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Attentional modulation of medial olivocochlear inhibition: Evidence for immaturity in children
Hearing Research 318 (2014) 31e36
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Research paper
Attentional modulation of medial olivocochlear inhibition: Evidence for immaturity in children Srikanta K. Mishra a, b, * a b
Department of Special Education and Communication Disorders, New Mexico State University, Las Cruces, NM 88003-8001, USA Department of Communication Sciences and Disorders, Butler University, 4600 Sunset Ave., Indianapolis, IN 46208, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 July 2014 Received in revised form 27 September 2014 Accepted 22 October 2014 Available online 29 October 2014
Efferent feedback shapes afferent auditory processing. Auditory attention has been shown to modulate medial olivocochlear (MOC) efferent activity in human adults. Since auditory attention continues to develop throughout childhood, the present study explored whether attentional control of medialefferent inhibition in 5e10 year-old children is adult-like. MOC inhibition was measured in adults (n ¼ 14) and children (n ¼ 12) during no-task (contralateral broadband noise), passive (contralateral noise with tone-pips) and active listening conditions (attended tone-pips embedded in contralateral broadband noise). A stronger MOC inhibition was observed when measured during the active listening condition for adults which is consistent with past work. However, the effect of auditory attention on MOC inhibition in children was not robust and was significantly lower compared to that observed for adults. These findings suggest the potential immaturity of the attentional mediation of MOC inhibition in tested children. © 2014 Elsevier B.V. All rights reserved.
1. Introduction The auditory system has an elaborate structure of descending efferent neural pathways that extend from the brain to the cochlea (Schofield, 2010; Suga et al., 2000; Xiao and Suga, 2002). Efferent effects shape or modulate the bottom-up afferent processing. The medial olivocochlear (MOC) efferents originate from the periolivary nuclei of the superior olivary complex (SOC) and contain large myelinated fibers that predominantly innervate outer hair cells via cholinergic synapses. Stimulation of MOC fibers causes changes in cochlear responses to sound, which are typically recorded using otoaoustic emissions (OAEs). The efferent-induced shift in OAEs is called MOC reflex or inhibition; in this report these two terms are used. The efferent connections from the auditory cortex (AC) innervate the SOC directly as well as via the inferior colliculus (IC) (Mulders and Robertson, 2000a; Spangler and Warr, 1991). Electrical activation of the neurons at the IC and the AC induces changes in cochlear mechanisms in animals (Mulders and Robertson, 2000b; Xiao and Suga, 2002), thought to be mediated by the uncrossed MOC fibers (Mulders and Robertson, 2002). This
* Tel.: þ1 575 646 7831 (Office). E-mail address: [email protected]. http://dx.doi.org/10.1016/j.heares.2014.10.009 0378-5955/© 2014 Elsevier B.V. All rights reserved.
suggests that cortical or higher-order processing could potentially modulate MOC inhibition. One approach to examine this cortical mediation in humans is to compare MOC inhibitions measured during active and passive listening conditions. Several studies provide evidence for attentional control of MOC inhibition in the cochlea (De Boer and Thornton, 2007; Harkrider and Bowers, 2009; Ferber-Viart et al., 1995; Garinis et al., 2011; Maison et al., 2001). However, the reported magnitude and direction of attention-induced alterations in MOC activity are not always consistent. Some studies demonstrated reductions (De Boer and Thornton, 2007; Harkrider and Bowers, 2009) while others showed enhancements in MOC inhibitions with auditory attention (Garinis et al., 2011; Maison et al., 2001). These discrepancies in the influence of attention on MOC inhibition appear to be primarily due to the direction of attention and the type of auditory task. MOC inhibition is enhanced when attention was directed towards the ear receiving contralateral acoustic stimulation (CAS) via a listening-innoise task (Garinis et al., 2011; Maison et al., 2001) and reduced when attention was directed to the OAE probe ear (De Boer and Thornton, 2007; Harkrider and Bowers, 2009). Whether such attentional mediation of MOC inhibition occurs for children remains unknown. The MOC reflex or reflexive MOC effects, i.e., changes in OAEs with CAS, is functionally mature around full-term birth (Abdala et al., 2013, 1999; Durante and Carvalho, 2002; Gkoritsa et al., 2007). In all maturational studies, the MOC reflex was measured under passive
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S.K. Mishra / Hearing Research 318 (2014) 31e36
conditions, that is, the adults merely stayed awake and neonates were typically required to stay asleep for obvious reasons. The study reported here focused on MOC measurements under active listening conditions in children. Since attention influences MOC inhibition, and auditory attention continues to develop throughout childhood (Coch et al., 2005; Cooley and Morris, 1990; Gomes et al., 2000; Klenberg et al., 2001; Pearson and Lane, 1991), the present study investigated whether the effect of attention on MOC activity in typically developing children is adult-like. Specifically, the aims of this study were to measure the effect of auditory attention on MOC inhibition in five to ten year-old children and compare this effect with those measured in adults. A secondary goal was to replicate the findings from earlier studies on adults (Garinis et al., 2011; Maison et al., 2001). To obtain an accurate description of MOC-induced changes, this study used refined CEOAE methods by recording emissions at a relatively low stimulus level and slow click rate, adopting a higher SNR criterion (6 dB) and carefully considering middle ear muscle reflexes and OAE probe-drifts. Since this study included children, a relatively simpler listening-in-noise task (tone detection in noise) was used to modulate attention. Besides theoretical interest, such as auditory modeling (Clark et al., 2012), characterizing the nature of task-dependent MOC inhibition in children has high translational significance for understanding, diagnosing and managing listening problems in children (Mishra, 2014; Muchnik et al., 2004; Veuillet et al., 2007). 2. Materials and methods 2.1. Overview MOC-induced changes in CEOAE amplitudes were computed by comparing OAEs recorded with and without three CAS conditions. The three CAS conditions were: broadband noise (BBN), designated as the no-task condition; tone-pips embedded in BBN, referred to as passive condition; and tone-pips embedded in BBN, where participants were required to respond to the tone-pips, termed the active condition. 2.2. Participants Experiments were conducted on 16 adults and 17 typically developing children with hearing thresholds of 15 dB HL or better at audiometric frequencies. Data from 14 adults and 12 children are reported here because two 4-year-olds were non-compliant with the test procedures and the CEOAEs in remaining participants did not meet the required SNR and other criteria. Individuals with musical training were excluded because their data could potentially bias the experimental outcomes (Perrot and Collet, 2014). Included adults (3 males and 11 females) were aged 19e34 years (x ¼ 25.8) and children (7 boys and 5 girls) were aged 5e10 years (x ¼ 7.2). Human experimentation was performed in accordance with the Butler University Institutional Review Board guidelines. Measurements were completed inside a double-walled sound booth. 2.3. CEOAEs recording and analysis CEOAEs were recorded using the HearID þ TE system (Mimosa Acoustics, Champaign, IL) with an ER-10C probe system (Etymotic Research, Elk Grove Village, IL). In-the-ear probe calibration for every subject applied a voltage correction to obtain the target click level. To evoke OAEs, 83.3 ms rectangular clicks were presented at 55 dB pSPL and a rate of 45 Hz using a linear recording paradigm with positive click polarity (Kemp et al.,1986). A standard 50 Hz click rate was not used to minimize unintended click-elicited MOC activity; a 40 Hz rate has been argued to be ideal for adults (Guinan
et al., 2003). However, this rate was found to be impractical for testing children due to longer test durations. A 55 dB pSPL was selected since this level produced repeatable responses with the desired criteria (see acceptance criteria) in all included children and adults. Repeatable OAEs could not be recorded with 2048 averages in many children (n ¼ 8) when lower click levels were used. Increasing the number of averages to 4096 in a few children (n ¼ 2) yielded acceptable results, but also significantly increased the test duration. Responses to a total of 2048 click trains were recorded with a time window of 2e20 ms. The noise rejection level was set at 47 dB SPL. If the total number of rejections per run was more than 600, then the entire run was repeated. The CEOAEs were filtered using a low-pass Butterworth filter (third-order) set to 5000 Hz with a 1000 Hz transition region, and the high-pass filter (sixth order) set to 1000 Hz and a 500 Hz transition. The filters were realized as zerophase forward-and-reverse infinite impulse response Butterworth filters. Responses were averaged into two alternate buffers: A and B. Signal was estimated from the A and B average waveform; noise was estimated from the AeB difference waveform. Data were accepted if the SNR was greater than 6 dB and the waveform reproducibility, an indicator of intra-run repeatability, was greater than 80%. 2.4. Contralateral acoustic stimulation The CEOAE recordings described in the preceding section were obtained in a no-CAS condition and in three CAS conditions. The CAS conditions were: (1) No-Task: Participants sat comfortably in a chair and were required to stay awake and as quiet as possible while contralateral BBN was presented. The tester visually monitored the subjects' state. (2) Passive: Participants did not receive any specific instruction except to remain awake while contralateral BBN embedded with tone-pips was presented. (3) Active: Participants were instructed to detect the tone-pips embedded in the contralateral BBN. They were asked to press a response button each time they heard the tone-pip and the percentage of correct responses were computed. In this condition, the CEOAE recordings were accepted if the behavioral response was greater than 70% to ensure that participants were attending to the tone-pips. The order of the no-CAS and various CAS conditions was random and counterbalanced across participants. Contralateral BBN (20e12,000 Hz) was presented at 50 dB SPL via an insert earphone (ER-3A, Etymotic Research, Elk Grove Village, IL) 5 seconds prior to the onset of OAE recordings. For the passive and active conditions, 1000 Hz tone-pips with a duration of 100-ms (20-ms cosine ramps) were embedded in the BBN. The tone-pips occurred randomly between the 8th and 11th seconds at 0 dB SNR. It was necessary to design a task such that there were no performance differences between the two tested groups. This particular auditory task was chosen because pilot experimentation (n ¼ 2) showed that children were able to perform the task with reasonable accuracy (>70%), suggesting they paid attention to the task. Increasing the task difficulty by decreasing the SNR or by making the task relatively complex with tone discrimination in noise indicated a lack of interest in the task and/or increased false positives for some children. Importantly, it caused anxiousness and anxiety-related bodily movements in children, leading to probedrift issues, higher rejection rates and poor SNRs for OAE recordings. All CEOAE measurements were completed during a single OAE probe insertion. When it was necessary to reinsert in a few participants, the entire measurements were repeated. 2.5. Middle ear muscle reflex (MEMR) Two approaches were used to control for potential MEMR contamination of OAE data. MEMRs were measured for each
S.K. Mishra / Hearing Research 318 (2014) 31e36
subject using a clinical immittance meter with 226-Hz probe tone (GSI 37 Auto Tymp Ear Analyzer, Grason-Stadler Inc., Eden Prairie, MN). Because clinical instruments typically give higher MEMR thresholds, a constant of 12 dB gleaned from wideband acoustic reflectance studies (Feeney et al., 2003; Keefe et al., 2010) was subtracted from each subject's clinical reflex thresholds to detect subclinical reflexes. The mean corrected MEMR threshold for adults was 82.54 dB SPL (SD ¼ 7.56) and for children was 82.09 dB SPL (SD ¼ 5.84). The contralateral BBN level (50 dB SPL) used for stimulating MOC activity was lower than the MEMR thresholds by a mean of 32 dB. Thus, it is unlikely that the contralateral BBN elicited MEMRs during MOC reflex measurements. Additionally, the actual click levels, converted to pressure (re; 20 mPa), were statistically compared between various CAS and no-CAS conditions. 2.6. Quantification of the MOC inhibition To obtain robust estimates of MOC inhibition for adults and children, CAS-induced changes in overall CEOAE amplitudes across frequency bands were examined. MOC inhibitions for no-task, passive and active listening conditions were computed by comparing the no-CAS condition with the corresponding CAS conditions. The MOC inhibition was quantified by two indices: (1) dB effect (DCEOAE) ¼ LNoCAS LCAS where Lce is CEOAE ce ce amplitude in dB SPL. As traditionally done, the effect of contralateral BBN was computed as the dB difference in CEOAE levels between no-CAS and CAS conditions for every participant. Positive values denote reductions in amplitude. NoCAS CAS (2) Normalized index (DCEOAEn) ¼ ðð Pce Pce Þ= NoCAS ð Pce ÞÞ 100 where Pce is CEOAE amplitude in pressure (mPa). The CEOAE amplitude in mPa was calculated for every participant. The CEOAE ear canal pressure in the no-CAS condition subtracted from pressure in the CAS condition, normalized to baseline CEOAE amplitude. This is a fraction and is reported as percentage. 3. Results The SNRs for CEOAEs recorded under various conditions for adults and children are shown in Fig. 1. Every participant had a SNR greater than 6 dB in all recording conditions. On average, the SNR was approximately 11 dB combined across conditions and age groups; this is almost double the required SNR criterion (6 dB) for data inclusion. It appears that the mean SNR was similar across
various CAS conditions and across subject groups. A repeated measures analysis of variance (RM-ANOVA), with four test conditions (no-CAS and three CAS conditions) as within-subject factors and age (children and adults) as between-subject factor, yielded no main effect of test conditions (F3,72 ¼ 0.40, p ¼ 0.75, h2p ¼ 0.02), age group (F3,72 ¼ 0.29, p ¼ 0.83, h2p ¼ 0.02) or any significant interaction between test conditions and age group (F1,24 ¼ 0.25, p ¼ 0.62, h2p ¼ 0.01) for the SNR of CEOAE responses. Although the mean OAE amplitudes were larger for children (x ¼ 4.68 dB SPL, SD ¼ 4.71) compared to adults (x ¼ 1.52 dB SPL, SD ¼ 5.40), an independent samples t-test showed no statistically significant group difference for the OAE amplitudes recorded in the no-CAS condition (t24 ¼ 1.58, p ¼ 0.13). Fig. 2 displays the noise floors for various CAS conditions for adults and children. It is evident that, for both adults and children, the mean noise floors were similar across CAS conditions. A Oneway ANOVA comparing the noise floors across CAS conditions separately for adults and children was not significant (adults: F3,52 ¼ 0.11, p ¼ 0.95, h2 ¼ 0.01; children: F3,44 ¼ 0.24, p ¼ 0.86, h2 ¼ 0.02). This indicates that the CEOAE noise floors were not significantly different across CAS conditions for adults and children. Although the click level was set to 55 dB pSPL, repeated recordings may have small drifts in click level over time, and thereby OAE levels, plausibly due to middle ear pressure fluctuations, OAE probe movement, etc (Backus, 2007). These drifts are likely to cancel each other in the group data; however, if the drift-induced variations are different across the CAS conditions or groups, it can make it appear that the response is different across the CAS conditions or groups. A significant change in click level with contralateral BBN also indicates MEMR activation (Guinan et al., 2003). The click levels (mPa) in four test conditions (no-CAS and three CAS conditions) were statistically compared to ensure that the levels did not change significantly with CAS for either group. Fig. 3 shows the mean and individual normalized MOC metric under various task conditions for adults and children. The effect of CAS conditions on MOC inhibition was assessed for dB and normalized MOC indices. For brevity, graphs are presented only for DCEOAEn because normalized metric has been argued to be a more valid index (Backus and Guinan, 2007; Garinis et al., 2011; Guinan et al., 2003; Mishra and Lutman, 2014, 2013). For DCEOAEn data, the assumption of sphericity was also violated (Mauchly's test, c2 ¼ 10.57, p < 0.01). A RM-ANOVA with Greenhouse-Geisser correction showed the main effect of CAS condition (F1.46,35.07 ¼ 12.98, p < 0.01, hp 2 ¼ 0.35), but no main effect of age group (F1,24 ¼ 0.12, p ¼ 0.73, hp 2 ¼ 0.01). A significant interaction effect between CAS conditions and age group (F1.46,35.07 ¼ 5.65, p ¼ 0.01, hp 2 ¼ 0.19) was observed.
Adults
Children
Children
Signal-to-Noise Ratio (dB)
Noise floor (dB SPL)
Adults
33
No-CAS No-Task Passive Active
No-CAS No-Task Passive Active
Fig. 1. Signal-to-noise ratio (SNR): Mean and individual SNRs of otoacoustic emissions for adults and children under various recording conditions.
No-CAS No-Task Passive Active
No-CAS No-Task Passive Active
Fig. 2. Noise floor: Mean and individual noise floors of otoacoustic emissions for adults and children under various recording conditions.
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S.K. Mishra / Hearing Research 318 (2014) 31e36
Children
MOC Effect: ΔCEOAEn (%)
Adults
No-Task Passive Active
No-Task Passive
Active
Fig. 3. Medial olivocochlear (MOC) inhibition: Mean and individual normalized MOC inhibitions (DCEOAEn) for adults and children under various task conditions. Error bars indicate ±95% confidence intervals for the mean.
Multiple comparisons with Bonferroni adjustments were performed a k to determine the nature of interaction effects. Notably, DunneSid corrections also yielded similar p-values. Table 1 presents summary of multiple comparison results with Bonferroni corrections (p ¼ 0.008 ¼ 0.05/6); it also shows results for DCEOAE data. These analyses indicate that the mean DCEOAEn index measured in the active condition was significantly larger than passive and no-task conditions for adults. The effect size was large (Cohen's d ¼ 1.0). However, for children, the mean MOC inhibition in the active condition, though slightly greater relative to passive and no-task conditions, did not reach the significance level. The dB (DCEOAE) index was analyzed in a similar way as the normalized metric. For adults, the mean DCEOAE for active condition (x ¼ 2.24 dB, SD ¼ 0.76) was larger than passive (x ¼ 1.47 dB, SD ¼ 0.84) and no-task (x ¼ 1.42 dB, SD ¼ 0.67) conditions. The mean DCEOAE for children seemed to be similar across conditions (no-task x ¼ 1.67 dB, SD ¼ 0.54; passive x ¼ 1.71 dB, SD ¼ 0.62; passive x ¼ 1.87 dB, SD ¼ 0.59). The Mauchly's test of sphericity indicated that the assumption of sphericity had been violated (c2 ¼ 9.68, p < 0.01). Greenhouse-Geisser correction for violation of sphericity assumption was applied. A RM-ANOVA with three CAS conditions (no-task, passive and active) as within-subject factors and age as the between-subject factor revealed the main effect of CAS condition (F1.48,35.72 ¼ 12.98, p < 0.01, hp 2 ¼ 0.34), but no effect of age group (F1,24 ¼ 0.03, p ¼ 0.87, hp 2 ¼ 0.01). A significant interaction between CAS conditions and age group (F1.48,35.72 ¼ 4.82, p ¼ 0.02, hp 2 ¼ 0.17) was found. Multiple comparisons (see Table 1) showed that the mean DCEOAE in the active condition was significantly larger than passive and no-task
Table 1 Summary of multiple comparison results for raw and normalized indices. Comparisons
Adults: No-Task vs Passive Passive vs Active No-Task vs Active Children: No-Task vs Passive Passive vs Active No-Task vs Active
dB index
Normalized index (%)
Mean difference
t
0.06
0.23
0.76 0.82 0.05 0.15 0.20
p-value
Mean difference
t
p-value
0.82
0.27
0.12
0.91
4.44 5.19 0.39
<0.01* <0.01* 0.70
7.88 7.62 0.42
4.85 5.41 0.36
<0.01* <0.01* 0.73
2.42 2.38
0.03 0.04
1.39 1.81
2.23 2.31
0.05 0.04
*Significant with Bonferroni adjustments (p ¼ 0.01) for multiple comparisons.
conditions for adults only with large effect size (Cohen's d ¼ 1.1). No such statistically significant effect was observed for children. In order to demonstrate group differences directly, the active and passive condition difference for DCEOAE and DCEOAEn was compared between adults and children. Levene's test for equality of variances revealed violation of the assumption of homogeneity of variance (DCEOAE F ¼ 26.06, p < 0.01; DCEOAEn F ¼ 24.10, p < 0.01). An independent samples t-test with unequal variances revealed significant mean difference between groups (DCEOAE adults x ¼ 0.76, SD ¼ 0.64, children x ¼ 0.15, SD ¼ 0.22, t16.45 ¼ 3.32, p < 0.01; DCEOAEn adults x ¼ 7.88, SD ¼ 6.07, children x ¼ 1.39, SD ¼ 2.17, t16.74 ¼ 3.72, p < 0.01). Thus, the effect of attention on MOC inhibition (both DCEOAE and DCEOAEn) for children was significantly lower than that for adults. To probe the potential source of the differences in task dependency of MOC inhibition between adults and children, the behavioral performance on tone-pips detection in noise during the active condition was compared between the two groups (adults x ¼ 91.42%, SD ¼ 3.05; children x ¼ 86.92%, SD ¼ 7.83). Levene's test for equality of variances showed that the assumption of homogeneity of variance had been violated (F ¼ 22.53, p < 0.01). An independent samples t-test with unequal variances showed no significant difference between adults and children (t13.86 ¼ 1.87, p ¼ 0.08). 4. Discussion The primary goal of this study was to determine whether auditory attention modulates the medial-efferent inhibition in five to ten year-old children to the same extent as it does in adults. The results suggest that the influence of attention on MOC inhibition was less pronounced for children compared to adults, particularly, the MOC inhibitions were significantly larger in the active relative to the passive and no-task conditions for adults, but not for children. The results also show that this group difference, in effect of attention, cannot be attributed to factors related to noise floor, SNR, middle-ear-muscle-reflexes, probe-drift related variations in click level or behavioral performance in the listening task. Therefore, the attentional modulation of medial efferent function is immature in five to ten year-old children. 4.1. MOC reflex strength in children The normative features of the MOC reflex for school-aged children are not well characterized. The measurement issues and repeatability of the MOC reflex in children are unknown. Measuring MOC reflex in children could be scientifically and clinically relevant for identifying children with listening problems (Mishra, 2014). Past work on children used relatively weaker methods, particularly low SNR (typically 3 dB) and higher click levels (Kumar and Vanaja, 2004; Muchnik et al., 2004; see Mishra, 2014 for review). To obtain robust data from a variable computed as a differencedthe MOC reflexdthe SNR of each independent measure (OAEs in no-CAS and CAS conditions) must be high enough so that the difference itself is not contaminated by noise. While the SNRs (~11 dB) in the present CEOAE measurements are unparalleled with past MOC work in children, Goodman et al. (2013) showed that a SNR of 20e25 dB is needed for determining MOC reflexes of the order of 1 dB in individual adults. It is currently not known whether a similar amount of SNR is needed for computing OAE differences from linear CEOAE recordings for making group comparisons. Nevertheless, our choice of SNR criteria (6 dB) was limited by practical constraints related to test duration and the age of children.
S.K. Mishra / Hearing Research 318 (2014) 31e36
This study found 1.67 dB of MOC reflex in the no-task condition for children, which is consistent with past work (e.g., Kumar and Vanaja, 2004; Muchnik et al., 2004). However, the click and the contralateral BBN levels used in this study were lower compared to previous studies. The normalized index showed a MOC inhibitory effect of 17.33% (SD ¼ 5.19), which was similar to that observed for adults (x ¼ 15.09%, SD ¼ 6.39). The lack of difference in MOC reflex in no-task and passive conditions may be interpreted as an indicator of good immediate test-retest repeatability of the reported measurements. Consistent with past work (Norton and Widen, 1990; Prieve et al., 1997), children's CEOAE amplitudes were slightly larger than adults. However, the SNRs were similar between the two age groups due to relatively higher recording noise in children. One of the many unique challenges in performing MOC reflex measurements in young children is to achieve a high SNR in the shortest possible test duration. A higher number of averages typically leads to robust CEOAEs with good SNR, but increases the test duration. With increased test duration comes the greater likelihood of rejections associated with bodily movements. From our experience with testing children, averages more than 2048 click trains per condition were not practically beneficial since we had several test conditions. 4.2. Attentional control of MOC inhibition: implications for maturation of the MOC inhibitions The MOC reflex is mature around full-term birth (Abdala et al., 2013, 1999; Durante and Carvalho, 2002; Gkoritsa et al., 2007). The present study showed that the effect of attention on the MOC inhibition in children is not similar to that in adults. Attending to tone-pips embedded in contralateral BBN produced a significant increase in the magnitude of MOC inhibition for adults, but not for children. Since other extraneous variables such as noise floor, SNR and MEMRs were controlled, the lack of a significant effect of attention for children suggests that attentional modulation of MOC inhibition is not adult-like in the tested children. The notion that attentional control of MOC inhibition is immature in children is further reinforced by studies on development of auditory cortex (Moore and Guan, 2001; Moore, 2002). The role of the auditory cortex in modulating peripheral mechanisms via the descending fibers has been demonstrated in animal experiments (He and Yu, 2010; Mulders and Robertson, 2000a,b; Suga et al., 2000; Xiao and Suga, 2002). In humans, a reduced MOC inhibition has been reported in epileptic patients with surgically removed Heschl's gyrus (Khalfa et al., 2001). The auditory cortex follows a prolonged course of maturation (Moore and Guan, 2001; Moore, 2002). Particularly relevant, maturation of commissural and association axons in the superficial cortical layers to allow communication between different subdivisions of the auditory cortex, necessary for more complex cortical processing of sound, occurs during the period of 5e12 years (Moore, 2002). These maturational changes suggest the possibility that the topdown control of listening in noise via medial efferents is likely under development during that period. In all likelihood, the cortical or top-down modulation of the MOC efferents is probably immature in the tested children, even though the MOC efferents are functionally mature at birth. This may also suggest an experience-dependent developmental plasticity of the MOC efferents, which is congruent with evidence that MOC inhibition can be altered with auditory training or musical training (De Boer and Thornton, 2008; Perrot and Collet, 2014; Veuillet et al., 2007). Since the present study showed that attentional modulation of MOC inhibition is immature in 5e10 year-old children, it would be interesting to investigate the maturational
35
trajectory. A complete timeline for maturation of attentional modulation of MOC inhibition would require inclusion of more children across a wider age range. While this study carefully controlled several MOC measurement related variables, one factor that may have influenced the present findings is the level of attentional effort. Although the behavioral performances in the active condition for both age groups were similar, there may have been a real difference in the level of listening effort or the auditory attention paid by the two groups. A confirmation of present findings may require balancing the level of auditory attention between the two groups, which may be potentially challenging to achieve, particularly in the context of simultaneous OAE measurements in children. 4.3. Comparison with previous measurements of attentionmediated changes in MOC inhibition Since this is the first study examining the effect of auditory attention on MOC inhibition for children, the results obtained from adults are compared with previous reports. Previous studies of changes in MOC inhibition with attention provide evidence for a cortical influence on the cochlea (De Boer and Thornton, 2007; Ferber-Viart et al., 1995; Garinis et al., 2011; Harkrider and Bowers, 2009; Maison et al., 2001). In the present experiment, contralateral BBN and tone-pips were presented to one ear while the CEOAEs were recorded from the other ear. A stronger MOC inhibition was evident during the active listening condition, consistent with past work (Garinis et al., 2011; Maison et al., 2001), showing that focusing attention to the ear receiving CAS enhances MOC inhibition. Since the MOC reflex pathway is bilateral (Guinan, 2006), evidence of increased inhibition in the probe ear may suggest that it is also increased in the contralateral ear. The magnitude of attentional effect in dB, i.e., difference between passive and active conditions (x ¼ 0.8), was greater than those reported (~0.4) by Maison et al. (2001) and (~0.2) by Garinis et al. (2011), possibly due to use of refined CEOAE methods, more specifically the higher SNR in our data. This difference may seem small, but the effect size was large. Further, it has been shown in adult cats that subtle alterations in cochlear mechanisms result in much larger changes on subsequent responses of auditory nerve fibers (Puria et al., 1996). 4.4. Summary The present study using refined CEOAE methods showed that the effect of auditory attention in children is much weaker than those observed in adults, suggesting potential immaturity of attentional or top-down modulation of MOC inhibition in tested children. This is exciting considering that the reflexive MOC reflex is mature around full-term birth. The current findings may be followed with a larger sample size with a wider age range and with measurement of time-frequency distribution of CEOAEs using wavelet transformations (Tognola et al., 1997) or other innovative methods. Acknowledgments This work was supported by a Faculty Research Award, Holcomb Awards Committee, Butler University. The author acknowledges BreeAnna Sawyer for her assistance with data collection. Carolyn Herbert is acknowledged for editorial assistance. References Abdala, C., Ma, E., Sininger, Y.S., 1999. Maturation of medial efferent system function in humans. J. Acoust. Soc. Am. 105, 2392e2402.
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Abdala, C., Mishra, S., Garinis, A., 2013. Maturation of the human medial efferent reflex revisited. J. Acoust. Soc. Am. 133, 938e950. Backus, B.C., 2007. Bias due to noise in otoacoustic emission measurements. J. Acoust. Soc. Am. 121, 1588e1603. Backus, B.C., Guinan, J.J., 2007. Measurement of the distribution of medial olivocochlear acoustic reflex strengths across normal-hearing individuals via otoacoustic emissions. J. Assoc. Res. Otolaryngol. 8, 484e496. Clark, N.R., Brown, G.J., Jürgens, T., Meddis, R., 2012. A frequency-selective feedback model of auditory efferent suppression and its implications for the recognition of speech in noise. J. Acoust. Soc. Am. 132, 1535e1541. Coch, D., Sanders, L.D., Neville, H.J., 2005. An event-related potential study of selective auditory attention in children and adults. J. Cogn. Neurosci. 17, 605e622. Cooley, E.L., Morris, R.D., 1990. Attention in children: a neuropsychologically based model for assessment. Dev. Neuropsychol. 6, 239e274. De Boer, J., Thornton, A.R.D., 2008. Neural correlates of perceptual learning in the auditory brainstem: efferent activity predicts and reflects improvement at a speech-in-noise discrimination task. J. Neurosci. 28, 4929e4937. De Boer, J., Thornton, A.R.D., 2007. Effect of subject task on contralateral suppression of click evoked otoacoustic emissions. Hear. Res. 233, 117e123. Durante, A.S., Carvalho, R.M.M., 2002. Contralateral suppression of otoacoustic emissions in neonates. Int. J. Audiol. 41, 211e215. Feeney, M.P., Keefe, D.H., Marryott, L.P., 2003. Contralateral acoustic reflex thresholds for tonal activators using wideband energy reflectance and admittance. J. Speech, Lang. Hear. Res. 46, 128e136. Ferber-Viart, C., Duclaux, R., Collet, L., G, F., 1995. Influence of auditory stimulation and visual attention on otoacoustic emissions. Physiol. Behav. 57, 1075e1079. Garinis, A., Glattke, T., Cone, B., 2011. The MOC reflex during active listening to speech. J. Speech, Lang. Hear. Res. 54, 1464e1477. Gkoritsa, E., Korres, S., Segas, I., Xenelis, I., Apostolopoulos, N., Ferekidis, E., 2007. Maturation of the auditory system: 2. Transient otoacoustic emission suppression as an index of the medial olivocochlear bundle maturation. Int. J. Audiol. 46, 277e286. Gomes, H., Molholm, S., Christodoulou, C., Ritter, W., Cowan, N., 2000. The development of auditory attention in children. Front. Biosci. 5, D108eD120. Goodman, S.S., Mertes, I.B., Lewis, J.D., Weissbeck, D.K., 2013. Medial olivocochlearinduced transient-evoked otoacoustic emission amplitude shifts in individual subjects. J. Assoc. Res. Otolaryngol. 14, 829e842. Guinan, J.J., 2006. Olivocochlear efferents: anatomy, physiology, function, and the measurement of efferent effects in humans. Ear Hear. 27, 589e607. Guinan, J.J., Backus, B.C., Lilaonitkul, W., Aharonson, V., 2003. Medial olivocochlear efferent reflex in humans: otoacoustic emission (OAE) measurement issues and the advantages of stimulus frequency OAEs. J. Assoc. Res. Otolaryngol. 4, 521e540. Harkrider, A.W., Bowers, C.D., 2009. Evidence for a cortically mediated release from inhibition in the human cochlea. J. Am. Acad. Audiol. 20, 208e215. He, J., Yu, Y., 2010. Role of descending control in the auditory pathway. In: Rees, A., Palmer, A. (Eds.), The Oxford Handbook of Auditory Science: the Auditory Brain. Oxford University Press, pp. 247e268. Keefe, D.H., Fitzpatrick, D., Liu, Y.-W., Sanford, C.A., Gorga, M.P., 2010. Wideband acoustic-reflex test in a test battery to predict middle-ear dysfunction. Hear. Res. 263, 52e65. Kemp, D.T., Bray, P., Alexander, L., Brown, A.M., 1986. Acoustic emission cochleographyepractical aspects. Scand. Audiol. Suppl. 25, 71e95. Khalfa, S., Bougeard, R., Morand, N., Veuillet, E., Isnard, J., Guenot, M., Ryvlin, P., Fischer, C., Collet, L., 2001. Evidence of peripheral auditory activity modulation by the auditory cortex in humans. Neuroscience 104, 347e358. Klenberg, L., Korkman, M., Lahti-Nuuttila, P., 2001. Differential development of attention and executive functions in 3- to 12-year-old Finnish children. Dev. Neuropsychol. 20, 407e428. Kumar, U.A., Vanaja, C.S., 2004. Functioning of olivocochlear bundle and speech perception in noise. Ear Hear. 25, 142e146. Maison, S., Micheyl, C., Collet, L., 2001. Influence of focused auditory attention on cochlear activity in humans. Psychophysiology 38, 35e40.
Mishra, S.K., Lutman, M.E., 2013. Repeatability of click-evoked otoacoustic emissionbased medial olivocochlear efferent assay. Ear Hear. 34, 789e798. Mishra, S.K., Lutman, M.E., 2014. Top-down influences of the medial olivocochlear efferent system in speech perception in noise. PLoS One 9, e85756. Mishra, S.K., 2014. Medial efferent mechanisms in children with auditory processing disorders. Front. Hum. Neurosci. 8, 860. Moore, J., Guan, Y., 2001. Cytoarchitectural and axonal maturation in human auditory cortex. J. Assoc. Res. Otolaryngol. 2, 297e311. Moore, J.K., 2002. Maturation of human auditory cortex: implications for speech perception. Ann. Otol. Rhinol. Laryngol. Suppl. 189, 7e10. Muchnik, C., Ari-Even Roth, D., Othman-Jebara, R., Putter-Katz, H., Shabtai, E.L., Hildesheimer, M., 2004. Reduced medial olivocochlear bundle system function in children with auditory processing disorders. Audiol. Neurootol 9, 107e114. Mulders, W.H., Robertson, D., 2000b. Effects on cochlear responses of activation of descending pathways from the inferior colliculus. Hear. Res. 149, 11e23. Mulders, W.H., Robertson, D., 2002. Inputs from the cochlea and the inferior colliculus converge on olivocochlear neurons. Hear. Res. 167, 206e213. Mulders, W.H., Robertson, D., 2000a. Evidence for direct cortical innervation of medial olivocochlear neurones in rats. Hear. Res. 144, 65e72. Norton, S.J., Widen, J.E., 1990. Evoked otoacoustic emissions in normal-hearing infants and children: emerging data and issues. Ear Hear. 11, 121e127. Pearson, D.A., Lane, D.M., 1991. Auditory attention switching: a developmental study. J. Exp. Child. Psychol. 51, 320e334. Perrot, X., Collet, L., 2014. Function and plasticity of the medial olivocochlear system in musicians: a review. Hear. Res. 308, 27e40. Prieve, B. a, Fitzgerald, T.S., Schulte, L.E., 1997. Basic characteristics of click-evoked otoacoustic emissions in infants and children. J. Acoust. Soc. Am. 102, 2860e2870. Puria, S., Guinan, J.J., Liberman, M.C., 1996. Olivocochlear reflex assays: effects of contralateral sound on compound action potentials versus ear-canal distortion products. J. Acoust. Soc. Am. 99, 500e507. Schofield, B.R., 2010. Structural organization of the descending auditory pathway. In: Rees, A., Palmer, A. (Eds.), The Oxford Handbook of Auditory Science: the Auditory Brain. Oxford University Press, pp. 43e64. Spangler, K., Warr, W., 1991. The descending auditory system. In: Altschuler, R.A. (Ed.), Neurobiology of Hearing: the Central Auditory System. Raven Press Ltd., New York, NY, pp. 27e45. Suga, N., Gao, E., Zhang, Y., Ma, X., Olsen, J.F., 2000. The corticofugal system for hearing: recent progress. Proc. Natl. Acad. Sci. U. S. A. 97, 11807e11814. Tognola, G., Grandori, F., Ravazzani, P., 1997. Time-frequency distributions of clickevoked otoacoustic emissions. Hear. Res. 106, 112e122. Veuillet, E., Magnan, A., Ecalle, J., Thai-Van, H., Collet, L., 2007. Auditory processing disorder in children with reading disabilities: effect of audiovisual training. Brain 130, 2915e2928. Xiao, Z., Suga, N., 2002. Modulation of cochlear hair cells by the auditory cortex in the mustached bat. Nat. Neurosci. 5, 57e63.
Abbreviations AC: Auditory cortex BBN: Broadband noise CAS: Contralateral acoustic stimulation CEOAEs: Click-evoked oto-acoustic emissions dB: Decibel HL: Hearing level IC: Inferior colliculus MOC: Medial olivocochlear OAEs: Otoacoustic emissions SD: Standard deviation SOC: Superior olivocochlear complex SPL: Sound pressure level DCEOAE: dB MOC index DCEOAEn: Normalized MOC index
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Research paper
Attentional modulation of medial olivocochlear inhibition: Evidence for immaturity in children Srikanta K. Mishra a, b, * a b
Department of Special Education and Communication Disorders, New Mexico State University, Las Cruces, NM 88003-8001, USA Department of Communication Sciences and Disorders, Butler University, 4600 Sunset Ave., Indianapolis, IN 46208, USA
a r t i c l e i n f o
a b s t r a c t
Article history: Received 17 July 2014 Received in revised form 27 September 2014 Accepted 22 October 2014 Available online 29 October 2014
Efferent feedback shapes afferent auditory processing. Auditory attention has been shown to modulate medial olivocochlear (MOC) efferent activity in human adults. Since auditory attention continues to develop throughout childhood, the present study explored whether attentional control of medialefferent inhibition in 5e10 year-old children is adult-like. MOC inhibition was measured in adults (n ¼ 14) and children (n ¼ 12) during no-task (contralateral broadband noise), passive (contralateral noise with tone-pips) and active listening conditions (attended tone-pips embedded in contralateral broadband noise). A stronger MOC inhibition was observed when measured during the active listening condition for adults which is consistent with past work. However, the effect of auditory attention on MOC inhibition in children was not robust and was significantly lower compared to that observed for adults. These findings suggest the potential immaturity of the attentional mediation of MOC inhibition in tested children. © 2014 Elsevier B.V. All rights reserved.
1. Introduction The auditory system has an elaborate structure of descending efferent neural pathways that extend from the brain to the cochlea (Schofield, 2010; Suga et al., 2000; Xiao and Suga, 2002). Efferent effects shape or modulate the bottom-up afferent processing. The medial olivocochlear (MOC) efferents originate from the periolivary nuclei of the superior olivary complex (SOC) and contain large myelinated fibers that predominantly innervate outer hair cells via cholinergic synapses. Stimulation of MOC fibers causes changes in cochlear responses to sound, which are typically recorded using otoaoustic emissions (OAEs). The efferent-induced shift in OAEs is called MOC reflex or inhibition; in this report these two terms are used. The efferent connections from the auditory cortex (AC) innervate the SOC directly as well as via the inferior colliculus (IC) (Mulders and Robertson, 2000a; Spangler and Warr, 1991). Electrical activation of the neurons at the IC and the AC induces changes in cochlear mechanisms in animals (Mulders and Robertson, 2000b; Xiao and Suga, 2002), thought to be mediated by the uncrossed MOC fibers (Mulders and Robertson, 2002). This
* Tel.: þ1 575 646 7831 (Office). E-mail address: [email protected]. http://dx.doi.org/10.1016/j.heares.2014.10.009 0378-5955/© 2014 Elsevier B.V. All rights reserved.
suggests that cortical or higher-order processing could potentially modulate MOC inhibition. One approach to examine this cortical mediation in humans is to compare MOC inhibitions measured during active and passive listening conditions. Several studies provide evidence for attentional control of MOC inhibition in the cochlea (De Boer and Thornton, 2007; Harkrider and Bowers, 2009; Ferber-Viart et al., 1995; Garinis et al., 2011; Maison et al., 2001). However, the reported magnitude and direction of attention-induced alterations in MOC activity are not always consistent. Some studies demonstrated reductions (De Boer and Thornton, 2007; Harkrider and Bowers, 2009) while others showed enhancements in MOC inhibitions with auditory attention (Garinis et al., 2011; Maison et al., 2001). These discrepancies in the influence of attention on MOC inhibition appear to be primarily due to the direction of attention and the type of auditory task. MOC inhibition is enhanced when attention was directed towards the ear receiving contralateral acoustic stimulation (CAS) via a listening-innoise task (Garinis et al., 2011; Maison et al., 2001) and reduced when attention was directed to the OAE probe ear (De Boer and Thornton, 2007; Harkrider and Bowers, 2009). Whether such attentional mediation of MOC inhibition occurs for children remains unknown. The MOC reflex or reflexive MOC effects, i.e., changes in OAEs with CAS, is functionally mature around full-term birth (Abdala et al., 2013, 1999; Durante and Carvalho, 2002; Gkoritsa et al., 2007). In all maturational studies, the MOC reflex was measured under passive
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conditions, that is, the adults merely stayed awake and neonates were typically required to stay asleep for obvious reasons. The study reported here focused on MOC measurements under active listening conditions in children. Since attention influences MOC inhibition, and auditory attention continues to develop throughout childhood (Coch et al., 2005; Cooley and Morris, 1990; Gomes et al., 2000; Klenberg et al., 2001; Pearson and Lane, 1991), the present study investigated whether the effect of attention on MOC activity in typically developing children is adult-like. Specifically, the aims of this study were to measure the effect of auditory attention on MOC inhibition in five to ten year-old children and compare this effect with those measured in adults. A secondary goal was to replicate the findings from earlier studies on adults (Garinis et al., 2011; Maison et al., 2001). To obtain an accurate description of MOC-induced changes, this study used refined CEOAE methods by recording emissions at a relatively low stimulus level and slow click rate, adopting a higher SNR criterion (6 dB) and carefully considering middle ear muscle reflexes and OAE probe-drifts. Since this study included children, a relatively simpler listening-in-noise task (tone detection in noise) was used to modulate attention. Besides theoretical interest, such as auditory modeling (Clark et al., 2012), characterizing the nature of task-dependent MOC inhibition in children has high translational significance for understanding, diagnosing and managing listening problems in children (Mishra, 2014; Muchnik et al., 2004; Veuillet et al., 2007). 2. Materials and methods 2.1. Overview MOC-induced changes in CEOAE amplitudes were computed by comparing OAEs recorded with and without three CAS conditions. The three CAS conditions were: broadband noise (BBN), designated as the no-task condition; tone-pips embedded in BBN, referred to as passive condition; and tone-pips embedded in BBN, where participants were required to respond to the tone-pips, termed the active condition. 2.2. Participants Experiments were conducted on 16 adults and 17 typically developing children with hearing thresholds of 15 dB HL or better at audiometric frequencies. Data from 14 adults and 12 children are reported here because two 4-year-olds were non-compliant with the test procedures and the CEOAEs in remaining participants did not meet the required SNR and other criteria. Individuals with musical training were excluded because their data could potentially bias the experimental outcomes (Perrot and Collet, 2014). Included adults (3 males and 11 females) were aged 19e34 years (x ¼ 25.8) and children (7 boys and 5 girls) were aged 5e10 years (x ¼ 7.2). Human experimentation was performed in accordance with the Butler University Institutional Review Board guidelines. Measurements were completed inside a double-walled sound booth. 2.3. CEOAEs recording and analysis CEOAEs were recorded using the HearID þ TE system (Mimosa Acoustics, Champaign, IL) with an ER-10C probe system (Etymotic Research, Elk Grove Village, IL). In-the-ear probe calibration for every subject applied a voltage correction to obtain the target click level. To evoke OAEs, 83.3 ms rectangular clicks were presented at 55 dB pSPL and a rate of 45 Hz using a linear recording paradigm with positive click polarity (Kemp et al.,1986). A standard 50 Hz click rate was not used to minimize unintended click-elicited MOC activity; a 40 Hz rate has been argued to be ideal for adults (Guinan
et al., 2003). However, this rate was found to be impractical for testing children due to longer test durations. A 55 dB pSPL was selected since this level produced repeatable responses with the desired criteria (see acceptance criteria) in all included children and adults. Repeatable OAEs could not be recorded with 2048 averages in many children (n ¼ 8) when lower click levels were used. Increasing the number of averages to 4096 in a few children (n ¼ 2) yielded acceptable results, but also significantly increased the test duration. Responses to a total of 2048 click trains were recorded with a time window of 2e20 ms. The noise rejection level was set at 47 dB SPL. If the total number of rejections per run was more than 600, then the entire run was repeated. The CEOAEs were filtered using a low-pass Butterworth filter (third-order) set to 5000 Hz with a 1000 Hz transition region, and the high-pass filter (sixth order) set to 1000 Hz and a 500 Hz transition. The filters were realized as zerophase forward-and-reverse infinite impulse response Butterworth filters. Responses were averaged into two alternate buffers: A and B. Signal was estimated from the A and B average waveform; noise was estimated from the AeB difference waveform. Data were accepted if the SNR was greater than 6 dB and the waveform reproducibility, an indicator of intra-run repeatability, was greater than 80%. 2.4. Contralateral acoustic stimulation The CEOAE recordings described in the preceding section were obtained in a no-CAS condition and in three CAS conditions. The CAS conditions were: (1) No-Task: Participants sat comfortably in a chair and were required to stay awake and as quiet as possible while contralateral BBN was presented. The tester visually monitored the subjects' state. (2) Passive: Participants did not receive any specific instruction except to remain awake while contralateral BBN embedded with tone-pips was presented. (3) Active: Participants were instructed to detect the tone-pips embedded in the contralateral BBN. They were asked to press a response button each time they heard the tone-pip and the percentage of correct responses were computed. In this condition, the CEOAE recordings were accepted if the behavioral response was greater than 70% to ensure that participants were attending to the tone-pips. The order of the no-CAS and various CAS conditions was random and counterbalanced across participants. Contralateral BBN (20e12,000 Hz) was presented at 50 dB SPL via an insert earphone (ER-3A, Etymotic Research, Elk Grove Village, IL) 5 seconds prior to the onset of OAE recordings. For the passive and active conditions, 1000 Hz tone-pips with a duration of 100-ms (20-ms cosine ramps) were embedded in the BBN. The tone-pips occurred randomly between the 8th and 11th seconds at 0 dB SNR. It was necessary to design a task such that there were no performance differences between the two tested groups. This particular auditory task was chosen because pilot experimentation (n ¼ 2) showed that children were able to perform the task with reasonable accuracy (>70%), suggesting they paid attention to the task. Increasing the task difficulty by decreasing the SNR or by making the task relatively complex with tone discrimination in noise indicated a lack of interest in the task and/or increased false positives for some children. Importantly, it caused anxiousness and anxiety-related bodily movements in children, leading to probedrift issues, higher rejection rates and poor SNRs for OAE recordings. All CEOAE measurements were completed during a single OAE probe insertion. When it was necessary to reinsert in a few participants, the entire measurements were repeated. 2.5. Middle ear muscle reflex (MEMR) Two approaches were used to control for potential MEMR contamination of OAE data. MEMRs were measured for each
S.K. Mishra / Hearing Research 318 (2014) 31e36
subject using a clinical immittance meter with 226-Hz probe tone (GSI 37 Auto Tymp Ear Analyzer, Grason-Stadler Inc., Eden Prairie, MN). Because clinical instruments typically give higher MEMR thresholds, a constant of 12 dB gleaned from wideband acoustic reflectance studies (Feeney et al., 2003; Keefe et al., 2010) was subtracted from each subject's clinical reflex thresholds to detect subclinical reflexes. The mean corrected MEMR threshold for adults was 82.54 dB SPL (SD ¼ 7.56) and for children was 82.09 dB SPL (SD ¼ 5.84). The contralateral BBN level (50 dB SPL) used for stimulating MOC activity was lower than the MEMR thresholds by a mean of 32 dB. Thus, it is unlikely that the contralateral BBN elicited MEMRs during MOC reflex measurements. Additionally, the actual click levels, converted to pressure (re; 20 mPa), were statistically compared between various CAS and no-CAS conditions. 2.6. Quantification of the MOC inhibition To obtain robust estimates of MOC inhibition for adults and children, CAS-induced changes in overall CEOAE amplitudes across frequency bands were examined. MOC inhibitions for no-task, passive and active listening conditions were computed by comparing the no-CAS condition with the corresponding CAS conditions. The MOC inhibition was quantified by two indices: (1) dB effect (DCEOAE) ¼ LNoCAS LCAS where Lce is CEOAE ce ce amplitude in dB SPL. As traditionally done, the effect of contralateral BBN was computed as the dB difference in CEOAE levels between no-CAS and CAS conditions for every participant. Positive values denote reductions in amplitude. NoCAS CAS (2) Normalized index (DCEOAEn) ¼ ðð Pce Pce Þ= NoCAS ð Pce ÞÞ 100 where Pce is CEOAE amplitude in pressure (mPa). The CEOAE amplitude in mPa was calculated for every participant. The CEOAE ear canal pressure in the no-CAS condition subtracted from pressure in the CAS condition, normalized to baseline CEOAE amplitude. This is a fraction and is reported as percentage. 3. Results The SNRs for CEOAEs recorded under various conditions for adults and children are shown in Fig. 1. Every participant had a SNR greater than 6 dB in all recording conditions. On average, the SNR was approximately 11 dB combined across conditions and age groups; this is almost double the required SNR criterion (6 dB) for data inclusion. It appears that the mean SNR was similar across
various CAS conditions and across subject groups. A repeated measures analysis of variance (RM-ANOVA), with four test conditions (no-CAS and three CAS conditions) as within-subject factors and age (children and adults) as between-subject factor, yielded no main effect of test conditions (F3,72 ¼ 0.40, p ¼ 0.75, h2p ¼ 0.02), age group (F3,72 ¼ 0.29, p ¼ 0.83, h2p ¼ 0.02) or any significant interaction between test conditions and age group (F1,24 ¼ 0.25, p ¼ 0.62, h2p ¼ 0.01) for the SNR of CEOAE responses. Although the mean OAE amplitudes were larger for children (x ¼ 4.68 dB SPL, SD ¼ 4.71) compared to adults (x ¼ 1.52 dB SPL, SD ¼ 5.40), an independent samples t-test showed no statistically significant group difference for the OAE amplitudes recorded in the no-CAS condition (t24 ¼ 1.58, p ¼ 0.13). Fig. 2 displays the noise floors for various CAS conditions for adults and children. It is evident that, for both adults and children, the mean noise floors were similar across CAS conditions. A Oneway ANOVA comparing the noise floors across CAS conditions separately for adults and children was not significant (adults: F3,52 ¼ 0.11, p ¼ 0.95, h2 ¼ 0.01; children: F3,44 ¼ 0.24, p ¼ 0.86, h2 ¼ 0.02). This indicates that the CEOAE noise floors were not significantly different across CAS conditions for adults and children. Although the click level was set to 55 dB pSPL, repeated recordings may have small drifts in click level over time, and thereby OAE levels, plausibly due to middle ear pressure fluctuations, OAE probe movement, etc (Backus, 2007). These drifts are likely to cancel each other in the group data; however, if the drift-induced variations are different across the CAS conditions or groups, it can make it appear that the response is different across the CAS conditions or groups. A significant change in click level with contralateral BBN also indicates MEMR activation (Guinan et al., 2003). The click levels (mPa) in four test conditions (no-CAS and three CAS conditions) were statistically compared to ensure that the levels did not change significantly with CAS for either group. Fig. 3 shows the mean and individual normalized MOC metric under various task conditions for adults and children. The effect of CAS conditions on MOC inhibition was assessed for dB and normalized MOC indices. For brevity, graphs are presented only for DCEOAEn because normalized metric has been argued to be a more valid index (Backus and Guinan, 2007; Garinis et al., 2011; Guinan et al., 2003; Mishra and Lutman, 2014, 2013). For DCEOAEn data, the assumption of sphericity was also violated (Mauchly's test, c2 ¼ 10.57, p < 0.01). A RM-ANOVA with Greenhouse-Geisser correction showed the main effect of CAS condition (F1.46,35.07 ¼ 12.98, p < 0.01, hp 2 ¼ 0.35), but no main effect of age group (F1,24 ¼ 0.12, p ¼ 0.73, hp 2 ¼ 0.01). A significant interaction effect between CAS conditions and age group (F1.46,35.07 ¼ 5.65, p ¼ 0.01, hp 2 ¼ 0.19) was observed.
Adults
Children
Children
Signal-to-Noise Ratio (dB)
Noise floor (dB SPL)
Adults
33
No-CAS No-Task Passive Active
No-CAS No-Task Passive Active
Fig. 1. Signal-to-noise ratio (SNR): Mean and individual SNRs of otoacoustic emissions for adults and children under various recording conditions.
No-CAS No-Task Passive Active
No-CAS No-Task Passive Active
Fig. 2. Noise floor: Mean and individual noise floors of otoacoustic emissions for adults and children under various recording conditions.
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S.K. Mishra / Hearing Research 318 (2014) 31e36
Children
MOC Effect: ΔCEOAEn (%)
Adults
No-Task Passive Active
No-Task Passive
Active
Fig. 3. Medial olivocochlear (MOC) inhibition: Mean and individual normalized MOC inhibitions (DCEOAEn) for adults and children under various task conditions. Error bars indicate ±95% confidence intervals for the mean.
Multiple comparisons with Bonferroni adjustments were performed a k to determine the nature of interaction effects. Notably, DunneSid corrections also yielded similar p-values. Table 1 presents summary of multiple comparison results with Bonferroni corrections (p ¼ 0.008 ¼ 0.05/6); it also shows results for DCEOAE data. These analyses indicate that the mean DCEOAEn index measured in the active condition was significantly larger than passive and no-task conditions for adults. The effect size was large (Cohen's d ¼ 1.0). However, for children, the mean MOC inhibition in the active condition, though slightly greater relative to passive and no-task conditions, did not reach the significance level. The dB (DCEOAE) index was analyzed in a similar way as the normalized metric. For adults, the mean DCEOAE for active condition (x ¼ 2.24 dB, SD ¼ 0.76) was larger than passive (x ¼ 1.47 dB, SD ¼ 0.84) and no-task (x ¼ 1.42 dB, SD ¼ 0.67) conditions. The mean DCEOAE for children seemed to be similar across conditions (no-task x ¼ 1.67 dB, SD ¼ 0.54; passive x ¼ 1.71 dB, SD ¼ 0.62; passive x ¼ 1.87 dB, SD ¼ 0.59). The Mauchly's test of sphericity indicated that the assumption of sphericity had been violated (c2 ¼ 9.68, p < 0.01). Greenhouse-Geisser correction for violation of sphericity assumption was applied. A RM-ANOVA with three CAS conditions (no-task, passive and active) as within-subject factors and age as the between-subject factor revealed the main effect of CAS condition (F1.48,35.72 ¼ 12.98, p < 0.01, hp 2 ¼ 0.34), but no effect of age group (F1,24 ¼ 0.03, p ¼ 0.87, hp 2 ¼ 0.01). A significant interaction between CAS conditions and age group (F1.48,35.72 ¼ 4.82, p ¼ 0.02, hp 2 ¼ 0.17) was found. Multiple comparisons (see Table 1) showed that the mean DCEOAE in the active condition was significantly larger than passive and no-task
Table 1 Summary of multiple comparison results for raw and normalized indices. Comparisons
Adults: No-Task vs Passive Passive vs Active No-Task vs Active Children: No-Task vs Passive Passive vs Active No-Task vs Active
dB index
Normalized index (%)
Mean difference
t
0.06
0.23
0.76 0.82 0.05 0.15 0.20
p-value
Mean difference
t
p-value
0.82
0.27
0.12
0.91
4.44 5.19 0.39
<0.01* <0.01* 0.70
7.88 7.62 0.42
4.85 5.41 0.36
<0.01* <0.01* 0.73
2.42 2.38
0.03 0.04
1.39 1.81
2.23 2.31
0.05 0.04
*Significant with Bonferroni adjustments (p ¼ 0.01) for multiple comparisons.
conditions for adults only with large effect size (Cohen's d ¼ 1.1). No such statistically significant effect was observed for children. In order to demonstrate group differences directly, the active and passive condition difference for DCEOAE and DCEOAEn was compared between adults and children. Levene's test for equality of variances revealed violation of the assumption of homogeneity of variance (DCEOAE F ¼ 26.06, p < 0.01; DCEOAEn F ¼ 24.10, p < 0.01). An independent samples t-test with unequal variances revealed significant mean difference between groups (DCEOAE adults x ¼ 0.76, SD ¼ 0.64, children x ¼ 0.15, SD ¼ 0.22, t16.45 ¼ 3.32, p < 0.01; DCEOAEn adults x ¼ 7.88, SD ¼ 6.07, children x ¼ 1.39, SD ¼ 2.17, t16.74 ¼ 3.72, p < 0.01). Thus, the effect of attention on MOC inhibition (both DCEOAE and DCEOAEn) for children was significantly lower than that for adults. To probe the potential source of the differences in task dependency of MOC inhibition between adults and children, the behavioral performance on tone-pips detection in noise during the active condition was compared between the two groups (adults x ¼ 91.42%, SD ¼ 3.05; children x ¼ 86.92%, SD ¼ 7.83). Levene's test for equality of variances showed that the assumption of homogeneity of variance had been violated (F ¼ 22.53, p < 0.01). An independent samples t-test with unequal variances showed no significant difference between adults and children (t13.86 ¼ 1.87, p ¼ 0.08). 4. Discussion The primary goal of this study was to determine whether auditory attention modulates the medial-efferent inhibition in five to ten year-old children to the same extent as it does in adults. The results suggest that the influence of attention on MOC inhibition was less pronounced for children compared to adults, particularly, the MOC inhibitions were significantly larger in the active relative to the passive and no-task conditions for adults, but not for children. The results also show that this group difference, in effect of attention, cannot be attributed to factors related to noise floor, SNR, middle-ear-muscle-reflexes, probe-drift related variations in click level or behavioral performance in the listening task. Therefore, the attentional modulation of medial efferent function is immature in five to ten year-old children. 4.1. MOC reflex strength in children The normative features of the MOC reflex for school-aged children are not well characterized. The measurement issues and repeatability of the MOC reflex in children are unknown. Measuring MOC reflex in children could be scientifically and clinically relevant for identifying children with listening problems (Mishra, 2014). Past work on children used relatively weaker methods, particularly low SNR (typically 3 dB) and higher click levels (Kumar and Vanaja, 2004; Muchnik et al., 2004; see Mishra, 2014 for review). To obtain robust data from a variable computed as a differencedthe MOC reflexdthe SNR of each independent measure (OAEs in no-CAS and CAS conditions) must be high enough so that the difference itself is not contaminated by noise. While the SNRs (~11 dB) in the present CEOAE measurements are unparalleled with past MOC work in children, Goodman et al. (2013) showed that a SNR of 20e25 dB is needed for determining MOC reflexes of the order of 1 dB in individual adults. It is currently not known whether a similar amount of SNR is needed for computing OAE differences from linear CEOAE recordings for making group comparisons. Nevertheless, our choice of SNR criteria (6 dB) was limited by practical constraints related to test duration and the age of children.
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This study found 1.67 dB of MOC reflex in the no-task condition for children, which is consistent with past work (e.g., Kumar and Vanaja, 2004; Muchnik et al., 2004). However, the click and the contralateral BBN levels used in this study were lower compared to previous studies. The normalized index showed a MOC inhibitory effect of 17.33% (SD ¼ 5.19), which was similar to that observed for adults (x ¼ 15.09%, SD ¼ 6.39). The lack of difference in MOC reflex in no-task and passive conditions may be interpreted as an indicator of good immediate test-retest repeatability of the reported measurements. Consistent with past work (Norton and Widen, 1990; Prieve et al., 1997), children's CEOAE amplitudes were slightly larger than adults. However, the SNRs were similar between the two age groups due to relatively higher recording noise in children. One of the many unique challenges in performing MOC reflex measurements in young children is to achieve a high SNR in the shortest possible test duration. A higher number of averages typically leads to robust CEOAEs with good SNR, but increases the test duration. With increased test duration comes the greater likelihood of rejections associated with bodily movements. From our experience with testing children, averages more than 2048 click trains per condition were not practically beneficial since we had several test conditions. 4.2. Attentional control of MOC inhibition: implications for maturation of the MOC inhibitions The MOC reflex is mature around full-term birth (Abdala et al., 2013, 1999; Durante and Carvalho, 2002; Gkoritsa et al., 2007). The present study showed that the effect of attention on the MOC inhibition in children is not similar to that in adults. Attending to tone-pips embedded in contralateral BBN produced a significant increase in the magnitude of MOC inhibition for adults, but not for children. Since other extraneous variables such as noise floor, SNR and MEMRs were controlled, the lack of a significant effect of attention for children suggests that attentional modulation of MOC inhibition is not adult-like in the tested children. The notion that attentional control of MOC inhibition is immature in children is further reinforced by studies on development of auditory cortex (Moore and Guan, 2001; Moore, 2002). The role of the auditory cortex in modulating peripheral mechanisms via the descending fibers has been demonstrated in animal experiments (He and Yu, 2010; Mulders and Robertson, 2000a,b; Suga et al., 2000; Xiao and Suga, 2002). In humans, a reduced MOC inhibition has been reported in epileptic patients with surgically removed Heschl's gyrus (Khalfa et al., 2001). The auditory cortex follows a prolonged course of maturation (Moore and Guan, 2001; Moore, 2002). Particularly relevant, maturation of commissural and association axons in the superficial cortical layers to allow communication between different subdivisions of the auditory cortex, necessary for more complex cortical processing of sound, occurs during the period of 5e12 years (Moore, 2002). These maturational changes suggest the possibility that the topdown control of listening in noise via medial efferents is likely under development during that period. In all likelihood, the cortical or top-down modulation of the MOC efferents is probably immature in the tested children, even though the MOC efferents are functionally mature at birth. This may also suggest an experience-dependent developmental plasticity of the MOC efferents, which is congruent with evidence that MOC inhibition can be altered with auditory training or musical training (De Boer and Thornton, 2008; Perrot and Collet, 2014; Veuillet et al., 2007). Since the present study showed that attentional modulation of MOC inhibition is immature in 5e10 year-old children, it would be interesting to investigate the maturational
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trajectory. A complete timeline for maturation of attentional modulation of MOC inhibition would require inclusion of more children across a wider age range. While this study carefully controlled several MOC measurement related variables, one factor that may have influenced the present findings is the level of attentional effort. Although the behavioral performances in the active condition for both age groups were similar, there may have been a real difference in the level of listening effort or the auditory attention paid by the two groups. A confirmation of present findings may require balancing the level of auditory attention between the two groups, which may be potentially challenging to achieve, particularly in the context of simultaneous OAE measurements in children. 4.3. Comparison with previous measurements of attentionmediated changes in MOC inhibition Since this is the first study examining the effect of auditory attention on MOC inhibition for children, the results obtained from adults are compared with previous reports. Previous studies of changes in MOC inhibition with attention provide evidence for a cortical influence on the cochlea (De Boer and Thornton, 2007; Ferber-Viart et al., 1995; Garinis et al., 2011; Harkrider and Bowers, 2009; Maison et al., 2001). In the present experiment, contralateral BBN and tone-pips were presented to one ear while the CEOAEs were recorded from the other ear. A stronger MOC inhibition was evident during the active listening condition, consistent with past work (Garinis et al., 2011; Maison et al., 2001), showing that focusing attention to the ear receiving CAS enhances MOC inhibition. Since the MOC reflex pathway is bilateral (Guinan, 2006), evidence of increased inhibition in the probe ear may suggest that it is also increased in the contralateral ear. The magnitude of attentional effect in dB, i.e., difference between passive and active conditions (x ¼ 0.8), was greater than those reported (~0.4) by Maison et al. (2001) and (~0.2) by Garinis et al. (2011), possibly due to use of refined CEOAE methods, more specifically the higher SNR in our data. This difference may seem small, but the effect size was large. Further, it has been shown in adult cats that subtle alterations in cochlear mechanisms result in much larger changes on subsequent responses of auditory nerve fibers (Puria et al., 1996). 4.4. Summary The present study using refined CEOAE methods showed that the effect of auditory attention in children is much weaker than those observed in adults, suggesting potential immaturity of attentional or top-down modulation of MOC inhibition in tested children. This is exciting considering that the reflexive MOC reflex is mature around full-term birth. The current findings may be followed with a larger sample size with a wider age range and with measurement of time-frequency distribution of CEOAEs using wavelet transformations (Tognola et al., 1997) or other innovative methods. Acknowledgments This work was supported by a Faculty Research Award, Holcomb Awards Committee, Butler University. The author acknowledges BreeAnna Sawyer for her assistance with data collection. Carolyn Herbert is acknowledged for editorial assistance. References Abdala, C., Ma, E., Sininger, Y.S., 1999. Maturation of medial efferent system function in humans. J. Acoust. Soc. Am. 105, 2392e2402.
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Abbreviations AC: Auditory cortex BBN: Broadband noise CAS: Contralateral acoustic stimulation CEOAEs: Click-evoked oto-acoustic emissions dB: Decibel HL: Hearing level IC: Inferior colliculus MOC: Medial olivocochlear OAEs: Otoacoustic emissions SD: Standard deviation SOC: Superior olivocochlear complex SPL: Sound pressure level DCEOAE: dB MOC index DCEOAEn: Normalized MOC index