Abstract

This article summarizes the cognitive and behavioral functions of the prefrontal cortex with an emphasis on executive cognitive functions and the clinical consequences associated with executive dysfunction. The clinical manifestations of lesions to the lateral prefrontal, orbitofrontal, medial prefrontal, and frontopolar cortex are reviewed. Traditional lesion studies have emphasized the role of a brain region in controlling a cognitive function. With advances in neurology, neuropsychology, and neuroimaging, the participation of the prefrontal cortex in large-scale networks has been established with recognition that cognitive dysfunction can arise not only from a lesion within a network but also from degenerative disease targeting these large-scale, dynamic neural networks. Although executive dysfunction can result from frontal lobe injury, this article highlights the role of distributed processes subserving executive functions. An atypical phenotype of Alzheimer disease has been described that selectively targets parietal-temporal-frontal networks important for core executive functions. Executive function comprises working memory, cognitive flexibility, and inhibition and depends on top-down (ie, goal-driven) control of distributed processes occurring throughout the brain. The exact behavioral output (ie, function) depends on the content of the processes being controlled. Prefrontal cortex regions serve key cognitive functions related to social, emotional, and motivational aspects of behavior. The dorsal lateral prefrontal cortex plays a role in working memory, goal-driven attention, task switching, planning, problem-solving, and novelty-seeking. The ventral lateral prefrontal cortex plays a role in inhibition, response selection, and monitoring; the medial prefrontal cortex in self-knowledge, motivation, emotional regulation, and updating goal-directed behavior; the orbitofrontal cortex in personality, inhibition, and emotional and social reasoning. Although dysexecutive syndromes have been traditionally associated with dorsolateral prefrontal cortex injury, it is now recognized that they can also result from an impaired parietal-temporal-frontal system, which is targeted in a distinct form of atypical Alzheimer disease. This dysexecutive Alzheimer phenotype is characterized by impaired task performance on a wide battery of neuropsychological tests and simple daily tasks that require executive control. In contrast, dysexecutive syndromes more localized to the frontal lobe involve impaired executive control of social, emotional, and motivational aspects of behavior.

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