Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes

Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding, to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cognitive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients.     

Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance

Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.     

Neurobehavioral evidence for individual differences in canine cognitive control: an awake fMRI study

Based on behavioral evidence, the domestic dog has emerged as a promising comparative model of human self-control. However, while research on human inhibition has probed heterogeneity and neuropathology through an integration of neural and behavioral evidence, there are no parallel data exploring the brain mechanisms involved in canine inhibition. Here, using a combination of cognitive testing and awake neuroimaging in domestic dogs, we provide evidence precisely localizing frontal brain regions underpinning response inhibition in this species and demonstrate the dynamic relationship between these regions and behavioral measures of control. Thirteen dogs took part in an in-scanner go/no-go task and an out-of-scanner A-not-B test. A frontal brain region was identified showing elevated neural activity for all subjects during successful inhibition in the scanner, and dogs showing greater mean brain activation in this region produced fewer false alarms. Better performance in the go/no-go task was also correlated with fewer errors in the out-of-scanner A-not-B test, suggesting that dogs show consistent neurobehavioral individual differences in cognitive control, as is seen in humans. These findings help establish parity between human and canine mechanisms of self-control and pave the way for future comparative studies examining their function and dysfunction.     

Neural and cognitive plasticity: from maps to minds

Some species and individuals are able to learn cognitive skills more flexibly than others. Learning experiences and cortical function are known to contribute to such differences, but the specific factors that determine an organism's intellectual capacities remain unclear. Here, an integrative framework is presented suggesting that variability in cognitive plasticity reflects neural constraints on the precision and extent of an organism's stimulus representations. Specifically, it is hypothesized that cognitive plasticity depends on the number and diversity of cortical modules that an organism has available as well as the brain's capacity to flexibly reconfigure and customize networks of these modules. The author relates this framework to past proposals on the neural mechanisms of intelligence, including (a) the relationship between brain size and intellectual capacity; (b) the role of prefrontal cortex in cognitive control and the maintenance of stimulus representations; and (c) the impact of neural plasticity and efficiency on the acquisition and performance of cognitive skills. The proposed framework provides a unified account of variability in cognitive plasticity as a function of species, age, and individual, and it makes specific predictions about how manipulations of cortical structure and function will impact intellectual capacity.     

Top-down predictions in the cognitive brain

The human brain is not a passive organ simply waiting to be activated by external stimuli. Instead, we propose that the brain continuously employs memory of past experiences to interpret sensory information and predict the immediately relevant future. The basic elements of this proposal include analogical mapping, associative representations and the generation of predictions. This review concentrates on visual recognition as the model system for developing and testing ideas about the role and mechanisms of top-down predictions in the brain. We cover relevant behavioral, computational and neural aspects, explore links to emotion and action preparation, and consider clinical implications for schizophrenia and dyslexia. We then discuss the extension of the general principles of this proposal to other cognitive domains.     

Beyond cognitive myopia: a patchwork approach to the concept of neural function

In this paper, I argue that looking at the concept of neural function through the lens of cognition alone risks cognitive myopia: it leads neuroscientists to focus only on mechanisms with cognitive functions that process behaviorally relevant information when conceptualizing “neural function”. Cognitive myopia tempts researchers to neglect neural mechanisms with noncognitive functions which do not process behaviorally relevant information but maintain and repair neural and other systems of the body. Cognitive myopia similarly affects philosophy of neuroscience because scholars overlook noncognitive functions when analyzing issues surrounding e.g., functional decomposition or the multifunctionality of neural structures. I argue that we can overcome cognitive myopia by adopting a patchwork approach that articulates cognitive and noncognitive “patches” of the concept of neural function. Cognitive patches describe mechanisms with causally specific effects on cognition and behavior which are likely operative in transforming sensory or other inputs into motor outputs. Noncognitive patches describe mechanisms that lack such specific effects; these mechanisms are enabling conditions for cognitive functions to occur. I use these distinctions to characterize two noncognitive functions at the mesoscale of neural circuits: subsistence functions like breathing are implemented by central pattern generators and are necessary to maintain the life of the organism. Infrastructural functions like gain control are implemented by canonical microcircuits and prevent neural system damage while cognitive processing occurs. By adding conceptual patches that describe these functions, a patchwork approach can overcome cognitive myopia and help us explain how the brain’s capacities as an information processing device are constrained by its ability to maintain and repair itself as a physiological apparatus.     

The emergence of social cognitive neuroscience

Social cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand phenomena in terms of interactions between 3 levels of analysis: the social level, which is concerned with the motivational and social factors that influence behavior and experience; the cognitive level, which is concerned with the information-processing mechanisms that give rise to social-level phenomena; and the neural level, which is concerned with the brain mechanisms that instantiate cognitive-level processes. The social cognitive neuroscience approach entails conducting studies and constructing theories that make reference to all 3 levels and contrasts with traditional social psychological and cognitive neuroscientific research that primarily makes reference to 2 levels. The authors present an introduction to and analysis of the field by reviewing current research and providing guidelines and suggested directions for future work.     

Insulin receptor signaling in long-term memory consolidation following spatial learning

Evidence has shown that the insulin and insulin receptor (IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus. After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region. These were correlated with a significant reduction in hippocampal IR protein levels. Learning-specific increases in levels of downstream molecules such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments. This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways such as the insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that insulin/IR signaling plays a modulatory role in learning and memory processing, which may be compensated for by alternative pathways in the brain when an insulin deficit occurs.     

Vector subtraction implemented neurally: a neurocomputational model of some sequential cognitive and conscious processes

Although great progress in neuroanatomy and physiology has occurred lately, we still cannot go directly to those levels to discover the neural mechanisms of higher cognition and consciousness. But we can use neurocomputational methods based on these details to push this project forward. Here we describe vector subtraction as an operation that computes sequential paths through high-dimensional vector spaces. Vector-space interpretations of network activity patterns are a fruitful resource in recent computational neuroscience. Vector subtraction also appears to be implemented neurally in primate frontal eye field activity, which computes dimensions of saccadic eye movements. We use this apparent neural implementation as a model and construct from it a general neurocomputational account of an important type of sequential cognitive and conscious process. We defend the biological plausibility of all components of the general model and show that it yields testable anatomical and physiological predictions. We close by suggesting some interesting consequences for consciousness if our model characterizes correctly the neural mechanisms producing a common type of episode in our conscious streams.     

拖延行为的认知神经模型及干预

拖延是一种普遍存在, 具有跨时间和跨情景稳定性的问题行为, 它会危害到人们的学习、工作和身心健康。然而目前拖延行为的认知神经机制仍不清晰, 且缺乏因果证据, 本项目拟从拖延的时间决策模型和三重神经结构网络模型出发, 构建拖延的认知神经模型, 并利用认知干预和神经调控技术, 检验和完善拖延行为的认知神经模型, 进而试图制定拖延的精准化干预方案。本项目分为3部分：(1)从记录与关联研究的视角出发, 利用多模态神经影像方法系统考察拖延行为的认知神经机制; (2)从因果/近因果研究视角出发, 利用认知干预和神经调控技术, 验证并完善拖延的认知神经模型; (3)从临床应用的视角出发, 建立拖延行为障碍的临床筛查-诊断体系, 并制定精准化治疗方案。本项目的开展对于探明拖延产生的核心认知神经机制具有十分重要的理论贡献, 同时对于拖延行为的有效预防和精准治疗具有重要的现实意义。     

Synchronous neural oscillations and cognitive processes

The central problem for cognitive neuroscience is to describe how cognitive processes arise from brain processes. This review summarizes the recent evidence that synchronous neural oscillations reveal much about the origin and nature of cognitive processes such as memory, attention and consciousness. Memory processes are most closely related to theta and gamma rhythms, whereas attention seems closely associated with alpha and gamma rhythms. Conscious awareness may arise from synchronous neural oscillations occurring globally throughout the brain rather than from the locally synchronous oscillations that occur when a sensory area encodes a stimulus. These associations between the dynamics of the brain and cognitive processes indicate progress towards a unified theory of brain and cognition.     

Neurodisruption of selective attention: insights and implications

Mechanisms of selective attention are vital for coherent perception and action. Recent advances in cognitive neuroscience have yielded key insights into the relationship between neural mechanisms of attention and eye movements, and the role of frontal and parietal brain regions as sources of attentional control. Here we explore the growing contribution of reversible neurodisruption techniques, including transcranial magnetic stimulation and microelectrode stimulation, to the cognitive neuroscience of spatial attention. These approaches permit unique causal inferences concerning the relationship between neural processes and behaviour, and have revealed fundamental mechanisms of attention in the human and animal brain. We conclude by suggesting that further advances in the neuroscience of attention will be facilitated by the combination of neurodisruption techniques with established neuroimaging methods.     

认知重评和表达抑制情绪调节策略的脑网络分析：来自EEG和ERP的证据

本文旨在对认知重评和表达抑制两种常用情绪调节策略的自发脑网络特征及认知神经活动进行深入探讨。研究采集36名在校大学生的静息态和任务态脑电数据, 经过源定位和图论分析发现节点效率与两种情绪调节显著相关的脑区, 以及脑区之间的功能连接。研究结果表明, 在使用认知重评进行情绪调节时会激活前额叶皮质、前扣带回、顶叶、海马旁回和枕叶等多个脑区, 在使用表达抑制进行情绪调节时会激活前额叶皮质、顶叶、海马旁回、枕叶、颞叶和脑岛等多个脑区。因此, 这些脑区的节点效率或功能连接强度可能成为评估个体使用认知重评和表达抑制调节情绪效果的指标。     

Emotions in cognitive conflicts are not aversive but are task specific

It has been suggested that cognitive conflicts require effortful processing and, therefore, are aversive (Botvinick, 2007). In the present study, we compared conflicts emerging from the inhibition of a predominant response tendency in a go/no-go task with those between incompatible response activations in a Simon task in a within-subjects design, using the same type of stimuli. Whereas no-go trials elicited reduced skin conductance and pupillometric responses, but prolonged corrugator muscle activity, as compared with go trials, incompatible and compatible Simon trials were indistinguishable with respect to these parameters. Furthermore, the conflictsensitive N2 components of the event-related brain potential were similar in amplitude, but showed significantly different scalp distributions, indicating dissociable neural generator systems. The present findings suggest the involvement of different emotional and cognitive processes in both types of cognitive conflicts—none being aversive, however. In addition, the N2 findings call into question claims of common monitoring systems for all kinds of cognitive conflicts.     

Neural predictive mechanisms and their role in cognitive incrementalism

Many neuroscientists view prediction as one of the core brain functions, especially on account of its support of fast movements in complex environments. This leads to the natural question whether predictive knowledge forms the cornerstone of our common-sense understanding of the world. However, there is little consensus as to the exact nature of predictive information and processes, or of the neural mechanisms that realize them. This paper compares procedural versus declarative notions of prediction, examines how the brain appears to carry out predictive functions, and discusses to what degree, and at what level, these neural mechanisms support cognitive incrementalism: the notion that high-level cognition stems from sensorimotor behavior.     

创造性认知重评在情绪调节中的迁移效应及其神经基础

认知重评在负性情绪调节中发挥着重要的作用。针对传统认知重评重构程度不够高、调节效果不明显的问题, 研究团队在先前的工作中提出了一种使消极情绪“转负为正”的高效情绪调节方法, 即创造性认知重评, 这种调节策略伴随着大脑海马的新颖联结形成和杏仁核的积极情绪唤醒。然而这些工作采用“指导式”的重评更像是对重评解读的“理解”而非主动的情绪调节; 鉴于主动情绪调节的产生难度较大, 造成创造性认知重评在实际应用上的两难困境。基于此, 本项目拟指导受试者进行创造性认知重评的学习, 通过学习将这种策略迁移并且应用到生活中的负性情绪调节事件中。具体研究内容包括：(1)行为学上, 探索创造性认知重评在大学生群体和青少年群体负性情绪调节中的迁移效应; (2)影像学上, 探索创造性认知重评迁移前后在脑认知表征模式上的变化。本项目是对已有工作基础的延伸和拓展, 为验证和推动创造性认知重评成为一种可学、可用、高效的情绪调节策略奠定理论基础。     

视频游戏对认知能力的影响及其神经基础

视频游戏是一类需要借助视听设备并基于一定剧情进行操作的游戏。先前研究大多关注暴力视频游戏对攻击等负面行为的影响,但本文着重探讨视频游戏对个体认知能力的积极影响及内在神经基础,以辩证看待视频游戏对个体心理和行为的作用。本文对前人研究归纳梳理发现,视频游戏训练能使个体认知能力得到持久改善,同时论述了视频游戏中脑神经基础和奖赏预期对认知能力的调控作用。未来研究应在规范视频游戏训练技术的基础上,用其干预靶脑区以提升个体特定脑功能。     

Lateral specialization in unilateral spatial neglect: a cognitive robotics model

In this paper, we present the experimental results of an embodied cognitive robotic approach for modelling the human cognitive deficit known as unilateral spatial neglect (USN). To this end, we introduce an artificial neural network architecture designed and trained to control the spatial attentional focus of the iCub robotic platform. Like the human brain, the architecture is divided into two hemispheres and it incorporates bio-inspired plasticity mechanisms, which allow the development of the phenomenon of the specialization of the right hemisphere for spatial attention. In this study, we validate the model by replicating a previous experiment with human patients affected by the USN and numerical results show that the robot mimics the behaviours previously exhibited by humans. We also simulated recovery after the damage to compare the performance of each of the two hemispheres as additional validation of the model. Finally, we highlight some possible advantages of modelling cognitive dysfunctions of the human brain by means of robotic platforms, which can supplement traditional approaches for studying spatial impairments in humans.     

The functional‐cognitive framework as a tool for accelerating progress in cognitive neuroscience: On the benefits of bridging rather than reducing levels of analyses

The subject matter of neuroscience research is complex, and synthesising the wealth of data from this research to better understand mental processes is challenging. A useful strategy, therefore, may be to distinguish explicitly between the causal effects of the environment on behaviour (i.e. functional analyses) and the mental processes that mediate these effects (i.e. cognitive analyses). In this article, we describe how the functional‐cognitive (F‐C) framework can accelerate cognitive neuroscience and also advance a functional treatment of brain activity. We first highlight that cognitive neuroscience can particularly benefit from the F‐C approach by providing an alternative to the problematic practice of reducing cognitive constructs to behavioural and/or neural proxies. Next, we outline how functional (behaviour–environment) relations can serve as a bridge between cognitive and neural processes by restoring mental constructs to their original role as heuristic tools. Finally, we give some examples of how both cognitive neuroscience and traditional functional approaches can mutually benefit from the F‐C framework.     

Bridges over troubled waters: education and cognitive neuroscience

Recently there has been growing interest in and debate about the relation between cognitive neuroscience and education. Our goal is to advance the debate beyond both recitation of potentially education-related cognitive neuroscience findings and the claim that a bridge between fields is chimerical. In an attempt to begin a dialogue about mechanisms among students, educators, researchers and practitioner-scientists, we propose that multiple bridges can be built to make connections between education and cognitive neuroscience, including teacher training, researcher training and collaboration. These bridges--concrete mechanisms that can advance the study of mind, brain and education--will benefit both educators and cognitive neuroscientists, who will gain new perspectives for posing and answering crucial questions about the learning brain.