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...

What are the neural mechanisms underlying working memory (WM)? One influential theory posits that neurons in lateral prefrontal cortex (lPFC) store WM information via persistent activity. In this review, we critically evaluate recent findings that together indicate that this model of WM needs revision. We argue that sensory cortex, not lPFC, maintains high-fidelity representations of WM content. In contrast, lPFC simultaneously maintains representations of multiple goal-related variables that serve to bias stimulus-specific activity in sensory regions. This work highlights multiple neural mechanisms supporting WM, including temporally dynamic population coding in addition to persistent activity. These new insights focus the question on understanding how the mechanisms that underlie WM are related, interact, and are coordinated in lPFC and sensory cortices.

The most compelling neural evidence for working memory is persistent neuronal activity bridging past sensory cues and their contingent future motor acts. This observation, however, does not answer what is actually being remembered or coded for by this activity. To address this fundamental issue, we imaged the human brain during maintenance of spatial locations and varied whether the memory-guided saccade was selected before or after the delay. An oculomotor delayed matching-to-sample task (match) was used to measure maintained motor intention because the direction of the forthcoming saccade was known throughout the delay. We used a nonmatching-to-sample task (nonmatch) in which the saccade was unpredictable to measure maintained spatial attention. Oculomotor areas were more active during match delays, and posterior parietal cortex and inferior frontal cortex were more active during nonmatch delays. Additionally, the fidelity of the memory was predicted by the delay-period activity of the frontal eye fields; the magnitude of delay-period activity correlated with the accuracy of the memory-guided saccade. Experimentally controlling response selection allowed us to functionally separate nodes of a network of frontal and parietal areas that usually coactivate in studies of working memory. We propose that different nodes in this network maintain different representational codes, motor and spatial. Which code is being represented by sustained neural activity is biased by when in the transformation from perception to action the response can be selected.

Priority maps are theorized to be composed of large populations of neurons organized topographically into a map of gaze-centered space whose activity spatially tags salient and behaviorally relevant information. Here, we identified four priority map candidates along human posterior intraparietal sulcus (IPS0–3) and two along the precentral sulcus (PCS) that contained reliable retinotopically organized maps of contralateral visual space. Persistent activity increased from posterior to anterior IPS areas and from inferior to superior PCS areas during the maintenance of a working memory representation, the maintenance of covert attention, and the maintenance of a saccade plan. Moreover, decoders trained to predict the locations on one task (e.g., working memory) cross-predicted the locations on other tasks (e.g., attention) in superior PCS and IPS2, suggesting that these patterns of maintenance activity may be interchangeable across the tasks. Such properties make these two areas in frontal and parietal cortex viable priority map candidates.

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