Prefrontal cortex
Encyclopedia
The prefrontal cortex is the anterior part of the frontal lobes of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, lying in front of the motor
Primary motor cortex
The primary motor cortex is a brain region that in humans is located in the posterior portion of the frontal lobe. Itworks in association with pre-motor areas to plan and execute movements. M1 contains large neurons known as Betz cells, which send long axons down the spinal cord to synapse onto...

 and premotor
Premotor cortex
The premotor cortex is an area of motor cortex lying within the frontal lobe of the brain. It extends 3 mm anterior to the primary motor cortex, near the Sylvian fissure, before narrowing to approximately 1 mm near the medial longitudinal fissure, which serves as the posterior border for...

 areas.

This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct 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
Psychology
Psychology is the study of the mind and behavior. Its immediate goal is to understand individuals and groups by both establishing general principles and researching specific cases. For many, the ultimate goal of psychology is to benefit society...

 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).

Many authors have indicated an integral link between a person's personality and the functions of the prefrontal cortex.

Definition

There are three possible ways to define the prefrontal cortex:
  • as the granular frontal cortex
  • as the projection zone of the mediodorsal nucleus of the thalamus
  • as that part of the frontal cortex whose electrical stimulation does not evoke movements


The prefrontal cortex has been defined based on cytoarchitectonics by the presence of a cortical granular layer IV
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

. 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
Gyrus rectus
The portion of the frontal lobe medial to the medial orbital gyrus is named the gyrus rectus , and is continuous with the superior frontal gyrus on the medial surface....

 and the gyrus
Gyrus
A gyrus is a ridge on the cerebral cortex. It is generally surrounded by one or more sulci .-Notable gyri:* Superior frontal gyrus, lat. gyrus frontalis superior* Middle frontal gyrus, lat. gyrus frontalis medius...

 rostralis (Campbell
Alfred Walter Campbell
-Further reading:...

, 1905; G. E. Smith
Grafton Elliot Smith
Sir Grafton Elliot Smith, FRS FRCP was an Australian anatomist and a proponent of the hyperdiffusionist view of prehistory.-Professional career:Smith was born in Grafton, New South Wales...

, 1907; Brodmann
Korbinian Brodmann
Korbinian Brodmann was a German neurologist who became famous for his definition of the cerebral cortex into 52 distinct regions from their cytoarchitectonic characteristics.-Life:...

, 1909; von Economo
Constantin von Economo
Constantin Freiherr von Economo was a Romanian psychiatrist and neurologist of Greek origin. He is mostly known for his discovery of encephalitis lethargica and his atlas of cytoarchitectonics.- Youth and schooling :Constantin Freiherr Economo von San Serff was born in Brăila, Romania, to Greek...

 and Koskinas
Georg N. Koskinas
Georg N. Koskinas was a Greek neurologist-psychiatrist. He was born on December 1, 1885 in Geraki, near Sparta. He studied medicine at the University of Athens, graduating in 1910, and subsequently trained as a resident in the Clinic of Psychiatry and Neurology of Aiginiteion Hospital under Michel...

, 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, 44, 45, 46, and 47 (to complicate matters, 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.

To define the prefrontal cortex as the projection zone of the mediodorsal nucleus
Medial dorsal nucleus
The medial dorsal nucleus is a large nucleus in the thalamus.It is believed to play a role in memory.-Anatomy:...

 of the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

 builds on the work of Rose and Woolsey who showed that this nucleus projects to anterior and ventral parts of the brain in nonprimates. Rose and Woolsey however termed this projection zone "orbitofrontal." It seems to have been Akert, who in 1964 for the first time 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
Joaquin Fuster
Joaquin M. Fuster is a neuroscientist whose research has made fundamental contributions to the understanding of the neural structures underlying cognition and behavior. His several books and hundreds of papers, particularly on memory and the prefrontal cortex, are widely cited.Born in Barcelona,...

), 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 which has stronger reciprocal connections with the mediodorsal nucleus than with any other thalamic nucleus. Uylings et al. acknowledge, however, that even with the application of this criterion it might be rather difficult to unequivocally define the prefrontal cortex.

A third definition of the prefrontal cortex is the area of frontal cortex whose electrical stimulation does not lead to observable movements. For example, in 1890 David Ferrier
David Ferrier
Sir David Ferrier, FRS was a pioneering Scottish neurologist and psychologist.-Life:Ferrier was born in Woodside, Aberdeen and educated at Aberdeen Grammar School before studying for an MA at Aberdeen University...

 used the term in this sense. One complication with this definition is that the electrically "silent" frontal cortex includes both granular and non-granular areas.

Etymology

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). It has been hypothesized that his choice of the term was based on the prefrontal bone
Prefrontal bone
The prefrontal bone is a bone separating the lacrimal and frontal bones in many tetrapod skulls. It first evolved in the sarcopterygian clade Rhipidistia, which includes lungfish and the Tetrapodomorpha. The prefrontal is found in most modern and extinct lungfish, amphibians and reptiles...

 present in most amphibians and reptiles.

Subdivisions

The table below shows different ways to subdivide the prefrontal cortex starting from Brodmann areas. Note that the term "dorsolateral" has been used to denote areas 8, 9, and 46 as well as areas 8, 9, 44, 45, 46, and lateral 47 and several terms are given to areas 47, 11 and 10.
8
9
46
44
45
lateral 47
orbital 47
11
10
dorsolateral
orbitofrontal
Orbitofrontal cortex
The orbitofrontal cortex is a prefrontal cortex region in the frontal lobes in the brain which is involved in the cognitive processing of decision-making...

, ventromedial
Ventromedial prefrontal cortex
The ventromedial prefrontal cortex is a part of the prefrontal cortex in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe and is implicated in the processing of risk, fear, and in decision making.- Anatomy :...

, basal, orbital
frontopolar, anterior, rostral
dorsolateral
ventrolateral
posterior dorsolateral
mid-dorsolateral

Interconnections

The prefrontal cortex is highly interconnected with much of the brain, including extensive connections with other cortical regions, as well as subcortical areas. The dorsal prefrontal cortex is especially interconnected with brain regions involved with attention, cognition and action, while the ventral prefrontal cortex interconnects with brain regions involved with emotion. The prefrontal cortex also receives inputs from the brainstem arousal systems, and its function is particularly dependent on its neurochemical environment. Thus, there is coordination between our state of arousal and our mental state.

Studies

Perhaps the seminal case in prefrontal cortex function is that of Phineas Gage
Phineas Gage
Phineas P. Gage was an American railroad construction foreman now remembered for his improbablesurvival of an accident in which a large iron rod was driven completely through his head, destroying much of his brain's left frontal lobe, and for that injury's reported effects on his personality and...

, one or both of whose frontal lobes was destroyed when a large iron rod was driven through his head in an 1848 accident. The standard presentation (e.g.) 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, afterwards he was unable to complete tasks. 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 that is 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.[needs citation]

There is much current research devoted to understanding the role of the prefrontal cortex in neurological disorders. Many disorders, such as schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

 and ADHD, have been related to dysfunction of the prefrontal cortex, and thus this area of the brain offers the potential for new treatments of these conditions.[needs citation] Clinical trials have begun on certain drugs that have been shown to improve prefrontal cortex function, including guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...

 which acts through the alpha-2A adrenergic receptor
Alpha-2A adrenergic receptor
The alpha-2A adrenergic receptor , also known as ADRA2A, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.-Role in Central Nervous System:...

. A downstream target of this drug, the HCN channel
HCN channel
Hyperpolarization-activated cyclic nucleotide-gated channels are proteins that serve as ion channels across the plasma membrane of heart and brain cells. HCN channels are sometimes referred to as “pacemaker channels” because they help to generate rhythmic activity within groups of heart and brain...

, is one of the most recent areas of exploration in prefrontal cortex pharmacology.

Interference theory
Interference theory
-History:Bergström, a German psychologist, is credited as conducting the first study regarding interference in 1892. His experiment was similar to the Stroop task and required subjects to sort two decks of card with words into two piles. When the location was changed for the second pile, sorting...

 can be broken into three kinds: proactive, retroactive, and output.

Proactive
Proactive Interference was localized to the ventrolateral and left anterior prefrontal cortex using the “recent-probes” task.


Retroactive Interference
Retroactive Interference has been localized to the left anterior ventral prefrontal cortex by magnetoencephalography
Magnetoencephalography
Magnetoencephalography is a technique for mapping brain activity by recording magnetic fields produced by electrical currents occurring naturally in the brain, using arrays of SQUIDs...

 studies investigating retroactive interference and working memory in elderly adults. The study found that adults 55–67 years of age showed less magnetic activity in their prefrontal cortices than the control group.


Output Interference
Output Interference

Executive Functions

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
Executive functions
The executive system is a theorized cognitive system in psychology that controls and manages other cognitive processes. It is responsible for processes that are sometimes referred to as the executive function, executive functions, supervisory attentional system, or cognitive control...

. 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”. Essentially 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”. An example of this can be portrayed in the Wisconsin card sort task (WCST)
Wisconsin card sort
The Wisconsin Card Sorting Test is a neuropsychological test of "set-shifting", i.e. the ability to display flexibility in the face of changing schedules of reinforcement. The WCST was written by David A. Grant and Esta A. Berg. The Professional Manual for the WCST was written by Robert K. Heaton,...

. 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”.

Other disorders

In the last few decades, brain imaging
Neuroimaging
Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

 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 those with Attention Deficit Hyperactivity Disorder, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, bipolar disorder
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...

, people subjected to repeated stressor
Stressor
Stressor is a chemical or biological agent, environmental condition, an external stimulus or an event that causes stress to an organism. An event that triggers the stress response may include for example:...

s, suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

 victims, incarcerated criminals, sociopaths, lead poisoning, and drug addicts. It is believed that at least some of the human abilities to feel guilt
Guilt
Guilt is the state of being responsible for the commission of an offense. It is also a cognitive or an emotional experience that occurs when a person realizes or believes—accurately or not—that he or she has violated a moral standard, and bears significant responsibility for that...

 or remorse, and to interpret reality
Reality
In philosophy, reality is the state of things as they actually exist, rather than as they may appear or might be imagined. In a wider definition, reality includes everything that is and has been, whether or not it is observable or comprehensible...

, lie in the prefrontal cortex. It is also widely believed that the size and number of connections in the prefrontal cortex relates directly to sentience
Sentience
Sentience is the ability to feel, perceive or be conscious, or to have subjective experiences. Eighteenth century philosophers used the concept to distinguish the ability to think from the ability to feel . In modern western philosophy, sentience is the ability to have sensations or experiences...

, as the prefrontal cortex in humans occupies a far larger percentage of the brain than any other animal. And it is theorized that as the brain has tripled in size over 5 million years of human evolution, the prefrontal cortex has increased in size sixfold.

See also

  • Attention versus memory in prefrontal cortex
    Attention versus memory in prefrontal cortex
    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 1935 that damage to the primate prefrontal cortex caused short-term memory deficits...

  • Self-model theory of subjectivity
    Self-model theory of subjectivity
    The self-model theory of subjectivity , also known as the human self model, is a theory of conscious experience. This concept comprises experiences of ownership, of body-centered spatial perspectivity, and of a long-term unity of beliefs and attitudes. These features are instantiated in the...


External links

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