Which part of the cerebral cortex is involved in higher level mental functioning?

Cognitive Studies in the Ventromedial Prefrontal Cortex

The ventral and medial sector of the frontal lobe has undergone extensive evolutionary development in humans in comparison to other primates. This region is implicated in the most human of behaviors, such as social interaction, moral judgment, fairness, self-control, prediction of the future, and decision making in conflict situations.88-90 A number of functional imaging studies have shown representation of these cognitive processes in this region of the brain.91-98 Individuals who sustain damage to this region of the brain do not exhibit deficits in cognition that can be measured with conventional neuropsychological tests; however, they often exhibit inappropriate social behavior and poor judgment with regard to their social and financial well-being.90,99 Their choices are more influenced by immediate rewards even though the consequences of their choices are predicted to cause substantial disadvantage to them.100,101

Anatomic studies have shown that the ventral and medial sectors of the prefrontal cortex have abundant connections with the sensory areas of multiple modalities and subcortical structures, including the hypothalamus, thalamus, amygdala, and brainstem.102-104 The connectivity of this region supports the proposed function of this area, specifically the processing of various multimodal sensory inputs to modulate behavior, including visceral and autonomic function, to match behavior to fit appropriately to the situation in which an individual is placed.

The vast majority of this knowledge has been derived from lesion and functional imaging studies in humans and electrophysiologic studies in animals. Because the frontal lobe and functions of the frontal lobes are the most developed in humans, there is a compelling rationale to investigate these functions in humans (and not in nonhuman primates). Some of the functions in this region, such as ethics, morality, and emotional valence, are extremely difficult to study in other animal systems because it remains debatable whether and to what extent such functions exist in animals. Functional imaging methods provide an overview of wide brain regions with superior spatial resolution, up to a millimeter in scale. However, the greatest disadvantage of functional imaging methods, as well as lesion methods, is poor temporal resolution. In contrast, electrophysiologic studies in animals have the advantage of investigating finely detailed neural responses with precise time resolution, up to the millisecond scale, with simultaneous precision in spatial specificity.

Intracranial recording in epilepsy patients has the potential to fill the gap between lesion and functional imaging studies in humans and electrophysiologic studies in animals. Although the extent of the field of view is restricted to the vicinity of the area covered by electrodes, the electrophysiologic method in humans provides an incomparable level of time resolution and superb spatial resolution that can localize the neural activity of interest with unsurpassed precision.

IV Conclusions

The prefrontal cortex is regarded as a critical portion of the cerebral cortex that mediates intellectual or executive functions. Its diverse but specific connectivity patterns, electrophysiological properties, neuroimaging correlates, and associated clinical sequelae all reinforce the complex role of the prefrontal cortex in mediating higher order behaviors. The prefrontal cortex can be viewed as a major component of a large-scale neurocognitive network where complex behaviors are organized at the interactive level of multifocal neural systems. This network contains a variety of anatomical projections for transferring informational content to and from the prefrontal cortex. Also important is complex local circuitry involved in the short-term storage of information, encoding of this information, and synthesis of the associated mental representations to achieve an appropriate goal-directed response. The significance of the prefrontal cortex, which is extensively developed in primates, is related to its involvement in dynamic mental functions that underlie behaviors in response to novel and challenging demands.

Prefrontal Cortex

The prefrontal cortex encompasses a large part of the frontal cortex just anterior to the motor cortex. Although no evidence exists for direct nociceptive connections, the area is mentioned here because of its role in higher cognitive function and endogenous modulation of pain. The prefrontal cortex is implicated in the majority of pain-related imaging studies and is even more frequently involved during chronic pain.14 The medial prefrontal cortex and dorsolateral prefrontal cortex are the subdivisions more commonly activated during pain, and both areas are involved in executive function, attention, and execution of high-order tasks. The dorsolateral prefrontal cortex is specifically involved in the placebo response, in which pain sensations are modulated by expectation.140

The prefrontal cortex is one of the last cortical regions to undergo full phylogenetic and ontogenetic development. It is profusely and reciprocally connected with subcortical and other cortical structures, notably the thalamus, the basal ganglia, the hypothalamus, the amygdala, the hippocampus, and cortices of association of the temporal and parietal lobes. Several neurotransmitter systems are represented in the prefrontal cortex, notably dopamine and cholinergic systems. Based on neuropsychological, neurophysiological, and neuroimaging studies, it can be concluded that the principal and most general function of the prefrontal cortex is the temporal organization of behavior, speech, and reasoning. That general function is supported by at least three cognitive functions in which the prefrontal cortex critically participates: active short-term memory (working memory), preparatory action set, and control of interference.

Prefrontal Cortex Mediates Working Memory and Decision Making

The part of each frontal lobe anterior to areas 4 and 6 is referred to asprefrontal cortex, and it has a different role from that of the other cortical areas considered in this chapter. Prefrontal cortex does not cause movements when stimulated, and it does not contain any primary sensory areas. Instead, it is centrally involved in controlling the activities of other cortical areas—to such an extent that it is seen as underlying theexecutive functions of the brain: planning, insight, foresight, and many of the most basic aspects of personality. Consistent with this, prefrontal cortex expanded dramatically during mammalian evolution (seeFig. 22.12) and now occupies the inside of the distinctively large forehead of humans.

Different prefrontal areas share extensive interconnections with the dorsomedial nucleus of the thalamus. These play an important role in the workings of this cortical area, as shown by the observation that lesions of the dorsomedial nucleus have effects that are in some ways similar to those of prefrontal damage. In a functional sense, and in terms of patterns of connections with other parts of the forebrain, there are two broad sets of prefrontal areas (Fig. 22.25). The parts exposed on the lateral convexity(dorsolateral prefrontal cortex) have massive interconnections with parietal multimodal cortex and somatosensory, visual, and auditory association areas (via the long association bundles mentioned earlier; seeFig. 22.9). Many neurons in analogous regions of monkey prefrontal cortex respond to various kinds of stimuli, but they respond especially vigorously when the stimulus is gone and the monkey's task is to remember it briefly to receive a reward. This is consistent with the idea that dorsolateral prefrontal cortex plays a critical role inworking memory, the ability to keep “in mind” recent events or the moment-to-moment results of mental processing. (A common example of working memory is remembering a telephone number until you have finished entering it.) Patients with damage in this prefrontal area have problems with planning, solving problems, and maintaining attention.

In contrast,ventromedial prefrontal cortex (extending into orbitofrontal and anterior cingulate areas) is interconnected more with limbic structures such as the amygdala, as described further inChapter 23. Patients with damage here are impulsive and have trouble suppressing inappropriate responses and emotional reactions; some psychopathic conditions are thought to be a reflection of orbitofrontal dysfunction. An early clue to the role of this area in human behavior was provided by an unfortunate accident in the 19th century. In 1848 Phineas Gage, the foreman of a railroad construction crew, was setting a charge of explosives in a hole in rock, using a 13-pound,

The prefrontal cortex is the association cortex of the frontal lobe. It is one of the last brain structures to develop in the course of evolution. In the human, it constitutes more than one-quarter of the entire cerebral cortex. The prefrontal cortex is profusely connected with many other parts of the brain, notably limbic formations and cortical regions of the parietal and temporal lobes. It has two major anatomical and functional subdivisions: the orbitomedial and the dorsolateral prefrontal regions. The Orbitomedial cortex is involved in sensory processing (taste and olfaction), regulation of the internal environment, control of drives, and emotional behavior. The dorsolateral cortex is involved in cognitive functions. The prefrontal cortex as a whole plays a cardinal role in the temporal organization of behavior and cognitive activities. It controls the execution, order and timing of sequential acts toward a goal. The dorsolateral prefrontal cortex, in particular, is essential for the planning and execution of complex new temporal structures of behavior, speech and logical reasoning. Two cognitive functions of temporal integration mediate the organization of these activities: short-term memory and preparatory set. The dorsolateral prefrontal cortex supports both these functions in cooperation with other cortical and subcortical structures.

Summary

The PFC subserves executive functions by organizing information required for future thought and action. A vast body of literature across species indicates that the cognitive tasks of the PFC are sensitive to a variety of neurochemicals and that different neurotransmitter systems have distinct roles in cognitive functions of the PFC. However, there are several formative obstacles to fully delineating the neurochemical modulation of executive functions, most notably, the myriad actions of specific receptors and the broad range of tasks regulated by the various subregions of the PFC. Understanding the intricacies of these powerful neurochemical influences on PFC function is key to our understanding of the etiology and treatment of many neuropsychiatric illnesses, including schizophrenia, ADHD, and PTSD, as well as the decline in PFC cognitive functions with advancing age.

7.3 Prefrontal—storage or executive control?

The prefrontal cortex is an important site for working memory function. According to one interpretation, this brain region participates directly in the storage of information. However, the PFC is also associated with control of working memory. Patients with left temporo-parietal damage may have a storage deficit in working memory and can't perform even simple maintenance tasks with auditory-verbal information. The findings from these patients can be contrasted with those from patients with damage to the PFC (D'Esposito & Postle, 1999). Some PFC patients show little impairment in passive maintenance of information over a delay. However, these patients were impaired in mentally manipulating or acting upon briefly stored information. Perhaps PFC supports the mental “work” performed on stored information, rather than as a site for storage itself. (D'Esposito & Chen, 2006).

One possibility is that different parts of the PFC do different things. This is the so-called “maintenance” versus “manipulation” distinction. It has been argued that all of the PFC has an executive function in working memory but that different subdivisions do this at different levels of analysis (Ranganath, 2006). The PFC may enhance relevant information in other parts of the cortex. When the information is specific, more ventral PFC regions are engaged. When the information involves integration of multiple items in memory, the dorsal PFC regions are engaged. More frontal regions of the PFC may coordinate and monitor different PFC regions. If this is true, the main role of the PFC is not working memory but working with memory (Moscovitch, 1992; Moscovitch & Winocur, 1992).

The prefrontal cortex

The prefrontal cortex region plays a role in the decreasing of pain sensation by inhibition of the pathway between the medial thalamus and the midbrain. Activation of the dorsolateral section of the prefrontal cortex has occurred in the study of the mechanism of placebo action. This phenomenon is explained by the functioning of the prefrontal cortex maintenance and integration of the pain relief. The anterolateral section of the prefrontal cortex regulates the anticipatory anxiety of pain. The activation of the prefrontal cortex is mostly parallel to the activation of the periaqueductal gray and the ventral tegmental area, and also to the cortex, posterior insula, and the anterior portion of the cingulate gyrus.

The Prefrontal Cortex

PFC has dramatically expanded in size and complexity across evolution, and its development correlates with the complexity of the behavioral repertoire exhibited by an organism. It has reached its pinnacle in humans, in which it accounts for approximately 30% of the total cortical area. It consists of a collection of cortical areas that differ from one another in terms of the size, density, and distribution of their neurons. Figure 2 shows the major PFC divisions of the monkey PFC, although anatomists have subdivided these further, describing at least 18 distinct areas. The subdivisions have partly unique, but overlapping, patterns of connections with the rest of the brain, which suggests some regional differences in function. As in much of the neocortex, however, there are local connections between different PFC areas that can result in an intermixing and synthesis of the disparate information needed for cognitive control.

PFC is anatomically in a good position for a central role in executive control. Collectively, the various PFC areas have interconnections with brain areas processing external information, including all sensory systems and cortical and subcortical motor system structures, as well as internal information from limbic and midbrain structures involved in affect, memory, and reward. Indeed, neuronal activity in PFC reflects the multimodal nature of its inputs. PFC neurons encode visual, auditory, tactile, olfactory, and gustatory cues, as well as recalled memories and behavioral responses such as voluntary limb and eye movements. In short, the functional and morphological anatomy of PFC is consistent with its role in synthesizing diverse information about the external and internal world in order to produce goal-directed behavior.