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Dorsolateral prefrontal cortex

Author: Dr Simon Moss


The dorsolateral prefrontal cortex, together with other connected areas, is assumed to be important in working memory and executive function--including the regulation of thinking and action. Damage to this region provokes dysexecutive syndrome.

Roles of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex

The difference between the dorsolateral prefrontal cortex and the ventrolateral prefrontal cortex aligns to the disparity between the dorsal and ventral pathways in the cortex, according to O'Reilly (2010). The dorsal pathways, which is primarily underpinned by the parietal cortex, attempts to ascertain which responses should be executed, called the how system. The ventral pathway, which is significantly underpinned by the temporal cortex, attempts to characterize the features and attributes of the stimuli in the environment, sometimes called the what system.

The dorsal pathways primarily terminate in the dorsolateral prefrontal cortex instead of the ventrolateral prefrontal cortex. The dorsolateral prefrontal cortex represents complex relationships that can be applied, such as mathematical rules or other algorithms, to convert stimuli into responses. The dorsolateral prefrontal cortex, for example, may be able to retain a rule that was imposed a few minutes ago onto the dorsal pathway to ensure responses apply to these constraints.

The ventral pathways primarily terminate in the ventrolateral prefrontal cortex instead of the dorsolateral prefrontal cortex. Presumably, which features or attributes of the environment should be processed depends on the goals of individuals. The ventrolateral prefrontal cortex represents these goals and thus affects which features or attributes are extracted. That is, the ventrolateral prefrontal cortex controls the ventral pathways.

O'Reilly (2010) accumulated considerable evidence to support this contention. For example, in one study, when individuals needed to apply complex rules to decide which responses to execute, but the stimuli could be readily differentiated, the dorsolateral prefrontal cortex was activated significantly. In contrast, when individuals needed to differentiate stimuli that differ only on subtle semantic properties, demanding the what system, the ventrolateral prefrontal cortex was activated significantly (Nagel et al., 2008).

Consequences of deficits in dorsolateral prefrontal cortex

Relationships and trust

Any damage to the dorsolateral prefrontal region--especially the anterior and mid sections--might impede commitment in relationships. In particular, damage to this region, as manifested by performance on working memory tasks, might be associated with impaired self-efficacy, which in turn can compromise commitment (Petrican & Schimmack, 2008).

The right dorsolateral prefrontal cortex, coupled with the left temporo-parietal junction, also seems to underpin the capacity of individuals to adopt the perspective of someone else, facilitating reciprocation and cooperation--a capacity that develops during adolescence. This proposition was substantiated by van den Bos, van Dijk, Westenberg, Rombouts, and Crone (2011).

Specifically, in this study, participants completed the trust game, in which one player receives money and is granted an opportunity to offer half or all to the other player. This recipient, if bestowed all the money, can then return a higher percentage to the sender. Participants were aged between 12 and 22. For some trials, the amount of money available was increased, representing greater risk.

In general, individuals were more likely to reciprocate when the risk or amount was increased: Presumably, when the risk is elevated, players who share half the money demonstrate their intention to form a reciprocal relationship. This tendency to reciprocate when the risk or amount is increased was not observed in the youngest adolescents, presumably because they had not as effectively developed this capacity to understand and accommodate the intentions of other people.

Furthermore, if individuals were the recipient of trust--that is, if they received all the money from the other person--the right dorsolateral prefrontal cortex and the left temporo-parietal junction were especially activated, but only in the older adolescents or young adults. Activation of the right dorsolateral prefrontal cortex may represent the attempt to suppress selfish behavior and consider the possibility of acting cooperatively. Activation of the left temporo-parietal junction may represent attempts to infer the intentions of other people. In contrast, activation of the anterior medial prefrontal cortex was elevated, especially in younger adolescents, when they decided to act selfishly and not reciprocate.


Traditionally, researchers have assumed the ventrolateral, and not the dorsolateral, prefrontal cortex is important in long term memory. Recent studies, however, have highlighted the roles of the dorsolateral prefrontal cortex in some facets of long term memory. In particular, to learn that two events, such as two words, are associated with each other, individuals might compare or contrast these items. This process enhances the capacity of individuals to remember the association between these items. Importantly, event-related fMRI indicates the dorsolateral prefrontal cortex is involved in this process of comparing the two events (Murray & Ranganath, 2007).

The right dorsolateral prefrontal cortex is especially likely to be involved in the memory of information that is personally meaningful. When this area is anaesthesized, for example, individuals cannot readily identify a picture of their own face (Keenan, Nelson, O'Connor, & Pascual-Leone, 2001).


Individuals who suffer from major depressive disorder show low levels of activity in the left dorsolateral prefrontal cortex but elevated levels of activity in the right dorsolateral prefrontal cortex, as reflect by event-related fMRI in response to emotional judgments. However, the elevated levels in the right dorsolateral prefrontal cortex transpired only when the emotional stimuli were expected (Grimm, Beck, Schuepbach, Hell, Boesiger, Bermpohl et al., 2008), indicating this region might be associated with attentional modulation.

Decision making

The dorsolateral prefrontal cortex is involved in both risky and moral decisions. For example, when individuals need to decide how to distribute limited resources, representing a moral decision, the dorsolateral prefrontal cortex is activated. Nevertheless, this region is especially active when the costs and benefits of each alternative, rather than emotional reactions to these options, are considered (e.g., Greene, Sommerville, Nystrom, Darley, & Cohen, 2001). This finding is consistent with the proposition that dorsolateral regions of the prefrontal cortex primarily underpin cognitive rather than emotional processes (Duncan & Owen, 2000).

The dorsolateral prefrontal cortex also tends to bias these moral decisions. To reach moral decisions, individuals often need to decide between two alternatives. One alternative will increase equity. The other alternative will reduce equity but increase the aggregate resources. To illustrate, governments might need to decide whether to fund all schools, which improves equality, or only the schools that perform well, which can improve performance on average but undermine equality. When the dorsolateral prefrontal cortex is activated, individuals prefer to optimize performance or utility, sometimes to the detriment of equity or equality (e.g., Greene, Nystrom, Engell, Darley, & Cohen, 2004).

Nevertheless, some evidence has challenged this conclusion. In a study conducted by Knoch, Treyer, Regard, Muri, Buck, and Weber (2006), participants completed the Ultimate Game task. That is, participants interacted with another person who had been bestowed a sum of money. This person was then instructed to share a small amount of this money with participants. If participants rejected the offer, neither they nor this person received any of the money--but the outcome was equitable. If participants accepted the offer, the other person did retain most of the money and, hence, the outcome was not equitable.

Transmagnetic stimulation was applied to inhibit the dorsolateral prefrontal cortex. When the dorsolateral prefrontal cortex was inhibited, participants tended to accept the offers, prioritizing utility over equality. This finding contradicts the proposition that activation of the dorsolateral prefrontal cortex fosters preferences towards utility.

Nevertheless, as Knoch and Fehr (2007) emphasize, the dorsolateral prefrontal cortex might underpin two distinct inclinations. First, the dorsolateral prefrontal cortex might evoke preferences towards utility. Second, the dorsolateral prefrontal cortex might curb the attraction of immediate financial gain. When this region is inhibited, therefore, individuals feel the need to seek equality but also fail to suppress the temptation to maximize personal gain. While completing the Ultimate Game task, the temptation to maximize personal gain might override the need to maintain equality.

Indeed, several studies indicate that activation of the dorsolateral prefrontal cortex, especially in the right hemisphere, enhances the capacity or tendency of individuals to suppress tempting responses (for discussions, see Duncan & Owen, 2000;; Miller & Cohen, 2001). This capacity might explain the findings that activation of the right, rather than left, dorsolateral prefrontal cortex, using transcranial direct current, tends to curb risk taking (Fecteau, Knoch, Dregni, Sultani, Boggio, & Pascual-Leone, 2007). Nevertheless, one of the complications of this study is that such stimulation of the dorsolateral prefrontal cortex can also activate connected regions, such as the ventromedial prefrontal cortex and the insula.


Deficits in the dorsolateral prefrontal region might underpin problem gambling. In particular, deficits in this region often manifest as undue perseveration--in which individuals do not shift their goals or states sufficiently. In addition, individuals who demonstrate problem gambling also show deficits in conditional association tasks, which are supposed to reflect functioning of the posterior-dorsolateral prefrontal region (Leiserson & Pihl, 2007).

Similarly, when the right dorsolateral prefrontal region is disrupted by TMS, participants are likely to gamble irresponsibly. While gambling, they choose alternatives that could return large amounts of money but are highly improbable (e.g., Knoch et al., 2006).


Abnormal activation of the dorsolateral prefrontal cortex has also been related to schizophrenia. For example, limited activation of the posterior left middle-frontal gyri in this region, as indicated by PET scans, are associated with the transition to schizophrenia (e.g., Harrison, Yucel, Shaw, Brewer, Nathan, Strother, et al., 2006).

Tasks that measure functioning of the dorsolateral prefrontal cortex

Performance on some tasks are especially likely to reflect functioning of the dorsolateral prefrontal cortex. One example is the Hayling Sentence Completion Test (Burgess & Shallice, 1997). In this task, a set of sentences are presented. In each instance, the last word is omitted. Usually, from the context, individuals can readily determine this word. An example might be "The captain wanted to stay with the sinking...".

In the first section, participants are instructed to complete the sentences with the appropriate word. In the previous example, the answer would be "ship". In the second section, participants are instructed to specify a different word--a term that diverges from the omitted word. In the previous example, an answer could be "rainbow". As brain imaging studies show, when participants need to inhibit the obvious word, activation of the prefrontal cortex, particularly the left dorsolateral prefrontal cortex, increases (see Nathaniel-James, Fletcher, & Frith, 1997;; Nathaniel-James & Frith, 2002).

Letter number sequencing, in contrast, reflects the functioning of several regions, including the dorsolateral prefrontal cortex (Haut, Kuwabara, Leach, & Arias, 2000). In this task, sometimes regarded as a test of working memory, a series of letters and numbers is presented. Participants are then asked to recite these letters and numbers. However, they must articulate the numbers in numerical order and the letters in alphabetical order. Effective performance on this task has been shown to demand the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the posterior parietal cortex (Haut, Kuwabara, Leach, & Arias, 2000).

Left versus right dorsolateral prefrontal cortex

Differences between the left and right dorsolateral prefrontal cortex have emerged.

Self assessment

The right, rather than left, dorsolateral prefrontal cortex seems to be important when individuals reflect upon their personal traits. In one study, conducted by Schmitz, Kawahara-Baccus, and Johnson (2004), participants received a list of adjectives. In one condition, their task was to ascertain whether these adjectives describe themselves. In another condition, their task was to ascertain whether these adjectives describe someone else. As fMRI scans revealed, activation of the right, relative to the left, dorsolateral prefrontal cortex was elevated when individuals related the adjectives to themselves.


The dorsolateral prefrontal cortex is a region in the frontal lobes of the brain, roughly equivalent to Brodmann areas 9 and 46, but sometimes considered broader.

The dorsolateral prefrontal cortex is connected to the orbitofrontal cortex as well as many primary and secondary areas of the cortex. Furthermore, the dorsolateral prefrontal cortex is connected to the dorsal caudate nucleus in the basal ganglia as well as the thalamus and hippocampus.

Organization of the dorsolateral prefrontal cortex

Many studies indicate that complex rules, with many if-then statements, are represented towards the front or rostral regions of the prefrontal cortex. In contrast, simpler rules are represented caudally. According to O'Reilly (2010), this distinction between complex and simple rules probably pertains to the dorsolateral prefrontal cortex. For example, Brodmann area 46 may represent more complex rules than Brodmann areas 8 and 9.

Dorsal cortical stream

The dorsolateral prefrontal cortex is regarded as part of the dorsal cortical stream. Specifically, according to Mayberg (1997), two cortical systems, which are distinct but related, underpin the regulation and processing of emotions. The first system is called the dorsal cortical stream and comprises the dorsolateral prefrontal cortex, coupled with the dorsal anterior cingulate, the dorsomedial prefrontal cortex, and the dorsal anterolateral prefrontal cortex. This stream underpins the intentional regulation of emotional behavior and experience as well as related executive functions, such as selective attention and planning (Davidson & Irwin, 1999).

The second system, in contrast, is the ventral cortical stream, which entails the subgenual cingulate gyrus, ventrolateral cortex, orbitofrontal cortex, the amygdala, anterior insula, ventral striatum, medial thalamas, and hippocampus--primarily located in paralimbic cortical, subcortical, and brainstem regions. This stream underpins the effortless forms of emotional regulation.

As neuroimaging studies have shown, clinical depression seems to attenuate activity in the dorsal cortical stream (see Drevets, 1999;; Soares & Mann, 1997), including the dorsolateral prefrontal cortex. In contrast, depression seems to augment brain activity in the ventral stream, as represented by blood flow and metabolism (e.g., Drevets, W. C., Videen, Price, Preskorn, Carmichael, & Raichle, 1992)-although some inconsistencies have been uncovered in some regions such as the subgenual cingulate gyrus (see Drevets, Price, Simpson, Todd, Reich, Vannier, & Raichle, 1997).

Arguably, the elevated activity in the ventral stream, especially the amygdala, is consistent with the proposition that depression coincides with a sensitivity to negative stimuli. Patients with depression, for example, recognize negative words more rapidly than positive words (Murphy, Sahakian, Rubinsztein, Michael, Rogers, Robbins, & Paykel, 1999).

Similarly, in another study, patients with depression were instructed to press a button whenever some target appeared. Targets that appeared at the same location as a sad face were recognized more rapidly by these patients than were targets that appeared at the same location as a neutral face. These findings imply that patients with depression seem to bias their attention towards negative emotions (see also Leppanen, 2006).

In addition to attention, the memory of depressed individuals is also biased towards negative states. That is, research demonstrates that patients with depression also remember negative facial expressions more readily than other facial expressions (for a review, see Leppanen, 2006).

Finally, appraisals of expressions are also biased in depressed individuals. These patients often perceive faces with ambiguous expressions as negative, rather than positive, in emotion (Bouhuys, Geerts, Gordijn 1999). Furthermore, these patients often misconstrue facial expressions. They perceive happy faces as neutral and neutral faces as sad (Gur, Erwin, Gur, Zwil, Heimberg, & Kraemer, 1992). These biases in attention, memory, and appraisal could all be ascribed to elevated activity in the amygdala and other regions of the ventral stream.

The dorsolateral prefrontal circuit

The effect of lesions to the dorsolateral prefrontal cortex resembles the effect of lesions to several subcortical regions, such as the dorsolateral caudate. This discovery, together with an examination of neuronal connections, culminated in the realization that several of these regions form a circuit, called the dorsolateral prefrontal circuit.

In particular, the dorsolateral prefrontal circuit originates in the dorsolateral prefrontal cortex, specifically Broadmann's areas 9 and 10. Neurons from these areas then project to a part of the striatum--a part of the basal ganglia--called the dorsolateral head of the caudate nucleus. From this region, neurons project to the globus pallidus interna, specifically the lateral mediodorsal part, and to the substantia nigra, particularly the rostrolateral part. From the globus pallidus and substantia nigra, neurons project to the parvocellular portions of the ventral anterior and mediodorsal thalamus, before projecting back to the dorsolateral prefrontal cortex (for a summary, see Tekin & Cummings, 2002;; for a definition of these terms, such as the basal ganglia, see Glossary of psychology terms).

Indeed, this sequence of regions represents one of five circuits: The other circuits are the lateral orbitofrontal circuit, the anterior cingulate circuit, the motor circuit, and the oculomotor circuit. The lateral orbitofrontal circuit underpins inhibition of behaviors or regulation of emotions& the anterior cingulate circuit is vital to motivation and attention. All of these circuits project from the frontal cortex and then traverse to the striatum, to the globus pallidus and substantia nigra, and then to the thalamus before returning to the frontal cortex (Alexander, DeLong, & Strick, 1986). Furthermore, in all of these circuits, projections from the frontal cortex to the striatum are excitatory, mediated by glutamate& projections from the striatum--which entails the caudate, putamen, and ventral striatum--to the globus pallidus and substantia nigra are inhibitory, mediated by GABA. Projections from these regions to the thalamus are also inhibitory and mediated by GABA. Finally, projections from the thalamus to the frontal cortex are excitatory, mediated by glutamate.

Other regions are also connected to the dorsolaterial prefrontal circuit. Parietal Area 7a, involved in visual processing and attention, and Broadmann Area 46, project onto this circuit. Furthermore, the circuit then projects onto the frontal eye fields. Furthermore, the circuit, like the other four loops, also comprises an indirect path that connects the caudate to the globus pallidus externa, then to the subthalamic nuclei, and back to the globus pallidus interna and substantia nigra.

The dorsolateral prefrontal circuit is critically involved in executive function: formulating, refining, and maintaining goals to regulate behavior and to solve problems (see Duffy & Campbell, 1994). To illustrate, when the dorsolateral prefrontal cortex is damaged, performance on the Wisconsin Card Sorting task is impaired, indicating that such individuals cannot readily shift their goals and strategies. Furthermore, fluency is also compromised (for a summary of impairments, see Tekin & Cummings, 2002). Similarly, subcortical dementia, especially lesions to the caudate, is characterized by similar problems.


Dopamine is one of the key neurotransmitters in the dorsolateral prefrontal cortex.


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Last Update: 6/8/2016