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Measuring cognitive load in multitasking using mobile fNIRS 利用移动 fNIRS 测量多任务处理中的认知负荷
Q4 Neuroscience Pub Date : 2024-11-19 DOI: 10.1016/j.ynirp.2024.100228
Katherine Boere , Francesca Anderson , Kent G. Hecker , Olav E. Krigolson
Cognitive load, or the mental effort required to process and retain information, is a critical factor in high-stakes environments where task demands often exceed working memory capacity, leading to performance declines and errors. However, most cognitive load research has relied on controlled, single-task paradigms, limiting its applicability to real-world multitasking situations. Addressing this gap, we used a mobile, two-channel functional near-infrared spectroscopy (fNIRS) device to measure cognitive load in a complex multitasking environment, simulating real-world cognitive demands. Thirty-one undergraduate participants engaged in single-task and multitask conditions to simulate real-world cognitive demands. Results showed that subjective cognitive load ratings were higher, performance scores were lower, and error rates increased in the multitask condition compared to the single-task condition. However, contrary to expectations, prefrontal cortex activation did not increase in the multitask condition, suggesting a "cognitive disengagement" effect, where the brain limits engagement to manage overload. This finding challenges the traditional one-to-one association between cognitive load and prefrontal activation, as seen in simpler validation studies. Our study highlights the value of mobile fNIRS for assessing cognitive load in ecologically valid settings and provides insights that could inform strategies for optimizing performance in high-stakes environments like aviation and healthcare.
认知负荷,即处理和保留信息所需的脑力劳动,是高风险环境中的一个关键因素,在这种环境中,任务要求往往超过工作记忆能力,从而导致成绩下降和失误。然而,大多数认知负荷研究都依赖于受控的单一任务范例,限制了其在现实世界多任务情况下的适用性。为了弥补这一不足,我们使用了移动式双通道功能性近红外光谱(fNIRS)设备来测量复杂多任务环境下的认知负荷,模拟真实世界的认知需求。31 名本科生参加了模拟真实世界认知需求的单任务和多任务条件。结果显示,与单任务条件相比,多任务条件下的主观认知负荷评分更高,成绩得分更低,错误率更高。然而,与预期相反的是,在多任务条件下,前额叶皮层的激活并没有增加,这表明存在 "认知脱离 "效应,即大脑限制参与以管理超负荷。这一发现挑战了认知负荷与前额叶激活之间一一对应的传统联系,正如在更简单的验证研究中所看到的那样。我们的研究凸显了移动 fNIRS 在生态有效环境中评估认知负荷的价值,并为航空和医疗保健等高风险环境中的绩效优化策略提供了启示。
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引用次数: 0
MRI-guided clustering of patients with mild dementia due to Alzheimer's disease using self-organizing maps 利用自组织图在磁共振成像引导下对阿尔茨海默病所致轻度痴呆患者进行聚类
Q4 Neuroscience Pub Date : 2024-11-18 DOI: 10.1016/j.ynirp.2024.100227
Kellen K. Petersen , Bhargav T. Nallapu , Richard B. Lipton , Ellen Grober , Ali Ezzati

Introduction

Alzheimer's disease (AD) is a phenotypically and pathologically heterogenous neurodegenerative disorder. This heterogeneity can be studied and disentangled using data-driven clustering techniques.

Methods

We implemented a self-organizing map clustering algorithm on baseline volumetric MRI measures from nine brain regions of interest (ROIs) to cluster 1041 individuals enrolled in the placebo arm of the EXPEDITION3 trial. Volumetric MRI differences were compared among clusters. Demographics as well as baseline and longitudinal cognitive performance metrics were used to evaluate cluster characteristics.

Results

Three distinct clusters, with an overall silhouette coefficient of 0.491, were identified based on MRI volumetrics. Cluster 1 (N = 400) had the largest baseline volumetric measures across all ROIs and the best cognitive performance at baseline. Cluster 2 (N = 269) had larger hippocampal and medial temporal lobe volumes, but smaller parietal lobe volumes in comparison with the third cluster (N = 372). Significant between-group mean differences were observed between Clusters 1 and 2 (difference, 2.38; 95% CI, 1.85 to 2.91; P < 0.001), Clusters 1 and 3 (difference, 1.93; 95% CI, 1.41 to 2.44; P < 0.001), but not between Clusters 2 and 3 (difference, 0.45; 95% CI, −0.11 to 1.02; P = 0.146) in ADAS-14.

Conclusions

Volumetric MRI can be used to identify homogenous clusters of amyloid positive individuals with mild dementia. The groups identified differ in baseline and longitudinal characteristics. Cluster 1 shows little ADAS-14 change over the first 40 weeks of study on placebo treatment and may be unsuitable for identifying early benefits of treatment.
导言阿尔茨海默病(AD)是一种表型和病理上异质性的神经退行性疾病。我们对来自九个大脑感兴趣区(ROIs)的基线容积 MRI 测量值实施了自组织图聚类算法,对参加 EXPEDITION3 试验安慰剂组的 1041 人进行了聚类。比较了聚类之间的磁共振成像容积差异。结果根据核磁共振成像的容积系数,确定了三个不同的群组,总体剪影系数为 0.491。群组 1(N = 400)所有 ROI 的基线容积测量值最大,基线认知表现最好。与第三组(N = 372)相比,第二组(N = 269)的海马和颞叶内侧体积较大,但顶叶体积较小。在第 1 组和第 2 组(差异为 2.38;95% CI,1.85 至 2.91;P <;0.001)、第 1 组和第 3 组(差异为 1.93;95% CI,1.41 至 2.44;P <;0.结论 超声核磁共振成像可用于识别淀粉样蛋白阳性的轻度痴呆患者的同质群。所确定的群组在基线和纵向特征方面存在差异。群组1在接受安慰剂治疗的前40周内ADAS-14变化不大,可能不适合用于识别治疗的早期益处。
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引用次数: 0
Evaluating state-based network dynamics in anhedonia 评估失乐症中基于状态的网络动力学
Q4 Neuroscience Pub Date : 2024-10-19 DOI: 10.1016/j.ynirp.2024.100225
Angela Pisoni , Jeffrey Browndyke , Simon W. Davis , Moria Smoski
Anhedonia is a transdiagnostic clinical syndrome associated with significant clinical impairment. In spite of this, a clear network-level characterization of anhedonia does not yet exist. The present study addressed this gap in the literature by taking a graph theoretical approach to characterizing state-based (i.e., reward anticipation, rest) network dynamics in a transdiagnostic sample of adults with clinically significant anhedonia (n = 77). Analyses focused on three canonical brain networks: the Salience Network (SN), the Default Mode Network (DMN) and the Central Executive Network (CEN), with hypotheses focusing on the role of saliency-mapping in anhedonia. Contrary to hypotheses, no significant relation was found between the SN and anhedonia symptom severity. Exploratory results revealed a significant association between anhedonia severity and DMN reorganization from rest to reward anticipation. Specifically, greater anhedonia severity was associated with less reward-related reorganization. This finding suggests that anhedonia severity may be associated with DMN hyposensitivity, such that individuals with more severe anhedonia may have a difficult time disengaging from their internal world in the context of potentially rewarding experiences. Although preliminary, this finding challenges the centrality of the SN in anhedonia severity and suggests the importance of the DMN. Clinical implications and future directions are explored.
失乐症是一种跨诊断的临床综合征,伴有严重的临床损害。尽管如此,关于失乐症的明确的网络层面特征描述尚不存在。本研究针对文献中的这一空白,采用图论方法描述了临床上患有明显失乐症的成人(n = 77)的跨诊断样本中基于状态(即奖赏预期、休息)的网络动力学特征。分析的重点是三个典型的大脑网络:显著性网络(SN)、默认模式网络(DMN)和中央执行网络(CEN),假设的重点是显著性映射在失乐症中的作用。与假设相反的是,SN 与失乐症症状严重程度之间没有发现明显的关系。探索性结果显示,失神症严重程度与从休息到奖赏预期的DMN重组之间存在显著关联。具体来说,失乐症严重程度越高,与奖赏相关的重组越少。这一发现表明,失乐症的严重程度可能与DMN的低敏感性有关,因此失乐症较严重的人可能很难在潜在奖赏体验的背景下脱离他们的内心世界。尽管是初步研究,但这一发现对SN在厌食症严重程度中的中心地位提出了质疑,并提示了DMN的重要性。本文探讨了这一发现对临床的影响以及未来的研究方向。
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引用次数: 0
Unresponsiveness induced by sevoflurane and propofol is associated with reduced basal forebrain cholinergic nuclei functional connectivity in humans, a pilot exploratory study 七氟醚和异丙酚引起的反应迟钝与人类前脑基底胆碱能核功能连接性降低有关,一项试验性探索研究
Q4 Neuroscience Pub Date : 2024-10-05 DOI: 10.1016/j.ynirp.2024.100224
Juliana Zimmermann , Rachel Nuttall , Daniel Golkowski , Gerhard Schneider , Andreas Ranft , Rüdiger Ilg , Afra Wohlschlaeger , Christian Sorg , Marlene Tahedl
Studies suggest the cholinergic system is involved in anesthesia-induced unconsciousness, hence unresponsiveness. A significant source of cholinergic innervation comes from basal forebrain cholinergic nuclei (BFCN), with bi-directional connections between anterior BFCN and the default mode network (DMN). Since DMN functional connectivity (FC) is consistently reduced during anesthesia-induced unresponsiveness in humans, we hypothesized that BFCN-FC during anesthesia-induced unresponsiveness is reduced and particularly, anterior BFCN-FC reductions might be related to DMN-FC reductions. Resting-state fMRI (rs-fMRI) signal correlations (i.e., a proxy for FC) were calculated. FC seeds were anterior and posterior BFCN and the DMN. Rs-fMRI data come from healthy male controls during wakefulness and anesthesia with sevoflurane (n = 15) (at fixed concentrations: 2 and 3 vol%) and propofol titrated to the endpoint of clinical unresponsiveness (n = 12), respectively. FC state differences were tested via paired t-tests; FC changes for anterior BFCN and DMN were associated via correlation analysis. We found reduced anterior and posterior BFCN-FC with sevoflurane and propofol compared to wakefulness. The correlation between reduced DMN-FC-and anterior BFCN-FC reductions was r = 0.57 (p = 0.01) for sevoflurane 3 vol%, r = 0.34 (p = 0.11) for sevoflurane 2 vol% and r = 0.47 (p = 0.06) for propofol. In summary, in this exploratory pilot study, we demonstrated reduced BFCN-FC and a potential correlation between reduced anterior BFCN-FC and DMN-FC during sevoflurane and propofol anesthesia. This suggests DMN changes as a potential factor of anterior BFCN-FC reductions during anesthesia-induced unresponsiveness and BFCN-FC reduction as a potential sign of such state.
研究表明,胆碱能系统参与了麻醉引起的昏迷,从而导致反应迟钝。胆碱能神经支配的一个重要来源是前脑基底胆碱能核(BFCN),前脑基底胆碱能核与默认模式网络(DMN)之间存在双向联系。由于人类在麻醉诱导的反应迟钝期间DMN功能连通性(FC)会持续降低,我们假设在麻醉诱导的反应迟钝期间BFCN-FC会降低,尤其是前部BFCN-FC的降低可能与DMN-FC的降低有关。我们计算了静息态 fMRI(rs-fMRI)信号相关性(即 FC 的替代物)。FC种子为前后BFCN和DMN。Rs-fMRI数据来自清醒时的健康男性对照组,以及分别使用七氟醚(n = 15)(固定浓度:2和3 vol%)和丙泊酚滴定至临床无反应终点(n = 12)进行麻醉时的健康男性对照组。FC 状态差异通过配对 t 检验进行检验;前部 BFCN 和 DMN 的 FC 变化通过相关性分析进行关联。我们发现,与清醒状态相比,七氟醚和异丙酚会降低前部和后部BFCN-FC。DMN-FC 减少与前部 BFCN-FC 减少之间的相关性为:七氟烷 3 vol% 时 r = 0.57(p = 0.01),七氟烷 2 vol% 时 r = 0.34(p = 0.11),异丙酚时 r = 0.47(p = 0.06)。总之,在这项探索性试验研究中,我们证明了在七氟醚和丙泊酚麻醉过程中,BFCN-FC 的减少以及前部 BFCN-FC 减少与 DMN-FC 之间的潜在相关性。这表明 DMN 变化是麻醉诱导反应迟钝时前部 BFCN-FC 减少的潜在因素,而 BFCN-FC 减少则是这种状态的潜在标志。
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引用次数: 0
Increased functional connectivity of amygdalar-frontal pathways in patients with alcohol use disorder and childhood trauma 酒精使用障碍和童年创伤患者杏仁核-额叶通路的功能连接性增强
Q4 Neuroscience Pub Date : 2024-10-02 DOI: 10.1016/j.ynirp.2024.100223
Elisabeth Jehli , Fabienne Burri , Niklaus Denier , Franz Moggi , Andrea Federspiel , Roland Wiest , Maria Stein , Tobias Bracht , Matthias Grieder , Leila M. Soravia
Childhood trauma (CT) often co-occurs with alcohol use disorder (AUD) and is associated with poor treatment outcome. We could demonstrated that patients with AUD and a history of childhood trauma showed reduced structural connectivity of the amygdala. Here, we additionally aimed to investigate fronto-limbic functional connectivity (FC) in patients with AUD with (AUD-CT) and without (AUD-noCT) CT. Based on findings in CT, we hypothesized reduced FC of the amygdala with the prefrontal cortex in AUD-CT and worse treatment outcome compared to AUD-noCT.
Resting state fMRI scans were acquired in abstinent inpatients with AUD and healthy controls (HCs). We compared bilateral amygdala FC between AUD-CT (n = 21), AUD-noCT (n = 22), and HC (n = 27) using seed-based connectivity (SBC) and region-of-interest to region-of-interest (ROI-ROI) analysis. Sociodemographic and alcohol-specific variables (percent days abstinent, PDA) were assessed at treatment admission and three-month follow-up. The Childhood Trauma Questionnaire (CTQ) assessed trauma severity. SBC analysis revealed that AUD-CT showed increased FC of the left and right amygdala with the medial prefrontal cortex and left paracingulate gyrus compared to HC. AUD-CT showed increased ROI-ROI FC of the left with the right amygdala and the right amygdala with the medial prefrontal cortex. Moreover, AUD-CT exhibited a greater reduction of PDA at three-month follow-up compared to AUD-noCT.
Increased FC of the amygdala, the medial prefrontal cortex, and paracingulate gyrus in AUD-CT might be a compensatory adaption to the reduced structural connectivity of the amygdala. Those specific alterations of FC in AUD-CT may represent a distinguishable neurobiological subtype of AUD, possibly underlying the complex clinical picture and worse treatment outcome.
童年创伤(CT)经常与酒精使用障碍(AUD)并发,并且与治疗效果不佳有关。我们已经证明,有童年创伤史的酒精使用障碍患者的杏仁核结构连接性降低。在此,我们还旨在研究患有 CT(AUD-CT)和未患有 CT(AUD-noCT)的 AUD 患者的前边缘功能连接(FC)。根据 CT 的研究结果,我们推测 AUD-CT 患者杏仁核与前额叶皮层的功能连通性降低,治疗效果也会比 AUD-noCT 患者更差。我们对戒断的 AUD 住院患者和健康对照组(HCs)进行了静息状态 fMRI 扫描。我们使用种子连接(SBC)和兴趣区对兴趣区(ROI-ROI)分析比较了AUD-CT(21人)、AUD-noCT(22人)和HC(27人)之间的双侧杏仁核FC。在入院治疗和三个月随访时对社会人口学变量和酒精特异性变量(戒酒天数百分比,PDA)进行了评估。儿童创伤问卷(CTQ)评估创伤的严重程度。SBC分析显示,与HC相比,AUD-CT显示左侧和右侧杏仁核与内侧前额叶皮层和左侧扣带回的FC增加。AUD-CT 显示左侧杏仁核与右侧杏仁核以及右侧杏仁核与内侧前额叶皮层的 ROI-ROI FC 增加。AUD-CT 中杏仁核、内侧前额叶皮层和扣带回的 FC 增加可能是对杏仁核结构连接性降低的一种补偿性适应。AUD-CT中FC的这些特定改变可能代表了AUD的一种可区分的神经生物学亚型,可能是其复杂的临床表现和较差的治疗效果的基础。
{"title":"Increased functional connectivity of amygdalar-frontal pathways in patients with alcohol use disorder and childhood trauma","authors":"Elisabeth Jehli ,&nbsp;Fabienne Burri ,&nbsp;Niklaus Denier ,&nbsp;Franz Moggi ,&nbsp;Andrea Federspiel ,&nbsp;Roland Wiest ,&nbsp;Maria Stein ,&nbsp;Tobias Bracht ,&nbsp;Matthias Grieder ,&nbsp;Leila M. Soravia","doi":"10.1016/j.ynirp.2024.100223","DOIUrl":"10.1016/j.ynirp.2024.100223","url":null,"abstract":"<div><div>Childhood trauma (CT) often co-occurs with alcohol use disorder (AUD) and is associated with poor treatment outcome. We could demonstrated that patients with AUD and a history of childhood trauma showed reduced structural connectivity of the amygdala. Here, we additionally aimed to investigate fronto-limbic functional connectivity (FC) in patients with AUD with (AUD-CT) and without (AUD-noCT) CT. Based on findings in CT, we hypothesized reduced FC of the amygdala with the prefrontal cortex in AUD-CT and worse treatment outcome compared to AUD-noCT.</div><div>Resting state fMRI scans were acquired in abstinent inpatients with AUD and healthy controls (HCs). We compared bilateral amygdala FC between AUD-CT (n = 21), AUD-noCT (n = 22), and HC (n = 27) using seed-based connectivity (SBC) and region-of-interest to region-of-interest (ROI-ROI) analysis. Sociodemographic and alcohol-specific variables (percent days abstinent, PDA) were assessed at treatment admission and three-month follow-up. The Childhood Trauma Questionnaire (CTQ) assessed trauma severity. SBC analysis revealed that AUD-CT showed increased FC of the left and right amygdala with the medial prefrontal cortex and left paracingulate gyrus compared to HC. AUD-CT showed increased ROI-ROI FC of the left with the right amygdala and the right amygdala with the medial prefrontal cortex. Moreover, AUD-CT exhibited a greater reduction of PDA at three-month follow-up compared to AUD-noCT.</div><div>Increased FC of the amygdala, the medial prefrontal cortex, and paracingulate gyrus in AUD-CT might be a compensatory adaption to the reduced structural connectivity of the amygdala. Those specific alterations of FC in AUD-CT may represent a distinguishable neurobiological subtype of AUD, possibly underlying the complex clinical picture and worse treatment outcome.</div></div>","PeriodicalId":74277,"journal":{"name":"Neuroimage. Reports","volume":"4 4","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421848","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}
引用次数: 0
Music literacy shapes the specialization of a right hemispheric word reading area 音乐素养塑造了右半球文字阅读区的特化能力
Q4 Neuroscience Pub Date : 2024-09-25 DOI: 10.1016/j.ynirp.2024.100219
Alice Mado Proverbio , Elham Sanoubari
This study aimed to examine differences in the brain activity of professional musicians and non-musicians, particularly in relation to neuroplastic changes that may be associated with musical training. Specifically, we investigated whether the ability to read complex musical notation might be linked to neurofunctional adaptations that could influence word reading mechanisms. The study involved 80 participants (half of which were musicians). High-density EEG recordings and swLORETA inverse solutions were employed to analyze brain activity related to word processing and orthographic analysis. The electromagnetic signals were analyzed in the temporal window corresponding to the latency of N170 component (150–190 ms). Musicians and musically naïve people (controls) were matched based on native language, sociocultural and educational status, age, and laterality preference. Behavioural data and reading proficiency tests demonstrated higher reading skills (for words, non-words and text), and faster RTs to target letters embedded in words, in musicians. Source reconstruction showed fundamental differences in word reading mechanisms between musicians and non-musicians, including a larger involvement of the right occipitotemporal cortex, in the former than the latter. In particular, musicians showed a bilateral activation of the middle occipital gyrus (BA19, Visual Word Form Area), which was strongly lateralized to the left hemisphere in controls, during word orthographic analysis. A relationship is proposed between music literacy, enhanced reading skills and the development of a right-sided reading area for notation recognition in musicians, which could serve as a potential protective factor for ‘surface’ dyslexia.
本研究旨在探讨专业音乐家和非音乐家大脑活动的差异,特别是与音乐训练可能相关的神经可塑性变化。具体来说,我们研究了阅读复杂音乐符号的能力是否可能与影响文字阅读机制的神经功能适应有关。这项研究涉及 80 名参与者(其中一半是音乐家)。我们采用了高密度脑电图记录和 swLORETA 逆解法来分析与文字处理和正字法分析相关的大脑活动。电磁信号在与 N170 分量潜伏期(150-190 毫秒)相对应的时间窗口内进行分析。根据母语、社会文化和教育状况、年龄和侧向偏好,将音乐家和音乐天真的人(对照组)进行配对。行为数据和阅读能力测试表明,音乐家的阅读能力(单词、非单词和文本)更高,对单词中嵌入的目标字母的反应时间更快。源重建显示,音乐家和非音乐家在单词阅读机制上存在根本差异,包括前者比后者更多地涉及右枕颞皮层。特别是,在单词正字法分析过程中,音乐家表现出枕骨中回(BA19,视觉单词形式区)的双侧激活,而在对照组中,该区域则强烈偏向左半球。研究提出了音乐素养、阅读能力的提高与音乐家右侧阅读区的发展之间的关系,音乐家右侧阅读区可作为 "表面 "阅读障碍的潜在保护因素。
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引用次数: 0
Quantitative 3D reconstruction of viral vector distribution in rodent and ovine brain following local delivery 局部给药后病毒载体在啮齿动物和绵羊大脑中分布的定量三维重建
Q4 Neuroscience Pub Date : 2024-09-23 DOI: 10.1016/j.ynirp.2024.100218
Roberta Poceviciute, Kenneth Mitchell, Angeliki Maria Nikolakopoulou, Suehyun K. Cho, Xiaobo Ma, Phillip Chen, Samantha Figueroa, Ethan J. Sarmiento, Aryan Singh, Oren Hartstein, William G. Loudon, Florent Cros, Alexander S. Kiselyov
Viral vectors are an active area of research and development to treat diseases of the central nervous system (CNS). However, systemic delivery of large-molecular weight biologics is complicated by limited crossing of the blood-brain barrier, immunological clearance from the circulation, off-target effects, and systemic or organ toxicity. Local drug delivery can mitigate these obstacles, however, the drug must still be distributed over sufficiently large tissue volume to achieve the desired efficacy. In the field of drug delivery, quantitative, high resolution spatial analysis of drug distribution in the brain and other organs poses a challenge. To address this issue, we introduce a computational pipeline to reconstruct and quantify 3D distribution of locally delivered viral vectors from 2D microscopy images of subsampled brain sections. This pipeline, which combined existing and newly developed machine-learning and other computational tools, effectively removed false positive artifacts abundant in large-scale images of uncleared tissue sections, and subsampling adequately predicted the dispersion of model viral vectors from the point of local drug delivery. Furthermore, the pipeline successfully captured differences in the distribution of adeno virus (AdV) and adeno-associated virus (AAV) vectors exhibiting varying sizes and transport properties. Notably, the proposed method is directly applicable to the distribution studies of therapeutics in large animal models. Thus, our developed pipeline is an accessible tool that can aid the research and development of local drug delivery strategies for the treatment of CNS diseases with viral vectors and potentially other therapeutics.
病毒载体是治疗中枢神经系统疾病的一个活跃研发领域。然而,大分子量生物制剂的全身给药由于难以穿越血脑屏障、血液循环中的免疫清除、脱靶效应以及全身或器官毒性而变得复杂。局部给药可减轻这些障碍,但药物仍必须分布在足够大的组织体积内才能达到预期疗效。在给药领域,对药物在大脑和其他器官中的分布进行定量、高分辨率的空间分析是一项挑战。为了解决这个问题,我们引入了一个计算管道,从亚取样脑切片的二维显微图像中重建和量化局部给药病毒载体的三维分布。该管道结合了现有和新开发的机器学习及其他计算工具,有效消除了未清除组织切片的大规模图像中大量存在的假阳性伪影,子采样充分预测了模型病毒载体从局部给药点的分散情况。此外,该管道还成功捕捉到了腺病毒(AdV)和腺相关病毒(AAV)载体在大小和运输特性上的分布差异。值得注意的是,所提出的方法可直接用于治疗药物在大型动物模型中的分布研究。因此,我们开发的流水线是一种易于使用的工具,可以帮助研究和开发局部给药策略,利用病毒载体和潜在的其他疗法治疗中枢神经系统疾病。
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引用次数: 0
Changes in functional and structural brain connectivity following bilateral hand transplantation 双侧手移植后大脑功能和结构连接的变化
Q4 Neuroscience Pub Date : 2024-09-21 DOI: 10.1016/j.ynirp.2024.100222
David J. Madden , Jenna L. Merenstein , Todd B. Harshbarger , Linda C. Cendales

As a surgical treatment following amputation or loss of an upper limb, nearly 200 hand transplantations have been completed to date. We report here a magnetic resonance imaging (MRI) investigation of functional and structural brain connectivity for a bilateral hand transplant patient (female, 60 years of age), with a preoperative baseline and three postoperative testing sessions each separated by approximately six months. We used graph theoretical analyses to estimate connectivity within and between modules (networks of anatomical nodes), particularly a sensorimotor network (SMN), from resting-state functional MRI and structural diffusion-weighted imaging (DWI). For comparison, corresponding MRI measures of connectivity were obtained from 10 healthy, age-matched controls, at a single testing session. The patient's within-module functional connectivity (both SMN and non-SMN modules), and structural within-SMN connectivity, were higher preoperatively than that of the controls, indicating a response to amputation. Postoperatively, the patient's within-module functional connectivity decreased towards the control participants' values, across the 1.5 years postoperatively, particularly for hand-related nodes within the SMN module, suggesting a return to a more canonical functional organization. Whereas the patient's structural connectivity values remained relatively constant postoperatively, some evidence suggested that structural connectivity supported the postoperative changes in within-module functional connectivity.

作为截肢或失去上肢后的一种外科治疗方法,迄今已完成近 200 例手部移植手术。我们在此报告了一项磁共振成像(MRI)研究,该研究针对一名双侧手部移植患者(女性,60 岁)的大脑功能和结构连通性进行了研究,该研究包括术前基线和三次术后测试,每次测试间隔约六个月。我们采用图论分析法,通过静息态功能磁共振成像和结构弥散加权成像(DWI)估算模块(解剖节点网络)内部和模块之间的连通性,尤其是感觉运动网络(SMN)。为了进行比较,还从 10 名健康、年龄匹配的对照组患者身上获得了相应的 MRI 连接性测量结果。患者术前的模块内功能连通性(包括 SMN 模块和非 SMN 模块)以及结构性 SMN 模块内连通性均高于对照组,这表明患者对截肢有反应。术后 1.5 年内,患者的模块内功能连通性向对照组参与者的值下降,尤其是 SMN 模块内与手有关的节点,这表明患者恢复了更典型的功能组织。虽然患者的结构连通性值在术后保持相对稳定,但有证据表明,结构连通性支持术后模块内功能连通性的变化。
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引用次数: 0
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial 利用定量易感性图谱研究继发性进行性多发性硬化症丘脑铁浓度与疾病严重程度之间的关系:MS-STAT2随机对照试验的横断面分析
Q4 Neuroscience Pub Date : 2024-09-01 DOI: 10.1016/j.ynirp.2024.100216
Thomas Williams , Nevin John , Alberto Calvi , Alessia Bianchi , Floriana De Angelis , Anisha Doshi , Sarah Wright , Madiha Shatila , Marios C. Yiannakas , Fatima Chowdhury , Jon Stutters , Antonio Ricciardi , Ferran Prados , David MacManus , Francesco Grussu , Anita Karsa , Becky Samson , Marco Battiston , Claudia A.M. Gandini Wheeler-Kingshott , Karin Shmueli , Judy Beveridge
<div><h3>Background</h3><p>Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration. However, it currently remains unknown whether susceptibility is abnormal in older progressive MS cohorts, and whether it correlates with disability.</p></div><div><h3>Objectives</h3><p>To investigate differences in mean regional susceptibility in deep grey matter between people with secondary progressive multiple sclerosis (SPMS) and healthy controls; to examine in patients the relationships between deep grey matter susceptibility and clinical and imaging measures of disease severity.</p></div><div><h3>Methods</h3><p>Baseline data from a subgroup of the MS-STAT2 trial (simvastatin vs. placebo in SPMS, NCT03387670) were included. The subgroup underwent clinical assessments and an advanced MRI protocol at 3T. A cohort of age-matched healthy controls underwent the same MRI protocol. Susceptibility maps were reconstructed using a robust QSM pipeline from multi-echo 3D gradient-echo sequence. Regions of interest (ROIs) in the thalamus, globus pallidus and putamen were segmented from 3D T1-weighted images, and lesions segmented from 3D fluid-attenuated inversion recovery images. Linear regression was used to compare susceptibility from ROIs between patients and controls, adjusting for age and sex. Where significant differences were found, we further examined the associations between ROI susceptibility and clinical and imaging measures of MS severity.</p></div><div><h3>Results</h3><p>149 SPMS (77% female; mean age: 53 yrs; median Expanded Disability Status Scale (EDSS): 6.0 [interquartile range 4.5–6.0]) and 33 controls (52% female, mean age: 57) were included.</p><p>Thalamic susceptibility was significantly lower in SPMS compared to controls: mean (SD) 28.6 (12.8) parts per billion (ppb) in SPMS vs. 39.2 (12.7) ppb in controls; regression coefficient: −12.0 [95% confidence interval: −17.0 to −7.1], p < 0.001. In contrast, globus pallidus and putamen susceptibility were similar between both groups.</p><p>In SPMS, a 10 ppb lower thalamic susceptibility was associated with a +0.13 [+0.01 to +0.24] point higher EDSS (p < 0.05), a −2.4 [−3.8 to −1.0] point lower symbol digit modality test (SDMT, p = 0.001), and a −2.4 [−3.7 to −1.1] point lower Sloan low contrast acuity, 2.5% (p < 0.01).</p><p>Lower thalamic susceptibility was also strongly associated with a higher T2 lesion volume (T2LV, p < 0.001) and lower normalised whole brain, deep grey matter and thalamic volumes (all p < 0.001).</p></div><div><h3>Conclusions</h3><p>The reduced thalamic susceptibility found in SPMS compared to controls sug
背景深部灰质病变是多发性硬化症患者残疾恶化的主要原因。定量磁感应强度图(QSM)是一种先进的磁共振成像(MRI)技术,它能通过局部磁场变化产生的相位变化来量化局部磁感应强度。在深部灰质中,先前已根据组织铁浓度验证了磁感应强度。目的 研究继发性进行性多发性硬化症(SPMS)患者与健康对照组之间深灰色物质平均区域磁感应强度的差异;研究患者深灰色物质磁感应强度与疾病严重程度的临床和影像测量之间的关系。该亚组接受了临床评估和先进的 3T 磁共振成像方案。年龄匹配的健康对照组也接受了相同的磁共振成像方案。利用多回波三维梯度回波序列的稳健 QSM 管道重建了易感性图。从三维T1加权图像中分割出丘脑、丘脑球和丘脑的感兴趣区(ROI),并从三维流体衰减反转恢复图像中分割出病灶。使用线性回归比较患者和对照组 ROI 的易感性,并对年龄和性别进行调整。在发现明显差异的地方,我们进一步研究了ROI易感性与多发性硬化症严重程度的临床和影像测量之间的关联。结果149名SPMS患者(77%为女性;平均年龄:53岁;中位数扩展残疾状态量表(EDSS):6.0[四分位数]:与对照组相比,SPMS 的丘脑敏感性显著降低:SPMS 的平均值(标清)为 28.6 (12.8) ppb,对照组为 39.2 (12.7) ppb;回归系数为-12.0 [95% 置信度]:回归系数:-12.0 [95% 置信区间:-17.0 至 -7.1],p < 0.001。相比之下,丘脑和丘脑易感性在两组之间相似。在SPMS中,丘脑易感性每降低10 ppb,EDSS就会增加+0.13 [+0.01 to +0.在 SPMS 中,丘脑易感性降低 10 ppb 与 EDSS 升高 +0.13 [+0.01 至 +0.24]点(p <;0.05)、符号数字模型测试(SDMT,p = 0.001)降低 -2.4 [-3.8 至 -1.0] 点和 Sloan 低对比度敏锐度降低 2.5% [-3.7 至 -1.1] 点(p <;0.01)有关。较低的丘脑易感性还与较高的 T2 病变体积(T2LV,p <0.001)和较低的正常化全脑、深灰质和丘脑体积(均为 p <0.001)密切相关。观察到的丘脑易感性降低与更严重的肢体、认知和视力残疾之间的关系表明,丘脑铁的降低可能与临床疾病进展的重要机制有关。这种机制似乎将丘脑铁的减少与较高的 T2LV 和丘脑萎缩的发展紧密联系在一起,从而鼓励了对 QSM 衍生的丘脑易感性作为 SPMS 疾病严重程度的生物标志物的进一步研究。
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引用次数: 0
Early alterations of thalami- and hippocampi-cortical functional connectivity as biomarkers of seizures after traumatic brain injury 丘脑和海马-皮层功能连接的早期改变是脑外伤后癫痫发作的生物标志物
Q4 Neuroscience Pub Date : 2024-09-01 DOI: 10.1016/j.ynirp.2024.100217
Marina Weiler , Evan S. Lutkenhoff , Brunno M. de Campos , Raphael F. Casseb , Paul M. Vespa , Martin M. Monti , for the EpiBioS4Rx Study Group

The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx, project 3) is a prospective multicenter clinical observational study to identify early biomarkers of epileptogenesis after moderate-to-severe traumatic brain injury (TBI). We used a seed-based approach applied to acute (i.e., ≤14 days) fMRI imaging data, directly testing the hypothesis that the presence of seizures up to two years following brain trauma is associated with functional changes within hippocampi and thalami-cortical networks. Additionally, we hypothesized that the network connectivity involving thalami and hippocampi circuits underlying early and late-onset seizures would differ. Approximately 30% of the initial dataset was deemed unusable due to MRI issues. Approximately 50% of the enrolled sample was lost to a 2-year follow-up. After preprocessing the fMRI data, approximately 40% of the follow-up sample had to be excluded from the analysis due to excessive in-scanner movements, as assessed by state-of-the-art quality control protocols. Only 37 patients provided data that was suitable for the seed-based analysis. Despite these challenges, the remaining, high-quality data returned noteworthy findings. We identified specific hippocampi and thalami biomarkers associated with both early and late seizures following TBI (p < .05, FWE-corrected at the cluster level). The predictive capability for the development of late seizures after TBI, when adding fMRI data to demographic and clinical data, provided 88% accuracy — an additional 8% improvement compared to using demographic and clinical data alone. Our findings highlight the potential of fMRI for uncovering, in hippocampal and thalamic cortical networks, biomarkers of early and late seizures following TBI. However, they also highlight the important challenges that need to be overcome in order for fMRI to become an effective biomarker and prognostic tool in the intensive care context.

抗癫痫治疗的癫痫生物信息学研究(EpiBioS4Rx,项目3)是一项前瞻性多中心临床观察研究,旨在确定中重度脑外伤(TBI)后癫痫发生的早期生物标志物。我们对急性期(即≤14天)的fMRI成像数据采用了基于种子的方法,直接测试了脑外伤后两年内癫痫发作与海马和丘脑-皮层网络功能变化相关的假设。此外,我们还假设涉及丘脑和海马回路的网络连接在早期和晚期癫痫发作时会有所不同。由于核磁共振成像问题,大约 30% 的初始数据集被认为无法使用。约50%的登记样本在2年的随访中丢失。在对 fMRI 数据进行预处理后,根据最先进的质量控制协议评估,约有 40% 的随访样本因扫描仪内移动过多而不得不排除在分析之外。只有 37 名患者提供的数据适合进行基于种子的分析。尽管存在这些挑战,但剩余的高质量数据仍提供了值得注意的发现。我们确定了与创伤性脑损伤后早期和晚期癫痫发作相关的特定海马和丘脑生物标志物(p < .05,在群集水平上进行了 FWE 校正)。当将 fMRI 数据添加到人口统计学和临床数据中时,对创伤后癫痫晚期发作的预测能力达到了 88% 的准确率,比单独使用人口统计学和临床数据提高了 8%。我们的研究结果凸显了 fMRI 在海马和丘脑皮层网络中发现创伤后癫痫早期和晚期发作生物标志物的潜力。不过,这些研究结果也强调了要使 fMRI 成为重症监护中有效的生物标记和预后工具所需要克服的重要挑战。
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