Proteomics of multiprotein complexes: answering fundamental questions in neuroscience

Proteomics tools offer new ways to analyse networks of proteins that control important neurobiological phenomena such as learning and memory. In this review, we discuss how a combined proteomic, pharmacological and genetic approach reveals that multiprotein complexes process neural information and encode memories. Simultaneous analysis of multiple proteins enables the development of new concepts and approaches for neuroscience research.     

Proteomics of multiprotein complexes: answering fundamental questions in neuroscience

Proteomics tools offer new ways to analyse networks of proteins that control important neurobiological phenomena such as learning and memory. In this review, we discuss how a combined proteomic, pharmacological and genetic approach reveals that multiprotein complexes process neural information and encode memories. Simultaneous analysis of multiple proteins enables the development of new concepts and approaches for neuroscience research.     

网络成瘾者奖赏系统和认知控制系统的神经机制

网络成瘾作为一种行为成瘾,已成为严重影响人们心理健康的全球性问题.根据大脑发育的神经生物模型,揭示网络成瘾者奖赏和认知控制系统的神经机制是解决网络成瘾问题的关键,也是心理学研究的重大问题.行为研究探讨了网络成瘾具有高奖赏寻求和低认知控制特征;神经机制研究揭示了奖赏和认知控制系统的缺陷是网络成瘾行为的高风险因素;与药物成瘾的比较研究发现,网络成瘾有着独特的奖赏机制.这些研究深化了对网络成瘾心理和神经机制的理解,但仍存在网络成瘾筛查和入组标准不科学、分型笼统、因果研究匮乏、干预和治疗效果具有争议、研究范式存在漏洞等一些急需解决的问题.     

Modeling motivational deficits in mouse models of schizophrenia: behavior analysis as a guide for neuroscience

In recent years it has become possible to develop animal models of psychiatric disease in genetically modified mice. While great strides have been made in the development of genetic and neurobiological tools with which to model psychiatric disease, elucidation of neural and molecular mechanisms thought to underlie behavioral phenotypes has been hindered by an inadequate analysis of behavior. This is unfortunate given the fact that the experimental analysis of behavior has created powerful methods for isolating and describing the functional properties of behavioral mechanisms that are capable of providing deep understanding of behavioral phenotypes. A better understanding of the biological basis of normal behavior and its disturbance in psychiatric disease will require the application of these rigorous behavior analytic tools to animal models. In this review we provide an example of a merging of genetic and behavioral methods and illustrate its utility in the analysis of a mouse model of the motivational deficits in schizophrenia. The synergy between basic behavior analysis, neuroscience, and animal models of psychiatric disease has great potential for achieving a deeper understanding of behavior and its neurobiological mechanisms as well as for leading to improvements in diagnosis and treatment in clinical settings.     

Aberrant auditory system and its developmental implications for autism

Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile. There is a large body of research on abnormal speech and language in children with autism. However, auditory development has been relatively under-investigated in autism research, despite its inextricable relationship with language development and despite researchers' ability to detect abnormalities in brain development and behavior in early infancy. In this review, we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children, children at high risk for autism, and children diagnosed with autism. We conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in autism. We then offer perspectives on the need for a systematic characterization of early auditory development in autism, and identified questions to be addressed in future research on the development of autism.     

Modeling neurodevelopmental cognitive deficits in tasks with cross‐species translational validity

Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to ‘develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures’ in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross‐species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains.     

Relationship between number of muscles,behavioral repertoire size,and encephalization in mammals

Behavior for mammals is built out of multiple muscles acting in a coordinated fashion. Prima facie, there are three principal ways to increase an animal's behavioral repertoire size. The first is to, for each new behavior type, create a set of new muscle types (e.g. triceps, sartorius, etc.) with new functions specifically devoted to the implementation of that behavior type. If this were the case, then although each behavior is built out of many muscles, behavior is not built in a combinatorial fashion out of muscles. The second is similar to the first in that new behavior types are implemented via new muscle types, but, instead, muscles are used in a combinatorial fashion, so that it is the combination of the new muscle type with existing muscle types that makes the new behavior type possible. This is analogous to the addition of new words in a language. The third way behavioral complexity may be scaled up is to increase the complexity of behavioral expressions themselves (rather than increasing the number of muscles types), namely by having more muscles involved in an average behavior. This is analogous to uttering longer sentences in a language. My main task in this paper is to examine which of these ways underlies the increase of behavioral complexity among mammals. Behavioral repertoire sizes from the ethology literature were accumulated for mammals from two dozen species across eight orders, and the number of muscle types was estimated from atlases of anatomy across eight mammalian orders. The manner in which behavioral complexity actually increases among mammals appears to favor the second possibility mentioned above: greater behavioral complexity is achieved primarily by increasing the number of muscle types, and by using muscles in a combinatorial fashion. The theoretical framework I describe allows us to interpret the manner in which the number of muscle types scales with behavioral repertoire size, and I conclude that the number of degrees of freedom in the construction of behavioral expressions is on the order of three, which is probably due to neurobiological limitations in forming behaviors. The ontogeny of behavior in rat is also discussed within this framework. Finally, I show that there is a strong positive relationship between behavioral repertoire size and encephalization among mammals.     

The genetics of addictions: uncovering the genes

The addictions are common chronic psychiatric diseases that today are prevented and treated using relatively untargeted and only partially effective methods. The addictions are moderately to highly heritable, which is paradoxical because these disorders require use; a choice that is itself modulated by both genes and environment. The addictions are interrelated and related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioural control and the anxiety or stress response. Our future understanding of addictions will be enhanced by the identification of genes that have a role in altered substance-specific vulnerabilities such as variation in drug metabolism or drug receptors and a role in shared vulnerabilities such as variation in reward or stress resiliency.     

Review. Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders

Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.     

Focus: Addiction: Case Report: Internet Gaming Disorder Associated With Pornography Use

Internet gaming disorder (IGD) is not currently a recognized diagnosis in the Diagnostic and Statistical Manual for Mental Disorders-5 (DSM-5). However, IGD has been noted to warrant further research for possible future inclusion in the DSM. In many ways, IGD strongly resembles substance and gambling addictions. Such characteristics include tolerance, withdrawal, and social and occupational neglect resulting from increased time invested in video game use and acquisition. The use of similar or closely related media is also seen, which mirrors the natural course of substance and gambling addictions. We present a case of a 22-year-old man who exhibited IGD and problems associated with pornography use. This case report exemplifies the sequelae of IGD. Our paper also reviews the possible mechanisms of behavioral addiction, as well as the status of IGD as a potential subcategory of behavioral addiction. Additional research is needed to determine if IGD co-occurs with problematic use of pornography.     

Recent progress in neurobiological mechanisms of depression

Revealing the neurobiological mechanism of depression has always been a big challenge in the field of neuroscience. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but also some symptoms are impossible to reproduce in animal models. Nevertheless, great progress has been made on the understanding and treatment of depression in recent years. In this review, we focus on key leading hypotheses in the neurobiological mechanism of depression, examine their strengths and weaknesses critically, and also highlight new insights that promise to extend the understanding of depression and its treatment.     

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.     

Non-coding RNA networks underlying cognitive disorders across the lifespan

Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. In this review, we discuss the emergence of many novel, diverse and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses and aging, and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases, as well as those that manifest throughout the lifespan.     

非药物干预治疗物质使用障碍

物质使用障碍（substance use disorder,SUD）是一个全球性的卫生和社会问题。针对大多数成瘾性物质，目前还没有有效的治疗药物，普遍还是采用心理治疗和行为矫治。近年来，针刺、深部脑刺激（DBS）、重复经颅磁刺激（rTMS）、经颅直流电刺激（tDCS）和运动等非药物干预手段在治疗神经系统疾病的有效性逐渐得到重视。越来越多的研究也开始关注非药物干预手段在治疗SUD中的应用。本综述在文献检索（如PubMed、Google Scholar等）的基础上总结了针刺、DBS、rTMS、tDCS和运动等非药物干预手段对阿片类药物、精神活性物质、尼古丁、酒精等不同成瘾性物质的心理渴求、戒断时间、使用剂量和成瘾伴随的情绪、认知功能障碍等的影响。研究表明，针刺、DBS、rTMS、tDCS和运动等非药物干预手段可以有效降低成瘾性物质引起的心理渴求、降低物质摄入量、增加戒断时间，同时改善长期使用成瘾性物质引起的认知障碍、焦虑和抑郁样行为等。如果非药物干预手段结合药物、心理等治疗方式，效果更佳。尽管非药物干预方法在现阶段主要作为辅助性治疗手段，未来的研究应注重明确非药物干预手段的神经生物学机制，...     

Psychophysiology of sports addictions (exercise addiction)

Addictive behavior is an attempt to escape real life by means of artificial changing one’s own psychical state by taking drugs or performing certain activities. Depending on the means of the escape, pharmacological or chemical and nonchemical or behavioral addictions may be distinguished. During recent years, researchers focused their attention on nonchemical addictions, in which a behavioral pattern becomes an object of dependence instead of a psychoactive substance. In Russia, the first classification of nonchemical addictions was suggested by Korolenko. He pointed out direct nonchemical addictions, such as gambling, addiction of relationships between individuals, sexual and love addiction, avoidance addiction, ergomania, overspending addiction, and urgent addiction and intermediate addictions, including eating addiction, i.e., either overeating or starvation, which involve biochemical mechanisms. In addition to the above-mentioned types of addictions, a substantial number of other nonchemical addictions have been described. Some of them are various dependences on computers or the Internet, addiction to exercises or sports, and others.     

Aggression in young children with concurrent callous–unemotional traits: can the neurosciences inform progress and innovation in treatment approaches?

Parenting is the 'clean water' of healthy psychological development and parenting interventions remain the number one treatment at the individual and community levels for early-onset aggression and antisocial behaviour in children. However, recent progress in child psychopathology research is specifying a number of biological mechanisms that interact with environmental risk to influence pathways into aggression and antisocial behaviour. After a brief review of the parent training literature, we focus on child factors, especially callous-unemotional traits, that parse 'aggressive' children into more homogeneous groupings, and then review selected ideas about the origins of aggression coming from the neurosciences (such as neurobehavioural responsivity to emotional stimuli; hypothalamic-pituitary axis abnormalities influencing low cortisol and low serotonin production). We review human and, where relevant, animal models of neurobiological system changes with particular attention to developmental timing and interactions with environmental factors, especially parenting. Based on this innovative research, we then discuss a number of ideas that hold potential for interventions. We conclude that the future will see the development of interventions that aim for synergy between specific biological processes and psychological experiences as they unfold developmentally. The use of D-cycloserine in fear extinction and oxytocin in affiliative bonds is used as an example of these futuristic approaches.     

蜜蜂大脑的分区与功能

蜜蜂Apis mellifera L.是神经生物学研究的重要模式生物。尽管工蜂脑的体积不足1mm3,包含的神经元数量不到百万,但却拥有丰富的个体和社会行为,甚至还有学习、记忆、认知等高级行为。如此微小的大脑也是通过不同结构分区来实现其丰富复杂的行为。本文对蜜蜂大脑的精细解剖结构以及脑区功能研究进行了综述,为昆虫科学和神经生物学研究提供参考。     

Diffusion tensor imaging of cerebral white matter integrity in cognitive aging

In this article we review recent research on diffusion tensor imaging (DTI) of white matter (WM) integrity and the implications for age-related differences in cognition. Neurobiological mechanisms defined from DTI analyses suggest that a primary dimension of age-related decline in WM is a decline in the structural integrity of myelin, particularly in brain regions that myelinate later developmentally. Research integrating behavioral measures with DTI indicates that WM integrity supports the communication among cortical networks, particularly those involving executive function, perceptual speed, and memory (i.e., fluid cognition). In the absence of significant disease, age shares a substantial portion of the variance associated with the relation between WM integrity and fluid cognition. Current data are consistent with one model in which age-related decline in WM integrity contributes to a decreased efficiency of communication among networks for fluid cognitive abilities. Neurocognitive disorders for which older adults are at risk, such as depression, further modulate the relation between WM and cognition, in ways that are not as yet entirely clear. Developments in DTI technology are providing a new insight into both the neurobiological mechanisms of aging WM and the potential contribution of DTI to understanding functional measures of brain activity. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.