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The guided activation theory of prefrontal cortex

Author: Dr Simon Moss


The prefrontal cortex is an extensive and important area of the human brain--approximately 30% of the cerebral cortex--that is situated in the front part of the frontal lobe. The guided activation theory of prefrontal cortex function attempts to characterize the main function of this set of regions (Miller & Cohen, 2001). This theory integrates some fascinating and diverse findings about the prefrontal cortex.

According to Miller and Cohen (2001), the prefrontal cortex represents persistent goals, rules, or retrieval cues. These goals, rules, or cues bias the associations between other regions of the brain. Using statistical language, the prefrontal cortex acts as a moderator and not as a mediator.

To illustrate, individuals often learn relationships between cues--such as tangible stimuli or private thoughts--and events, including behaviors or other cognitions. For example, when someone seems angry, representing a cue, they might tend to flee, representing a response. Alternatively, when they feel tired, they might yawn.

However, in some contexts, these responses might not be appropriate. If they are auditioning for a play, they would not flee if their collaborator seems angry. If they are seeking a job, they would not yawn if tired.

The complication, however, is the context in which individuals operate is not always apparent in the immediate environment. Someone might be auditioning for a play or seeking a job in any environment: in a house, office, or cafe, for example. The immediate cues in the environment, therefore, do not determine whether or not individuals should flee if someone is angry. These cues do not determine whether yawning is appropriate if a person feels tired.

Thus, to ascertain the appropriate response, the context--such as the goals, rules, or means--of individuals must be retained in memory. This context is retained in the prefrontal cortex. The prefrontal cortex then biases the associations between other regions of the brain. For example, if the goal is to audition for a play, the prefrontal cortex will inhibit the relationship between expressions that represent anger and the inclination to flee. If the goal is to seek a job, the prefrontal cortex will inhibit the relationship between a feeling of fatigue and the inclination to yawn.

Variations in control

Sometimes, individuals need to monitor and control their behavior carefully--driving in difficult conditions or speaking to fragile people. In these instances, individuals realize they probably will need to override their natural response to some cue. In other words, according to the guided activation theory of prefrontal cortex function, in these instances, this cortical region should be especially activated. Individuals should be particularly inclined to control their behavior and inhibit their inclinations.

Hence, in threatening or brittle contexts, the prefrontal cortex needs to be especially activated. Conceivably, the anterior cingulate cortex activates the prefrontal cortex in these instances. That is, the anterior cingulate cortex identifies potential and significant conflicts--instances in which a cue seems to elicit competing tendencies (for a discussion, see Botvinick, Nystrom, Fissell, Carter, & Cohen, 1999). The anterior cingulate cortex will then increase activation of the prefrontal cortex. In essence, the anterior cingulate cortex identifies the potential conflict, and the prefrontal cortex controls behavior vigilantly, overriding unsuitable inclinations, in response to these conflicts.

Functional organization

According to Miller and Cohen (2001), the orbital prefrontal cortex might be especially likely to bias processes, thwarting the dominant responses to cues. In contrast, the dorsal areas of the prefrontal cortex might not be as involved in biasing responses. As a consequence, the orbital prefrontal cortex is more likely to be involved in instances in which conflicting inclinations arise--and thus seem to be more involved in emotional or social settings.

When these subdivisions are considered, variations in terminology need to be recognized. For example, some researchers divide the prefrontal cortex into three main sections: the dorsolateral, the orbitofrontal, and the frontopolar. The dorsolateral--areas 8, 9, 46, 44, 45, and lateral 47--is roughly the back half of the prefrontal cortex. This region comprises two main parts: the top, which is sometimes called the dorsolateral prefrontal cortex, comprising areas 8, 9, and 46, as well as the bottom, sometimes called the ventrolateral prefrontal cortex. The orbitofrontal cortex also comprises the ventromedial, basal, and orbital areas.

Evidence of the guided activation theory of prefrontal cortex

Active maintenance of goals and means

The prefrontal cortex somehow needs to sustain goals, rules, or means over an extended time. That is, the contexts, goals, rules, or means this region needs to represent are seldom evoked by cues in the immediate environment. Specifically, the prefrontal cortex must maintain these contexts, goals, rules, or means despite distractions.

Many of the properties of neurons in the prefrontal cortex align with this capacity. For example, neurons in this region often remain active when some cue is presented to when a delayed response is executed, indicative of the capacity to sustain some goal until this objective is fulfilled (Fuster & Alexander, 1971;; see also Cohen, Perlstein, Braver, Nystrom, & Noll, et al., 1997, for human studies& Courtney, Ungerleider, Keil, & Haxby, 1997).

Many other regions, such as the inferior temporal or posterior parietal areas, also exhibit this property (see Miyashita & Chang, 1988). Nevertheless, relative to these regions, the prefrontal cortex is more likely to sustain activity despite distractions. For example, when monkeys must attend to stimuli during this delay, neurons in the prefrontal cortex, but not visual areas like the inferior temporal or posterior parietal regions, are still able to sustain this level of activation.

Plasticity and flexibility

According to the guided activation theory of prefrontal cortex, this region must demonstrate plasticity. That is, this region must be able to represent novel goals, rules, or means--goals, rules, or means that become increasingly complex over time. Similarly, neurons in this region must be able to represent more complex associations.

Consistent with this condition, over 40% of the neurons in the prefrontal regions, especially the lateral divisions, represent complex associations. For example, the activation of these neurons is not related to specific responses, such as flee or yawn. Instead, these neurons are related to specific associations--one neuron might be activated only when the flee is associated with enjoyment rather than anger.

Research also highlights the plasticity and flexibility of the prefrontal cortex. Some neurons in the prefrontal might not initially be sensitive to particular features. If these features are relevant--that is, if these features determine whether or not a specific response to a cue is reinforced--the sensitivity of these neurons changes. They become sensitive to this feature. Bichot, Schall, and Thompson (1996), for example, examined neurons in the bow of the arcuate sulcus. Usually, activation of these neurons does not depend on the form or color of a stimulus. If animals learnt their responses should be contingent on these features, these neurons became sensitive to form or color.

Consistent with these arguments, when the prefrontal cortex is damaged, flexibility in behavior diminishes (Dias, Robbins, & Roberts, 1996). Performance on the Wisconsin card sorting task decinles, for example. To complete this task, participants are instructed to sort a deck of cards--cards with geometric shapes of various colors--into piles. Participants are not told whether each pile should correspond to one color, shape, or number of symbols. However, they are told whether they are correct or incorrect after each card is placed in a pile. Gradually, they begin to sort the cards into correct piles. Once ten consecutive cards are placed in the right pile, another rule is constructed. Individuals with prefrontal damage tend to rely on a previous rule--perhaps by sorting cards into piles with the same color--even when this rule no longer applies.

Updating representations

The prefrontal cortex not only maintains contexts, goals, and needs, but also must update these representations occasionally. For example, when auditioning for a play, individuals might need to disregard an angry expression in a collaborator. The representation associated with auditioning is maintained. Nevertheless, during the audition, the collaborator might genuinely become angry. The context has changed& the prefrontal cortex must update the representation of this context.

The prefrontal cortex, although resistant to distractions, must nevertheless be sensitive to relevant changes in the context. Several authors, such as Durstewitz, Seamans, and Sejnowski (2000), have delineated the mechanisms that could underpin this function. Specifically, midbrain dopaminergic neurons tend to be activated in response to unexpected rewards (see Mirenowicz & Schultz 1996). Furthermore, these neurons tend to be activated before, but not after, expected rewards are received. Activation of these neurons seems to increase the likelihood that representations of contexts, goals, rules, and needs in the prefrontal cortex are updated.

This possibility is clearly adaptive. As Miller and Cohen (2001) highlight, if you notice money on the ground--an expectation of reward--you would need to change your goal to accrue the benefit. Thus, the possibility of unexpected benefits should shift prefrontal representations.

Convergence of diverse information

According to the guided activation theory of prefrontal cortex, this set of regions must be able to integrate diverse modes of information (Miller & Cohen, 2001). First, many cues, from sensory information to affective states, should be able to shape the goals, rules, and contexts the prefrontal cortex represents. Second, the prefrontal cortex should present output to many regions as well.

Consistent with this need, the prefrontal cortex, overall, is connected to many regions of the brain. Furthermore, the subdivisions of the prefrontal cortex are extensively connected to one another.

To illustrate, the prefrontal cortex, especially the lateral and mid-dorsal but not the ventromedial divisions, are connected extensively to the sensory regions of the neocortex: the temporal, occipital, and parietal regions that receive visual, auditory, and somatosensory information (e.g., Petrides & Pandya 1984, 1999). These regions tend to receive information from more than one modality--or from sites that integrate multiple modalities. The prefrontal cortex, for example, receives information from the rostral superior temporal sulcus, which comprises neurons that response to trimodal responses (Bruce, Desimone, & Gross, 1981).

The prefrontal cortex is also connected to many motor areas. The dorsolateral division, for example, is connected to the motor areas of the medial prefrontal lobe: the supplementary motor area, the pre-supplementary motor area, and the rostral cingulate. The dorsolateral prefrontal cortex is also connected to the premotor cortex in the lateral frontal lobe. Finally, this dorsolateral division is connected to the cerebellum and superior colliculus (e.g., Schmahmann & Pandya, 1997).

The prefrontal cortex is also intimately connected to the medial temporal limbic structure, which facilitate the retrieval of long term memory and process internal states, such as affect and motivation. For example, the prefrontal cortex connects directly with the hippocampus--as well as indirectly via the medial dorsal thalamus. The prefrontal cortex is also connected to the amygdala.

Feedback to many brain regions

According to guided activation theory of prefrontal cortex, the prefrontal cortex should be able to bias a diverse range of regions. That is, goals, rules, and contexts should bias almost all forms of responses, from overt behavior to private reflections. Hence, this set of regions should direct feedback to many areas of the brain.

Certainly, the prefrontal cortex does project to many parts of the neocortex (e.g., Pandya, & Yeterian, 1990). Furthermore, activation of the prefrontal cortex does affect the extent to which other cortical regions respond to specific cues. When activation of the lateral prefrontal cortex is attenuated, for example, some visual cortical areas, especially the inferior temporal or posterior parietal regions, become less responsive to particular cues (e.g., Chafee & Goldman-Rakic, 2000).

Related topics

Taxonomies of executive functions

The guided activation theory of the prefrontal cortex, and indeed most conceptualizations of the prefrontal cortex, assume these regions underpin executive functioning. Executive functions are psychological processes that supersede habitual, but unsuitable, inclinations with novel responses to maintain and to fulfill goals. Several distinct sets of executive functions have been differentiated (see Unsworth, Miller, Lakey, Young, Meeks, Campbell, & Goodie, 2009), such as working memory, response inhibition, fluency, and vigilance. Working memory, thus, might represent a subset of executive functions.

In the literature on executive functions, working memory is usually conceptualized as the capacity to maintain information and goals in an active state. The operation span is often utilized to assess this capacity. Specifically, a sequence of mathematical equations are presented, which participants must solve. Beside each equation is a letter. Participants must memorize up to seven of these letters (Unsworth, Miller, Lakey, Young, Meeks, Campbell, & Goodie, 2009).

The second primary class of executive functions is response inhibition. Response inhibition is the capacity to substitute a dominant inclination for another response. To assess this function, participants might need to execute antisaccades (Unsworth, Miller, Lakey, Young, Meeks, Campbell, & Goodie, 2009). In particular, on each trial, a flash may be presented on one side of the screen, followed by a letter on the other side. Participants need to identify the letter as rapidly as possible. Effective performance, thus, is predicated on the capacity to override the automatic inclination of individuals to shift their eyes towards the flash.

Alternatively, any task in which individuals receive conflicting stimuli assess response inhibition. A traditional example is the flanker task. Typically, three stimuli, such as arrows, are presented simultaneously, arranged along a row. Participants must respond to the identity of the central stimulus. They might, for example, press one button if the central arrow points to the left and another button if the central arrow points in the right. On some trials, the surrounding stimuli contradict the central stimulus. The surrounding arrows, for example, might point to the left, while the central arrow might point to the right. The extent to which responses to the central stimulus are independent of the surrounding stimuli represents response inhibition.

The third primary category of executive functions is fluency, which represents the capacity to generate unique exemplars of some category. Participants, for example, might be asked to specify as many animals as possible or words that begin with F within one minute (Unsworth, Miller, Lakey, Young, Meeks, Campbell, & Goodie, 2009).

A fourth category of executive functions is vigilance--the capacity to sustain attention on a monotonous task. These tasks often last more than 10 minutes. For example, a series of Ds or backwards Ds might be presented over the course of 12 minutes. The task of participants was to detect every instance in which a 0 appeared in lieu of a D or backward D (Unsworth, Miller, Lakey, Young, Meeks, Campbell, & Goodie, 2009).

Hierarchy model of relational reasoning

In everyday life, individuals often need to appreciate the relationships between objects and events. For example, when people meet someone, they are often uncertain how to behave. To resolve this issue, they might ascertain whether this person is similar or different to other people they know. If they can identify similarities between this person and past friends, they can form a better insight into how they should behave. Comparing people represents one example of identifying the relationships--the similarities and differences--between objects and events.

According to the hierarchy model of relational reasoning (Krawczyk, McClelland, & Donovan, 2011), when the comparisons between objects are simple--perhaps because they differ on one attribute only--the back or posterior parts of the frontal cortex is activated. As the comparisons become more complex, activation shifts closer to the front or anterior parts of the prefrontal cortex.

This model was substantiated by Krawczyk, McClelland, and Donovan (2011). In their study, participants completed a series of tasks, all of which demanded relational reasoning. Some of the tasks were simple. For example, in one task, a series of three pictures were presented. The pictures were identical, except one element changed across this series in a systematic sequence. For example, a circle shifted from the left top corner, to the right top corner, and then to the bottom corner. Participants had to decide whether the series of pictures formed a sequence or varied randomly.

In addition, they completed similar tasks that were more complex, with two or three attributes that varied across the pictures. Furthermore, they undertook other tasks, such as analogies, that also varied in complexity.

In general, the simplest tasks increased activation of only the premotor cortex. Tasks in which two features varied across the items also activated the dorsolateral prefrontal cortex and inferior frontal gyrus, anterior to the premotor cortex. Tasks in which three features varied across the items also activated the frontopolar or rostrolateral prefrontal cortex (Brodmann area 10), anterior to the dorsolateral prefrontal cortex. These findings are consistent with the hierarchy model of relational reasoning.


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Last Update: 7/7/2016