Fig. 2.

Salicylate induces time-dependent parallel changes to reaction time, cortical, and subcortical response-intensity functions in a manner consistent with temporary hearing loss, increased loudness perception and central gain enhancement. A-C: Mean (n = 8) (A) RT-I functions, (B) AC LFP I/O functions, and (C) IC LFP I/O functions from behaviorally trained rats with chronically implanted electrodes before and after sodium salicylate (SS) administration (200 mg.kg, i. p.); data shown before (black), 2 h post-SS (orange), and 24 h post-SS (gray). Baseline (black) represents average response across three baseline sessions. For ease of comparison, all responses were normalized to maximum average baseline response to account for between-subject differences in absolute RTs and AC/IC response size. Data points represent mean +/−SEM. Lines represent linear fit of RT, AC, and IC response functions, which were used to determine changes in response slope (see Table 1). Two-way repeated measure ANOVAs found significant main effects of SS treatment and sound intensity, as well as an interaction between the two, for RT (SS: F_2,98 = 8.84, ^**p = 0.0003, ${\eta }_{\text{p}}^2=0.14$; Intensity: F_6,98 = 28.82, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.81$; interaction: F_12,98 = 6.14, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.40$), AC responses (SS: F_2,98 = 35.64, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.42$; Intensity: F_6,98 = 22.03, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.87$; interaction: F_12,98 = 8.90, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.51$) and IC responses (SS F_2,98 = 25.18, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.34$; Intensity: F_6,98 = 17.83, ^***p < 0.0001, ${\eta }_{\text{p}}^2=0.92$; interaction F_12,98 = 4.67, ^***p < 0.0001, 0.46). Post-hoc significance for intensity-dependent effects of SS at 2 h compared to baseline signified as: *p < 0.05, ^**p < 0.01, ^***p < 0.0001. No significant effects of were found between baseline and 24 h post-SS. D-F: Scatter plots comparing the average normalized baseline response at each intensity against the normalized response 2 h post-SS (orange-brown) or 24 h post-SS (gray-black) of equivalent intensity for (D) RT, (E) AC LFP, and (F) IC LFP responses. The slope of the linear fit (R_Gain) provides an estimate of the change in response gain across conditions where R_Gain = 1 indicates a response growth rate matched to baseline levels while R_Gain > 1 and R_Gain < 1 indicate a multiplicative enhancement or divisive decrease in response growth rate compared to baseline, respectively. Shading represents 95% confidence interval of linear fit. A two-tailed F-test determined that R_Gain was significantly different from 1 at 2 h post-SS for RT-I, AC, and IC LFP functions (RT: R_Gain = 1.959, F_(1,54) = 21.89, ^***p < 0.0001, d = 3.31; AC: R_Gain = 2.040, F_(1,54) = 31.84, ^***p < 0.0001, d = 3.99; IC: R_Gain = 1.609, F_(1,54) = 26.19, ^***p < 0.0001, d = 3.62). A 24 h post-SS, no response gain significantly deviated from 1 (RT: R_Gain = 1.032, F_(1,54) = 0.070, p = 0.792, d = 0.187; AC: R_Gain = 1.108, F_(1,54) = 0.596, p = 0.444, d = 0.546; IC: R_Gain = 0.9464, F_(1,54) = 0.190, p = 0.665, d = 0.308).