If basic research studies find such a clear effect of auditory deprivation on brain and behavior, why are the data linking childhood OM to amblyaudia so equivocal? We propose that this discrepancy can be traced to four principal causes:
First, animal models of OM typically employ continuous monaural or binaural deprivation for weeks or months. In contrast, a single bout of OM is expected to last approximately 4 to 6 weeks, followed by up to 60 OM-free weeks, depending on disease severity. Moreover, levels of CHL reported in animal studies typically range from 20 to 50 dB, whereas CHL stemming from OM in humans can be substantially milder. Additionally, while the presence of amblyaudia is often probed immediately following reinstatement of hearing in animal models, years of “typical” auditory experience often precede probes of amblyaudia in human studies. In other words, animal studies could be said to model the worst-case scenario of auditory signal degradation associated with OM. Clearly, data from animal studies that utilize more realistic levels and durations of auditory deprivation would be of considerable interest.
Second, basic research studies uniformly point toward the paramount importance of developmental age when assessing the impact of auditory deprivation on brain and behavior. In many of the studies cited above, the same manipulation that profoundly affected neural representations of auditory stimuli and perceptual acuity in young animals had no effect when performed at later ages. The central importance of developmental critical periods for normal auditory perception is firmly established in the context of language development and even in the efficacy of cochlear implants in congenitally deaf children (Dorman et al. 2007
; Kuhl 2010
). However, studies linking OM to amblyaudia often do not take the timing of OM episodes into account, nor is it known which brain areas are most adversely affected by OM and when, during development, their organization is most susceptible to the structure of afferent activity patterns.
Third, while animal models of OM have probed anatomy, physiology and binaural perception of their subjects, most human studies have assessed speech, language, behavioral, and academic skills of children with histories of OM. These developmental markers may have the greatest external validity to health care providers, educators, and policy makers but are the most challenging to understand in terms of their underlying neural substrates. Instead, psychophysical assessments that relate to established neural pathways for binaural signal representations may prove more valuable in the short-term when addressing amblyaudia.
Finally, and perhaps most importantly, the independent variables in the animal and human studies are very often different. Animal studies that describe striking changes in brain and behavior often bypass the middle ear effusion altogether and directly degrade afferent signal quality by disrupting the sound transmission mechanisms of the middle or outer ear. Human studies, by and large, relate amblyaudia (or lack thereof) to the presence of OM. As described earlier, significant degradation of the afferent signal (CHL of >25 dB HL) would only be expected in <15% of children diagnosed with OM, suggesting that subjects in the OM-positive group, from whom amblyaudia would be expected, are substantially intermingled with—or even outnumbered by—subjects who would not be expected to present with amblyaudia.
This last point could be addressed experimentally in human studies that longitudinally characterize the auditory afferent signal quality in the form of elevated hearing thresholds at multiple points during infant development. While hearing threshold is just one of many potential metrics that index the quality of the afferent signal reaching the brain (albeit not even the most direct), it still offers a far more direct correlate than a positive diagnosis for OM alone. Indeed, when the question “Is early OM associated with amblyaudia?” is rephrased as “Is early OM that also causes CHL associated with amblyaudia?” the answer becomes much less equivocal. Figures A and B illustrate that while prospective longitudinal and randomized control studies that attempt to relate OM to amblyaudia have equivocal outcomes, the available data suggest that a history of CHL during childhood OM is clearly and deleteriously associated with auditory pathophysiology and deficits in binaural listening as well as receptive language skills. Overall, 65% of all study samples reported symptoms of amblyaudia following a history of childhood OM. Further analysis revealed that while only 53% of study samples show amblyaudia as a sequela of OM, 89% of studies reported amblyaudia as a consequence of OM occurring along with CHL. Tables and expand the simplified data profiles in Figure to include sample sizes, ages of participants and metrics of amblyaudia employed in studies listed.
FIG. 1 Early, degraded afferent signal quality (ASQ) is clearly associated with amblyaudia while otitis media (OM) is ambiguously related. Prospective studies which have investigated the relationship between OM or OM-associated degraded ASQ and amblyaudia are (more ...)
The presence of effusion in the middle ear space is ambiguously related to the development of amblyaudia
Degraded afferent signal quality resultant from OM is a clear risk factor for development of amblyaudia
Delays in the maturation of neural circuitry that subserve speech comprehension represent one of the longest-standing and most contentious central sequela associated with childhood OM. Purported delays in receptive language need not be independent of irregularities in perceptual thresholds as difficulties associated with listening in complex auditory environments (such as a classroom) could also be expected to interfere with classroom learning and continued refinement of speech and language skills. Two recent reviews have concluded that while a history of OM is associated with auditory processing and speech perception deficits, convincing evidence of deficits in speech production, receptive and expressive language, as well as academic achievement do not currently exist (Roberts et al. 2004a
; Jung et al. 2005
). These sentiments were echoed in a recent meta-analysis of prospective and randomized control trials that have examined the relation between (1) OM and language development as well as (2) OM-mediated CHL and language development (Roberts et al. 2004b
). Consistent with the central hypothesis we advance here, these reviews also concluded that in most studies, hearing is often not assessed regularly enough (if at all) to investigate the role of CHL in later development, despite the fact that it is hearing loss and not the presence of excessive mucin in the middle ear space that may underlie abnormal imprinting of speech patterns and later developmental deficits. In fact, Roberts and colleagues (2004b
) identified only three studies that met the authors’ criteria and attempted to correlate transient conductive hearing loss with general outcome measures of language between the years of 1966 and 2002 (studies numbered 9, 18, and 19 in Fig. ). Again, looking only at studies that relate poor auditory processing and language skills to a history of hearing loss and OM rather than OM alone, the evidence unambiguously shows that early CHL increases a child’s risk for abnormalities in brainstem physiology, binaural hearing and receptive language skills (Fig. B and Table ).
Returning to the third discrepancy between the animal and human literature, abnormal physiology of the auditory brainstem has consistently been observed in children with chronic OM and CHL. Multiple studies have shown that years after the resolution of CHL and OM, absolute and interpeak wave latencies of the auditory brainstem response are abnormally delayed, potentially suggesting immaturity in neural conduction (Folsom et al. 1983
; Anteby et al. 1986
; Gunnarson and Finitzo 1991
; Hall and Grose 1993
; Ferguson et al. 1998
; Gravel et al. 2006
). In addition, elevation of the brainstem mediated contralateral acoustic stapedial reflex threshold is also observed in children with a history of OM and CHL, further suggesting persistent dysfunction of the neuronal circuitry within the auditory brainstem (Gravel et al. 2006
The link between OM and amblyaudia has also been made more explicit in a subset of studies through the use of carefully controlled psychophysical tasks that map onto known principles of binaural stimulus representations in the brain, rather than tests of language or scholastic ability. The masking level difference (MLD) is a perceptual test that affords researchers with an objective and parametric assessment of perceptual acuity that also relates to the real-world experience of hearing in noisy environments, such as classrooms or gymnasiums, by measuring a participant’s sensitivity to interaural time and amplitude cues. This test has been widely employed in studies that have prospectively and periodically documented CHL in conjunction with OM or retrospectively examined children with histories of chronic OM and reported CHL. Together, these studies have consistently shown disrupted binaural processing for years following reinstatement of hearing through either spontaneous resolution of effusion or placement of tympanostomy tubes (Moore et al. 1991
; Pillsbury et al. 1991
; Hall et al. 1995
; Gravel et al. 1996
; Hogan and Moore 2003
). The same effect on MLD thresholds has been obtained in ferrets reared with unilateral earplugs, providing a direct link between the animal and human literature on developmental auditory deprivation (Moore et al. 1999
In addition to binaural unmasking (MLD), children with histories of OM and reversible CHL have also been shown to localize sound sources less accurately and demonstrate deficits in monaural spectrotemporal processing (Besing and Koehnke 1995
; Hall and Grose 1994
; Hall et al. 1998
). Similar decrements in binaural processing have also been demonstrated in children with reversible CHL secondary to aural atresia that has been surgically corrected (Gray et al. 2009
; Wilmington et al. 1994
). These shared abnormalities in perceptual outcomes of early reversible CHL suggest a causative role of developmental auditory deprivation in later perception regardless of the specific mechanisms that underlie the conductive hearing loss.
On a final note, even if amblyaudia is a legitimate sequela for untreated OM, the specific pathophysiological and perceptual sequelae are unlikely to persist past adolescence. While the precise time-course with which amblyaudia “normalizes” has yet to be delineated, it is clear that these deficits largely disappear after a slow recovery following a few years of typical auditory experience (Hall et al. 1995
). Similarly, delays in language skills have also been reported to be transient in these children, with early testing demonstrating delays while later scores are normal (Maw et al. 1999
). However, we would argue that impermanence does not suggest a developmentally trivial role for this sensory disorder. Due to the cumulative nature of childhood development, even transient perceptual and language delays are expected to feed forward to later behavior and academic achievement. In other words, even if the amblyaudia resolves by late childhood, the linguistic, cognitive and social functions coming online at these ages would be deleteriously affected by the absence of actionable auditory inputs. This raises the possibility that a transient auditory disorder could have “ripple effects” that extend into adolescence and beyond.