Dorsolateral prefrontal cortex
|Brain: Dorsolateral Prefrontal Cortex|
|Latin||Cortex praefrontalis dorsolateralis|
DorsoLateral Prefrontal Cortex (DLPFC) is one of the most evolved parts of the human brain. It undergoes an extremely prolonged period of maturation that lasts until adulthood. The DLPFC is an area in the anterior region of humans and primates brain called Prefrontal Cortex. DLPFC is not an anatomical structure, but rather a functional one. This region lays in the middle frontal gyrus of humans (i.e., lateral part of Brodmann's area (BA) 9 and 46  and in macaque monkeys, this region is around the principal sulcus (i.e., in Walker's area 46 ). Other sources considered that DLPFC is attributed anatomically to BA 9 and 46  and BA 8, 9 and 10. DLPFC is connected to the Orbitofrontal Cortex, and to a variety of brain areas, which include the Thalamus, parts of the Basal Ganglia (specifically, the dorsal Caudate Nucleus), the Hippocampus, and primary and secondary association areas of Neocortex, including posterior temporal, parietal, and occipital areas. Also, DLPFC is the end point for the Dorsal Pathway (Stream) that tells the brain how to interact with the stimuli. On the other hand, the Ventrolateral Prefrontal Cortex (located more inferior/ventral to DLPFC) is the end point of the Ventral Pathway (Stream) that brings information about the stimuli’s characteristics.
As DLPFC is composed of spatial selective neurons, 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 Dorsolateral Prefrontal cortex is defined by its connection to: superior temporal cortex, posterior parietal cortex, anterior and posterior cingulate, premotor cortex, retrosplenial cortex, and Neocerebellum, as these connections allows DLPFC to regulate the activity of those regions and as well receive information from, and be regulated by those regions. Apart from the interconnections, DLPFC is primarily known for its involvement in the A-not-B or delayed response task. This task requires holding the information in mind (working memory) which scientists believe is one of the function of DLPFC. Its relation to working memory is strengthened by researches involving study of A-not-B task with adult macaques. These researches concluded that lesions that destroy DLPFC disrupt the macaques’ performance of the A-not-B task. However, lesions to other brain parts didn’t impair their performance on this A-not-B task.
DLPFC, however, is not required for the memory of a single item. So, our recognition memory remains unimpaired even after damage to the Dorsolateral Prefrontal Cortex. Nevertheless, if two items must be compared in the memory, then involvement of DLPFC is required. Researchers have found that the people with damaged DLPFC were 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.
DLPFC is involved in both risky and moral decision making; studies show that when individuals have to make moral decisions like how to distribute limited resource, DLPFC is activated. This region is also active when costs and benefits of alternative choices are of interests. Similarly, when options for choosing alternatives are present, DLPFC evokes preference towards most equitable option and suppresses temptation to maximizing personal gain.
The right DLPFC in conjunction with right temporo-parietal junction establishes the capacity for individuals to adopt the perspective of someone else. This facilitates cooperation and correspondence. A study conducted to monitor activation of DLPFC through administration of a trust game concluded that activation of the right DLPFC may represent the attempt to suppress selfish behavior and consider the possibility of acting cooperatively. In contrast, activation of the left temporo-parietal junction in left DLPFC may represent one's attempts to infer the intentions of other people. Furthermore, it was discovered that activation of the anterior medial prefrontal cortex elevated, especially in younger adolescents, when they decided to act selfishly and not correspond. Besides trust and issues of correspondence, DLPFC is also related in relationship commitment. Damage to anterior and mid sections of the DLPFC might impede commitment in a relationship due to impaired self-efficacy.
The DLPFC is a major factor in controlling functions such as attention, executive function, and working memory. Working Memory is an ability that humans and primates have, which allows for more information to be held along with coherent thoughts and ideas, making it be called the “mental sketch-pad” or a “on-line memory”. However, working memory has a capacity limit that can cause hypofrontality, or a reduction in the activity of the Prefrontal Cortex, in people who are healthy or with DLPFC dysfunctions, such as those with schizophrenia. Working Memory is dependent upon the functionality of the DLPFC as reduced activity in the area correlates to poor performance on working memory tasks. However, the cognitive functions of working memory is prominent in other areas of the brain as well, not limited to just the DLPFC.
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. Using MRIs "Lie was discriminated from truth on a single-event level with an accuracy of 78%." More recent research has found a connection between the DLPFC and lucid dream states in which executive function is retained. Additionally, supporting evidence suggests that the DLPFC may also play a role in conflict-induced behavioral adjustment. To find the correlation between the two, several tests have helped researchers see important connections. One way in which this has been tested is through the Stroop test. In this experiment, 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 color printed. During this experiment, researchers tracked subjects’ brain activity and found that noticeable activity occurs within the DLPFC. The activation of the DLPFC correlated with the behavioral performance suggests that this region maintains the high demands of the task to resolve conflict and in theory plays a role in taking control.
In further studies, DLPFC activity indicated that human intelligence may be associated with this region. To investigate this hypothesis, researchers took a closer look at patients with DLPFC damage and administered the Wechsler Adult Intelligence Scale (WAIS) to assess this area’s necessity for performance. The WAIS, more specifically, was used as a way to examine the DLPFC’s function for general intelligence. In doing so, studies showed that patients with DLPFC damage in comparison to healthy patients did consistently worse in tasks requiring working memory and processing speed. It’s important to take note that studies like these have found a correlation between the DLPFC and human intelligence, but do not claim 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 and fMRI indicate DLPFC involvement in deductive, 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 (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 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.
Relation to Neurotransmitters
As DLPFC undergoes long maturational changes, one change that has been attributed to DLPFC for making early cognitive advances is the increasing level of neurotransmitter Dopamine in DLPFC. Studies where the adult macaques' Dopamine receptors were blocked, it was seen that the adult macaques had deficit in the A-not-B task, as if the whole DFPLC was taken out altogether. Similar situation was seen when the macaques were injected with MPTP injection as it 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 neurotransmitter acetylcholine is essential for working memory function of the DLPFC.
Schizophrenia may be partially attributed to a lack in activity in the frontal lobe. Especially, Dorsolateral prefrontal cortex is hypoactive when a person suffers from chorionic schizophrenia. Schizophrenia is also related to lack of dopamine neurotransmitter in the frontal lobe. The DLPFC dysfunctions are unique among the schizophrenia patients as patients 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 functionally, thus reduced activation of it causes for 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 DPLFC, such as memory, attention, and higher order processing, are the functions that once distorted contribute to the factors of the illness.
Along with regions of the brains such as the limbic system, the dorsolateral prefrontal cortex deals heavily with major depressive disorder (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 activate the DLPFC normally, it has been found that the brain also may have grey matter volume abnormalities in this region. This decrease is hypothesized as the DLPFC has been found to have a decrease in activity in MDD. The DLPFC may also have ties to the ventromedial prefrontal cortex 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.
Exposure to severe stress 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 (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 (PTSD), for example, daily sessions of right dorsolateral prefrontal repetitive transcranial magnetic stimulation (rTMS) at a frequency of 10 Hz resulted in more effective therapeutic stimulation.
Substance abuse of drugs, or substance use disorder (SUD), has links to the diminished executive functions of the dorsolateral prefrontal cortex. Those who abuse 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 display drug abuse may have a connection that is lessen from risk factoring areas such as the Anterior cingulate cortex and Insula. This weaken 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. And of the results of lesion of the DLPFC includes irresponsibility and freedom from inhibitions, the abuse of drugs can invoke the same response of daring activity.
Alcohol can create an effect on the functionality of the Prefrontal Cortex and can contribute to the regulation of alcoholism. As the ACC 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.
- Attention versus memory in prefrontal cortex
- Attentional shift
- Cognitive control
- Mesocortical pathway
- Working memory
- Wisconsin Card Sorting Test
- Ventromedial prefrontal cortex
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