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Effects of a 12-Week Periodized Resistance Training Program on Resting Brain Activity and Cerebrovascular Function: A Nonrandomized Pilot Trial. 12周周期抗阻训练计划对静息脑活动和脑血管功能的影响:一项非随机试验。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221119441
Timothy R Macaulay, Amy Hegarty, Lirong Yan, Dominique Duncan, Judy Pa, Jason J Kutch, Marianna La Rocca, Christianne J Lane, E Todd Schroeder

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = -0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes.

抗阻训练是促进健康认知衰老的有效策略;然而,抗阻训练对认知有益的大脑机制尚未确定。在这里,我们研究了12周的阻力训练计划对20名健康老年人(14名女性,平均年龄69.1岁)静息脑活动和脑血管功能的影响。在这项单组临床试验中,在3个时间点进行多模态3t磁共振成像:基线(12周对照期之前)、干预前和干预后。随着流体认知的显著改善(d = 1.27),干预后发现静息脑活动减少的4个显著体向簇(小脑、右侧颞中回、左侧顶叶下小叶和右侧顶叶下小叶),但未发现静息脑血流量的变化。使用单独的感兴趣区域方法,我们提供了脑血流量改善的估计,与初始控制期间的下降相比,在与认知障碍相关的区域,如海马血流量(d = 0.40)和后扣带血流量(d = 0.61)。最后,阻力训练对脑白质病变体积(脑白质病变体积是脑血管疾病的一种生物标志物)的年龄相关进展有较小的抑制作用(rank-双序列= -0.22)。这些概念验证数据支持更大规模的试验,以确定阻力训练是否可以减轻甚至逆转显著的神经退行性过程。
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引用次数: 0
Harnessing Spinal Interneurons for Spinal Cord Repair. 利用脊髓中间神经元修复脊髓。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221101607
Lyandysha V Zholudeva, Michael A Lane

Interest in spinal interneurons (SpINs), their heterogeneity in the naive spinal cord and their varying responses to central nervous system injury or disease has been steadily increasing. Our recent review on this topic highlights the vast phenotypic heterogeneity of SpINs and the efforts being made to better identify and classify these neurons. As our understanding of SpIN phenotype, connectivity, and neuroplastic capacity continues to expand, new therapeutic targets are being revealed and novel treatment approaches developed to harness their potential. Here, we expand on that initial discussion and highlight how SpINs can be used to develop advanced, targeted cellular therapies and personalized medicines.

对脊髓中间神经元(spin)、它们在幼稚脊髓中的异质性以及它们对中枢神经系统损伤或疾病的不同反应的兴趣一直在稳步增加。我们最近对这一主题的综述强调了旋转神经元的巨大表型异质性以及为更好地识别和分类这些神经元所做的努力。随着我们对SpIN表型、连通性和神经可塑性的理解不断扩大,新的治疗靶点正在被发现,新的治疗方法正在开发,以利用它们的潜力。在这里,我们扩展了最初的讨论,并强调了如何使用自旋来开发先进的靶向细胞疗法和个性化药物。
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引用次数: 1
Brain Networks of Connectionally Unique Basolateral Amygdala Cell Types 连接独特的基底外侧杏仁核细胞类型的脑网络
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221080175
Houri Hintiryan, Hong-wei Dong
Different brain regions structurally interconnected through networks regulate behavior output. Therefore, understanding the functional organization of the brain in health and disease necessitates a foundational anatomic roadmap to its network organization. To provide this to the research community, our lab has systematically traced thousands of pathways in the mouse brain and has applied computational measures to determine the network architecture of major brain systems. Toward this effort, the brain-wide networks of the basolateral amygdalar complex (BLA) were recently generated. The data revealed uniquely connected cell types within the same BLA nucleus that were constituents of distinct neural networks. Here, we elaborate on how these connectionally unique BLA cell types fit within the larger cortico-basal ganglia and limbic networks that were previously described by our team. The significance and utility of high quality, detailed anatomic data is also discussed.
通过网络在结构上相互连接的不同大脑区域调节行为输出。因此,了解大脑在健康和疾病中的功能组织需要一个网络组织的基础解剖路线图。为了向研究界提供这一点,我们的实验室系统地追踪了小鼠大脑中的数千条通路,并应用计算方法确定了主要大脑系统的网络结构。为此,最近产生了基底外侧杏仁核复合体(BLA)的全脑网络。数据揭示了同一BLA核内独特连接的细胞类型,这些细胞类型是不同神经网络的组成部分。在这里,我们详细阐述了这些连接独特的BLA细胞类型如何适应我们团队之前描述的更大的皮质基底神经节和边缘网络。还讨论了高质量、详细的解剖数据的重要性和实用性。
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引用次数: 2
Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA 蛋白质网络分析揭示了ALS和SMA失调过程的功能连通性
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221087740
S. Kubinski, P. Claus
Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi-genic disease with over 50 identified disease-causing genes and involvement of environmental risk factors. Although these diseases have different causes, they partially share identical phenotypes and pathomechanisms. To analyze and identify functional connections and to get a global overview of altered pathways in both diseases, protein network analyses are commonly used. Here, we used an in silico tool to test for functional associations between proteins that are involved in actin cytoskeleton dynamics, fatty acid metabolism, skeletal muscle metabolism, stress granule dynamics as well as SMA or ALS risk factors, respectively. In network biology, interactions are represented by edges which connect proteins (nodes). Our approach showed that only a few edges are necessary to present a complex protein network of different biological processes. Moreover, Superoxide dismutase 1, which is mutated in ALS, and the actin-binding protein profilin1 play a central role in the connectivity of the aforementioned pathways. Our network indicates functional links between altered processes that are described in either ALS or SMA. These links may not have been considered in the past but represent putative targets to restore altered processes and reveal overlapping pathomechanisms in both diseases.
脊髓性肌萎缩症(SMA)和肌萎缩侧索硬化症(ALS)是神经退行性疾病,其特征是中枢神经系统内运动神经元的丧失。肌萎缩侧索硬化症是一种由运动神经元蛋白存活水平降低引起的单基因疾病,而肌萎缩侧索硬化症是一种多基因疾病,已确定的致病基因超过50个,并涉及环境危险因素。虽然这些疾病有不同的病因,但它们部分具有相同的表型和病理机制。为了分析和确定功能联系,并获得这两种疾病中改变的途径的总体概况,蛋白质网络分析是常用的。在这里,我们使用了一个计算机工具来测试参与肌动蛋白细胞骨架动力学、脂肪酸代谢、骨骼肌代谢、应激颗粒动力学以及SMA或ALS危险因素的蛋白质之间的功能关联。在网络生物学中,相互作用由连接蛋白质(节点)的边表示。我们的方法表明,只需要几个边缘来呈现不同生物过程的复杂蛋白质网络。此外,在ALS中发生突变的超氧化物歧化酶1 (Superoxide dismutase 1)和肌动蛋白结合蛋白(actin-binding protein profin1)在上述通路的连接中起着核心作用。我们的网络表明在ALS或SMA中描述的改变过程之间的功能联系。这些联系在过去可能没有被考虑到,但代表了恢复改变过程的假定目标,并揭示了两种疾病中重叠的病理机制。
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引用次数: 4
Commentary: How Do Microglia Regulate Neural Circuit Connectivity and Activity in the Adult Brain? 评论:小胶质细胞如何调节成人大脑中的神经回路连接和活动?
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055211071124
Yong-Jun Liu, Kim N Green, Todd C Holmes, Xiangmin Xu

Microglia are the primary immune cells in CNS. Recent work shows that microglia are also essential for proper brain development through synaptic pruning and remodeling during early life development. But the question of whether and how microglia regulate synaptic connectivity in the adult brain remains open. Our recently published study provides new insights into the functional roles of microglia in the adult mouse brain. We find that chronic depletion of microglia via CSF1R inhibitors in the visual cortex in adult mice induces a dramatic increase in perineuronal nets, and enhances neural activities of both excitatory neurons and parvalbumin interneurons. These findings highlight new potential therapeutic avenues to enhance adult neural plasticity by manipulating microglia.

小胶质细胞是中枢神经系统的初级免疫细胞。最近的研究表明,在生命早期发育过程中,小胶质细胞也通过突触修剪和重塑对大脑的正常发育至关重要。但是关于小胶质细胞是否以及如何调节成人大脑中的突触连接的问题仍然没有定论。我们最近发表的研究为小胶质细胞在成年小鼠大脑中的功能作用提供了新的见解。我们发现,成年小鼠视觉皮层中的CSF1R抑制剂慢性消耗小胶质细胞可诱导神经元周围网络的急剧增加,并增强兴奋性神经元和小白蛋白中间神经元的神经活动。这些发现强调了通过操纵小胶质细胞来增强成人神经可塑性的新的潜在治疗途径。
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引用次数: 1
A Tailored Music-Motor Therapy and Real-Time Biofeedback Mobile Phone App (‘GotRhythm’) to Promote Rehabilitation Following Stroke: A Pilot Study 定制的音乐-运动疗法和实时生物反馈手机应用程序(“gorhythm”)促进中风后康复:一项试点研究
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2022-01-01 DOI: 10.1177/26331055221100587
Katherine Hankinson, A. Shaykevich, A. Vallence, J. Rodger, Michael A. Rosenberg, C. Etherton-Beer
Background: Stroke persists as an important cause of long-term disability world-wide with the need for rehabilitation strategies to facilitate plasticity and improve motor function in stroke survivors. Rhythm-based interventions can improve motor function in clinical populations. This study tested a novel music-motor software application ‘GotRhythm’ on motor function after stroke. Methods: Participants were 22 stroke survivors undergoing inpatient rehabilitation in a subacute stroke ward. Participants were randomised to the GotRhythm intervention (combining individualised music and augmented auditory feedback along with wearable sensors to deliver a personalised rhythmic auditory stimulation training protocol) or usual care. Intervention group participants were offered 6-weeks of the GotRhythm intervention, consisting of a supervised 20-minute music-motor therapy session using GotRhythm conducted 3 times a week for 6 weeks. The primary feasibility outcomes were adherence to the intervention and physical function (change in the Fugl-Meyer Assessment of Motor Recovery score) measured at baseline, after 3-weeks and at end of the intervention period (6-weeks). Results: Three of 10 participants randomised to the intervention did not receive any of the GotRhythym music-motor therapy. Of the remaining 7 intervention group participants, only 5 completed the 3-week mid-intervention assessment and only 2 completed the 6-week post-intervention assessment. Participants who used the intervention completed 5 (IQR 4,7) sessions with total ‘dose’ of the intervention of 70 (40, 201) minutes. Conclusion: Overall, adherence to the intervention was poor, highlighting that application of technology assisted music-based interventions for stroke survivors in clinical environments is challenging along with usual care, recovery, and the additional clinical load.
背景:中风仍然是世界范围内长期残疾的重要原因,需要康复策略来促进中风幸存者的可塑性和改善运动功能。心律干预可以改善临床人群的运动功能。本研究测试了一种新的音乐-运动软件应用程序“gorhythm”对中风后运动功能的影响。方法:参与者是22名在亚急性中风病房接受住院康复治疗的中风幸存者。参与者被随机分配到gorhythm干预组(结合个性化音乐和增强听觉反馈以及可穿戴传感器来提供个性化节奏听觉刺激训练方案)或常规护理组。干预组参与者接受为期6周的gotrhym干预,包括使用gotrhym进行监督的20分钟音乐运动治疗,每周进行3次,持续6周。主要可行性结果是在基线、3周后和干预期结束(6周)时测量的干预依从性和身体功能(Fugl-Meyer运动恢复评分的变化)。结果:随机分配到干预组的10名参与者中有3名没有接受任何gotrhyrhythm音乐运动疗法。在其余7名干预组参与者中,只有5名完成了3周的干预中期评估,只有2名完成了6周的干预后评估。使用干预的参与者完成了5个疗程(IQR 4,7),干预的总“剂量”为70(40,201)分钟。结论:总体而言,干预的依从性较差,突出表明在临床环境中应用技术辅助的基于音乐的干预对中风幸存者的日常护理,康复和额外的临床负荷具有挑战性。
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引用次数: 7
Combining fMRI and Eye-tracking for the Study of Social Cognition. 结合fMRI和眼动追踪技术研究社会认知。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-12-16 eCollection Date: 2021-01-01 DOI: 10.1177/26331055211065497
Kristin Marie Rusch

The study of social cognition with functional magnetic resonance imaging (fMRI) affords the use of complex stimulus material. Visual attention to distinct aspects of these stimuli can result in the involvement of remarkably different neural systems. Usually, the influence of gaze on neural signal is either disregarded or dealt with by controlling gaze of participants through instructions or tasks. However, behavioral restrictions like this limit the study's ecological validity. Thus, it would be preferable if participants freely look at the stimuli while their gaze traces are measured. Yet several impediments hamper a combination of fMRI and eye-tracking. In our recent work on neural Theory of Mind processes in alexithymia, we propose a simple way of integrating dwell time on specific stimulus features into general linear models of fMRI data. By parametrically modeling fixations, we were able to distinguish neural processes asssociated with specific stimulus features looked at. Here, I discuss opportunities and obstacles of this approach in more detail. My goal is to motivate a wider use of parametric models - usually implemented in common fMRI software packages - to combine fMRI and eye-tracking data.

功能磁共振成像(fMRI)研究社会认知提供了复杂刺激材料的使用。对这些刺激的不同方面的视觉注意会导致涉及到显著不同的神经系统。通常,注视对神经信号的影响要么被忽略,要么通过指令或任务来控制被试的注视。然而,像这样的行为限制限制了研究的生态有效性。因此,如果参与者自由地看着刺激物,同时测量他们的注视轨迹,这将是可取的。然而,有几个障碍阻碍了功能磁共振成像和眼球追踪的结合。在我们最近对述情障碍的神经心理理论过程的研究中,我们提出了一种简单的方法,将特定刺激特征的停留时间整合到fMRI数据的一般线性模型中。通过参数化建模固定,我们能够区分与特定刺激特征相关的神经过程。在这里,我将更详细地讨论这种方法的机遇和障碍。我的目标是推动参数化模型的更广泛使用——通常在通用的功能磁共振成像软件包中实现——将功能磁共振成像和眼动追踪数据结合起来。
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引用次数: 1
Progression of Cognitive Impairment to Alzheimer's Disease: Through the Lens of Salivary Extracellular Vesicles. 认知障碍到阿尔茨海默病的进展:通过唾液细胞外囊泡的透镜。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-11-25 eCollection Date: 2021-01-01 DOI: 10.1177/26331055211058687
Simran Rastogi, Komal Rani, Saroj Kumar

The elusiveness encircling around the domain of cognition, its impairment, and the poor prognosis of Alzheimer's disease has made early diagnosis a necessity. The noticeable symptoms in these conditions appear years later after the neuropathological changes occur in the brain. Exosomes, a small-sized extracellular vesicle facilitate intercellular communication of disease pathologies and their cargo can provide molecular information about its place of origin. The study titled "A novel approach to correlate the salivary exosomes and their protein cargo in the progression of cognitive impairment into Alzheimer's disease" was an attempt toward understanding the role of salivary small-sized extracellular vesicular (EV's) cargo in monitoring the progression. Outcomes of the study represent, that the salivary small-sized EV's (ssEV's) levels were higher in the cognitively impaired and Alzheimer's diseased as well the differential expression of the protein in the cargo correlates well with the disease severity staging. Thus, it can help in the development of an early non-invasive screening method.

认知领域的难以捉摸、认知障碍以及阿尔茨海默病的不良预后使得早期诊断成为必要。在这些情况下,明显的症状在大脑神经病变发生多年后才出现。外泌体是一种小型的细胞外囊泡,促进疾病病理的细胞间交流,它们的货物可以提供有关其起源的分子信息。这项名为“一种将认知障碍进展为阿尔茨海默病的唾液外泌体及其蛋白质货物联系起来的新方法”的研究试图了解唾液小尺寸细胞外泡(EV)货物在监测进展中的作用。研究结果表明,认知障碍和阿尔茨海默病患者的唾液小尺寸EV (ssEV's)水平较高,并且货物中蛋白质的差异表达与疾病严重程度分期密切相关。因此,它可以帮助开发一种早期的非侵入性筛查方法。
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引用次数: 1
The Spanish Composer Manuel de Falla and His Eyes: The Musical Brain. 西班牙作曲家曼努埃尔·德·法拉和他的眼睛:音乐大脑。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-10-26 eCollection Date: 2021-01-01 DOI: 10.1177/26331055211049778
Alicia García-Falgueras, Dick F Swaab

Manuel de Falla was a Spanish musician of the XIXth and XXth centuries who had international recognition likely due to his musical fusion talent. His knowledge about Spanish musical traditions gave to his early compositions a new and fresh intellectual interpretation for the typical Spanish folk music. However, in the middle of his musical career, he suffered a strange disease of his eyes named recurrent acute iridocyclitis. This eye flushing is caused by an inflammation of 2 structures of the anterior pole of the ocular globe, the iris, and the ciliary body. It is usually a symptom of another disease and it causes many psychological impairments and disabilities (severe eye pain in bright light, blurry vision, headache, stress for organization (orderliness), and depression in some cases). This soreness of his eyes had an effect over Falla's compositions and marked an inflection point in his line of musical creations. Eyes in music have been so relevant in another composers and musicians throughout history.

曼努埃尔·德·法拉是19世纪和20世纪的西班牙音乐家,可能是由于他的音乐融合天赋而获得了国际认可。他对西班牙音乐传统的了解使他的早期作品对典型的西班牙民间音乐有了全新的知识诠释。然而,在他的音乐生涯中期,他遭受了一种奇怪的疾病,他的眼睛被称为复发性急性虹膜周炎。这种眼睛潮红是由眼球前极虹膜和睫状体两个结构的炎症引起的。它通常是另一种疾病的症状,它会导致许多心理损伤和残疾(在强光下严重的眼痛、视力模糊、头痛、组织压力(有序),在某些情况下还会导致抑郁)。这种眼睛的疼痛对法拉的作品产生了影响,标志着他的音乐创作路线的转折点。纵观历史,音乐中的眼睛一直与其他作曲家和音乐家密切相关。
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引用次数: 1
Engineering Safer Psychedelics for Treating Addiction. 工程更安全的迷幻药治疗成瘾。
IF 3.6 Q2 NEUROSCIENCES Pub Date : 2021-07-20 eCollection Date: 2021-01-01 DOI: 10.1177/26331055211033847
Jamie Peters, David E Olson

Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens-molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.

对成瘾的最好描述是一种不适应的神经可塑性紊乱,涉及同时加强驱动强迫性药物寻求的奖励回路和削弱涉及对有害行为的执行控制的回路。迷幻药在治疗成瘾方面显示出巨大的前景,许多人将其治疗效果归因于在药物影响下获得的洞察力。然而,致幻剂也是一种有效的精神质体——一种能够迅速重新连接成人大脑的分子。具有抗成瘾特性的非致幻性精神致生剂的出现,提出了一种有趣的可能性,即只要潜在的病理神经回路能够得到纠正,幻觉可能不是所有以迷幻为基础的药物的治疗效果所必需的。在与酒精和阿片类药物成瘾相关的临床前模型中,其中一种非致幻性精神质体,他伯南他洛(TBG)似乎具有持久的治疗效果。在这里,我们讨论了这些结果对成瘾治疗发展的影响,以及下一步推进TBG和相关非致幻性精神质体作为成瘾治疗的步骤。
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引用次数: 14
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