The auditory cortex mediates the perceptual effects of acoustic temporal expectation

Abstract

When events occur at predictable instants, anticipation improves performance. Knowledge of event timing modulates motor circuits and thereby improves response speed. By contrast, the neuronal mechanisms that underlie changes in sensory perception resulting from expectation are not well understood. We developed a behavioral procedure for rats in which we manipulated expectations about sound timing. Valid expectations improved both the speed and the accuracy of the subjects' performance, indicating not only improved motor preparedness but also enhanced perception. Single-neuron recordings in primary auditory cortex showed enhanced representation of sounds during periods of heightened expectation. Furthermore, we found that activity in auditory cortex was causally linked to the performance of the task and that changes in the neuronal representation of sounds predicted performance on a trial-by-trial basis. Our results indicate that changes in neuronal representation as early as primary sensory cortex mediate the perceptual advantage conferred by temporal expectation.

Figure 1. Task and manipulation of temporal expectation

(a) Subjects initiated each trial by poking into the center port of the operant chamber^,. After a variable (250–350 ms) silent period, a stimulus consisting of a frequency-modulated target immersed in a train of pure tone distractors was presented. Subjects were required to stay in the port until the target was presented. The center frequency of the target (either 6.5 kHz or 31 kHz) indicated the side-port where water reward would be delivered on each trial (left or right, respectively). (b) The stimulus consisted of a sequence of 100ms pure tones (ranging from 5 to 40 kHz) separated by 50 ms, which was presented for as long as the animal stayed in the port. The frequency-modulated target was presented in place of one of the tones in each trial. (c) Temporal expectation was manipulated by changing the ratio of trials with early or late targets within each block of 150–200 trials.

Figure 2. Valid temporal expectation improved performance

(a) Behavioral responses were faster on trials with expected targets. Example of the reaction time distribution from one animal at the easiest difficulty tested (TMD~25%) for early targets that were expected (blue) or unexpected (green). Reaction time was defined as the time between the onset of a target and the moment when the animal left the center port. (b) Median reaction time for each animal (gray dots) on the easiest difficulty tested, and average across all 8 subjects for early targets that were expected (blue) or unexpected (green). Stars represent statistical significance (** p<0.01). (c) Behavioral responses were more accurate on trials with expected targets. Example for one animal of the percentage of correct trials as a function of difficulty, varied here by the modulation depth of the target (TMD). Error bars correspond to the 95% confidence intervals on estimates. The dashed line corresponds to 75% performance used for calculating thresholds in d. (d) Modulation depth needed to achieve 75% correct trials for each subject (gray dots), and average across all 8 subjects (colored bars). Stars represent statistical significance (** p<0.01).

Figure 3. Inactivation of auditory cortex decreased performance

(a) Bilateral reversible inactivation of auditory cortex (AC) was performed by applying the GABA_A receptor agonist muscimol on the surface of the exposed dura mater. Craniotomies were protected by implanted wells. Darker and lighter colored regions indicate primary and secondary auditory cortices respectively. (b) Performance on expected early targets as a function of difficulty on interleaved inactivation (gray) and control (black) sessions. The plot shows the average over 5 animals. Error bars indicate s.e.m. across animals.

Figure 4. Temporal expectation modulated neuronal activity in auditory cortex

(a) Responses of a single neuron to the same sequence of tones under two temporal expectation conditions: expecting an early (blue) or a late (red) target. Expected early targets appeared after 450ms, whereas expected late targets (not visible here) were presented after 1500ms. Trials are aligned to the onset of the first tone (gray vertical line) for the spike raster (top) and the peristimulus time histogram for each condition (bottom). The session included more than two blocks of trials, but all expect-early or expect-late blocks are grouped together here for illustration purposes. The frequency and duration of each tone is indicated by the gray boxes. The largest difference in evoked activity is seen for the tone immediately preceding the early target. The stimuli presented after 450ms are not the same on each trial; average responses in this case are shown as dashed lines. (b) Modulation index of 44 responsive cells recorded during sessions where all tones preceding the early targets had fixed frequencies. A positive modulation index indicates a stronger response on expect-early trials. Cells with statistically significant modulation (p<0.05 Wilcoxon rank-sum test) are shown in black. The gray triangle indicates the mean of the modulation index. The white triangle shows the modulation index for the example in a. (c) Evoked local field potential (mean ± s.e.m.) at one recording site. The onset of the early target is indicated by the blue triangle. (d) Modulation of local field potentials. Colors as in b.

Figure 5. Modulation of neuronal activity was specific to driven activity

(a) Frequency tuning of a single cell, estimated from responses to the third tone in each expectation condition (see Supplementary Fig. 10). Each marker represents the mean ± s.e.m. firing rate for each tone frequency. Significance levels are indicated by stars (* p<0.05, *** p<0.001, Wilcoxon rank-sum test). (b) Average frequency tuning of 58 cells recorded with a third tone of random frequency. Individual tuning curves were aligned according to the preferred frequency (PF) of each cell and normalized before averaging. Each marker indicates the mean ± s.e.m. across neurons. Significance levels are indicated by stars (* p<0.05, paired Wilcoxon signed-rank test).

Figure 6. Neuronal response increased as the expected moment of the target approached

(a) Frequency tuning of cell in Fig. 5a, as the time of the late target approaches. For each time-slot preceding the late target, the estimated tuning curve is plotted in a different color. The color-bar shows the time of each time-slot with respect to the target onset. (b) Neuronal response to each cell’s preferred frequency (PF) as the time of the target approaches. Responses were normalized with respect to the response to the fourth tone (−1050 ms from late target onset). Each point corresponds to the median across cells, with error bars proportional to the median absolute deviation. Only responses to the preferred frequency for each cell are presented, and only cells with responses above spontaneous firing for each time-slot were included (N=20). The significance level of the difference with respect to the response to the fourth tone is indicated at each time-slot by stars (* p<0.05, ** p<0.01, paired Wilcoxon signed-rank test).

Figure 7. Neuronal activity in auditory cortex was correlated to behavioral performance

(a) Average evoked LFP from a single electrode for trials with expected early targets grouped according to reaction time. Averages are taken over those trials with the 20% fastest (blue solid), or the 20% slowest (blue dashed) reaction times. Evoked LFP for trials with late targets is shown in red for comparison. The light-colored bands surrounding each trace indicate the s.e.m. across trials. The stimulus (third tone with fixed frequency across trials) is indicated by the gray bar, and the onset time of an early target is represented by the blue triangle. (b) Evoked LFPs were larger on trials with faster behavioral responses. Difference in evoked LFP magnitude between trials with the fastest and slowest behavioral responses. The difference is quantified by a modulation index between the average response on fast (LFP_F) and slow (LFP_S) trials for each recording site (N=59). Sites with a significant difference (p<0.05, permutation test) are shown in black. The gray triangle indicates the mean modulation index. (c) Evoked spiking activity was larger on trials with faster behavioral responses. Difference in evoked activity on single cells between trials with the fastest and slowest behavioral responses. The difference is quantified by a modulation index between the average response on fast (RF) and slow (RS) trials for each cell (N=44). Cells with a significant difference (p<0.05, Wilcoxon rank-sum test) are shown in black. The gray triangle indicates the mean modulation index. Only sessions where the third tone had the same frequency on all trials were included in this analysis.