Elsevier

Clinical Neurophysiology

Volume 114, Issue 9, September 2003, Pages 1671-1680
Clinical Neurophysiology

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

https://doi.org/10.1016/S1388-2457(03)00153-6Get rights and content

Abstract

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=800ms). 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.

Introduction

Autism was first described by Kanner (1943) and is now considered to be an etiologically heterogeneous and biologically determined developmental disorder characterized by severe disturbances in reciprocal social relations, impaired development of language and communication skills and by limited repertoire of behavioral patterns with a restricted ability of abstraction (American Psychiatric Association, 1994). In recent years, the number of subjects being diagnosed with autism and associated syndromes has shown a significant increase (Powell et al., 2000, Chakrabarti and Fombonne, 2001, Kaye et al., 2001); for this reason, research on autism is assuming increasing importance.

The causes of autism have not yet been fully identified; however, it is well known that it can be caused by a variety of pathological events affecting brain development and which can occur before, during or after birth. Genetic factors might be of primary importance (Bailey et al., 1995) but the exact location of the eventually relevant genes has not yet been identified. In the absence of specific biological markers, autism is defined purely in terms of the behavioral patterns displayed, and its diagnosis is based on internationally accepted classification systems, such as the DSM-IV (American Psychiatric Association, 1994) and the ICD-10 (World Health Organization, 1992).

Among the numerous deficits in autistic children, abnormalities in central sensory input processing have been described by different authors (Verbaten et al., 1991, Kemner et al., 1994); for this reason, a number of studies involving the measurement of event-related potentials (ERPs) in autistic children were carried out and results mostly regarding the analysis of the P300 were reported (Courchesne et al., 1989, Ciesielski et al., 1990, Lincoln et al., 1993, Lincoln et al., 1995). Almost all these studies showed a decrease in the auditory P300 amplitude, and the results were interpreted as the difficulty of autistic children in modifying their expectancies to contextually relevant sequences of information.

In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two additional automatic components of the auditory ERP: the mismatch negativity (MMN)—a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced (Näätänen, 2000)—and the novelty-related P3 (or P3a) which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli (Escera et al., 2000, Friedman et al., 2001).

Section snippets

Subjects and methods

Ten male subjects, mean age 12.3 years (SD 4.95, range 6–19), affected by autism and mental retardation were admitted to this study. The diagnosis of autism was made according to the DSM-IV (American Psychiatric Association, 1994) criteria for autistic disorder and a score on the Childhood Autism Rating Scale (Schopler et al., 1980) between 30 and 50. All patients were also mentally retarded and were drug-free from at least 2 weeks before the study began. All subjects were evaluated from a

N1

Table 1 shows the comparison between N1 latency and amplitude recorded from 3 scalp locations (Fz, Cz and Pz), in normal controls and autistic patients, and evoked by the standard stimuli. In this table, it is possible to see that no statistically significant difference was found in the amplitude of auditory evoked potentials recorded after the presentation of standard stimuli between the two groups. On the contrary, the latency of the N1 component was significantly shorter in the autistic

Discussion

As already said in Section 1, abnormalities in central sensory input processing have been described by different authors in autistic children (Verbaten et al., 1991, Kemner et al., 1994); for this reason, a number of studies involving the measurement of ERPs in autistic children were carried out and results mostly regarding the analysis of the P300 (or P3b) were reported (Courchesne et al., 1989, Ciesielski et al., 1990, Lincoln et al., 1993, Lincoln et al., 1995). Almost all of these studies

References (44)

  • T Rinne et al.

    Separate time behaviors of the temporal and frontal mismatch negativity sources

    Neuroimage

    (2000)
  • M Sallinen et al.

    Is the appearance of mismatch negativity during stage 2 sleep related to the elicitation of K-complex?

    Electroenceph clin Neurophysiol

    (1994)
  • S Seri et al.

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

    Clin Neurophysiol

    (1999)
  • N.K Squires et al.

    Two varieties of long-latency positive waves evoked by unpredictable auditory stimuli in man

    Electroenceph clin Neurophysiol

    (1975)
  • J Townsend et al.

    Event-related brain response abnormalities in autism: evidence for impaired cerebello-frontal spatial attention networks

    Brain Res Cogn Brain Res

    (2001)
  • K Alho

    Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes

    Ear Hear

    (1995)
  • American Psychiatric Association

    Diagnostic and statistical manual of mental disorders

    (1994)
  • A Bailey et al.

    Autism as a strongly genetic disorder: evidence from a British twin study

    Psychol Med

    (1995)
  • S Chakrabarti et al.

    Pervasive developmental disorders in preschool children

    J Am Med Assoc

    (2001)
  • E Courchesne

    Neuroanatomic imaging in autism

    Pediatrics

    (1991)
  • E Courchesne et al.

    Pathophysiologic findings in nonretarded autism and receptive developmental language disorder

    J Autism Dev Disord

    (1989)
  • E Courchesne et al.

    Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic an hyperplastic subgroups with MR imaging

    Am J Roentgenol

    (1994)
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