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The limitations of investigating appetite through circuit manipulations: are we biting off more than we can chew? 通过神经回路操作来研究食欲的局限性:我们是否吃了超出我们能力范围的东西?
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-04-25 DOI: 10.1515/revneuro-2022-0072
Joshua Wang, Kate Beecher, Fatemeh Chehrehasa, Hayley Moody

Disordered eating can underpin a number of debilitating and prevalent chronic diseases, such as obesity. Broader advances in psychopharmacology and biology have motivated some neuroscientists to address diet-induced obesity through reductionist, pre-clinical eating investigations on the rodent brain. Specifically, chemogenetic and optogenetic methods developed in the 21st century allow neuroscientists to perform in vivo, region-specific/projection-specific/promoter-specific circuit manipulations and immediately assess the impact of these manipulations on rodent feeding. These studies are able to rigorously conclude whether a specific neuronal population regulates feeding behaviour in the hope of eventually developing a mechanistic neuroanatomical map of appetite regulation. However, an artificially stimulated/inhibited rodent neuronal population that changes feeding behaviour does not necessarily represent a pharmacological target for treating eating disorders in humans. Chemogenetic/optogenetic findings must therefore be triangulated with the array of theories that contribute to our understanding of appetite. The objective of this review is to provide a wide-ranging discussion of the limitations of chemogenetic/optogenetic circuit manipulation experiments in rodents that are used to investigate appetite. Stepping into and outside of medical science epistemologies, this paper draws on philosophy of science, nutrition, addiction biology and neurophilosophy to prompt more integrative, transdisciplinary interpretations of chemogenetic/optogenetic appetite data. Through discussing the various technical and epistemological limitations of these data, we provide both an overview of chemogenetics and optogenetics accessible to non-neuroscientist obesity researchers, as well as a resource for neuroscientists to expand the number of lenses through which they interpret their circuit manipulation findings.

饮食失调会导致许多使人衰弱和流行的慢性疾病,比如肥胖。精神药理学和生物学的广泛进展促使一些神经科学家通过对啮齿动物大脑进行简化的临床前饮食研究来解决饮食引起的肥胖问题。具体来说,21世纪发展起来的化学遗传学和光遗传学方法使神经科学家能够在体内进行区域特异性/投影特异性/启动子特异性回路操作,并立即评估这些操作对啮齿动物摄食的影响。这些研究能够严格地得出一个特定的神经元群是否调节摄食行为的结论,并希望最终开发出食欲调节的机械神经解剖学图谱。然而,人工刺激/抑制啮齿动物神经元群改变摄食行为并不一定代表治疗人类饮食失调的药理学靶点。因此,化学遗传学/光遗传学的发现必须与一系列有助于我们理解食欲的理论进行三角测量。这篇综述的目的是提供一个广泛的讨论在啮齿类动物中用于研究食欲的化学发生/光遗传电路操作实验的局限性。从医学认识论的角度出发,本文借鉴了科学哲学、营养学、成瘾生物学和神经哲学,以促进对化学发生/光遗传食欲数据的更综合、跨学科的解释。通过讨论这些数据的各种技术和认识论限制,我们为非神经科学家肥胖研究人员提供了化学遗传学和光遗传学的概述,同时也为神经科学家提供了一种资源,以扩大他们解释电路操纵发现的镜头数量。
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引用次数: 0
A systematic review of transcranial direct current stimulation on eye movements and associated psychological function. 经颅直流电刺激对眼球运动及相关心理功能的系统回顾。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-04-25 DOI: 10.1515/revneuro-2022-0082
Ashwin Subramaniam, Sicong Liu, Liam Lochhead, Lawrence Gregory Appelbaum

The last decades have seen a rise in the use of transcranial direct current stimulation (tDCS) approaches to modulate brain activity and associated behavior. Concurrently, eye tracking (ET) technology has improved to allow more precise quantitative measurement of gaze behavior, offering a window into the mechanisms of vision and cognition. When combined, tDCS and ET provide a powerful system to probe brain function and measure the impact on visual function, leading to an increasing number of studies that utilize these techniques together. The current pre-registered, systematic review seeks to describe the literature that integrates these approaches with the goal of changing brain activity with tDCS and measuring associated changes in eye movements with ET. The literature search identified 26 articles that combined ET and tDCS in a probe-and-measure model and are systematically reviewed here. All studies implemented controlled interventional designs to address topics related to oculomotor control, cognitive processing, emotion regulation, or cravings in healthy volunteers and patient populations. Across these studies, active stimulation typically led to changes in the number, duration, and timing of fixations compared to control stimulation. Notably, half the studies addressed emotion regulation, each showing hypothesized effects of tDCS on ET metrics, while tDCS targeting the frontal cortex was widely used and also generally produced expected modulation of ET. This review reveals promising evidence of the impact of tDCS on eye movements and associated psychological function, offering a framework for effective designs with recommendations for future studies.

在过去的几十年里,人们越来越多地使用经颅直流电刺激(tDCS)来调节大脑活动和相关行为。同时,眼动追踪(ET)技术也得到了改进,可以更精确地定量测量凝视行为,为研究视觉和认知机制提供了一个窗口。当tDCS和ET结合在一起时,提供了一个强大的系统来探测大脑功能并测量对视觉功能的影响,导致越来越多的研究将这些技术结合在一起。当前的预注册系统综述旨在描述将这些方法与tDCS改变大脑活动和测量ET相关眼动变化的目标相结合的文献。文献检索确定了26篇将ET和tDCS结合在一个探针-测量模型中的文章,并在此进行系统综述。所有的研究都实施了控制干预设计,以解决健康志愿者和患者群体中与动眼肌控制、认知加工、情绪调节或渴望相关的主题。在这些研究中,与对照刺激相比,主动刺激通常会导致注视的数量、持续时间和时间的变化。值得注意的是,一半的研究涉及情绪调节,每项研究都显示了tDCS对ET指标的假设影响,而针对额叶皮层的tDCS被广泛使用,也通常产生了预期的ET调节。这篇综述揭示了tDCS对眼动和相关心理功能影响的有希望的证据,为有效的设计提供了框架,并为未来的研究提供了建议。
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引用次数: 1
The role and mechanism of tryptophan - kynurenine metabolic pathway in depression. 色氨酸-犬尿氨酸代谢途径在抑郁症中的作用及机制。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-04-25 DOI: 10.1515/revneuro-2022-0047
Xiaoli Gong, Rui Chang, Ju Zou, Sijie Tan, Zeyi Huang

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients' physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN's neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression.

重度抑郁症(MDD)是一种常见的精神疾病,以持续的情绪低落和快感缺乏为特征,通常伴有认知障碍。由于其发病率不断上升、复发率和致残率高,重度抑郁症对患者的身心健康构成了重大威胁,也给社会带来了巨大的经济成本。然而,MDD的病因和发病机制尚不清楚。慢性炎症可能会导致吲哚胺-2,3-双加氧酶(IDO)在整个身体和大脑中变得过度活跃,导致大脑中喹啉酸(QUIN)过量,kynuric酸(KYNA)减少。QUIN的神经毒性损害神经胶质细胞和神经元,加速神经元凋亡,阻碍神经可塑性,并因炎症引起抑郁。因此,异常的TRP-KYN代谢途径及其代谢物与MDD密切相关,提示TRP-KYN代谢途径的改变可能与MDD有关。此外,以TRP-KYN为靶点的中药治疗MDD效果良好。本文综述了近年来抑郁症中TRP-KYN代谢途径及其代谢物的研究进展,为探索抑郁症的病因病机提供理论依据。
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引用次数: 10
Frontmatter 头版头条
3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-03-29 DOI: 10.1515/revneuro-2023-frontmatter3
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引用次数: 0
Efficient, continual, and generalized learning in the brain - neural mechanism of Mental Schema 2.0. 心理图式2.0的脑神经机制中的高效、持续和广义学习。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-03-27 Print Date: 2023-12-15 DOI: 10.1515/revneuro-2022-0137
Takefumi Ohki, Naoto Kunii, Zenas C Chao

There has been tremendous progress in artificial neural networks (ANNs) over the past decade; however, the gap between ANNs and the biological brain as a learning device remains large. With the goal of closing this gap, this paper reviews learning mechanisms in the brain by focusing on three important issues in ANN research: efficiency, continuity, and generalization. We first discuss the method by which the brain utilizes a variety of self-organizing mechanisms to maximize learning efficiency, with a focus on the role of spontaneous activity of the brain in shaping synaptic connections to facilitate spatiotemporal learning and numerical processing. Then, we examined the neuronal mechanisms that enable lifelong continual learning, with a focus on memory replay during sleep and its implementation in brain-inspired ANNs. Finally, we explored the method by which the brain generalizes learned knowledge in new situations, particularly from the mathematical generalization perspective of topology. Besides a systematic comparison in learning mechanisms between the brain and ANNs, we propose "Mental Schema 2.0," a new computational property underlying the brain's unique learning ability that can be implemented in ANNs.

在过去的十年里,人工神经网络(ANNs)取得了巨大的进步;然而,人工神经网络与作为学习设备的生物大脑之间的差距仍然很大。为了缩小这一差距,本文通过关注人工神经网络研究中的三个重要问题:效率、连续性和泛化来回顾大脑中的学习机制。我们首先讨论了大脑利用各种自组织机制来最大化学习效率的方法,重点讨论了大脑自发活动在形成突触连接以促进时空学习和数值处理中的作用。然后,我们研究了实现终身持续学习的神经元机制,重点关注睡眠期间的记忆回放及其在大脑启发的人工神经网络中的实现。最后,我们探索了大脑在新情况下对所学知识进行泛化的方法,特别是从拓扑学的数学泛化角度。除了对大脑和人工神经网络之间的学习机制进行系统比较外,我们还提出了“心智模式2.0”,这是一种新的计算特性,可以在人工神经网络中实现大脑独特的学习能力。
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引用次数: 1
Neural correlates of multisensory integration in the human brain: an ALE meta-analysis. 人脑多感觉整合的神经关联:一项ALE荟萃分析。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-02-23 DOI: 10.1515/revneuro-2022-0065
Sebastian Scheliga, Thilo Kellermann, Angelika Lampert, Roman Rolke, Marc Spehr, Ute Habel

Previous fMRI research identified superior temporal sulcus as central integration area for audiovisual stimuli. However, less is known about a general multisensory integration network across senses. Therefore, we conducted activation likelihood estimation meta-analysis with multiple sensory modalities to identify a common brain network. We included 49 studies covering all Aristotelian senses i.e., auditory, visual, tactile, gustatory, and olfactory stimuli. Analysis revealed significant activation in bilateral superior temporal gyrus, middle temporal gyrus, thalamus, right insula, and left inferior frontal gyrus. We assume these regions to be part of a general multisensory integration network comprising different functional roles. Here, thalamus operate as first subcortical relay projecting sensory information to higher cortical integration centers in superior temporal gyrus/sulcus while conflict-processing brain regions as insula and inferior frontal gyrus facilitate integration of incongruent information. We additionally performed meta-analytic connectivity modelling and found each brain region showed co-activations within the identified multisensory integration network. Therefore, by including multiple sensory modalities in our meta-analysis the results may provide evidence for a common brain network that supports different functional roles for multisensory integration.

以往的fMRI研究发现颞上沟是视听刺激的中枢整合区。然而,对跨感官的一般多感觉整合网络知之甚少。因此,我们对多种感觉模式进行了激活似然估计荟萃分析,以确定一个共同的大脑网络。我们纳入了49项研究,涵盖了所有亚里士多德的感官,即听觉、视觉、触觉、味觉和嗅觉刺激。分析显示双侧颞上回、颞中回、丘脑、右岛和左额下回明显激活。我们假设这些区域是由不同功能角色组成的一般多感觉整合网络的一部分。在这里,丘脑作为第一个皮层下中继将感觉信息投射到颞上回/沟的高级皮层整合中心,而作为脑岛和额下回的冲突处理脑区促进不一致信息的整合。我们还进行了元分析连接建模,发现每个大脑区域在确定的多感觉整合网络中都显示了共同激活。因此,通过在我们的荟萃分析中包括多种感觉模式,结果可能为支持多感觉整合的不同功能角色的共同大脑网络提供证据。
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引用次数: 6
Dual-site TMS as a tool to probe effective interactions within the motor network: a review. 双位点经颅磁刺激作为探测运动网络内有效相互作用的工具:综述。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-02-23 DOI: 10.1515/revneuro-2022-0020
Shanti Van Malderen, Melina Hehl, Stefanie Verstraelen, Stephan P Swinnen, Koen Cuypers

Dual-site transcranial magnetic stimulation (ds-TMS) is well suited to investigate the causal effect of distant brain regions on the primary motor cortex, both at rest and during motor performance and learning. However, given the broad set of stimulation parameters, clarity about which parameters are most effective for identifying particular interactions is lacking. Here, evidence describing inter- and intra-hemispheric interactions during rest and in the context of motor tasks is reviewed. Our aims are threefold: (1) provide a detailed overview of ds-TMS literature regarding inter- and intra-hemispheric connectivity; (2) describe the applicability and contributions of these interactions to motor control, and; (3) discuss the practical implications and future directions. Of the 3659 studies screened, 109 were included and discussed. Overall, there is remarkable variability in the experimental context for assessing ds-TMS interactions, as well as in the use and reporting of stimulation parameters, hindering a quantitative comparison of results across studies. Further studies examining ds-TMS interactions in a systematic manner, and in which all critical parameters are carefully reported, are needed.

双点经颅磁刺激(ds-TMS)非常适合研究大脑远端区域对初级运动皮层的因果关系,无论是在休息时还是在运动表现和学习期间。然而,考虑到广泛的增产参数集,哪些参数对识别特定相互作用最有效的清晰度是缺乏的。在这里,证据描述间和内半球的相互作用在休息和运动任务的背景下进行了审查。我们的目标有三个:(1)提供关于半球间和半球内连通性的ds-TMS文献的详细概述;(2)描述这些相互作用对运动控制的适用性和贡献;(3)讨论实践意义和未来发展方向。在筛选的3659项研究中,有109项被纳入并进行了讨论。总的来说,在评估ds-TMS相互作用的实验环境中,以及在刺激参数的使用和报告中,存在显著的可变性,阻碍了研究结果的定量比较。需要以系统的方式进一步研究ds-TMS相互作用,并仔细报告所有关键参数。
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引用次数: 4
Two-photon microscopy: application advantages and latest progress for in vivo imaging of neurons and blood vessels after ischemic stroke. 双光子显微镜:缺血性中风后神经元和血管活体成像的应用优势和最新进展。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-02-01 Print Date: 2023-07-26 DOI: 10.1515/revneuro-2022-0127
Jiarui Li, Xuan Wu, Yu Fu, Hao Nie, Zhouping Tang

Two-photon microscopy (TPM) plays an important role in the study of the changes of the two important components of neurovascular units (NVU) - neurons and blood vessels after ischemic stroke (IS). IS refers to sudden neurological dysfunction caused by focal cerebral ischemia, which is one of the leading causes of death and disability worldwide. TPM is a new and rapidly developing high-resolution real-time imaging technique used in vivo that has attracted increasing attention from scientists in the neuroscience field. Neurons and blood vessels are important components of neurovascular units, and they undergo great changes after IS to respond to and compensate for ischemic injury. Here, we introduce the characteristics and pre-imaging preparations of TPM, and review the common methods and latest progress of TPM in the neuronal and vascular research for injury and recovery of IS in recent years. With the review, we clearly recognized that the most important advantage of TPM in the study of ischemic stroke is the ability to perform chronic longitudinal imaging of different tissues at a high resolution in vivo. Finally, we discuss the limitations of TPM and the technological advances in recent years.

双光子显微镜(TPM)在研究缺血性中风(IS)后神经血管单元(NVU)的两个重要组成部分--神经元和血管--的变化中发挥着重要作用。缺血性脑卒中是指局灶性脑缺血引起的突发性神经功能障碍,是全球死亡和残疾的主要原因之一。TPM 是一种快速发展的新型体内高分辨率实时成像技术,越来越受到神经科学领域科学家的关注。神经元和血管是神经血管单元的重要组成部分,它们在 IS 后会发生巨大变化,以应对和补偿缺血性损伤。在此,我们介绍了 TPM 的特点和成像前的准备工作,并回顾了近年来 TPM 在神经元和血管研究中用于 IS 损伤和恢复的常用方法和最新进展。通过回顾,我们清楚地认识到 TPM 在缺血性脑卒中研究中最重要的优势是能在体内对不同组织进行高分辨率的慢性纵向成像。最后,我们讨论了 TPM 的局限性和近年来的技术进步。
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引用次数: 2
Frontmatter 头版头条
3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-02-01 DOI: 10.1515/revneuro-2023-frontmatter2
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引用次数: 0
Functional changes in brain oscillations in dementia: a review. 痴呆症患者脑振荡的功能改变:综述。
IF 4.1 3区 医学 Q2 NEUROSCIENCES Pub Date : 2023-01-27 DOI: 10.1515/revneuro-2022-0010
Andreina Giustiniani, Laura Danesin, Beatrice Bozzetto, AnnaRita Macina, Silvia Benavides-Varela, Francesca Burgio

A growing body of evidence indicates that several characteristics of electroencephalography (EEG) and magnetoencephalography (MEG) play a functional role in cognition and could be linked to the progression of cognitive decline in some neurological diseases such as dementia. The present paper reviews previous studies investigating changes in brain oscillations associated to the most common types of dementia, namely Alzheimer's disease (AD), frontotemporal degeneration (FTD), and vascular dementia (VaD), with the aim of identifying pathology-specific patterns of alterations and supporting differential diagnosis in clinical practice. The included studies analysed changes in frequency power, functional connectivity, and event-related potentials, as well as the relationship between electrophysiological changes and cognitive deficits. Current evidence suggests that an increase in slow wave activity (i.e., theta and delta) as well as a general reduction in the power of faster frequency bands (i.e., alpha and beta) characterizes AD, VaD, and FTD. Additionally, compared to healthy controls, AD exhibits alteration in latencies and amplitudes of the most common event related potentials. In the reviewed studies, these changes generally correlate with performances in many cognitive tests. In conclusion, particularly in AD, neurophysiological changes can be reliable early markers of dementia.

越来越多的证据表明,脑电图(EEG)和脑磁图(MEG)的一些特征在认知中发挥功能作用,并可能与一些神经系统疾病(如痴呆)的认知能力下降的进展有关。本文回顾了以往的研究,研究了与最常见的痴呆类型相关的脑振荡变化,即阿尔茨海默病(AD)、额颞叶变性(FTD)和血管性痴呆(VaD),目的是确定病理特异性改变模式,并支持临床实践中的鉴别诊断。纳入的研究分析了频率功率、功能连通性和事件相关电位的变化,以及电生理变化与认知缺陷之间的关系。目前的证据表明,AD、VaD和FTD的特征是慢波活动(即θ波和δ波)的增加以及较快频段(即α波和β波)功率的普遍降低。此外,与健康对照相比,AD表现出最常见事件相关电位的潜伏期和振幅的改变。在回顾的研究中,这些变化通常与许多认知测试的表现有关。总之,特别是在阿尔茨海默病中,神经生理变化可以作为痴呆症的可靠早期标志。
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引用次数: 6
期刊
Reviews in the Neurosciences
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