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Cortical auditory evoked potentials in autism: a review
International Journal of Psychophysiology 53 (2004) 161 – 169 www.elsevier.com/locate/ijpsycho
Review
Cortical auditory evoked potentials in autism: a review Marie D. Bomba a, Elizabeth W. Pang a,b,* a
Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada b University of Toronto, Toronto, ON, Canada
Received 20 November 2003; received in revised form 29 January 2004; accepted 1 April 2004 Available online
Abstract The question of etiology in autism remains elusive primarily due to the fact that autism does not result from a single dysfunction but is multi-faceted in nature. Investigations into etiology have ranged from identifying abnormalities in the genome to describing structural/functional brain abnormalities. Bearing in mind the risk of over-simplification, there is still utility in isolating a specific deficit to examine its etiologic contribution. It is known that individuals with autism have difficulty processing auditory information at the cortical level but this is not consistently seen subcortically. In recent years, cortical auditory processing has been extensively researched using event-related potentials (ERPs); however, these results in relation to autism have not been reviewed. This paper will examine this literature and discuss implications for future research. D 2004 Elsevier B.V. All rights reserved. Keywords: Auditory; Autism; Cortical evoked potentials; Event-related potentials (ERP); N1; Mismatch negativity (MMN); P3; Review
1. Introduction Kanner (1943) first described autism as a disorder encompassing abnormal social reciprocity, abnormal language use, and an intense desire for sameness. Sixty years later, this description still captures the essence of autistic behavior (Tager-Flusberg et al., 2001) although the etiology of this disorder remains unknown. This elusive issue of etiology is likely due to the fact that autism does not result from a single dysfunction or deficit. Consequently, attempts to elucidate the underlying causes of autism have ranged from identifying abnormalities in the genome to * Corresponding author. Division of Neurology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.: +1-416-813-6548; fax: +1-416-813-6334. E-mail address: [email protected] (E.W. Pang). 0167-8760/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpsycho.2004.04.001
describing structural/functional abnormalities in the brain (Bauman, 1996; Rapin, 1995; Rapin and Katzman, 1998; Spence, 2001; Tager-Flusberg et al., 2001). Despite the multi-faceted nature of autism, there is still utility in isolating a specific deficit to examine its etiologic contribution. For instance, clinical and research observations in autism indicate defective processing of incoming auditory and verbal stimuli (Hoffmann and Prior, 1982; Lockyer and Rutter, 1970; Novick et al., 1980; Ornitz, 1974; Rutter, 1979). Data from evoked potential studies indicate that individuals with autism have difficulties in the cognitive processing of auditory information despite intact basic sensory perception (Minshew, 1996). There is increasing evidence that abnormal cortical processing of auditory stimuli is one of the core deficits in autism. While substantial strides in our understanding of cortical auditory processing have
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been made, the relationship between auditory cortex function and autism has not been reviewed. In this comprehensive review, we will describe past neurophysiological findings related to autism in order to highlight patterns, inconsistencies, and directions for future studies. Our discussion will be broadly separated into sub-cortical and cortical auditory components, and then specifically, the BAEP, MLR, P1, P2, Nc, N1, P3, T-Complex, MMN and Nd waveforms will be defined and discussed in turn.
2. Sub-cortical auditory processing Auditory stimuli generate signals that are transmitted through the brainstem to the thalamus and into auditory cortex. The relationship between autism and brainstem auditory evoked responses (BAEP/BAER/ABR) has been examined and it is generally accepted that although brainstem abnormalities may be present, they are not necessary for the emergence of autism since many individuals with autism display normal BAEPs (see review: Klin, 1993; Rosenhall et al., 2003). In addition, when BAEPs are impaired, the abnormality might not be specific to autism. For example, prolonged BAEPs have been associated with other nonspecific delays including language development with or without mental retardation (Lahat et al., 1995; Purvis and Tannock, 1997; Zafeiriou et al., 2000). Studies continue to demonstrate equivocal findings and now emphasize the likelihood that BAEP abnormalities are subtle and probably useful for characterizing autistic subgroups (Maziade et al., 2000; McClelland et al., 1992; Rosenhall et al., 2003; Thivierge et al., 1990; Wong and Wong, 1991), and possibly their first-degree relatives (August et al., 1981; Nagy and Loveland, 2002; Plumet et al., 1995). Despite valiant, large-scale efforts (e.g. Maziade et al., 2000; Rosenhall et al., 2003), the relationship between BAEPs and autism has not yet been clearly delineated. This is not surprising given that autism is a complex, genetic disorder with multiple and/or interacting causal factors. Another subcortical response that has been studied in individuals with autism is the Mid-Latency Auditory Response (MLR). The MLR reflects transmission of the auditory signal through the thalamus
and into primary auditory cortex (Picton et al., 1974; Woods et al., 1987). Like the BAEP, MLRs have been shown to be normal in adults with autism (Buchwald et al., 1992; Grillon et al., 1989) suggesting that in at least some subtypes of autism, auditory processing dysfunction at the subcortical level is not a necessary condition for autistic symptomology. Having said this, it is important to clarify that other subcortical structures, not related to processing via the primary auditory pathway, have been implicated in autism. There is a body of literature, first proposed by Ornitz (1985), suggesting that autism results from dysfunctions of the brainstem – thalamic system mediating arousal and attention; since then, this has been expanded to include the cerebellum which also coordinates and controls selective attention (Courchesne et al., 1994). Given that auditory stimulation generates activity in two or more parallel central nervous system pathways (Elberling et al., 1981; Graybiel, 1973; Pantev et al., 1988; Weinberger and Diamond, 1987), and that the secondary auditory pathway receives input from the reticular activating system (RAS), a part of the brainstem – thalamic system (Erwin and Buchwald, 1986), it would not be surprising if evoked potential waveforms generated by auditory stimuli activating the RAS would show abnormalities. Examples of evoked potentials receiving RAS input are the P1, P2 and Nc waveforms. The P1 has been found to be significantly smaller in amplitude in an autistic group (Buchwald et al., 1992) and thus interpreted as indicating both a decreased sensitivity to stimuli and a dysfunctional recovery cycle in the RAS – thalamic pathway. The P2, which is sensitive to attentional levels (Picton and Hillyard, 1974), stimulus intensity, and stimulus frequency (Squires et al., 1975), shows equivocal results with regards to autism. One study using click stimuli reported smaller P2 amplitudes in adolescent males with autism (Novick et al., 1980), while two other studies, using tones (Lincoln et al., 1995) and words (Courchesne et al., 1984), reported no significant decreases. While this may be an issue of power since all three studies used fewer than 10 subjects, the role of differing arousal and attention levels cannot be ruled out. The Nc is the most extensively studied of this group of waveforms. Described in detail by Courchesne et al. (1989), it is
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known that the Nc is a cephalically recorded frontocentral negativity triggered by input from the RAS. It is modality non-specific, thought to be the earliest endogenous component to appear during human brain development, and it can be elicited from infancy through young adulthood. In individuals with autism, Nc responses were reduced or absent (see review: Courchesne, 1990). This is in line with the previous suggestion that evoked potentials generated by RASlinked systems are abnormal in autism. While subcortical generators related to auditory processing can appear normal in individuals with autism, subcortical generators related to arousal and attention (particularly the RAS) may be abnormal. For the purposes of this paper, our aim is to focus on deficits in cortical auditory processing while partitioning out other significant contributing factors such as arousal and attention. Admittedly this is a limited spotlight since auditory evoked potentials represent only one level of analysis in a multi-dimensional complex disease; however, it is hoped that this narrow concentration will shed light on one of the core aspects of autism that may lead to a better understanding of the interconnections between underlying biological causes and the observed cognitive – behavioral manifestations of this disorder.
3. Cortical auditory event-related potentials The cortical auditory evoked potentials, or eventrelated potentials (ERP), reflect activation of neural structures in auditory cortex, auditory association areas, and areas related to higher order cognitive processes such as memory. They can be approximately divided into long-latency and short-latency ERPs, where the long-latency responses reflect more cognitive, higher-level, less modality-specific processing and the short-latency ERPs reflect more basic, modality-specific processing, which can be nevertheless still sensitive to various cognitive factors. All the short-latency ERPs have at least one generator in the auditory cortex of the temporal lobe. The most extensively studied long-latency ERP is the P300. The following review will commence with a synopsis of the literature examining the P300 and autism, and then look specifically at the auditory short-latency ERPs.
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3.1. P300 The P300, P3, or P3b (see review: Picton, 1992) is a large positive waveform that occurs at approximately 300 ms after stimulus onset in adults and appears to originate in the association cortex of the parietal lobes. The P3 is modality non-specific, meaning that it can be evoked in the visual, somatosensory and auditory modalities. While this waveform generally appears 300 ms after stimulus onset, there is some variation as a function of modality, age and task. For example, the latency of the auditory P3b decreases rapidly from infancy to childhood to adolescence reflecting an increasing efficiency in information processing with maturity (Goodin et al., 1978; Ohlrich et al., 1978; Pearce et al., 1989; Polich et al., 1990). Auditory P3b amplitudes increase slightly with age, but not significantly (Johnson, 1989; Polich et al., 1990). However, in general, the P3b is elicited by cognitive parameters such as stimulus probability, meaningfulness and task relevance (Donchin, 1981). Both the auditory and visual P300 have been well-studied in normal children and adults. In the autism literature, this ERP is often termed the A/Cz/P3 (Courchesne et al., 1984, 1985) to clarify that it is the P3 evoked by auditory stimuli measured at the Cz electrode. In individuals with autism, from as young as age 5 (Oades et al., 1988) and 8 years (Dawson et al., 1988; Lincoln et al., 1993) through to adulthood, the most consistent, and frequently reported, abnormality is a P3b or A/Cz/P3 amplitude attenuation with auditory stimulus presentation. Amplitude decreases have been reported with clicks (Novick et al., 1980), tones (Ciesielski et al., 1990; Courchesne et al., 1989; Lincoln et al., 1993; Oades et al., 1988), phonemes (Dawson et al., 1988), and novel sounds (Courchesne et al., 1984, 1985, 1986) in auditory-only and auditory/visual switching tasks (Ciesielski et al., 1990; Courchesne et al., 1985, 1989) but not with musical chords (Dawson et al., 1988) nor with words (Courchesne et al., 1984, 1985, 1986; Erwin et al., 1991). P3b latency remains unaffected (Ciesielski et al., 1990; Courchesne et al., 1984, 1985, 1986, 1989; Dawson et al., 1988; Erwin et al., 1991; Lincoln et al., 1993; Novick et al., 1980; Oades et al., 1988). Three explanations are put forth for the P3b amplitude attenuation. One, the P3b is thought to reflect
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a limited capacity mechanism whereby attention is consciously allocated to specific information in the environment (Picton, 1992; Posner, 1978). Thus, the reduced P3b may reflect either a failure to allocate appropriate attention to stimuli (Holcomb et al., 1985), or, a misallocation of attentional resources to less important stimuli (Dawson et al., 1988). Evidence for this hypothesis stems from reports of P3b amplitude attenuation in a wide range of childhood disorders including ADHD (Holcomb et al., 1985), reading disorders (Dainer et al., 1981; Holcomb et al., 1985), and hyperactivity (Loiselle et al., 1980). Two, P3b amplitude is inversely related to stimulus probability (i.e. a low-probability unexpected stimulus elicits a large P3b). A smaller P3b may reflect either a difficulty in attaching significance to unexpected stimuli (Oades et al., 1988) or a defect related to the modification of expectancies based on previous experience (Lincoln et al., 1993). This may explain why individuals with autism, who have rigid expectations and thus difficulty extracting information in a way that leads to a re-integration of previously learned information (Lincoln et al., 1993), have smaller P3b’s. Three, P3 amplitude attenuations may simply be due to latency jitter. Since background EEG activity is more variable in diseased conditions compared to healthy controls, latency jitter has been suggested as a possibility for explaining the lower amplitude late components in various disorders (Regan, 1989). Interestingly, although one of the core deficits in autism is with language, and it has been suggested that individuals with autism show atypical left hemisphere activation during processing of auditory linguistic stimuli (Dawson et al., 1988), there are no hemispheric differences on P3 amplitude using word stimuli (Courchesne et al., 1984, 1985; Erwin et al., 1991). Furthermore, children, teens, and adults with receptive developmental language disorders (RDLD) did not show P3b amplitude attenuations (Courchesne et al., 1989; Lincoln et al., 1993). This dissociation in P3b response to word versus tone stimuli supports the hypothesis that autism involves basic defects in cortical auditory processing, and that the severe language disorder observed in autism may be secondary to these deficits (Novick et al., 1980). This is further supported by the finding that the P3b attenuation is specific to the auditory modality as demonstrated by negative findings for visual experiments using letters
(Courchesne et al., 1986, 1989), words (Courchesne et al., 1985) and written phrases (Strandburg et al., 1993).
4. Auditory short-latency ERP The N1 is a short-latency ERP specific to the auditory modality that reflects basic auditory processing and is well understood in adults (for review: see Na¨a¨ta¨nen and Picton, 1987) and shows extensive developmental changes (Martin et al., 1988; Pang and Taylor, 2000; Ponton et al., 2000; TonnquistUhlen et al., 1995). This complex waveform consists of several obligatory waveforms: the N1b and Tcomplex; as well as difference waveforms: the mismatch negativity (MMN) and the negative difference (Nd), all of which are thought to be generated in different neural areas. The N1 components are differentiable by the eliciting features of the stimulus, the state of the subject, and scalp distribution. 4.1. N1b The N1b, measured at the vertex and generated in the supra-temporal cortex, reflects changes in stimulus presentation and the physical properties of a stimulus. Early studies have generally reported no effect of autism on N1b amplitude and latency (Courchesne et al., 1984; Erwin et al., 1991; Kemner et al., 1995; Lincoln et al., 1995; Nakamura et al., 1986; Novick et al., 1980). However, amplitude increases (Oades et al., 1988) and decreases (Courchesne et al., 1985) in individuals with autism compared to controls have been reported. This inconsistency in results can probably be explained by the extensive developmental changes in N1b topography, amplitude and latency, which until recently were unknown (Bruneau et al., 1997; Martin et al., 1988; Pang and Taylor, 2000; Ponton et al., 2000; Tonnquist-Uhlen et al., 1995). Taking these developmental changes into account, recent studies (Bruneau et al., 1999; Seri et al., 1999) have found that N1b amplitude decreased significantly in children with autism (Bruneau et al., 1999) and in children with co-morbid tuberous sclerosis and autism (Seri et al., 1999). These findings were interpreted as an indication that autism is related to ineffective regulation of auditory sensory input.
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4.2. The T-complex (N1a/N1c) The second component of the N1, the T-complex (Wolpaw and Penry, 1975), is generated on the superior temporal gyrus by radially oriented dipoles, and is best seen at temporal electrodes (Hackley et al., 1990; Perrault and Picton, 1984). It consists of biphasic deflections: the N1a (or Ta) which reflects the activation of neural generators underlying stimulus detection, and the N1c (or Tb) which reflects generators underlying stimulus discrimination (Na¨a¨ta¨nen and Picton, 1987). In children, this waveform is the most easily observable of the N1 components and becomes less prominent with maturity (Bruneau et al., 1997; Ponton et al., 2002). In the only study examining the N1c, Bruneau et al. (1999) observed the N1c to be of smaller amplitude and longer latency in children with autism. Furthermore, the pattern of dysfunction suggests that autistic subjects process both verbal and non-verbal auditory stimuli in the right cerebral hemisphere, whereas normal subjects process verbal information in the left hemisphere only. This is consistent with other nonelectrophysiological evidence finding right hemispheric dominance in the processing of verbal and non-verbal auditory stimuli by autistic individuals (Dawson et al., 1982; Hoffmann and Prior, 1982). Taken as a whole, these results support the hypothesis of role reorganization of the left and right hemispheres for auditory processing during early brain development in individuals with autism rather than attributing dysfunction to the left hemisphere alone. 4.3. Mismatch negativity (MMN) The mismatch negativity (MMN) is a difference waveform that reflects the processing required to compare a different incoming stimulus with the neural representation already stored in transient auditory memory. This waveform is only evident when the frequently occurring stimuli are subtracted from the infrequent stimuli; without this subtraction, the MMN would not be evident. The MMN is thought to be a pre-perceptual measure of central auditory function (Na¨a¨ta¨nen, 1990). The MMN has generators on both supratemporal planes of the auditory cortices (see review: Alho, 1995) and in frontal cortex (Giard et al., 1990). The MMN is
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evoked independent of attention or response requirements, and is responsive to even minimal changes in acoustic parameters. The supratemporal MMN appears to be a neurophysiological index of the fine discrimination of acoustic features (Na¨a¨ta¨nen, 1990, 1991; Na¨a¨ta¨nen et al., 1982; Na¨a¨ta¨nen and Picton, 1987), while the frontal MMN is related to the initiation of involuntary switching of attention to stimulus changes (Giard et al., 1990). Not only is the MMN well understood in adults, it has been examined in children (Ceponiene et al., 1998; Csepe´, 1995; Kraus et al., 1993) and infants (Alho et al., 1990; Cheour et al., 1998, 2000; CheourLuhtanen et al., 1995; Kurtzberg et al., 1995). Kemner et al. (1995) reported normal latency and amplitude of the MMN in children with autism; however, they used high functioning autistic children and an unusually long ISI of several seconds which could have accounted for their results. A more recent study examining MMN in children with autism (Gomot et al., 2002) found that left hemisphere MMN peak latency was earlier in the autistic compared to the control group and the topography of the MMN differed between the groups. In the autistic group, the right hemisphere showed the supratemporal MMN component, whereas the left temporal MMN was shortened by the appearance of an abnormal deviance-related positivity in left pre-frontal cortex, generated by non-primary thalamo-cortical projections (Martinez-Moreno et al., 1987; Kraus et al., 1994; Yago et al., 2001). Although the RAS is not specifically mentioned, it has been suggested that this parallel pathway results in a higher cerebral reactivity to the deviancy that allows children with autism to become hypersensitive to acoustic changes. Further support for this idea stems from a recent study by Ferri et al. (2003) who compared the MMN in males between the ages of 6 and 19 with a diagnosis of autism and mental retardation to healthy age-matched controls. They found that the MMN amplitude of the autistic group was significantly enhanced and occurred at a shorter latency, but only to the deviant stimuli, thus, their results support a dysfunction that influences the pre-perceptual processing of auditory sensory information. Two studies have examined children with different sub-types of autism. Seri et al. (1999) studied children with autism within a sub-group of children with
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tuberous sclerosis and found a significantly lower MMN amplitude with longer latency in the children with autism. Based on these results, they suggested that it is likely that children with autism have some difficulty encoding information into transient memory. Research at the other end of the autism spectrum reported very similar findings. Jansson-Verkasalo et al. (2003) demonstrated longer MMN latencies in children with Asperger’s Syndrome to both tones and speech sounds. This delayed MMN finding was present in both cerebral hemispheres to tone stimuli and only in the right hemisphere to speech stimuli. They interpreted this as an indication of auditory discrimination difficulties probably resulting from faulty transient memory encoding mechanisms. Furthermore, the asymmetry in hemispheric abnormalities to the different types of stimuli support the idea that autism etiology may encompass either impaired right hemisphere functioning or abnormal interhemispheric specialization. 4.4. Negative difference (Nd) The negative difference (Nd) waveform is thought to be related to selective attention. Like the MMN, the Nd is obtained from a subtraction. In this case, subjects in a dichotic listening paradigm are instructed to attend to a stimulus stream in one ear, and the ERP from the attended stimuli are subtracted from the unattended stimuli. Nd latency is sensitive to changes in inter-stimulus interval and ease of discriminability between attended and unattended stimuli (Hansen and Hillyard, 1980; Na¨a¨ta¨nen and Picton, 1987). To date, only one study (Ciesielski et al., 1990) has examined the Nd in individuals with autism. This study reports that despite normal performance on the tasks, the Nd waveform was absent in individuals with autism; however, the authors conclude that this does not necessarily reflect an inability to select, rather, individuals with autism may be using different mechanisms not measured by the Nd.
5. Conclusion With the exception of the P3, research on other long-latency cortical ERPs in autism has been sparse and results are often inconsistent. This may be due, in
part, to the diagnostic and identification issues surrounding autism. With the current opinion that autistic symptomology can be described along a spectrum, it is crucial that future studies set stricter criterion to delineate autistic subtypes for examination. As well, with recent discoveries that cortical ERPs undergo extensive developmental changes into the teenage years, some of the inconsistencies reported in the data may simply be due to non-controlled developmental changes. However, whether developmental or chronological age-matching for controls is more important is still unclear and this answer may depend on the types of paradigms used. To date, results from ERP studies that have controlled for diagnostic and developmental issues are very promising. To summarize, it has been suggested that the N1b may reflect ineffective regulation of auditory sensory input in autism (Bruneau et al., 1999; Seri et al., 1999). Measurements of the Tcomplex N1 support the hypothesis that autism may affect auditory processing by reorganizing the roles of the left and right hemispheres (Bruneau et al., 1999). Furthermore, MMN studies suggest that children with autism may have difficulty encoding information in transient memory (Gomot et al., 2002; Jansson-Verkasalo et al., 2003; Seri et al., 1999), while the Nd suggests that autism may affect selective attention (Ciesielski et al., 1990). Admittedly, these are single studies with small sample sizes; however, this body of literature does indicate that the examination of cortical auditory ERPs (i.e. the N1b, T-complex, MMN, and Nd) holds great potential for contributing to our knowledge of autism, and eventually, for shedding light on our understanding of the pathogenesis and etiology of this disease. References Alho, K., 1995. Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. Ear Hear. 16, 38 – 51. Alho, K., Sainio, K., Sajaniemi, N., Reinikainen, K., Na¨a¨ta¨nen, R., 1990. Event-related brain potential of human newborns to pitch change of an acoustic stimulus. Electroencephalogr. Clin. Neurophysiol. 77, 151 – 155. August, G.J., Stewart, M.A., Tsai, L., 1981. The incidence of cognitive disabilities in the siblings of autistic children. Br. J. Psychiatry 138, 416 – 422. Bauman, M.L., 1996. Brief report: neuroanatomic observations of
M.D. Bomba, E.W. Pang / International Journal of Psychophysiology 53 (2004) 161–169 the brain in pervasive developmental disorders. J. Autism Dev. Disord. 26, 199 – 203. Bruneau, N., Roux, S., Guerin, P., Barthe´le´my, C., Lelord, G., 1997. Temporal prominence of auditory evoked potentials (N1 wave) in 4 – 8 year old children. Psychophysiology 34, 32 – 38. Bruneau, N., Roux, S., Adrien, J.L., Barthe´le´my, C., 1999. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave – T Complex). Clin. Neurophysiol. 110, 1927 – 1934. Buchwald, J.S., Erwin, R., Van Lancker, D., Guthrie, D., Schwafel, J., Tanguay, P., 1992. Midlatency auditory evoked responses: P1 abnormalities in adult autistic subjects. Electroencephalogr. Clin. Neurophysiol. 84, 164 – 171. Ceponiene, R., Cheour, M., Na¨a¨ta¨nen, R., 1998. Interstimulus interval and auditory event-related potentials in children: evidence for multiple generators. Electroencephalogr. Clin. Neurophysiol. 108, 345 – 354. Cheour, M., Alho, K., Ceponiene´, R., Reinikainen, K., Sainio, K., Pohjavuori, M., Aaltonen, O., Na¨a¨ta¨nen, R., 1998. Maturation of mismatch negativity in infants. Int. J. Psychophysiol. 29, 217 – 226. Cheour, M., Leppanen, P.H., Kraus, N., 2000. Mismatch negativity (MMN) as a tool for investigating auditory discrimination and sensory memory in infants and children. Clin. Neurophysiol. 111, 4 – 16. Cheour-Luhtanen, M., Alho, K., Kujala, T., Sainio, K., Reinikainen, K., Renlund, M., Aaltonen, O., Eerola, O., Na¨a¨ta¨nen, R., 1995. Mismatch negativity indicates vowel discrimination in newborns. Hear. Res. 82, 53 – 58. Ciesielski, K.T., Courchesne, E., Elmasian, R., 1990. Effects of focused selective attention tasks on event-related potentials in autistic and normal individuals. Electroencephalogr. Clin. Neurophysiol. 75, 207 – 220. Courchesne, E., 1990. Chronology of postnatal human brain development: ERP, PET, myelinogenesis, and synaptogenesis studies. In: Rohrbaugh, R., Parasuraman, R., Johnson, R. (Eds.), EventRelated Brain Potentials: Basic Issues and Applications. Oxford, New York, NY, pp. 210 – 241. Courchesne, E., Kilman, B.A., Galambos, R., Lincoln, A.J., 1984. Autism: processing of novel auditory information assessed by event-related brain potentials. Electroencephalogr. Clin. Neurophysiol. 59, 238 – 248. Courchesne, E., Lincoln, A.J., Kilman, B.A., Galambos, R., 1985. Event-related brain potential correlates of the processing of novel visual and auditory information in autism. J. Autism Dev. Disord. 15, 55 – 76. Courchesne, E., Lincoln, A.J., Kilman, B.A., Galambos, R., 1986. Visual and auditory ERPs in autism. In: McCallum, W.C., Zappoli, R., Denoth, F. (Eds.), Cerebral Psychophysiology: Studies in Event-Related Potentials. Electroenceph. Clin. Neurophys., Suppl., vol. 38. Elsevier, Amsterdam, pp. 446 – 448. Courchesne, E., Lincoln, A.J., Yeung-Courchesne, R., Elmasian, R., Grillon, C., 1989. Pathophysiologic findings in nonretarded autism and receptive developmental disorder. J. Autism Dev. Disord. 19, 1 – 17. Courchesne, E., Townsend, J.P., Ashoomoff, N.A., Yeung-Courchesne, R., Press, G.A., Murakami, J.W., Lincoln, A.J., James,
167
H.E., Saitoh, O., Egaas, B., Haas, R.H., Schreibman, L., 1994. A new finding: Impairment in shifting attention in autistic cerebellar patients. In: Broman, S.H., Grafman, J. (Eds.), Atypical Cognitive Deficits in Developmental Disorders: Implications for Brain Function. Lawrence Erlbaum, Hillsdale, NJ, 101 – 137. Csepe´, V., 1995. On the origin and development of the mismatch negativity. Ear Hear. 16, 91 – 104. Dainer, K.B., Klorman, R., Salzman, L.F., Hess, D.W., Davidson, P.W., Michael, R.L., 1981. Learning disordered children’s evoked potentials during sustained attention. J. Abnorm. Child Psychol. 9, 79 – 94. Dawson, G., Warrenburg, S., Fuller, P., 1982. Cerebral lateralization in individuals diagnosed as autistic in early childhood. Brain Lang. 15, 353 – 368. Dawson, G., Finley, C., Phillips, S., Galpert, L., Lewy, A., 1988. Reduced P3 amplitude of the event-related brain potential: its relationship to language ability in autism. J. Autism Dev. Disord. 18, 493 – 504. Donchin, E., 1981. Surprise!... Surprise? Psychophysiology 18, 493 – 513. Elberling, C., Bak, C., Kofoed, B., Lebech, J., Saermark, K., 1981. Auditory magnetic fields from the human cortex. Influence of stimulus intensity. Scand. Audiol. 10, 203 – 207. Erwin, R., Buchwald, J.S., 1986. Midlatency auditory evoked responses: differential effects of sleep in the human. Electroencephalogr. Clin. Neurophysiol. 65, 383 – 392. Erwin, R., Van Lancker, D., Guthrie, D., Schwafel, J., Tanguay, P., Buchwald, J.S., 1991. P3 responses to prosodic stimuli in adult autistic subjects. Electroencephalogr. Clin. Neurophysiol. 80, 561 – 571. Ferri, R., Elia, M., Agarwal, N., Lanuzza, B., Musumeci, S.A., Pennisi, G., 2003. The mismatch negativity and the P3a components of the auditory event-related potentials in autistic lowfunctioning subjects. Clin. Neurophysiol. 114, 1671 – 1680. Giard, M.-H., Perrin, F., Pernier, J., Bouchet, P., 1990. Brain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study. Psychophysiology 27, 627 – 640. Gomot, M., Giard, M-H., Adrien, J-L., Barthelemy, C., Bruneau, N., 2002. Hypersensitivity to acoustic change in children with autism: electrophysiological evidence of left frontal cortex dysfunctioning. Psychophysiology 39, 577 – 584. Goodin, D.S., Squires, K.C., Henderson, B.H., Starr, A., 1978. Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Electroencephalogr. Clin. Neurophysiol. 44, 447 – 458. Graybiel, A.M., 1973. The thalamo-cortical projection of the socalled posterior nuclear group: a study with anterograde degeneration methods in the cat. Brain Res. 49, 229 – 244. Grillon, C., Courchesne, E., Akshoomoff, N., 1989. Brainstem and middle latency auditory evoked potentials in autism and developmental language disorder. J. Autism Dev. Disord. 19, 255 – 269. Hackley, S.A., Woldorff, M., Hillyard, S.A., 1990. Cross-modal selective attention effects on retinal, myogenic, brainstem and cerebral evoked potentials. Psychophysiology 27, 195 – 208. Hansen, J.C., Hillyard, S.A., 1980. Endogenous brain potentials
168
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associated with selective attention. Electroencephalogr. Clin. Neurophysiol. 49, 277 – 290. Hoffmann, W.L., Prior, M.R., 1982. Neuropsychological dimensions of autism in children: a test of the hemispheric dysfunction hypotheses. J. Clin. Neuropsychol. 4, 27 – 41. Holcomb, P.J., Ackerman, P.T., Dykman, R.A., 1985. Cognitive event-related brain potentials in children with attention and reading deficits. Psychophysiology 22, 656 – 667. Jansson-Verkasalo, E., Ceponiene, R., Kielinen, M., Suominen, K., Ja¨ntti, V., Linna, S.-L., Moilanen, I., Na¨a¨ta¨nen, R., 2003. Deficient auditory processing in children with Asperger Syndrome, as indexed by event-related potentials. Neurosci. Lett. 338, 197 – 200. Johnson, R.J., 1989. Developmental evidence for modality-dependent P300 generators: a normative study. Psychophysiology 26, 651 – 667. Kanner, L., 1943. Autistic disturbances of affective contact. Nerv. Child 2, 217 – 250. Kemner, C., Verbaten, M.N., Cuperus, J.M., Camfferman, G., van Engeland, H., 1995. Auditory event-related brain potentials in autistic children and three different control groups. Biol. Psychiatry 38, 150 – 165. Klin, A., 1993. Auditory brainstem responses in autism: brainstem dysfunction or peripheral hearing loss? J. Autism Dev. Disord. 23, 15 – 35. Kraus, N., McGee, T., Micco, A., Sharma, A., Carrell, T., Nicol, T., 1993. Mismatch negativity in school-age children to speech stimuli that are just perceptibly different. Electroencephalogr. Clin. Neurophysiol. 88, 123 – 130. Kraus, N., McGee, T., Littman, T., Nicol, T., King, C., 1994. Nonprimary auditory thalamic representation of acoustic change. J. Neurophysiol. 72, 1270 – 1277. Kurtzberg, D., Vaughan Jr., H.G., Kreuzer, J.A., Fliegler, K.Z., 1995. Developmental studies and clinical application of mismatch negativity: problems and prospects. Ear Hear. 16, 105 – 117. Lahat, E., Avital, E., Barr, J., Berkovitch, M., Arlazoroff, A., Aladjem, M., 1995. BAEP studies in children with attention deficit disorder. Dev. Med. Child Neurol. 37, 119 – 123. Lincoln, A.J., Courchesne, E., Harms, L., Allen, M., 1993. Contextual probability evaluation in autistic, receptive developmental language disorder and control children: event-related brain potential evidence. J. Autism Dev. Disord. 23, 37 – 58. Lincoln, A.J., Courchesne, E., Harms, L., Allen, M., 1995. Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: event-related brain potential evidence. J. Autism Dev. Disord. 25, 521 – 539. Lockyer, L., Rutter, M., 1970. A five to fifteen year follow-up study of infantile psychosis: IV. Patterns of cognitive ability. Br. J. Soc. Clin. Psychol. 9, 1952 – 1963. Loiselle, D.L., Stamm, J.S., Maitinsky, S., Whipple, S.C., 1980. Evoked potential and behavioral signs of attention dysfunction in hyperactive boys. Psychophysiology 17, 193 – 201. Martin, L., Barajas, J.J., Fernandez, R., Torres, E., 1988. Auditory event-related potentials in well-characterized groups of children. Electroencephalogr. Clin. Neurophysiol. 71, 375 – 381. Martinez-Moreno, E., Llama, A., Avendano, C., Renes, E., Rein-
oso-Suarez, F., 1987. General plan of the thalamic projections to the prefrontal cortex in the cat. Brain Res. 407, 17 – 26. Maziade, M., Merette, C., Cayer, M., Roy, M.-A., Szatmari, P., Cote, R., Thivierge, J., 2000. Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives. Arch. Gen. Psychiatry 57, 1077 – 1083. McClelland, R.J., Eyre, D.G., Watson, D., Clavert, G.J., Sherrard, E., 1992. Central conduction time in childhood autism. Br. J. Psychiatry 160, 659 – 663. Minshew, N.J., 1996. Brief report: brain mechanisms in autism: functional and structural abnormalities. J. Autism Dev. Disord. 26, 205 – 209. Nagy, E., Loveland, K.A., 2002. Prolonged brainstem auditory evoked potentials: an autism-specific or autism-nonspecific marker. Arch. Gen. Psychiatry 59, 288 – 290. Na¨a¨ta¨nen, R., 1990. The role of attention in auditory information processing as revealed by ERPs and other brain measures of cognitive function. Behav. Brain Sci. 13, 201 – 288. Na¨a¨ta¨nen, R., 1991. Mismatch negativity outside strong attentional focus: a commentary on Woldorff et al. (1991). Psychophysiology 28, 478 – 484. Na¨a¨ta¨nen, R., Picton, T.W., 1987. The N1 wave of the human electric and magnetic response to sound. A review and an analysis of the component structure. Psychophysiology 24, 375 – 425. Na¨a¨ta¨nen, R., Simpson, M., Loveless, N.E., 1982. Stimulus deviance and evoked potentials. Biol. Psychol. 14, 53 – 98. Nakamura, K., Toshima, T., Takemura, I., 1986. The comparative developmental study of auditory information processing in autistic adults. J. Autism Dev. Disord. 16, 105 – 118. Novick, B., Vaughan Jr., H.G., Kurtzberg, D., Simson, R. 1980. An electrophysiologic indication of auditory processing defects in autism. Psychiatry Res. 3, 107 – 114. Oades, R.D., Walker, M.K., Geffen, L.B., Stern, L.M., 1988. Eventrelated potentials in autistic and healthy children on an auditory choice reaction task. Int. J. Psychophysiol. 6, 25 – 37. Ohlrich, E.S., Barnet, A.B., Weiss, I.P., Shanks, B.L., 1978. Auditory evoked potential development in early childhood: a longitudinal study. Electroencephalogr. Clin. Neurophysiol. 44, 411 – 423. Ornitz, E.M., 1974. The modulation of sensory input in autistic children. J. Autism Child. Schizophrenia 4, 197 – 215. Ornitz, E.M., 1985. Neurophysiology of infantile autism. J. Am. Acad. Child Adolesc. Psych. 24, 251 – 262. Pang, E.W., Taylor, M.J., 2000. Tracking the development of the N1 from age 3 to adulthood: an examination of speech and nonspeech stimuli. Clin. Neurophysiol. 111, 388 – 397. Pantev, C., Hoke, M., Lehnertz, K., Lutkenhoner, B., Anogianakis, G., Wittkowski, W., 1988. Tonotopic organization of the human auditory cortex revealed by transient auditory evoked magnetic fields. Electroencephalogr. Clin. Neurophysiol. 69, 160 – 170. Pearce, J.W., Crowell, D.H., Tokioka, A., Pacheco, G.P., 1989. Childhood developmental changes in the auditory P300. J. Child Neurol. 4, 100 – 106. Perrault, N., Picton, T.W., 1984. ERPs recorded from the scalp and nasopharynx: I. N1 and P2. Electroencephalogr. Clin. Neurophysiol. 39, 609 – 620.
M.D. Bomba, E.W. Pang / International Journal of Psychophysiology 53 (2004) 161–169 Picton, T.W., 1992. The P300 wave of the human event-related potential. J. Clin. Neurophysiol. 9, 456 – 479. Picton, T.W., Hillyard, S.A., 1974. Human auditory evoked potentials: II. Effects of attention. Electroencephalogr. Clin. Neurophysiol. 36, 191 – 200. Picton, T.W., Hillyard, S.A., Kraus, H.I., Galambos, R., 1974. Human auditory evoked potentials: I. Evaluation of components. Electroencephalogr. Clin. Neurophysiol. 36, 179 – 190. Plumet, M.H., Goldblum, M.C., Leboyer, M., 1995. Verbal skills in relatives of autistic females. Cortex 31, 723 – 733. Polich, J., Ladish, C., Burns, T., 1990. Normal variation of P300 in children: age, memory span and head size. Int. J. Psychophysiol. 9, 237 – 248. Ponton, C.W., Eggermont, J.J., Don, M., Waring, M.D., Kwong, B., Cunningham, J., Trautwein, P., 2000. Maturation of the mismatch negativity: effects of profound deafness and cochlear implant use. Audiol. Neuro-otol. 5, 167 – 185. Ponton, C.W., Eggermont, J.J., Khosla, D., Kwong, B., Don, M., 2002. Maturation of human central auditory system activity: separating auditory evoked potentials by dipole source modeling. Clin. Neurophysiol. 113, 407 – 420. Posner, M., 1978. Chronometric Explorations of Mind. Erlbaum, Hillsdale, NJ. Purvis, K.L., Tannock, R., 1997. Language abilities in children with attention deficit hyperactivity disorder, reading disabilities, and normal controls. J. Abnorm. Child Psychol. 25, 133 – 144. Rapin, I., 1995. Autistic regression and disintegrative disorder: how important is the role of epilepsy? Semin. Pediatr. Neurol. 2, 278 – 285. Rapin, I., Katzman, R., 1998. Neurobiology of autism. Ann. Neurol. 43, 7 – 14. Regan, D.M., 1989. Human Brain Electrophysiology: evoked Potentials and Evoked Magnetic Fields in Science and Medicine. Elsevier, Amsterdam, p. 53. Rosenhall, U., Nordin, V., Branberg, K., Gillberg, C., 2003. Autism and auditory brain stem. Ear Hear. 24, 206 – 214. Rutter, M., 1979. Language, cognition and autism. Res. Publ.Assoc. Res. Nerv. Ment. Dis. 57, 247 – 264. Seri, S., Cerquiglini, A., Pisani, F., Curatolo, P., 1999. Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing. Clin. Neurophysiol. 110, 1825 – 1830.
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Spence, M.A., 2001. The genetics of autism. Curr. Opin. Pediatr. 13, 561 – 565. Squires, N.K., Squires, K.C., Hillyard, S.A., 1975. Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroencephalogr. Clin. Neurophysiol. 38, 387 – 401. Strandburg, R.J., Marsh, J.T., Brown, W.S., Asarnow, R.F., Guthrie, D., Higa, J., 1993. Event-related potentials in high-functioning adult autistics: linguistic and nonlinguistic visual information processing tasks. Neuropsychologia 31, 413 – 434. Tager-Flusberg, H., Joseph, R., Folstein, S., 2001. Current directions in research on autism. Ment. Retard. Dev. Disabil. Res. Rev. 7, 21 – 29. Thivierge, J., Be´dard, C., Coˆte´, R., Maziade, M., 1990. Brainstem auditory evoked response and subcortical abnormalities in autism. Am. J. Psychiatry 147, 1609 – 1613. Tonnquist-Uhlen, I., Borg, E., Spens, K., 1995. Topography of auditory evoked long latency potentials in normal children, with particular reference to the N1 component. Electroencephalogr. Clin. Neurophysiol. 95, 34 – 41. Weinberger, N.M., Diamond, D.M., 1987. Physiological plasticity in auditory cortex: rapid induction by learning. Prog. Neurobiol. 29, 1 – 55. Wolpaw, J.R., Penry, J.K., 1975. A temporal component of the auditory evoked response. Electroencephalogr. Clin. Neurophysiol. 39, 609 – 620. Wong, V., Wong, S.N., 1991. Brainstem auditory evoked potential study in children with autistic disorder. J. Autism Dev. Disord. 21, 329 – 340. Woods, D.L., Clayworth, C.C., Knight, R.T., Simpson, G.V., Naeser, M.A., 1987. Generators of middle- and long-latency auditory evoked potentials: implications from studies of patients with bitemporal lesions. Electroencephalogr. Clin. Neurophysiol. 68, 132 – 148. Yago, E., Escera, C., Alho, K., Giard, M.H., 2001. Cerebral mechanisms underlying orienting of attention towards auditory frequency changes. NeuroReport 12, 2583 – 2587. Zafeiriou, D.I., Andreou, A., Karasavidou, K., 2000. Utility of brainstem auditory evoked potentials in children with spastic cerebral palsy. Acta Paediatr. 89, 194 – 197.
Review
Cortical auditory evoked potentials in autism: a review Marie D. Bomba a, Elizabeth W. Pang a,b,* a
Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada b University of Toronto, Toronto, ON, Canada
Received 20 November 2003; received in revised form 29 January 2004; accepted 1 April 2004 Available online
Abstract The question of etiology in autism remains elusive primarily due to the fact that autism does not result from a single dysfunction but is multi-faceted in nature. Investigations into etiology have ranged from identifying abnormalities in the genome to describing structural/functional brain abnormalities. Bearing in mind the risk of over-simplification, there is still utility in isolating a specific deficit to examine its etiologic contribution. It is known that individuals with autism have difficulty processing auditory information at the cortical level but this is not consistently seen subcortically. In recent years, cortical auditory processing has been extensively researched using event-related potentials (ERPs); however, these results in relation to autism have not been reviewed. This paper will examine this literature and discuss implications for future research. D 2004 Elsevier B.V. All rights reserved. Keywords: Auditory; Autism; Cortical evoked potentials; Event-related potentials (ERP); N1; Mismatch negativity (MMN); P3; Review
1. Introduction Kanner (1943) first described autism as a disorder encompassing abnormal social reciprocity, abnormal language use, and an intense desire for sameness. Sixty years later, this description still captures the essence of autistic behavior (Tager-Flusberg et al., 2001) although the etiology of this disorder remains unknown. This elusive issue of etiology is likely due to the fact that autism does not result from a single dysfunction or deficit. Consequently, attempts to elucidate the underlying causes of autism have ranged from identifying abnormalities in the genome to * Corresponding author. Division of Neurology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.: +1-416-813-6548; fax: +1-416-813-6334. E-mail address: [email protected] (E.W. Pang). 0167-8760/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpsycho.2004.04.001
describing structural/functional abnormalities in the brain (Bauman, 1996; Rapin, 1995; Rapin and Katzman, 1998; Spence, 2001; Tager-Flusberg et al., 2001). Despite the multi-faceted nature of autism, there is still utility in isolating a specific deficit to examine its etiologic contribution. For instance, clinical and research observations in autism indicate defective processing of incoming auditory and verbal stimuli (Hoffmann and Prior, 1982; Lockyer and Rutter, 1970; Novick et al., 1980; Ornitz, 1974; Rutter, 1979). Data from evoked potential studies indicate that individuals with autism have difficulties in the cognitive processing of auditory information despite intact basic sensory perception (Minshew, 1996). There is increasing evidence that abnormal cortical processing of auditory stimuli is one of the core deficits in autism. While substantial strides in our understanding of cortical auditory processing have
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been made, the relationship between auditory cortex function and autism has not been reviewed. In this comprehensive review, we will describe past neurophysiological findings related to autism in order to highlight patterns, inconsistencies, and directions for future studies. Our discussion will be broadly separated into sub-cortical and cortical auditory components, and then specifically, the BAEP, MLR, P1, P2, Nc, N1, P3, T-Complex, MMN and Nd waveforms will be defined and discussed in turn.
2. Sub-cortical auditory processing Auditory stimuli generate signals that are transmitted through the brainstem to the thalamus and into auditory cortex. The relationship between autism and brainstem auditory evoked responses (BAEP/BAER/ABR) has been examined and it is generally accepted that although brainstem abnormalities may be present, they are not necessary for the emergence of autism since many individuals with autism display normal BAEPs (see review: Klin, 1993; Rosenhall et al., 2003). In addition, when BAEPs are impaired, the abnormality might not be specific to autism. For example, prolonged BAEPs have been associated with other nonspecific delays including language development with or without mental retardation (Lahat et al., 1995; Purvis and Tannock, 1997; Zafeiriou et al., 2000). Studies continue to demonstrate equivocal findings and now emphasize the likelihood that BAEP abnormalities are subtle and probably useful for characterizing autistic subgroups (Maziade et al., 2000; McClelland et al., 1992; Rosenhall et al., 2003; Thivierge et al., 1990; Wong and Wong, 1991), and possibly their first-degree relatives (August et al., 1981; Nagy and Loveland, 2002; Plumet et al., 1995). Despite valiant, large-scale efforts (e.g. Maziade et al., 2000; Rosenhall et al., 2003), the relationship between BAEPs and autism has not yet been clearly delineated. This is not surprising given that autism is a complex, genetic disorder with multiple and/or interacting causal factors. Another subcortical response that has been studied in individuals with autism is the Mid-Latency Auditory Response (MLR). The MLR reflects transmission of the auditory signal through the thalamus
and into primary auditory cortex (Picton et al., 1974; Woods et al., 1987). Like the BAEP, MLRs have been shown to be normal in adults with autism (Buchwald et al., 1992; Grillon et al., 1989) suggesting that in at least some subtypes of autism, auditory processing dysfunction at the subcortical level is not a necessary condition for autistic symptomology. Having said this, it is important to clarify that other subcortical structures, not related to processing via the primary auditory pathway, have been implicated in autism. There is a body of literature, first proposed by Ornitz (1985), suggesting that autism results from dysfunctions of the brainstem – thalamic system mediating arousal and attention; since then, this has been expanded to include the cerebellum which also coordinates and controls selective attention (Courchesne et al., 1994). Given that auditory stimulation generates activity in two or more parallel central nervous system pathways (Elberling et al., 1981; Graybiel, 1973; Pantev et al., 1988; Weinberger and Diamond, 1987), and that the secondary auditory pathway receives input from the reticular activating system (RAS), a part of the brainstem – thalamic system (Erwin and Buchwald, 1986), it would not be surprising if evoked potential waveforms generated by auditory stimuli activating the RAS would show abnormalities. Examples of evoked potentials receiving RAS input are the P1, P2 and Nc waveforms. The P1 has been found to be significantly smaller in amplitude in an autistic group (Buchwald et al., 1992) and thus interpreted as indicating both a decreased sensitivity to stimuli and a dysfunctional recovery cycle in the RAS – thalamic pathway. The P2, which is sensitive to attentional levels (Picton and Hillyard, 1974), stimulus intensity, and stimulus frequency (Squires et al., 1975), shows equivocal results with regards to autism. One study using click stimuli reported smaller P2 amplitudes in adolescent males with autism (Novick et al., 1980), while two other studies, using tones (Lincoln et al., 1995) and words (Courchesne et al., 1984), reported no significant decreases. While this may be an issue of power since all three studies used fewer than 10 subjects, the role of differing arousal and attention levels cannot be ruled out. The Nc is the most extensively studied of this group of waveforms. Described in detail by Courchesne et al. (1989), it is
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known that the Nc is a cephalically recorded frontocentral negativity triggered by input from the RAS. It is modality non-specific, thought to be the earliest endogenous component to appear during human brain development, and it can be elicited from infancy through young adulthood. In individuals with autism, Nc responses were reduced or absent (see review: Courchesne, 1990). This is in line with the previous suggestion that evoked potentials generated by RASlinked systems are abnormal in autism. While subcortical generators related to auditory processing can appear normal in individuals with autism, subcortical generators related to arousal and attention (particularly the RAS) may be abnormal. For the purposes of this paper, our aim is to focus on deficits in cortical auditory processing while partitioning out other significant contributing factors such as arousal and attention. Admittedly this is a limited spotlight since auditory evoked potentials represent only one level of analysis in a multi-dimensional complex disease; however, it is hoped that this narrow concentration will shed light on one of the core aspects of autism that may lead to a better understanding of the interconnections between underlying biological causes and the observed cognitive – behavioral manifestations of this disorder.
3. Cortical auditory event-related potentials The cortical auditory evoked potentials, or eventrelated potentials (ERP), reflect activation of neural structures in auditory cortex, auditory association areas, and areas related to higher order cognitive processes such as memory. They can be approximately divided into long-latency and short-latency ERPs, where the long-latency responses reflect more cognitive, higher-level, less modality-specific processing and the short-latency ERPs reflect more basic, modality-specific processing, which can be nevertheless still sensitive to various cognitive factors. All the short-latency ERPs have at least one generator in the auditory cortex of the temporal lobe. The most extensively studied long-latency ERP is the P300. The following review will commence with a synopsis of the literature examining the P300 and autism, and then look specifically at the auditory short-latency ERPs.
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3.1. P300 The P300, P3, or P3b (see review: Picton, 1992) is a large positive waveform that occurs at approximately 300 ms after stimulus onset in adults and appears to originate in the association cortex of the parietal lobes. The P3 is modality non-specific, meaning that it can be evoked in the visual, somatosensory and auditory modalities. While this waveform generally appears 300 ms after stimulus onset, there is some variation as a function of modality, age and task. For example, the latency of the auditory P3b decreases rapidly from infancy to childhood to adolescence reflecting an increasing efficiency in information processing with maturity (Goodin et al., 1978; Ohlrich et al., 1978; Pearce et al., 1989; Polich et al., 1990). Auditory P3b amplitudes increase slightly with age, but not significantly (Johnson, 1989; Polich et al., 1990). However, in general, the P3b is elicited by cognitive parameters such as stimulus probability, meaningfulness and task relevance (Donchin, 1981). Both the auditory and visual P300 have been well-studied in normal children and adults. In the autism literature, this ERP is often termed the A/Cz/P3 (Courchesne et al., 1984, 1985) to clarify that it is the P3 evoked by auditory stimuli measured at the Cz electrode. In individuals with autism, from as young as age 5 (Oades et al., 1988) and 8 years (Dawson et al., 1988; Lincoln et al., 1993) through to adulthood, the most consistent, and frequently reported, abnormality is a P3b or A/Cz/P3 amplitude attenuation with auditory stimulus presentation. Amplitude decreases have been reported with clicks (Novick et al., 1980), tones (Ciesielski et al., 1990; Courchesne et al., 1989; Lincoln et al., 1993; Oades et al., 1988), phonemes (Dawson et al., 1988), and novel sounds (Courchesne et al., 1984, 1985, 1986) in auditory-only and auditory/visual switching tasks (Ciesielski et al., 1990; Courchesne et al., 1985, 1989) but not with musical chords (Dawson et al., 1988) nor with words (Courchesne et al., 1984, 1985, 1986; Erwin et al., 1991). P3b latency remains unaffected (Ciesielski et al., 1990; Courchesne et al., 1984, 1985, 1986, 1989; Dawson et al., 1988; Erwin et al., 1991; Lincoln et al., 1993; Novick et al., 1980; Oades et al., 1988). Three explanations are put forth for the P3b amplitude attenuation. One, the P3b is thought to reflect
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a limited capacity mechanism whereby attention is consciously allocated to specific information in the environment (Picton, 1992; Posner, 1978). Thus, the reduced P3b may reflect either a failure to allocate appropriate attention to stimuli (Holcomb et al., 1985), or, a misallocation of attentional resources to less important stimuli (Dawson et al., 1988). Evidence for this hypothesis stems from reports of P3b amplitude attenuation in a wide range of childhood disorders including ADHD (Holcomb et al., 1985), reading disorders (Dainer et al., 1981; Holcomb et al., 1985), and hyperactivity (Loiselle et al., 1980). Two, P3b amplitude is inversely related to stimulus probability (i.e. a low-probability unexpected stimulus elicits a large P3b). A smaller P3b may reflect either a difficulty in attaching significance to unexpected stimuli (Oades et al., 1988) or a defect related to the modification of expectancies based on previous experience (Lincoln et al., 1993). This may explain why individuals with autism, who have rigid expectations and thus difficulty extracting information in a way that leads to a re-integration of previously learned information (Lincoln et al., 1993), have smaller P3b’s. Three, P3 amplitude attenuations may simply be due to latency jitter. Since background EEG activity is more variable in diseased conditions compared to healthy controls, latency jitter has been suggested as a possibility for explaining the lower amplitude late components in various disorders (Regan, 1989). Interestingly, although one of the core deficits in autism is with language, and it has been suggested that individuals with autism show atypical left hemisphere activation during processing of auditory linguistic stimuli (Dawson et al., 1988), there are no hemispheric differences on P3 amplitude using word stimuli (Courchesne et al., 1984, 1985; Erwin et al., 1991). Furthermore, children, teens, and adults with receptive developmental language disorders (RDLD) did not show P3b amplitude attenuations (Courchesne et al., 1989; Lincoln et al., 1993). This dissociation in P3b response to word versus tone stimuli supports the hypothesis that autism involves basic defects in cortical auditory processing, and that the severe language disorder observed in autism may be secondary to these deficits (Novick et al., 1980). This is further supported by the finding that the P3b attenuation is specific to the auditory modality as demonstrated by negative findings for visual experiments using letters
(Courchesne et al., 1986, 1989), words (Courchesne et al., 1985) and written phrases (Strandburg et al., 1993).
4. Auditory short-latency ERP The N1 is a short-latency ERP specific to the auditory modality that reflects basic auditory processing and is well understood in adults (for review: see Na¨a¨ta¨nen and Picton, 1987) and shows extensive developmental changes (Martin et al., 1988; Pang and Taylor, 2000; Ponton et al., 2000; TonnquistUhlen et al., 1995). This complex waveform consists of several obligatory waveforms: the N1b and Tcomplex; as well as difference waveforms: the mismatch negativity (MMN) and the negative difference (Nd), all of which are thought to be generated in different neural areas. The N1 components are differentiable by the eliciting features of the stimulus, the state of the subject, and scalp distribution. 4.1. N1b The N1b, measured at the vertex and generated in the supra-temporal cortex, reflects changes in stimulus presentation and the physical properties of a stimulus. Early studies have generally reported no effect of autism on N1b amplitude and latency (Courchesne et al., 1984; Erwin et al., 1991; Kemner et al., 1995; Lincoln et al., 1995; Nakamura et al., 1986; Novick et al., 1980). However, amplitude increases (Oades et al., 1988) and decreases (Courchesne et al., 1985) in individuals with autism compared to controls have been reported. This inconsistency in results can probably be explained by the extensive developmental changes in N1b topography, amplitude and latency, which until recently were unknown (Bruneau et al., 1997; Martin et al., 1988; Pang and Taylor, 2000; Ponton et al., 2000; Tonnquist-Uhlen et al., 1995). Taking these developmental changes into account, recent studies (Bruneau et al., 1999; Seri et al., 1999) have found that N1b amplitude decreased significantly in children with autism (Bruneau et al., 1999) and in children with co-morbid tuberous sclerosis and autism (Seri et al., 1999). These findings were interpreted as an indication that autism is related to ineffective regulation of auditory sensory input.
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4.2. The T-complex (N1a/N1c) The second component of the N1, the T-complex (Wolpaw and Penry, 1975), is generated on the superior temporal gyrus by radially oriented dipoles, and is best seen at temporal electrodes (Hackley et al., 1990; Perrault and Picton, 1984). It consists of biphasic deflections: the N1a (or Ta) which reflects the activation of neural generators underlying stimulus detection, and the N1c (or Tb) which reflects generators underlying stimulus discrimination (Na¨a¨ta¨nen and Picton, 1987). In children, this waveform is the most easily observable of the N1 components and becomes less prominent with maturity (Bruneau et al., 1997; Ponton et al., 2002). In the only study examining the N1c, Bruneau et al. (1999) observed the N1c to be of smaller amplitude and longer latency in children with autism. Furthermore, the pattern of dysfunction suggests that autistic subjects process both verbal and non-verbal auditory stimuli in the right cerebral hemisphere, whereas normal subjects process verbal information in the left hemisphere only. This is consistent with other nonelectrophysiological evidence finding right hemispheric dominance in the processing of verbal and non-verbal auditory stimuli by autistic individuals (Dawson et al., 1982; Hoffmann and Prior, 1982). Taken as a whole, these results support the hypothesis of role reorganization of the left and right hemispheres for auditory processing during early brain development in individuals with autism rather than attributing dysfunction to the left hemisphere alone. 4.3. Mismatch negativity (MMN) The mismatch negativity (MMN) is a difference waveform that reflects the processing required to compare a different incoming stimulus with the neural representation already stored in transient auditory memory. This waveform is only evident when the frequently occurring stimuli are subtracted from the infrequent stimuli; without this subtraction, the MMN would not be evident. The MMN is thought to be a pre-perceptual measure of central auditory function (Na¨a¨ta¨nen, 1990). The MMN has generators on both supratemporal planes of the auditory cortices (see review: Alho, 1995) and in frontal cortex (Giard et al., 1990). The MMN is
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evoked independent of attention or response requirements, and is responsive to even minimal changes in acoustic parameters. The supratemporal MMN appears to be a neurophysiological index of the fine discrimination of acoustic features (Na¨a¨ta¨nen, 1990, 1991; Na¨a¨ta¨nen et al., 1982; Na¨a¨ta¨nen and Picton, 1987), while the frontal MMN is related to the initiation of involuntary switching of attention to stimulus changes (Giard et al., 1990). Not only is the MMN well understood in adults, it has been examined in children (Ceponiene et al., 1998; Csepe´, 1995; Kraus et al., 1993) and infants (Alho et al., 1990; Cheour et al., 1998, 2000; CheourLuhtanen et al., 1995; Kurtzberg et al., 1995). Kemner et al. (1995) reported normal latency and amplitude of the MMN in children with autism; however, they used high functioning autistic children and an unusually long ISI of several seconds which could have accounted for their results. A more recent study examining MMN in children with autism (Gomot et al., 2002) found that left hemisphere MMN peak latency was earlier in the autistic compared to the control group and the topography of the MMN differed between the groups. In the autistic group, the right hemisphere showed the supratemporal MMN component, whereas the left temporal MMN was shortened by the appearance of an abnormal deviance-related positivity in left pre-frontal cortex, generated by non-primary thalamo-cortical projections (Martinez-Moreno et al., 1987; Kraus et al., 1994; Yago et al., 2001). Although the RAS is not specifically mentioned, it has been suggested that this parallel pathway results in a higher cerebral reactivity to the deviancy that allows children with autism to become hypersensitive to acoustic changes. Further support for this idea stems from a recent study by Ferri et al. (2003) who compared the MMN in males between the ages of 6 and 19 with a diagnosis of autism and mental retardation to healthy age-matched controls. They found that the MMN amplitude of the autistic group was significantly enhanced and occurred at a shorter latency, but only to the deviant stimuli, thus, their results support a dysfunction that influences the pre-perceptual processing of auditory sensory information. Two studies have examined children with different sub-types of autism. Seri et al. (1999) studied children with autism within a sub-group of children with
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tuberous sclerosis and found a significantly lower MMN amplitude with longer latency in the children with autism. Based on these results, they suggested that it is likely that children with autism have some difficulty encoding information into transient memory. Research at the other end of the autism spectrum reported very similar findings. Jansson-Verkasalo et al. (2003) demonstrated longer MMN latencies in children with Asperger’s Syndrome to both tones and speech sounds. This delayed MMN finding was present in both cerebral hemispheres to tone stimuli and only in the right hemisphere to speech stimuli. They interpreted this as an indication of auditory discrimination difficulties probably resulting from faulty transient memory encoding mechanisms. Furthermore, the asymmetry in hemispheric abnormalities to the different types of stimuli support the idea that autism etiology may encompass either impaired right hemisphere functioning or abnormal interhemispheric specialization. 4.4. Negative difference (Nd) The negative difference (Nd) waveform is thought to be related to selective attention. Like the MMN, the Nd is obtained from a subtraction. In this case, subjects in a dichotic listening paradigm are instructed to attend to a stimulus stream in one ear, and the ERP from the attended stimuli are subtracted from the unattended stimuli. Nd latency is sensitive to changes in inter-stimulus interval and ease of discriminability between attended and unattended stimuli (Hansen and Hillyard, 1980; Na¨a¨ta¨nen and Picton, 1987). To date, only one study (Ciesielski et al., 1990) has examined the Nd in individuals with autism. This study reports that despite normal performance on the tasks, the Nd waveform was absent in individuals with autism; however, the authors conclude that this does not necessarily reflect an inability to select, rather, individuals with autism may be using different mechanisms not measured by the Nd.
5. Conclusion With the exception of the P3, research on other long-latency cortical ERPs in autism has been sparse and results are often inconsistent. This may be due, in
part, to the diagnostic and identification issues surrounding autism. With the current opinion that autistic symptomology can be described along a spectrum, it is crucial that future studies set stricter criterion to delineate autistic subtypes for examination. As well, with recent discoveries that cortical ERPs undergo extensive developmental changes into the teenage years, some of the inconsistencies reported in the data may simply be due to non-controlled developmental changes. However, whether developmental or chronological age-matching for controls is more important is still unclear and this answer may depend on the types of paradigms used. To date, results from ERP studies that have controlled for diagnostic and developmental issues are very promising. To summarize, it has been suggested that the N1b may reflect ineffective regulation of auditory sensory input in autism (Bruneau et al., 1999; Seri et al., 1999). Measurements of the Tcomplex N1 support the hypothesis that autism may affect auditory processing by reorganizing the roles of the left and right hemispheres (Bruneau et al., 1999). Furthermore, MMN studies suggest that children with autism may have difficulty encoding information in transient memory (Gomot et al., 2002; Jansson-Verkasalo et al., 2003; Seri et al., 1999), while the Nd suggests that autism may affect selective attention (Ciesielski et al., 1990). Admittedly, these are single studies with small sample sizes; however, this body of literature does indicate that the examination of cortical auditory ERPs (i.e. the N1b, T-complex, MMN, and Nd) holds great potential for contributing to our knowledge of autism, and eventually, for shedding light on our understanding of the pathogenesis and etiology of this disease. References Alho, K., 1995. Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. Ear Hear. 16, 38 – 51. Alho, K., Sainio, K., Sajaniemi, N., Reinikainen, K., Na¨a¨ta¨nen, R., 1990. Event-related brain potential of human newborns to pitch change of an acoustic stimulus. Electroencephalogr. Clin. Neurophysiol. 77, 151 – 155. August, G.J., Stewart, M.A., Tsai, L., 1981. The incidence of cognitive disabilities in the siblings of autistic children. Br. J. Psychiatry 138, 416 – 422. Bauman, M.L., 1996. Brief report: neuroanatomic observations of
M.D. Bomba, E.W. Pang / International Journal of Psychophysiology 53 (2004) 161–169 the brain in pervasive developmental disorders. J. Autism Dev. Disord. 26, 199 – 203. Bruneau, N., Roux, S., Guerin, P., Barthe´le´my, C., Lelord, G., 1997. Temporal prominence of auditory evoked potentials (N1 wave) in 4 – 8 year old children. Psychophysiology 34, 32 – 38. Bruneau, N., Roux, S., Adrien, J.L., Barthe´le´my, C., 1999. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave – T Complex). Clin. Neurophysiol. 110, 1927 – 1934. Buchwald, J.S., Erwin, R., Van Lancker, D., Guthrie, D., Schwafel, J., Tanguay, P., 1992. Midlatency auditory evoked responses: P1 abnormalities in adult autistic subjects. Electroencephalogr. Clin. Neurophysiol. 84, 164 – 171. Ceponiene, R., Cheour, M., Na¨a¨ta¨nen, R., 1998. Interstimulus interval and auditory event-related potentials in children: evidence for multiple generators. Electroencephalogr. Clin. Neurophysiol. 108, 345 – 354. Cheour, M., Alho, K., Ceponiene´, R., Reinikainen, K., Sainio, K., Pohjavuori, M., Aaltonen, O., Na¨a¨ta¨nen, R., 1998. Maturation of mismatch negativity in infants. Int. J. Psychophysiol. 29, 217 – 226. Cheour, M., Leppanen, P.H., Kraus, N., 2000. Mismatch negativity (MMN) as a tool for investigating auditory discrimination and sensory memory in infants and children. Clin. Neurophysiol. 111, 4 – 16. Cheour-Luhtanen, M., Alho, K., Kujala, T., Sainio, K., Reinikainen, K., Renlund, M., Aaltonen, O., Eerola, O., Na¨a¨ta¨nen, R., 1995. Mismatch negativity indicates vowel discrimination in newborns. Hear. Res. 82, 53 – 58. Ciesielski, K.T., Courchesne, E., Elmasian, R., 1990. Effects of focused selective attention tasks on event-related potentials in autistic and normal individuals. Electroencephalogr. Clin. Neurophysiol. 75, 207 – 220. Courchesne, E., 1990. Chronology of postnatal human brain development: ERP, PET, myelinogenesis, and synaptogenesis studies. In: Rohrbaugh, R., Parasuraman, R., Johnson, R. (Eds.), EventRelated Brain Potentials: Basic Issues and Applications. Oxford, New York, NY, pp. 210 – 241. Courchesne, E., Kilman, B.A., Galambos, R., Lincoln, A.J., 1984. Autism: processing of novel auditory information assessed by event-related brain potentials. Electroencephalogr. Clin. Neurophysiol. 59, 238 – 248. Courchesne, E., Lincoln, A.J., Kilman, B.A., Galambos, R., 1985. Event-related brain potential correlates of the processing of novel visual and auditory information in autism. J. Autism Dev. Disord. 15, 55 – 76. Courchesne, E., Lincoln, A.J., Kilman, B.A., Galambos, R., 1986. Visual and auditory ERPs in autism. In: McCallum, W.C., Zappoli, R., Denoth, F. (Eds.), Cerebral Psychophysiology: Studies in Event-Related Potentials. Electroenceph. Clin. Neurophys., Suppl., vol. 38. Elsevier, Amsterdam, pp. 446 – 448. Courchesne, E., Lincoln, A.J., Yeung-Courchesne, R., Elmasian, R., Grillon, C., 1989. Pathophysiologic findings in nonretarded autism and receptive developmental disorder. J. Autism Dev. Disord. 19, 1 – 17. Courchesne, E., Townsend, J.P., Ashoomoff, N.A., Yeung-Courchesne, R., Press, G.A., Murakami, J.W., Lincoln, A.J., James,
167
H.E., Saitoh, O., Egaas, B., Haas, R.H., Schreibman, L., 1994. A new finding: Impairment in shifting attention in autistic cerebellar patients. In: Broman, S.H., Grafman, J. (Eds.), Atypical Cognitive Deficits in Developmental Disorders: Implications for Brain Function. Lawrence Erlbaum, Hillsdale, NJ, 101 – 137. Csepe´, V., 1995. On the origin and development of the mismatch negativity. Ear Hear. 16, 91 – 104. Dainer, K.B., Klorman, R., Salzman, L.F., Hess, D.W., Davidson, P.W., Michael, R.L., 1981. Learning disordered children’s evoked potentials during sustained attention. J. Abnorm. Child Psychol. 9, 79 – 94. Dawson, G., Warrenburg, S., Fuller, P., 1982. Cerebral lateralization in individuals diagnosed as autistic in early childhood. Brain Lang. 15, 353 – 368. Dawson, G., Finley, C., Phillips, S., Galpert, L., Lewy, A., 1988. Reduced P3 amplitude of the event-related brain potential: its relationship to language ability in autism. J. Autism Dev. Disord. 18, 493 – 504. Donchin, E., 1981. Surprise!... Surprise? Psychophysiology 18, 493 – 513. Elberling, C., Bak, C., Kofoed, B., Lebech, J., Saermark, K., 1981. Auditory magnetic fields from the human cortex. Influence of stimulus intensity. Scand. Audiol. 10, 203 – 207. Erwin, R., Buchwald, J.S., 1986. Midlatency auditory evoked responses: differential effects of sleep in the human. Electroencephalogr. Clin. Neurophysiol. 65, 383 – 392. Erwin, R., Van Lancker, D., Guthrie, D., Schwafel, J., Tanguay, P., Buchwald, J.S., 1991. P3 responses to prosodic stimuli in adult autistic subjects. Electroencephalogr. Clin. Neurophysiol. 80, 561 – 571. Ferri, R., Elia, M., Agarwal, N., Lanuzza, B., Musumeci, S.A., Pennisi, G., 2003. The mismatch negativity and the P3a components of the auditory event-related potentials in autistic lowfunctioning subjects. Clin. Neurophysiol. 114, 1671 – 1680. Giard, M.-H., Perrin, F., Pernier, J., Bouchet, P., 1990. Brain generators implicated in the processing of auditory stimulus deviance: a topographic event-related potential study. Psychophysiology 27, 627 – 640. Gomot, M., Giard, M-H., Adrien, J-L., Barthelemy, C., Bruneau, N., 2002. Hypersensitivity to acoustic change in children with autism: electrophysiological evidence of left frontal cortex dysfunctioning. Psychophysiology 39, 577 – 584. Goodin, D.S., Squires, K.C., Henderson, B.H., Starr, A., 1978. Age-related variations in evoked potentials to auditory stimuli in normal human subjects. Electroencephalogr. Clin. Neurophysiol. 44, 447 – 458. Graybiel, A.M., 1973. The thalamo-cortical projection of the socalled posterior nuclear group: a study with anterograde degeneration methods in the cat. Brain Res. 49, 229 – 244. Grillon, C., Courchesne, E., Akshoomoff, N., 1989. Brainstem and middle latency auditory evoked potentials in autism and developmental language disorder. J. Autism Dev. Disord. 19, 255 – 269. Hackley, S.A., Woldorff, M., Hillyard, S.A., 1990. Cross-modal selective attention effects on retinal, myogenic, brainstem and cerebral evoked potentials. Psychophysiology 27, 195 – 208. Hansen, J.C., Hillyard, S.A., 1980. Endogenous brain potentials
168
M.D. Bomba, E.W. Pang / International Journal of Psychophysiology 53 (2004) 161–169
associated with selective attention. Electroencephalogr. Clin. Neurophysiol. 49, 277 – 290. Hoffmann, W.L., Prior, M.R., 1982. Neuropsychological dimensions of autism in children: a test of the hemispheric dysfunction hypotheses. J. Clin. Neuropsychol. 4, 27 – 41. Holcomb, P.J., Ackerman, P.T., Dykman, R.A., 1985. Cognitive event-related brain potentials in children with attention and reading deficits. Psychophysiology 22, 656 – 667. Jansson-Verkasalo, E., Ceponiene, R., Kielinen, M., Suominen, K., Ja¨ntti, V., Linna, S.-L., Moilanen, I., Na¨a¨ta¨nen, R., 2003. Deficient auditory processing in children with Asperger Syndrome, as indexed by event-related potentials. Neurosci. Lett. 338, 197 – 200. Johnson, R.J., 1989. Developmental evidence for modality-dependent P300 generators: a normative study. Psychophysiology 26, 651 – 667. Kanner, L., 1943. Autistic disturbances of affective contact. Nerv. Child 2, 217 – 250. Kemner, C., Verbaten, M.N., Cuperus, J.M., Camfferman, G., van Engeland, H., 1995. Auditory event-related brain potentials in autistic children and three different control groups. Biol. Psychiatry 38, 150 – 165. Klin, A., 1993. Auditory brainstem responses in autism: brainstem dysfunction or peripheral hearing loss? J. Autism Dev. Disord. 23, 15 – 35. Kraus, N., McGee, T., Micco, A., Sharma, A., Carrell, T., Nicol, T., 1993. Mismatch negativity in school-age children to speech stimuli that are just perceptibly different. Electroencephalogr. Clin. Neurophysiol. 88, 123 – 130. Kraus, N., McGee, T., Littman, T., Nicol, T., King, C., 1994. Nonprimary auditory thalamic representation of acoustic change. J. Neurophysiol. 72, 1270 – 1277. Kurtzberg, D., Vaughan Jr., H.G., Kreuzer, J.A., Fliegler, K.Z., 1995. Developmental studies and clinical application of mismatch negativity: problems and prospects. Ear Hear. 16, 105 – 117. Lahat, E., Avital, E., Barr, J., Berkovitch, M., Arlazoroff, A., Aladjem, M., 1995. BAEP studies in children with attention deficit disorder. Dev. Med. Child Neurol. 37, 119 – 123. Lincoln, A.J., Courchesne, E., Harms, L., Allen, M., 1993. Contextual probability evaluation in autistic, receptive developmental language disorder and control children: event-related brain potential evidence. J. Autism Dev. Disord. 23, 37 – 58. Lincoln, A.J., Courchesne, E., Harms, L., Allen, M., 1995. Sensory modulation of auditory stimuli in children with autism and receptive developmental language disorder: event-related brain potential evidence. J. Autism Dev. Disord. 25, 521 – 539. Lockyer, L., Rutter, M., 1970. A five to fifteen year follow-up study of infantile psychosis: IV. Patterns of cognitive ability. Br. J. Soc. Clin. Psychol. 9, 1952 – 1963. Loiselle, D.L., Stamm, J.S., Maitinsky, S., Whipple, S.C., 1980. Evoked potential and behavioral signs of attention dysfunction in hyperactive boys. Psychophysiology 17, 193 – 201. Martin, L., Barajas, J.J., Fernandez, R., Torres, E., 1988. Auditory event-related potentials in well-characterized groups of children. Electroencephalogr. Clin. Neurophysiol. 71, 375 – 381. Martinez-Moreno, E., Llama, A., Avendano, C., Renes, E., Rein-
oso-Suarez, F., 1987. General plan of the thalamic projections to the prefrontal cortex in the cat. Brain Res. 407, 17 – 26. Maziade, M., Merette, C., Cayer, M., Roy, M.-A., Szatmari, P., Cote, R., Thivierge, J., 2000. Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives. Arch. Gen. Psychiatry 57, 1077 – 1083. McClelland, R.J., Eyre, D.G., Watson, D., Clavert, G.J., Sherrard, E., 1992. Central conduction time in childhood autism. Br. J. Psychiatry 160, 659 – 663. Minshew, N.J., 1996. Brief report: brain mechanisms in autism: functional and structural abnormalities. J. Autism Dev. Disord. 26, 205 – 209. Nagy, E., Loveland, K.A., 2002. Prolonged brainstem auditory evoked potentials: an autism-specific or autism-nonspecific marker. Arch. Gen. Psychiatry 59, 288 – 290. Na¨a¨ta¨nen, R., 1990. The role of attention in auditory information processing as revealed by ERPs and other brain measures of cognitive function. Behav. Brain Sci. 13, 201 – 288. Na¨a¨ta¨nen, R., 1991. Mismatch negativity outside strong attentional focus: a commentary on Woldorff et al. (1991). Psychophysiology 28, 478 – 484. Na¨a¨ta¨nen, R., Picton, T.W., 1987. The N1 wave of the human electric and magnetic response to sound. A review and an analysis of the component structure. Psychophysiology 24, 375 – 425. Na¨a¨ta¨nen, R., Simpson, M., Loveless, N.E., 1982. Stimulus deviance and evoked potentials. Biol. Psychol. 14, 53 – 98. Nakamura, K., Toshima, T., Takemura, I., 1986. The comparative developmental study of auditory information processing in autistic adults. J. Autism Dev. Disord. 16, 105 – 118. Novick, B., Vaughan Jr., H.G., Kurtzberg, D., Simson, R. 1980. An electrophysiologic indication of auditory processing defects in autism. Psychiatry Res. 3, 107 – 114. Oades, R.D., Walker, M.K., Geffen, L.B., Stern, L.M., 1988. Eventrelated potentials in autistic and healthy children on an auditory choice reaction task. Int. J. Psychophysiol. 6, 25 – 37. Ohlrich, E.S., Barnet, A.B., Weiss, I.P., Shanks, B.L., 1978. Auditory evoked potential development in early childhood: a longitudinal study. Electroencephalogr. Clin. Neurophysiol. 44, 411 – 423. Ornitz, E.M., 1974. The modulation of sensory input in autistic children. J. Autism Child. Schizophrenia 4, 197 – 215. Ornitz, E.M., 1985. Neurophysiology of infantile autism. J. Am. Acad. Child Adolesc. Psych. 24, 251 – 262. Pang, E.W., Taylor, M.J., 2000. Tracking the development of the N1 from age 3 to adulthood: an examination of speech and nonspeech stimuli. Clin. Neurophysiol. 111, 388 – 397. Pantev, C., Hoke, M., Lehnertz, K., Lutkenhoner, B., Anogianakis, G., Wittkowski, W., 1988. Tonotopic organization of the human auditory cortex revealed by transient auditory evoked magnetic fields. Electroencephalogr. Clin. Neurophysiol. 69, 160 – 170. Pearce, J.W., Crowell, D.H., Tokioka, A., Pacheco, G.P., 1989. Childhood developmental changes in the auditory P300. J. Child Neurol. 4, 100 – 106. Perrault, N., Picton, T.W., 1984. ERPs recorded from the scalp and nasopharynx: I. N1 and P2. Electroencephalogr. Clin. Neurophysiol. 39, 609 – 620.
M.D. Bomba, E.W. Pang / International Journal of Psychophysiology 53 (2004) 161–169 Picton, T.W., 1992. The P300 wave of the human event-related potential. J. Clin. Neurophysiol. 9, 456 – 479. Picton, T.W., Hillyard, S.A., 1974. Human auditory evoked potentials: II. Effects of attention. Electroencephalogr. Clin. Neurophysiol. 36, 191 – 200. Picton, T.W., Hillyard, S.A., Kraus, H.I., Galambos, R., 1974. Human auditory evoked potentials: I. Evaluation of components. Electroencephalogr. Clin. Neurophysiol. 36, 179 – 190. Plumet, M.H., Goldblum, M.C., Leboyer, M., 1995. Verbal skills in relatives of autistic females. Cortex 31, 723 – 733. Polich, J., Ladish, C., Burns, T., 1990. Normal variation of P300 in children: age, memory span and head size. Int. J. Psychophysiol. 9, 237 – 248. Ponton, C.W., Eggermont, J.J., Don, M., Waring, M.D., Kwong, B., Cunningham, J., Trautwein, P., 2000. Maturation of the mismatch negativity: effects of profound deafness and cochlear implant use. Audiol. Neuro-otol. 5, 167 – 185. Ponton, C.W., Eggermont, J.J., Khosla, D., Kwong, B., Don, M., 2002. Maturation of human central auditory system activity: separating auditory evoked potentials by dipole source modeling. Clin. Neurophysiol. 113, 407 – 420. Posner, M., 1978. Chronometric Explorations of Mind. Erlbaum, Hillsdale, NJ. Purvis, K.L., Tannock, R., 1997. Language abilities in children with attention deficit hyperactivity disorder, reading disabilities, and normal controls. J. Abnorm. Child Psychol. 25, 133 – 144. Rapin, I., 1995. Autistic regression and disintegrative disorder: how important is the role of epilepsy? Semin. Pediatr. Neurol. 2, 278 – 285. Rapin, I., Katzman, R., 1998. Neurobiology of autism. Ann. Neurol. 43, 7 – 14. Regan, D.M., 1989. Human Brain Electrophysiology: evoked Potentials and Evoked Magnetic Fields in Science and Medicine. Elsevier, Amsterdam, p. 53. Rosenhall, U., Nordin, V., Branberg, K., Gillberg, C., 2003. Autism and auditory brain stem. Ear Hear. 24, 206 – 214. Rutter, M., 1979. Language, cognition and autism. Res. Publ.Assoc. Res. Nerv. Ment. Dis. 57, 247 – 264. Seri, S., Cerquiglini, A., Pisani, F., Curatolo, P., 1999. Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing. Clin. Neurophysiol. 110, 1825 – 1830.
169
Spence, M.A., 2001. The genetics of autism. Curr. Opin. Pediatr. 13, 561 – 565. Squires, N.K., Squires, K.C., Hillyard, S.A., 1975. Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man. Electroencephalogr. Clin. Neurophysiol. 38, 387 – 401. Strandburg, R.J., Marsh, J.T., Brown, W.S., Asarnow, R.F., Guthrie, D., Higa, J., 1993. Event-related potentials in high-functioning adult autistics: linguistic and nonlinguistic visual information processing tasks. Neuropsychologia 31, 413 – 434. Tager-Flusberg, H., Joseph, R., Folstein, S., 2001. Current directions in research on autism. Ment. Retard. Dev. Disabil. Res. Rev. 7, 21 – 29. Thivierge, J., Be´dard, C., Coˆte´, R., Maziade, M., 1990. Brainstem auditory evoked response and subcortical abnormalities in autism. Am. J. Psychiatry 147, 1609 – 1613. Tonnquist-Uhlen, I., Borg, E., Spens, K., 1995. Topography of auditory evoked long latency potentials in normal children, with particular reference to the N1 component. Electroencephalogr. Clin. Neurophysiol. 95, 34 – 41. Weinberger, N.M., Diamond, D.M., 1987. Physiological plasticity in auditory cortex: rapid induction by learning. Prog. Neurobiol. 29, 1 – 55. Wolpaw, J.R., Penry, J.K., 1975. A temporal component of the auditory evoked response. Electroencephalogr. Clin. Neurophysiol. 39, 609 – 620. Wong, V., Wong, S.N., 1991. Brainstem auditory evoked potential study in children with autistic disorder. J. Autism Dev. Disord. 21, 329 – 340. Woods, D.L., Clayworth, C.C., Knight, R.T., Simpson, G.V., Naeser, M.A., 1987. Generators of middle- and long-latency auditory evoked potentials: implications from studies of patients with bitemporal lesions. Electroencephalogr. Clin. Neurophysiol. 68, 132 – 148. Yago, E., Escera, C., Alho, K., Giard, M.H., 2001. Cerebral mechanisms underlying orienting of attention towards auditory frequency changes. NeuroReport 12, 2583 – 2587. Zafeiriou, D.I., Andreou, A., Karasavidou, K., 2000. Utility of brainstem auditory evoked potentials in children with spastic cerebral palsy. Acta Paediatr. 89, 194 – 197.