Integrating orbitofrontal cortex into prefrontal theory: common processing themes across species and subdivisions

Currently, many theories highlight either representational memory or rule representation as the hallmark of prefrontal function. Neurophysiological findings in the primate dorsolateral prefrontal cortex indicate that both features may characterize prefrontal processing. Neurons in the dorsolateral prefrontal cortex encode information in working memory, and this information is represented when relevant to the rules governing performance in a task. In this review, we discuss recent reports of encoding in primate and rat orbitofrontal regions indicating that these features also characterize activity in the orbitofrontal subdivision of the prefrontal cortex. These data indicate that (1) neural activity in the orbitofrontal cortex links the current incentive value of reinforcers to cues, rather than representing the physical features of cues or associated reinforcers; (2) this incentive-based information is represented in the orbitofrontal cortex when it is relevant to the rules guiding performance in a task; and (3) incentive information is also represented in the orbitofrontal cortex in working memory during delays when neither the cues nor reinforcers are present. Therefore, although the orbitofrontal cortex appears to be uniquely specialized to process incentive or motivational information, it may be integrated into a more global framework of prefrontal function characterized by representational encoding of performance-relevant information.     

人际互动中社会学习的计算神经机制

人类在社会互动中通过他人的行为对他人特质、意图及特定情境下的社会规范进行学习, 是优化决策、维护积极社会互动的重要条件。近年来, 越来越多的研究通过结合计算模型与神经影像技术对社会学习的认知计算机制及其神经基础进行了深入考察。已有研究发现, 人类的社会学习过程能够较好地被强化学习模型与贝叶斯模型刻画, 主要涉及的认知计算过程包括主观期望、预期误差和不确定性的表征以及信息整合的过程。大脑对这些计算过程的执行主要涉及奖惩加工相关脑区(如腹侧纹状体与腹内侧前额叶)、社会认知加工相关脑区(如背内侧前额叶和颞顶联合区)及认知控制相关脑区(如背外侧前额叶)。需要指出的是, 计算过程与大脑区域之间并不是一一映射的关系, 提示未来研究可借助多变量分析与脑网络分析等技术从系统神经科学的角度来考察大尺度脑网络如何执行不同计算过程。此外, 将来研究应注重生态效度, 利用超扫描技术考察真实互动下的社会学习过程, 并更多地关注内隐社会学习的计算与神经机制。     

Spiking Phineas Gage: a neurocomputational theory of cognitive-affective integration in decision making

The authors present a neurological theory of how cognitive information and emotional information are integrated in the nucleus accumbens during effective decision making. They describe how the nucleus accumbens acts as a gateway to integrate cognitive information from the ventromedial prefrontal cortex and the hippocampus with emotional information from the amygdala. The authors have modeled this integration by a network of spiking artificial neurons organized into separate areas and used this computational model to simulate 2 kinds of cognitive-affective integration. The model simulates successful performance by people with normal cognitive-affective integration. The model also simulates the historical case of Phineas Gage as well as subsequent patients whose ability to make decisions became impeded by damage to the ventromedial prefrontal cortex.     

PET studies of encoding and retrieval: The HERA model

We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.     

Neural mediation of memory for time: Role of the hippocampus and medial prefrontal cortex

Within the context of the neurobiology of attribute model, memory for the temporal attribute is composed of at least three features—memory for duration, memory for succession, or temporal order, and memory for past and future time perspective within a dual-based (data and knowledge) memory system. Research aimed at testing the assumption that the hippocampus and interconnected neural circuits mediate the temporal attribute within the data-based memory system and the prefrontal cortex and interconnected neural circuits mediate the temporal attribute within the knowledge-based memory system in animals and humans is reviewed. The research indicates that (1) memory for the duration feature of the temporal attribute is mediated by the hippocampus, but not prefrontal cortex, in both animals and humans, (2) memory for the temporal order feature of the temporal attribute based on new information is subserved by both the hippocampus and the prefrontal cortex, but that based on prior knowledge or the ability to use prior knowledge is supported only by prefrontal cortex, and not the hippocampus, in both animals and humans, and (3) memory for the past (time perspective) feature of the temporal attribute is mediated by the hippocampus, whereas memory for the future (time perspective) feature of the temporal attribute is supported by the prefrontal cortex in both animals and humans. There is a clear parallel between animals and humans in terms of hippocampal and prefrontal cortex mediation of the temporal attribute, supporting the assumption of evolutionary continuity. There is support for a greater involvement of the hippocampus in comparison with the prefrontal cortex in mediating temporal attribute information within the data-based memory system. Conversely, there is support for a greater involvement of the prefrontal cortex in comparison with the hippocampus in mediating temporal attribute information within the knowledge-based memory system. Future research needs to concentrate on the development of new paradigms to measure memory for different temporal features and to uncover the critical neural circuits that subserve these temporal features.     

The mid-ventrolateral prefrontal cortex and active mnemonic retrieval

The role of the mid-ventrolateral prefrontal cortex in memory retrieval is examined and compared with the role of the mid-dorsolateral prefrontal cortex in the monitoring of information in memory. It has been argued that the mid-ventrolateral prefrontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from posterior cortical association areas. Active retrieval is required when stimuli in memory do not bear stable relations to each other and therefore retrieval cannot be automatically driven by strong, stable, and unambiguous stimulus or context relations. Data from functional activation studies with normal human subjects are presented that have demonstrated specific changes in activity within the mid-ventrolateral region of the frontal cortex in relation to the active retrieval of information from memory. By contrast, increases in activity in the mid-dorsolateral region of the frontal cortex occur when the performance of the tasks requires monitoring of information in memory.     

The effects of prefrontal lesions on working memory performance and theory

The effects of experimental lesions of the monkey prefrontal cortex have played a predominant role in current conceptualizations of the functional organization of the lateral prefrontal cortex, especially with regard to working memory. The loss or sparing of certain performance abilities has been shown to be attributable to differences in the specific requirements of behavioral testing (e.g., spatial vs. nonspatial memoranda) along with differences in the specific locations of applied ablations (e.g., dorsal vs. ventral prefrontal cortex). Such findings, which have accumulated now for over a century, have led to widespread acceptance that the dorsolateral and ventrolateral aspects of the prefrontal cortex may perform different, specialized roles in higher order cognition. Nonetheless, it remains unclear and controversial how the lateral prefrontal cortex is functionally organized. Two main views propose different types of functional specialization of the dorsal and ventral prefrontal cortex. The first contends that the lateral prefrontal cortex is segregated according to the processing of spatial and nonspatial domains of information. The second contends that domain specialization is not the key to the organization of the prefrontal cortex, but that instead, the dorsal and ventral prefrontal cortices perform qualitatively different operations. This report critically reviews all relevant monkey lesion studies that have served as the foundation for current theories regarding the functional organization of the prefrontal cortex. Our goals are to evaluate how well the existing lesion data support each theory and to enumerate caveats that must be considered when interpreting the relevant literature.     

前额叶损害对个体一般智力、认知策略与自我监控能力影响的研究

本研究随机挑选了15名因外伤而造成的前额叶损害者和15名正常成人,采用韦氏成人智力量表和自编的图片分类作业,考查了他们在一般智力、认知策略与自我监控能力方面的差异,研究结果表明:(1)前额叶损害对个体的一般智力产生显著的影响,但是其智力仍然处于正常范围,可见智力的脑结构范围极为广泛,智力是一个具有多重性的系统。(2)前额叶损害者对无关刺激的抑制,对有效信息的提取与加工放大的心理活动受到极大影响,认知策略转换能力明显低于正常人,表现出了明显的认知不随意性,额叶可能更多的与个体的计划、认知策略选择、自我监控密切相关;(3)前额叶损害者对具体概念与抽象概念的自我监控能力表现出了不同的影响,对前者的损害显著大于后者,这表明个体依据具体概念进行的形象思维与凭借抽象概念进行的逻辑思维有不同的脑机制。     

Beyond HERA: Contributions of specific prefrontal brain areas to long-term memory retrieval

Recent neuroimaging studies have provided a wealth of information about areas within prefrontal cortex involved in long-term memory. These studies prompted a proposal by Tulving and colleagues (Tulving, Kapur, Craik, Habib, & Houle, 1994) that prefrontal contributions to memory function are related to laterality differences (the hemispheric encoding/retrieval asymmetry model). This review goes beyond a general characterization of prefrontal lobes to a more specific analysis of distinct areas within the prefrontal cortex. Separate prefrontal areas, sometimes within the same hemisphere, are discussed in terms of selective contributions that they might make to memory retrieval. In the end, it is concluded that a framework which tries to understand prefrontal function in terms of specific areas is a useful complement to models, like HERA, which attempt to find unifying principles across multiple areas.     

Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes

The prefrontal cortex (PFC) is known to actively hold information "online" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.     

Decreased levels of N-acetylaspartate in dorsolateral prefrontal cortex in a case of intractable severe sympathetically mediated chronic pain (complex regional pain syndrome,type I)

In our previous in vivo proton magnetic resonance spectroscopy ((1)H MRS) study we found reduced levels of N-acetylaspartate in dorsolateral prefrontal cortex of chronic back pain patients. This study tests whether these chemical abnormalities can be detected in other pain states. Using (1)H MRS, we measured levels for N-acetylaspartate and other identifiable chemicals relative to creatine in four bilateral brain regions, including dorsolateral prefrontal cortex, orbitofrontal cortex, cingulate, and thalamus, in a case of intractable severe sympathetically mediated chronic pain [complex regional pain syndrome (CRPS) type I]. The subject's chemical variations in the brain were compared to the same regional chemicals in 10 normal subjects (age- and sex-matched). Univariate statistics showed reduced levels of N-acetylaspartate in bilateral dorsolateral prefrontal cortex and increased levels of myo-inositol in left orbitofrontal cortex of the patient with intractable severe CRPS type I. These data support our original hypothesis that depletion of N-acetylaspartate in dorsolateral prefrontal cortex is a chemical marker of chronic pain, indicating for neuronal degeneration. Unpredicted changes of orbitofrontal myo-inositol may be related to the specific mood/affective state in an extreme pain perception. This is the first report, which identifies chemical markers in the prefrontal cortex for objective measurement and monitoring of CRPS type I. This information might lead to valuable insights into diagnosis and future effective interventions of CRPS type I (e.g., prefrontal brain stimulation).     

自我控制资源与认知资源相互影响的机制:整合模型

尽管有学者认为自我控制资源和认知资源应该是两种独立的资源,但近期的研究却表明两种资源是互相影响的.以往研究从执行控制的角度解释两种资源为什么相互影响,但却没有指出两种资源如何影响执行控制,以及缺乏考虑神经机制和自我控制资源调节变量在其中的作用.为更系统地解释两种资源相互影响的机制,作者提出了一个整合模型,该模型指出:(1)两种资源相互影响的主要原因是两者都受到执行控制和前额叶皮层的影响;(2)个体进行自我控制或认知加工会消耗能量,产生心理疲劳,降低执行任务的动机,表现为前额叶皮层激活水平下降;(3)前额叶皮层激活不足进一步限制了执行控制在随后的自我控制和认知加工任务中的作用,因而影响后续自我控制或认知加工任务的表现;(4)自我控制资源调节变量通过提高个体对疲劳的耐受性、补充能量和提高动机等方法,使前额叶皮层和执行控制在完成前一阶段任务后仍然能够正常发挥作用,从而维持个体在后续自我控制或认知加工任务上的表现.未来的研究可考察自我控制资源与其他认知加工的关系;用动态的认知神经研究方法,建立前额叶皮层激活水平在前后两阶段任务之间的中介作用模型,以及研究自我控制资源调节变量的神经机制.     

An information theoretical approach to prefrontal executive function

The prefrontal cortex subserves executive control--that is, the ability to select actions or thoughts in relation to internal goals. Here, we propose a theory that draws upon concepts from information theory to describe the architecture of executive control in the lateral prefrontal cortex. Supported by evidence from brain imaging in human subjects, the model proposes that action selection is guided by hierarchically ordered control signals, processed in a network of brain regions organized along the anterior-posterior axis of the lateral prefrontal cortex. The theory clarifies how executive control can operate as a unitary function, despite the requirement that information be integrated across multiple distinct, functionally specialized prefrontal regions.     

Medial prefrontal cortex lesions abolish contextual control of competing responses

There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (congruent trials) or different (incongruent trials) responses during training. In sham-operated controls, contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control of responding was not evident in individual rats with large amounts of damage that included the prelimbic and cingulate subregions of the prefrontal cortex. Experiment 2 further dissociated the result of Experiment 1, demonstrating that lesions specific to the anterior cingulate cortex were sufficient to produce a deficit early on during presentation of an incongruent stimulus compound but that performance was unimpaired as presentation progressed. This early deficit suggests a role for the anterior cingulate cortex in the detection of response conflict, and for the medial prefrontal cortex in the contextual control of competing responses, providing evidence for functional specialization within the rat prefrontal cortex.     

Prefrontal cortex regulates inhibition and excitation in distributed neural networks.

Prefrontal cortex provides both inhibitory and excitatory input to distributed neural circuits required to support performance in diverse tasks. Neurological patients with prefrontal damage are impaired in their ability to inhibit task-irrelevant information during behavioral tasks requiring performance over a delay. The observed enhancements of primary auditory and somatosensory cortical responses to task-irrelevant distractors suggest that prefrontal damage disrupts inhibitory modulation of inputs to primary sensory cortex, perhaps through abnormalities in a prefrontal-thalamic sensory gating system. Failure to suppress irrelevant sensory information results in increased neural noise, contributing to the deficits in decision making routinely observed in these patients. In addition to a critical role in inhibitory control of sensory flow to primary cortical regions, and tertiary prefrontal cortex also exerts excitatory input to activity in multiple sub-regions of secondary association cortex. Unilateral prefrontal damage results in multi-modal decreases in neural activity in posterior association cortex in the hemisphere ipsilateral to damage. This excitatory modulation is necessary to sustain neural activity during working memory. Thus, prefrontal cortex is able to sculpt behavior through parallel inhibitory and excitatory regulation of neural activity in distributed neural networks.     

Domain-dependent activation during spatial and nonspatial auditory working memory

Visual system has been proposed to be divided into two, the ventral and dorsal, processing streams. The ventral pathway is thought to be involved in object identification whereas the dorsal pathway processes information regarding the spatial locations of objects and the spatial relationships among objects. Several studies on working memory (WM) processing have further suggested that there is a dissociable domain-dependent functional organization within the prefrontal cortex for processing of spatial and nonspatial visual information. Also the auditory system is proposed to be organized into two domain-specific processing streams, similar to that seen in the visual system. Recent studies on auditory WM have further suggested that maintenance of nonspatial and spatial auditory information activates a distributed neural network including temporal, parietal, and frontal regions but the magnitude of activation within these activated areas shows a different functional topography depending on the type of information being maintained. The dorsal prefrontal cortex, specifically an area of the superior frontal sulcus (SFS), has been shown to exhibit greater activity for spatial than for nonspatial auditory tasks. Conversely, ventral frontal regions have been shown to be more recruited by nonspatial than by spatial auditory tasks. It has also been shown that the magnitude of this dissociation is dependent on the cognitive operations required during WM processing. Moreover, there is evidence that within the nonspatial domain in the ventral prefrontal cortex, there is an across-modality dissociation during maintenance of visual and auditory information. Taken together, human neuroimaging results on both visual and auditory sensory systems support the idea that the prefrontal cortex is organized according to the type of information being maintained in WM.     

时间认知的脑机制研究

从神经心理学和脑成像2个领域综述了有关时间认知脑机制的研究。神经心理学及脑损伤的研究结果表明小脑可能与内部时钟功能有关,前额叶可能调节时间认知中的注意过程。PET和fMRI脑成象研究结果显示,基底神经节、小脑和前额叶在所有的计时作业中都被激活。ERP的研究结果还证实,时间信息加工和非时间信息加工存在时间历程上的差异,并且时间信息加工还存在的显著半球优势效应。因此基底神经节、小脑和前额叶可能是时间认知的主要脑机制,但由于研究材料、方法和程序的不同,大脑皮层的广泛区域都有可能参与时间信息的加工。     

Remembering the time: a continuous clock

The neural mechanisms for time measurement are currently a subject of much debate. This article argues that our brains can measure time using the same dorsolateral prefrontal cells that are known to be involved in working memory. Evidence for this is: (1) the dorsolateral prefrontal cortex is integral to both cognitive timing and working memory; (2) both behavioural processes are modulated by dopamine and disrupted by manipulation of dopaminergic projections to the dorsolateral prefrontal cortex; (3) the neurons in question ramp their activity in a temporally predictable way during both types of processing; and (4) this ramping activity is modulated by dopamine. The dual involvement of these prefrontal neurons in working memory and cognitive timing supports a view of the prefrontal cortex as a multipurpose processor recruited by a wide variety of tasks.     

前额叶皮质损伤患者的情绪异常

人类前额叶皮质与情绪之间有着密切的关系,文章在相关的临床和神经成像研究结果基础上,分析了前额叶皮质损伤对情绪行为造成的影响,分别概述了精神分裂症、重性抑郁和焦虑患者的情绪变化、前额叶切除对情绪的影响以及左右前额叶皮质与情绪的关系,重点阐述了前额叶功能异常的神经生理学特点,认为情绪的改变会随着前额叶皮质不同部位的结构缺损或功能变化而有所不同,此有利于对前额叶皮质损伤患者情绪异常的评价与防治。