Dissociation of LFP Power and Tuning in the Frontal Cortex during Memory

Abstract

Working memory, the ability to maintain and manipulate information in the brain, is critical for cognition. During the memory period of spatial memory tasks, neurons in the prefrontal cortex code for memorized locations via persistent, spatially tuned increases in activity. Local field potentials (LFPs) are understood to reflect summed synaptic activity of local neuron populations and may offer a window into network-level processing. We recorded LFPs from areas 8A and 9/46 while two male cynomolgus macaques (Macaca fascicularis) performed a long duration (5.1-15.6 s) memory-guided saccade task. Greater than ∼16 Hz, LFP power was contralaterally tuned throughout the memory period. Yet power for both contralateral and ipsilateral targets fell gradually after the first second of the memory period, dropping below baseline after a few seconds. Our results dissociate absolute LFP power from mnemonic tuning and are consistent with modeling work that suggests that decreasing synchronization within a network may improve the stability of memory coding.SIGNIFICANCE STATEMENT The frontal cortex is an important site for working memory. There, individual neurons reflect memorized information with selective increases in activity, but how collections of neurons work together to achieve memory is not well understood. In this work, we examined rhythmic electrical activity surrounding these neurons, which may reflect the operation of recurrent circuitry that could underlie memory. This rhythmic activity was spatially tuned with respect to memorized locations as long as memory was tested (∼7.5 s). Surprisingly, however, the overall magnitude of rhythmic activity decreased steadily over this period, dropping below baseline levels after a few seconds. These findings suggest that collections of neurons may actively desynchronize to promote stability in memory circuitry.

Keywords: frontal eye fields; local field potential; macaque; prefrontal cortex; working memory.

Figure 1.

Memory-guided saccade task. A, The subject began each trial with 1.5 s of fixation at a central point (black square). Then, a peripheral target (red square) appeared for 300 ms at a random location about a circle (dotted line; invisible to the subject). Next, the target disappeared, and the subject maintained fixation for 5.1, 7.6, or 15.6 s, plus an additional 0–0.5 s of random duration. Finally, the fixation point disappeared, signaling the subject to make an eye movement (arrow) to the remembered target location. B, Distance of eye positions from the memory target for Monkeys C and W after a memory-guided saccadic response and just before the target reappeared. Data are separated by the trial memory period duration. Data are rotationally aligned about the fixation point (black square) by the location of the memory target. Red points indicate saccades that landed within 8 dva horizontally and 10 dva vertically (before rotational alignment) of the memory target, i.e., successful saccades. Black points indicate the eye positions at the end of error trials. In some trials, animals land within the 16 by 20 dva window but move out of it before the target reappears, resulting in red points far from the target. Only data from trials with memory target eccentricities of 10 deg are shown. C, D, Metrics of memory-guided behavior over time for Monkeys C (black) and W (gray). The hit rate (i.e., percentage of successful saccades) and the reliability of saccade endpoints (measured as 1/SD of the saccadic error, or “saccade precision”) decreased with longer memory periods. Saccade precision is plotted with error bars showing 95% bootstrapped CIs. Note that, for normally distributed data, 95% confidence limits are ∼2 SEM, so that these error bars are twice as large as conventional error bars.

Figure 2.

Recording locations. LFP recording locations for Monkeys C (A) and W (B). Recording locations (red dots) are projected onto a representative anatomical MR image. Electrodes were inserted orthogonally to the plane of these images. LFPs were recorded from area 8A near the arcuate sulcus (A.S.) and from area 9/46 near the principal sulcus (P.S.). The blue highlighted region in Monkey C's image marks an MR-lucent manganese injection, used to verify recording site location.

Figure 3.

Evoked LFPs. A, The population-averaged evoked LFP (215 sites) shows a transient response to stimulus presentation (0–0.3 s; red horizontal bar in x-axis) and to reward delivery (7.8 and 12.8 s after the stimulus onset; red vertical lines), but exhibits no sustained memory response. B, The average evoked LFP with rewards at 6.3, 10.3, and 12.3 s after stimulus onset exhibits responses immediately after those rewards (20 sites from Monkey C). C, The average evoked LFP with rewards every 2.5 s exhibits responses immediately after those rewards (27 sites from Monkey W). In all plots, the solid trace depicts the mean and the shaded region depicts the bootstrapped 95% CI. The data are plotted for the fixation (before 0 s), stimulus (0–0.3 s), and memory periods (0.3–15.3 s poststimulus onset). All trials contribute data from −1.5 to +5.3 s of stimulus onset. Trials with memory periods of ∼7.5 and ∼15 s contribute data from 5.3 to 7.8 s, whereas only ∼15 s trials contribute data from 7.8 to 15 s.

Figure 4.

LFP power spectral density. A, The mean power spectral densities (4–128 Hz in 2 Hz steps) from baseline (1.5–0 s before the stimulus; black), a peristimulus interval (0–1 s after stimulus onset; blue), and the memory interval (2–7.8 s after stimulus onset; orange) were all similar with subtle, frequency-specific differences. The spectrum of each site was normalized by mean broadband power (summed across 4–128 Hz) during baseline before averaging across sites. The dip at 60 Hz is caused by a 60 Hz notch filter in the amplifier. B, Mean percentage difference from baseline of the power spectral density for the peristimulus (blue) and memory interval (orange). The solid traces depict mean and the shading depicts the bootstrapped 95% CI (approximately twice the size of conventional error bars). Power in the theta (4–8 Hz) and alpha bands (8–16 Hz) was greater for the peristimulus interval, whereas baseline and memory power were similar. Beta-band (16–32 Hz) power was greatest for baseline, followed by memory and then the peristimulus interval. Gamma-(32–64 Hz) and high-gamma-band power (64–128 Hz) was greatest for the peristimulus interval, followed by baseline and then memory.

Figure 5.

Time course of LFP power. A, Mean percentage modulation of LFP power spectral density from baseline. The stimulus appears at time 0 for 300 ms (x-axis, red bar). The vertical dashed line indicates the time of the first midtrial reward. B–F, Percentage modulation from baseline of theta- (B; 4–8 Hz), alpha- (C; 8–16 Hz), beta- (D; 16–32 Hz), gamma- (E; 32–64 Hz), and high-gamma-band (F; 64–128 Hz) power during the task. Power generally increases with the stimulus, with the exception of the beta band, which then climbs above baseline ∼1 s later. All bands return to baseline within 1–3 s after stimulus onset. Beta-, gamma-, and high-gamma-band power drop below baseline by 3, 1, and 5 s after stimulus onset, respectively, and continue to decrease through 7.5 s of memory. The solid line is the mean across all recording sites, and the shading is the 95% CI (approximately twice the size of conventional error bars). Thin dashed lines show averages for areas 8A and 9/46, which are very similar to one another and to the global average. Note that responses to stimuli and rewards appear earlier in the theta-band data (B) because the spectral analysis window is larger (see Materials and Methods).

Figure 6.

LFP power directional tuning. Distribution of preferred directions of LFP power during the peristimulus interval (0–1 s after stimulus onset). LFP preferred directions were clustered in the contralateral direction (0 deg) for theta (4–8 Hz; A), alpha (8–16 Hz; B), beta (16–32 Hz; C), gamma (32–64 Hz; D), and high-gamma power (64–128 Hz; E). In each plot, dark colors represent sites with significant tuning (p < 0.05; F test) and light colors represent sites without significant tuning.

Figure 7.

LFP power directional tuning. Distribution of preferred directions of LFP power during the early memory interval (2–5.3 s after stimulus onset) intervals. Theta- (A) and alpha-band (B) preferred directions became uniformly clustered, whereas beta- (C), gamma- (D), and high-gamma-band (E) preferred directions remained contralaterally clustered. Format as in Figure 6.

Figure 8.

Time course of LFP power tuning. The difference in LFP power between contralateral and ipsilateral stimuli; format as in Figure 5. A, Mean tuning of LFP power spectral density as a percentage of absolute baseline power spectral density. B–F, Tuning of individual bands as a percentage of absolute baseline power. All but beta are tuned for the stimulus. Within ∼1 s, theta (B) and alpha (C) become untuned, whereas gamma (E) and high-gamma bands (F) remain tuned throughout 7.5 s of memory. Beta-band tuning (D) ramps up over ∼1 s and persists for the remainder of the ∼15 s memory period. Both area 8A and area 9/46 resembled the global averages when considered separately (thin dashed lines). Shaded region corresponds to the 95% CI, which is approximately twice the size of conventional error bars.