Preparatory attention relies on dynamic interactions between prelimbic cortex and anterior cingulate cortex

Abstract

An emerging view of prefrontal cortex (PFC) function is that multiple PFC areas process information in parallel, rather than as distinct modules. Two key functions assigned to the PFC are the regulation of top-down attention and stimulus-guided action. Electrophysiology and lesion studies indicate the involvement of both the anterior cingulate cortex (ACC) and prelimbic cortex (PL) in these functions. Little is known, however, about how these cortical regions interact. We recorded single unit spiking and local field potentials (LFPs) simultaneously in rodents during a sustained attention task and assessed interactions between the ACC and PL by measuring spike-LFP phase synchrony and LFP-LFP phase synchrony between these areas. We demonstrate that the magnitude of synchrony between the ACC and PL, before stimulus onset, predicts the subjects' behavioral choice after the stimulus. Furthermore, neurons switched from a state of beta synchrony during attention to a state of delta synchrony before the instrumental action. Our results indicate that multiple PFC areas interact during attention and that the same neurons may participate in segregated assemblies that support both attention and action.

Figure 1.

Summary of the method of analysis of spike–LFP phase locking. Spike times (A, top) and LFP (A, black) were recorded simultaneously. (A) Data are plotted for a single example trial during the 2 s before stimulus onset (t = 0). The LFP was convolved with a complex Morlet wavelet. The amplitude (blue) and phase angle (red) at 40 Hz are plotted below the raw data. Spike times are indicated by black dots on the plot of phase angle (red). In this trial, the spikes tend to occur around the mean resultant angle (dotted black line), which was calculated using spike times from all trials for this neuron. (B) Spikes from the 2 s before stimulus onset combined across all trials, for the same neuron as in (A). The neuron was significantly phase locked (Rayleigh's test for circular uniformity, Z = 8.936, P < 0.0001) and the mean phase angle was 3.504 radians.

Figure 2.

Prestimulus broadband LFP power is correlated with trial type. The spectrogram shows the mean normalized LFP power averaged across 4 rats. Stimulus onset is at t = 0 s. Power was normalized within trial and then averaged across trials, within subject. Data are shown for correct trials (left) and incorrect trials (middle) for both the ACC (A) and PL (B). A t-test was used to compare each time-frequency bin between trial types. The results are plotted (right) using black if P was not significant, gray if 0.05 ≤ P < 0.08, and white if P < 0.05. In both brain regions, delta (1–4 Hz), alpha (8–12 Hz), and beta (13–30 Hz) powers are greater on correct trials. However, the time course and frequency spread is not the same in both brain regions. Although not different between trial types, the power of alpha oscillations fluctuated over time in a periodic manner.

Figure 3.

Within-region phase locking during the prestimulus period. (A) A schematic illustrating that the top panel (A,C,E) are data using ACC spikes and ACC field potentials. The proportion of neurons that were significantly (Rayleigh's test, P < 0.05) phase locked to frequencies between 1.5 and 50.0 Hz, during −2 to 0 s before stimulus onset, on correct (red, solid) and incorrect (blue, dotted) trials. The width of the vertical bar indicates frequencies at which there was a reduction in the proportion of phase locked neurons on incorrect trials (Chi-squared test, P < 0.05). (C) Mean, time-resolved, phase locking strength (Rayleigh's Z) is averaged across ACC neurons that phase locked to ACC delta (1–4 Hz) oscillations before stimulus onset. Stimulus onset is at t = 0 s. Rayleigh's Z was calculated in 2-s windows that were slid in 200 ms steps. Delta phase locking was reduced during incorrect trials. (E) The median phase angle of each ACC neuron illustrates that neurons are all phase locked to the trough of ACC delta oscillations (circular analog of Kruskal–Wallis test, P = not significant indicating no difference in phase angle distribution between neurons). (B,D,F) Same as above. (B) A schematic illustrating that the bottom panel is data using PL spikes and PL LFP. A larger proportion of neurons phase locked to beta (13–30 Hz) oscillations on correct trials. (D) These neurons phase locked to beta oscillations during the prestimulus period on correct trials and phase locking strength was reduced on incorrect trials. (F) The PL neurons phase locked to the peak of PL beta oscillations.

Figure 4.

Between-region phase locking during the prestimulus period. (A) A schematic illustrating that the top panel (A–C) uses ACC neuron spikes and PL LFP oscillations. The proportion of neurons, between 1.5 and 50.0 Hz, that significantly phase lock to LFP from −2 to 0 s before stimulus onset on correct (red, solid) and incorrect (blue, dotted) trials. The width of the vertical bar indicates frequencies at which there was a reduction in the proportion of phase locked neurons on incorrect trials (Chi-squared test, P < 0.05). (B) Mean time-resolved phase locking strength (Rayleigh's Z) is averaged across the ACC neurons that phase locked to PL beta (13–30 Hz) LFP oscillations before stimulus onset. Stimulus is at t = 0 s. Rayleigh's Z was calculated in 2-s windows that were slid in 200-ms steps. Beta phase locking was present on correct trials and was not present on incorrect trials. The Between-region spike–field phase locking was centered at 22 Hz. (C) Prestimulus phase synchrony between the LFP signals recorded in the ACC and PL at 22 Hz. LFP–LFP phase synchrony was quantified over time using a within trial PLV. Stimulus onset is at t = 0 s. The mean PLV and its standard error (across rats) are shown for correct trials (orange), incorrect trials (green), and trial shuffled surrogate data (blue). During both correct and incorrect trials, a significantly high (compared with surrogate) level of LFP–LFP phase synchrony exists at 22 Hz before stimulus onset. (D–F) Same as above. (D) A schematic illustrating that the bottom panel uses PL neuron spikes and ACC LFP oscillations. A larger proportion of neurons phase locked to alpha oscillations on correct trials. (E) These PL neurons phase locked to ACC alpha (8–12 Hz) oscillations on correct trials, rather than incorrect trials, during the prestimulus period. The Between-region phase locking was centered at 12 Hz. (F) Prestimulus LFP–LFP phase synchrony at 12 Hz increases over time on correct (orange) and incorrect (green) trials. In both trial types, a significantly high level of LFP–LFP synchrony occurs at 12 Hz before stimulus onset.

Figure 5.

(A) A schematic illustrating that the top panel uses spikes from ACC neurons that were phase locked to PL beta oscillations during the prestimulus period. Neural activity is aligned to the onset of instrumental action (nose poke) at t = 0 s. The mean time-resolved phase locking strength was calculated across these neurons using a 1-s window, slid in 100-ms steps. Between-region delta oscillation phase locking occurs before the action during both correct and incorrect trials. (B) During the same time period, PL delta power is increased.