为了设计实验范式对前额区进行调研，可以用于测试的功能侧重在短期记忆、语义处理、计算？

提及实验：
go/no-go task
digit span task
Wisconsin Card Sorting Test (WCST)

Prefrontal Cortex

In mammalian brain anatomy, the prefrontal cortex (PFC) is the cerebral cortex which covers the front part of the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, and BA47

This brain region has been implicated in planning complex cognitive behavior, personality expression, decision making, and moderating social behavior. The basic activity of this brain region is considered to be orchestration of thoughts and actions in accordance with internal goals.
The most typical psychological term for functions carried out by the prefrontal cortex area is executive function. Executive function relates to abilities to differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outcomes, expectation based on actions, and social “control” (the ability to suppress urges that, if not suppressed, could lead to socially unacceptable outcomes).

Brodmann areas

• BA8
  It includes the frontal eye fields.The cortical area called frontal eye field (FEF) plays an important role in the control of visual attention and eye movements.
  The area is involved in the management of uncertainty. A fMRI study demonstrated that brodmann area 8 activation occurs when test subjects experience uncertainty, and that with increasing uncertainty there is increasing activation.
  Variants of uncertainty in decision-making and their neural correlates
  An alternative interpretation is that this activation in frontal cortex encodes hope, a higher-order expectation positively correlated with uncertainty.

• BA9
  The area is involved in short term memory, evaluating recency, overriding automatic responses, verbal fluency, error detection, auditory verbal attention, inferring the intention of others,inferring deduction from spatial imagery,inductive reasoning,attributing intention, sustained attention involved in counting a series of auditory stimuli, and lower levels of energy consumption in individuals suffering from bipolar disorder.
  The area found on the left hemisphere is at least partially responsible for empathy, idioms,processing pleasant and unpleasant emotional scenes,self criticisms and attention to negative emotions.
  On the right hemisphere the region is involved in attributing intention, theory of mind, suppressing sadness,working memory,spatial memory, recognition,recall,recognizing the emotions of others, planning, calculation,semantic and perceptual processing of odors,religiosity, and attention to positive emotions.

• BA10
  BA10 is the largest cytoarchitectonic area in the human brain. It has been described as “one of the least well understood regions of the human brain”.[2] Present research suggests that it is involved in strategic processes in memory recall and various executive functions. During human evolution, the functions in this area resulted in its expansion relative to the rest of the brain.
  Although this region is extensive in humans, its function is poorly understood. Koechlin & Hyafil have proposed that processing of cognitive branching is the core function of the frontopolar cortex. Cognitive branching enables a previously running task to be maintained in a pending state for subsequent retrieval and execution upon completion of the ongoing one. Many of our complex behaviors and mental activities require simultaneous engagement of multiple tasks, and they suggest the anterior prefrontal cortex may perform a domain-general function in these scheduling operations. Thus, the frontopolar cortex shares features with the central executive in Baddeley’s model of working memory. However, other hypotheses have also been proffered, such as those by Burgess et al. These also take into consideration the influence of the limbic system, to which the frontopolar cortex is connected through the ventromedial prefrontal cortex. A 2006 meta-analysis found that the rostral prefrontal cortex was involved in working memory, episodic memory and multiple-task coordination.[13] This area has also been implicated in decision making prior to the decision being available to conscious awareness .

• BA11
  Brodmann area 11 is one of Brodmann’s cytologically defined regions of the brain. It is involved in decision making and processing rewards, planning , encoding new information into long-term memory, and reasoning.

• BA46
  The dorsolateral prefrontal cortex plays a central role in sustaining attention and managing working memory, and has recently been shown to regulate self-control. It is one of the few cortical areas whose activity diminishes during REM sleep.
  The high connectivity of this area within the frontal lobe as well as other parts of the brain means that damage can have a wide variety of effects. Lesions impair short-term memory, cause difficulty inhibiting responses, impair the ability to judge the relevance of stimuli, and cause problems in organization.
  Recent research has shed light on the mechanism of working memory and the role of the dorsolateral prefrontal cortex. Studies using transcranial direct current stimulation (tDCS) observe changes in cortical activity due to either depolarization or hyperpolarization of underlying areas. The effect of these voltage shifts on activity in other structures is then measured. The goal of the studies is to identify the role of the dorsolateral prefrontal cortex in memory circuit modulation and learning.
  In a limited research study, participants tested their baseline working memory with digit span exercises, then underwent tDCS for ten minutes before being retested with the exercises. Contrary to expectations, tDCS showed only minimal effects on working memory.[2]
  Due to the lack of coherent resources and data of the experiment, more WM experiments using tDCS need to be evaluated. Some applications being discussed involve using tDCS adjunctively with cognitive remediation to enhance WM in neurologic and psychiatric conditions.
  A recent study found that targeting Transcranial magnetic stimulation to Brodmann area 46 has better clinical efficacy treating depression, as its functionally is connected (negatively correlated) to Brodmann area 25.[3]

• BA44
  Together with left-hemisphere BA 45, the left hemisphere BA 44 comprises Broca’s area a region involved in semantic tasks. Some data suggest that BA44 is more involved in motor aspect of speech (how speaking). Some recent findings also suggest the implication of this region in music perception.[2] Recent neuroimaging studies show BA44 involvement in selective response suppression in go/no- go tasks and is therefore believed to play an important role in the suppression of response tendencies. Neuroimaging studies also demonstrate that area 44 is related to hand movements.

• BA45
  Together with BA44, BA45 comprises Broca’s area, a region that is active in semantic tasks, such as semantic decision tasks (determining whether a word represents an abstract or a concrete entity) and generation tasks (generating a verb associated with a noun).
  Pars triangularis has been shown to have a role in cognitive control of memory. There are more ways than one to remember something. When a person remembers, (s)he retrieves information from storage in a memory center of the brain. This information may be the muscle contraction sequence for shoe-tying, the face of a loved one, or anything in between. When someone remembers something automatically, without concentrating on it and without trying, it is called “bottom-up” processing. But sometimes, people really have to struggle to remember something. A student taking a test and trying to remember the answer to a question is concentrating their attention on retrieving the memory. The student is exhibiting cognitive control over their memory. This type of processing is directed, in part, by the ventrolateral prefrontal cortex (VLPFC). Pars triangularis is found in this region.

• BA47
  BA47 has been implicated in the processing of syntax in oral and sign languages, musical syntax, and semantic aspects of language.

Function

Executive function（高级认知功能的基础）

The original studies of Fuster and of Goldman-Rakic emphasized the fundamental ability of the prefrontal cortex to represent information not currently in the environment, and the central role of this function in creating the “mental sketch pad”. Goldman-Rakic spoke of how this representational knowledge was used to intelligently guide thought, action, and emotion, including the inhibition of inappropriate thoughts, distractions, actions, and feelings. In this way, working memory can be seen as fundamental to attention and behavioral inhibition. Fuster speaks of how this prefrontal ability allows the wedding of past to future, allowing both cross-temporal and cross-modal associations in the creation of goal-directed, perception-action cycles. This ability to represent underlies all other higher executive functions.

Shimamura proposed Dynamic Filtering Theory to describe the role of the prefrontal cortex in executive functions. The prefrontal cortex is presumed to act as a high-level gating or filtering mechanism that enhances goal-directed activations and inhibits irrelevant activations. This filtering mechanism enables executive control at various levels of processing, including selecting, maintaining, updating, and rerouting activations. It has also been used to explain emotional regulation.

Miller and Cohen proposed an Integrative Theory of Prefrontal Cortex Function, that arises from the original work of Goldman-Rakic and Fuster. The two theorize that “cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represents goals and means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task”.[24] In essence, the two theorize that the prefrontal cortex guides the inputs and connections, which allows for cognitive control of our actions.

The prefrontal cortex is of significant importance when top-down processing is needed. Top-down processing by definition is when behavior is guided by internal states or intentions. According to the two, “The PFC is critical in situations when the mappings between sensory inputs, thoughts, and actions either are weakly established relative to other existing ones or are rapidly changing”.[24] An example of this can be portrayed in the Wisconsin Card Sorting Test (WCST) . Subjects engaging in this task are instructed to sort cards according to the shape, color, or number of symbols appearing on them. The thought is that any given card can be associated with a number of actions and no single stimulus-response mapping will work. Human subjects with PFC damage are able to sort the card in the initial simple tasks, but unable to do so as the rules of classification change.

Miller and Cohen conclude that the implications of their theory can explain how much of a role the PFC has in guiding control of cognitive actions. In the researchers’ own words, they claim that, “depending on their target of influence, representations in the PFC can function variously as attentional templates, rules, or goals by providing top-down bias signals to other parts of the brain that guide the flow of activity along the pathways needed to perform a task”.[24]

Experimental data indicate a role for the prefrontal cortex in mediating normal sleep physiology, dreaming and sleep-deprivation phenomena.[25]

When analyzing and thinking about attributes of other individuals, the medial prefrontal cortex is activated, however, it is not activated when contemplating the characteristics of inanimate objects.[26]

Studies using fMRI have shown that the medial prefrontal cortex (mPFC), specifically the anterior medial prefrontal cortex (amPFC), may modulate mimicry behavior. Neuroscientists are suggesting that social priming influences activity and processing in the amPFC, and that this area of the prefrontal cortex modulates mimicry responses and behavior.[27]

As of recent, researchers have used neuroimaging techniques to find that along with the basal ganglia, the prefrontal cortex is involved with learning exemplars, which is part of the exemplar theory, one of the three main ways our mind categorizes things. The exemplar theory states that we categorize judgements by comparing it to a similar past experience within our stored memories.[28]

A 2014 meta-analysis by Professor Nicole P.Yuan from the University of Arizona found that larger prefrontal cortex volume and greater PFC cortical thickness were associated with better executive performance.[29]

Attention and memory

A widely accepted theory regarding the function of the brain’s prefrontal cortex is that it serves as a store of short-term memory. This idea was first formulated by Jacobsen, who reported in 1936 that damage to the primate prefrontal cortex caused short-term memory deficits.[31] Karl Pribram and colleagues (1952) identified the part of the prefrontal cortex responsible for this deficit as area 46, also known as the dorsolateral prefrontal cortex (dlPFC).[32] More recently, Goldman-Rakic and colleagues (1993) evoked short-term memory loss in localized regions of space by temporary inactivation of portions of the dlPFC.[33] Once the concept of working memory (see also Baddeley’s model of working memory) was established in contemporary neuroscience by Alan Baddeley (1986), these neuropsychological findings contributed to the theory that the prefrontal cortex implements working memory and, in some extreme formulations, only working memory.[34] In the 1990s this theory developed a wide following, and it became the predominant theory of PF function, especially for nonhuman primates. The concept of working memory used by proponents of this theory focused mostly on the short-term maintenance of information, and rather less on the manipulation or monitoring of such information or on the use of that information for decisions. Consistent with the idea that the prefrontal cortex functions predominantly in maintenance memory, delay-period activity in the PF has often been interpreted as a memory trace. (The phrase “delay-period activity” applies to neuronal activity that follows the transient presentation of an instruction cue and persists until a subsequent “go” or “trigger” signal.)

To explore alternative interpretations of delay-period activity in the prefrontal cortex, Lebedev et al. (2004) investigated the discharge rates of single prefrontal neurons as monkeys attended to a stimulus marking one location while remembering a different, unmarked location.[30] Both locations served as potential targets of a saccadic eye movement. Although the task made intensive demands on short-term memory, the largest proportion of prefrontal neurons represented attended locations, not remembered ones. These findings showed that short-term memory functions cannot account for all, or even most, delay-period activity in the part of the prefrontal cortex explored. The authors suggested that prefrontal activity during the delay-period contributes more to the process of attentional selection (and selective attention) than to memory storage.