Figure 3. The control sequences. A. The three control conditions. In the ‘Diverse’ sequences, narrow and broad, the available frequencies were evenly spaced on a logarithmic frequency scale. The range of frequencies was narrow (about twice Df) in the Diverse-narrow sequence, and wide (11Df) in the Diverse-broad sequence. In the ‘Deviant-alone f1’ and ‘Deviant-alone f2’ sequences, the other 95% of the presentations were silent. B. The average LFP responses to frequencies f1 and f2 embedded in the control sequences (same recording site as Fig. 1). The responses in the two Deviant-alone sequences are superimposed. Error bars: 6 s.e.m., shaded interval: stimulus. C. MUA Responses at the same site. doi:10.1371/journal.pone.0023369.g003 presented in 5% of the presentation intervals, as in the Deviant-f1 oddball sequence, but the standard presentations were replaced by silence. Similarly, the ‘Deviant-alone f2’ sequence presented the deviant f2 against a silent background. These two sequences matched the oddball sequences in terms of rarity and uniqueness of the rare stimulus (unlike the diverse sequences), but unlike all other sequences, in the Deviant-alone sequences there was no interaction with any other stimulus. Figure 3B shows the LFP responses to f1 and f2 in the three control sequences, recorded from the same recording site as the Deviance Detection in Rat Auditory Cortex data presented in Figs. 1B and 1C. The responses to f1 and f2 in each of these sequences were similar. The responses in the Diverse-narrow sequence were smaller than those of the Diverse- broad or the Deviant-alone sequences, demonstrating the presence of cross-frequency adaptation. On the other hand, the responses in the Diverse-broad and the Deviant-alone sequences were comparable. The MUA responses shown in Fig. 3C showed similar trends, except that cross-frequency adaptation in the Diverse-narrow sequence was stronger for frequency f2 than for frequency f1, possibly because f1 was closer to the best frequency of the MUA at this site. We therefore had seven different sequences (Deviant-f1 and -f2, Equal probability, Diverse-narrow and -broad, and Deviant-alone f1 and f2) that tested both f1 and f2 in six conditions. The collection of responses to one frequency in all six conditions is termed ‘a set’ below. Figure 4A re-plots the responses from Figs. 1 and 3, grouped by frequency rather than by presentation sequence. It therefore illustrates the influence of context on the responses to tones of each of the two frequencies. Figure 4B shows responses recorded from the same recording site as in Fig. 4A, but to another pair of frequencies. Two other typical cases from another animal are shown in Fig. 4C and 4D, all with Df = 44%. Note that the peak response of the MUA to f1 in the Deviant condition in Fig. 4B occurred about 40 ms after stimulus onset, while the peak responses to the other conditions occurred about 20 ms after stimulus onset. This was an effect of the rather long window used here to identify the peak responses (see Methods for justification). Because the same procedure was used in all conditions, such long windows could increase the variability in the data, rendering the conclusions more conservative. The pattern of response was quite similar between sets across animals and recording sites. Figure 5 shows a summary of the responses to all six conditions for all the data with Df = 44%. In order to account for general differences in response amplitude across animals and recording sites, the responses in each recording site and each frequency were normalized to the response to that frequency in the deviant-alone condition of the same set, since this is presumably the least adapted response. When a tone was rare and well separated spectrally from other stimuli in the sequence, as in the deviant and diverse-broad conditions, the responses it evoked remained relatively high. On the other hand, when the tone was presented often (as in the Standard and Equal-probability conditions), or mixed with many tones with nearby frequencies (as in the Diverse-narrow condition), the responses it evoked were smaller. A 1-way ANOVA on all six conditions showed significant effect of condition on responses. However, post-hoc comparisons failed to show a significant difference between the three conditions with large responses (Deviant, Diverse-broad and Deviant-alone). The approximate equality of the responses in the Deviant and the Diverse-broad conditions is particularly important for the interpretation of these findings in the Discussion. Figures 5C and 5D display the LFP and MUA responses in the Diverse-broad condition against the responses in the Deviant condition in each recording site separately. Both responses are normalized to the Deviant-alone condition. The responses in the Deviant condition were correlated with the Diverse-broad in the same recording locations for both LFP (r = 0.62, p = 7*10224) and for MUA (r = 0.4, p = 1.5*1024). Interestingly, in some recording locations the Deviant responses were larger than the responses in the Deviant-alone condition (normalized Deviant responses greater than 1, LFP: 50/214, 23%; MUA: 18/85, 21%). In many recording locations, the Deviant responses were larger than in the Diverse-broad condition (points below the diagonal of Figs. 5C and 5D, LFP: 83/214, 39%; MUA: 43/85, 51%). In some PLoS ONE | www.plosone.org 4 August 2011 | Volume 6 | Issue 8 | e23369