海马-前额叶神经回路与工作记忆

学习和记忆是神经科学研究的热点。已证实大脑中的海马、前额叶和海马−前额叶回路均参与工作记忆功能。本文对海马−前额叶回路的解剖和生理特性以及海马、前额叶和海马−前额叶回路在工作记忆中的作用的研究进展做一概述。     

恒河猴,懒猴和树Qu的短时空间记忆功能与前额叶背侧部进化水平的相关性

本文研究探讨了进化地位不同的三种动物的短时空间记忆功能及其与前额叶背侧部进化水平的相关性。结果表明,在延缓反应作业中,经1000次训练后,7只恒河猴对空间位置的记忆时间平均为7.7±3.2 min,懒猴为3.8±0.44 min,而树qu即使在延缓时间几乎为零秒的延缓反应中,其正确反应率也未达到90%标准。一种延缓时间仅测试一个单元,即不经训练的实验表明,恒河猴在延缓期为“0”-5 min的各测试单元中,正确反应率稳定在80%以上;懒猴在延缓时间为“0”-4 min的各测试单元中,平均正确反应率与恒河猴无明显差异,而当延缓时间增加到5 min时,在延缓反应作业中取得的成绩显著下降;树qu在延缓时间为1-5 min的作业中取得的正确反应率在70%以下。3种动物在视觉辨别学习作业中却无明显差异。形态学研究表明,灵长类大脑前额叶的面积和结构的复杂性在进化过程中逐渐增大,如恒河猴大脑前额叶的表面积占大脑半球表面积的11.5%（Brodmann,1929）,其内颗粒层发达,背侧部明显凸起,主沟区发达;懒猴的前额叶表面积占其大脑半球表面积的8.3%,背侧部凸起不显著,主沟未形成,额极内颗粒层分化明显,背侧部的内颗粒层较内侧部的发达程度差（Sanides,1967）;树qu的前额叶表面积占7.5%,额极的内颗粒层分化不明显,为非颗粒化区,此区之后为颗粒区和运动前区,颗粒区背侧部的发育程度明显较内侧部差。恒河猴前额叶损伤研究结果表明,短时空间记忆功能依赖前额叶背侧部的完整性。本研究提示,短时空间记忆功能的发达程度与大脑前额叶背侧部的进化程度有相关性。     

前额叶皮层和纹状体的局域场电位的功率编码奖励信息

前额叶皮层和纹状体是大脑内两个重要的区域,研究表明它们都参与了许多高级认知过程,如学习记忆、奖励信息处理、行为决策等。单细胞电生理记录实验已显示前额叶皮层和纹状体的神经元能够编码奖励信息,但不清楚这两个区域的局域场电位(local field potential,LFP)是否也能编码奖励信息。为研究这个问题,当猴子在进行一个奖励预测实验时,用多通道电极同时记录了前额叶皮层和纹状体的LFP。采用短时傅里叶变换,将记录的LFP转换为时、频域上的信号,比较不同奖励条件(大容量水奖励和小容量水奖励)下功率值的分布。结果显示前额叶皮层和纹状体的LFP的功率能够区分不同的奖励条件,并且小容量水奖励条件下的功率值大于大容量水奖励条件下的功率值;进一步研究显示LFP在β频段(14~30 Hz)能更好地编码奖励信息。以上结果表明前额叶皮层和纹状体的LFP能够有效地编码奖励信息,有助于进一步理解LFP在处理奖励信息过程中的作用。     

基于非线性Wigner-Ville分析的多通道局部场电位θ和γ同步振荡对大鼠工作记忆事件的编码

基于非线性Wigner-Ville distribution(WVD)方法,对大鼠在工作记忆过程中前额叶皮层多通道局部场电位(local field potentials,LFPs)进行相位同步分析,研究LFPs与工作记忆有关的θ及γ频段的同步振荡模式及其对工作记忆事件的编码.实验数据为大鼠在工作记忆过程中前额叶皮层的...     

恒河猴、懒猴和树鼩的短时空间记忆功能与前额叶背侧部进化水平的相关性(英文)

本文研究探讨了进化地位不同的三种动物的短时空间记忆功能及其与前额叶背侧部进化水平的相关性。结果表明,在延缓反应作业中,经1000次训练后,7只恒河猴对空间位置的记忆时间平均为7.7±3.2min,懒猴为3.8±0.44min,而树鼩即使在延缓时间几乎为零秒的延缓反应中,其正确反应率也未达到90％标准。一种延缓时间仅测试一个单元,即不经训练的实验表明,恒河猴在延缓期为“0”—5min的各测试单元中,正确反应率稳定在80％以上;懒猴在延缓时间为“0”—4min的各测试单元中,平均正确反应率与恒河猴无明显差异,而当延缓时间增加到5min时,在延缓反应作业中取得的成绩显著下降;树鼩在延缓时间为1—5min的作业中取得的正确反应率在70％以下。3种动物在视觉辨别学习作业中却无明显差异。形态学研究表明,灵长类大脑前额叶的面积和结构的复杂性在进化过程中逐渐增大,如恒河猴大脑前额叶的表面积占大脑半球表面积的11.5％(Brodmann,1929),其内颗粒层发达,背侧部明显凸起,主沟区发达;懒猴的前额叶表面积占其大脑半球表面积的8.3％,背侧部凸起不显著,主沟未形成,额极内颗粒层分化明显,背侧部的内颗粒层较内侧部的发达程度差(Sanides,1967);树鼩的前额叶表面积占7.5％,额极的内颗粒层分化不明显,为非颗粒化区,此区之后为颗粒区     

内侧前额叶在“延迟期间”电活动对工作记忆任务学习的贡献

<正>"工作记忆"(working memory)是一种重要的短时程记忆,它负责对实时信息进行短暂的储存和运用。这个短暂储存的时间被称为记忆的"延迟期"(delay period)[1-3]。比如在做心算时(例如17×24),大脑需要按照运算法则对不同数位的数字进行依次运算,而中间结果需要在记忆延迟期内暂时存储下来,最后得到计算结果。又如在打电话时,当被告知一个陌生号码时,我们需要在工作记忆中把这个号     

本刊编委FraserA．W．Wilson博士简介

Fraser A.W.Wilson博士1983年毕业于牛津大学实验心理学系,后到耶鲁大学医学院,从师于著名的神经科学学家Goldman-Rakic研究员,长期从事非人灵长类前额叶功能的研究。1996年到美国Arizona大学心理学系就职。其间,发表了很多实验论文。其中,1993年以第一作者在Science发表有关前额叶功能的论文,该文至今仍是前额叶研究的经典文献。1997年,与其他研究人员合作,再次在Science上发表另一篇有关前额叶的研究论文。他的主要发现是:背侧前额叶主要涉及到“以头为中心”的空间坐标系。在猕猴前额叶研究中作出了突出贡献。2005年1月,Wilson博士从…     

大脑前额叶皮层与免疫机能的关系Ⅰ.损毁前额叶皮层对猕猴淋巴细胞免疫机能的影响

用临床细胞免疫学检测方法,对损毁大脑前额叶背外侧部皮层手术前、手术后７天和手术后３０天的猕猴外周血液淋巴细胞的４种免疫花环（Ｅｔ、Ｅａ、ＺＹＣ和ＭＥ花环）进行了跟踪监测,并与假手术组进行对照。结果表明：损毁大脑前额叶皮层后,其外周血活化Ｔ淋巴细胞花环率（Ｅａ）和Ｂ淋巴细胞的小鼠红细胞花环率（ＭＥ）均在手术后７天显著下降;直到手术后３０天仍显著低于手术前。而总Ｔ淋巴细胞花环率（Ｅｔ）和酵母多糖补体复合物花环率（ＺＹＣ）则在手术后７天显著下降,在手术后３０天又回复。这些结果提示：大脑前额叶皮层对机体免疫机能具有一定的调节联系作用,损毁大脑前额叶皮层后,可引起机体淋巴细胞免疫功能下降,其作用机理尚待进一步研究     

间歇性θ节律经颅磁刺激改善大鼠工作记忆的海马与前额叶跨脑区神经网络效应研究

目的 间歇性θ节律刺激（iTBS）作为一种新型的经颅磁刺激模式，已经广泛应用于探索大脑认知功能和神经调控等方面，但其电生理调控机制尚不清晰，探索iTBS对大脑认知功能的影响及其电生理机制，对脑疾病的治疗和磁刺激的临床应用具有重要意义。方法 本文利用iTBS制备磁刺激大鼠模型，采集记录大鼠在执行工作记忆（WM）任务过程中腹侧海马（vHPC）和内侧前额叶皮层（mPFC）的局部场电位（LFPs）信号，应用格兰杰因果网络分析方法，研究了iTBS对大鼠WM过程中vHPC与mPFC跨脑区神经网络协同和信息交互的影响。结果 iTBS增强了大鼠的学习记忆能力，使其完成工作记忆任务所需时长减少（2.67±1.63）d（P<0.05），iTBS显著改善了大鼠的行为学表现；同时iTBS增强了大鼠在WM期间vHPC与mPFC脑区的自因果网络连接，增加了网络连接强度、连接密度和全局效率（P<0.05）；并且iTBS增强了vHPC与mPFC脑区的跨脑区网络连接，增加了vHPC-mPFC跨脑区的节点度和因果流向（P<0.05）。结论 iTBS磁刺激对大鼠工作记忆行为学及相关脑区神经网络均有显著的积极作用，iTBS可以促进大鼠认知能力，提高大脑神经网络的信息交互和传递效率，iTBS的神经调控机制可能是通过增强大脑vHPC与mPFC之间的网络连接和信息交互来提高工作记忆能力。     

内侧前额叶与社会认知

早期的研究表明杏仁核、前额叶、颞上沟、前扣带回等与人类的社会认知活动有关;随着多种新技术的应用。越来越多的研究发现其它一些脑区结构(如岛叶、基底节、白质等)也与社会认知和行为有关。本文综述了内侧前额叶在社会认知中的作用,重点介绍了内侧前额叶在心灵理论、情绪认知、社会推理与决策、道德判断、自我认知等社会认知活动中的作用。未来研究希望能从整体和动态上认识内侧前额叶在社会认知活动中的作用。     

Spatial modulation of primate inferotemporal responses by eye position

Background

A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information.

Methodology/Principal Findings

We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of recorded neurons with small gaze angle shifts from central fixation. Although eye position modulates responses, it does not change shape selectivity.

Conclusions/Significance

These data demonstrate that spatial information is available in AIT for the representation of objects and scenes within a non-retinocentric frame of reference. More generally, the availability of spatial information in AIT calls into questions the classic dichotomy in visual processing that associates object shape processing with ventral structures such as AIT but places spatial processing in a separate anatomical stream projecting to dorsal structures.     

Eye position affects activity in primary auditory cortex of primates

BACKGROUND: Neurons in primary auditory cortex are known to be sensitive to the locations of sounds in space, but the reference frame for this spatial sensitivity has not been investigated. Conventional wisdom holds that the auditory and visual pathways employ different reference frames, with the auditory pathway using a head-centered reference frame and the visual pathway using an eye-centered reference frame. Reconciling these discrepant reference frames is therefore a critical component of multisensory integration. RESULTS: We tested the reference frame of neurons in the auditory cortex of primates trained to fixate visual stimuli at different orbital positions. We found that eye position altered the activity of about one third of the neurons in this region (35 of 113, or 31%). Eye position affected not only the responses to sounds (26 of 113, or 23%), but also the spontaneous activity (14 of 113, or 12%). Such effects were also evident when monkeys moved their eyes freely in the dark. Eye position and sound location interacted to produce a representation for auditory space that was neither head- nor eye-centered in reference frame. CONCLUSIONS: Taken together with emerging results in both visual and other auditory areas, these findings suggest that neurons whose responses reflect complex interactions between stimulus position and eye position set the stage for the eventual convergence of auditory and visual information.     

What makes the prefrontal cortex so appealing in the era of brain imaging? a network analytical perspective

It is thought that the prefrontal cortex (PFC) subserves cognitive control processes by coordinating the flow of information in the cerebral cortex. In the network of cortical areas the central position of the PFC makes difficult to dissociate processing and the cognitive function mapped to this region, especially when using whole brain imaging techniques, which can detect frequently activated regions. Accordingly, the present study showed particularly high rate of increase of published studies citing the PFC and imaging as compared to other fields of the neurosciences on the PubMed. Network measures used to characterize the role of the areas in signal flow indicated specialization of the different regions of the PFC in cortical processing. Notably, areas of the dorsolateral PFC and the anterior cingulate cortex, which received the highest number of citations, were identified as global convergence points in the network. These prefrontal regions also had central position in the dominant cluster consisted exclusively by the associational areas of the cortex. We also present findings relevant to models suggesting that control processes of the PFC are depended on serial processing, which results in bottleneck effects. The findings suggest that PFC is best understood via its role in cortical information processing.     

Eye position influences auditory responses in primate inferior colliculus

We examined the frame of reference of auditory responses in the inferior colliculus in monkeys fixating visual stimuli at different locations. Eye position modulated the level of auditory responses in 33% of the neurons we encountered, but it did not appear to shift their spatial tuning. The effect of eye position on auditory responses was substantial-comparable in magnitude to that of sound location. The eye position signal appeared to interact with the auditory responses in at least a partly multiplicative fashion. We conclude that the representation of sound location in primate IC is distributed and that the frame of reference is intermediate between head- and eye-centered coordinates. The information contained in these neurons appears to be sufficient for later neural stages to calculate the positions of sounds with respect to the eyes.     

Prefrontal cortex lesions impair object-spatial integration

How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC.     

Perceived surface slant is systematically biased in the actively-generated optic flow

Humans make systematic errors in the 3D interpretation of the optic flow in both passive and active vision. These systematic distortions can be predicted by a biologically-inspired model which disregards self-motion information resulting from head movements (Caudek, Fantoni, & Domini 2011). Here, we tested two predictions of this model: (1) A plane that is stationary in an earth-fixed reference frame will be perceived as changing its slant if the movement of the observer's head causes a variation of the optic flow; (2) a surface that rotates in an earth-fixed reference frame will be perceived to be stationary, if the surface rotation is appropriately yoked to the head movement so as to generate a variation of the surface slant but not of the optic flow. Both predictions were corroborated by two experiments in which observers judged the perceived slant of a random-dot planar surface during egomotion. We found qualitatively similar biases for monocular and binocular viewing of the simulated surfaces, although, in principle, the simultaneous presence of disparity and motion cues allows for a veridical recovery of surface slant.     

Spatial coding of the predicted impact location of a looming object

Avoiding or intercepting looming objects implies a precise estimate of both time until contact and impact location. In natural situations, extrapolating a movement trajectory relative to some egocentric landmark requires taking into account variations in retinal input associated with moment-to-moment changes in body posture. Here, human observers predicted the impact location on their face of an approaching stimulus mounted on a robotic arm, while we systematically manipulated the relation between eye, head, and trunk orientation. The projected impact point on the observer's face was estimated most accurately when the target originated from a location aligned with both the head and eye axes. Eccentric targets with respect to either axis resulted in a systematic perceptual bias ipsilateral to the trajectory's origin. We conclude that (1) predicting the impact point of a looming target requires combining retinal information with eye position information, (2) that this computation is accomplished accurately for some, but not all, possible combinations of these cues, (3) that the representation of looming trajectories is not formed in a single, canonical reference frame, and (4) that the observed perceptual biases could reflect an automatic adaptation for interceptive/defensive actions within near peripersonal space.     

Functional correlates of the lateral and medial entorhinal cortex: objects,path integration and local–global reference frames

The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between ‘where’ versus ‘what’ needs revision. We propose a refinement of this model, which is more complex than the simple spatial–non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience.     

Catecholamine release and uptake in the mouse prefrontal cortex

Monitoring the release and uptake of catecholamines from terminals in weakly innervated brain regions is an important step in understanding their importance in normal brain function. To that end, we have labeled brain slices from transgenic mice that synthesize placental alkaline phosphatase (PLAP) on neurons containing tyrosine hydroxylase with antibody-fluorochrome conjugate, PLAP-Cy5. Excitation of the fluorochrome enables catecholamine neurons to be visualized in living tissue. Immunohistochemical fluorescence with antibodies to tyrosine hydroxylase and dopamine beta-hydroxylase revealed that the PLAP labeling was specific to catecholamine neurons. In the prefrontal cortex (PFC), immunohistochemical fluorescence of the PLAP along with staining for dopamine transporter (DAT) and norepinephrine transporter (NET) revealed that all three exhibit remarkable spatial overlap. Fluorescence from the PLAP antibody was used to position carbon-fiber microelectrodes adjacent to catecholamine neurons in the PFC. Following incubation with L-DOPA, catecholamine release and subsequent uptake was measured and the effect of uptake inhibitors examined. Release and uptake in NET and DAT knockout mice were also monitored. Uptake rates in the cingulate and prelimbic cortex are so slow that catecholamines can exist in the extracellular fluid for sufficient time to travel approximately 100 microm. The results support heterologous uptake of catecholamines and volume transmission in the PFC of mice.     

Diverse synchrony of firing reflects diverse cell-assembly coding in the prefrontal cortex

In the present paper, we focus on the coding by cell assemblies in the prefrontal cortex (PFC) and discuss the diversity of the coding, which results in stable and dynamic representations and the processing of various information in that higher brain region. The key activity that reflects cell-assembly coding is the synchrony of the firing of multiple neurons when animals are performing cognitive and memory tasks. First, we introduce some studies that have shown task-related synchrony of neuronal firing in the monkey PFC. These studies have reported fixed and several types of dynamic synchronous firing during working memory, long-term visual memory, and goal selection. The results of these studies have indicated that cell assemblies in the PFC can contribute to both the stability and the dynamics of various types of information. Second, we refer to rat studies and introduce the findings of cellular interactions that contribute to synchrony in working memory, learning-induced changes in synchrony in spatial tasks, and interactions of the PFC and hippocampus in dynamic synchrony. These studies have proposed neuronal mechanisms of cell-assembly coding in the PFC and its critical role in the learning of task demands in problematic situations. Based on the monkey and rat studies, we conclude that cell-assembly coding in the PFC is diverse and has various facets, which allow multipotentiality in the higher brain region. Finally, we discuss the problem of the sizes of cell assembly, how diverse the sizes are in the PFC, and the technical problems in their investigation. We introduce a unique spike-sorting method that can detect small and local cell assemblies that consist of closely neighboring neurons. Then, we describe the findings of our study that showed that the monkey PFC has both small and large cell assemblies, which have different roles in information coding in the working brain.