A number of neuroimaging findings have been interpreted as evidence that the left inferior frontal gyrus (IFG) subserves retrieval of semantic knowledge. We provide a fundamentally different interpretation, that it is not retrieval of semantic knowledge per se that is associated with left IFG activity but rather selection of information among competing alternatives from semantic memory. Selection demands were varied across three semantic tasks in a single group of subjects. Functional magnetic resonance imaging signal in overlapping regions of left IFG was dependent on selection demands in all three tasks. In addition, the degree of semantic processing was varied independently of selection demands in one of the tasks. The absence of left IFG activity for this comparison counters the argument that the effects of selection can be attributed solely to variations in degree of semantic retrieval. Our findings suggest that it is selection, not retrieval, of semantic knowledge that drives activity in the left IFG.What parts of the brain subserve the retrieval of semantic knowledge? A number of recent neuroimaging studies, using a range of different tasks, implicate the left inferior frontal gyrus (IFG) (1-8). Despite the impressive convergence of localizations across tasks as disparate as verb generation, stem completion, and abstract͞concrete judgments, the conclusion that semantic retrieval critically involves left IFG remains uncertain for two reasons. First, a smaller but still significant number of neuroimaging studies have failed to find left IFG activation during semantic retrieval tasks. For example, neither naming pictures nor verifying word associations consistently leads to left IFG activation, despite the prima facie involvement of semantic knowledge in both tasks (9, 10). Additionally, practice of a semantic retrieval task, even after just a single repetition, causes a marked decrease in left IFG activation (2,8). Second, neuropsychological studies of patient populations have so far failed to demonstrate the necessity of left IFG for semantic retrieval. Instead, impairments of semantic knowledge are most associated with temporal lobe pathology (11-13).The goal of this article is to propose and test an alternative interpretation of the activation of left IFG during semantic retrieval tasks, based on recent theorizing about the role of prefrontal cortex in nonsemantic domains. Cohen and ServanSchreiber (14) argued that prefrontal cortex enables flexible and context-sensitive responses, particularly in tasks where a response other than the prepotent one must be selected. Kimberg and Farah (15) characterized the role of prefrontal cortex in cognition as mediating the selection of action by the weighting of information active in working memory. When the contents of working memory are not critical for action selection, because the action is prepotent, or when the contents of working memory overwhelming support one action, then demands on prefrontal cortex are low. Their model implies that demands on pre...

Brain dopamine has long been implicated in cognitive control processes, including working memory. However, the precise role of dopamine in cognition is not well understood, partly because there is large variability in the response to dopaminergic drugs both across different behaviors and across different individuals. We review evidence from a series of studies with experimental animals, healthy humans and patients with Parkinson’s disease, which highlight two important factors that contribute to this large variability. First, the existence of an optimum dopamine level for cognitive function implicates the need to take into account baseline levels of dopamine when isolating dopamine’s effects. Second, cognitive control is a multi-factorial phenomenon, requiring a dynamic balance between cognitive stability and cognitive flexibility. These distinct components might implicate the prefrontal cortex and the striatum respectively. Manipulating dopamine will thus have paradoxical consequences for distinct cognitive control processes depending on distinct basal or optimal levels of dopamine in different brain regions.

The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in working memory. Notably, persistent activity in the DLPFC is often observed during the retention interval of delayed response tasks. The code carried by the persistent activity remains unclear, however. We critically evaluate how well recent findings from functional magnetic resonance imaging studies are compatible with current models of the role of the DLFPC in working memory. These new findings suggest that the DLPFC aids in the maintenance of information by directing attention to internal representations of sensory stimuli and motor plans that are stored in more posterior regions.Working memory refers to the temporary representation of information that was just experienced or just retrieved from long-term memory. These active representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goaldirected behavior. Most definitions of working memory include both storage and (executive) control components [1]. Cognitive neuroscientists are searching for ways to disassociate the separate components of working memory in attempts to localize and clearly characterize their neural implementation. The prefrontal cortex (PFC) is thought to be the most important substrate for working memory (Fig. 1). Two key findings from studies of monkeys performing delayed response tasks suggest a crucial role for the PFC in working memory. First, experimental lesions of the principal sulcus in the dorsolateral prefrontal cortex (DLPFC) cause delay-dependent impairments [2][3][4]. That is, forgetting increases not only when a delay is imposed but increases with the length of the delay. Second, neurophysiological unit recordings from the DLPFC often show persistent, sustained levels of neuronal firing during the retention interval of delayed response Fig. 1. Lateral surface of (a) macaque and (b) human brain. The PFC is composed of lateral, medial, and orbital sectors that are believed to be functionally distinct given the selective effects of damage and distribution of afferent and efferent projections. The tinted areas correspond to those defined by Petrides and Pandya [71] based on cytoarchitecture and connectivity. Notably, the mid-DLPFC comprises areas 46 and 9/46 and the mid-VLPFC comprises areas 45 and 47/12. Note that much of area 46 lies in the depths of the principle sulcus of the monkey and the intermediate frontal sulcus of the human. Frontal premotor regions are also highlighted. The frontal eye field (F) in the macaque lies in the anterior bank of the arcuate sulcus in area 8A. In the human, F is found in the vicinity of the precentral sulcus and superior frontal sulcus junction (area 6 and maybe the caudal-most portion of 8A). The frontal eye field is a premotor region involved in the control of eye movements. Broca's area (B, area 44) is also a premotor area that is involved in the product...

For over 50 years, psychologists and neuroscientists have recognized the importance of a “working memory” to coordinate processing when multiple goals are active, and to guide behavior with information that is not present in the immediate environment. In recent years, psychological theory and cognitive neuroscience data have converged on the idea that information is encoded into working memory via the allocation of attention to internal representations – be they semantic long-term memory (e.g., letters, digits, words), sensory, or motoric. Thus, information-based multivariate analyses of human functional MRI data typically find evidence for the temporary representation of stimuli in regions that also process this information in nonworking-memory contexts. The prefrontal cortex, on the other hand, exerts control over behavior by biasing the salience of mnemonic representations, and adjudicating among competing, context-dependent rules. The “control of the controller” emerges from a complex interplay between PFC and striatal circuits, and ascending dopaminergic neuromodulatory signals.

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