Tuning the engine of cognition: a focus on NMDA/D1 receptor interactions in prefrontal cortex

The prefrontal cortex of the primate frontal lobes provides the capacity for judgment which can constantly adapt behavior in order to optimize its outcome. Adjudicating between long-term memory programs and prepotent responses, this capacity reviews all incoming information and provides an interpretation dependent on the events that have just occurred, the events that are predicted to happen, and the alternative response strategies that are available in the given situation. It has been theorized that this function requires two essential integrated components, a central executive which guides selective attention based on mechanisms of associative memory, as well as the second component, working memory buffers, in which information is held online, abstracted, and translated on a mental sketchpad of work in progress. In this review, we critically outline the evidence that the integration of these processes and, in particular, the induction and maintenance of persistent activity in prefrontal cortex and related networks, is dependent upon the interaction of dopamine D1 and glutamate NMDA receptor signaling at critical nodes within local circuits and distributed networks. We argue that this interaction is not only essential for representational memory, but also core to mechanisms of neuroadaptation and learning. Understanding its functional significance promises to reveal major new insights into prefrontal dysfunction in schizophrenia and, hence, to target a new generation of drugs designed to ameliorate the debilitating working memory deficits in this disorder.     

Using TD learning to simulate working memory performance in a model of the prefrontal cortex and basal ganglia

Delayed-response tasks (DRTs) have been used to assess working memory (WM) processes in human and nonhuman animals. Experiments have shown that the basal ganglia (BG) and dorsolateral prefrontal cortex (DLPFC) subserve DRT performance. Here, we report the results of simulation studies of a systems-level model of DRT performance. The model was trained using the temporal difference (TD) algorithm and uses an actor-critic architecture. The matrisomes of the BG represent the actor and the striosomes represent the critic. Unlike existing models, we hypothesize that the BG subserve the selection of both motor- and cognitive-related information in these tasks. We also assume that the learning of both processes is based on reward presentation. A novel feature of the model is the incorporation of delay-active neurons in the matrisomes, in addition to DLPFC. Another novel feature of the model is the subdivision of the matrisomal neurons into segregated winner-take-all (WTA) networks consisting of delay- versus transiently-active units.Our simulation model proposes a new neural mechanism to account for the occurrence of perseverative responses in WM tasks in striatal-, as well as in prefrontal damaged subjects. Simulation results also show that the model both accounts for the phenomenon of time shifting of dopamine phasic signals and the effects of partial reinforcement and reward magnitude on WM performance at both behavioral and neural levels. Our simulation results also found that the TD algorithm can subserve learning in delayed-reversal tasks.     

空难发生地高中生焦虑性心理应激的影响因素

采用《艾森克人格问卷》、自编的《空难发生地高中生心理应激问卷Ⅰ、Ⅱ》和《职业期望问卷》,分别在空难发生后一周内、一年后对空难发生地和非空难发生地重点中学高中生进行问卷调查,探究空难发生地不同人格特征和不同职业期望高中生在空难发生后心理应激的差异。结果表明：高职业期望和高神经质是空难发生地高中生焦虑性心理应激水平的影响因素;突发事件预案中应考虑中学生这一特殊群体的心理干预工作。     

表象建构的面积评估

通过视觉或触觉给被试呈现完整的三角形,或呈现构成一个三角形所必要而又充分的一组部件以在表象上形成一个三角形,并评估其大小。结果发现,被试在表象中利用部件建构起来的三角形面积的增长,与实际知觉的三角形一样,均遵从幂函数定律,且幂函数指数均小于１,显示出表象与知觉的机能等价。     

The neural basis of cognitive control: Response selection and inhibition

The functional neuroanatomy of tasks that recruit different forms of response selection and inhibition has to our knowledge, never been directly addressed in a single fMRI study using similar stimulus–response paradigms where differences between scanning time and sequence, stimuli, and experimenter instructions were minimized. Twelve right-handed participants were scanned on two standard cognitive control tasks, a stimulus–response incompatibility task, and a response inhibition task. A compound trial design allowed comparison of preparing to inhibit an upcoming automatic response to wholly inhibiting an automatic response. Furthermore, inhibiting an automatic response to perform an alternative task-relevant response was compared to wholly inhibiting an automatic response. No differences were found in prefrontal activity when preparing to inhibit an automatic response was compared to wholly inhibiting an automatic response, suggesting a mostly common network. The left inferior frontal gyrus was found to be commonly recruited during both tasks when controlled responses were required, likely due to its role in response selection. In contrast, the right inferior frontal gyrus was found to be more involved when task demands were stronger for response inhibition. Our results are largely consistent with models of cognitive control that postulate that separate psychological constructs, such as response selection and inhibition, are related processes largely served by a common prefrontal network. This prefrontal network is recruited to a greater or lesser extent depending on specific task demands.     

The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response

We designed an animal model to examine the mechanisms of differences in individual responses to aversive stimuli. We used the rat freezing response in the context fear test as a discriminating variable: low responders (LR) were defined as rats with a duration of freezing response one standard error or more below the mean value, and high responders (HR) were defined as rats with a duration of freezing response one standard error or more above the mean value. We sought to determine the colocalisation of c-Fos and glucocorticoid receptors-immunoreactivity (GR-ir) in HR and LR rats subjected to conditioned fear training, two extinction sessions and re-learning of a conditioned fear. We found that HR animals showed a marked decrease in conditioned fear in the course of two extinction sessions (16 days) in comparison with the control and LR groups. The LR group exhibited higher activity in the cortical M2 and prelimbic areas (c-Fos) and had an increased number of cells co-expressing c-Fos and GR-ir in the M2 and medial orbital cortex after re-learning a contextual fear. HR rats showed increased expression of c-Fos, GR-ir and c-Fos/GR-ir colocalised neurons in the basolateral amygdala and enhanced c-Fos and GR-ir in the dentate gyrus (DG) in comparison with LR animals. Our data indicate that recovery of a context-related behaviour upon re-learning of contextual fear is accompanied in HR animals by a selective increase in c-Fos expression and GRs-ir in the DG area of the hippocampus.     

What has fMRI told us about the Development of Cognitive Control through Adolescence?

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic resonance imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain, and in establishing long range connections that support top-down modulation of behavior, more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed.     

Asymmetric prefrontal cortex functions predict asymmetries in number space

Little is known about the neuropsychological factors that contribute to individual differences in the asymmetric orientation along the mental number line. The present study documents healthy subjects’ preference for small numbers over large numbers in a random number generation task. This preference, referred to as “small-number bias” (SNB), varied with prefrontal functional lateralization: it was larger in participants with over-proportionately better performance in design fluency compared to letter fluency than in participants with over-proportionately better performance in letter fluency when compared to design fluency. Asymmetries in learning and memory tasks (verbal vs. non-verbal) were not related to direction or size of the SNB. We conclude that hemispheric asymmetries of specifically prefrontal executive functions are predictive of an individual’s lateral orientation bias along the mental number line. Therefore, the focus on parietal contributions to spatial-numerical associations may not be justified. Random number generation may be a helpful method to further explore these associations uncontaminated by the asymmetric involvement of response effectors.     

心理分析治疗中"界限"的概念体系及意义

从心理分析的角度出发,通过文献研究和临床方法,首次系统提出并论证了界限的概念体系及与之相应的系统行为:“界内行为”、“越界行为”、“违界行为”和“侵界行为”;并就界限设置的双重意义以及治疗师系统行为的意义进行了讨论。     

THE HUMAN BEING SHAPING AND TRANSCENDING ITSELF: WRITTEN LANGUAGE,BRAIN, AND CULTURE

Recent theological anthropology emphasizes a dynamic and integral understanding of the human being, which is also related to Karl Rahner's idea of active self‐transcendence and to the imago Dei doctrine. The recent neuroscientific discovery of the “visual word form area” for reading, regarded in light of the concept of cultural neural reuse, will produce fresh implications for the interrelation of brain biology and human culture. The theological and neuroscientific parts are shown in their mutual connections thus articulating the notion that human beings shape and transcend themselves both at the biological and at the cultural level. This will have relevant implications for the timely topic of human uniqueness in science and theology, and in proposing a new research perspective in which theology may consider culture along with its biological import, but not necessarily in strictly evolutionary terms alone.