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The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
of the
primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including huma ...
brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts until adulthood. The DLPFC is not an anatomical structure, but rather a functional one. It lies in the middle frontal gyrus of humans (i.e., lateral part of Brodmann's area (BA) 9 and 46). In macaque monkeys, it is around the principal sulcus (i.e., in Brodmann's area 46). Other sources consider that DLPFC is attributed anatomically to BA 9 and 46 and BA 8, 9 and 10. The DLPFC has connections with the
orbitofrontal cortex The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 1 ...
, as well as the
thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
, parts of the
basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
(specifically, the dorsal
caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's d ...
), the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, and primary and secondary association areas of neocortex (including posterior temporal, parietal, and occipital areas). The DLPFC is also the end point for the dorsal pathway (stream), which is concerned with how to interact with stimuli. An important function of the DLPFC is the
executive functions In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and suc ...
, such as
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
,
cognitive flexibility Cognitive flexibility is an intrinsic property of a cognitive system often associated with the mental ability to adjust its activity and content, switch between different task rules and corresponding behavioral responses, maintain multiple con ...
, planning, inhibition, and abstract reasoning. However, the DLPFC is not exclusively responsible for executive functions. All complex mental activity requires the additional cortical and subcortical circuits with which the DLPFC is connected. The DLPFC is also the highest cortical area that is involved in motor planning, organization and regulation.


Structure

As the DLPFC is composed of spatial selective
neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
, it has a neural circuitry that encompasses the entire range of sub-functions necessary to carry out an integrated response, such as: sensory input, retention in short-term memory, and motor signaling. Historically, the DLPFC was defined by its connection to: the superior
temporal cortex The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in pro ...
, the
posterior parietal cortex The posterior parietal cortex (the portion of parietal neocortex posterior to the primary somatosensory cortex) plays an important role in planned movements, spatial reasoning, and attention. Damage to the posterior parietal cortex can produce a ...
, the anterior and posterior cingulate, the
premotor cortex The premotor cortex is an area of the motor cortex lying within the frontal lobe of the brain just anterior to the primary motor cortex. It occupies part of Brodmann's area 6. It has been studied mainly in primates, including monkeys and humans ...
, the retrosplenial cortex, and the
neocerebellum The posterior lobe of cerebellum or neocerebellum, is the portion of the cerebellum below the primary fissure. The posterior lobe is much larger than anterior lobe. The anterior lobe is separated from the posterior lobe by the primary fissure, and ...
. These connections allow the DLPFC to regulate the activity of those regions, as well as to receive information from and be regulated by those regions.


Function


Primary functions

The DLPFC is known for its involvement in the executive functions, which is an umbrella term for the management of
cognitive processes Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
,Elliott R (2003). Executive functions and their disorders. British Medical Bulletin. (65); 49–59 including
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
,
cognitive flexibility Cognitive flexibility is an intrinsic property of a cognitive system often associated with the mental ability to adjust its activity and content, switch between different task rules and corresponding behavioral responses, maintain multiple con ...
, and planning. A couple of tasks have been very prominent in the research on the DLPFC, such as the
A-not-B task The A-not-B error is an incomplete or absent schema of object permanence, normally observed during the sensorimotor stage of Jean Piaget's Theory of Cognitive Development. A typical A-not-B task goes like this: An experimenter hides an attractive ...
, the delayed response task and object retrieval tasks. The behavioral task that is most strongly linked to DLPFC is the combined A-not-B/delayed response task, in which the subject has to find a hidden object after a certain delay. This task requires holding information in mind (
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
), which is believed to be one of the functions of DLPFC. The importance of DLPFC for working memory was strengthened by studies with adult macaques. Lesions that destroyed DLPFC disrupted the macaques' performance of the A-not-B/delayed response task, whereas lesions to other brain parts did not impair their performance on this task. DLPFC is not required for the memory of a single item. Thus, damage to the dorsolateral prefrontal cortex does not impair
recognition memory Recognition memory, a subcategory of declarative memory, is the ability to recognize previously encountered events, objects, or people.Medina, J. J. (2008)The biology of recognition memory. ''Psychiatric Times''. When the previously experienced ev ...
. Nevertheless, if two items must be compared from memory, the involvement of DLPFC is required. People with damaged DLPFC are not able to identify a picture they had seen, after some time, when given the opportunity to choose from two pictures. Moreover, these subjects also failed in Wisconsin Card-Sorting Test as they lose track of the currently correct rule and persistently organize their cards in the previously correct rule. In addition, as DLPFC deals with waking thought and reality testing, it is not active when one is asleep. Likewise, DLPFC is most frequently related to the dysfunction of drive, attention and motivation. Patients with minor DLPFC damage display disinterest in their surroundings and are deprived of spontaneity in language as well as behavior. Patients may also be less alert than normal to people and events they know. Damage to this region in a person also leads to the lack of motivation to do things for themselves and/or for others.


Decision making

The DLPFC is involved in both risky and moral
decision making In psychology, decision-making (also spelled decision making and decisionmaking) is regarded as the cognitive process resulting in the selection of a belief or a course of action among several possible alternative options. It could be either rati ...
; when individuals have to make moral decisions like how to distribute limited resources, the DLPFC is activated. This region is also active when costs and benefits of alternative choices are of interest. Similarly, when options for choosing alternatives are present, the DLPFC evokes a preference towards the most equitable option and suppresses the temptation to maximize personal gain.


Working memory

Working memory is the system that actively holds multiple pieces of transitory information in the mind, where they can be manipulated. The DLPFC is important for working memory; reduced activity in this area correlates to poor performance on working memory tasks. However, other areas of the brain are involved in working memory as well. There is an ongoing discussion if the DLPFC is specialized in a certain ''type'' of working memory, namely computational mechanisms for monitoring and manipulating items, or if it has a certain ''content'', namely visuospatial information, which makes it possible to mentally represent coordinates within the spatial domain. There have also been some suggestions that the function of the DLPFC in verbal and spatial working memory is lateralised into the left and right hemisphere, respectively. Smith, Jonides and Koeppe (1996) observed a lateralisation of DLPFC activations during verbal and visual working memory. Verbal working memory tasks mainly activated the left DLPFC and visual working memory tasks mainly activated the right DLPFC. Murphy et al. (1998) also found that verbal working memory tasks activated the right and left DLPFC, whereas spatial working memory tasks predominantly activated the left DLPFC. Reuter-Lorenz et al. (2000) found that activations of the DLPFC showed prominent lateralisation of verbal and spatial working memory in young adults, whereas in older adults this lateralisation was less noticeable. It was proposed that this reduction in lateralisation could be due to recruitment of neurons from the opposite hemisphere to compensate for neuronal decline with ageing.


Secondary functions

The DLPFC may also be involved in the act of deception and lying, which is thought to inhibit normal tendency to truth telling. Research also suggests that using TMS on the DLPFC can impede a person's ability to lie or to tell the truth. Additionally, supporting evidence suggests that the DLPFC may also play a role in conflict-induced behavioral adjustment, for instance when an individual decides what to do when faced with conflicting rules. One way in which this has been tested is through the Stroop test, in which subjects are shown a name of a color printed in colored ink and then are asked to name the color of the ink as fast as possible. Conflict arises when the color of the ink does not match the name of the printed color. During this experiment, tracking of the subjects' brain activity showed a noticeable activity within the DLPFC. The activation of the DLPFC correlated with the behavioral performance, which suggests that this region maintains the high demands of the task to resolve conflict, and thus in theory plays a role in taking control. DLPFC may also be associated with human intelligence. However, even when correlations are found between the DLPFC and human intelligence, that does not mean that all human intelligence is a function of the DLPFC. In other words, this region may be attributed to general intelligence on a broader scale as well as very specific roles, but not all roles. For example, using imaging studies like
PET A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence ...
and
fMRI Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area ...
indicate DLPFC involvement in
deductive Deductive reasoning is the mental process of drawing deductive inferences. An inference is deductively valid if its conclusion follows logically from its premises, i.e. if it is impossible for the premises to be true and the conclusion to be fals ...
, syllogistic reasoning. Specifically, when involved in activities that require syllogistic reasoning, left DLPFC areas are especially and consistently active. The DLPFC may also be involved in threat-induced anxiety. In one experiment, participants were asked to rate themselves as behaviorally inhibited or not. Those who rated themselves as behaviorally inhibited, moreover, showed greater tonic (resting) activity in the right-posterior DLPFC. Such activity is able to be seen through
Electroencephalogram Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
(EEG) recordings. Individuals who are behaviorally inhibited are more likely to experience feelings of stress and anxiety when faced with a particularly threatening situation. In one theory, anxiety susceptibility may increase as a result of present vigilance. Evidence for this theory includes
neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incr ...
studies that demonstrate DLPFC activity when an individual experiences vigilance. More specifically, it is theorized that threat-induced anxiety may also be connected to deficits in resolving problems, which leads to uncertainty. When an individual experiences uncertainty, there is increased activity in the DLPFC. In other words, such activity can be traced back to threat-induced anxiety.


Social cognition

Among the prefrontal lobes, the DLPFC seems to be the one that has the least direct influence on social behavior, yet it does seem to give clarity and organization to
social cognition Social cognition is a sub-topic of various branches of psychology that focuses on how people process, store, and apply information about other people and social situations. It focuses on the role that cognitive processes play in social interacti ...
. The DLPFC seems to contribute to social functions through the operation of its main speciality the executive functions, for instance when handling complex social situations. Social areas in which the role of the DLPFC is investigated are, amongst others, social perspective taking and inferring the intentions of other people, or
theory of mind In psychology, theory of mind refers to the capacity to understand other people by ascribing mental states to them (that is, surmising what is happening in their mind). This includes the knowledge that others' mental states may be different fro ...
; the suppression of selfish behavior, and commitment in a relationship.


Relation to neurotransmitters

As the DLPFC undergoes long maturational changes, one change that has been attributed to the DLPFC for making early cognitive advances is the increasing level of the neurotransmitter dopamine in the DLPFC. In studies where adult macaques' dopamine receptors were blocked, it was seen that the adult macaques had deficits in the A-not-B task, as if the DFPLC was taken out altogether. A similar situation was seen when the macaques were injected with
MPTP MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study d ...
, which reduces the level of dopamine in the DLPFC. Even though there have been no physiological studies about involvement of cholinergic actions in sub-cortical areas, behavioral studies indicate that the neurotransmitter
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
is essential for working memory function of the DLPFC.


Clinical significance


Schizophrenia

Schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
may be partially attributed to a lack in activity in the frontal lobe. The dorsolateral prefrontal cortex is especially underactive when a person has chronic schizophrenia. Schizophrenia is also related to lack of dopamine neurotransmitter in the
frontal lobe The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove be ...
. The DLPFC dysfunctions are unique among the schizophrenia patients as those that are diagnosed with depression do not tend to have the same abnormal activation in the DLPFC during working memory-related tasks. Working memory is dependent upon the DLPFC's stability and functionality, thus reduced activation of the DLPFC causes schizophrenic patients to perform poorly on tasks involving working memory. The poor performance contributes to the added capacity limitations in working memory that is greater than the limits on normal patients. The cognitive processes that deal heavily with the DLPFC, such as memory, attention, and higher order processing, are the functions that once distorted contribute to the illness.


Depression

Along with regions of the brains such as the limbic system, the dorsolateral prefrontal cortex deals heavily with
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
(MDD). The DLPFC may contribute to depression due to being involved with the disorder on an emotional level during the suppression stage. While working memory tasks seem to activate the DLPFC normally,Cite error: The named reference Functional_Genomics was invoked but never defined its decreased grey matter volume correlates to its decreased activity. The DLPFC may also have ties to the
ventromedial prefrontal cortex The ventromedial prefrontal cortex (vmPFC) is a part of the prefrontal cortex in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe at the bottom of the cerebral hemispheres and is implicated in the processing of r ...
in their functions with depression. This can be attributed to how the DLPFC's cognitive functions can also involve emotions, and the VMPFC's emotional effects can also involve self-awareness or self-reflection. Damage or lesion to the DLPFC can also lead to increased expression of depression symptoms.


Stress

Exposure to severe
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
may also be linked to damage in the DLPFC. More specifically, acute stress has a negative impact on the higher cognitive function known as
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term memory, ...
(WM), which is also traced to be a function of the DLPFC. In an experiment, researchers used functional magnetic resonance imaging (fMRI) to record the neural activity in healthy individuals who participated in tasks while in a stressful environment. When stress successfully impacted the subjects, their neural activity showed reduced working memory related activity in the DLPFC. These findings not only demonstrate the importance of the DLPFC region in relation to stress, but they also suggest that the DLPFC may play a role in other psychiatric disorders. In patients with
post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on ...
(PTSD), for example, daily sessions of right dorsolateral prefrontal
repetitive transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse ge ...
(rTMS) at a frequency of 10 Hz resulted in more effective therapeutic stimulation.


Substance use

Substance use disorders (SUD) may correlate with dorsolateral prefrontal cortex dysfunction. Those who recreationally use drugs have been shown to engage in increased risky behavior, possibly correlating with a dysfunction of the DLPFC. The executive controlling functions of the DLPFC in individuals who recreationally use drugs may have a connection that is lessen from risk factoring areas such as the
anterior cingulate cortex In the human brain, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involved ...
and insula. This weakened connection is even shown in healthy subjects, such as a patient who continued to make risky decisions with a disconnect between their DLPFC and insula. Lesions of the DLPFC may result in irresponsibility and freedom from inhibitions, and the use of drugs can invoke the same response of willingness or inspiration to engage in the daring activity.


Alcohol

Alcohol creates deficits on the function of the prefrontal cortex. As the anterior cingulate cortex works to inhibit any inappropriate behaviors through processing information to the executive network of the DLPFC, as noted before this disruption in communication can lead to these actions being made. In a task known as Cambridge risk task, SUD participants have been shown to have a lower activation of their DLPFC. Specifically in a test related to alcoholism, a task called the Wheel of Fortune (WOF) had adolescents with a family history of alcoholism present lower DLPFC activation. Adolescents that have had no family members with a history of alcoholism did not exhibit the same decrease of activity.


See also

*
Attention versus memory in prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46 ...
*
Attentional shift Attentional shift (or shift of attention) occurs when directing attention to a point increases the efficiency of processing of that point and includes inhibition to decrease attentional resources to unwanted or irrelevant inputs. Shifting of attenti ...
*
Brodmann area 46 Brodmann area 46, or BA46, is part of the frontal cortex in the human brain. It is between BA10 and BA45. BA46 is known as middle frontal area 46. In the human brain it occupies approximately the middle third of the middle frontal gyrus and the ...
*
Cognitive control In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and suc ...
*
Dorsomedial prefrontal cortex The dorsomedial prefrontal cortex (dmPFC or DMPFC is a section of the prefrontal cortex in some species' brain anatomy. It includes portions of Brodmann areas BA8, BA9, BA10, BA24 and BA32, although some authors identify it specifically wi ...
*
Mesocortical pathway The mesocortical pathway is a dopaminergic pathway that connects the ventral tegmentum to the prefrontal cortex. It is one of the four major dopamine pathways in the brain. It is essential to the normal cognitive function of the dorsolateral pref ...
*
Wisconsin Card Sorting Test The Wisconsin Card Sorting Test (WCST) is a neuropsychological test of set-shifting, which is the capability to show flexibility when exposed to changes in reinforcement.E. A. Berg. (1948). A simple objective technique for measuring flexibility in ...
*
Frontoparietal network The frontoparietal network (FPN), generally also known as the central executive network (CEN) or, more specifically, the lateral frontoparietal network (L-FPN) (see Nomenclature), is a large-scale brain network primarily composed of the dorsol ...


References

{{Cerebral cortex Cerebral cortex