Brainstem auditory evoked potential study in children with autistic disorder

Brainstem auditory evoked potentials were compared in 109 children with infantile autism, 38 with autistic condition, 19 with mental retardation, and 20 normal children. Children with infantile autism or autistic condition had significantly longer brainstem transmission time than normal (p<.001). Autistic features, rather than age, sex, or lower mentality, correlated with brainstem transmission time (p<.0001). The autistic characteristics may be related to dysfunction of the brainstem which affects the processing of the sensory input through the auditory pathway. The brainstem lesion may be part of a generalized process of neurological damage that accounts for the deviant language, cognitive, and social development in the spectrum of autistic disorder.We thank R. Ko and F. Pun for their scretarial assistance.     

Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing.

OBJECTIVE: Autism is a frequent manifestation of tuberous sclerosis complex (TSC) being reported in up to 60% of the patients. Its presence is in association with cortical and subcortical lesions involving the temporal lobes. This study was designed to shed light on the functional mechanisms linking anatomical lesions of TSC and behavioural phenotype by investigating scalp recorded event related potentials to auditory stimuli. METHODS: Fourteen children with TSC, seven of which fulfilled the DSM IV criteria for autistic disorder were selected for this study. All of the subjects underwent high resolution MRI, EEG, brainstem auditory evoked potentials, cognitive and behavioural evaluation. Electrical evoked responses to two different pitches, presented with different probability (80% 1000 Hz, 20% 1500 Hz) were recorded from 21 scalp electrodes in the autistic and non-autistic subgroups, to assess central auditory processing and automatic memory. RESULTS: The first component of the long latency auditory response (N1) had a significantly prolonged latency with lower amplitude in all of the patients with autistic behaviour who, contrary to non-autistics had MRI lesions involving one or both temporal lobes. A mismatch negativity was detected in all subjects and had a longer latency in subjects with autistic behaviour. CONCLUSIONS: To our knowledge this is the first electrophysiological evidence of a deficit in auditory information processing and automatic memory in TSC patients with autistic behaviour.     

Brainstem auditory evoked potentials and middle latency auditory evoked potentials in young children

Measurements of brainstem auditory evoked potentials (BAEP) and middle latency auditory evoked potentials (MLAEP) are readily available neurophysiologic assessments. The generators for BAEP are believed to involve the structures of cochlear nerve, cochlear nucleus, superior olive complex, dorsal and rostral pons, and lateral lemniscus. The generators for MLAEP are assumed to be located in the subcortical area and auditory cortex. BAEP are commonly used in evaluating children with autistic and hearing disorders. However, measurement of MLAEP is rarely performed in young children. To explore the feasibility of this procedure in young children, we retrospectively reviewed our neurophysiology databank and charts for a 3-year period to identify subjects who had both BAEP and MLAEP performed. Subjects with known or identifiable central nervous system abnormalities from the history, neurologic examination and neuroimaging studies were excluded. This cohort of 93 children up to 3 years of age was divided into 10 groups based on the age at testing (upper limits of: 1 week; 1, 2, 4, 6, 8, 10 and 12 months; 2 years; and 3 years of age). Evolution of peak latency, interpeak latency and amplitude of waveforms in BAEP and MLAEP were demonstrated. We concluded that measurement of BAEP and MLAEP is feasible in children, as early as the first few months of life. The combination of both MLAEP and BAEP may increase the diagnostic sensitivity of neurophysiologic assessment of the integrity or functional status of both the peripheral (acoustic nerve) and the central (brainstem, subcortical and cortical) auditory conduction systems in young children with developmental speech and language disorders.     

Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave-T complex).

OBJECTIVES: Auditory processing at the cortical level was investigated with late auditory evoked potentials (N1 wave-T complex) in 4-8-year-old autistic children with mental retardation and compared to both age-matched normal and mentally retarded children (16 children in each group). METHODS: Two negative peaks which occurred in the 80-200 ms latency range were analyzed according to stimulus intensity level (50 to 80 dB SPL): the first culminated at fronto-central sites (N1b) and the second at bitemporal sites (N1c, equivalent to Tb of the T complex). The latter wave was the most prominent and reliable response in normal children at this age. RESULTS: Our results in autistic children indicated abnormalities of this wave with markedly smaller amplitude at bitemporal sites and pronounced peak latency delay (around 20 ms). Moreover, in both reference groups the intensity effect was found on both sides whereas in autistic children it was absent on the left side but present on the right. CONCLUSION: These findings in autistic children showing very disturbed verbal communication argue for dysfunction in brain areas involved in N1c generation i.e., the auditory associative cortex in the lateral part of the superior temporal gyrus, with more specific left side defects when auditory stimulus have to be processed.     

Brainstem auditory evoked response and subcortical abnormalities in autism

Previous studies of the neurobiology of autism that have used the brainstem auditory evoked response have given contradictory results. The authors of this study considered two supplementary aspects; they added an ipsilateral masking procedure, and they compared the results for every subject to the values (corrected for age and sex) of a large number of normal children. Twenty autistic (according to DSM-III-R criteria) and 13 mentally retarded (nonverbal IQ less than 75) subjects were assessed. Eighty percent of the autistic subjects had abnormal interpeak latencies, compared to 15% of the mentally retarded subjects. The I-V and III-V prolonged interpeak latency values were seen only in the autistic subjects. The ipsilateral masking procedure doubled the rate of detection of higher-brainstem abnormalities in the autistic children.     

Auditory sensory processing in autism: a magnetoencephalographic study.

BACKGROUND: Patients with autism show clinical features suggestive of abnormal processing of auditory and other sensory information. We hypothesized that low-functioning autistic subjects present abnormalities in discriminating simple auditory stimuli at sensory system preconscious stages of cortical processing. METHODS: To verify our hypothesis, we used magnetoencephalographic measurements of mismatch field (MMF), which reflects the detection of a change in the physical characteristics of a repetitive sound. Fourteen patients (aged 8-32 years) who met DSM-IV diagnostic criteria for autistic disorder participated in an auditory oddball experiment. Ten healthy participants matched for age and gender acted as control subjects. RESULTS: Significant differences in cerebral responses between patients and control subjects were recorded. Whereas control subjects showed a clearly identifiable MMF, with distinct generators in the M100 brain wave with regard to latency, position, and strength, no identifiable MMF was present in the autistic group. CONCLUSIONS: Our findings suggest that low-functioning autistic subjects present a dysfunction at preconscious stages of cortical auditory discrimination, playing a role in the abnormal processing of auditory sensory afferences. The attention independence of the MMF allows for exclusion of an effect related to impaired attention or task-related responses.     

Delayed magnetic mismatch negativity field, but not auditory M100 response, in specific language impairment

Recent studies show that electrophysiological markers of auditory processing such as the cortical 100 ms response (M100) and the mismatch field, derived from magnetoencephalography, might be used to identify children with autism spectrum disorders--M100 peak latency--and to stratify children with autism according to the degree of language impairment--mismatch field peak latency. The present study examined the latency of right superior temporal gyrus M100 and mismatch field in a cohort of children and young adolescents with specific language impairment (n=17), in comparison with age-matched and nonverbal intelligence quotient-matched typically developing controls (n=21). Neither group showed symptoms associated with autism. Although M100 latency (reflecting early auditory processing) did not distinguish controls from children with specific language impairment, the later 'change detection' mismatch field response was significantly delayed (by >50 ms) in the specific language impairment group. Linear discriminant analysis confirmed the role of mismatch field latency (92%) but not M100 latency (8%) in distinguishing groups. The present results lend support to the claim that a delayed M100 is specific to autism spectrum disorders (with relative independence of degree of language impairment) and that a delayed mismatch field reflects an abnormality more generally associated with language impairment, suggesting that mismatch field delay in the present specific language impairment group and previously reported in autistic children with language impairment may be indicative of a common neural system dysfunction.     

Brain stem auditory evoked potentials in the normal and autistic child

From a neurophysiological viewpoint a hypothesis for the etiology of early infantile autism suggests that the symptoms are a result of abnormalities in processing sensory input at the level of the brain-stem. The methods for recording auditory evoked responses (BAERs) seemed particularly well suited to study a failure at this level. BAERs to brief monaural and binaural stimulation were studied in 17 autistic children ranging in age from 3 to 9 years (mean = 6.1). They were age and sex matched to normal controls. Electrodes were placed at the vertex and at the mastoid ipsilateral to the stimulation. Signals were amplified 10(5) using an amplifier with bandpass filters set at 160 Hz and 3 kHz. Stimuli were clicks (120 microsec) delivered to subjects through earphones at 2 intensities: 70 and 90 dB. Stimuli were presented in blocks of 3000 clicks (1500 clicks for each intensity) with a rate of 10/sec. No sedative medication was used. There was no difference between autistic and normal children for the latencies of peak I. Latencies of peaks II, III, IV and V were found to be shorter in autistic than in normal children. The I-II and II-III interpeak transmission times were significantly decreased in the autistic group, but not III-V interpeak transmission time. Autistic children showed V-VN amplitude greater than normal children. Our findings suggest that in the autistic syndrome, there is a defect of the modulation processing input related to intensity at brain-stem level.     

脑干听觉诱发电位在听阈正常的语言发育迟缓患儿中的意义

目的 探讨脑干听觉诱发电位（BAEP）在听阈正常而语言发育迟缓患儿中的变化规律及应用价值.方法 分析100例听阈正常而语言发育迟缓患儿BAEP的变化规律;按年龄分组比较两个年龄段之间各波的延长时间.结果 （1）BAEP正常10例,异常90例,BAEP表现为Ⅰ、Ⅴ波潜伏期（PL）延长,Ⅲ~Ⅴ、Ⅰ~Ⅴ波峰间期（IPL）延长;（2）随着年龄增长,Ⅴ波PL与Ⅲ~Ⅴ波IPL延长时间越长.结论 Ⅰ波、Ⅴ波延长对早期诊断听阈正常而语言发育迟缓患儿具有一定的意义,说明即使听阈正常也可能存在听觉传导通路异常,且随着年龄增加,脑干上段受损越严重.     

Auditory brainstem responses in 10 inbred strains of mice

The auditory brainstem response (ABR) is an evoked potential response of auditory activity in the auditory nerve and subsequent fiber tracts and nuclei within the auditory brainstem pathways. The threshold, amplitude, and latency analysis of the ABR provides information on the peripheral hearing status and the integrity of brainstem pathways. In this study, we compared the threshold, amplitude, and latency of ABRs recorded from 149 mice of 10 commonly used inbred strains (BALB/cJ, C3HeB/FeJ, C3H/HeJ, CAST/EiJ, CBA/CaJ, CBA/J, FVB/NJ, MRL/MpJ, NZB/BlNJ, and SJL/J) using clicks of different intensities. The ABR thresholds of these strains ranged from 32 to 43 dB SPL. The amplitude of both waves I and IV of ABRs, which increased monotonically with click intensity in most strains, differed significantly among different strains at each intensity tested. Moreover, the amplitude of both waves was inversely correlated with the body weight of each strain at most intensities tested. In general, the amplitude of wave IV was smaller than that of wave I resulting in the IV/I amplitude ratio of <1.0 in all strains. The peak latency of both waves I and IV decreased significantly with click intensity in each strain. However, this intensity-dependent decrease was greater for wave IV than for wave I such that the wave I-IV inter-peak latency also decreased significantly with increasing intensity. I-IV inter-peak latencies for MRL/MpJ, C3HeB/FeJ, NZB/BlNJ, and C3H/HeJ strains are longer than FVB/NJ, SJL/J, or CAST/EiJ. This work is the first step to study the genetic basis underlying strain-related differences in auditory pathway.     

Reduced P3 amplitude of the event-related brain potential: Its relationship to language ability in austism

Several studies have found that P3 amplitude of the auditory event-related potential is smaller in autistic than in normal children. The present study investigated whether this characteristic bears any relationship to the degree of language impairment and/or level of intellectual ability of autistic persons. Seventeen autistic children, ranging from 8–19 years of age, and 17 age- and gender-matched normal children participated. Event-related potentials to phonetic (Da) and chord (piano) stimuli were recorded from three scalp locations: vertex (Cz), right hemisphere (RH), and left hemisphere (LH), during a discrimination task. A battery of language tests was given to autistic children. Compared to normal subjects, autistic subjects showed a significantly smaller P3 amplitude to phonetic stimuli for Cz and LH recording sites. However, no group difference in P3 amplitude to the phonetic stimulus was found for the RH. Furthermore, no group differences in P3 amplitude were found for the chord stimulus at any recording site. Impaired language ability was related to greater RH P3 amplitude, particularly to the chord stimulus. The possibility of differential hemispheric involvement in the attentional deficits of autistic children is raised.The present study was supported by National Institute of Mental Health Grant No. MH33612 awarded to Geraldine Dawson. The authors thank the autistic children and their families, and the staff at Division TEACCH for their many hours of cooperation. Drs. Harold Pillsbury and Grady Thomas, Department of Surgery, School of Medicine, UNC-CH, generously made available the auditory evoked-response equipment and laboratory. Teresa Frei, Mary Evers, Karen Cotten, Mary Hyde, and Joan Keyser assisted in data collection and scoring. Faulder Colby and Chris Gullion helped with data analyses. Clarrisa Brame, Sallie McCarthy, and Kathrinn Fitzpatrick provided secretarial support.     

Effect of early onset otitis media on brainstem and cortical auditory processing

Background

Otitis media (OM) leads to significant reduction in the hearing sensitivity. The reduced auditory input, if in the early years of life when the auditory neural system is still maturing, may adversely influence the structural as well as functional development of the system. Past research has reported abnormalities in both the structure and function of brainstem nuclei following auditory deprivation, but, it has not necessarily focused on children who had OM in their first year of life. It can also be said that if auditory processing is affected at the brainstem level because of early onset OM (reduced auditory input in the crucial periods of neural development), then, it may be said that auditory processing is also affected at the cortical level because it receives distorted input from the brainstem. Therefore, the purpose of this study was to document the effects of early onset OM on auditory processing, if any, at the brainstem as well as at cortical levels. A related purpose of the study was to investigate the persistence of the effects of early onset OM, if any, on auditory processing.

Methods

A cross sectional approach and a standard group comparison design was used in the study. Thirty children, who had OM between 6 and 12 months of age and who were in the age range of 3.1 – 5.6 years participated in the study. Children with OM were divided into 3 groups based on their age. Click evoked auditory brainstem responses (ABRs) and late latency responses (LLRs) were recorded from these children, and the responses were compared with those from age and gender matched normal children without any history of OM. The data from the 2 groups was statistically analyzed through independent t test. Pearson's Product Moment correlation was computed to examine the relationship between results of ABR and LLR in children with early onset OM.

Results

The mean central conduction time was significantly increased and the mean amplitude of wave I and III of ABRs was significantly reduced in children with early onset OM compared to normal children. Also, the latency of all LLR waves was significantly less in children with early onset OM than in normal children. However, significant differences in mean values of either ABR or LLR (latencies or interwave intervals as the case may be) were observed only in 3-year old children. There was a significant, but negative association between central conduction time and latency of LLRs.

Conclusion

OM in the first year of life leads to negative effects on brainstem signal processing even if it has occurred only for a short duration (maximum of 3 months). In such a situation, auditory cortical structures probably show compensatory changes through central gain to offset the prolonged central conduction time. Although the results of the present study showed that the negative effects of early onset OM (occurring in the first year of life) on auditory processing disappeared by the time the children were 4.1 years, there is need for longitudinal studies on this to confirm the findings.     

Functioning of the brain-stem auditory pathway in non-retarded autistic individuals

Functioning of auditory brain-stem pathways was examined in non-retarded autistic individuals (14-28 years of age). Functioning was assessed by recording ERPs (event-related brain potentials) generated by these auditory pathways. These ERPs were evoked by click stimuli and occurred within the first 8 msec following the onset of the click. To assess the ability of these early auditory pathways to process sensory stimuli of varying characteristics, we systematically varied click intensity, rate of stimulation, ear of stimulation, and polarity of clicks. The results show that non-retarded autistic individuals have normal functioning of the brain-stem auditory pathways which generate these ERPs: every autistic subject had normal ERPs. So, disorder in auditory brain-stem pathways which generate these ERPs is not necessary for autism to occur. The dysfunctioning neural systems directly responsible for autism in non-retarded individuals must be sought elsewhere. Ten of the autistic subjects in this study, whom we found to have normal auditory brain-stem ERPs, had previously been found to have abnormalities in longer latency cognitive ERP components (Courchesne et al. 1984, 1985). We conclude, therefore, that those abnormalities in longer latency components are not the downstream consequences of abnormalities in the structures generating the auditory brain-stem ERPs recorded in the present study.     

Effect of stimulus intensity variation on brain-stem auditory evoked potentials: comparison between neonates and adults

Brain auditory evoked potentials (BAEPs) were recorded from 40 adult subjects and 40 neonates at 80 and 60 dB (nHL) to compare the effects of stimulus intensity variation on waves I, III and V and on intervals I-III, III-V and I-V. The results show that the changes in latency for wave, I, I-III and I-V intervals are significantly greater in neonates than in adults. So the effects of stimulus intensity variation on BAEPs are different in neonates and in adults and a major effect is in the peripheral auditory mechanism.     

Auditory brain-stem response in zitter rats with genetic spongiform encephalopathy.

Zitter rats with genetic spongiform encephalopathy and hypomyelination developed an abnormal auditory brain-stem response (ABR) before the appearance of spongy lesions in the central nervous system (CNS). The ABR abnormalities were characterized by a dual peak of wave I, with a longer latency than in normal rats, and decreased or absent waves III and IV. Hypomyelination in both peripheral and central nerves may have been responsible for these abnormalities. The slow negative wave became wide and obscure with aging. These changes accompanied age-dependent progression of spongy changes in the CNS. These findings suggest that at least two mechanisms, one involving hypomyelination and the other causing spongy lesions, are responsible for the brain-stem auditory pathway dysfunction in zitter rats.     

Phonological investigation of verbal autistic and mentally retarded subjects

A review of the pertinent literature indicates that autistic children are likely to show normal but delayed development of speech sounds. In contrast, atypical phonological development is suggested by experiments demonstrating that autistic subjects are deficient in their ability to extract the components of structured auditory input. A systematic investigation of the speech sound systems of verbal autistic and mentally retarded children reveals a delay in phoneme acquisition, as well as a relative uniformity of error types in both groups. The autistic subjects, however, differ significantly from the mentally retarded in the phonemic substitutions which they make. Autistic subjects are also characterized by a high correlation between frequency of phonological errors and level of overall language development. The findings are interpreted as supporting the hypothesis that the autistic group shows a more global delay in language development.This investigation was supported by Grant MA-5525, Medical Research Council, Ottawa, Ontario, Canada. It was supported previously for a period of three months by the Ontario Ministry of Health, Project No. PR 474C. Subjects were provided by the Ontario Society for Autistic Children, the Thistletown Regional Centre, Rexdale, Ontario, and the Hamilton Public School System. Gail Martin assisted in the coordination of this study. Informed consent was obtained from the parents of the children following explanation of the procedures used in our work.     

Prolonged brainstem transmission time in autism

Brainstem auditory evoked potentials (BAEPs) to clicks presented monaurally were gathered for 16 institutionalized children with a prior diagnosis of autism and with no hearing loss as tested by standard audiometry. Twenty age-matched normal children served as controls. Brainstem transmission time, defined as BAEP interpeak I-V latency, was prolonged significantly on the average in the autistic sample on both left and right sides. Individually, BAEPs for 9 of the 16 autistic children (or 56%) on whom some electrophysiological data were gathered were classified as abnormal when compared to the norms established in the control group. The most common BAEP abnormality was a prolonged interpeak III-V latency on the left side.     

Autism: processing of novel auditory information assessed by event-related brain potentials

Event-related brain potentials (ERPs) of 13-21-year-old autistic subjects and age-matched controls were elicited by auditory stimuli in a variation of orienting response paradigms. Unexpected, novel sounds (bizarre concoctions of human, mechanical and computer sounds) were randomly inserted as probes in a sequence of expected, non-novel sounds (the word 'me'). In order to help ensure that both subject groups were attending to this stream of information, each subject was required to press a button to a specified target sound (the word 'you') also randomly inserted in the sequence of expected non-novel sounds. The ERP results showed that in both groups, unexpected, novel probes and also targets evoked a different neurophysiological response than did expected, non-novel sounds. This suggests that the autistic group did not misperceive novel information as non-novel and were able to make simple classification decisions as accurately as normal controls. However, in the autistic group, there may be less 'processing' of the novel probes and of targets: compared to the control group, the autistic group had smaller amplitudes of two long-latency components to novels and smaller P3b amplitudes to targets. The two components to novels were termed A/Pcz/300 (A = auditory; P = positive; cz = electrode site of maximum amplitude; 300 = latency in msec) and A/Ncz/800. In another sequence of sounds, subjects simply listened to frequently presented 'me' sounds (90%) and infrequently presented 'you' sounds (10%). In this no-task condition, no differences between autistic and normal control subjects were found.     

Effect of noise masking on the brain-stem and middle-latency auditory evoked potentials: central and peripheral components

Brain-stem (BAEP) and middle-latency (MLAEP) auditory evoked potentials were recorded in zero noise and in 3 levels of continuous ipsilateral broadband noise. New information is presented on the effects of noise on BAEP wave I. Latency of wave I was not changed by increasing noise, but wave V latency linearly increased. Amplitude of waves I and V decreased non-linearly. The amplitude decrease was equivalent for both waves and occurred only at the higher noise levels. The dissociation of latency effects for waves I and V indicates a central component for the effect of noise on latency. The parallel amplitude change for waves I and V suggests a largely peripheral component. The MLAEP Pa latency also increased with increasing noise further supporting a central mechanism.     

The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects.

OBJECTIVE: In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two automatic components of the auditory event-related potentials (ERPs): the mismatch negativity (MMN)--a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced--and the novelty-related P3a which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli. METHODS: Ten male subjects, mean age 12.3 years (SD 4.95), affected by autism and mental retardation were admitted to this study. All patients were also mentally retarded. Ten normal male subjects, mean age 12.2 years (SD 3.94), were used as controls. Auditory evoked potentials were recorded from 19 scalp electrodes (10-20 system), and stimuli were presented in sequences consisting of 2000 tones (70 dB, ISI=800 ms). Three types of stimuli were presented: (1) standard stimuli (1000 Hz tones, 80% of total stimuli), (2) deviant stimuli (1300 Hz tones, 10% of total stimuli), and (3) novel stimuli (complex and non-monotonal, 10% of total stimuli). To quantify the MMN, the evoked response to the standard tones was subtracted from the corresponding deviant stimulus response and its amplitude and latency at peak were measured over Fz, Cz and Pz; similarly, the P3a component of the ERP was obtained by subtracting the response to the standard tone from that to the novel stimuli and its amplitude and latency at peak were measured over Fz, Cz and Pz. Also, the amplitude and latency at peak for the N1 component of the auditory evoked potential obtained with the standard stimuli were measured over Fz, Cz and Pz. The correlation between age and MMN and P3a amplitude was also analyzed. RESULTS: N1 showed significantly shorter latencies in the autistic groups. MMN elicited by deviant stimuli, but not that elicited by novel stimuli, was found to be significantly larger in autistic children than in normal controls. P3a showed higher amplitude in autistic subjects than in normal controls during childhood; the opposite was observed during young adulthood. DISCUSSION: Our findings indicate that significant changes in ERPs can also be seen in non-cooperative individuals with autism and mental retardation, which might be different from the changes already reported for high-functioning autistic subjects and deserve further insight. These changes show developmental modifications that should be taken into consideration when analyzing data from autistic subjects.