Neurons in medial prefrontal cortex signal memory for fear extinction

Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.     

Neuronal correlates of parametric working memory in the prefrontal cortex.

Humans and monkeys have similar abilities to discriminate the difference in frequency between two mechanical vibrations applied sequentially to the fingertips. A key component of this sensory task is that the second stimulus is compared with the trace left by the first (base) stimulus, which must involve working memory. Where and how is this trace held in the brain? This question was investigated by recording from single neurons in the prefrontal cortex of monkeys while they performed the somatosensory discrimination task. Here we describe neurons in the inferior convexity of the prefrontal cortex whose discharge rates varied, during the delay period between the two stimuli, as a monotonic function of the base stimulus frequency. We describe this as 'monotonic stimulus encoding', and we suggest that the result may generalize: monotonic stimulus encoding may be the basic representation of one-dimensional sensory stimulus quantities in working memory. Thus we predict that other behavioural tasks that require ordinal comparisons between scalar analogue stimuli would give rise to monotonic responses similar to those reported here.     

Single neurons in prefrontal cortex encode abstract rules.

The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules.     

The role of the anterior prefrontal cortex in human cognition.

Complex problem-solving and planning involve the most anterior part of the frontal lobes including the fronto-polar prefrontal cortex (FPPC), which is especially well developed in humans compared with other primates. The specific role of this region in human cognition, however, is poorly understood. Here we show, using functional magnetic resonance imaging, that bilateral regions in the FPPC alone are selectively activated when subjects have to keep in mind a main goal while performing concurrent (sub)goals. Neither keeping in mind a goal over time (working memory) nor successively allocating attentional resources between alternative goals (dual-task performance) could by themselves activate these regions. Our results indicate that the FPPC selectively mediates the human ability to hold in mind goals while exploring and processing secondary goals, a process generally required in planning and reasoning.     

Categorization of behavioural sequences in the prefrontal cortex

Although it has long been thought that the prefrontal cortex of primates is involved in the integrative regulation of behaviours, the neural architecture underlying specific aspects of cognitive behavioural planning has yet to be clarified. If subjects are required to remember a large number of complex motor sequences and plan to execute each of them individually, categorization of the sequences according to the specific temporal structure inherent in each subset of sequences serves to facilitate higher-order planning based on memory. Here we show, using these requirements, that cells in the lateral prefrontal cortex selectively exhibit activity for a specific category of behavioural sequences, and that categories of behaviours, embodied by different types of movement sequences, are represented in prefrontal cells during the process of planning. This cellular activity implies the generation of neural representations capable of storing structured event complexes at an abstract level, exemplifying the development of macro-structured action knowledge in the lateral prefrontal cortex.     

NR1基因敲除对小鼠前额叶脑区LTP的影响

用前脑特异性NR1基因敲除小鼠,采用离体脑片场电位技术,研究了NR1亚基在前额叶脑区突触可塑性中的作用.刺激强度—反应(input-output curve)和双脉冲抑制反应(paired pulse depression, PPD)的结果表明,与同窝对照组小鼠相比,NR1基因敲除小鼠前额叶脑区的基本突触传递无明显变化.采用高频刺激(100 Hz, 1 000 ms ×2, 间隔30 s)在小鼠的前额叶脑区诱导长时程增强(long-term potentiation, LTP),与对照组小鼠相比,NR1基因敲除小鼠前额叶脑区的LTP明显受损.以上数据提示,NR1亚基在前额叶脑区LTP的诱导中起着重要的作用.     

Watching cartoons activates the medial prefrontal cortex in children

The medial prefrontal cortex (MPFC) of human adults is involved in attributing mental states to real human agents but not to virtual artificial characters. This study examined whether such differential MPFC activity can be observed in children who are more fascinated by cartoons than adults. We measured brain activity using functional magnetic resonance imaging (fMRI) while 10-year-old children watched movie and cartoon clips, simulating real and virtual visual worlds, respectively. We showed neuroimaging evidence that, in contrast to adults, the MPFC of children was activated when perceiving both human agents and artificial characters in coherent visual events. Our findings suggest that, around the age of 10 years, the MPFC activity in children is different from that in adults in that it can be spontaneously activated by non-human agents in a virtual visual world.     

Long-term potentiation of prefrontal cortex in NR1 knockout mice

利用前脑特异性NR1基因敲除小鼠,采用离体脑片场电位技术,研究了NR1亚基在前额叶脑区突触可塑性中的作用.刺激强度—反应( input-output curve)和双脉冲抑制反应(paired pulse depression,PPD)的结果表明,与同窝对照组小鼠相比,NR1基因敲除小鼠前额叶脑区的基本突触传递无明显变化.采用高频刺激(100 Hz,1 000 ms×2,间隔30 s)在小鼠的前额叶脑区诱导长时程增强( long-term potentiation,LTP),与对照组小鼠相比,NR1基因敲除小鼠前额叶脑区的LTP明显受损.以上数据提示,NR1亚基在前额叶脑区LTP的诱导中起着重要的作用.     

前额叶Gamma频段tACS对工作记忆影响的研究

基于行为学与脑电(Electroencephalogram EEG) 特征评估40Hz经颅交流电刺激（transcranial alternating current stimulation, tACS）对工作记忆的影响,进一步探究40Hz经颅交流电刺激对脑电与认知功能的调节作用。选取34名被试,并在伪刺激或真刺激后参与工作记忆任务,同时采集被试的行为学数据与脑电数据,最终通过MATLAB与SPSS-26.0进行数据分析,得出40Hz经颅交流电刺激对脑电、行为学数据指标的影响。通过数据分析发现事件相关电位中P3a成分与P3b成分的幅值在不同刺激、不同任务量下表现出显著性,且被试在真刺激后顶叶区的theta-gamma相位幅值耦合显著提升。因此可以得出40Hz经颅交流电刺激使得事件相关电位(Event-related potential, ERP)相关成分幅值有显著变化,且能显著提升被试脑内的相位幅值耦合程度,从而提升了专注度,进而显著提升工作记忆的能力,使得相关行为学数据显著提高。     

Different time courses of learning-related activity in the prefrontal cortex and striatum

To navigate our complex world, our brains have evolved a sophisticated ability to quickly learn arbitrary rules such as 'stop at red'. Studies in monkeys using a laboratory test of this capacity--conditional association learning--have revealed that frontal lobe structures (including the prefrontal cortex) as well as subcortical nuclei of the basal ganglia are involved in such learning. Neural correlates of associative learning have been observed in both brain regions, but whether or not these regions have unique functions is unclear, as they have typically been studied separately using different tasks. Here we show that during associative learning in monkeys, neural activity in these areas changes at different rates: the striatum (an input structure of the basal ganglia) showed rapid, almost bistable, changes compared with a slower trend in the prefrontal cortex that was more in accordance with slow improvements in behavioural performance. Also, pre-saccadic activity began progressively earlier in the striatum but not in the prefrontal cortex as learning took place. These results support the hypothesis that rewarded associations are first identified by the basal ganglia, the output of which 'trains' slower learning mechanisms in the frontal cortex.     

Top-down gain control of the auditory space map by gaze control circuitry in the barn owl

High-level circuits in the brain that control the direction of gaze are intimately linked with the control of visual spatial attention. Immediately before an animal directs its gaze towards a stimulus, both psychophysical sensitivity to that visual stimulus and the responsiveness of high-order neurons in the cerebral cortex that represent the stimulus increase dramatically. Equivalent effects on behavioural sensitivity and neuronal responsiveness to visual stimuli result from focal electrical microstimulation of gaze control centres in monkeys. Whether the gaze control system modulates neuronal responsiveness in sensory modalities other than vision is unknown. Here we show that electrical microstimulation applied to gaze control circuitry in the forebrain of barn owls regulates the gain of midbrain auditory responses in an attention-like manner. When the forebrain circuit was activated, midbrain responses to auditory stimuli at the location encoded by the forebrain site were enhanced and spatial selectivity was sharpened. The same stimulation suppressed responses to auditory stimuli represented at other locations in the midbrain map. Such space-specific, top-down regulation of auditory responses by gaze control circuitry in the barn owl suggests that the central nervous system uses a common strategy for dynamically regulating sensory gain that applies across modalities, brain areas and classes of vertebrate species. This approach provides a path for discovering mechanisms that underlie top-down gain control in the central nervous system.     

Recollection-like memory retrieval in rats is dependent on the hippocampus

Recognition memory may be supported by two independent types of retrieval, conscious recollection of a specific experience and a sense of familiarity gained from previous exposure to particular stimuli. In humans, signal detection techniques have been used to distinguish recollection and familiarity, respectively, in asymmetrical and curvilinear components of their receiver operating characteristic (ROC) curves, standard curves that represent item recognition across different levels of confidence or bias. To determine whether animals also employ multiple processes in recognition memory and to explore the anatomical basis of this distinction, we adapted these techniques to examine odour recognition memory in rats. Their ROC curve had asymmetrical and curvilinear components, indicating the existence of both recollection and familiarity in rats. Furthermore, following selective damage to the hippocampus the ROC curve became entirely symmetrical and remained curvilinear, supporting the view that the hippocampus specifically mediates the capacity for recollection.     

记忆与执行功能及有关精神健康的认知神经科学研究

中国科学技术大学1999年建立了脑功能与医学成像联合实验室, 其主要研究方向是:以认知心理学、脑功能成像(fMRI、ERP)等认知神经科学的方法,研究高级认知功能(工作记忆、选择性注意、执行控制、决策等);及相关的认知障碍和精神健康,如老年人和神经内分泌疾病病人的记忆功能、网络游戏成瘾等.在这些方面已经获得了一些有意义的结果. 今后将进一步关注积极心理学中的重要问题,如情绪及幸福感的认知神经机制等.     

Protein methylation in behavioural control mechanisms and in signal transduction.

In both prokaryotes and eukaryotes methyl groups can be added to and removed from the carboxyl groups of proteins. Recent work has revealed that these reactions have a role in several behavioural phenomena. The nature of this role has been uncovered in one case--that of bacterial chemotaxis.     

控制职能对大学执行力的影响

以我国部分高等院校为研究对象,在总结国内外学者关于执行力影响因素的研究结论基础上,构建了控制职能对大学执行力影响因素模型.研究结果显示控制职能的两个方面,即确立标准与信息沟通,对大学执行力水平影响显著.提出了加强大学管理控制职能,促进大学执行力水平提高的建议.     

Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory

Cortical plasticity seems to be critical for the establishment of permanent memory traces. Little is known, however, about the molecular and cellular processes that support consolidation of memories in cortical networks. Here we show that mice heterozygous for a null mutation of alpha-calcium-calmodulin kinase II (alpha-CaMKII+/-) show normal learning and memory 1-3 days after training in two hippocampus-dependent tasks. However, their memory is severely impaired at longer retention delays (10-50 days). Consistent with this, we found that alpha-CaMKII+/- mice have impaired cortical, but not hippocampal, long-term potentiation. Our results represent a first step in unveiling the molecular and cellular mechanisms underlying the establishment of permanent memories, and they indicate that alpha-CaMKII may modulate the synaptic events required for the consolidation of memory traces in cortical networks.     

Capacity limit of visual short-term memory in human posterior parietal cortex

At any instant, our visual system allows us to perceive a rich and detailed visual world. Yet our internal, explicit representation of this visual world is extremely sparse: we can only hold in mind a minute fraction of the visual scene. These mental representations are stored in visual short-term memory (VSTM). Even though VSTM is essential for the execution of a wide array of perceptual and cognitive functions, and is supported by an extensive network of brain regions, its storage capacity is severely limited. With the use of functional magnetic resonance imaging, we show here that this capacity limit is neurally reflected in one node of this network: activity in the posterior parietal cortex is tightly correlated with the limited amount of scene information that can be stored in VSTM. These results suggest that the posterior parietal cortex is a key neural locus of our impoverished mental representation of the visual world.