Neural correlates of short-term memory in primate auditory cortex

Abstract

Behaviorally-relevant sounds such as conspecific vocalizations are often available for only a brief amount of time; thus, goal-directed behavior frequently depends on auditory short-term memory (STM). Despite its ecological significance, the neural processes underlying auditory STM remain poorly understood. To investigate the role of the auditory cortex in STM, single- and multi-unit activity was recorded from the primary auditory cortex (A1) of two monkeys performing an auditory STM task using simple and complex sounds. Each trial consisted of a sample and test stimulus separated by a 5-s retention interval. A brief wait period followed the test stimulus, after which subjects pressed a button if the sounds were identical (match trials) or withheld button presses if they were different (non-match trials). A number of units exhibited significant changes in firing rate for portions of the retention interval, although these changes were rarely sustained. Instead, they were most frequently observed during the early and late portions of the retention interval, with inhibition being observed more frequently than excitation. At the population level, responses elicited on match trials were briefly suppressed early in the sound period relative to non-match trials. However, during the latter portion of the sound, firing rates increased significantly for match trials and remained elevated throughout the wait period. Related patterns of activity were observed in prior experiments from our lab in the dorsal temporal pole (dTP) and prefrontal cortex (PFC) of the same animals. The data suggest that early match suppression occurs in both A1 and the dTP, whereas later match enhancement occurs first in the PFC, followed by A1 and later in dTP. Because match enhancement occurs first in the PFC, we speculate that enhancement observed in A1 and dTP may reflect top-down feedback. Overall, our findings suggest that A1 forms part of the larger neural system recruited during auditory STM.

Keywords: A1; Macaca mulatta; primary auditory cortex; recognition memory; rhesus macaque; working memory.

Figure 1

Diagram of the auditory short-term memory task. Each trial consisted of 500-ms sample and test sounds separated by a 5-s retention interval. For match trials, the sounds were identical and the correct response was a button press, whereas for non-match trials the sounds were non-identical and the correct response was to withhold from pressing the button. Sample and test sounds were pseudorandomly selected for each trial from a variety of naturalistic and artificial sound exemplars (see Methods). A pre-response wait period followed the test stimulus, after which the response button was illuminated to signal the response window. Responses outside of the response window (e.g., during the sound presentations or wait period) aborted the trial and these trials were not included in subsequent analyses. Overhead lighting provided constant low-level illumination throughout the session, and a second overhead light was turned on during the ITI to serve as a cue by which trials could be segregated.

Figure 2

Example units with significant changes in firing rate during the retention interval. Many units exhibited a diminishing firing rate throughout the retention interval (units i–vi). In some cases (units i–iv), the firing rate fell below baseline during the latter portion of the retention interval. In other cases (units v–vi), the firing rate returned to baseline levels from a significantly elevated firing rate earlier in the retention interval. Other units exhibited a trend toward increased firing rates during the retention interval (units vii–ix). The periods denoted by dashed lines with asterisks indicate successive 500-ms bins that were significantly different from baseline (mean firing rate 500 ms prior to trial onset). Shaded gray areas indicate sample and test stimulus presentation periods.

Figure 3

Summary of significant changes in firing rate from baseline during the retention interval. (A) Many units exhibited increased firing rates immediately after the offset of the sample stimulus, but for the majority of units, firing rates returned to baseline thereafter. Suppression was somewhat less common immediately following sample stimulus offset, but was observed more frequently further into the retention interval. Suppression was also more common in the latter retention interval bins prior to test stimulus onset. FR, firing rate. (B) Consistent with the firing rate changes observed in individual units, the mean population firing rate was briefly elevated at the offset of the sample stimulus, but then temporarily fell below baseline. After returning to baseline near the midpoint of the retention interval, firing rates again fell significantly below baseline during the latter portion of the retention interval prior to the test stimulus. Asterisks indicate retention interval periods that differed significantly from baseline (500 ms prior to trial onset) indicated by the dashed line.

Figure 4

Example units showing match enhancement, suppression, or no change. (A) Example units for which enhanced firing rates were elicited by matching compared to non-match test sounds. (B) Example units for which suppressed firing rates were elicited by matching compared to non-match test sounds. (C) Examples of units for which there were no significant differences in firing rate elicited by matching and non-matching test stimuli at any point during the cue, offset, or pre-response wait periods. Gray bars indicate the test stimulus presentation period. Black bars above the firing rate histograms indicate significant differences in firing rate between trial types (assessed with a 100-ms sliding window, advancing in 20-ms steps). Note that very brief changes in firing rate were not reported (such as those observed for unit i at stimulus onset and unit iv at stimulus offset), inasmuch as differences were only accepted if significant effects were obtained for two or more consecutive steps.

Figure 5

Population spiking activity during auditory short-term memory task. Firing rates elicited by matching and non-matching test stimuli are depicted in the right panel, and firing rates elicited by the sample stimuli are shown in the left panel as a control comparison. Beginning during the latter portion of the test stimulus presentation period, firing rates became significantly higher for match compared to non-match trials. This difference was sustained with minimal interruption throughout the offset and pre-response wait periods. The black bars below the firing rate histograms indicate significant differences between trial types (assessed with a 100-ms sliding window, advancing in 20-ms steps). Differences were only accepted if significant effects were obtained for two or more consecutive steps. The gray bars above the abscissae indicate the sample and test stimulus presentation periods (0–500 ms from cue onset) as a well as the onset of the response window (R.W.).

Figure 6

Single-unit subpopulation spiking activity during auditory short-term memory task. Firing rates elicited by matching and non-matching test stimuli are depicted in the right panel, and firing rates elicited by the sample stimuli are shown in the left panel as a control comparison. Similar trends were observed in the population (Figure 5) and single-unit subpopulation analyses. However, early match suppression effects reached significance only in the single unit subpopulation. In addition, the elevated firing rates beginning during the latter portion of the test stimulus were less robust, reaching significance only during the late pre-response period. The black bars below the firing rate histograms indicate significant differences between trial types (assessed with a 100-ms sliding window, advancing in 20-ms steps). Differences were only accepted if significant effects were obtained for two or more consecutive steps. The gray bars above the abscissae indicate the sample and test stimulus presentation periods (0–500 ms from cue onset) as a well as the onset of the response window (R.W.).

Figure 7

Population spiking activity observed on error trials during auditory short-term memory task. Firing rates elicited by sample and test stimuli are depicted in the left and right panels, respectively. No significant differences in firing rate were observed for non-match error trials during pretrial baseline, the sample stimulus presentation period, or the retention interval. During the latter portion of the test stimulus period, firing rates on non-match error trials were significantly higher than on correct non-match trials (similar to match trials). During the cue offset and pre-response wait periods, firing rates on non-match error trials were intermediate between correct match and correct non-match trials. The blue and red bars below the firing rate histograms indicate significant differences between non-match error trials and correct non-match and match trials, respectively, (assessed with a 100-ms sliding window, advancing in 20-ms steps). Differences were only accepted if significant effects were obtained for two or more consecutive steps. The gray bars above the abscissae indicate the sample and test stimulus presentation periods (0–500 ms from cue onset) as a well as the onset of the response window (R.W.).

Figure 8

Summary of population-averaged neurophysiological activity in three cortical areas for matching and non-matching test sounds. (A) In PFC, firing rates on match trials became elevated relative to non-match trials during the early sound presentation period. Elevated firing rates were similarly observed on match trials in (B) primary auditory cortex and (C) dorsal temporal pole. However, these effects occurred later than in PFC, during the sound period or cue offset period, consistent with the notion that elevated firing in these areas may reflect top–down feedback originating in PFC. In contrast to these late match enhancement effects, significant suppression was observed on match trials in the early sound period in dorsal temporal pole. Early match suppression was also observed in auditory cortex in a portion of the individual units as well as in the single-unit subpopulation (Table 1, Figures 4, 6). The gray bars above the abscissae indicate the test stimulus presentation period (0–500 ms from cue onset). (A) Adapted from Plakke et al. (2013); (C) adapted from Ng et al. (2014). Each of the summarized experiments were conducted using the same subjects and auditory short-term memory task (see Methods for details).