The Neural Mechanisms of Re-Experiencing Mental Fatigue Sensation: A Magnetoencephalography Study

There have been several studies which have tried to clarify the neural mechanisms of fatigue sensation; however fatigue sensation has multiple aspects. We hypothesized that past experience related to fatigue sensation is an important factor which contributes to future formation of fatigue sensation through the transfer to memories that are located within specific brain structures. Therefore, we aimed to investigate the neural mechanisms of fatigue sensation related to memory. In the present study, we investigated the neural activity caused by re-experiencing the fatigue sensation that had been experienced during a fatigue-inducing session. Thirteen healthy volunteers participated in fatigue and non-fatigue experiments in a crossover fashion. In the fatigue experiment, they performed a 2-back test session for 40 min to induce fatigue sensation, a rest session for 15 min to recover from fatigue, and a magnetoencephalography (MEG) session in which they were asked to re-experience the state of their body with fatigue that they had experienced in the 2-back test session. In the non-fatigue experiment, the participants performed a free session for 15 min, a rest session for 15 min, and an MEG session in which they were asked to re-experience the state of their body without fatigue that they had experienced in the free session. Spatial filtering analyses of oscillatory brain activity showed that the delta band power in the left Brodmann’s area (BA) 39, alpha band power in the right pulvinar nucleus and the left BA 40, and beta band power in the left BA 40 were lower when they re-experienced the fatigue sensation than when they re-experienced the fatigue-free sensation, indicating that these brain regions are related to re-experiencing the fatigue sensation. Our findings may help clarify the neural mechanisms underlying fatigue sensation.     

The Neural Substrates of Self-Evaluation of Mental Fatigue: A Magnetoencephalography Study

There have been several studies of the neural mechanisms underlying sensation of fatigue. However, little is known about the neural mechanisms underlying self-evaluation of the level of fatigue. The aim of this study was to identify the neural substrates involved in self-evaluation of the level of mental fatigue. We used magnetoencephalography (MEG) with high temporal resolution on 14 healthy participants. During MEG recordings, participants were asked to evaluate their level of mental fatigue in time with execution cues (evaluation trials) or to do nothing in time with execution cues (control trials). The MEG data were analyzed with equivalent current dipole (ECD) and spatial filtering methods to localize the neural activity related to the evaluation of mental fatigue. The daily level of fatigue sensation was assessed using the Checklist Individual Strength questionnaire. In evaluation trials, ECDs were observed in the posterior cingulate cortex (PCC) in seven of 14 participants, with a mean latency of 366.0 ms. The proportion of the participants with ECDs in the PCC was higher in evaluation trials than in control trials (P<0.05, McNemar test). The extent of the decreased delta band power in the PCC (Brodmann’s area 31) 600–700 ms after the onset of the execution cue and that in the dorsolateral prefrontal cortex (DLPFC; Brodmann’s area 9) 800–900 ms after the onset of the execution cue were greater in the evaluation trials than in the control trials. The decrease in delta band power in the DLPFC was positively related to that in the PCC and to the daily level of fatigue sensation. These data suggest that the PCC and DLPFC are involved in the self-evaluation of mental fatigue.     

Neural Mechanisms Underlying the Cost of Task Switching: An ERP Study

Background

When switching from one task to a new one, reaction times are prolonged. This phenomenon is called switch cost (SC). Researchers have recently used several kinds of task-switching paradigms to uncover neural mechanisms underlying the SC. Task-set reconfiguration and passive dissipation of a previously relevant task-set have been reported to contribute to the cost of task switching.

Methodology/Principal Findings

An unpredictable cued task-switching paradigm was used, during which subjects were instructed to switch between a color and an orientation discrimination task. Electroencephalography (EEG) and behavioral measures were recorded in 14 subjects. Response-stimulus interval (RSI) and cue-stimulus interval (CSI) were manipulated with short and long intervals, respectively. Switch trials delayed reaction times (RTs) and increased error rates compared with repeat trials. The SC of RTs was smaller in the long CSI condition. For cue-locked waveforms, switch trials generated a larger parietal positive event-related potential (ERP), and a larger slow parietal positivity compared with repeat trials in the short and long CSI condition. Neural SC of cue-related ERP positivity was smaller in the long RSI condition. For stimulus-locked waveforms, a larger switch-related central negative ERP component was observed, and the neural SC of the ERP negativity was smaller in the long CSI. Results of standardized low resolution electromagnetic tomography (sLORETA) for both ERP positivity and negativity showed that switch trials evoked larger activation than repeat trials in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC).

Conclusions/Significance

The results provide evidence that both RSI and CSI modulate the neural activities in the process of task-switching, but that these have a differential role during task-set reconfiguration and passive dissipation of a previously relevant task-set.     

Neural Mechanisms Underlying the Computation of Hierarchical Tree Structures in Mathematics

Whether mathematical and linguistic processes share the same neural mechanisms has been a matter of controversy. By examining various sentence structures, we recently demonstrated that activations in the left inferior frontal gyrus (L. IFG) and left supramarginal gyrus (L. SMG) were modulated by the Degree of Merger (DoM), a measure for the complexity of tree structures. In the present study, we hypothesize that the DoM is also critical in mathematical calculations, and clarify whether the DoM in the hierarchical tree structures modulates activations in these regions. We tested an arithmetic task that involved linear and quadratic sequences with recursive computation. Using functional magnetic resonance imaging, we found significant activation in the L. IFG, L. SMG, bilateral intraparietal sulcus (IPS), and precuneus selectively among the tested conditions. We also confirmed that activations in the L. IFG and L. SMG were free from memory-related factors, and that activations in the bilateral IPS and precuneus were independent from other possible factors. Moreover, by fitting parametric models of eight factors, we found that the model of DoM in the hierarchical tree structures was the best to explain the modulation of activations in these five regions. Using dynamic causal modeling, we showed that the model with a modulatory effect for the connection from the L. IPS to the L. IFG, and with driving inputs into the L. IFG, was highly probable. The intrinsic, i.e., task-independent, connection from the L. IFG to the L. IPS, as well as that from the L. IPS to the R. IPS, would provide a feedforward signal, together with negative feedback connections. We indicate that mathematics and language share the network of the L. IFG and L. IPS/SMG for the computation of hierarchical tree structures, and that mathematics recruits the additional network of the L. IPS and R. IPS.     

The Neural Mechanisms Underlying the Acute Effect of Cigarette Smoking on Chronic Smokers

Although previous research had related structural changes and impaired cognition to chronic cigarette smoking, recent neuroimaging studies have associated nicotine, which is a main chemical substance in cigarettes, with improvements in cognitive functions (e.g. improved attention performance). However, information about the alterations of whole-brain functional connectivity after acute cigarette smoking is limited. In this study, 22 smokers underwent resting-state functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for 12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to smoke two cigarettes (state of satisfaction, SOS) before they underwent a second rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition, high-resolution 3D T1-weighted images were acquired using the same magnetic resonance imaging(fMRI)scanner for all participants. The results showed that smokers had structural changes in insula, thalamus, medial frontal cortex and several regions of the default mode network (DMN) compared with non-smokers. Voxel-wise group comparisons of newly developed global brain connectivity (GBC) showed that smokers in the SOA condition had higher GBC in the insula and superior frontal gyrus compared with non-smokers. However, smokers in the SOS condition demonstrated significantly lower GBC in several regions of the DMN, as compared with smokers in the SOA condition. These results suggest that structural integrity combined with dysfunction of the DMN might be involved in relapses after a short period of time among smokers.     

人参皂苷Rg1调控神经干细胞衰老作用及机制探讨

用三丁基过氧化氢(t-BHP)构建神经干细胞(NSC)体外衰老模型,探讨人参皂苷Rgl延缓NSC衰老的作用及机制,为寻找延缓NSC衰老新途径提供理论和实验依据。将从新生SD大鼠海马组织中分离纯化的第三代NSC随机分为五组。对照组:在NSC完全培养基中培养2 h;衰老模型组:在对照组基础上加入终浓度为100μmol/L的t-BHP培养2 h;Rg1组:在对照组基础上加入终浓度为10μg/mL的Rg1培养2 h;Rg1抗衰老组:在衰老造模同时加入终浓度为10μg/mL的Rg1培养2h;Rg1治疗衰老组:终浓度为100μmol/L的t-BHP培养2h后再加入终浓度为10μg/mL的Rg1继续培养2 h。MTT法、神经球计数、分化细胞计数以及衰老相关β-半乳糖苷酶(SA-β-Gal)染色阳性神经球计数分析Rg1调控NSC衰老的生物学作用,RT-PCR检测衰老相关基因p16~(1NK4a)、p21~(Cipl/Wafl)mRNA的表达。结果显示,与衰老组比较,Rg1抗衰老组和治疗衰老组NSC的增殖能力和多向分化能力显著增强;衰老特异性SA-β-Gal染色阳性神经球百分比显著降低,p16~(INK4a)、p21~(Cip...     

Neural Mechanisms Underlying Stop-and-Restart Difficulties: Involvement of the Motor and Perceptual Systems

The ability to suddenly stop a planned movement or a movement being performed and restart it after a short interval is an important mechanism that allows appropriate behavior in response to contextual or environmental changes. However, performing such stop-and-restart movements smoothly is difficult at times. We investigated performance (response time) of stop-and-restart movements using a go/stop/re-go task and found consistent stop-and-restart difficulties after short (∼100 ms) stop-to-restart intervals (SRSI), and an increased probability of difficulties after longer (>200 ms) SRSIs, suggesting that two different mechanisms underlie stop-and-restart difficulties. Next, we investigated motor evoked potentials (MEPs) in a moving muscle induced by transcranial magnetic stimulation during a go/stop/re-go task. In re-go trials with a short SRSI (100 ms), the MEP amplitude continued to decrease after the re-go-signal onset, indicating that stop-and-restart difficulties with short SRSIs might be associated with a neural mechanism in the human motor system, namely, stop-related suppression of corticomotor (CM) excitability. Finally, we recorded electroencephalogram (EEG) activity during a go/stop/re-go task and performed a single-trial-based EEG power and phase time-frequency analysis. Alpha-band EEG phase locking to re-go-signal, which was only observed in re-go trials with long SRSI (250 ms), weakened in the delayed re-go response trials. These EEG phase dynamics indicate an association between stop-and-restart difficulties with long SRSIs and a neural mechanism in the human perception system, namely, decreased probability of EEG phase locking to visual stimuli. In contrast, smooth stop-and-restart human movement can be achieved in re-go trials with sufficient SRSI (150–200 ms), because release of stop-related suppression and simultaneous counter-activation of CM excitability may occur as a single task without second re-go-signal perception. These results suggest that skilled motor behavior is subject to various constraints in not only motor, but also perceptual (and attentional), systems.     

遗忘的神经机制及其与神经系统疾病的相关性

遗忘是记忆系统的重要组成部分.一方面,生理条件下,正常的遗忘有助于维持大脑记忆系统稳态;另一方面,异常的遗忘与多种病理条件下记忆障碍的发生发展密切相关.或者说,遗忘是为了更好的记忆.对不愉快或者不必要记忆的遗忘有利于机体及时地获取新信息以适应环境的变化;而遗忘出现异常很可能会导致相关记忆障碍.例如,阿尔茨海默症(Alz...     

Neural Mechanisms Underlying Axial/Appendicular Steering Reactions in Locust Flight

SYNOPSIS. Steering during flight in the locust involves complexchanges in wingbeat, bending of thorax and head, and rudderingmovements of abdomen and hindlegs. Most of these behavioralsubcomponents involve coordinated modification of axial andappendicular musculature control. Some of the mechanisms underlyingthis neural modification have been analysed at the cellularlevel. During steering via wingbeat, sensory information aboutcourse deviations leads to highly coordinated and asymmetricchanges in the flight motor's output through the following mechanisms.Identified feature detector neurons in the locust brain integratesensory information concerning specific types of course deviation.Each of these descending detector neurons makes connectionswith a population of thoracic interneurons. These thoracic interneuronshave two important properties. First, they relay deviation informationto flight motoneurons. Second, they are under the gating controlof the flight central oscillator. Through this gating controlthe descending sensory signal is phase-coupled to the flightrhythm and delivered to appropriate flight motoneurons in oneand the same step. Although most of the recent cellular studieshave been aimed at unraveling the neural basis of wingbeat alterations,similar (but not identical) principles of neural organizationseem to be involved in the steering reactions produced by axialmotor systems.     

A PET Study of the Brain Mechanisms Underlying Perception of Phrases with Syntagmatic Splitting

Positron emission tomography (PET) was used to localize the brain regions involved in the processing of pauses and intonation changes, which underlie the syntactically correct perception of auditory verbal stimuli. Subjects were asked to listen to a phrase and to choose a correct answer from two variants presented on a monitor screen. Differences in cerebral blood circulation were mapped for perception of phrases containing or lacking a pause determining the meaning. Conscious analysis of the phrase structure was associated with activation of the right lower prefrontal area and the right posterior medial area of the cerebellum. The possible role of these brain structures in analyzing factors of syntagmatic splitting is discussed.     

二甲双胍抗肿瘤作用及其分子机制的研究进展

二甲双胍是全球范围内治疗2型糖尿病最常用的药物之一,具有使用方便、疗效好、价格低廉且毒副作用小等优点。近年来大量的流行病学研究及体内外实验研究发现二甲双胍能够用于多种肿瘤的治疗及预防,然而其分子机制尚不十分明确;主要包括调节体内胰岛素/IGF-1轴、激活AMPK信号通路、调控micro RNAs的表达、活化Caspase分子、阻断AGEs-RAGE系统等,这些机制为将来二甲双胍应用于肿瘤的预防及临床治疗提供了重要的理论依据。本文针对糖尿病治疗药物二甲双胍在抗肿瘤中的作用及其分子机制进行全面综述。     

Oscillations in a Simple Neuromechanical System: Underlying Mechanisms

A half-center neural oscillator was coupled to a simple mechanical system to study the closed-loop interactions between a central pattern generator and its effector muscles. After a review of the open-loop mechanisms that were previously introduced by Skinner et al. (1994), we extend their geometric approach and introduce four additional closed-loop mechanisms by the inclusion of an antagonistic muscle pair acting on a mass and connected to the half-center neural oscillator ipsilaterally. Two of the closed-loop mechanisms, mechanical release mechanisms, have close resemblance to open-loop release mechanisms whereas the latter two, afferent mechanisms, have a strong dependence on the mechanical properties of the system. The results also show that stable oscillations can emerge in the presence of sensory feedback even if the neural system is not oscillatory. Finally, the feasibility of the closed-loop mechanisms was shown by weakening the idealized assumptions of the synaptic and the feedback connections as well as the rapidity of the oscillations.     

The Neural Mechanisms of Moral Cognition: A Multiple-Aspect Approach to Moral Judgment and Decision-Making

We critically review themushrooming literature addressing the neuralmechanisms of moral cognition (NMMC), reachingthe following broad conclusions: (1) researchmainly focuses on three inter-relatedcategories: the moral emotions, moral socialcognition, and abstract moral reasoning. (2)Research varies in terms of whether it deploysecologically valid or experimentallysimplified conceptions of moral cognition. Themore ecologically valid the experimentalregime, the broader the brain areas involved.(3) Much of the research depends on simplifyingassumptions about the domain of moral reasoningthat are motivated by the need to makeexperimental progress. This is a valuablebeginning, but as more is understood about theneural mechanisms of decision-making, morerealistic conceptions will need to replace thesimplified conceptions. (4) The neuralcorrelates of real-life moral cognition areunlikely to consist in anything remotely like a``moral module' or a ``morality center.' Moralrepresentations, deliberations and decisionsare probably highly distributed and notconfined to any particular brainsub-system. Discovering the basic neuralprinciples governing planning, judgment anddecision-making will require vastly more basicresearch in neuroscience, but correlatingactivity in certain brain regions withwell-defined psychological conditions helpsguide neural level research. Progress on socialphenomena will also require theoreticalinnovation in understanding the brain'sdistinctly biological form of computationthat is anchored by emotions, needs, drives,and the instinct for survival.     

有无反馈对欺骗过程的神经机制的调控作用

欺骗行为会导致欺骗结果的产生,欺骗结果又会直接影响欺骗行为的发生及其内在机制.虽然有研究表明,欺骗结果会对相应的欺骗过程产生调控作用,但对这一调控作用的机制并不清楚.本研究采用功能核磁共振技术,对两组被试分别使用有、无反馈(欺骗结果)的GKT范式并记录两组被试在进行诚实反应和欺骗反应时的大脑激活模式.结果发现,有反馈组与无反馈组相比,有反馈组的诚实反应和欺骗反应都导致了左侧顶叶皮层、左背部前扣带皮层、左侧脑岛、双侧视皮层和右侧小脑的更大激活;对两组而言,欺骗反应和诚实反应都导致了右腹外侧前额区域、双侧缘上回、左侧脑岛、右后内侧额叶、右侧颞中回和右侧纹状体的更大激活;此外,与无反馈组相比,有反馈组的欺骗反应与诚实反应在双侧纹状体和左侧脑岛上的激活差异更加明显.这些结果表明,有无欺骗结果对欺骗过程的神经机制具有调控作用,当需要面临欺骗结果时,欺骗过程将更大程度地涉及到奖赏预期和风险厌恶过程的参与.     

Mechanisms Underlying the Process of Demyelination in Multiple Sclerosis

The author generalizes and analyzes the published data and her own findings related to the cellular and molecular mechanisms underlying a demyelinating disease, multiple sclerosis. The mechanisms of the immunopathogenic process in multiple sclerosis, the involvement of microglia and astrocytes in destruction of the myelin sheaths, and injury of oligodendrocytes are discussed. Experimental models used for examination of the processes of demyelination of the nerve tissue in vitro (tissue cultures) and in vivo (experimental allergic encephalomyelitis) are also described.     

Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: a Review

Major depression is a public health problem, affecting 121 million people worldwide. Patients suffering from depression present high rates of morbidity, causing profound economic and social impacts. Furthermore, patients with depression present cognitive impairments, which could influence on treatment adherence and long-term outcomes. The pathophysiology of major depression is not completely understood yet but involves reduced levels of monoamine neurotransmitters, bioenergetics, and redox disturbances, as well as inflammation and neuronal loss. Treatment with anti-depressants provides a complete remission of symptoms in approximately 50% of patients with major depression. However, these drugs may cause side effects, as sedation and weight gain. In this context, there is increasing interest in studies focusing on the anti-depressant effects of natural compounds found in the diet. Resveratrol is a polyphenolic phytoalexin (3,4′,5-trihydroxystilbene; C₁₄H₁₂O₃; MW 228.247 g/mol) and has been found in peanuts, berries, grapes, and wine and induces anti-oxidant, anti-inflammatory, and anti-apoptotic effects in several mammalian cell types. Resveratrol also elicits anti-depressant effects, as observed in experimental models using animals. Therefore, resveratrol may be viewed as a potential anti-depressant agent, as well as may serve as a model of molecule to be modified aiming to ameliorate depressive symptoms in humans. In the present review, we describe and discuss the anti-depressant effects of resveratrol focusing on the mechanism of action of this phytoalexin in different experimental models.     

条件化恐惧记忆消退的神经振荡机制

恐惧作为个体应对内外界危险因素形成的自我保护机制的一部分,在生物体的生存中发挥着重要作用.但过度的恐惧不仅对个体生存无益,反而易引发创伤后应激障碍、焦虑等精神疾病,严重影响个体生活质量.临床上通常采用基于行为学研究结果的暴露疗法对恐惧相关疾病进行治疗,然而在患者处于治疗环境之外的时候,上述症状经常会复发.因此,解析恐惧记忆相关神经环路内信息处理的神经机制,对于理解这些疾病的发生发展,寻求切实有效的治疗方案至关重要.大量研究表明与恐惧记忆消退相关的脑区主要涉及杏仁核、内侧前额叶和海马.在恐惧消退的过程中,这3个脑区表现出特定的神经振荡模式,而且这些活动也具有同步性,构成了恐惧记忆成功消退的神经基础.未来可利用基于神经神经振荡的无创性脑刺激手段干预恐惧记忆消退的神经环路,以促进恐惧记忆的消退并避免复发,为恐惧相关障碍的临床治疗提供重要的科学依据.