The mismatch negativity (MMN)--a unique window to disturbed central auditory processing in ageing and different clinical conditions.

In this article, we review clinical research using the mismatch negativity (MMN), a change-detection response of the brain elicited even in the absence of attention or behavioural task. In these studies, the MMN was usually elicited by employing occasional frequency, duration or speech-sound changes in repetitive background stimulation while the patient was reading or watching videos. It was found that in a large number of different neuropsychiatric, neurological and neurodevelopmental disorders, as well as in normal ageing, the MMN amplitude was attenuated and peak latency prolonged. Besides indexing decreased discrimination accuracy, these effects may also reflect, depending on the specific stimulus paradigm used, decreased sensory-memory duration, abnormal perception or attention control or, most importantly, cognitive decline. In fact, MMN deficiency appears to index cognitive decline irrespective of the specific symptomatologies and aetiologies of the different disorders involved.

Improvement of renal function after conversion to mycophenolate mofetil combined with low-level calcineurin inhibitor in liver transplant recipients with chronic renal dysfunction.

INTRODUCTION: Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction. PATIENTS AND METHODS: We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 +/- 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4-1.7 mg/dL (group I; n = 41); 1.8-2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5-2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria. RESULTS: Creatinine values after conversion were 1.4 +/- 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected. CONCLUSION: Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.

Prospective interventional study to evaluate the efficacy and safety of liposomal amphotericin B as prophylaxis of fungal infections in high-risk liver transplant recipients.

INTRODUCTION: Invasive fungal infections are a life-threatening complication in transplant recipients. The prevalence of fungal infection after orthotopic liver transplantation (OLT) is 5% to 42%. The most common isolated pathogens are Candida and Aspergillus species. High-risk liver transplant recipients are more susceptible to the development of invasive fungal infections, with prevalence >40% and mortality rates of 78% to 100%. The strategy for fungal prophylaxis in this population has not been defined. PATIENTS AND METHODS: Among 100 consecutive OLT followed for 28 months, 21 recipients (15 men, overall mean age of 48.5 years, range 23-65 years) were considered to be high risk for the development of fungal infections when they presented at least one of the following criteria: acute liver failure, assisted ventilation >7 days, retransplantation, relaparotomy, antibiotic therapy >14 days, transfusion requirements >20 red blood cells units, and/or biliary leakage. This group received intravenous liposomal amphotericin B (1 mg/kg/d for 7-10 days). RESULTS: One-year survival in the high-risk group was 80%. Prevalence of invasive fungal infection was 9.5%. No Candida infection was observed. Two patients developed Aspergillus infection: an abdominal aspergillosis treated with percutaneous drainage and liposomal amphotericin B (5 mg/kg/d) showed a favorable clinical outcome. The other patient who developed brain aspergillosis died 25 days after OLT. Adverse events related to the drug were hypokalemia (n = 2), back pain (n = 3), and renal dysfunction (n = 2). None of these events required withdrawal of the prophylaxis regimen. CONCLUSION: In our series, prophylaxis with liposomal amphotericin B in high-risk liver graft recipients showed a low rate of severe fungal infections. More studies are needed in order to determine the highest risk population and the best drug dosage.

Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness.

Experience-related changes in central nervous system (CNS) activity have been observed in the adult brain of many mammalian species, including humans. In humans, late-onset profound unilateral deafness creates an opportunity to study plasticity in the adult CNS consequent to monaural auditory deprivation. CNS activity was assessed by measuring long-latency auditory evoked potentials (AEPs) recorded from teens and adults with late-onset (post-childhood) profound unilateral deafness. Compared to monaurally stimulated normal-hearing subjects, the AEPs recorded from central electrode sites located over auditory cortical areas showed significant increases in inter-hemispheric waveform cross-correlation coefficients, and in inter-hemispheric AEP peak amplitude correlations. These increases provide evidence of substantial changes from the normal pattern of asymmetrical (contralateral > ipsilateral amplitude) and asynchronous (contralateral earlier than ipsilateral) central auditory system activation in the normal-hearing population to a much more symmetrical and synchronous activation in the unilaterally deaf. These cross-sectional analyses of AEP data recorded from the unilaterally deaf also suggest that the changes in cortical activity occur gradually and continue for at least 2 years after the onset of hearing loss. Analyses of peak amplitude correlations suggest that the increased inter-hemispheric symmetry may be a consequence of changes in the generators producing the N (approximately 100 ms peak latency) potential. These experience-related changes in central auditory system activity following late-onset profound unilateral deafness thus provide evidence of the presence and the time course of auditory system plasticity in the adult brain.

Central auditory plasticity: changes in the N1-P2 complex after speech-sound training.

OBJECTIVE: To determine whether the N1-P2 complex reflects training-induced changes in neural activity associated with improved voice-onset-time (VOT) perception. DESIGN: Auditory cortical evoked potentials N1 and P2 were obtained from 10 normal-hearing young adults in response to two synthetic speech variants of the syllable /ba/. Using a repeated measures design, subjects were tested before and after training both behaviorally and neurophysiologically to determine whether there were training-related changes. In between pre- and post-testing sessions, subjects were trained to distinguish the -20 and -10 msec VOT /ba/ syllables as being different from each other. Two stimulus presentation rates were used during electrophysiologic testing (390 msec and 910 msec interstimulus interval). RESULTS: Before training, subjects perceived both the -20 msec and -10 msec VOT stimuli as /ba/. Through training, subjects learned to identify the -20 msec VOT stimulus as "mba" and -10 msec VOT stimulus as "ba." As subjects learned to correctly identify the difference between the -20 msec and -10 msec VOT syllabi, an increase in N1-P2 peak-to-peak amplitude was observed. The effects of training were most obvious at the slower stimulus presentation rate. CONCLUSIONS: As perception improved, N1-P2 amplitude increased. These changes in waveform morphology are thought to reflect increases in neural synchrony as well as strengthened neural connections associated with improved speech perception. These findings suggest that the N1-P2 complex may have clinical applications as an objective physiologic correlate of speech-sound representation associated with speech-sound training.

Of kittens and kids: altered cortical maturation following profound deafness and cochlear implant use.

Profoundly deaf children who use a cochlear implant (CI) provide a unique opportunity to investigate the effects of auditory sensory deprivation on the maturing human central nervous system. Previous results suggest that children fitted with a CI show evidence of altered auditory cortical maturation, based on evoked potentials. This altered maturation was characterized by both latency delays and morphological changes in the cortical auditory evoked potentials (AEPs). Based on prolonged P(1) latencies compared to age-matched normal-hearing (NH) peers, these data suggested a delayed maturation nearly equivalent to the period of deafness. However, rates of maturation for this AEP peak were essentially the same in NH and CI children. This suggests that, given enough time, the AEPs of CI children would assume the characteristic morphology found in older NH teens and NH adults. However, the data also indicated a substantial alteration of the typical set of obligatory P(1)-N(1b)-P(2) peaks, specifically related to the absence of the N(1) potential. Recent analyses of more extensive sets of longitudinal and cross-sectional data indicate that even after many years of implant use, the AEPs of CI users in their late teens remain very different from those of their NH peers. The P(1) peak latency remains prolonged and P(1) amplitude remains much larger in CI users than in age-matched NH teens. These findings suggested that age-related changes in the P(1) peak are completed by 12 years of age. In addition, the normal N(1b) peak fails to emerge in virtually all of the CI children tested in our laboratory. A major new interpretation of the abnormal maturation of AEP waveforms in CI children is presented. It is based on direct evidence showing that a persistent immaturity of the superficial layer axons has persistent negative effects on the generation of the N(1b) and, consequently, on the morphology of the AEPs. A comparison of scalp-recorded AEPs from implanted children with local field potentials measured from the cortical surface in deaf white kittens suggests the effects of deafness and CI use are similar across these mammalian species. For both species, a period of profound deafness followed by CI stimulation reveals a substantial immaturity in cortical activation even after a period of electrical stimulation by the CI.

Maturation of the mismatch negativity: effects of profound deafness and cochlear implant use.

The use of cochlear implants to restore auditory sensation in deaf children is increasing, with a trend toward earlier implantation. However, little is known about how auditory deprivation and subsequent cochlear implant use affect the maturing human central auditory system. Our previous studies have demonstrated that the obligatory auditory evoked potentials (AEPs) of implanted children are very different from those of normal-hearing children. Unlike the obligatory potentials, which primarily reflect neural responses to stimulus onset, the mismatch negativity (MMN) provides a neurophysiological measure of auditory short-term memory and discrimination processes. The purpose of this investigation is to review our studies of the effects of auditory deprivation due to profound deafness and cochlear implant use on the maturation of the MMN in children, placed in the context of overall age-related changes in the AEPs. The development and application of a statistical technique to assess the MMN in individuals is also reviewed. Results show that although the morphology of the obligatory AEPs is substantially altered by the absence of a normal N(1) peak, the MMN is robustly present in a group of implanted children who have good spoken language perception through their device. Differences exist in the scalp distribution of the MMN between implanted and normal-hearing children. Specifically, the MMN appears to be more symmetrical in amplitude over both hemispheres, whereas it is initially much larger over the contralateral hemisphere in normal-hearing children. These findings suggest that, compared to N(1), the MMN is a better measure of basic auditory processes necessary for the development of spoken language perception skills in profoundly deaf children and adults who use a cochlear implant.

Maturation of human central auditory system activity: evidence from multi-channel evoked potentials.

OBJECTIVE: The purpose of this study was to evaluate central auditory system maturation based on detailed data from multi-electrode recordings of long-latency auditory evoked potentials (AEPs). METHODS: AEPs were measured at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Analyses focused on age-related latency and amplitude changes in the P1, N1b, P2, and N2 peaks of the AEPs generated by a brief train of clicks presented to the left ear. RESULTS: Substantial and unexpected changes that extend well into adolescence were found for both the amplitude and latency of the AEP components. While the maturational changes in latency followed a pattern of gradual change, amplitude changes tended to be more abrupt and step-like. Age-related latency decreases were largest for the P1 and N1b peaks. In contrast, P2 latency did not change significantly and the N2 peak increased in latency as a function of age. Abrupt changes in P1, P1-N1b, and N2 peak amplitude (also RMS amplitude) were observed around age 10 at the lateral electrode locations C3 and C4, but not at the midline electrodes Cz and Fz. These changes in amplitude coincided with a sharp increase and plateau in AEP peak and RMS amplitude variability from 9 to 11 years of age. CONCLUSIONS: These analyses demonstrated that the observed pattern of AEP maturation depends on the scalp location at which the responses are recorded. The distinct maturational time courses observed for individual AEP peaks support a model of AEP generation in which activity originates from two or more at least partly independent central nervous system pathways. A striking parallel was observed between previously reported maturational changes in auditory cortex synaptic density and, in particular, the age-related changes in P1 amplitude. The results indicate that some areas of the brain activated by sound stimulation have a maturational time course that extends into adolescence. Maturation of certain auditory processing skills such as speech recognition in noise also has a prolonged time course. This raises the possibility that the emergence of adult-like auditory processing skills may be governed by the same maturing neural processes that affect AEP latency and amplitude.

Activating separate ascending auditory pathways produces different human thalamic/cortical responses.

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors in cases of neurofibromatosis type 2, a sense of hearing may be restored by means of an auditory brainstem implant (ABI), which electrically stimulates the cochlear nucleus. Electrically evoked auditory brainstem responses recorded from ABI subjects exhibit a variety of waveforms due to the presence or absence of different components. Evidently, ABI stimulation activates different ascending auditory pathways in different individuals. This study examined whether such differences at the brainstem level are associated with corresponding differences at higher levels. Multichannel recordings of electrically evoked middle-latency and late auditory responses were obtained from two ABI subjects whose very different electrically evoked auditory brainstem responses represent distinct categories of waveform morphology. The waveforms of both types of response were qualitatively similar in that for each condition tested there were corresponding main peaks and troughs. Quantitatively, however, there were differences in the scalp distributions and magnitudes of all components present. One subject had distributions suggesting bilateral activation and an N1-P2 complex of large amplitude, whereas the other subject had distributions suggesting unilateral activation contralateral to the side of stimulation and an N1-P2 complex of small amplitude. The differences suggest that activation of different ascending pathways in the auditory system results in different spatial and temporal patterns of neural activity in the thalamic and/or cortical auditory areas.

Prolonged deafness limits auditory system developmental plasticity: evidence from an evoked potentials study in children with cochlear implants.

The use of cochlear implants to restore hearing in profoundly deaf children is increasing, with a trend toward earlier implantation. However, little is known about how auditory deprivation and subsequent implant use affects the maturing central auditory system. Previously reported results indicate that stimulation of the auditory system by a cochlear implant is sufficient to restore at least some aspects of central auditory pathway maturation, as reflected by age-related changes in the auditory evoked potentials. We review animal and human studies on sensory deprivation and report new results based on longitudinal evoked potentials data recorded from two individuals. Analyses show that age-related changes in the EPs may asymptote at levels very different from those found in the adult normal-hearing population. These results suggest that maturation of at least some aspects of central auditory system activity is limited by the onset and duration of the period of deafness prior to implantation.

The effects of sensory hearing loss on cochlear filter times estimated from auditory brainstem response latencies.

Derived-band auditory brainstem responses (ABRs) were obtained in 43 normal-hearing and 80 cochlear hearing-impaired individuals using clicks and high-pass noise masking. The response times across the cochlea [the latency difference between wave V's of the 5.7- and 1.4-kHz center frequency (CF) derived bands] were calculated for five levels of click stimulation ranging from 53 to 93 dB p.-p.e. SPL (23 to 63 dB nHL) in 10-dB steps. Cochlear response times appeared to shorten significantly with hearing loss, especially when the average pure tone (1 to 8 kHz) hearing loss exceeded 30 dB. Examination of derived-band latencies indicates that this shortening is due to a dramatic decrease of wave V latency in the lower CF derived band. Estimates of cochlear filter times in terms of the number of periods to maximum response (Nmax) were calculated from derived-band latencies corrected for gender-dependent cochlear transport and neural conduction times. Nmax decreased as a function of hearing loss, especially for the low CF derived bands. The functions were similar for both males and females. These results are consistent with broader cochlear tuning due to peripheral hearing loss. Estimating filter response times from ABR latencies enhances objective noninvasive diagnosis and allows delineation of the differential effects of pathology on the underlying cochlear mechanisms involved in cochlear transport and filter build-up times.

Integrated mismatch negativity (MMNi): a noise-free representation of evoked responses allowing single-point distribution-free statistical tests.

If the repeated presentation of a single (standard) auditory stimulus is randomly interspersed with a second acoustically different (deviant) stimulus, the cortical activity evoked by the deviant stimulus can contain a negative component known as the mismatch negativity (MMN). The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. When the magnitude of the response is small or the signal-to-noise ratio is poor, it is difficult to judge the presence or absence of the MMN simply by visual inspection, and statistical detection techniques become necessary. A method of analysis is proposed to quantify the magnitude and statistically evaluate the presence of the MMN based on time-integrated evoked responses. This paper demonstrates the use of this integrated mismatch negativity (MMNi) analysis to detect the MMN evoked by stimulus contrasts near the perceptual threshold of two subjects. The MMNi, by virtue of being equivalent to a low-pass filtered response, presents an almost noise-free estimate of MMN magnitude. A single measure of the integrated evoked response at a fixed time point is used in a distribution-free statistic that compares the magnitude of the averaged response evoked by the deviant stimulus with a magnitude distribution derived from 200 subaveraged responses to the standard stimulus (with the number of sweeps per average equal to that of the deviant stimulus). This allows a calculation of the exact probability for the null hypothesis that the negative magnitude of the response evoked by the deviant stimulus is drawn from the magnitude distribution of responses evoked by the standard stimulus. Rejection of this hypothesis provides objective evidence of the presence of the MMN.

Maturational delays in cortical evoked potentials in cochlear implant users.

We studied the effects of prolonged auditory deprivation in children in whom auditory stimulation was restored by a cochlear implant. The latency of the P1 component of the late cortical potential was used as the indicator of auditory system maturation. For normal-hearing children there is a gradual evolution of evoked potential features that extends through adolescence with P1 latency becoming adult-like at about age 15. It appears that maturation of P1 latency in normal and implanted children occurs at the same rate, but the time to maturity in implanted subjects is delayed by an amount approximately equal to the duration of deafness.

Auditory system plasticity in children after long periods of complete deafness.

Deaf children fitted with a cochlear implant provide a unique opportunity to examine the effects of auditory deprivation on the maturation of the human auditory system. We compared cortical evoked potentials recorded in implanted and normal-hearing children and found that age-dependent latency changes for the P1 component, fitted to a decaying exponential curve, showed the same rate of maturation. For implanted children, however, maturational delays for P1 latency approximated the period of auditory deprivation prior to implantation. This indicates the auditory system does not mature without stimulation. Nonetheless, the auditory system retains its plasticity during the period of deafness since the re-introduction of stimulation by the cochlear implant resumes the normal maturational sequence.

Comparison of distortion product otoacoustic emission (DPOAE) and auditory brain stem response (ABR) traveling wave delay measurements suggests frequency-specific synapse maturation.

OBJECTIVE: To determine whether the source of age-dependent latency changes for ABR wave I results from cochlear mechanics or the haircell-neuron synapse. DESIGN: Cochlear traveling wave delays were estimated on the basis of derived ABR response latencies and DPOAE phase delays. The difference in travel time between adjacent one octave-separated frequencies was calculated for four age groups: 30 to 33 wk old, 34 to 37 wk old, 38 to 42 wk old (term), and young adults. RESULTS: We found that there were essentially no travel time differences between newborns in the 34 to 37 and the 38 to 42 wk conceptional age (CA) groups as estimated from DPOAE phase delays. For the 30- to 33-wk-olds, DPOAE travel times were increased at all frequencies, likely due to mild (about 10 to 15 dB) conductive hearing losses. Differences in travel times between adjacent bands, however, were not different from the other neonatal groups. Estimates on basis of wave I latency showed delays for the high-frequency region, 6 to 11 kHz, that were still immature at term. CONCLUSIONS: A comparison of frequency-dependent travel times calculated for wave I and DPOAE data in comparable age groups suggests mature cochlear functioning at 35 wk CA and a delayed maturation for the haircell-auditory nerve synapses relative to the preneural components for the basal turn with center frequencies above 6 kHz.

Auditory brain stem response generation by parallel pathways: differential maturation of axonal conduction time and synaptic transmission.

In attempting to correlate developmental anatomical data with electrophysiological data on maturation of the auditory brain stem response (ABR), a model of ABR generation was necessary to match neuroanatomical structures to ABR components. This model has been developed by reviewing quantitative studies of human brain stem nuclei, results of intrasurgical recordings, studies of correlation of pathology with ABR waveform alterations, and findings from direct stimulation of the human cochlear nuclei through a brain stem implant device. Based on this material, it was assumed that waves I and II are generated peripherally in the auditory nerve and that waves III, IV, and V are generated centrally, i.e., by brain stem structures. It was further assumed that wave III is generated by axons emerging from the cochlear nuclei in the ventral acoustic stria and that waves IV and V reflect activity in parallel subpopulations of these ascending axons at a higher brain stem level. Beyond the cochlear nucleus, the largest component of the brain stem auditory pathway consists of axons projecting without interruption from the cochlear nuclei to the contralateral lateral lemniscus and inferior colliculus. In the proposed model of ABR generation, the III-IV interwave interval is assumed to reflect only axonal conduction in this asynaptic pathway. Electrophysiological data from infants indicate that the III-IV interwave interval becomes adult-like by the time of term birth. The second largest component of the brain stem auditory pathway is the bilateral projection through the medial olivary nucleus. The model assumes that activity in this monosynaptic pathway, consisting of axonal conduction time plus one synaptic delay, is reflected in the III-V interwave interval. If both of the preceding assumptions are true, the IV-V interwave interval represents the difference between the two pathways, i.e., the time of transmission across one synapse. The electrophysiological ABR data indicates that the IV-V interval does not mature until one year of age. It is also possible to apply this model to the peripherally generated portion of the ABR. The I-II interwave interval, assumed to solely represent conduction in VIIIth nerve axons, is adult-like before the time of term birth. The II-III interval, presumed to contain a synapse in the cochlear nuclear complex, does not reach an adult level until between 1 and 2 yr postnatal age.

Perinatal maturation of the auditory brain stem response: changes in path length and conduction velocity.

OBJECTIVE: The goal of this study was to correlate developmental data on brain stem auditory path length with data on auditory brain stem response (ABR) conduction time. This was done to estimate changing axonal conduction velocity during the perinatal period. DESIGN: Pathway length was determined by three-dimensional reconstruction of postmortem fetal and infant brain stems in an AutoCAD system. Brain stem conduction time was obtained from previous ABR studies of premature, term, and post-term infants. The process of correlation of path length and conduction time was based on a model of ABR generation (Ponton, Moore, & Eggermont, this issue) that assumes that the III-IV interpeak interval represents activity in an asynaptic pathway and, thus, consists of only axonal conduction time. RESULTS: Brain stem conduction time is adult-like by the time of term birth. However, the brain stem auditory pathway continues to lengthen postnatally, with portions of the pathway not reaching adult dimensions until 3 yr of age. We determined lengths at various perinatal ages for three different segments of the auditory pathway. Each segment began at the cochlear nucleus (site of wave III generation) and ended at a more rostral location that is a possible site of wave IV generation. Conduction velocity was estimated by dividing path length by axonal conduction time (III-IV interpeak interval). All three assumed sites of generation of wave IV gave estimates of a threefold increase in conduction velocity between 29 wk CA and adulthood. However, three highly discrepant measures of absolute conduction velocity were obtained for the different path segments. The most reasonable conduction velocity estimates, from 5 m/sec at 29 wk conceptional age to 20 m/sec in adults, were produced by assuming a site of generation for wave IV near the contralateral medial superior olivary nucleus. CONCLUSIONS: Prenatally, increasing conduction velocity more than compensates for increasing path length, causing ABR conduction time to decrease. Postnatally, increasing conduction velocity exactly compensates for increasing path length while ABR conduction time remains stable. Different aspects of myelin development may underlie these two phenomena.

Maturation of human cortical auditory function: differences between normal-hearing children and children with cochlear implants.

OBJECTIVE: We investigated maturation of cortical auditory function in normal-hearing children and in children who receive stimulation of their auditory system through a cochlear implant. DESIGN: As a measure of cortical auditory function, auditory evoked responses (AERs) were recorded from normal-hearing children and adults as well as from children and adults fitted with a cochlear implant. Morphological and latency changes for evoked responses recorded at electrode Cz are reported. RESULTS: For normal-hearing children, there is a gradual evolution of AER features that extends through adolescence, with P1 latency becoming adult-like in the late teens. Latency changes for P1 occur at the same rate for implanted children, but the overall maturation sequence is delayed. By extrapolation from the existing data, the age at which P1 latency becomes adult-like is delayed by approximately 5 yr for the implanted population. Other typical features of the AER, namely N1 and P2, are either delayed in developing or absent in the implanted children. CONCLUSIONS: These preliminary findings suggest both similarities and differences in cortical auditory maturation for normal-hearing and implanted children. For implanted children, the 5 yr delay for maturation of P1 latency roughly corresponds to the average 4.5 yr interval between the onset of deafness and the time of implantation. These findings suggest that during the period of deafness, maturation of cortical auditory function does not progress. However, some, if not all, maturational processes resume after stimulation is reintroduced.

Variable effects of click polarity on auditory brain-stem response latencies: analyses of narrow-band ABRs suggest possible explanations.

The auditory brain-stem responses (ABRs) to rarefaction and condensation clicks were obtained for 12 normal-hearing subjects in quiet, and high-pass masking at 8, 4, 2, 1, and 0.5 kHz. Derived narrow-band wave V latency differences were analyzed with respect to (1) stimulus polarity, (2) absolute differences irrespective of polarity. The analyses revealed no significant stimulus polarity effects on latency for the derived bands. Absolute latency differences regardless of polarity tended to be greater for those derived bands having lower characteristic frequencies (CFs). However, these differences were smaller than the expected half-period of the theoretical CF. Further analyses in three additional subjects using repeated runs of the same polarity indicate that this increase in absolute latency difference with lower derived band CF does not reflect a simple half-period change owing to polarity, but rather to the increase variability in measuring the peak latency of the lower CF derived bands. The variability is consistent with variability of eighth nerve PST histograms behavior observed in animal work [Kiang et al., "Discharge patterns of single fibers in the cat's auditory nerve," Research Monograph No. 35 (MIT, Cambridge, MA, 1965)]. Thus claimed polarity effects observed in other ABR work using absolute values may have been affected by this variability. It appears from these current data that half-period latency shifts of wave V owing to stimulus polarity differences are not observed in derived bands responses initiated from frequency specific regions of the cochlea.

Possible application of functional imaging of the human auditory system in the study of acclimatization and late onset deprivation.

After some period of experience with a single hearing aid, speech recognition performance may increase for material presented to the aided ear. Conversely, performance may decline for material presented to the unaided ear. Improved performance for the normally aided ear beyond that observed at the initial fitting of the hearing aid has been described as the acclimatization effect. The decline in speech recognition for material presented to the unaided ear has been described as the late onset auditory deprivation effect. For both the acclimatization and deprivation effects, the observed changes in performance are not considered to be a consequence of a change in the functional status of the cochlea. Rather, the benefits and decrements in speech recognition performance presumably reflect functional changes or reorganization in the central auditory pathway. In nonhuman species, changes in central auditory function can be examined by physiological recordings directly from various structures along the auditory pathway. However, these techniques are invasive and inappropriate for studying possible changes in central function for the human auditory system. The purpose of this review is to describe noninvasive "imaging" techniques appropriate for use with human subjects and the ways they could be applied to objectively identify physiological changes that might be associated with either acclimatization or late onset deprivation effects. Currently, few of these techniques have been applied to the study of acclimatization and late onset auditory deprivation. Possible application of these techniques to assess the differential performance changes for material presented to the normally aided and normally unaided ear will be discussed.