Hearing Loss Disrupts AM Processing Figure 6. Neurometrics and psychometrics correlate with CHL treatment. Cells with BMFs of 5 Hz are compared with 5 Hz behavioral detection. (A) Individual neural d9 curves calculated from power at the modulation frequency (PMF) were truncated by displaying only that portion that crossed threshold (horizontal dashed line) until the peak d9 value was attained, with all curves truncated at d9 = 4.0. Neurons whose curves never reached threshold are in grey. In CTRs (top, black) there are visibly more cells with sensitive thresholds than in CHL animals (bottom, orange): cells with thresholds ,30% MD (vertical dashed line) are shown with thick lines. (B) The distribution of PMF-based neural d9 thresholds (bars) was shifted significantly toward lower modulation depths for CTRs compared with CHLs. The behavioral performance of CTR and CHL animals (circles) is plotted at the top of each graph. The blue shaded bars indicate the region of CTR thresholds that do not overlap those of CHLs. (C) A pooling neurometric that represents a downstream neuron’s input summed across cells reveals better detection thresholds at low modulation depths for CTR versus CHL animals (top). The summed activity from which detection is computed is shown in the bottom graph. The larger symbols and dotted lines represent the baseline power in response to the lowest tested modulation depth, against which the other values were compared. * = p,.05. doi:10.1371/journal.pone.0041514.g006 animals with increasingly difficult AM depths on successive days, we can state that asymptotic performance is better in control versus CHL animals. However, this outcome could result either from a stable perceptual impairment, or limitation in the amount of improvement that can be achieved through practice (i.e., perceptual learning). Consistent with the diminished behavioral performance in CHL animals, single auditory cortex neuron responses to slow, but not fast, modulated sAM tones were significantly poorer in CHL animals when evaluated with metrics that incorporated firing magnitude (Fig. 5A). Compared with CTRs, the d9 neurometric revealed significantly fewer CHL neurons with low sAM detection thresholds (Fig. 6A,B). Similarly, a pooling neurometric revealed poorer detection performance across the population of CHL neurons (Fig. 6C). Cortical responses to unmodulated tones were consistent with this finding: CHL neurons displayed significantly reduced firing rates at equivalent sensation levels, as compared to CTRs; however, other response metrics did not differ between groups (Fig. 4). Taken together, the hearing loss-induced behavioral impairment in temporal detection can be attributed, in part, to a decline in sensory information about sAM depth. The impairments reported here were produced by a CHL induced during early postnatal development. The question remains whether similar changes might be produced by a CHL incurred during some later stage of development or in adulthood. Since our primary intent was examine the relationship between neural and behavioral metrics in a manipulated system, future studies will address variables such as age of hearing loss onset, duration of hearing loss, and age at which function is restored. Binaural Deprivation Effects on Neural Coding and Perception Conductive hearing loss is associated with anatomical and physiological changes, from spiral ganglion cells to the auditory cortex [47,48,49,50]. However, there are few studies that relate neural outcome measures to behavior. Unilateral deprivation is closely associated with deficits in sound localization and unmask- ing tasks that involve binaural integration [4,6]. One experiment examined the behavioral effects of binaural deprivation with ear plugs, resulting in impaired frequency discrimination that was not attributable to a cochlear deficit [51]. Therefore, our findings that CHL-induced effects were similar across behavioral and physio- logical measures are broadly consistent with the literature. CHL reduced behavioral detection d9 thresholds by ,4% MD, and physiological d9 thresholds by ,3% MD. Although we do not know whether the perturbed coding properties recorded in ACx are the exclusive source of behavioral differences, they are a plausible source, as temporal processing is reliant on auditory cortical activity [52,53,54,55]. PLoS ONE | www.plosone.org 10 July 2012 | Volume 7 | Issue 7 | e41514