Article Figures & Data
Figures
- Figure 1.
Schematics for the design of (A) the rule-visible and (B) the rule-memorized pro- and antisaccade task. (C) The placement of recording chambers and (D) structural magnetic resonance images that verify the chamber placement in Monkey A and (E) Monkey C.
- Figure 2.
Effects of ketamine and saline injection on the percentage of (A) correct response and (B) saccadic reaction times. Performance on RV trials are shown as solid lines and RM trials as dashed lines. Prosaccade trials are shown in blue and antisaccade trials in red. Error bars indicate the standard deviation of the mean.
- Figure 3.
Dose–response plots for (A) performance and (B) saccadic reaction times. The black dot denotes the first session at the given dose. Subsequent sessions were plotted in increasingly lighter shades of gray. A, Higher doses tended to be linked to greater impairment in the performance—a correlation significant in Monkey A (left) but not C (right). Tolerance to ketamine treatment would be visible as lighter gray dots being higher than darker dots, which was not always the case. B, Higher doses tended to be linked to a greater increase in SRT, which was significant in Monkey A (left) but not C (right). Tolerance would be visible as darker dots being higher than lighter gray dots, which was generally not the case.
- Figure 4.
An example of the effects of ketamine on the aperiodic and oscillatory components of the LFPs. A, Ketamine reduced both the exponent (visible as the slope) and the offset of the aperiodic component of the LFP power (visible as the lower position of intersection with the y-axis; dashed, pre-injection; solid, post-injection). B, In this case, ketamine increased the central frequency of the oscillatory component of the LFP, without changing its amplitude. C, Total LFP power with both the aperiodic and oscillatory components combined.
- Figure 5.
The effect of ketamine on the aperiodic component of LFPs. In both (A) Monkey A and (B) Monkey C and in both RV and RM tasks, ketamine injection led to a reduction in the offset of the aperiodic LFP. In both monkeys, the offset was significantly higher in the PPC than lPFC. Similarly, in both (C) Monkey A and (D) Monkey C and in both tasks, ketamine led to a reduction in the exponent of the aperiodic LFP. The exponent was also significantly higher in the PPC than lPFC.
- Figure 6.
Effects of ketamine on the oscillatory components of LFP. A, Distribution of central frequencies of oscillatory components across all channels from both monkeys. Based on this plot, we divided all oscillations into three frequency bands: theta (8–10 Hz), mid-frequency (10–45 Hz), and high-frequency (45–100 Hz) oscillations. B, Central frequency of theta band did not change following ketamine injection in either region, in either animal. C, Similarly, the amplitude of theta oscillation did not show any effect of ketamine. D, Central frequency of mid-frequency oscillations increased in both areas in Monkey A (left panel) and in the PPC of Monkey C (right panel). In Monkey C, the central frequency had a regional difference. E, Amplitude of mid-frequency oscillations did not change except in the PPC of Monkey A. In both animals, the mid-frequency amplitude was greater in the PPC. F, The central frequency of high-frequency oscillations reduced following ketamine injection in the PPC of Monkey A and the lPFC in Monkey C. G, Amplitudes of high-frequency oscillations were not affected by ketamine. *p < 0.05, **p < 0.01.
- Figure 7.
The effect of ketamine on rule selectivity in LFP oscillations across regions and tasks, in Monkey A and Monkey C, in theta band (A, B), mid-range frequencies encompassing alpha, beta, and low gamma bands (C, D), and in high gamma band (E, F). The empty bars denote pre-injection rule selectivity, and the filled bars represent post-injection values. The lPFC is shown in orange, and the PPC is in purple. *p < 0.05.
- Figure 8.
Changes in coherence within the lPFC and PPC, measured as debiased weighted phase lag index (dWPLI), following ketamine treatment. A, Within the lPFC, in Monkey A: Left, In the RV task, delay-period coherence did not increase (positive numbers) or decrease (negative numbers) significantly following ketamine injections in Monkey A, in either pro- (blue) or antisaccade (red) trials. Right, In the RM task, intra-lPFC coherence decreased in the gamma band ∼50 Hz under both rules. The blue and red horizontal bars indicate p < 0.05 for pro- and antisaccade rules, respectively, after family-wise error adjustment. B, Within the lPFC, in Monkey C: Left, In the RV task, ketamine had no effect. Right, In the RM task, under the prosaccade rule, ketamine increased the coherence in high gamma. C, Within the PPC, in Monkey A: under both rules and tasks, ketamine reduced coherence in beta frequencies. It also increased coherence in the low gamma band in RV prosaccade trials. D, Within the PPC, in Monkey C: ketamine reduced coherence in both tasks and rules across several frequency bands.
- Figure 9.
Ketamine affected lPFC–PPC coherence in multiple frequency bands in both (A) Monkey A and (B) Monkey C, in both RV and RM tasks and under both pro- (blue) and antisaccade (red) rule. The blue and red horizontal bars indicate p < 0.05 for pro- and antisaccade rules, respectively, after family-wise error adjustment.
- Figure 10.
Ketamine affected the directional connectivity between the lPFC and PPC in the time domain (Granger prediction). A, In Monkey A, Granger prediction is overall stronger in the lPFC-lead than the PPC-lead model (left vs right set of bars). Ketamine significantly reduced their connectivity in both RV and RM tasks and under both prosaccade (light vs dark red) and antisaccade (light vs dark blue) rules. B, In Monkey C, ketamine induced the same set of changes in Granger prediction. *p < 0.05, **p < 0.005, ***p < 0.0005.
- Figure 11.
Ketamine-related changes in the level of performance were in some cases positively correlated with ketamine-related changes in lPFC–PPC Granger prediction, such as in the RV task, under the antisaccade rule in both (B) Monkey A and (D) Monkey C. This was not the case under the prosaccade rule in either monkey, as shown in A and C. The red lines depict the linear relationship between the drug-related changes. Also shown are Pearson's r and its associated p value.
- Figure 12.
Ketamine-related changes in SRT were in some cases negatively correlated with ketamine-related changes in lPFC–PPC Granger prediction, as in the RM task under the “antisaccade” rule in both (B) Monkey A and (D) Monkey C. This was also the case under the “prosaccade” rule in (C) Monkey C but not in (A) Monkey A. The red lines depict the linear relationship between the drug-related changes. Also shown are Pearson's r and its associated p value.
- Figure 13.
Rule selectivity (d′) during different epochs in all single units recorded from the (A) lPFC in Monkey A and (B) Monkey C and from the (C) PPC in Monkey A and (D) Monkey C. The third epoch from RV trials is the later part of the prolonged cue period, which matched the delay period in RM trials. Solid lines, RV trials; dashed lines, RM trials. pre-injection, gray; post-injection, black. Error bars indicate the standard deviation of the mean. **p < 0.005, ***p < 0.0005.
