Common Neural Mechanisms Underlying Reversal Learning by Reward and Punishment

Impairments in flexible goal-directed decisions, often examined by reversal learning, are associated with behavioral abnormalities characterized by impulsiveness and disinhibition. Although the lateral orbital frontal cortex (OFC) has been consistently implicated in reversal learning, it is still unclear whether this region is involved in negative feedback processing, behavioral control, or both, and whether reward and punishment might have different effects on lateral OFC involvement. Using a relatively large sample (N = 47), and a categorical learning task with either monetary reward or moderate electric shock as feedback, we found overlapping activations in the right lateral OFC (and adjacent insula) for reward and punishment reversal learning when comparing correct reversal trials with correct acquisition trials, whereas we found overlapping activations in the right dorsolateral prefrontal cortex (DLPFC) when negative feedback signaled contingency change. The right lateral OFC and DLPFC also showed greater sensitivity to punishment than did their left homologues, indicating an asymmetry in how punishment is processed. We propose that the right lateral OFC and anterior insula are important for transforming affective feedback to behavioral adjustment, whereas the right DLPFC is involved in higher level attention control. These results provide insight into the neural mechanisms of reversal learning and behavioral flexibility, which can be leveraged to understand risky behaviors among vulnerable populations.     

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.     

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.     

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.     

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...     

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.     

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.     

Physiological Mechanisms Underlying Fruit Sunburn

Sunburn is a physiological disorder that can be observed in fruits of several crops growing in areas with warm climates, as a result of photodamage due to an excess of heat and/or light irradiance (visible and ultraviolet light). The main cause is thought to be an increase in reactive oxygen species production which causes oxidative damage due to the incapacity of the fruit to recover from stress. This can result in a characteristic morphological and structural phenotype unacceptable to consumers, leading to severe losses in productivity for farmers. Fruits have a great array of mechanisms to mitigate or reduce reactive oxygen species production and the inactivation of photosynthetic apparatus, such as enhanced xanthophyll cycle-dependent energy dissipation, accumulation of photoprotective pigments and heat-shock proteins, and the biosynthesis of antioxidants, among others. Nevertheless, these mechanisms become inefficient when the stress factors altering the fruit surface exceed a certain threshold (of both duration and intensity). Although this disorder has been studied in detail and previous efforts have provided significant advances in understanding the underlying mechanisms causing sunburn in a number of fruits, further research is still needed. This will undoubtedly provide new approaches and tools for improving current mitigation strategies.     

Semiotic Mechanisms Underlying Niche Construction

The explanatory value of niche construction can be strengthened by firm footing in semiotic theory. Anthropologists have a unique perspective on the integration of such diverse approaches to human action and evolutionary processes. Here, we seek to open a dialogue between anthropology and biosemiotics. The overarching aim of this paper is to demonstrate that niche construction, including the underlying mechanism of reciprocal causation, is a semiotic process relating to biological development (sensu stricto) as well as cognitive development and cultural change. In making this argument we emphasize the semiotic mechanisms underlying the niche concept. We argue that the “niche” in ecology and evolutionary biology can be consistent with the Umwelt of Jakob von Uexkull. Following John Deely we therefore suggest that investigations into the organism—environment interface constituting niche construction should emphasize the semiotic basis of experience. Peircean signs are pervasive and allow for flexible interpretations of phenomena in relation to the perceptual and cognitive capacities of the behaving organism, which is particularly pertinent for understanding the relation of proximate/ultimate selective forces as co-productive (i.e., reciprocal). Additionally, theoretical work by Kinji Imanishi on the evolution of daily life and Gregory Bateson’s relational view of evolution both support the linkage between proximate and ultimate evolutionary processes of causation necessitated by the niche construction perspective. We will then apply this theoretical framework to two specific examples: 1) hominin evolution, including uniquely human cultural behaviors with niche constructive implications; and 2) the multispecies and anthropocentric niche of human-dog coevolution from which complex cognitive capacities and semiotic relationships emerged. The intended outcome of this paper is the establishment of concrete semiotic mechanisms and theory underlying niche constructive behavior which can then be applied to a broad spectrum of organisms to contextualize the reciprocal relation between proximate and ultimate drivers of behavior.     

量子点细胞毒性及其作用机制

纳米粒子(NPS)在工业和研究中的使用急剧增加,因而这种材料面临一个其潜在毒性的问题。不幸的是,对纳米颗粒与纳米/生物界面可能发生的相互作用没有足够的了解。广大科技工作者正在积极寻求日益关注的纳米技术对人类的影响答案。我们将从NPS在生物媒体中的浓度,尺寸大小,电荷,和配位体的稳定性方面来了解纳米粒子的性质和他们在生物环境中对细胞毒所起的作用;并初步探讨已知的机制,量子点可以破坏细胞,包括氧化应激引起的活性氧(ROS)。微小浓度量子点足以造成长期持久的,甚至是跨代的影响。本文讨论了从纳摩尔到皮摩尔浓度的诱导细胞损伤的量子点(QDS)的浓度,这意味着含镉量子点可以发挥表观遗传毒性,纳米基因毒性,重金属基因的毒性。在此为评估包括量子点的在内的纳米毒性的的纳米材料,我们采用量子点作为一个例证,来阐述以科学为基础的发展到纳米毒理学的相关的问题。     

Analysis of Mechanisms Underlying Adaptation Processes

A system of elementary adaptation mechanisms is presented. The adaptations are considered as transients to a new homeostatic condition induced by an environmental change. We propose to distinguish adaptation mechanisms not directly related to gene expression (changes in the rate of synthesis and degradation of proteins, protein–ligand interactions, changes in viscosity of the membrane lipids) and the mechanisms relying on gene expression (changes in expression of already functioning genes, expression of new genes, mutations). Most of these mechanisms have phenotypic nature and just one (mutations) is genotypic. By the nature and time pattern of the environmental influence the adaptation processes can be divided into four types: phenotypic adaptations under rapidly (A) or gradually (B) alternating environmental factors, genotypic adaptations induced by an instant change (mutation) (C), and step adaptational changes (several or many mutations) (D). We propose a model based on a (second-order) linear differential equation qualitatively describing all four types of the adaptation processes.     

Molecular Mechanisms Underlying Differentiation of Thymocytes

A review of the main molecular events occurring during differentiation of T-lymphocytes in the thymus: T-cell specialization of early intrathymic precursors, formation and expression of antigen receptor, formation of antigen recognizing cell repertoire, and /- and CD4/CD8-commitment. The mechanisms of glucocorticoid-induced apoptosis of thymocytes and its blockade during antigen-dependent activation are considered. A special attention is paid to the analysis of intracellular signals underlying the clonal selection of thymocytes.     

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...     

Serotonin and Central Mechanisms Underlying Motor Control

The review considers in a historical aspect the published data on the role of serotonin in brain activity, as well as on the structure and organization of neuronal projections of serotonergic nuclei. In addition, information on the facilitatory and inhibitory effects of serotonin on neurons of various brain regions under both in vivo and in vitro conditions is presented. General characteristics of the main types of central serotonin receptors are also given. It is emphasized that such receptors form a heterogeneous group, and this is the reason for the diversity of the effects when agonists and antagonists are applied. Regularities characteristic of changes in the activity of serotonergic system over the sleep-wakefulness cycle are also analyzed in this review; data on the involvement of serotonin in motor control are cited. Possible reasons for the complexity and multiplicity of the effects evoked by serotonin at different levels of the CNS and within various neuronal structures in the course of motor behavior are discussed.     

Deducing Underlying Mechanisms from Protein Recruitment Data

By using fluorescent labelling techniques, the distribution and dynamics of proteins can be measured within living cells, allowing to study in vivo the response of cells to a triggering event, such as DNA damage. In order to evaluate the reaction rate constants and to identify the proteins and reactions that are essential for the investigated process, mechanistic models are used, which often contain many proteins and associated parameters and are therefore underdetermined by the data. In order to establish criteria for assessing the significance of a model, we present here a systematic investigation of the information that can be reliably deduced from protein recruitment data, assuming that the complete set of reactions that affect the data of the considered protein species is not known. To this purpose, we study in detail models where one or two proteins that influence each other are recruited to a substrate. We show that in many cases the kind of interaction between the proteins can be deduced by analyzing the shape of the recruitment curves of one protein. Furthermore, we discuss in general in which cases it is possible to discriminate between different models and in which cases it is impossible based on the data. Finally, we argue that if different models fit experimental data equally well, conducting experiments with different protein concentrations would allow discrimination between the alternative models in many cases.     

Mechanisms Underlying Metabolic and Neural Defects in Zebrafish and Human Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)

In humans, mutations in electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.     

The Neural Mechanisms Underlying the Decision to Rest in the Presence of Fatigue: A Magnetoencephalography Study

Adequate rest is essential to avoid fatigue and disruption of homeostasis. However, the neural mechanisms underlying the decision to rest are not well understood. In the present study, we aimed to clarify the neural mechanisms of this decision-making process using magnetoencephalography. Fifteen healthy volunteers participated in decision and control experiments performed in a cross-over fashion. In the decision experiment, participants performed 1,200 reverse Stroop test trials and were intermittently asked to decide whether they wanted to take a rest or continue. In the control experiments, participants performed 1,200 reverse Stroop test trials and were instructed to press a response button intermittently without making any decision. Changes in oscillatory brain activity were assessed using a narrow-band adaptive spatial filtering method. The levels of decrease in theta (4–8 Hz) band power in left Brodmann''s area (BA) 31, alpha (8–13 Hz) band power in left BA 10 and BA 9, and beta (13–25 Hz) band power in right BA 46 and left BA 10 were greater in trials when the participant opted to rest (rest trials) than those in control trials. The decrease in theta band power in BA 31 in the rest trials was positively correlated with the subjective level of fatigue after the decision experiment. These results demonstrated that the dorsolateral prefrontal cortex, frontal pole, and posterior cingulate cortex play a role in the decision to rest in the presence of fatigue. These findings may help clarify the neural mechanisms underlying fatigue and fatigue-related problems.