Aberrant learning and memory in addiction

Over the past several years, drug addiction has increasingly been accepted to be a disease of the brain as opposed to simply being due to a lack of willpower or personality flaw. Exposure to addictive substances has been shown to create enduring changes in brain structure and function that are thought to underlie the transition to addiction. Specific genetic and environmental vulnerability factors also influence the impact of drugs of abuse on the brain and can enhance the likelihood of becoming an addict. Long-lasting alterations in brain function have been found in neural circuits that are known to be responsible for normal appetitive learning and memory processes and it has been hypothesized that drugs of abuse enhance positive learning and memory about the drug while inhibiting learning about the negative consequences of drug use. Therefore, the addict's behavior becomes increasingly directed towards obtaining and using drugs of abuse, while at the same time developing a poorer ability to stop using, even when the drug is less rewarding or interferes with functioning in other facets of life. In this review we will discuss the clinical evidence that addicted individuals have altered learning and memory and describe the possible neural substrates of this dysfunction. In addition, we will explore the pre-clinical evidence that drugs of abuse cause a progressive disorder of learning and memory, review the molecular and neurobiological changes that may underlie this disorder, determine the genetic and environmental factors that may increase vulnerability to addiction, and suggest potential strategies for treating addiction through manipulations of learning and memory.     

音乐训练对统计学习能力的促进作用

统计学习能力作为快速习得环境中信息规则的先决条件之一,有助于个体以较小的消耗代价适应环境。音乐训练作为一种由多个感官共同参与的强化活动,被广泛认为是有助于提升认知能力的有效手段。随着统计学习在音乐适应中核心地位的确认以及音乐训练效应的反复验证,近年来,陆续有研究在行为表现和脑机制上证实了音乐训练能够增强个体对输入信息中统计规则的敏感性、促进听觉统计学习能力的提升。然而,关于音乐训练能否促进视觉等其他模态的统计学习能力,目前还存在不一致的结果。未来研究还应对跨模态统计学习能力的音乐训练促进效应做进一步探索;也可选用新手被试进行音乐训练干预,以明确音乐训练与各模态统计学习能力增强之间的因果关系。     

Learning and adult neurogenesis: survival with or without proliferation?

Recent high quality papers have renewed interest in the phenomenon of neurogenesis within the adult mammalian brain. Many studies now show that neurogenesis can be modulated by environmental factors including physical activity, stress, and learning. These findings have considerable implications for neuroscience in general, including the study of learning and memory, neural network plasticity, aging, neurodegeneration, and the recovery from brain injury. Although new light has been shed on this field, many contradictory findings have been reported. Here we propose two principle issues which underlie these inconsistencies, with particular focus on the interaction between learning and neurogenesis. The first issue relates to the basic methodology of measuring the generation of new brain cells, i.e., proliferation, as compared to survival of the newly made cells. Mostly, measures of neurogenesis reported are a combination of proliferation and survival, making it impossible to distinguish between these separate processes. The second aspect is in regards to the role of environmental factors which can affect both proliferation and survival independently. Especially the interaction between stress and learning is of importance since these might counteract each other in some circumstances. Reviewing the literature while taking these issues into account indicates that, in contrast to some findings, cell proliferation in the dentate gyrus of the hippocampus as a result of learning cannot be ruled out yet. On the other hand, increased survival of granule cells in the dentate gyrus as a result of hippocampal-dependent learning has been clearly demonstrated. Moreover, this learning-induced survival of granule cells, which were born before the actual learning experience, might provide a molecular mechanism for the 'use it or lose it' principle.     

第二语言学习与脑可塑性

脑可塑性指人脑会因为环境刺激、认知需求和行为经验而产生功能或结构改变。近10年来的单双语者对比和语言训练研究结果表明, 不论儿童、青年或老年人, 第二语言学习和使用都能改变其脑运行模式并带来相应结构变化, 包括灰质(GM)体积和白质(WM)密度增加, 且长期持续的双语经验还能形成认知优势, 帮助抵制由老化导致的负面认知影响。基于脑可塑性概念及其研究证据, 从双语经验与语言训练两方面, 对比分析了长期和短期第二语言学习引起脑功能或结构变化及其内在机制, 并对未来相关研究进行了展望。     

丰富环境对脑缺血大鼠突触界面结构修饰和PSD-95基因表达的影响

探讨丰富环境干预对局部脑缺血大鼠突触界面结构修饰和突触后致密物-95 (postsynaptic density-95,PSD-95 ) mRNA表达的影响。栓塞健康雄性Sprague-Dawley大鼠的右侧大脑中动脉,建立脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型后,分为丰富环境缺血组(IE)、标准环境缺血组(IS),同时分别设丰富环境假手术组(SE)、标准环境假手术组(SS)。以Morris水迷宫检测大鼠的空间学习记忆能力,应用透射电镜、图像分析和细胞形态计量学技术,观察海马CA1区和额叶皮层突触界面结构变化,采用RT-PCR检测突触后脚手架蛋白PSD-95 mRNA的表达。结果表明：丰富环境干预能有效改善脑缺血导致的空间学习记忆能力下降,并对正常大鼠的空间学习记忆能力也有改善作用。同时,丰富环境干预能抑制局部脑缺血导致的突触数密度减少,该作用对额叶皮层特别明显;丰富环境干预不同程度地逆转脑缺血造成的突触界面参数变化,特别使突触间隙宽度显著减小、PSD厚度明显增加;并有效抑制因脑缺血诱导的PSD-95 mRNA表达下调。以上结果提示,丰富环境改善脑缺血大鼠的空间学习记忆能力可能与其促进缺血区边缘组织突触界面结构修饰,提高PSD-95 mRNA表达有关     

Programmed to learn? The ontogeny of mirror neurons

Mirror neurons are increasingly recognized as a crucial substrate for many developmental processes, including imitation and social learning. Although there has been considerable progress in describing their function and localization in the primate and adult human brain, we still know little about their ontogeny. The idea that mirror neurons result from Hebbian learning while the child observes/hears his/her own actions has received remarkable empirical support in recent years. Here we add a new element to this proposal, by suggesting that the infant's perceptual‐motor system is optimized to provide the brain with the correct input for Hebbian learning, thus facilitating the association between the perception of actions and their corresponding motor programs. We review evidence that infants (1) have a marked visual preference for hands, (2) show cyclic movement patterns with a frequency that could be in the optimal range for enhanced Hebbian learning, and (3) show synchronized theta EEG (also known to favour synaptic Hebbian learning) in mirror cortical areas during self‐observation of grasping. These conditions, taken together, would allow mirror neurons for manual actions to develop quickly and reliably through experiential canalization. Our hypothesis provides a plausible pathway for the emergence of mirror neurons that integrates learning with genetic pre‐programming, suggesting new avenues for research on the link between synaptic processes and behaviour in ontogeny.     

Superior formation of cortical memory traces for melodic patterns in musicians

The human central auditory system has a remarkable ability to establish memory traces for invariant features in the acoustic environment despite continual acoustic variations in the sounds heard. By recording the memory-related mismatch negativity (MMN) component of the auditory electric and magnetic brain responses as well as behavioral performance, we investigated how subjects learn to discriminate changes in a melodic pattern presented at several frequency levels. In addition, we explored whether musical expertise facilitates this learning. Our data show that especially musicians who perform music primarily without a score learn easily to detect contour changes in a melodic pattern presented at variable frequency levels. After learning, their auditory cortex detects these changes even when their attention is directed away from the sounds. The present results thus show that, after perceptual learning during attentive listening has taken place, changes in a highly complex auditory pattern can be detected automatically by the human auditory cortex and, further, that this process is facilitated by musical expertise.     

Neonatal exposure to novel environment enhances hippocampal-dependent memory function during infancy and adulthood

Early life experience affects behavior and brain mechanisms. Handling rats during the first three weeks in life can slow age-related cognitive decline (as measured by a hippocampal-dependent spatial learning task) and reduce age-related hippocampal neuron loss. It is not clear, however, whether this early environmental influence on learning is selective for old age or is more general, affecting cognitive development during infancy and young adulthood as well. We briefly exposed neonatal rats to a novel non-home environment for 3 min daily during the first three weeks of life (as a component of the handling method). We found that this brief early environmental manipulation resulted in enhanced hippocampal-dependent learning immediately after weaning and that this learning enhancement persisted into adulthood. These results suggest that subtle early life events can affect cognitive development in all developmental stages and that changes in neural mechanisms other than neuron number are likely to mediate the learning enhancement at multiple developmental stages.     

Tracing trajectories of audio‐visual learning in the infant brain

Although infants begin learning about their environment before they are born, little is known about how the infant brain changes during learning. Here, we take the initial steps in documenting how the neural responses in the brain change as infants learn to associate audio and visual stimuli. Using functional near‐infrared spectroscopy (fNRIS) to record hemodynamic responses in the infant cortex (temporal, occipital, and frontal cortex), we find that across the infant brain, learning is characterized by an increase in activation followed by a decrease. We take this U‐shaped response as evidence of repetition enhancement during early stages of learning and repetition suppression during later stages, a result that mirrors the Hunter and Ames model of infant visual preference. Furthermore, we find that the neural response to violations of the learned associations can be predicted by the shape of the learning curve in temporal and occipital cortex. These data provide the first look at the shape of the neural response during audio‐visual associative learning in infancy establishing that diverse regions of the infant brain exhibit systematic changes across the time‐course of learning.     

Plasticity of nonneuronal brain tissue: roles in developmental disorders

Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes are dependent on the type of experience and learning. Increased neurogenesis in the hippocampal dentate gyrus is a well-documented response to environmental complexity ("enrichment") and learning. Exposure to challenging experiences and learning opportunities also alters existing glial cells (i.e., astrocytes and oligodendrocytes), and up-regulates gliogenesis, in the cerebral cortex and cerebellum. Such glial plasticity often parallels neuronal remodeling in both time and place, and this enhanced morphological synergism may be important for optimizing the functional interaction between glial cells and neurons. Aberrant structural plasticity of nonneuronal elements is a contributing factor, as is aberrant neuron plasticity, to neurological and developmental disorders such as epilepsy, autism, and mental retardation (i.e., fragile X syndrome). Some of these nonneuronal pathologies include abnormal cerebral and cerebellar white matter and myelin-related proteins in autism; abnormal myelin basic protein in fragile X syndrome (FXS); and abnormal astrocytes in autism, FXS, and epilepsy. A number of recent studies demonstrate the possibility of using environmental and experiential intervention to reduce or ameliorate some of the neuronal and nonneuronal abnormalities, as well as behavioral deficits, present in these neurological and developmental disorders.     

The preprogramming of behavior patterns by changing the neurotransmitter metabolism in the early postnatal ontogenesis of albino rats]

Changes in neurotransmitter concentrations, which are brought about by the administration of neurotropic pharmaceuticals to albino rats at the time of differentiation of the brain, may have a lasting effect upon the reactivity and adaptability of adult animals to environmental factors and give rise to specific patterns of behavior. 1. Pargyline, when administered neonatally, resulted in a reduction of learning power, decrease in the power of retention, as well as reduction of the decision-making ability. 2. Reserpine gave an improvement of learning power, but simultaneously decreased both the power of retaining what had been learnt and the decision-making ability. 3. Pyridostigmine gave a marked improvement of adaptability which was evidenced in higher learning power, greater retentiveness, and better decision-making ability.     

Principles that are invoked in the acquisition of words, but not facts

A controversial question is whether language acquisition is the result of domain-general or domain-specific principles. Focusing on word-learning, Markson and Bloom (Nature 385(6619) (1997) 813) recently argued that the ability to learn and retain new words (count nouns) is the result of abilities that are not specific to language. In the current experiment, we replicate their empirical finding, but challenge their domain-general interpretation by highlighting a crucial distinction between the principles involved in learning a count noun, as compared to learning a fact. The current results confirm that learning count nouns and facts involve (at least) two common components: establishing a mapping to a designated individual, and retaining this mapping over time. However, these results go further to document that the processes invoked in the acquisition of words differ from those invoked in the acquisition of facts. Children spontaneously and systematically extended a novel count noun exclusively to other members of the same category, but revealed no such systematicity when extending a fact. This illustrates that there are principles that are invoked in learning a novel count noun that are not invoked in learning a fact.     

What is learning? On the nature and merits of a functional definition of learning

Learning has been defined functionally as changes in behavior that result from experience or mechanistically as changes in the organism that result from experience. Both types of definitions are problematic. We define learning as ontogenetic adaptation—that is, as changes in the behavior of an organism that result from regularities in the environment of the organism. This functional definition not only solves the problems of other definitions, but also has important advantages for cognitive learning research.     

Imaging the developing brain with fMRI

Advancements in magnetic imaging techniques have revolutionized our ability to study the developing human brain in vivo. The ability to noninvasively image both anatomy and function in healthy volunteers, including young children, has already enhanced our understanding of brain and behavior relations. The application of these techniques to developmental research offers the opportunity to further explore these relationships and allows us to ask questions about where, when and how cognitive abilities develop in relation to changes in underlying brain systems. It is also possible to explore the contributions of maturation versus learning in the development of these abilities through cross-sectional and longitudinal research involving training and intervention procedures. Current imaging methodologies, in conjunction with new and rapidly evolving techniques, hold the promise of even greater insights into developmental issues in the near future. These methodologies and their application to development and learning are discussed in the current paper.     

Enriching the environment of alphaCaMKIIT286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP

alphaCaMKII(T286A) mutant mice lack long-term potentiation (LTP) in the hippocampal CA1 region and are impaired in spatial learning. In situ hybridization confirms that the mutant mice show the same developmental expression of alphaCaMKII as their wild-type littermates. A simple hypothesis would suggest that if LTP is a substrate for learning, then enriching the environment should cause learning-dependent changes in wild-type mice that have LTP. Such changes would not be seen in LTP-deficient alphaCaMKII(T286A) mutants. Excitatory synaptic currents in CA1 neurons, recorded with patch clamp in brain slices, revealed that enrichment induces an increase in glutamate release probability and a decreased miniature current amplitude. Confocal microscopy also showed dendritic spine density to be reduced. However, contrary to the hypothesis above, these enrichment-induced changes occur only in the mutant mice and are not detectable in wild-type littermates. We suggest that enrichment induces alphaCaMKII-independent changes in both wild-type and mutant mice. Such changes may be subsequently reversed in wild-type animals via alphaCaMKII-dependent mechanisms, such as LTP. Reversal of plasticity has long been hypothesized to be essential for the hippocampus to maintain its role in memory processing. The inability to reverse plasticity in alphaCaMKII(T286A) mutant mice would then result in impairment of spatial learning.     

Effects of feedback reliability on feedback-related brain activity: A feedback valuation account

Adaptive decision making relies on learning from feedback. Because feedback sometimes can be misleading, optimal learning requires that knowledge about the feedback’s reliability be utilized to adjust feedback processing. Although previous research has shown that feedback reliability indeed influences feedback processing, the underlying mechanisms through which this is accomplished remain unclear. Here we propose that feedback processing is adjusted by the adaptive, top-down valuation of feedback. We assume that unreliable feedback is devalued relative to reliable feedback, thus reducing the reward prediction errors that underlie feedback-related brain activity and learning. A crucial prediction of this account is that the effects of feedback reliability are susceptible to contrast effects. That is, the effects of feedback reliability should be enhanced when both reliable and unreliable feedback are experienced within the same context, as compared to when only one level of feedback reliability is experienced. To evaluate this prediction, we measured the event-related potentials elicited by feedback in two experiments in which feedback reliability was varied either within or between blocks. We found that the fronto-central valence effect, a correlate of reward prediction errors during reinforcement learning, was reduced for unreliable feedback. But this result was obtained only when feedback reliability was varied within blocks, thus indicating a contrast effect. This suggests that the adaptive valuation of feedback is one mechanism underlying the effects of feedback reliability on feedback processing.     

Integrating brain science research with intelligence research

Understanding the possible causes of differences in intelligence is crucial if children are to achieve their full potential. Such understanding has been hampered until recently, however, because researchers who study intelligence have neglected recent findings in the brain sciences suggesting that the brain develops in response to environmental stimulation. These findings have seemed to contradict intelligence research that suggests that intellectual abilities are inherited. However, the findings from intelligence research and the brain sciences can be integrated if it is accepted that there are individual differences in the process by which the brain adapts to the environment, such that some people's brains are better at adapting than others'. The findings obtained from intelligence research are consistent with this integrated model. Such an integration has implications for better understanding the nature of intelligence.     

言语学习引起的脑功能和结构变化

文章系统介绍了言语学习引起的脑功能和结构可塑性变化研究的最新进展,例如：第二语言的词汇——语义学习引起的脑功能变化主要受熟练程度的影响,而句法学习引起的脑功能变化主要受获得年龄的影响;实验室言语训练可以引起语言加工相关区域激活增强或减弱,以及出现新的激活区域;第二语言学习导致了左侧顶下皮层灰质密度增加。此外,文章还总结了言语学习的脑成像研究中常用的实验范式,并提出了有待于进一步解决的关键问题     

Translocation and activation of Rac in the hippocampus during associative contextual fear learning

Small G proteins including Rac are mediators of changes in neuronal morphology associated with synaptic plasticity. Previous studies in our laboratory showed that Rac is highly expressed in the adult mouse hippocampus, a brain area that exhibits robust synaptic plasticity and is crucial for the acquisition of memories. In this study, we investigated whether Rac was involved in NMDA receptor-dependent associative fear learning in the area CA1 of adult mouse hippocampus. We found that Rac translocation and activation was increased in the hippocampus following associative fear conditioning in mice, and that these increases are blocked by intraperitoneal injection of the NMDA receptor channel blocker MK801 at the acquisition stage. Our data indicate that NMDA receptor-dependent associative fear learning alters Rac localization and function in the mouse hippocampus.     

Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).