Facilitation of Extinction of Conditioned Fear by D-Cycloserine

Abstract— Excessive fear and anxiety are characteristic of disorders such as post-traumatic stress disorder (PTSD) and phobias and are believed to reflect abnormalities in neural systems governing the development and reduction of conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposure to a feared stimulus in the absence of an aversive event leads to a gradual reduction in the fear response to that stimulus. Like conditioned fear learning, extinction is dependent on a particular protein (the N-methyl-D-aspartate or NMDA receptor) in a part of the brain called the amygdala. Blockade of this receptor blocks extinction and improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Because exposure-based psychotherapy for fear disorders in humans resembles extinction in several respects, we investigated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with findings from the animal laboratory, patients receiving D-cycloserine benefited more from exposure-based psychotherapy than did placebo-treated controls. Although very preliminary, these data provide initial support for the use of cognitive enhancers in psychotherapy and demonstrate that preclinical studies in rodents can have direct benefits to humans.     

SIMPLIFYING HEURISTICS VERSUS CAREFUL THINKING: SCIENTIFIC ANALYSIS OF MILLENNIAL SPIRITUAL ISSUES

There is ample evidence that humans (and other primates) possess a knowledge instinct—a biologically driven impulse to make coherent sense of the world at the highest level possible. Yet behavioral decision‐making data suggest a contrary biological drive to minimize cognitive effort by solving problems using simplifying heuristics. Individuals differ, and the same person varies over time, in the strength of the knowledge instinct. Neuroimaging studies suggest which brain regions might mediate the balance between knowledge expansion and heuristic simplification. One region implicated in primary emotional experience is more activated in individuals who use primitive heuristics, whereas two areas of the cortex are more activated in individuals with a strong knowledge drive: one region implicated in detecting risk or conflict and another implicated in generating creative ideas. Knowledge maximization and effort minimization are both evolutionary adaptations, and both are valuable in different contexts. Effort minimization helps us make minor and routine decisions efficiently, whereas knowledge maximization connects us to the beautiful, to the sublime, and to our highest aspirations. We relate the opposition between the knowledge instinct and heuristics to the biblical story of the fall, and argue that the causal scientific worldview is mathematically equivalent to teleological arguments from final causes. Elements of a scientific program are formulated to address unresolved issues.     

Cognitive Emotion Regulation: Insights From Social Cognitive and Affective Neuroscience

ABSTRACT— Recent developments in the study of cognitive emotion regulation illustrate how functional imaging is extending behavioral analyses. Imaging studies have contributed to the development of a multilevel model of emotion regulation that describes the interactions between neural systems implicated in emotion generation and those implicated in emotional control. In this article, we review imaging studies of one type of cognitive emotion regulation: reappraisal. We show how imaging studies have contributed to the construction of this model, illustrate the interplay of psychological theory and neuroscience data in its development, and describe how this model can be used as the basis for future basic and translational research.     

Neuroimaging and Depression: Current Status and Unresolved Issues

ABSTRACT— Major depression is among the most debilitating, prevalent, and recurrent of all psychiatric disorders. Over the past decade, investigators have examined the neural mechanisms associated with this disorder. In this article we present an overview of neuroimaging research that has assessed the structure and functioning of the amygdala, subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex in major depression. We then describe results of studies that have attempted to elucidate the nature of the relations among these brain structures. The picture that emerges from these investigations is one in which heightened activity in limbic structures that underlie the experience and expression of emotion dampens activation in dorsal cortical structures that are involved in affect regulation, reducing their ability to influence limbic activation. We conclude by highlighting unresolved issues concerning the roles of these structures in depression and their relation to specific symptoms of this disorder.     

疼痛恐惧的形成及其对疼痛知觉的影响

脑岛、杏仁核是疼痛恐惧形成的重要神经网络中心。疼痛恐惧增强了慢性疼痛患者的疼痛知觉体验, 进而加剧抑郁、焦虑情绪和功能损伤程度。脑岛、杏仁核、前额皮层和前扣带回是疼痛恐惧影响疼痛知觉的重要神经基础。通过认知方法干预疼痛恐惧可以改善患者的抑郁、焦虑情绪, 减少功能损伤。未来研究应拓展疼痛恐惧的测量工具, 采用功能磁共振成像技术进一步揭示疼痛恐惧影响慢性疼痛患者疼痛知觉的神经机制。     

Inactivation of the basolateral amygdala impairs the retrieval of recent and remote taste-potentiated odor aversion memory

Memory reorganization as a time-dependent process can be investigated using various learning tasks such as the taste-potentiated odor aversion (TPOA). In this paradigm rats acquire a strong aversion to an olfactory cue presented simultaneously with a gustatory cue. Together these cues are paired with a delayed visceral illness. The basolateral amygdaloid nucleus (BLA) plays a key role in TPOA acquisition but its involvement in retrieval remains unclear. We investigated the involvement of the BLA in either recent or remote retrieval of TPOA. In each case, the number of licks observed in response to the presentation of either the odor or the taste was used to assess retrieval. Before the retrieval test, rats received a bilateral infusion of lidocaine to inactivate the BLA. We observed that both recent and remote TPOA retrieval tests induced by the odor presentation were disrupted in the lidocaine-injected rats. By contrast, the BLA inactivation had no effect upon the aversion towards the taste cue regardless of the time of retrieval. The present study provides evidence that BLA functioning is necessary for retrieval of aversive odor memory, even with a long post-acquisition delay.     

社会认知的神经基础

人类的社会技能高于其它任何动物,能够形成对社会环境的高级表征,并能利用这些表征进行十分灵活的推理判断。但是社会认知的神经基础目前仍不十分明了。来自于人类和其它灵长类动物的研究已经发现有一些脑结构（如杏仁核、前额叶、颞上沟、扣带前回等）在社会认知中起着特殊重要的作用。此外,越来越多的研究表明其它一些脑区结构（如右侧躯体体感区、岛叶、基底节、白质等）也共同参与社会认知加工过程。文章对近年来关于社会认知的神经基础研究做了较为详细的综述。     

Unique characteristics of neonatal classical conditioning: The role of the amygdala and locus coeruleus

The central nervous system of altricial infants is specialized for optimizing attachments to their caregiver. During the first postnatal days, infant rats show a sensitive period for learning and particularly susceptible to learning an attraction to their mother’s odor. Classical conditioning appears to underlie this learning that is expressed behaviorally as anincreased ability to acquire odor preferences and a decreased ability to acquire odor aversions. Specifically, in neonatal rats, pairing an odor with moderately painful shock (0.5mA) or milk produces a subsequent relativepreference for that odor. The neural circuitry supporting theincreased ability to acquire odor preferences appears to be the heightened functioning of the noradrenergic pontine nucleus locus coeruleus. Indeed, norepinephrine from the locus coeruleus appears to be both necessary and sufficient for learning during the sensitive period. On the other hand, thedecreased ability to acquire odor aversions seems to be due to the lack of participation of the amygdala in at least some aversive learning situations. The site of plasticity in the pup’s brain appears to be limited to the olfactory bulb. This neonatal sensitive period for learning ends around postnatal day 9–10, at which time pups make the transition from crawling to walking and classical conditioning becomes “adultlike”. The neonatal behavioral and neural induced changes are retained into adulthood where it modifies sexual behavior.     

The role of the amygdala in emotional experience during retrieval of personal memories

ABSTRACT

Although the role of the amygdala in emotional memory retrieval has long been established, how such engagement varies depending on valence and retrieval context is less clearly understood. Participants retrieved personal memories associated with primarily positive, primarily negative, and mixed-valence images, pressing a button when successful. The button press divided trials into search and elaboration phases. Participants provided positivity and negativity ratings immediately following each trial, and then again in a post-retrieval survey. The relation between amygdala recruitment and emotionality exhibited a four-way interaction, with no other significant main effects or interactions. The interaction was driven by a temporal shift in the role of amygdala recruitment during retrieval of memories associated with mixed-valence images: Negativity ratings were supported more by search-related activity whereas positivity was more strongly associated with elaboration. Amygdala activity during retrieval relates to emotional experience in more complicated ways than previously understood. When participants were able to consider positive and negative aspects of the same event, amygdala recruitment during search and elaboration were associated with opposite behavioural effects. Such findings suggest that the amygdala may support distinct aspects of emotional experience for the same memory depending on when during retrieval it is recruited.