Prefrontal cortex

There are three possible ways to define the prefrontal cortex:

The prefrontal cortex has been defined based on cytoarchitectonics by the presence of a cortical granular layer IV. It is not entirely clear who first used this criterion. Many of the early cytoarchitectonic researchers restricted the use of the term prefrontal to a much smaller region of cortex including the gyrus rectus and the gyrus rostralis (Campbell, 1905; G. E. Smith, 1907; Brodmann, 1909; von Economo and Koskinas, 1925). In 1935, however, Jacobsen used the term prefrontal to distinguish granular prefrontal areas from agranular motor and premotor areas. In terms of Brodmann areas, the prefrontal cortex traditionally includes areas 8, 9, 10, 11, 12, 13, 14, 24, 25, 32, 44, 45, 46, and 47, however, not all of these areas are strictly granular – 44 is dysgranular, caudal 11 and orbital 47 are agranular. The main problem with this definition is that it works well only in primates but not in nonprimates, as the latter lack a granular layer IV. In a recent research study, scientists stimulated the amygdala area in monkeys, where they found that the auditory and prefrontal cortices got activated, which is similar to what happens in humans.

To define the prefrontal cortex as the projection zone of the mediodorsal nucleus of the thalamus builds on the work of Rose and Woolsey, who showed that this nucleus projects to anterior and ventral parts of the brain in nonprimates, however, Rose and Woolsey termed this projection zone "orbitofrontal." It seems to have been Akert, who, for the first time in 1964, explicitly suggested that this criterion could be used to define homologues of the prefrontal cortex in primates and nonprimates. This allowed the establishment of homologies despite the lack of a granular frontal cortex in nonprimates.

The projection zone definition is still widely accepted today (e.g. Fuster), although its usefulness has been questioned. Modern tract tracing studies have shown that projections of the mediodorsal nucleus of the thalamus are not restricted to the granular frontal cortex in primates. As a result, it was suggested to define the prefrontal cortex as the region of cortex that has stronger reciprocal connections with the mediodorsal nucleus than with any other thalamic nucleus. Uylings et al. …

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 integration of past and 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. 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. 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.

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". …

In the last few decades, brain imaging systems have been used to determine brain region volumes and nerve linkages. Several studies have indicated that reduced volume and interconnections of the frontal lobes with other brain regions is observed in patients diagnosed with mental disorders; those subjected to repeated stressors; those who excessively consume sexually explicit materials; suicides; criminals; sociopaths; those affected by lead poisoning; it is believed that at least some of the human abilities to feel guilt or remorse, and to interpret reality, are dependent on a well-functioning prefrontal cortex. The advanced neurocircuitry and self-regulatory function of the human prefrontal cortex is also associated with the higher sentience and sapience of humans, as the prefrontal cortex in humans occupies a far larger percentage of the brain than in any other animal. It is theorized that, as the brain has tripled in size over five million years of human evolution, the prefrontal cortex has increased in size sixfold.

A review on executive functions in healthy exercising individuals noted that the left and right halves of the prefrontal cortex, which is divided by the medial longitudinal fissure, appears to become more interconnected in response to consistent aerobic exercise. Two reviews of structural neuroimaging research indicate that marked improvements in prefrontal and hippocampal gray matter volume occur in healthy adults that engage in medium intensity exercise for several months.

Chronic intake of alcohol leads to persistent alterations in brain function including altered decision-making ability. The prefrontal cortex of chronic alcoholics has been shown to be vulnerable to oxidative DNA damage and neuronal cell death.

Perhaps the seminal case in prefrontal cortex function is that of Phineas Gage, whose left frontal lobe was destroyed when a large iron rod was driven through his head in an 1848 accident. The standard presentation is that, although Gage retained normal memory, speech and motor skills, his personality changed radically: He became irritable, quick-tempered, and impatient—characteristics he did not previously display — so that friends described him as "no longer Gage"; and, whereas he had previously been a capable and efficient worker, afterward he was unable to complete. However, careful analysis of primary evidence shows that descriptions of Gage's psychological changes are usually exaggerated when held against the description given by Gage's doctor, the most striking feature being that changes described years after Gage's death are far more dramatic than anything reported while he was alive.

Subsequent studies on patients with prefrontal injuries have shown that the patients verbalized what the most appropriate social responses would be under certain circumstances. Yet, when actually performing, they instead pursued behavior aimed at immediate gratification, despite knowing the longer-term results would be self-defeating.

The interpretation of this data indicates that not only are skills of comparison and understanding of eventual outcomes harbored in the prefrontal cortex but the prefrontal cortex (when functioning correctly) controls the mental option to delay immediate gratification for a better or more rewarding longer-term gratification result. This ability to wait for a reward is one of the key pieces that define optimal executive function of the human brain.

There is much current research devoted to understanding the role of the prefrontal cortex in neurological disorders. Clinical trials have begun on certain drugs that have been shown to improve prefrontal cortex function, including guanfacine, which acts through the alpha-2A adrenergic receptor. A downstream target of this drug, the HCN channel, is one of the most recent areas of exploration in prefrontal cortex pharmacology.

The term "prefrontal" as describing a part of the brain appears to have been introduced by Richard Owen in 1868. For him, the prefrontal area was restricted to the anterior-most part of the frontal lobe (approximately corresponding to the frontal pole). …