Fig 1.
(a) Item stimuli. (b) Item-location association pattern. Two items, one from set A (e.g., I-A) and the other from set B (e.g., I-B), were assigned to each location (e.g., co-location I) on the background image. Scale bar for both item-cue and background-cue stimuli, 5° visual angle. (c) Schematic diagram of the CMP task. An item cue and background cue were chosen pseudorandomly in each trial. The monkeys should maintain fixation on the center until the end of the background-cue period including Delay 2, then saccade to the target location (red arrow) during the choice period. Monkeys were trained using every 0.1° step in orientation from −90° to 90°, though only 5 orientations (−90°, −45°, 0°, 45°, and 90°) were tested during the data acquisition. Relative sizes of the item-cue stimuli to the background-cue stimuli were magnified for display purpose. CMP, constructive memory-perception.
Fig 2.
Representation of the retrieved memory during the item-cue period.
(a) Example of an item-selective neuron with the co-location effect. Black lines indicate SDFs in trials with the Optimal and its Pair items (i.e., best co-location items) of the neuron. Gray line indicates averaged response in the other trials (Other). Brown bar, presentation of the item cue. (b) Mean discharge rates and SEM of the same neuron during the item-cue period for each item. Black bars, set A. White bars, set B. r, co-location index. ***P < 0.0001, permutation test, 2-tailed. (c) Population-averaged response of item-selective neurons (n = 136). SDFs in trials with the best co-location items (i.e., Optimal and Pair) and other items. Shading, SEM. Purple line, time duration indicating a significant (P < 0.01, t-test, 2-tailed) difference between pair and other. (d) Distributions of co-location indices for item-selective neurons (n = 136). r, median value. ***P < 0.0001, Wilcoxon’s signed-rank test, 2-tailed. (e) Response discriminability between the optimal and its paired items of the same example neuron in Fig 2A. (Left) ROC curve. (Right) Solid vertical line, AUC value of the example neuron. Gray area and dashed vertical line, distribution of simulated AUC values and its median. (f) Response discriminability between best and other co-locations of the same neuron. ***P < 0.0001, permutation test, 1-tailed. (g) Two-dimensional scatter plots of AUC values between the item (ordinate) and co-location (abscissa) discriminations for item-selective neurons with high co-location index (r > 0.6; n = 109). Each circle indicates one neuron. Arrow, median of real AUC values for each discrimination. Dashed line, median of simulation AUC values for each discrimination. ***P < 0.0001, Wilcoxon’s signed-rank test, 2-tailed. s, significant, P < 0.05 for each neuron, permutation test, one-tailed. Source data are available in S1 Data. AUC, area under curve; ns, nonsignificant; ROC, receiver operating characteristic; SDF, spike density function.
Fig 3.
Retrieval signal after background-cue.
(a) Example of an item-selective neuron with co-location effect. Black lines indicate SDFs in trials with the Optimal and its Pair items (i.e., best co-location items) of the neuron. Gray line indicates averaged response in the other trials (Other). Brown bar, presentation of the item-cue. Gray bar, presentation of the background cue. (b) Mean discharge rate and SEM of the same neuron during the background-cue period for each item. Black bars, set A. White bars, set B. r, co-location index. ***P < 0.0001, permutation test, 2-tailed. (c) Cumulative frequency histograms of the co-location index. Black line, item-selective neurons during B-Cue period. Gray line, item-selective neurons during I-Cue period. r, median of the co-location index values. ***P < 0.0001, Wilcoxon’s signed-rank test, 2-tailed. †P < 0.01, Kolmogorov–Smirnov test. (d) Two-dimensional scatter plot of AUC values for item-selective neurons during the background-cue period (n = 47). Same format as Fig 2G. ***P < 0.0001, Wilcoxon’s signed-rank test, 2-tailed. s, significant, P < 0.05, permutation test, 1-tailed. Source data are available in S1 Data. AUC, area under curve; B-Cue, background cue; I-Cue, item cue; ns, nonsignificant; SDF, spike density function.
Fig 4.
Convergence of the retrieved memory and incoming perception.
(a) Example neuron signaling background effect. (Top) Each row contains an SDF for each combination of I- and B-Cues. (Middle) Time courses of F values. Brown bar, presentation of the I-Cue. Gray bar, presentation of the B-Cue. (Bottom) Mean discharge rate for each combination of I- and B-Cues during 60–1,000 milliseconds after B-Cue onset. White, gray, and black bars indicate −90°, 0°, and 90° orientations of background cue, respectively. Two bars with the same grayscale indicate the co-location items (e.g., left bar, I-A; right bar, I-B). (b) Example neuron signaling background and co-location effects in a “convergent” manner. Same format as Fig 4A. r, Pearson correlation coefficient between the orientation tunings (responses to −90°, 0°, and 90° during the B-Cue period) for “best co-location” (III) and for “second-best co-location” (IV). (c) Time course of similarity of orientation tuning r(t). Line and shading, means and SEMs of the similarity of the orientation tunings for co-location-selective neurons. Purple line, time duration in which the similarity was significantly positive (P < 0.01, n = 66, Wilcoxon’s signed-rank test for each time step, 2-tailed). Source data are available in S1 Data. B-Cue, background cue; I-Cue, item cue; SDF, spike density function.
Fig 5.
Representation of retrieved location and target location.
(a) Example neuron signaling a particular co-location during the item-cue period and a particular “targeting” location during the B-Cue period. Same format as Fig 4A, except that target locations in the bar graph are indicated by colors (bottom panel). For example, yellow color corresponds to the bottom-left of the target location on the display. (b) Potential matching patterns between the co-location and target location. (c) Median value of matching index for each matching pattern (using neurons signaling both co-location-selectivity during the item-cue period and target-selectivity during the background-cue period, n = 49). Error bar, quarter value. ***P < 0.0001, Wilcoxon signed-rank test, 2-tailed. Source data are available in S1 Data. B-Cue, background cue; BL, bottom left; BR, bottom right; I-IV, co-location I-IV; I-Cue, item cue; TL, top left; TR, top right.
Fig 6.
Construction of goal-directed information.
(a) Example neuron showing the “transference” effect ([I, 90°] and [III, −90°] for the bottom-right). Same format as Fig 5A. Bottom panel shows a schematic diagram of “transference” from the retrieved location (co-locations I and III) into the same target location (bottom right, green). (b) Example neuron showing multiple operations. (c) Target-selective responses (“best” minus “others”) in trials with −90°, 0°, and 90° background cues for target-selective neurons (n = 72). Curves and shadings depict means and SEMs of population-averaged SDFs. Top lines, time duration in which target-selective responses (“best” minus “others”) were significantly positive in trials with 0° background cues (black) and with either −90° or 90° background cues (gray) (P < 0.05, t test, 2-tailed). Purple line, time duration in which the “best” target responses were significantly larger in trials with either −90° or 90° compared with 0° background cue (P < 0.05). The best target locations of the target-selective neurons in each hemisphere (animal) covered not only the contra-lateral side but also ipsi-lateral side (S2 Table). Source data are available in S1 Data. B-Cue, background cue; I-Cue, item cue; SDF, spike density function.
Fig 7.
Neuronal signal predicting animals’ behavior.
(a) Example neuron exhibiting target-selective activity. (Left) Raster displays of correct trials sorted by target locations. Colors indicate target locations on display. The neuron exhibited preferred responses when the target location was the top left (red). (Right) Raster displays of error trials and SDFs (σ = 20 milliseconds). False Alarm, top left as the incorrect positions the subjects chose (black). Miss, top left as the correct positions the subjects missed (gray). Correct trials, top left as the correct positions the subjects chose (red). (b) Error analysis for target-selective neurons with at least 10 error trials (n = 50). False Alarm, the false positions the subjects chose. Miss, the correct positions the subjects missed. Each dot indicates 1 neuron. ***P < 0.0005, Wilcoxon’s signed-rank test, 2-tailed. Source data are available in S1 Data. SDF, spike density function.
Fig 8.
Constructive process for the flexible use of memory.
Schematic diagram of neuronal signals during a trial of the CMP task, in which the item cue and the orientation of background cue were I-B and 90°, respectively. In the HPC, the retrieved location of the item is represented relative to the 0° background image, which may correspond to the top right in egocentric space. The incoming perceptual signal is integrated with the memory signal to construct an updated information signaling the target location by following sequential neuronal operations: convergence (i.e., memory [co-location I on the 0° background] + perception [90° background]), transference (i.e., from the top right [co-location I on the 0° background] into the bottom right [co-location I on the 90° background]), and targeting (i.e., coding bottom right). It is still unknown which brain area is involved first in the retrieval of item-location association memory and whether the retrieved memory content is same as the memory signal in the HPC. CMP, constructive memory-perception; HPC, hippocampus.