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A Polyunsaturated Fatty Acid (PUFA) Theory of Schizophrenia 精神分裂症的多不饱和脂肪酸 (PUFA) 理论
Pub Date : 2024-08-13 DOI: arxiv-2408.06794
Ari Rappoport
I present a theory of schizophrenia (SZ) that mechanistically explains itsetiology, symptoms, pathophysiology, and treatment. SZ involves the chronicrelease of membrane polyunsaturated fatty acids (PUFAs) and their utilizationfor the synthesis of stress-induced plasticity agents such as endocannabinoids(ECBs). The causal event in SZ is prolonged stress during a sensitive period,which can induce prolonged and heritable changes. The physiological effect ofthe released PUFAs and their products is to disconnect neurons from theirinputs and promote intrinsic excitability. I show that these effects canexplain the positive, negative, cognitive, and mood symptoms of SZ, as well asthe mechanisms of many known triggers of psychosis. The theory is supported byoverwhelming evidence addressing lipids, immunity, ECBs, neuromodulators,hormones, neurotransmitters, and cortical parameters in SZ. It explains whyantipsychotic drugs are effective against positive symptoms, and why they donot affect the other symptoms. Finally, I present promising treatmentdirections implied by the theory, including some that are immediatelyavailable.
我提出的精神分裂症(SZ)理论从机理上解释了精神分裂症的病因、症状、病理生理学和治疗。精神分裂症涉及膜多不饱和脂肪酸(PUFAs)的慢性释放及其用于合成应激诱导的可塑性物质(如内源性大麻素(ECBs))。SZ 的致病因素是敏感期内的长期应激,这种应激可诱发长期的遗传性变化。释放的 PUFAs 及其产物的生理效应是切断神经元与其输入的联系,并促进内在兴奋性。我的研究表明,这些效应可以解释 SZ 的积极、消极、认知和情绪症状,以及许多已知的精神病诱因的机制。这一理论得到了大量证据的支持,这些证据涉及 SZ 中的血脂、免疫、ECB、神经调节剂、激素、神经递质和皮质参数。它解释了为什么抗精神病药物对阳性症状有效,而对其他症状无效。最后,我介绍了该理论所隐含的有希望的治疗方向,包括一些立即可用的治疗方向。
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引用次数: 0
A Sympathetic Nervous System Theory of Migraine 偏头痛的交感神经系统理论
Pub Date : 2024-08-13 DOI: arxiv-2408.06780
Ari Rappoport
Migraine (MGR) ranks first among diseases in terms of years of lost healthylife in young adult and adult women. Currently, there is no theory of MGR. Thispaper presents a complete theory of migraine that explains its etiology,symptoms, pathology, and treatment. Migraine involves partially saturated(usually chronically high) sympathetic nervous system (SNS) activity, mainlydue to higher sensitivity of the metabolic sensors that recruit it. MGRheadache occurs when SNS activity is desensitized or excessive, resulting inhyperexcitability of baroreceptors, oxidative stress, and activation of painpathways via TRPV1 channels and CGRP. The theory is supported by overwhelmingevidence, and explains the properties of current MGR treatments.
偏头痛(MGR)在青壮年女性健康寿命损失年数方面位居各种疾病之首。目前,还没有关于偏头痛的理论。本文提出了一套完整的偏头痛理论,解释了偏头痛的病因、症状、病理和治疗。偏头痛涉及交感神经系统(SNS)活动的部分饱和(通常是长期处于高水平),这主要是由于招募交感神经系统的代谢传感器的敏感性较高所致。当交感神经系统活动脱敏或过度时,就会导致气压感受器过度兴奋、氧化应激以及通过 TRPV1 通道和 CGRP 激活疼痛通路,从而引发交感神经系统性头痛。该理论得到了大量证据的支持,并解释了当前 MGR 治疗方法的特性。
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引用次数: 0
Mechanical problem solving in Goffin's cockatoos -- Towards modeling complex behavior 戈芬凤头鹦鹉解决机械问题的能力 -- 建立复杂行为模型
Pub Date : 2024-08-12 DOI: arxiv-2408.05967
Manuel Baum, Theresa Roessler, Antonio J. Osuna-Mascaró, Alice Auersperg, Oliver Brock
Research continues to accumulate evidence that Goffin's cockatoos (Cacatuagoffiniana) can solve wide sets of mechanical problems, such as tool use, toolmanufacture, and solving mechanical puzzles. However, the proximate mechanismsunderlying this adaptive behavior are largely unknown. In this study, weanalyze how three Goffin's cockatoos learn to solve a specific mechanicalpuzzle, a lockbox. The observed behavior results from the interaction between acomplex environment (the lockbox) and different processes that jointly governthe animals' behavior. We thus jointly analyze the parrots' (1) engagement, (2)sensorimotor skill learning, and (3) action selection. We find that neither ofthese aspects could solely explain the animals' behavioral adaptation and thata plausible model of proximate mechanisms (including adaptation) should thusalso jointly address these aspects. We accompany this analysis with adiscussion of methods that may be used to identify such mechanisms. A majorpoint we want to make is, that it is implausible to reliably identify adetailed model from the limited data of one or a few studies. Instead, weadvocate for a more coarse approach that first establishes constraints onproximate mechanisms before specific, detailed models are formulated. Weexercise this idea on the data we present in this study.
研究不断积累的证据表明,戈芬凤头鹦鹉(Cacatuagoffiniana)能够解决各种机械问题,如使用工具、制造工具和解决机械难题。然而,这种适应行为的基本机制在很大程度上是未知的。在这项研究中,我们分析了三只戈芬凤头鹦鹉是如何学习解决一个特定的机械谜题--锁箱的。观察到的行为是复杂环境(锁盒)与共同支配动物行为的不同过程之间相互作用的结果。因此,我们对鹦鹉的(1)参与、(2)感觉运动技能学习和(3)行动选择进行了联合分析。我们发现,这两个方面都不能单独解释动物的行为适应性,因此一个合理的近似机制(包括适应性)模型也应共同解决这些方面的问题。在进行分析的同时,我们还讨论了可用于确定此类机制的方法。我们想提出的一个主要观点是,从一项或几项研究的有限数据中可靠地确定一个详细的模型是不可能的。相反,我们主张采用一种更粗略的方法,在制定具体、详细的模型之前,首先建立对近似机制的约束。我们在本研究中提供的数据上实践了这一想法。
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引用次数: 0
Time Makes Space: Emergence of Place Fields in Networks Encoding Temporally Continuous Sensory Experiences 时间创造空间:时空连续感官体验编码网络中地点场的出现
Pub Date : 2024-08-11 DOI: arxiv-2408.05798
Zhaoze Wang, Ronald W. Di Tullio, Spencer Rooke, Vijay Balasubramanian
The vertebrate hippocampus is believed to use recurrent connectivity in areaCA3 to support episodic memory recall from partial cues. This brain area alsocontains place cells, whose location-selective firing fields implement mapssupporting spatial memory. Here we show that place cells emerge in networkstrained to remember temporally continuous sensory episodes. We model CA3 as arecurrent autoencoder that recalls and reconstructs sensory experiences fromnoisy and partially occluded observations by agents traversing simulated rooms.The agents move in realistic trajectories modeled from rodents and environmentsare modeled as high-dimensional sensory experience maps. Training ourautoencoder to pattern-complete and reconstruct experiences with a constrainton total activity causes spatially localized firing fields, i.e., place cells,to emerge in the encoding layer. The emergent place fields reproduce keyaspects of hippocampal phenomenology: a) remapping (maintenance of andreversion to distinct learned maps in different environments), implemented viarepositioning of experience manifolds in the network's hidden layer, b)orthogonality of spatial representations in different arenas, c) robust placefield emergence in differently shaped rooms, with single units showing multipleplace fields in large or complex spaces, and d) slow representational drift ofplace fields. We argue that these results arise because continuous traversal ofspace makes sensory experience temporally continuous. We make testablepredictions: a) rapidly changing sensory context will disrupt place fields, b)place fields will form even if recurrent connections are blocked, but reversionto previously learned representations upon remapping will be abolished, c) thedimension of temporally smooth experience sets the dimensionality of placefields, including during virtual navigation of abstract spaces.
脊椎动物的海马体被认为是利用CA3区的递归连接来支持通过部分线索回忆外显记忆。该脑区还含有位置细胞,其位置选择性发射场实现了支持空间记忆的图谱。在这里,我们展示了位置细胞在记忆时间上连续的感觉事件的网络中出现。我们将 CA3 建模为电流自动编码器,该编码器能从穿越模拟房间的代理所观察到的噪声和部分遮挡中回忆和重建感觉经验。代理按照啮齿动物的真实轨迹移动,而环境则被建模为高维感觉经验图。训练我们的自动编码器以完成模式化并重建具有总活动限制的经验,会导致编码层出现空间局部的发射场,即位置细胞。新出现的场所场再现了海马现象学的关键方面:a)重映射(在不同环境中维持和反转不同的已学地图),通过经验流形在网络隐藏层中的重新定位来实现;b)不同领域中空间表征的正交性;c)不同形状房间中场所场的稳健出现,单个单元在大型或复杂空间中显示多个场所场;d)场所场缓慢的表征漂移。我们认为,这些结果的出现是因为空间的连续穿越使感官体验具有时间连续性。我们提出了一些可检验的预测:a)快速变化的感官环境会破坏场所场;b)即使循环连接被阻断,场所场也会形成,但在重映射时对先前所学表征的还原将被取消;c)时间上平滑的体验维度设定了场所场的维度,包括在抽象空间的虚拟导航过程中。
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引用次数: 0
Status epilepticus and thinning of the entorhinal cortex 癫痫状态和内叶皮层变薄
Pub Date : 2024-08-11 DOI: arxiv-2408.05789
Jonathan Horsley, Yujiang Wang, Callum Simpson, Vyte Janiukstyte, Karoline Leiberg, Beth Little, Jane de Tisi, John Duncan, Peter N. Taylor
Status epilepticus (SE) carries risks of morbidity and mortality.Experimental studies have implicated the entorhinal cortex in prolongedseizures; however, studies in large human cohorts are limited. We hypothesisedthat individuals with temporal lobe epilepsy (TLE) and a history of SE wouldhave more severe entorhinal atrophy compared to others with TLE and no historyof SE. 357 individuals with drug resistant temporal lobe epilepsy (TLE) and 100healthy controls were scanned on a 3T MRI. For all subjects the cortex wassegmented, parcellated, and the thickness calculated from the T1-weightedanatomical scan. Subcortical volumes were derived similarly. Cohen's d andWilcoxon rank-sum tests respectively were used to capture effect sizes andsignificance. Individuals with TLE and SE had reduced entorhinal thickness compared tothose with TLE and no history of SE. The entorhinal cortex was more atrophicipsilaterally (d=0.51, p<0.001) than contralaterally (d=0.37, p=0.01).Reductions in ipsilateral entorhinal thickness were present in both left TLE(n=22:176, d=0.78, p<0.001), and right TLE (n=19:140, d=0.31, p=0.04), albeitwith a smaller effect size in right TLE. Several other regions exhibitedatrophy in individuals with TLE, but these did not relate to a history of SE. These findings suggest potential involvement or susceptibility of theentorhinal cortex in prolonged seizures.
实验研究表明,内黑质皮层与癫痫发作时间延长有关;然而,对大型人类群体的研究却很有限。我们假设颞叶癫痫(TLE)患者和有 SE 病史的人与其他颞叶癫痫患者和没有 SE 病史的人相比,会有更严重的内叶萎缩。357 名耐药性颞叶癫痫(TLE)患者和 100 名健康对照者接受了 3T 磁共振成像扫描。对所有受试者的皮层进行了分割、切片,并通过 T1 加权解剖扫描计算出厚度。皮层下容积的计算方法与此类似。分别使用Cohen's d和Wilcoxon秩和检验来确定效应大小和显著性。与患有TLE且无SE史的患者相比,患有TLE且有SE史的患者的内叶厚度减少。左侧TLE(n=22:176, d=0.78, p<0.001)和右侧TLE(n=19:140, d=0.31, p=0.04)的同侧内侧皮层厚度均有减少,但右侧TLE的影响较小。其他几个区域在TLE患者中也表现出萎缩,但与SE病史无关。这些研究结果表明,脑皮质可能参与或易受癫痫长期发作的影响。
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引用次数: 0
A broken duet: multistable dynamics of dyadic interactions 破碎的二重奏:二元相互作用的多稳态动力学
Pub Date : 2024-08-07 DOI: arxiv-2408.03809
Johan Medrano, Noor Sajid
Misunderstandings in dyadic interactions often persist despite our bestefforts, particularly between native and non-native speakers, resembling abroken duet that refuses to harmonise. This paper delves into the computationalmechanisms underpinning these misunderstandings through the lens of the brokenLorenz system -- a continuous dynamical model. By manipulating a specificparameter regime, we induce bistability within the Lorenz equations, therebyconfining trajectories to distinct attractors based on initial conditions. Thismirrors the persistence of divergent interpretations that often result inmisunderstandings. Our simulations reveal that differing prior beliefs betweeninterlocutors result in misaligned generative models, leading to stable yetdivergent states of understanding when exposed to the same percept.Specifically, native speakers equipped with precise (i.e., overconfident)priors expect inputs to align closely with their internal models, thusstruggling with unexpected variations. Conversely, non-native speakers withimprecise (i.e., less confident) priors exhibit a greater capacity to adjustand accommodate unforeseen inputs. Our results underscore the important role ofgenerative models in facilitating mutual understanding (i.e., establishing ashared narrative) and highlight the necessity of accounting for multistabledynamics in dyadic interactions.
尽管我们已经尽了最大努力,但在二人互动中的误解却经常持续存在,尤其是在母语者和非母语者之间,就像被破坏的二重奏一样,无法和谐统一。本文通过断裂的洛伦兹系统(一种连续动态模型)的视角,深入探讨了造成这些误解的计算机制。通过操纵特定参数机制,我们在洛伦兹方程中诱发了双稳态,从而根据初始条件将轨迹限定在不同的吸引子上。这反映了分歧解释的持续存在,而分歧解释往往会导致误解。我们的模拟揭示出,对话者之间不同的先验信念会导致生成模型的错位,从而导致对同一感知的理解出现稳定而又不同的状态。具体来说,母语使用者拥有精确的(即过于自信的)先验信念,他们希望输入与自己的内部模型保持一致,从而与意想不到的变化作斗争。相反,拥有精确(即不太自信)先验的非母语者则表现出更强的调整能力,以适应不可预见的输入。我们的研究结果强调了生成模型在促进相互理解(即建立共同叙事)方面的重要作用,并突出了在二元互动中考虑多动力的必要性。
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引用次数: 0
Towards principles of brain network organization and function 探索大脑网络组织和功能的原理
Pub Date : 2024-08-05 DOI: arxiv-2408.02640
Suman Kulkarni, Dani S. Bassett
The brain is immensely complex, with diverse components and dynamicinteractions building upon one another to orchestrate a wide range of functionsand behaviors. Understanding patterns of these complex interactions and howthey are coordinated to support collective neural activity and function iscritical for parsing human and animal behavior, treating mental illness, anddeveloping artificial intelligence. Rapid experimental advances in imaging,recording, and perturbing neural systems across various species now provideopportunities and challenges to distill underlying principles of brainorganization and function. Here, we take stock of recent progresses and reviewmethods used in the statistical analysis of brain networks, drawing from fieldsof statistical physics, network theory and information theory. Our discussionis organized by scale, starting with models of individual neurons and extendingto large-scale networks mapped across brain regions. We then examine theorganizing principles and constraints that shape the biological structure andfunction of neural circuits. Finally, we describe current opportunities aimedat improving models in light of recent developments and at bridging acrossscales to contribute to a better understanding of brain networks.
大脑是极其复杂的,其不同的组成部分和动态相互作用相互依存,从而协调各种功能和行为。了解这些复杂互动的模式以及它们如何协调以支持集体神经活动和功能,对于解析人类和动物行为、治疗精神疾病和开发人工智能至关重要。目前,各种物种的神经系统成像、记录和扰动实验进展迅速,为提炼大脑组织和功能的基本原理提供了机会和挑战。在此,我们从统计物理学、网络理论和信息论等领域出发,总结了最近的进展,并回顾了大脑网络统计分析中使用的方法。我们的讨论是按规模组织的,从单个神经元模型开始,扩展到跨脑区的大规模网络映射。然后,我们将研究塑造神经回路生物结构和功能的组织原理和制约因素。最后,我们描述了当前的机遇,这些机遇旨在根据最新发展改进模型,并在不同尺度之间架起桥梁,从而有助于更好地理解大脑网络。
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引用次数: 0
Efficient coding with chaotic neural networks: A journey from neuroscience to physics and back 混沌神经网络的高效编码:从神经科学到物理学再到物理学的旅程
Pub Date : 2024-08-04 DOI: arxiv-2408.01949
Jonathan Kadmon
This essay, derived from a lecture at "The Physics Modeling of Thought"workshop in Berlin in winter 2023, explores the mutually beneficialrelationship between theoretical neuroscience and statistical physics throughthe lens of efficient coding and computation in cortical circuits. Ithighlights how the study of neural networks has enhanced our understanding ofcomplex, nonequilibrium, and disordered systems, while also demonstrating howneuroscientific challenges have spurred novel developments in physics. Thepaper traces the evolution of ideas from seminal work on chaos in random neuralnetworks to recent developments in efficient coding and the partial suppressionof chaotic fluctuations. It emphasizes how concepts from statistical physics,such as phase transitions and critical phenomena, have been instrumental inelucidating the computational capabilities of neural networks. By examining the interplay between order and disorder in neural computation,the essay illustrates the deep connection between theoretical neuroscience andthe statistical physics of nonequilibrium systems. This synthesis underscoresthe ongoing importance of interdisciplinary approaches in advancing bothfields, offering fresh perspectives on the fundamental principles governinginformation processing in biological and artificial systems. Thismultidisciplinary approach not only advances our understanding of neuralcomputation and complex systems but also points toward future challenges at theintersection of neuroscience and physics.
这篇文章源自 2023 年冬季在柏林举行的 "思维物理建模 "研讨会上的演讲,通过皮层电路中的高效编码和计算这一视角,探讨了理论神经科学与统计物理学之间的互利关系。论文强调了神经网络研究如何增强了我们对复杂、非平衡和无序系统的理解,同时也展示了神经科学的挑战如何激发了物理学的新发展。论文追溯了从随机神经网络中的混沌开创性工作到高效编码和部分抑制混沌波动的最新发展的思想演变过程。论文强调了相变和临界现象等统计物理学概念如何有助于阐明神经网络的计算能力。通过研究神经计算中有序与无序之间的相互作用,文章说明了理论神经科学与非平衡系统的统计物理学之间的深刻联系。这篇综述强调了跨学科方法在推动这两个领域发展方面的持续重要性,为生物和人工系统信息处理的基本原理提供了全新视角。这种多学科方法不仅推进了我们对神经计算和复杂系统的理解,还指明了神经科学和物理学交叉领域未来的挑战。
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引用次数: 0
State-dependent Filtering of the Ring Model 环形模型的状态滤波
Pub Date : 2024-08-03 DOI: arxiv-2408.01817
Jing Yan, Yunxuan Feng, Wei Dai, Yaoyu Zhang
Robustness is a measure of functional reliability of a system againstperturbations. To achieve a good and robust performance, a system must filterout external perturbations by its internal priors. These priors are usuallydistilled in the structure and the states of the system. Biophysical neuralnetwork are known to be robust but the exact mechanisms are still elusive. Inthis paper, we probe how orientation-selective neurons organized on a 1-D ringnetwork respond to perturbations in the hope of gaining some insights on therobustness of visual system in brain. We analyze the steady-state of therate-based network and prove that the activation state of neurons, rather thantheir firing rates, determines how the model respond to perturbations. We thenidentify specific perturbation patterns that induce the largest responses fordifferent configurations of activation states, and find them to be sinusoidalor sinusoidal-like while other patterns are largely attenuated. Similar resultsare observed in a spiking ring model. Finally, we remap the perturbations inorientation back into the 2-D image space using Gabor functions. The resultedoptimal perturbation patterns mirror adversarial attacks in deep learning thatexploit the priors of the system. Our results suggest that based on differentstate configurations, these priors could underlie some of the illusionaryexperiences as the cost of visual robustness.
鲁棒性是衡量一个系统抵御扰动的功能可靠性。要实现良好的鲁棒性能,系统必须通过其内部先验过滤掉外部扰动。这些先验通常体现在系统的结构和状态中。众所周知,生物物理神经网络具有鲁棒性,但其确切机制仍难以捉摸。在本文中,我们探究了组织在一维环状网络上的方向选择性神经元如何对扰动做出反应,希望能对大脑视觉系统的鲁棒性有一些启发。我们分析了基于神经元网络的稳态,证明神经元的激活状态而非其发射率决定了模型对扰动的响应。然后,我们确定了特定的扰动模式,这些模式在不同的激活状态配置下会引起最大的响应,并发现它们是正弦或类似正弦的,而其他模式在很大程度上会减弱。在尖峰环模型中也观察到了类似的结果。最后,我们使用 Gabor 函数将方向扰动重映射回二维图像空间。最终得出的最优扰动模式反映了深度学习中利用系统先验的对抗性攻击。我们的研究结果表明,基于不同的状态配置,这些先验可能是一些幻觉体验的基础,也是视觉鲁棒性的代价。
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引用次数: 0
Probabilistic modeling reveals coordinated social interaction states and their multisensory bases 概率建模揭示协调的社会互动状态及其多感官基础
Pub Date : 2024-08-03 DOI: arxiv-2408.01683
Sarah Josephine Stednitz, Andrew Lesak, Adeline L Fecker, Peregrine Painter, Phil Washbourne, Luca Mazzucato, Ethan K Scott
Social behavior across animal species ranges from simple pairwiseinteractions to thousands of individuals coordinating goal-directed movements.Regardless of the scale, these interactions are governed by the interplaybetween multimodal sensory information and the internal state of each animal.Here, we investigate how animals use multiple sensory modalities to guidesocial behavior in the highly social zebrafish (Danio rerio) and uncover thecomplex features of pairwise interactions early in development. To identifydistinct behaviors and understand how they vary over time, we developed a newhidden Markov model with constrained linear-model emissions to automaticallyclassify states of coordinated interaction, using the movements of one animalto predict those of another. We discovered that social behaviors alternatebetween two interaction states within a single experimental session,distinguished by unique movements and timescales. Long-range interactions, akinto shoaling, rely on vision, while mechanosensation underlies rapidsynchronized movements and parallel swimming, precursors of schooling.Altogether, we observe spontaneous interactions in pairs of fish, develop novelhidden Markov modeling to reveal two fundamental interaction modes, andidentify the sensory systems involved in each. Our modeling approach topairwise social interactions has broad applicability to a wide variety ofnaturalistic behaviors and species and solves the challenge of detectingtransient couplings between quasi-periodic time series.
动物物种的社会行为从简单的配对互动到数千个个体协调目标导向的运动不等。无论规模如何,这些互动都受多模态感官信息和每个动物内部状态之间相互作用的支配。在这里,我们研究了动物如何利用多种感官模态来指导高度社会化斑马鱼(Danio rerio)的社会行为,并揭示了发育早期配对互动的复杂特征。为了识别不同的行为并了解它们是如何随时间变化的,我们开发了一种新的隐藏马尔可夫模型,该模型具有受限线性模型排放,可以自动分类协调互动的状态,并利用一种动物的运动来预测另一种动物的运动。我们发现,在一次实验过程中,社会行为会在两种互动状态之间交替,并以独特的动作和时间尺度加以区分。我们观察了成对鱼类的自发互动,建立了新颖的隐藏马尔可夫模型,揭示了两种基本互动模式,并确定了每种互动模式所涉及的感官系统。我们的空智社会互动建模方法广泛适用于各种自然行为和物种,并解决了检测准周期时间序列之间瞬时耦合的难题。
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引用次数: 0
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arXiv - QuanBio - Neurons and Cognition
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