Left Prefrontal Cortex: What Does It Do? This article has focused on functional neuroimaging analyses of psychological processing in one brain region, the left prefrontal cortex. It has not reviewed a wealth of related evidence about language (semantic, phonological, and orthographic) or memory processes in other brain regions, except for a brief consideration of right cerebellar activation. We have chosen this somewhat atypical approach because it emphasizes a goal of the functional neuroimaging of cognition that is not often emphasized, namely the attempt to define the large-scale functional units of cognition. Studies often report multiple activations associated with particular tasks (or more precisely task comparisons) and then interpret the significance of each activation in terms of what process may plausibly be mediated by that brain region. In principle, that same process and brain region ought to be invoked by a broad range of tasks that require the same sort of mental operation.
We have proposed that the left prefrontal activations of the kind reviewed above signify a domain-specific process of semantic working memory (6, 8, 29). This proposal builds upon the idea from Goldman-Rakic (51) that prefrontal cortex mediates domain-specific working memory representations that guide mental action in the absence of external, perceptual cues. Domain-specific working memory activations have been reported in right prefrontal cortex for spatial working memory tasks (52) and in posterior left prefrontal cortex for phonological working memory tasks (53). Similarly, it may be hypothesized that left inferior prefrontal cortex is activated to the extent that semantic information must be held temporarily in working memory (in mind) to answer a particular semantic question.
Thus, more semantic information must be held in mind to generate a verb than to read a noun or to answer a question about the meaning of a word (abstract/concrete or living/nonliving) than about the sound of a word (rhyme or syllable judgments) or the appearance of a word (uppercase/lowercase). More semantic information (or the same semantic information but for a shorter time) must be held in mind to make an initial than a repeated semantic judgment about a word or picture. More semantic (or lexical) information must be held in mind when a person must select one of many appropriate answers than when one must search carefully for even one appropriate answer. In all of these conditions, left prefrontal activation occurs in conditions that require a greater amount, a longer duration, or more selection of semantic knowledge held in working memory. Further, the more people think about the meaning of a word, or other stimuli, the better they later remember that stimulus (superior episodic encoding). Thus, the semantic working hypothesis can account for most relevant findings in a unified fashion.
In psychological research on cognition, it is common for different researchers to focus on language, on working memory, on episodic memory, or on implicit memory. The brain and mind, however, need not be organized in the same way that researchers divide cognitive domains. Indeed, one promise of functional neuroimaging is to reveal the natural organization of the brain and mind. Although there is a great deal yet to be understood about the mental operations mediated by the left prefrontal cortex, including how many distinct but adjacent operations occur in that region, it seems already that those operations may be the same whether they are considered in the context of language, working memory, episodic memory, or implicit memory. The left prefrontal cortex thus serves as a crossroads between meaning in language and memory.
We thank Matthew Prull and Mark Won for assistance in preparing this manuscript. The research reported herein and the writing of this article was supported by National Institutes of Health Grants NIA AG12995, NIA AG09466, NIMH MN53673, NIAAA AA10723, and NINDS NS09628 and the McDonnell-Pew Program in Cognitive Neuroscience.
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