Prefrontal cortex (PFC) is centrally involved in higher cognitive processes such as planning, problem solving and language, and appears to play an important role in major psychiatric illnesses, such as schizophrenia. Despite its role in uniquely human behavior, and illness, will still know relatively little about the function or organization of this brain structure. Neuropsychological and neurophysiological studies have suggested at least two possible principles by which PFC might be organized: representational content and processing function. However, studies of animals and neuropsychiatric patients provide only indirect information about the normal functioning of PFC in humans. Neuroimaging is another method for studying PFC function, that can provide information about the brain activity of normal human subjects as they are performing cognitive tasks. This project used functional magnetic resonance imaging (fMRI) to study PFC, and to test hypotheses derived from computational models of its function and organization in humans. Three sets of experiments are proposed, that will use fMRI to study activation of PFC during performance of cognitive tasks. The first set of experiments will test the idea that PFC is organized by representational content; that is, that different regions support the processing of different types of information. Patterns of activation will be compared in tasks matched for processing function, but involving different types of information (e.g., memory for object vs. spatial and verbal vs. non-verbal information). The second set of experiments will test the idea that PFC is organized by function, by comparing activation in tasks that are matched for information type, but rely on different processing functions (working memory vs. inhibition). Finally, a third set of experiments will examine the role of PFC in distributed cortical circuits involving other brain regions, such as parietal and temporal cortex. An important motivation for these experiments is to test the hypothesis, stemming from computational models of PFC, that the primary function of PFC is the representation and maintenance of context information. Two strong, testable claims follow from this hypothesis: 1) memory and inhibition reflect the operation of a single underlying processing mechanism subserved by PFC; and 2) PFC is organized primarily by representational content. Neuroimaging findings that show activation of different regions of PFC by different types of information would provide support for our hypothesis, while findings showing activation of different regions of PFC by memory and inhibition tasks (i.e., organization by function) would weigh against our hypothesis. Whether our hypothesis is confirmed or refused, however, the results of these studies will provide detailed new information about the function and organization of PFC. A better understanding of PFC promises to provide important insights into the mechanisms underlying uniquely human cognitive abilities, such as problem solving and language, and their disturbance in diseases such as schizophrenia.
| D'Ardenne, Kimberlee; Eshel, Neir; Luka, Joseph et al. (2012) Role of prefrontal cortex and the midbrain dopamine system in working memory updating. Proc Natl Acad Sci U S A 109:19900-9 |
| Lenartowicz, Agatha; Yeung, Nick; Cohen, Jonathan D (2011) No-go trials can modulate switch cost by interfering with effects of task preparation. Psychol Res 75:66-76 |
| Lenartowicz, Agatha; Escobedo-Quiroz, Rafael; Cohen, Jonathan D (2010) Updating of context in working memory: an event-related potential study. Cogn Affect Behav Neurosci 10:298-315 |
| Yeung, Nick; Nystrom, Leigh E; Aronson, Jessica A et al. (2006) Between-task competition and cognitive control in task switching. J Neurosci 26:1429-38 |
| Polyn, Sean M; Natu, Vaidehi S; Cohen, Jonathan D et al. (2005) Category-specific cortical activity precedes retrieval during memory search. Science 310:1963-6 |
| Carter, C S; Braver, T S; Barch, D M et al. (1998) Anterior cingulate cortex, error detection, and the online monitoring of performance. Science 280:747-9 |
