Clayton E. Curtis

Persistent activity in the prefrontal cortex during working memory

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.

Maintenance of Spatial and Motor Codes during Oculomotor Delayed Response Tasks

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.

Prefrontal and parietal contributions to spatial working memory

Functional neuroimaging studies consistently implicate a widespread network of human cortical brain areas that together support spatial working memory. This review summarizes our recent functional magnetic resonance imaging studies of humans performing delayed-saccades. These studies have isolated persistent activity in dorsal prefrontal regions, like the frontal eye fields, and the posterior parietal cortex during the maintenance of positional information. We aim to gain insight into the type of information coded by this activity. By manipulating the sensory and motor demands of the working memory task, we have been able to modulate the frontal eye fields and posterior parietal cortex delay-period activity. These findings are discussed in the context of other neurophysiological and lesion-based data and some hypotheses regarding the differential contributions of frontal and parietal areas to spatial working memory are offered. Namely, retrospective sensory coding of space may be more prominent in the posterior parietal cortex, while prospective motor coding of space may be more prominent in the frontal eye fields.

Revisiting the role of persistent neural activity during working memory.

What are the neural mechanisms underlying working memory (WM)? One influential theory posits that neurons in the 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 the lPFC, maintains high-fidelity representations of WM content. By contrast, the 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 the lPFC and sensory cortex.

Sustained Activity in Topographic Areas of Human Posterior Parietal Cortex during Memory-Guided Saccades

In a previous study, we identified three cortical areas in human posterior parietal cortex that exhibited topographic responses during memory-guided saccades [visual area 7 (V7), intraparietal sulcus 1 (IPS1), and IPS2], which are candidate homologs of macaque parietal areas such as the lateral intraparietal area and parietal reach region. Here, we show that these areas exhibit sustained delay-period activity, a critical physiological signature of areas in macaque parietal cortex. By varying delay duration, we disambiguated delay-period activity from sensory and motor responses. Mean time courses in the parietal areas were well fit by a linear model comprising three components representing responses to (1) the visual target, (2) the delay period, and (3) the eye movement interval. We estimated the contributions of each component: the response amplitude during the delay period was substantially smaller (<30%) than that elicited by the transient visual target. All three parietal regions showed comparable delay-period response amplitudes, with a trend toward larger responses from V7 to IPS1 and IPS2. Responses to the cue and during the delay period showed clear lateralization with larger responses to trials in which the target was placed in the contralateral visual field, suggesting that both of these components contributed to the topography we measured.

Beyond working memory: the role of persistent activity in decision making

Since its first discovery in the prefrontal cortex, persistent activity during the interval between a transient sensory stimulus and a subsequent behavioral response has been identified in many cortical and subcortical areas. Such persistent activity is thought to reflect the maintenance of working memory representations that bridge past events with future contingent plans. Indeed, the term persistent activity is sometimes used interchangeably with working memory. In this review, we argue that persistent activity observed broadly across many cortical and subcortical areas reflects not only working memory maintenance, but also a variety of other cognitive processes, including perceptual and reward-based decision making.

Common neural mechanisms supporting spatial working memory, attention and motor intention

The prefrontal cortex (PFC) and posterior parietal cortex (PPC) are critical neural substrates for working memory. Neural activity persists in these regions during the maintenance of a working memory representation. Persistent activity, therefore, may be the neural mechanism by which information is temporarily maintained. However, the nature of the representation or what is actually being represented by this persistent activity is not well understood. In this review, we summarize the recent functional magnetic resonance imaging (fMRI) studies conducted in our laboratory that test hypotheses about the nature of persistent activity during a variety of spatial cognition tasks. We find that the same areas in the PFC and PPC that show persistent activity during the maintenance of a working memory representation also show persistent activity during the maintenance of spatial attention and the maintenance of motor intention. Therefore, we conclude that persistent activity is not specific to working memory, but instead, carries information that can be used generally to support a variety of cognitions. Specifically, activity in topographically organized maps of prioritized space in PFC and PPC could be read out to guide attention allocation, spatial memory, and motor planning.

Working memory functioning in schizophrenia patients and their first-degree relatives: Cognitive functioning shedding light on etiology

There is accumulating evidence for involvement of the prefrontal cortex (PFC) in the pathophysiology of schizophrenia. A primary function supported by the PFC is working memory (WM). Findings from WM studies in schizophrenia can provide insight into the nature of clinical symptoms and cognitive deficits associated with this disorder, as well as begin to suggest areas of underlying neuropathology. To date, studies have not adequately investigated different WM domains (e.g., verbal, spatial, or object) or processing requirements (e.g., maintenance, monitoring, or manipulation), shown to be associated with distinct patterns of neural activation, in schizophrenia patients and their well relatives. Accordingly, this study evaluated the performance of schizophrenia patients, their first-degree biological relatives, and nonpsychiatric controls on a comprehensive battery of WM tasks and investigated the association among WM deficits and schizophrenia-spectrum psychopathology. The findings indicate that schizophrenia patients are consistently impaired on WM tasks, irrespective of WM domain or processing requirements. In contrast, their unaffected relatives are only impaired on WM tasks with higher central executive processing requirements. This pattern of WM performance may further implicate DLPFC dysfunction in the liability for schizophrenia and has implications for future cognitive, genetic, and neurodevelopmental research.

Differential effects of distraction during working memory on delay-period activity in the prefrontal cortex and the visual association cortex

Maintaining relevant information for later use is a critical aspect of working memory (WM). The lateral prefrontal cortex (PFC) and posterior sensory cortical areas appear to be important in supporting maintenance. However, the relative and unique contributions of these areas remain unclear. We have designed a WM paradigm with distraction to probe the contents of maintenance representations in these regions. During delayed recognition trials of faces, selective interference was evident behaviorally with face distraction leading to significantly worse performance than with scene distraction. Event-related fMRI of the human brain showed that maintenance activity in the lateral PFC, but not in visual association cortex (VAC), was selectively disrupted by face distraction. Additionally, the functional connectivity between the lateral PFC and the VAC was perturbed during these trials. We propose a hierarchical and distributed model of active maintenance in which the lateral PFC codes for abstracted mnemonic information, while sensory areas represent specific features of the memoranda. Furthermore, persistent coactivation between the PFC and sensory areas may be a mechanism by which information is actively maintained.

Prioritized Maps of Space in Human Frontoparietal Cortex

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–IPS3) 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.