Diminished Behavioral and Neural Sensitivity to Sound Modulation Is Associated with Moderate Developmental Hearing Loss Merri J. Rosen1*, Emma C. Sarro2, Jack B. Kelly4, Dan H. Sanes2,3 1 Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio, United States of America, 2 Center for Neural Science, New York University, New York, New York, United States of America, 3 Department of Biology, New York University, New York, New York, United States of America, 4 Department of Psychology, Carleton University, Ottawa, Ontario, Canada Abstract The acoustic rearing environment can alter central auditory coding properties, yet altered neural coding is seldom linked with specific deficits to adult perceptual skills. To test whether developmental hearing loss resulted in comparable changes to perception and sensory coding, we examined behavioral and neural detection thresholds for sinusoidally amplitude modulated (sAM) stimuli. Behavioral sAM detection thresholds for slow (5 Hz) modulations were significantly worse for animals reared with bilateral conductive hearing loss (CHL), as compared to controls. This difference could not be attributed to hearing thresholds, proficiency at the task, or proxies for attention. Detection thresholds across the groups did not differ for fast (100 Hz) modulations, a result paralleling that seen in humans. Neural responses to sAM stimuli were recorded in single auditory cortex neurons from separate groups of awake animals. Neurometric analyses indicated equivalent thresholds for the most sensitive neurons, but a significantly poorer detection threshold for slow modulations across the population of CHL neurons as compared to controls. The magnitude of the neural deficit matched that of the behavioral differences, suggesting that a reduction of sensory information can account for limitations to perceptual skills. Citation: Rosen MJ, Sarro EC, Kelly JB, Sanes DH (2012) Diminished Behavioral and Neural Sensitivity to Sound Modulation Is Associated with Moderate Developmental Hearing Loss. PLoS ONE 7(7): e41514. doi:10.1371/journal.pone.0041514 Editor: M. Fabiana Kubke, University of Auckland, New Zealand Received March 5, 2012; Accepted June 22, 2012; Published July 26, 2012 Copyright: 2012 Rosen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by National Institutes of Health DC009165 (MJR), National Organization for Hearing Research Foundation (MJR), National Institutes of Health DC009237 (DHS), and New York University Research Challenge Fund (DHS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mrosen@neomed.edu Introduction The loss of sensory experience leads to profound effects on the form and function of central neurons, and these changes are thought to disrupt sensory perception in adulthood. Support for this theory draws largely from studies in which developing animals are unilaterally deprived of sensory stimulation. In the visual system, studies of amblyopia demonstrate a compelling correlation between cortical encoding mechanisms and deficits in visual perception [1]. Similarly, in the auditory system, unilateral hearing loss leads to changes in binaural coding properties that are closely associated with perceptual deficits [2,3,4,5,6,7]. The deleterious effects of unilateral deprivation are thought to reflect the competition between active and inactive pathways. However, even the original studies of bilateral visual deprivation noted that 79% of primary cortical cells responded abnormally or were unresponsive to sensory stimulation [8]. Moreover, moderate binaural deprivation during development has a broad impact on synaptic function in auditory cortex [9,10,11,12,13], and these changes persist in adults [14]. Taken together, these findings suggest that developmental auditory deprivation should lead to deficits in auditory detection tasks, with clear correlates to neural encoding, even in the absence of neural competition. Here, we tested this idea by measuring behavioral and neural detection thresholds for amplitude modulated stimuli in the gerbil. Animal communication sounds are composed of low frequency amplitude fluctuations and, for humans, these envelope cues are necessary and sufficient for speech comprehension [15,16,17,18,19]. The detection of small fluctuations, commonly assessed with sinusoidally amplitude modulated (sAM) tones or noise, displays a relatively prolonged maturation [20,21,22] and may remain vulnerable to developmental deprivation. Human studies suggest that early hearing loss perturbs temporal processing [23,24]. Furthermore, children with cochlear implants have poorer sAM sensitivity than implanted adults, suggesting a greater effect of early auditory deprivation [25]. Prolonged conductive hearing loss (CHL), which can occur as a consequence of chronic otitis media, has been associated with deficits in perception and speech processing [26]. However, it is challenging to establish the long-term effects of developmental hearing loss in humans because most studies consider individuals with different ages of hearing loss onset, and who receive varying levels of remediation. Furthermore, most developmental studies consider subjects with significant inner ear damage (e.g., sensorineural hearing loss), such that deficits in temporal processing may reflect a reduction of cochlear compressive non- linearities [27], as well as central factors. To circumvent these problems, we induced CHL in gerbils just prior to hearing onset [28] and measured behavioral and neural sAM detection PLoS ONE | www.plosone.org 1 July 2012 | Volume 7 | Issue 7 | e41514