New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders

Serotonin (5-HT) modulates numerous processes in the central nervous system that are relevant to neuropsychiatric function and dysfunction. It exerts significant effects on anxiety, mood, impulsivity, sleep, ingestive behavior, reward systems, and psychosis. Serotonergic dysfunction has been implicated in several psychiatric conditions but efforts to more clearly understand the mechanisms of this influence have been hampered by the complexity of this system at the receptor level. There are at least 14 distinct receptors that mediate the effects of 5-HT as well as several enzymes that control its synthesis and metabolism. Pharmacologic agents that target specific receptors have provided clues regarding the function of these receptors in the human brain. 5-HT is also an important modulator of neural development and several groups have employed a genetic strategy relevant to behavior. Several inactivation mutations of specific 5-HT receptors have been generated producing interesting behavioral phenotypes related to anxiety, depression, drug abuse, psychosis, and cognition. In many cases, knockout mice have been used to confirm what has already been suspected based on pharmacologic studies. In other instances, mutations have demonstrated new functions of serotonergic genes in development and behavior.     

Multiple serotonergic mechanisms contributing to sensitization in aplysia: evidence of diverse serotonin receptor subtypes

The neurotransmitter serotonin (5-HT) plays an important role in memory encoding in Aplysia. Early evidence showed that during sensitization, 5-HT activates a cyclic AMP-protein kinase A (cAMP-PKA)-dependent pathway within specific sensory neurons (SNs), which increases their excitability and facilitates synaptic transmission onto their follower motor neurons (MNs). However, recent data suggest that serotonergic modulation during sensitization is more complex and diverse. The neuronal circuits mediating defensive reflexes contain a number of interneurons that respond to 5-HT in ways opposite to those of the SNs, showing a decrease in excitability and/or synaptic depression. Moreover, in addition to acting through a cAMP-PKA pathway within SNs, 5-HT is also capable of activating a variety of other protein kinases such as protein kinase C, extracellular signal-regulated kinases, and tyrosine kinases. This diversity of 5-HT responses during sensitization suggests the presence of multiple 5-HT receptor subtypes within the Aplysia central nervous system. Four 5-HT receptors have been cloned and characterized to date. Although several others probably remain to be characterized in molecular terms, especially the Gs-coupled 5-HT receptor capable of activating cAMP-PKA pathways, the multiplicity of serotonergic mechanisms recruited into action during learning in Aplysia can now be addressed from a molecular point of view.     

An evaluation of early and late stage attentional processing of positive and negative information in dysphoria

Depressive disorders may be characterised by hyperattention toward negative information, hypoattention toward positive information, or a combination of both processing biases. In two studies, a dot-probe task was utilised to better ascertain the specific direction and time-course of these biases. In both studies, the dysphoric group showed significantly less attentional allocation toward positive stimuli than the non-dysphoric group. In study two, the dysphoric group also showed greater attentional allocation toward depression-specific stimuli. Importantly, the bias toward depression-specific stimuli, and the bias away from positive stimuli, were uncorrelated with each other. It may be that both biases can act as sufficient, but not necessary, characteristics of dysphoric processing. An additional possibility is that the relative level of each bias type may best characterise dysphoric processing. Each of these possibilities is discussed in turn.     

Exposure to disgust-evoking imagery and information processing biases in blood-injection-injury phobia

Biased processing of threat-relevant information is a central construct among contemporary theories of anxiety. However, biases in attentional and memory processes have not been systematically investigated in blood-injection-injury (BII) phobia. Theory has suggested that disgust rather than fear characterizes BII phobia and may mediate processing biases differently. We investigated the effects of a disgust mood induction on attention and memory in BII phobic and nonphobic participants. The Stroop task failed to demonstrate an attentional bias toward medical and disgust words, even under conditions of disgust provocation. However, an implicit memory task showed that BII phobics completed more medical and disgust word stems than nonphobics. These results suggest that BII phobia may be characterized by a similar implicit memory, but not an attentional, bias found in other anxiety disorders. As such, information processing in BII phobia may be qualitatively different from other anxiety disorders. Implications for further research regarding information processing biases in BII phobia are discussed.     

Centrally elicited aggressive behavior: A model system for the study of episodic neurobehavioral pathologies?

Studies in which the predatory-like attack of a cat upon a rat has been elicited by electrical brain stimulation have been briefly reviewed with an emphasis on the question of where within the central nervous system such brain stimulation is producing its behaviorally meaningful effects. Two opposing but by no means mutually exclusive views are considered. The first is that brain stimulation elicits this behavior pattern primarily because it affects a specific motivated behavior system that is organized discretely in the midbrain and pons. The second is that forebrain neural activity is modulated in behaviorally significant ways by brainstem stimulation, which elicits predatory-like aggressive behavior in the cat. The possibility that further research on the altered state of central nervous system activity, induced by brain stimulation which elicits aggressive behavior in the cat, may lead to a further understanding of the altered states of central nervous system activity that underlie the aggressive dyscontrol syndrome and other episodic state disorders is discussed.     

Demythologizing the emotions: adaptation,cognition, and visceral representations of emotion in the nervous system

This article highlights four issues about the neurobiology of emotions: adaptation vs. dysfunction, peripheral and central representations of emotion, the regulation of the internal milieu, and whether emotions are cognitive. It is argued that the emotions evolved to play diverse adaptive roles and are biologically vital sources of information processing. They were not designed as pieces of pathology, though they certainly can underlie some psychophathologies. Emotions are, in part, appraisal systems that are operative at numerous level of the nervous system from the brainstem to the cortex. Like other information processing systems they are not perfect cognitive systems. Emotional systems often utilize somatic and visceral information for appraisals of events to facilitate decisions of whether to approach or avoid objects. The neural systems of emotions traverse the entire neural axis and are linked to the regulation of the internal milieu. Thus, in addition to the experiential aspects of emotions, emotions embody appraisal systems that are pervasive to all levels of the brain to facilitate function, adaptation, and survival.     

疼痛恐惧相关的注意偏向及其矫正

疼痛恐惧是影响和维持慢性痛的重要因素。不同材料和被试类型情况下, 疼痛恐惧均主要作用于个体对疼痛相关信息的早期注意加工阶段, 表现为注意警觉模式。该注意模式使个体将注意维持在疼痛上, 从而干扰了对非疼信息的注意能力。矫正疼痛恐惧相关注意偏向可以改善疼痛体验。未来研究应采用更具生态效度的任务测量疼痛恐惧相关的注意偏向及其神经基础, 进一步考察矫正疼痛恐惧相关注意偏向能否改善慢痛患者的忧郁和功能丧失等问题。     

On the role of space and time in auditory processing

Unlike visual and tactile stimuli, auditory signals that allow perception of timbre, pitch and localization are temporal. To process these, the auditory nervous system must either possess specialized neural machinery for analyzing temporal input, or transform the initial responses into patterns that are spatially distributed across its sensory epithelium. The former hypothesis, which postulates the existence of structures that facilitate temporal processing, is most popular. However, I argue that the cochlea transforms sound into spatiotemporal response patterns on the auditory nerve and central auditory stages; and that a unified computational framework exists for central auditory, visual and other sensory processing. Specifically, I explain how four fundamental concepts in visual processing play analogous roles in auditory processing.     

Broadening of activity with flow across neural structures

Synfire chains have long been suggested as a substrate for perception and information processing in the nervous system. However, embedding activation chains in a densely connected nervous matrix risks spread of signal that will obscure or obliterate the message. We used computer modeling and physiological measurements in rat hippocampus to assess this problem of activity broadening. We simulated a series of neural modules with feedforward propagation and random connectivity within each module and from one module to the next. We found that activity broadened as it propagated from one module to the next. This occurred over a wide array of parameters with greater broadening seen with increasing excitatory-excitatory synaptic strength. Activity broadening correlated positively with propagation velocity. Multi-electrode measurements of activity propagation in disinhibited CA1 slice demonstrated broadening of about 50% over 1 mm. Such broadening is a problem for information transfer that must be dealt with in a fully functioning nervous system.     

大学生负面身体自我认知加工偏好

基于负面身体自我图式理论,采用词汇判断任务的实验范式,探讨负面身体自我者的认知加工偏好。研究1考察胖负面身体自我大学生对胖相关的身体信息词加工偏好,结果表明,加工胖身体相关词的编码速度比对照组显著更快,对胖消极和隐喻词偏好量大于积极词。研究2考察瘦负面身体自我大学生对瘦相关的身体信息词的加工偏好,发现对瘦相关词的编码速度显著比对照组更快,但对瘦积极词、消极词、隐喻词、形似词编码的偏好量不存在差异。结果支持负面身体自我图式指导认知加工     

BDNF serum levels in subjects developing or not post-traumatic stress disorder after trauma exposure

Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome.     

Attentional and interpretative biases in appearance concern: An investigation of biases in appearance-related information processing

The present study examined associations between high levels of appearance concern and information processing biases in interpretation and attention. An opportunity sample (N = 79) categorised ambiguous stimuli as related or unrelated to appearance. Participants then responded to the same stimuli in a modified visual dot-probe task assessing attentional bias. Participant responses were assessed in relation to level of appearance concern. The results indicated a valence specific bias towards interpretation of ambiguous stimuli as negative and appearance-related in individuals with higher levels of concern. There was also evidence of attentional bias towards information perceived as appearance-related in participants with higher levels of appearance concern. The study findings suggest that association between appearance-orientated information processing biases and level of appearance concern; this association may lead to mutually reinforcing bias and concern.     

Central localization of plasticity involved in appetitive conditioning in Lymnaea

Learning to associate a conditioned (CS) and unconditioned stimulus (US) results in changes in the processing of CS information. Here, we address directly the question whether chemical appetitive conditioning of Lymnaea feeding behavior involves changes in the peripheral and/or central processing of the CS by using extracellular recording techniques to monitor neuronal activity at two stages of the sensory processing pathway. Our data show that appetitive conditioning does not affect significantly the overall CS response of afferent nerves connecting chemosensory structures in the lips and tentacles to the central nervous system (CNS). In contrast, neuronal output from the cerebral ganglia, which represent the first central processing stage for chemosensory information, is enhanced significantly in response to the CS after appetitive conditioning. This demonstrates that chemical appetitive conditioning in Lymnaea affects the central, but not the peripheral processing of chemosensory information. It also identifies the cerebral ganglia of Lymnaea as an important site for neuronal plasticity and forms the basis for detailed cellular studies of neuronal plasticity.     

Beliefs, Persons and Practices: Beyond Tolerance

The central thesis of this paper is that, for most issues of multiculturalism, regarding them as a problem of tolerance puts us on the wrong track because there are certain biases inherent in the principle of tolerance. These biases – individualism, combined with a focus on religion and a focus on beliefs rather than on persons or practices – can be regarded as distinctly Protestant. Extending the scope of tolerance may seem a solution but if we really want to counter these biases, the principle of tolerance becomes so general that it loses any distinctive meaning. Therefore, we should accept the limited scope of tolerance and its biases. The principle of tolerance can still be useful for some problems where there is a clear and direct link to political or religious beliefs. Moreover, it should be cherished as a more general attitude or practice in Dutch society. For most problems of multiculturalism, however, we should appeal to broader theoretical frameworks that do justice to persons and practices.     

抑郁的内隐认知与治疗

认知模型认为抑郁个体存在认知加工的偏向,但是,相对于外显认知,抑郁的内隐认知研究较少。现有研究表明：抑郁个体沉迷于特定的内隐认知偏向：抑郁个体倾向于注意环境中的负性刺激;在概念驱动内隐记忆测验中表现出偏向;更可能呈现出无望感的内隐态度。内隐认知可能是抑郁个体维持抑郁的重要因素,在治疗中,可采用知觉内隐认知、扩展功能失调思维记录、记忆日志和增进注意控制等认知技术改变抑郁患者的内隐认知偏向。     

Rational learning and information sampling: on the "naivety" assumption in sampling explanations of judgment biases

Recent research has argued that several well-known judgment biases may be due to biases in the available information sample rather than to biased information processing. Most of these sample-based explanations assume that decision makers are "naive": They are not aware of the biases in the available information sample and do not correct for them. Here, we show that this "naivety" assumption is not necessary. Systematically biased judgments can emerge even when decision makers process available information perfectly and are also aware of how the information sample has been generated. Specifically, we develop a rational analysis of Denrell's (2005) experience sampling model, and we prove that when information search is interested rather than disinterested, even rational information sampling and processing can give rise to systematic patterns of errors in judgments. Our results illustrate that a tendency to favor alternatives for which outcome information is more accessible can be consistent with rational behavior. The model offers a rational explanation for behaviors that had previously been attributed to cognitive and motivational biases, such as the in-group bias or the tendency to prefer popular alternatives.     

细胞因子和抑郁症

在心理神经免疫学领域,越来越多的证据表明神经和免疫之间存在双向交流通路,免疫系统可能在一些心理精神障碍中具有重要作用。“抑郁症的细胞因子假说”认为细胞因子作为神经调质,可能在抑郁症的病因和病理过程中具有重要作用。这个假说得到了很多证据的支持。而在动物身上应用前炎性细胞因子也能够引起与人类抑郁症行为症状非常类似的“病态行为”。研究认为外周细胞因子通过信号传导进入脑内与中枢产生的细胞因子共同作用于下丘脑－垂体－肾上腺轴和5－羟色胺系统,从而导致抑郁症。细胞因子的中枢效应可以解释很多抑郁症状,“抑郁症的细胞因子假说”为探讨抑郁症状的机制和治疗抑郁症提供了一个新的视角     

听觉中脑声定位的机制

人和动物对声源方位的感知和心理确定建立在神经生理基础之上,得到了大量来自神经细胞电生理研究证据的支持。听中枢神经元可通过比较到达两耳声信号的不同特征和参量来体现其精确的声源定位能力。研究表明,声源定位过程是听觉系统复杂综合作用的结果,听觉中脑核团-下丘在这一过程中起着重要作用,下丘中大量双耳听觉反应神经元可编码声音(源)方位信息,甚至双侧下丘间的联合投射也有可能参与双耳听觉反应的调制。     

Distance perception during self-movement

The perception of distance in open fields was widely studied with static observers. However, it is a fact that we and the world around us are in continuous relative movement, and that our perceptual experience is shaped by the complex interactions between our senses and the perception of our self-motion. This poses interesting questions about how our nervous system integrates this multisensory information to resolve specific tasks of our daily life, for example, distance estimation. This study provides new evidence about how visual and motor self-motion information affects our perception of distance and a hypothesis about how these two sources of information can be integrated to calibrate the estimation of distance. This model accounts for the biases found when visual and proprioceptive information is inconsistent.     

Information processing biases and panic disorder: relationships among cognitive and symptom measures

To test cognitive models of panic disorder, a range of information processing biases were examined among persons with panic disorder (N=43) and healthy control participants (N=38). Evidence for automatic associations in memory was assessed using the Implicit Association Test, interference effects related to attention biases were assessed using a modified supraliminal Stroop task, and interpretation biases were assessed using the Brief Body Sensations Interpretation Questionnaire. In addition, the relationship between information processing biases and clinical markers of panic (including affective, behavioral, and cognitive symptom measures) was investigated, along with the relationships among biases. Results indicated more threat biases among the panic (relative to control) group on each of the information processing measures, providing some of the first evidence for an implicit measure of panic associations. Further, structural equation modeling indicated that the information processing bias measures were each unique predictors of panic symptoms, but that the bias indicators did not relate to one another. These findings suggest that cognitive factors may independently predict panic symptoms, but not covary. Results are discussed in terms of their support for cognitive models of panic and the potential for automatic versus strategic processing differences across the tasks to explain the low relationships across the biases.