Prefrontal cortex

Definition

This section needs to be updated. Please help update this article to reflect recent events or newly available information. (March 2017)

There are three possible ways to define the prefrontal cortex:^{[citation needed]}

• as the granular frontal cortex
• as the projection zone of the medial dorsal nucleus of the thalamus
• as that part of the frontal cortex whose electrical stimulation does not evoke movements

Subdivisions

This section needs attention from an expert in neuroscience. See the talk page for details. WikiProject Neuroscience may be able to help recruit an expert. (May 2019)

According to Striedter,^[21] the PFC of humans can be delineated into two functionally, morphologically, and evolutionarily different regions: the ventromedial PFC (vmPFC) consisting of:

1. the ventral prefrontal cortex (VPFC)
2. the medial prefrontal cortex present in all mammals (MPFC)

and the lateral prefrontal cortex (LPFC), consisting of:

1. the dorsolateral prefrontal cortex (DLPFC)
2. the ventrolateral prefrontal cortex (VLPFC) present only in primates.

The LPFC contains the Brodmann areas BA8, BA9, BA10, BA45, BA46, and BA47. Some researchers also include BA44. The vmPFC contains the Brodmann areas BA12, BA25, BA32, BA33, BA24, BA11, BA13, and BA14.

The table below shows different ways to subdivide parts of the human prefrontal cortex based upon Brodmann areas.^[1]

• The dorsolateral prefrontal cortex is composed of the BA8, BA9, BA10, and BA46.^[1]
• The ventrolateral prefrontal cortex is composed of areas BA45, BA47, and BA44.^[1]
• The medial prefrontal cortex (mPFC) is composed of BA12, BA25, and anterior cingulate cortex: BA32, BA33, BA24.^[1] Within that area is the dorsal nexus, which interconnects many parts of the brain.^[22]
• The ventral prefrontal cortex is composed of areas BA11, BA13, and BA14.^[1] (Also see the definition of the orbitofrontal cortex.)
• The dorsolateral prefrontal cortex contains BA8, including the frontal eye fields.^[1]
• The ventrolateral prefrontal cortex contains BA45 which is part of Broca's area.^[23] Some researchers also include BA44 the other part of Broca's area.

Interconnections

The prefrontal cortex is highly interconnected with much of the brain, including extensive connections with other cortical, subcortical and brain stem sites.^[24] The dorsal prefrontal cortex is especially interconnected with brain regions involved with attention, cognition and action,^[25] while the ventral prefrontal cortex interconnects with brain regions involved with emotion.^[26] The prefrontal cortex also receives inputs from the brainstem arousal systems, and its function is particularly dependent on its neurochemical environment.^[27] Thus, there is coordination between one's state of arousal and mental state.^[28] The interplay between the prefrontal cortex and socioemotional system of the brain is relevant for adolescent development, as proposed by the Dual Systems Model.

The medial prefrontal cortex has been implicated in the generation of slow-wave sleep (SWS), and prefrontal atrophy has been linked to decreases in SWS.^[29] Prefrontal atrophy occurs naturally as individuals age, and it has been demonstrated that older adults experience impairments in memory consolidation as their medial prefrontal cortices degrade.^[29] In older adults, instead of being transferred and stored in the neocortex during SWS, memories start to remain in the hippocampus where they were encoded, as evidenced by increased hippocampal activation compared to younger adults during recall tasks, when subjects learned word associations, slept, and then were asked to recall the learned words.^[29]

The ventrolateral prefrontal cortex (VLPFC) has been implicated in various aspects of speech production and language comprehension. The VLPFC is richly connected to various regions of the brain including the lateral and medial temporal lobe, the superior temporal cortex, the infertemporal cortex, the perirhinal cortex, and the parahippoccampal cortex.^[30] These brain areas are implicated in memory retrieval and consolidation, language processing, and association of emotions. These connections allow the VLPFC to mediate explicit and implicit memory retrieval and integrate it with language stimulus to help plan coherent speech.^[31] In other words, choosing the correct words and staying "on topic" during conversation come from the VLPFC.

Executive function

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.^[32] In this way, working memory can be seen as fundamental to attention and behavioral inhibition. Fuster speaks of how this prefrontal ability allows the integration of past and future, allowing both cross-temporal and cross-modal associations in the creation of goal-directed, perception-action cycles.^[33] This ability to represent underlies all other higher executive functions. The prefrontal cortex is responsible for many executive functions, such as remembering information, cognitive flexibility, and inhibitory control. Although the prefrontal cortex does this, it does not carry out these responsibilities alone as other brain regions also play important roles during this.^[34] For example, the amygdala sends signals to the prefrontal cortex area known as 46d in order for one to comprehend the situation and to determine how to react.^[15]

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.^[35]

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".^[36] 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".^[36] 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".^[36]

Experimental data indicate a role for the prefrontal cortex in mediating normal sleep physiology, dreaming and sleep-deprivation phenomena.^[37]

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.^[38]

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.^[39]

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.^[40]

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.^[41]

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.^[43] 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).^[44] 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.^[45] 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.^[46] 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.^[42] 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.^[10][47]

Speech production and language

Various areas of the prefrontal cortex have been implicated in a multitude of critical functions regarding speech production, language comprehension, and response planning before speaking.^[9] Cognitive neuroscience has shown that the left ventrolateral prefrontal cortex is vital in the processing of words and sentences.

The right prefrontal cortex has been found to be responsible for coordinating the retrieval of explicit memory for use in speech, whereas the deactivation of the left is responsible for mediating implicit memory retrieval to be used in verb generation.^[9] Recollection of nouns (explicit memory) is impaired in some amnesic patients with damaged right prefrontal cortices, but verb generation remains intact because of its reliance on left prefrontal deactivation.^[31]

Many researchers now include BA45 in the prefrontal cortex because together with BA44 it makes up an area of the frontal lobe called Broca's area.^[23] Broca's Area is widely considered the output area of the language production pathway in the brain (as opposed to Wernicke's area in the medial temporal lobe, which is seen as the language input area). BA45 has been shown to be implicated for the retrieval of relevant semantic knowledge to be used in conversation/speech.^[9] The right lateral prefrontal cortex (RLPFC) is implicated in the planning of complex behavior, and together with bilateral BA45, they act to maintain focus and coherence during speech production.^[31] However, left BA45 has been shown to be activated significantly while maintaining speech coherence in young people. Older people have been shown to recruit the right BA45 more so than their younger counterparts.^[31] This aligns with the evidence of decreased lateralization in other brain systems during aging.

In addition, this increase in BA45 and RLPFC activity in combination of BA47 in older patients has been shown to contribute to "off-topic utterances." The BA47 area in the prefrontal cortex is implicated in "stimulus-driven" retrieval of less-salient knowledge than is required to contribute to a conversation.^[31] In other words, elevated activation of the BA47 together with altered activity in BA45 and the broader RLPFC has been shown to contribute to the inclusion of less relevant information and irrelevant tangential conversational speech patterns in older subjects.

Etymology

The term "prefrontal" as describing a part of the brain appears to have been introduced by Richard Owen in 1868.^[12] For him, the prefrontal area was restricted to the anterior-most part of the frontal lobe (approximately corresponding to the frontal pole). It has been hypothesized that his choice of the term was based on the prefrontal bone present in most amphibians and reptiles.^[12]