Auditory brainstem evoked responses in autistic children.

Auditory brainstem evoked responses (ABRs) were studied in 16 autistic children. Three children had severe delays in wave I latency, indicating defective functioning of the peripheral auditory pathway. The remaining subjects also had delayed wave I latency but only for right ear stimulation at the lowest stimulus intensity. Eight autistic children (and no control subjects) had ABR transmission time values 3 SDs beyond the normal mean, suggesting auditory processing defects peripheral to or within the brainstem auditory pathway. These findings (1) may have no causal relationship to the child's autistic handicaps, (2) may represent distortions in auditory input that impair the learning of language, and (3) may reflect an earlier state in which abnormal input directly caused maldevelopment of forebrain systems necessary for language and cognitive function.

Influence of language structure on brain-behavior development.

Lack of exposure to specific sensory patterns during critical periods of development can result in a lack of responsiveness to those stimuli in adulthood. The present study extends these observations to native speakers of Japanese, a language which does not contain the contrastive /r/ and /l/ sounds present in English. Both electrophysiological (P3 event-related evoked potential) and behavioral results indicate deficient or absent discrimination of /r/ versus /l/ sounds in Japanese adults compared to native speakers of English. Thus, language structure appears to provide a subtle yet measurable effect on specific aspects of brain development and function.

P3 responses to prosodic stimuli in adult autistic subjects.

Autistic persons are known to have serious abnormalities in speech prosody. The present study attempted to ascertain whether autistic persons could discriminate and/or recognize prosodic contrasts in auditory stimuli. A group of 11 adult autistic subjects with normal IQ and an age-matched group of normal subjects were studied electrophysiologically and behaviorally during presentations of prosodic and phonemic stimuli. The cognitive P3 potential was recorded in response to rare (20%)/frequent (80%) presentations of phonemic stimuli, 'ba/pa,' linguistic-prosodic stimuli, 'Bob.' (statement)/'Bob?' (question), and emotional-prosodic stimuli, 'Bob' (happy)/'Bob' (angry). Behaviorally, auditory discrimination was tested by requiring a button-press response to each presentation of the rare target stimulus and cognitive association was tested by requiring a match between the verbalized stimulus and an appropriate picture/word. Contrary to our hypothesis, the autistic subjects generally showed normal P3 responses to all stimuli and performed at a normal level in all behavioral tests. However, a significant autistic P3 response to the phoneme 'pa' was not demonstrated. This surprising result was reexamined and shown to reflect an unusually large autistic response to 'pa' as the frequent stimulus in the first recording block, this initial hyper-reactivity prevented a 'frequent/rare' differential when 'pa' was presented as the rare stimulus in a later recording block. In the P3 latency window, both the autistic and control groups showed the largest amplitude responses to emotional-prosodic stimuli; neither the N1 nor P2 showed these stimulus effects. Thus, 'emotional sounds' appear to be particularly effective in activating the neural substrate of the P3 generator system. Overall, these data indicate remarkably normal P3 and behavioral processing of prosodic stimuli by the high-functioning autistic subjects of this study.

Midlatency auditory evoked responses: differential effects of a cholinergic agonist and antagonist.

The effects of a cholinergic antagonist (scopolamine) and agonist (physostigmine) on the auditory middle latency evoked responses (MLRs) were studied in 7 normal male volunteers. Scalp recordings were made from a central (Cz) electrode referenced to linked ear lobes on one channel and to a non-cephalic, sternovertebral reference on a second channel. Three components were statistically analyzed for changes in latency and amplitude: Pa, with peak positivity in the 25-40 msec latency range, Nb, with peak negativity 40-50 msec, and P1, with peak positivity 50-65 msec. Control recordings included responses to click rates of 1, 5, 8 and 10/sec; as has been previously reported, P1 showed a marked decrease and disappeared at the faster rates of stimulation whereas Pa showed no change in amplitude. Intravenous injections of scopolamine resulted in a rapid and complete disappearance of P1 and a slight increase in Pa; concurrently, the subjects reported feeling drowsy but were awake with eyes open through the recordings. Subsequent injections of physostigmine resulted in a rapid reversal of the scopolamine effects so that the subjects became alert, Pa decreased, and P1 reappeared and increased to control amplitudes. Rapid click rates caused P1 to diminish, as in the control period, indicating a common P1 recovery cycle in both the control and physostigmine conditions. These data are discussed in terms of the hypothesis that the P1 generator system is comprised of a cholinergic brain-stem-thalamic component of the ascending reticular activating system.

Midlatency auditory evoked responses: P1 abnormalities in adult autistic subjects.

MLR recordings from a group of 11 high-functioning adult autistic subjects were compared with those from a control group of 11 normal subjects. Components selected for analysis were "Pa", the maximum positivity in the 25-40 msec latency range following stimulus onset, "P1", the maximum positivity within the 50-65 msec latency range, and "Nb," the maximum negative deflection in the 40-50 msec latency range. Statistical analyses of amplitude and latency data were conducted using repeated measures analysis of variance and t test group comparisons. The Pa component showed no significant difference between autistic and control groups. However, 2 types of abnormality were noted in the P1 component: (1) the P1 component was significantly smaller in the autistic subjects at slow rates of stimulation, and (2) the autistic P1 did not change as rates of click stimulation increased from 0.5 to 10/sec, in contrast to the normally produced P1 decrement. Data from the P1 model in the cat, and complementary data from the human, closely link the generator substrate of the P1 potential to cholinergic components of the ascending reticular activating system (RAS) and their thalamic target cells. This is the first report of abnormal P1 responses in autism and strongly suggests that the RAS and/or its post-synaptic thalamic targets may be dysfunctional in this syndrome.

Sources of variability in auditory brain stem evoked potential measures over time.

Auditory brain stem EPs elicited in 10 normal adults by monaural clicks delivered at 72 dB HL, 20/sec showed no significant change in wave latencies or in the ratio of wave I to wave Y amplitude across 250 trial subsets, across 250 trial subsets, across 1500 trial blocks within a test session, or across two test sessions separated by several months. Sources of maximum variability were determined by using mean squared differences with all but one condition constant. 'Subjects' was shown to contribute the most variability followed by 'ears', 'sessions' and 'runs'; collapsing across conditions, wave III latencies were found to be the least variable, while wave II showed the most variability. Some EP morphologies showed extra peaks between waves II and IV, missing wave IV or wave IV fused with wave V. Such variations in wave form morphology were independent of EMG amplitude and were characteristic of certain individuals.