Representation of Attended Versus Remembered Locations in Prefrontal Cortex PDF

Open access, freely available online PLoS BIOLOGY Representation of Attended Versus Remembered Locations in Prefrontal Cortex Mikhail A. Lebedev*, Adam Messinger, Jerald D. Kralik, Steven P. Wise Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, Maryland, United States of America A great deal of research on the prefrontal cortex (PF), especially in nonhuman primates, has focused on the theory that it functions predominantly in the maintenance of short-term memories, and neurophysiologists have often interpreted PF’s delay-period activity in the context of this theory. Neuroimaging results, however, suggest that PF’s function extends beyond the maintenance of memories to include aspects of attention, such as the monitoring and selection of information. To explore alternative interpretations of PF’s delay-period activity, we investigated the discharge rates of single PF neurons as monkeys attended to a stimulus marking one location while remembering a different, unmarked location. Both locations served as potential targets of a saccadic eye movement. Although the task made intensive demands on short-term memory, the largest proportion of PF neurons represented attended locations, not remembered ones. The present findings show that short-term memory functions cannot account for all, or even most, delay-period activity in the part of PF explored. Instead, PF’s delay-period activity probably contributes more to the process of attentional selection. Citation: Lebedev MA, Messinger A, Kralik JD, Wise SP (2004) Representation of attended versus remembered locations in prefrontal cortex. PLoS Biol 2(11): e365. Consistent with the idea that PF functions predominantly in maintenance memory, delay-period activity in PF has often been interpreted as a memory trace (e.g., Funahashi et al. 1989; Romo et al. 1999; Constantinidis et al. 2001). The phrase delay-period activity applies to neuronal activity that follows the transient presentation of an instruction cue and persists until a subsequent ‘‘go’’ or ‘‘trigger’’ signal. The description of delay-period activity in PFdl appeared very early in the history of behavioral neurophysiology (Fuster and Alexander 1971; Kubota and Niki 1971; Fuster 1973), and, in accord with the maintenance-memory theory, some PF cells appear to buffer activity representing remembered information, even when distracting stimuli appear during the delay period (di Pellegrino and Wise 1993b; Miller et al. 1996; Moody et al. 1998). Although the interpretation of delay-period activity in terms of the short-term memory of a stimulus has a long history, many studies have explored alternatives. Neurophysiological experiments designed to explore alternatives to the maintenance-memory interpretation of delayperiod activity ﬁrst attempted to dissociate sensory from motor signals. These studies showed that PFdl neurons Introduction Jacobsen (1935, 1936) ﬁrst discovered that damage to the primate prefrontal cortex (PF) appeared to cause a shortterm memory deﬁcit. In his experiments, monkeys and chimpanzees with bilateral damage to PF failed to retrieve food from one of two opaque cups when the food had been out of sight for even a few seconds. Intact animals could ﬁnd the food 5 min or more after they had last seen it. Pribram et al. (1952) later identiﬁed the part of PF responsible for this deﬁcit as area 46, also known as the dorsolateral prefrontal cortex (PFdl). More recently, temporary inactivations of portions of PFdl caused what appeared to be a short-term memory loss in localized regions of space (Funahashi et al. 1993a). Once the concept of working memory (Baddeley 1986) became established in contemporary neuroscience (see Postle et al. 2003), these neuropsychological ﬁndings contributed to the theory that PF functions in working memory (GoldmanRakic 1987) and, in some extreme formulations, only in working memory. In the 1990s this theory developed a wide following, and the idea that PFdl functions in spatial working memory, with other parts of PF functioning in different kinds of working memory, became the predominant theory of PF function, especially for nonhuman primates. As important, the concept of working memory used by proponents of this theory focused mostly on the short-term maintenance of information, and rather less on the manipulation or monitoring of such information or on the use of that information for decisions. Accordingly, we refer to the former aspect of working memory as maintenance memory to distinguish it from the broader concept and do not use the phrase working memory elsewhere in this report. Note, however, that when we use the phrase maintenance memory, many authorities would use ‘‘working memory’’ instead. PLoS Biology | www.plosbiology.org Received April 28, 2004; Accepted August 23, 2004; Published October 26, 2004 DOI: 10.1371/journal.pbio.0020365 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modiﬁed, built upon, or otherwise used by anyone for any lawful purpose. Abbreviations: Att-trial, attended-location trial; IAtt, attended-location index; IQR, interquartile range; IRem, remembered-location index; PETH, peri-event time histogram; PF, prefrontal cortex; PFdl, dorsolateral prefrontal cortex; Rem-trial, remembered-location trial Academic Editor: Wolfram Schultz, University of Cambridge *To whom correspondence should be addressed. E-mail: [email protected] Current address: Center for Neuroengineering, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, United States of America 1919 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex point in any one of the four cardinal directions (Figure 1A, part a): left, right, up, or down from center. Next, as central ﬁxation continued, the gray circle revolved clockwise or counterclockwise around the ﬁxation point, moving along a circular trajectory (arrow in Figure 1A, part b). It then stopped at one of the four cardinal directions from center, after having revolved 908, 1808, 2708, or 3608 (Figure 1A, part b). After a variable delay period of 1.0–2.5 s, the circle brightened or dimmed for 150 ms (Figure 1A, part c) and then disappeared (Figure 1A, part d). The change in the circle’s brightness served as the trigger signal for a saccadic eye movement (arrows in Figure 1A, part d). On control trials, the circle either did not move or revolved 3608 and stopped at its initial location for that trial. During those trials, both dimming and brightening of the circle instructed a saccade toward its location. During other trials, dimming and brightening of the circle guided both the timing of the response and the choice between two alternative saccade targets. Brightening of the circle indicated that the monkeys should make a saccade to the circle’s initial location on that trial, which the monkeys had to remember in order to perform the task correctly (Figure 1A, parts c and d, bottom). Accordingly, we called these trials remembered-location trials (Rem-trials). Dimming of the circle signaled that the monkeys should make an eye movement to its current location (Figure 1A, parts c and d, top). We called these trials attended-location trials (Atttrials), for the following reasons. As a key feature of the experimental design, the circle’s brightness changed only subtly and remained visible in its new form only brieﬂy. Because the monkeys could not predict whether the circle would brighten or dim and because that subtle, short-lived event provided essential information about the time and target of the response, the monkeys had to attend to the circle intently during the period preceding the trigger signal. As a result of the central ﬁxation requirement, this attention was necessarily covert, although it seems likely that the monkeys would have attended overtly to the circle (i.e., ﬁxated it), had they been allowed to do so. Indeed, the monkeys did so during training. The Discussion takes up the issues of divided attention, multiple motor plans, default motor plans, and other interpretational issues. By varying the ﬁnal location of the circle from trial to trial, we could test for signiﬁcant spatial tuning for attended locations, and by varying the initial location of the circle, we could test for signiﬁcant spatial tuning for remembered locations. In addition, we tested the monkeys’ performance in a ‘‘no-memory’’ condition, which had the same the sequence of events as in the standard version of the task. In the ‘‘nomemory’’ condition, however, the initial location of the circle remained marked by a stationary stimulus identical to the circle that revolved around the ﬁxation point. preferentially reﬂected sensory signals, which supported the idea that these neurons encode stimulus memory over the short term. For example, one inﬂuential study used the ‘‘antisaccade’’ task (Funahashi et al. 1993b), in which a stimulus in one direction (from a central ﬁxation point) instructed an eye movement in the opposite direction. More than twice as many PFdl neurons represented the location of the sensory stimulus as represented the target (or direction) of movement. In another experiment, when a given spatial cue guided two different reaching movements, motor factors affected PFdl neurons only rarely and weakly compared to neurons in the premotor cortex (di Pellegrino and Wise 1993b), especially when viewed at a population level (Wise et al. 1996a). These results supported the idea that more delayperiod activity in PFdl reﬂected the memory of sensory cues than represented motor preparation or movement targets, but did not explore other alternative interpretations of delayperiod activity. Neuroimaging studies have provided support for some of these alternatives. At ﬁrst, neuroimaging studies appeared to back the maintenance-memory theory of PF function, which bolstered the interpretation of PF’s delay-period activity in the context of that theory. After an initial period of nearly uniform support, however, subsequent neuroimaging studies have suggested that PFdl plays a role in aspects of attention and other functions instead of, or in addition to, maintenance memory. Indeed, one recent report disputed whether PF plays any role in short-term memory at all. To quote the investigators, ‘‘no part of frontal cortex, including PF, stores mnemonic representation[s] . . . reliably across distracted delay periods. Rather, working memory storage . . . is mediated by a domain-speciﬁc network in posterior cortex’’ (Postle et al. 2003). Passingham and his colleagues have used the phrases attention to action, attention to intention, and attentional selection to describe certain PFdl functions (Rowe et al. 2000; Rowe and Passingham 2001). Petrides and his colleagues have, likewise, emphasized a role for PFdl in monitoring items in memory (Owen et al. 1996; Petrides et al. 2002). These alternative views of PF function point to a role in top-down control of attention and are supported by other neuroimaging and neuropsychological ﬁndings implicating PF in attentional functions (see Discussion). In sum, then, neuroimaging and neuropsychological ﬁndings bring into question the interpretation of PFdl’s delayperiod activity mainly in terms of maintenance memory. Previous neurophysiological experiments have ruled out motor factors, such as motor planning and the representation of the targets of movement, for most of PFdl’s delay-period activity, but have typically lacked control over spatial attention. The present experiment tested an alternative to the maintenance-memory interpretation of PFdl’s delayperiod activity by pitting the representation of a remembered location against the representation of an attended location, when either location could serve as the target of an upcoming saccadic eye movement. Behavior Figure 1B shows selected eye-position records, matched to the trials illustrated in Figure 1A. Table 1 shows that both monkeys achieved a high level of performance on this challenging task. For Rem-trials, these data show that the monkeys remembered the circle’s initial location, and— because they could not know the trial type in advance of the trigger signal—they must have also done so for Att-trials. Table 1 also shows the reaction times for each monkey. Taking the two monkeys together, saccades to the remem- Results Two monkeys performed the task depicted in Figure 1A. Brieﬂy, the monkeys maintained ﬁxation on a spot presented at the center of a video screen, called the ﬁxation point. A solid gray circle then appeared at a ﬁxed distance from the ﬁxation PLoS Biology | www.plosbiology.org 1920 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 1. Task and Behavior Behavioral task (A) and representative horizontal and vertical eye position records (B). (A) Each trial began when the monkeys pressed a button to make a ﬁxation point (FP) appear at the center of the video monitor. Some time after the monkeys ﬁxated the FP (dashed lines), a gray circle (depicted here as white) appeared at one of four peripheral locations. The ﬁgure illustrates its appearance at the 08 location (part a). The monkeys had to remember this location later in the task; hence we termed it the remembered location. On most trials, the circle subsequently revolved around the FP to a different location, as the monkeys maintained central ﬁxation. The ﬁgure illustrates its termination at the 908 location (part b). A small change in the circle’s luminance (part c) signaled the monkeys where to look next. This cue persisted for 150 ms, then disappeared. Because the monkeys depended on this subtle and brief cue for both timing and targeting information, we termed this the attended location. If the circle dimmed (dark gray, part c, top), the monkeys had to make a saccade to the attended location (Att-trials, part d, top). If the circle brightened (starburst, part c, bottom), the monkeys had to make a saccade to the remembered location (Rem-trials, part d, bottom). After saccade initiation, the central FP disappeared and, if the monkeys made a saccade to the correct location, a new FP appeared there (not shown). The monkeys had to ﬁxate the new FP and, after it dimmed, release the button to produce a fruit juice reward. (Monkey drawing courtesy of Dr. Michael Shadlen.) DOI: 10.1371/journal.pbio.0020365.g001 circle brightened (as it did on Rem-trials) than on trials when it dimmed (as it did on Att-trials). Thus, factors other than the orientation of attention probably contributed to reactiontime differences. bered location began approximately 36 ms later than those to the attended location, a difference that was highly signiﬁcant (Wilcoxon rank sum test, p , 0.001). We can only speculate about the cause of this difference, but reaction times on Remtrials may have been longer because attention had to be disengaged from the circle’s location and reoriented to the remembered one prior to the response. For the ‘‘no-memory’’ condition (not given in Table 1), reaction times for Att-trials increased approximately 16 ms compared to the standard version of the task, whereas reaction times for Rem-trials decreased approximately 22 ms (both highly signiﬁcant differences, Wilcoxon rank sum test, p , 0.001). These data are consistent with the idea that each of the two marked locations attracted attention in the no-memory condition, whereas the monkeys directed most of their covert attentional resources to the attended location in the standard version of the task. We acknowledge, however, that there are other interpretations of these data. On control trials, for example, when the saccade was always toward the circle, saccade initiation was approximately 18 ms slower when the Single-Neuron Analysis Figure 2 illustrates the activity of a neuron tuned to the attended location during the delay period. Only activity collected during correctly executed trials appears in any of the analyses presented in this report. The ﬁgure shows histogram and raster displays of neuronal activity aligned on the trigger signal for Att-trials (Figure 2A) and Rem-trials (Figure 2B), arranged in the form of a matrix, as illustrated and labeled in Figure 2C. Delay-period activity, enclosed by the red rectangles in Figures 2A and 2B, varied with the attended location (columns), but not with the remembered location (rows). The ﬁring rate during the delay period was highest when the monkey attended to the 908 location (up from screen center, see Figure 1A, part b). We called this the cell’s preferred location. The lowest ﬁring rate occurred when Table 1. Task Performance and Reaction Times for Each Monkey Performance Variable Trial Type Monkey 1 08 Trials correct (%) Reaction times (ms) Att-trials Rem-trials Att-trials Rem-trials 96.3 95.4 207.5 222.6 Monkey 2 908 6 6 6 6 0.3 0.3 0.5 1.0 95.9 88.9 213.9 245.3 1808 6 6 6 6 0.2 0.3 0.4 0.5 96.5 88.0 221.1 247.0 08 6 6 6 6 0.3 0.4 0.6 0.9 908 99.4 97.7 231.0 251.9 6 6 6 6 0.1 0.4 1.2 1.3 98.6 77.6 197.5 241.3 1808 6 6 6 6 0.1 0.5 0.4 0.5 98.7 75.9 198.4 238.2 6 6 6 6 0.2 0.8 0.5 0.8 The percentage of correctly executed trials comes from the trials on which the monkey maintained fixation until the trigger signal occurred and then performed a saccade to the instructed (correct) or some other (incorrect) location. The reaction times come from correct trials only. Means (6 SEM) are presented for different angular differences between the remembered and attended locations (08, 908, or 1808). For control trials, which correspond to a 08 difference (3608 revolutions excluded), Att-trials are trials on which the circle dimmed, and Rem-trials are those on which the circle brightened. DOI: 10.1371/journal.pbio.0020365.t001 PLoS Biology | www.plosbiology.org 1921 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 2. Example Neuron Representing the Attended Location In (A–C), the four rows correspond to different remembered locations and the four columns to different attended locations (see key in [C]). (A and B) PETHs and raster displays aligned on the trigger signal (vertical line). In the rasters, each dot represents a neuronal spike, and each line of dots shows a sequence of spikes during a single behavioral trial. (A) Trials in which the stimulus dimmed and the monkey made a saccade to the attended location (Att-trials). (B) Trials in which the stimulus brightened and the monkey made a saccade to the remembered location (Remtrials). The activity of this neuron depended on where the monkey attended, with a preferred location of 908. Note the large variation in ﬁring rate from column to column (across the attended locations) and relative constancy of rate within columns (across remembered locations). (C) Compact representation of spatial tuning pattern shown in (A) and (B), combined. Each circle’s area is proportional to the average ﬁring rate during the 800-ms period immediately preceding the trigger signal (red rectangle in [A] and [B]). Note that the major diagonal of this ﬁring-rate matrix, running from the upper left to the lower right corner, corresponds to the control trials, which lacked a memory requirement. F, maximal ﬁring rate; sp/s, spikes per second. DOI: 10.1371/journal.pbio.0020365.g002 not, as memory cells for the opposite result, and as hybrid cells if both indexes showed statistical signiﬁcance. Figure 3A–3C shows examples of an attention cell, a memory cell, and two hybrid cells. (Figures S1–S3 show the trial-by-trial activity for each of these four cells, both before and after the trigger signal.) Neurons tuned to the attended location (attention cells) dominated the neuronal sample in both monkeys, comprising 61% of cells spatially tuned during the pretrigger delay period (Table 2). Neurons tuned to the remembered location (memory cells) made up 16% of the spatially tuned neurons, and those tuned to both locations (hybrid cells) amounted to 23%. For 27% of the hybrid cells, the monkey attended to the 2708 location, termed the least preferred location. For each neuron, we assessed the extent of spatial tuning for the attended location with an index called attended-location index (IAtt), which measured the variability in discharge rate among attended locations. We assessed the extent of spatial tuning for the remembered locations with a related index called remembered-location index (IRem) (see Materials and Methods). A neuron was considered spatially tuned if IAtt, IRem, or both signiﬁcantly exceeded 1.0 (randomization test, p , 0.01; see Materials and Methods). We classiﬁed neurons as attention cells if IAtt attained statistical signiﬁcance but IRem did PLoS Biology | www.plosbiology.org 1922 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 3. Example Firing Rate Matrices and a Scatter Plot of Tuning Indexes PFdl neurons with different classes of spatial tuning. Firing rate matrices (A–C) in the format of Figure 2C; (E) gives the key. Tuning selectivity indexes (IAtt and IRem) and ﬁring rate scale (F) appear adjacent to each ﬁring rate matrix. (A) A neuron tuned to the attended location (different from the cell shown in Figure 2). (B) A neuron tuned to the remembered location. Its ﬁring rate primarily varied across rows. (C) Two cells tuned to both the attended and remembered locations (hybrid neurons). One neuron (part a) exhibited a high ﬁring rate when either the attended or remembered location was at 2708. The other neuron (part b) showed its highest activity when the remembered location was at 1808, but was inhibited when that was the attended location. (D) Scatter plot of spatial tuning indexes for attended (IAtt) and remembered (IRem) locations for each spatially tuned neuron in both monkeys. The different neuronal classes are color coded as in (A–C): blue corresponds to attention cells, red to memory cells, and green to hybrid cells. DOI: 10.1371/journal.pbio.0020365.g003 remembered location (Wilcoxon matched-pairs test, p , 0.001). We examined whether these results merely reﬂected the presence of a stimulus in the monkey’s visual ﬁeld and found strong evidence to the contrary. We compared tuning for the circle’s location during the 800 ms before the circle started moving (called the early period) and during the last 800 ms of the delay period, immediately prior to the trigger signal (the late period). (Figures S5 and S6 show activity during a slightly different early period than measured here, but they illustrate the same basic result.) Despite the fact that the sensory inputs were identical in screen-centered, allocentric, retinocentric, ﬁxation-centered, head-centered, and body-centered coordinates, the activity of PFdl neurons and their degree of spatial tuning differed in these two task periods. This result rules out a purely sensory response. For the entire PFdl sample, the late tuning index (1.29 6 0.03) signiﬁcantly exceeded the early one (1.16 6 0.02; p , 0.001; Wilcoxon matched-pairs test). This measure is devoid of any bias caused by a cell’s tuning properties in one task period or the other, but it includes the contribution of the spatially untuned cells. When we restricted the comparison to neurons that had any type of signiﬁcant spatial tuning, in either the early or late periods, the late tuning index (1.76 6 0.07) continued to exceed the early one (1.42 6 0.05) signiﬁcantly (p , 0.001). Most important, we obtained similar results for neurons with signiﬁcant tuning to the circle’s location, which characterizes attention and hybrid cells (1.83 6 0.08 late versus 1.46 6 0.05 early; p , 0.001). Table 3 and Figure S4 present this analysis for all cell classes, alone, and in various combinations. Note the attended and remembered locations associated with the highest ﬁring rate were the same (Figure 3C, part a); in the remaining 73% of the hybrid cells, these preferred locations differed (Figure 3C, part b). Figure 3D illustrates the degree of tuning for both the attended (IAtt) and remembered (IRem) locations. Each data point on the scatter plot represents a single spatially tuned neuron (both monkeys combined). Tuning for the remembered location (red symbols) was both weaker and less frequent than tuning for the attended location (blue symbols). Note that hybrid cells (green symbols) ﬁll most of the space between the other two classes and that relatively few cells represent a single location exclusively. For example, many of the neurons classed as memory cells show some sensitivity to the attended location, albeit not a statistically signiﬁcant one by the test that we employed. For the entire group of spatially tuned neurons (n = 303, both monkeys and all three cell classes combined), the mean selectivity indexes (6 SEM) for the attended and remembered locations were IAtt = 1.84 6 0.08 (median = 1.39, interquartile range [IQR] = 0.73) and IRem = 1.21 6 0.02 (median = 1.08, IQR = 0.23), which differed signiﬁcantly at the p , 0.001 level (Wilcoxon matched-pairs test). Table 3 shows comparable data for each cell class and Figure S4 gives similar data for various combinations of these classes. The selectivity for the attended location also exceeded that for the remembered one when expressed in terms of ﬁring rates. For the attended location, the difference in ﬁring rate between the preferred and least preferred locations averaged 8.8 6 0.5 spikes/s, which was signiﬁcantly greater than the 5.3 6 0.3 spikes/s for the PLoS Biology | www.plosbiology.org 1923 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Cells with signiﬁcant memory signals (memory and hybrid cells, combined) composed 70% of the spatially tuned population in dorsomedial PFdl, but only 20% in ventrolateral PFdl. Based on a cytoarchitectonic analysis conducted on two of the three hemispheres, all of the cells situated ventrolateral to the fundus of the principal sulcus were located within area 46 and none were located in area 12. The area 46/12 architectonic boundary was ﬁrst described by Walker (1940) and was subsequently conﬁrmed with different methods (Preuss and Goldman-Rakic 1991). This boundary could be discerned in both monkeys as a distinct thinning of the internal granular layer in area 12 compared to area 46 and a more substantial departure in that area from the classic, homotypical appearance typical of area 46. The reconstructed location of recording sites showed that the small group of cells located caudomedially in both monkeys (see Figure 4B and 4C) was located in the postarcuate cortex (area 6) and in area 8, as indicated by the agranular and dysgranular cytoarchitecture of these two regions, respectively. This small group of cells was eliminated from the present analysis. Table 2. Cell Classification Cell Class Monkey 1 Monkey 2 Total Percent Attention Memory Hybrid 107 (60%) 13 (7%) 59 (33%) 79 (64%) 34 (27%) 11 (9%) 61% 16% 23% Number of neurons that significantly (p , 0.01) encoded the attended location (Attention), the remembered location (Memory), or both locations (Hybrid) during the 800 ms immediately prior to the trigger signal. DOI: 10.1371/journal.pbio.0020365.t002 that these indexes do not reﬂect a generalized increase in ﬁring rate: They were normalized to remove the effects of ﬁring rate per se. The section entitled Population Analysis presents a conﬁrmatory result in terms of activity levels. Further conﬁrming this result on a cell-by-cell basis, signiﬁcant spatial tuning to the circle’s location occurred more frequently during the late delay period (256 attention and hybrid cells) than during the early one (194 cells, of which 41 lost their spatial tuning in the late period). Thus, the representation of the circle’s location in PFdl grew stronger around the time of the trigger signal, when it was important for the monkeys to attend to the circle. These ﬁndings rule out the mere presence of the circle in something akin to a visual receptive ﬁeld as a complete account of the tuning of attention and hybrid cells. Population Analysis Figure 6 displays the degree of spatial tuning for the different cell classes in the form of population histograms. The analysis of attention tuning (Figure 6A and 6B) used the 800 ms immediately preceding the trigger signal to measure mean ﬁring rates for different attended locations. We excluded control trials from this analysis. These rates were then ranked from the largest (i.e., the preferred attended location) to the smallest (the least preferred location). For each neuron, the preferred location chosen by this analysis was designated as preferred for all task periods displayed in the population histograms. (Similar results were obtained when the ranking was done for each individual task period.) The left side of the ﬁgure shows the mean attention signal for both attention (Figure 6A) and hybrid (Figure 6B) cells. After a transient response to the appearance of the circle (at a latency of approximately 100 ms), neuronal activity in both of these cell classes remained elevated when the circle stopped at the preferred location (blue curve) and became slightly suppressed when it was at the least preferred location (black curve). The right side of Figure 6 shows the mean memory signal for memory (Figure 6C) and hybrid (Figure 6D) cells. These population histograms were calculated on the basis of Histological Analysis Figures 4 and 5 show the locations of the cells in each class: Figure 4 as a function of electrode-penetration sites for both monkeys and Figure 5 as section reconstructions for monkey 2. The attention cells were concentrated more ventrolaterally than either the memory or the hybrid cells. Neurons located ventrolateral to the fundus of the principal sulcus (n = 551) were predominantly attention cells (28% to 2% memory and 5% hybrid cells, with 65% lacking spatial tuning, both monkeys combined). Neurons dorsomedial to the fundus (n = 412) fell into the three cell classes approximately equally (8% attention, 9% memory, and 10% hybrid cells, with 73% lacking spatial tuning). These regional differences within PFdl were highly signiﬁcant for each monkey (p , 0.0001, v2 test). Table 3. Spatial Tuning Indexes Early Versus Late in the Trial Cell Class Tuning Index (I) Early Attended-Location Index (IAtt) Late Remembered-Location Index (IRem) Late Attention Memory Hybrid Untuned 1.49 1.10 1.52 1.03 2.01 1.06 1.96 1.02 1.04 1.28 1.62 1.01 6 6 6 6 0.07 0.03 0.10 0.01 (p (p (p (p , . , . 0.001) 0.6; n.s.) 0.001) 0.9; n.s.) 6 6 6 6 0.11 0.01 0.13 0.01 6 6 6 6 0.01 0.04 0.08 0.01 Tuning indexes (mean 6 SEM) were calculated from both the 800 ms immediately preceding circle movement (Early, I) and the 800 ms immediately preceding the trigger signal (Late, IAtt, IRem). For both attention and hybrid cells, spatial tuning to the attended location was significantly stronger (Wilcoxon matched-pairs test) late in the trial, when the monkeys awaited the trigger signal. Values for memory tuning (IRem) appear for completeness, not for statistical testing. See also Figure S4. DOI: 10.1371/journal.pbio.0020365.t003 PLoS Biology | www.plosbiology.org 1924 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 4. Surface Projections Showing the Location of Neurons in Each Class All hemispheres are displayed so that rostral is to the left and dorsomedial is up. Reconstructed surface projections of the left hemispheres of monkey 1 (A) and monkey 2 (B). (C) Surface projection of the (inverted) right hemisphere of monkey 1. (D) A lateral view of the hemisphere shown in (C), with the region included in (C) approximated by the dashed box. The dotted ellipse encloses the cells deemed to lie inside the PFdl by histological analysis, but does not correspond to the cytoarchitectonic boundaries of area 46. DOI: 10.1371/journal.pbio.0020365.g004 preferred remembered locations, ranked according to the pretrigger modulation. This location was then designated ‘‘preferred’’ for all task periods displayed in the plots. For memory cells (Figure 6C), the population averages were almost identical when the circle remained stationary at its initial location and that location did not yet need to be remembered. That is, on average it did not matter noticeably whether the circle initially appeared at a cell’s preferred location or at its least preferred location (Figure 6C, red versus black curves). This ﬁnding is somewhat surprising because prior studies suggested that PFdl’s memory cells had activity that began shortly after stimulus onset and continued throughout the delay period. In our memory cells, spatial tuning did not develop to any appreciable extent until after the circle began revolving around the central ﬁxation point. This result shows that tuning to the remembered location developed during the trial and was not a simple replica of the tuning pattern during the initial presentation of the circle. Hybrid cells (Figure 6D) exhibited a weak spatial signal following the appearance of the circle consistent with their memory tuning prior to the trigger. Note that after the circle stopped moving, memory cells showed less of a difference between preferred and least preferred locations than did attention cells (Figure 6C versus 6A). This ﬁnding supports the results presented in Tables 2 and 3 and Figure 3D, which show a predominance of nonmemory signals (see also Figure S4). Population representations of the attended and remembered locations were further analyzed using a neuronPLoS Biology | www.plosbiology.org dropping analysis. Neuron-dropping curves express the strength of spatial tuning as the ability to estimate a spatial variable from the activity of a neuronal ensemble, as a function of ensemble size. We randomly selected an ensemble from the population of recorded PFdl neurons and used a single trial of activity from each cell to estimate both the attended and remembered locations. The ﬁndings of the neuron-dropping analysis agree with those from the analysis of single-cell activity and the population histograms and thus provide independent support. However, neuron-dropping analysis offers several advantages over the population histograms, in addition to providing conﬁrmation of those results. In neuron-dropping, the estimation of either an attended or remembered location does not depend on any assumptions about the nature of the spatial tuning curve or the relative importance of very active cells versus those showing less activity. It does not ascribe any special signiﬁcance to increases in activity relative to baseline (excitation) versus decreases (inhibition) or to the most preferred and least preferred locations. Each cell’s activity contributes to the population estimation for all locations regardless of the direction of its modulation relative to baseline and whether that modulation signiﬁcantly differs from baseline levels. Furthermore, the computation makes no assumption about any relationship between tuning for attended locations and remembered ones. This analysis also has the advantage that its results are expressed as a percentage of correct estimations by the neuronal ensemble, thereby facilitating comparison with the monkeys’ performance, which in this 1925 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 5. Section Reconstructions for Monkey 2 (A–G) Coronal sections taken at the planes indicated in the surface drawing (H). Dashed lines mark the borders between PFdl (area 46) and area 12. Solid lines show the tracks of the marking pins (irregular outlines in sections [B] and [C]) and the estimated location of electrode penetrations. Colored hash marks show the estimated depth of neurons in each class, using the same color code as in Figures 3 and 4. Longer hash marks indicate simultaneous recordings of more than one neuron of the same class. (H) Lateral view of left PF depicting surface projections of spatially tuned neurons. Black circles show the locations of pin holes used for localization, and gray squares show their predicted locations. DOI: 10.1371/journal.pbio.0020365.g005 dorsomedial subpopulation represented both locations comparably, with estimation of the attended location being slightly better in one monkey and estimation of the remembered location being slightly better in the other. Of the two subpopulations, the dorsomedial neurons showed a more reliable estimation of the remembered location. We also used a neuron-dropping analysis to examine the ensemble’s properties during response selection and execution. Figure 7E and 7F show these time-dependent neuralestimation curves for monkey 1; Figure 8 does so for both monkeys combined. Note from Figure 7D–7F that the timeestimation curves come from a random sample of neurons, much smaller than the sampled population, to avoid the effects of signal saturation. The estimations at each time point reﬂect activity averaged over the previous 200 ms. Prior to the trigger signal, the estimation of the attended location (blue curves in Figures 7E, 7F, 8D and 8E) was superior to that of the remembered location (red curves) for all spatially tuned neurons, as well as for attention cells (Figure 8A). This ﬁnding is consistent with the greater number and stronger spatial tuning of attention than memory cells. On Att-trials, the estimation of the attended location (solid blue curves in Figures 7E and 8A–D) improved following the dimming of the circle and remained elevated during the saccade to that location. This improvement continued for the initial 200 ms of ﬁxation there. Then the signal decreased. Note that the monkey maintained ﬁxation at the target location for at least 1.0 s after the saccade. In contrast, the estimation of the remembered location on Att-trials (solid red curves) gradually decreased following the trigger signal. The fading of this representation most likely reﬂected the fact that the remembered location was no longer behaviorally relevant. experiment always exceeded 75% correct and sometimes approached 100% (Table 1). Figure 7 shows the neuron-dropping curves for each cell class (A–C) and all spatially tuned neurons combined (D) in monkey 1. Neuron-dropping curves for monkey 2 showed similar results, and Figure S7 presents the data for both monkeys combined. As expected, the neuron-dropping curves computed for attention cells yielded much better estimations of the attended location than the remembered one (see Figure 7A, blue versus red curves). Note, however, that the attention cells also provided a better-than-chance estimation of the remembered location. This result reﬂects the fact that many cells with signiﬁcant tuning for the attended location also showed some tuning for the remembered location (see blue data points in Figure 3D with IRem . 1.0). Figure 7A also conﬁrms the comparison of activity early versus late in the trial (blue versus gray curves), providing further evidence against a purely sensory account of this subpopulation’s activity. Also as expected, memory cells yielded a better estimation of the remembered location than the attended one (Figure 7B, red versus blue curves), but these cells, too, yielded a fairly reliable estimation of the other spatial variable. Neuron-dropping curves for hybrid neurons showed comparable estimations for both locations (Figure 7C). When all spatially tuned neurons were combined (Figure 7D; see also Figure S7D), the resultant neuron-dropping curves showed that PFdl activity was a much more reliable estimator of the attended location than the remembered one. The same analysis was applied to the ventromedial and dorsolateral regions within the PFdl, described in the section entitled Histological Analysis, above (not shown). The ventrolateral subpopulation of PFdl neurons (see Figure 4A–4C) overwhelmingly represented the attended location. The PLoS Biology | www.plosbiology.org 1926 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 6. Attention and Memory Signals in Population Histograms (A) and (B) Representation of an attention signal by attention cells (A) and hybrid cells (B). (C) and (D) Representation of a memory signal by memory cells (C) and hybrid cells (D). In each panel, activity is shown centered on the appearance of the circle (left vertical line), on the time that the circle stopped moving (middle vertical line), and on the trigger signal (right vertical line). Attention and memory signals are reﬂected in the degree of separation in the average population histograms for different ranks. In (A) and (B), the data for the period immediately prior to the end of the circle’s movement have been eliminated because the circle came from different initial locations. DOI: 10.1371/journal.pbio.0020365.g006 Alternatively, the saccade target may have been represented because the monkeys attended to the ﬁxation spot at this location, so that when it dimmed they could quickly release the button to produce their reward (see Materials and Methods, below, for a description of that aspect of the task). On Rem-trials (dashed curves in Figures 7F, 8A–8C, and 8E), the circle’s brightening instructed a saccade to the remembered location (marked by the red ‘‘R’’ in Figure 8E). We expected that redirecting attention toward the saccade target (yellow spot in Figure 8E, right) would degrade the neuronal representation of the formerly attended location and improve the representation of the formerly remembered—but eventually ﬁxated—one. The estimation of the attended location initially improved on Rem-trials following the trigger signal there (blue dashed curves in Figures 7F, 8A– 8C, and 8E). However, in accord with our expectation, that estimate decreased dramatically in accuracy after saccade onset, as the attended location became behaviorally irrelevant. In contrast, the estimation of the formerly remembered (and soon to be ﬁxated) location (red dashed curves) improved sharply (Figure 8E), especially in attention cells (Figure 8A). Thus, PFdl neurons became more reliable encoders of that location. Given that these averages ‘‘look back’’ 200 ms, this development must have preceded the saccade. On both Att-trials and Rem-trials, the neuronal ensemble remained a reliable indicator of the saccade target relatively long after the target had been acquired (see solid blue and dashed red curves in Figures 7E, 7F, and 8). This signal might encode the ﬁxated location, which could be important for monitoring performance, as suggested for nearby areas of frontal cortex (Stuphorn et al. 2000; Ito et al. 2003). PLoS Biology | www.plosbiology.org Discussion In tasks involving short-term memory requirements, delayperiod activity in PFdl has consistently been interpreted in terms of the maintenance-memory theory of PF function (e.g., Funahashi et al. 1989; Romo et al. 1999; Constantinidis et al. 2001), despite the existence of viable alternatives. However, our results show that much of PFdl’s delay-period activity in such tasks reﬂects nonmemory functions. Accordingly, the maintenance-memory theory of PF function (Goldman-Rakic 1987, 1990), taken to its extreme, fails to account for PFdl’s delay-period activity. Indeed, we found that, compared to the remembered location, the attended location was more frequently and more robustly encoded at both the neuronal and population levels. The present results thus support extensive neuropsychological (Rueckert and Grafman 1996; Stuss et al. 1999; Koski and Petrides 2001, 2002) and neuroimaging (Corbetta et al. 1993; Gitelman et al. 1999; Kastner et al. 1999; Rosen et al. 1999; Cabeza and Nyberg 2000; Hopﬁnger et al. 2000, 2001; Vandenberghe et al. 2000; Astaﬁev et al. 2003; Small et al. 2003; Thiel et al. 2004; 1927 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 7. Neuron-Dropping Curves for Different Subpopulations of PFdl Neurons in Monkey 1 Each curve represents the percentage of correct single-trial estimations of location as a function of the number of neurons in the assembled populations. The curves show predictions of the attended locations (blue lines) or remembered locations (red lines) during the 800 ms immediately preceding the trigger signal, after the circle had stopped revolving around the central ﬁxation point. Also shown is the estimation for the 800-ms period immediately preceding the onset of the circle’s movement (gray lines). The dotted line indicates the chance level of estimation, 25% correct. Neuron-dropping curves are shown for neurons tuned to the attended location (A), the remembered location (B), both locations (C), and all spatially tuned neurons (D). (E) and (F) Dynamic changes in estimations of the attended (blue) and remembered (red) locations for 20 spatially tuned neurons (marked by the dashed gray line and arrows), using a 200-ms sliding window. Dashed and solid lines in (E) and (F) are shown for consistency with Figure 8. Note that the estimations in (D) are higher than in (E) and (F) because the former is based on an 800-ms interval, and the latter are based on only a 200-ms interval. DOI: 10.1371/journal.pbio.0020365.g007 that the monkeys attended to the circle in the period immediately prior to the trigger signal. The remaining interpretational questions to be addressed, then, are: Do monkeys devote any attentional resources to what we call the remembered location? Do they ‘‘remember,’’ in some sense, what we call the attended location? Does the activity we interpret in terms of attention or memory reﬂect motor factors? And, given that the monkeys could anticipate and predict rewards, do the signals reﬂect these processes? We address each of these four questions, in turn, in the remainder of this section. First, although we contend that the monkeys must have devoted substantial attentional resources to the location of trigger signal, this does not necessarily rule out additional covert allocations of attention to the remembered location. However, there was no stimulus or expected signal at the remembered location to warrant the allocation of attentional resources there. In addition, the demands of ﬁxating the central location (overt attention), while attending covertly to a stimulus located in peripheral visual space, make it unlikely that attention was further divided (Hunt and Kingstone 2003; Woldorff et al. 2004) research that points to a much more general role for PF than encompassed by the maintenancememory theory, including the top-down control of selective attention. Interpretational Issues and Limitations The present experiment is the ﬁrst neurophysiological study to achieve a degree of independent control over both spatial attention and spatial memory, so a detailed consideration of both its advantages and limitations is in order. A complete dissociation of these two spatial variables is probably impossible, but we achieved this goal to a considerable degree. Our experimental design, however, has several limitations and raises a number of questions. For example, is what we call attention really attention? We have elaborated on our usage of the term attention in the Results section. Although we did not quantify the degree of attention, it seems to us a reasonable assumption that the monkeys attended to the circle, given that its brightening or dimming was subtle, brief, and crucial to their correct performance. Moreover, the reaction-time data are consistent with the idea PLoS Biology | www.plosbiology.org 1928 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex Figure 8. Time-Dependent Changes in Estimating the Attended Location and Remembered Location, for Both Monkeys Combined Solid lines, trials in which the monkeys made a saccade to the attended location; dashed lines, trials in which the monkey made a saccade to the remembered location. Blue lines, estimation of the attended location; red lines, estimation of the remembered location. All records are centered on the onset of the trigger signal (using data for the 200 ms prior to that time). Vertical lines at t . 0 show the average saccade latency on Att-trials (solid) and Rem-trials (dashed). The thick bar at the bottom of the plots shows the approximate onset of the peripheral ﬁxation spot, which the monkeys continued ﬁxating beyond the limit of the plot. Estimations for each monkey were calculated using the same methods as for Figures 7E and 7F, except that the ensemble size for monkey 2 was 60 neurons. This number of neurons was chosen to avoid ceiling effects (i.e., 100% correct). The plotted curves show the average for the two monkeys. Location estimations for attention (A), memory (B), hybrid cells (C), and all spatially tuned neurons on Att-trials (D) and Rem-trials (E). Above the plots are schematic depictions of an example trial, of the type illustrated in Figure 1A. The red ‘‘R’’ marks the remembered location. In both D and E, prior to the trigger signal (left schematic), the monkeys ﬁxated (dashed lines) centrally and covertly attended to the circle (yellow spot at the attended location). During this period, estimation of the attended location exceeded that of the remembered location. Following the saccade, the monkeys ﬁxated a peripheral light spot (right schematic) and attended to this target to detect when it dimmed. On Att-trials (D), the monkeys’ gaze shifted to the attended location, and the ensemble’s estimation of this now overtly attended location improved (solid blue curve), while the representation of the now irrelevant, remembered location gradually decayed (solid red curve). On Rem-trials (E), the monkeys’ gaze (dashed lines) and focus of attention (yellow spot) shifted to the (previously) remembered location. The estimation of this location consequently improved (red dashed curve), while the estimation of the previously attended (and now irrelevant) location gradually decayed. Abbreviations: Att, attended; Rem, remembered. DOI: 10.1371/journal.pbio.0020365.g008 Muller et al. 2003). Accordingly, although we cannot completely rule out the possibility that the monkeys attended to the remembered location during the delay period, it seems implausible that they did so. If one adopts the view that they did, then some or all of the neurons we class as memory cells might instead have activity better interpreted as reﬂecting some aspect of highly divided attention. Second, the monkeys were required to remember the place where the circle ﬁrst appeared on each trial, and their performance shows that they did so. Did they also ‘‘remember’’ the attended location? There is ample precedent for skepticism about the proposition that monkeys are not remembering some location. However, there is no basis for assuming a ‘‘memory’’ of a currently visible stimulus. It seems especially unlikely that the monkeys ‘‘remembered’’ the attended location in the context of the requirement that they centrally ﬁxate while attending somewhere and remembering somewhere else. Third, we cannot rule out the participation of neurons we class as attention or memory cells in a variety of processes involved in preparing or planning the movement or selecting the response target. Prior to the trigger signal, the monkeys PLoS Biology | www.plosbiology.org may have prepared to make a movement to the remembered location, to the attended location, to both, or to neither. Cisek and Kalaska (2002) have shown that some neurons in the premotor cortex encode a possible movement target before a particular one has been speciﬁed, but their experiment has yet to be done for PFdl neurons. In view of prior evidence arguing against interpreting much of PFdl’s delayperiod activity in terms of motor signals (Funahashi et al. 1989, 1993b; di Pellegrino and Wise 1993b; Asaad et al. 1998; Romo et al. 1999; Constantinidis et al. 2001) and the absence of a contemporary ‘‘motor theory’’ of PF function, the present experiment was not designed to address this issue. Future work along these lines, perhaps combining the design of di Pellegrino and Wise (1993b) with the present one, might be indicated by the present results. We believe, however, that a simple ‘‘motor’’ explanation for most of PFdl’s delay-period activity is an unlikely outcome of such studies. A ‘‘motor’’ interpretation probably does, however, account for a small proportion of PFdl’s delay-period activity, consistent with the results of Funahashi et al. (1993b). On certain assumptions about a default motor plan, such neurons could have the tuning properties of the hybrid cell illustrated in Figure 3C, 1929 November 2004 | Volume 2 | Issue 11 | e365 Nonmemory Signals in the Prefrontal Cortex continuum with attention and memory cells at the extremes, and hybrid cells in between. Interestingly, the neuron-dropping curves for the hybrid cells (see Figures 7C and 8C) showed effective estimation of both the attended and remembered locations. Hybrid neurons with dissimilar preferences for the two locations facilitated such estimations. For instance, the neuron shown in Figure 3C, part b had a low ﬁring rate when the monkey attended to the 1808 location and a high ﬁring rate when it remembered that place. Hybrid cells with dissimilar preferences can resolve the ambiguity inherent in cell activity like that illustrated in Figure 3C, part a, which cannot distinguish between attended and remembered locations. part a. It is important to emphasize, however, that the present experiment tested whether the maintenance-memory theory could account for all delay-period activity in PFdl. It cannot. We view this result as supporting an important role for PF in the top-down control of attention. If one takes a motor theory of PF function more seriously than most expert opinion currently does, then it is possible to interpret the present result as indicating a role in context-dependent response or goal selection or in terms of the preparation of movements to remembered targets versus current stimuli. Neither interpretation is consistent with an interpretation of PFdl’s delay-period activity entirely in terms of a maintenance-memory function. Fourth, we need to consider the possibility that the neural signals we observed reﬂect the prediction or anticipation of reward. Maunsell (2004) has recently pointed out that neural signals interpreted as arising from attention could instead reﬂect reward anticipation or prediction (and vice versa). In the present study, however, reward-related information processing could not have accounted for the properties of attention cells because, until the trigger signal, one alternative place (the remembered location) was associated with reward to the same degree as the attended location. Previous Neurophysiological Studies Previous neurophysiological studies of PFdl’s delay-period activity have been interpreted in terms of the maintenancememory theory. However, the lack of control over spatial attention in these studies raises questions about these interpretations. Constantinidis et al. (2001), for example, trained monkeys to make delayed saccades toward the location of the brighter of two visual stimuli that brieﬂy ﬂashed on the video screen. They reported that the activity of PFdl neurons reﬂected the brightness of the stimuli. Although these authors interpreted their ﬁndings as demonstrating a purely sensory-mnemonic function for PFdl neurons, brighter stimuli, being more salient, are well known to attract attention to their location. Similar problems affect the interpretation of data from the ‘‘antisaccade’’ task (Funahashi et al. 1993b). In their antisaccade task, Funahashi et al. trained a monkey to respond to a stimulus to the left of a ﬁxation point by making a saccade to the right and vice versa. They interpreted their data as demonstrating a function for PFdl in spatial memory because the largest number of neurons reﬂected the stimulus location rather than the movement target. They showed that during the delay period, when nothing was present on the screen, some neurons reﬂected where the stimulus had occurred, and these were interpreted as memory cells. Note, however, that where ever the stimulus appeared, whether in antisaccade or prosaccade trials, it served as an attention attractor. If the response to that signal persisted, then interpreting it exclusively as a sensory memory trace would be problematic. Many studies suggest that, for neurons in PF, the history of what has happened or the context in which it happens often affects neuronal activity in an important and persistent way (Rainer et al. 1998; Asaad et al. 2000; Wallis and Miller 2003), sometimes regardless of relevancy (Chen et al. 2001). Such persistent signals can be viewed as components of working memory in a general sense, but not in the narrow sense implied by the concept of maintenance memory. Enhancement Effects The general term attention has been used to cover many disparate concepts, including the effects of attention on sensory processing and the mechanisms that mediate those inﬂuences. We emphasize that the present ﬁnding differs from previous ones describing effects of attention on phasic, sensory-like responses. Often called the enhancement effect, the ﬁnding that sensory responses are larger when a stimulus or location is more attended was ﬁrst described for the superior colliculus (Wurtz and Goldberg 1972) and has been repeatedly demonstrated for many cortical areas, including PFdl (Mikami et al. 1982; Boch and Goldberg 1989; di Pellegrino and Wise 1993a; Rainer et al. 1998; DeSouza and Everling 2004). In some instances, and especially in frontal cortex, the enhancement effect depends on the attended location being the target of a movement (Goldberg and Bushnell 1981), but in other cases it does not (Bushnell et al. 1981). It has often been suggested that the source of attention effects, including the enhancement effect, match enhancement, and related phenomena, depends on signals emanating from PF (Miller et al. 1996; Kastner et al. 1999; Reynolds et al. 1999) or from the frontal eye ﬁeld (Thompson et al. 1997; Moore and Fallah 2004). The present results are consistent with this idea. They cannot, however, be considered as yet another example of the enhancement effect, which involves attention-dependent augmentation of a phasic sensory response. Neurons Encoding Both Attended and Remembered Locations Neuroimaging and Neuropsychological Results from Humans Most neurons did not encode an attended or remembered location exclusively; rather, they exhibited varying degrees of tuning for both variables. The neuron-dropping curves (see Figure 7) show that attention cells were able to make limited, but above-chance, estimations of the remembered location and vice versa. As can be seen from the spatial tuning indexes in Figure 3D, few individual neurons were pure attention or memory encoders (data points along the axes). Thus, the population of

Representation of Attended Versus Remembered Locations in Prefrontal Cortex PDF

Document Details

Tags

Related

Summary

Full Transcript

Upgrade to continue