The ability to manipulate information in working memory is a key factor in cognitive development. Here, we used event-related functional MRI to test the hypothesis that developmental improvements in manipulation, relative to pure maintenance, are associated with increased recruitment of dorsolateral (DL) prefrontal cortex (PFC) and superior parietal cortex. Three age groups (8 -12 years old, 13-17 years old, and 18 -25 years old) performed an object-working memory task with separate maintenance and manipulation conditions. We found that 8-to 12-year-olds did not perform the task as well as adolescents or adults, particularly on trials requiring manipulation in addition to maintenance. In this study, no age differences were observed in the activation profile of ventrolateral PFC, a region associated with online maintenance. In contrast, unlike the older participants, 8-to 12-year-olds failed to recruit right DL PFC and bilateral superior parietal cortex during the delay period for manipulation relative to maintenance. This group difference was observed specifically during the delay period, while participants reordered items in working memory, and could not be accounted for by group differences in performance. Across participants, activation levels in right DL PFC and superior parietal cortex, but not ventrolateral PFC, were positively correlated with performance on manipulation trials. These results indicate that increased recruitment of right DL PFC and bilateral parietal cortex during adolescence is associated with improvements in the ability to work with object representations.prefrontal cortex ͉ children ͉ executive function ͉ intelligence W orking memory, or the ability to keep information in a highly accessible state (1), improves over the course of childhood (2-4). The ability to keep information in mind is essential for a variety of cognitive abilities, including reading, mathematical calculation, and problem-solving (5, 6), and working memory capacity predicts school performance (7). Developmental changes in the ability to maintain information online are observed in school-aged children (e.g., 8). However, these changes are more dramatic when children must manipulate, or work with, this information (9, 10). In this study, we focus on the neural substrates that support developmental changes in the ability to manipulate information in working memory.The finding that children have particular difficulty on tasks involving manipulation could be explained in several ways. One possibility is a unitary account (e.g., 11), whereby general improvements in working memory occur over childhood, and challenging working memory tasks, which often involve manipulation, are associated with protracted behavioral changes. Another possibility is a process-specific account of working memory development, following up on the neuroscientific studies that suggest that maintenance and manipulation are dissociable components of working memory (12)(13)(14). Under the process-specific account of working memory development, manipulati...

The ability to retrieve and flexibly switch between task rules is seen as an important component of cognitive control. It is often assumed that lateral prefrontal cortex (latPFC) is important for switching between rules. However, activation associated with rule-switching is less reliably observed in latPFC than in medial PFC (specifically, pre-supplementary motor area). In this study, we tested the hypothesis that medial PFC is important for reconfiguration of task sets, whereas latPFC is important for retrieving, maintaining and implementing relevant rules (i.e. rule representation). Twenty young adults participated in a functional magnetic resonance imaging study in which they determined the correct response to a target stimulus on the basis of an instructional cue. For bivalent targets, the appropriate response depended on the currently relevant rule. In contrast, univalent targets were always associated with the same response. Brain regions of interest were characterized according to their responsiveness to bivalent and univalent targets, on both rule-switch and rule-repetition trials. The data support the hypothesis that rule representation and task-set reconfiguration are separable cognitive processes, associated with dissociable neural activation in latPFC and medial PFC, respectively. Activation profiles of posterior parietal cortex, basal ganglia and rostrolateral PFC are also examined and discussed.

The present study examined the contributions of prefrontal cortex (PFC) subregions to two component processes underlying verbal analogical reasoning: semantic retrieval and integration. Event-related functional magnetic resonance imaging data were acquired while subjects performed propositional analogy and semantic decision tasks. On each trial, subjects viewed a pair of words (pair 1), followed by an instructional cue and a second word pair (pair 2). On analogy trials, subjects evaluated whether pair 2 was semantically analogous to pair 1. On semantic trials, subjects indicated whether the pair 2 words were semantically related to each other. Thus, analogy--but not semantic--trials required integration across multiple retrieved relations. To identify regions involved in semantic retrieval, we manipulated the associative strength of pair 1 words in both tasks. Anterior left inferior PFC (aLIPC) was modulated by associative strength, consistent with a role in controlled semantic retrieval. Left frontopolar cortex was insensitive to associative strength, but was more sensitive to integration demands than was aLIPC, consistent with a role in integrating the products of semantic retrieval to evaluate whether distinct representations are analogous. Right dorsolateral PFC exhibited a profile consistent with a role in response selection rather than retrieval or integration. These findings indicate that verbal analogical reasoning depends on multiple, PFC-mediated computations.

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Objective-Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control.Method-Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-leveldependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control.Results-Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning.Conclusions-These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia. Kraepelin (1) described the behavioral disorganization and cognitive deficits in schizophrenia as "an orchestra without a conductor," which presciently suggests that cognitive control-the coordination of thoughts and actions that facilitates goal-oriented behavior-is one of the key higher-order cognitive processes impaired in individuals with schizophrenia. The findings of basic studies in cognitive neuroscience suggest that the neural correlate of cognitive control is the coordinated activity of task-relevant brain regions, and the dorsolateral prefrontal cortex plays a key role in this process (2-4).Although dorsolateral prefrontal cortex dysfunction has been one of the most rep...