结果揭示了MTG对感知到的社会支持和心理健康的重要性,并提出感知社会支持可以解释MTG与心理健康之间的关系。
    UNASSIGNED: Perceived social support is considered to play a significant role in promoting individuals\' health and well-being, and yet the neural correlates of perceived social support were not fully understood. An exploration of the neural correlates of individual differences in the SPS can help us to gain more comprehensive understanding about the neural correlates of perceived social support. What\'s more, our study will explore the relationship among perceived social support, brain regions, and psychological well-being, which may provide new insights into the neural correlates underlying the relationship between perceived social support and psychological well-being from the perspective of cognitive neuroscience.
    UNASSIGNED: Herein, we used the Social Provisions Scale to assess individuals\' perceived social support, and magnetic resonance imaging was used to measure the gray matter (GM) volume of the whole brain. What\'s more, we also measured psychological well-being using the Psychological Well-Being Scale, and mediation analysis was used to explore the relationship among perceived social support, brain regions, and psychological well-being.
    UNASSIGNED: The voxel-based morphometry analysis of the whole brain revealed that perceived social support was positively correlated with GM volume of the left middle temporal gyrus (MTG). The finding indicated that a person with greater GM volume in the left MTG perceived more social support. More importantly, the left MTG GM volume observed above was also associated with psychological well-being, and the link between the two was mediated by perceived social support.
    UNASSIGNED: These results revealed the importance of MTG for perceived social support and psychological well-being, and also suggested that perceived social support might explain the relationship between MTG and psychological well-being.
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  • 文章类型: Journal Article
    慢性踝关节不稳(CAI)被认为是一种神经生理学疾病,具有体感和运动系统兴奋性功能障碍的症状。康复已被认为是CAI的有效治疗方法。然而,很少有研究探讨康复对CAI人群神经可塑性的影响。
    本研究的目的是研究康复对CAI患者姿势控制的皮质活动的影响,并发现皮质活动的变化与患者报告的结果(PRO)之间的相关性。
    13名CAI参与者(6名女性,7男,年龄=33.8±7.7岁,BMI=24.7±4.9kg/m2)每天接受约40分钟的家庭锻炼计划,每周四天和六周,包括踝关节活动范围锻炼,肌肉加强,平衡活动。皮质活化,评估和比较康复前后的PRO和Y平衡测试结果。通过功能近红外光谱(fNIRS)检测到皮质激活,而参与者执行单腿站立任务。
    参与者在康复后有更好的PRO和Y平衡测试结果。在初级体感皮层中观察到更大的皮层激活(S1,d=0.66,p=0.035),颞上回(STG,d=1.06,p=0.002)和颞中回(MTG,康复后CAI患者的d=0.66,p=0.035)。此外,踝关节症状恢复与S1(r=0.74,p=0.005)和STG(r=0.72,p=0.007)皮质活化变化呈正相关。
    目前的研究表明,6周的康复可以导致S1、STG和MTG的皮质激活。皮质激活的增加表明感知体感刺激的能力更好,并且可能在功能改善中具有代偿作用。
    UNASSIGNED: Chronic ankle instability (CAI) has been considered a neurophysiological disease, having as symptoms dysfunction in somatosensory and motor system excitability. Rehabilitation has been considered an effective treatment for CAI. However, few studies have explored the effects of rehabilitation on neuroplasticity in the CAI population.
    UNASSIGNED: The purpose of this study was to investigate the effects of rehabilitation on cortical activities for postural control in CAI patients and to find the correlation between the change in cortical activities and patient-reported outcomes (PROs).
    UNASSIGNED: Thirteen participants with CAI (6 female, 7 male, age = 33.8 ± 7.7 years, BMI = 24.7 ± 4.9 kg/m2) received a home exercise program for about 40 min per day, four days per week and six weeks, including ankle range-of-motion exercise, muscle strengthening, and balance activities. Cortical activation, PROs and Y-balance test outcomes were assessed and compared before and after rehabilitation. Cortical activation was detected via Functional near-infrared spectroscopy (fNIRS) while the participants performed single-leg stance tasks.
    UNASSIGNED: The participants had better PROs and Y balance test outcomes after rehabilitation. Greater cortical activation was observed in the primary somatosensory cortex (S1, d = 0.66, p = 0.035), the superior temporal gyrus (STG, d = 1.06, p = 0.002) and the middle temporal gyrus (MTG, d = 0.66, p = 0.035) in CAI patients after rehabilitation. Moreover, significant positive correlations were observed between the recovery of ankle symptoms and the change of cortical activation in S1 (r = 0.74, p = 0.005) and STG (r = 0.72, p = 0.007) respectively.
    UNASSIGNED: The current study reveals that six weeks of rehabilitation can cause greater cortical activation in S1, STG and MTG. This increase in cortical activation suggested a better ability to perceive somatosensory stimuli and may have a compensatory role in function improvement.
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  • 文章类型: Preprint
    年龄是神经退行性疾病的主要常见危险因素,包括老年痴呆症,帕金森病,和肌萎缩侧索硬化症.先前的研究报道,实际年龄与不同大脑区域的差异基因表达相关。然而,先前的数据集尚未消除表达与年龄的关联是否归因于每个细胞的细胞数量和/或基因表达的变化。在这项研究中,我们利用单核RNA测序(snRNAseq)来检查四个不同脑区的细胞比例和转录组的变化,每个来自12个20-30岁(年轻)或60-85岁(年龄)的捐赠者。我们从与神经退行性疾病或增生性生态位相关的两个皮质区域(内嗅皮质和颞中回)和两个皮质下区域(壳核和脑室下区)采样了155,192个核。我们发现,随着健康的衰老,不同大脑区域的细胞组成没有变化。令人惊讶的是,我们确实发现每个大脑区域都有不同的衰老特征,在不同区域的差异相关基因中只有轻微的重叠。此外,每种细胞类型都显示出明显的与年龄相关的表达变化,包括皮质抑制性神经元中蛋白质合成基因的缺失,兴奋性神经元和少突胶质细胞前体细胞的轴突发生基因,增强星形胶质细胞中的胶质细胞标记和小胶质细胞中的疾病相关标记,和对神经胶质细胞通讯至关重要的基因。重要的是,我们发现年龄关联的细胞类型特异性富集与阿尔茨海默病和帕金森病全基因组关联研究(GWAS)提名的基因,如载脂蛋白E(APOE),和小胶质细胞中富含亮氨酸的重复激酶2(LRRK2)独立于跨细胞类型的整体表达水平。我们将这些数据作为一种新的资源来展示,首先,健康衰老中区域和细胞类型特异性转录组变化可能导致选择性脆弱性,第二,为在相关亚型中检测GWAS提名的疾病风险基因和制定更有针对性的治疗策略提供背景.数据易于访问,而无需在公共网站中提供广泛的计算支持,https://brainexp-hykyffa56a-uc.a.run.app/.
    在四个大脑区域中建立人类衰老的单核图集每个区域和细胞类型都表现出独特的与衰老相关的转录组特征基因表达变化在没有明显细胞丢失的情况下发生,并且在整个细胞类型中是绝对独特的。在健康衰老的背景下,神经系统疾病相关基因在特定细胞类型中具有与年龄相关的表达模式。
    Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer\'s disease, Parkinson\'s disease, and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether expression associations with age are due to changes in cell numbers and/or gene expression per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) to examine changes in cell proportions and transcriptomes in four different brain regions, each from 12 donors aged 20-30 years (young) or 60-85 years (old). We sampled 155,192 nuclei from two cortical regions (entorhinal cortex and middle temporal gyrus) and two subcortical regions (putamen and subventricular zone) relevant to neurodegenerative diseases or the proliferative niche. We found no changes in cellular composition of different brain regions with healthy aging. Surprisingly, we did find that each brain region has a distinct aging signature, with only minor overlap in differentially associated genes across regions. Moreover, each cell type shows distinct age-associated expression changes, including loss of protein synthesis genes in cortical inhibitory neurons, axonogenesis genes in excitatory neurons and oligodendrocyte precursor cells, enhanced gliosis markers in astrocytes and disease-associated markers in microglia, and genes critical for neuron-glia communication. Importantly, we find cell type-specific enrichments of age associations with genes nominated by Alzheimer\'s disease and Parkinson\'s disease genome-wide association studies (GWAS), such as apolipoprotein E (APOE), and leucine-rich repeat kinase 2 (LRRK2) in microglia that are independent of overall expression levels across cell types. We present this data as a new resource which highlights, first, region- and cell type-specific transcriptomic changes in healthy aging that may contribute to selective vulnerability and, second, provide context for testing GWAS-nominated disease risk genes in relevant subtypes and developing more targeted therapeutic strategies. The data is readily accessible without requirement for extensive computational support in a public website, https://brainexp-hykyffa56a-uc.a.run.app/.
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  • 文章类型: Journal Article
    我们研究了人脑如何整合特定事件的经验,以建立有关典型事件结构的一般知识。我们检查了一个对时间关系很重要的情景记忆区域,前外侧内嗅皮层,和一个对动作概念很重要的语义记忆区,颞中回,了解这些领域如何以及何时对这些过程做出贡献。参与者进行了功能磁共振成像,同时学习和回顾了两个间隔1周的新事件之间的时间关系。在不同的背景下,事件之间的个体时间关系可以是一致的,也可以是不一致的。在每个上下文中,在召回阶段,我们将关联编码测量为相关事件对与无关事件对之间多体素相关性的差异。形成整合表示的神经区域在一致性中应表现出比不一致上下文更强的关联编码。我们发现了在前外侧内嗅皮层(在第1阶段)中迅速出现的整合表征的证据,随后仅在颞中回,这表明会议之间发生了重大变化。在学习过程中,发现了一种互补的发现模式。这表明整合表征在前外侧内嗅皮层的早期建立,并且可能是后来在中颞回出现语义知识的途径。
    We investigated how the human brain integrates experiences of specific events to build general knowledge about typical event structure. We examined an episodic memory area important for temporal relations, anterior-lateral entorhinal cortex, and a semantic memory area important for action concepts, middle temporal gyrus, to understand how and when these areas contribute to these processes. Participants underwent functional magnetic resonance imaging while learning and recalling temporal relations among novel events over two sessions 1 week apart. Across distinct contexts, individual temporal relations among events could either be consistent or inconsistent with each other. Within each context, during the recall phase, we measured associative coding as the difference of multivoxel correlations among related vs unrelated pairs of events. Neural regions that form integrative representations should exhibit stronger associative coding in the consistent than the inconsistent contexts. We found evidence of integrative representations that emerged quickly in anterior-lateral entorhinal cortex (at session 1), and only subsequently in middle temporal gyrus, which showed a significant change across sessions. A complementary pattern of findings was seen with signatures during learning. This suggests that integrative representations are established early in anterior-lateral entorhinal cortex and may be a pathway to the later emergence of semantic knowledge in middle temporal gyrus.
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