Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults

Background

Autism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism.

Methods

Brain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli.

Results

In controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical.

Conclusions

Overall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.

     

Neurophysiological indexes of speech processing deficits in children with specific language impairment

We used neurophysiological and behavioral measures to examine whether children with specific language impairment (SLI) have deficits in automatic processing of brief, phonetically similar vowels, and whether attention plays a role in such deficits. The neurophysiological measure mismatch negativity (MMN) was used as an index of discrimination in two tasks; one in which children ignored the auditory stimuli and watched a silent video and a second in which they attended to the auditory modality. Children with SLI showed good behavioral discrimination, but significantly poorer behavioral identification of the brief vowels than the children with typical language development (TLD). For the TLD children, two neurophysiological measures (MMN and a later negativity, LN) indexed discrimination of the vowels in both tasks. In contrast, only the LN was elicited in either task for the SLI group. We did not see a direct correspondence between the absence of MMN and poor behavioral performance in the children with SLI. This pattern of findings indicates that children with SLI have speech perception deficiencies, although the underlying cause may vary.     

Early and late auditory event-related potentials in cognitively high functioning male adolescents with autism spectrum disorder

Event-related potentials (ERP) studies have offered diverging results in characterizing the basic nature of abnormal sensory processing and discrimination in autism spectrum disorders (ASDs). In the present study we report duration mismatch negativity (MMN) and later ERP components (P3a and P3b) derived from auditory odd-ball paradigms in a homogenous sample of cognitively high functioning male adolescents with ASD. We find significantly reduced frontal and temporal MMN amplitudes and no differences in P3a or P3b amplitudes or latencies compared to controls. These findings are in contrast to recent studies reporting enhanced ERP amplitudes to auditory stimuli, and are more in support of a weakened automatic auditory sensory processing as being central to the abnormal auditory behavioral responses commonly encountered in ASD.     

Automatic processing of tones and speech stimuli in children with specific language impairment

It is well known from behavioural experiments that children with specific language impairment (SLI) have difficulties discriminating consonant-vowel (CV) syllables such as /ba/, /da/, and /ga/. Mismatch negativity (MMN) is an auditory event-related potential component that represents the outcome of an automatic comparison process. It could, therefore, be a promising tool for assessing central auditory processing deficits for speech and non-speech stimuli in children with SLI. MMN is typically evoked by occasionally occurring 'deviant' stimuli in a sequence of identical 'standard' sounds. In this study MMN was elicited using simple tone stimuli, which differed in frequency (1000 versus 1200 Hz) and duration (175 versus 100 ms) and to digitized CV syllables which differed in place of articulation (/ba/, /da/, and /ga/) in children with expressive and receptive SLI and healthy control children (n=21 in each group, 46 males and 17 females; age range 5 to 10 years). Mean MMN amplitudes between groups were compared. Additionally, the behavioural discrimination performance was assessed. Children with SLI had attenuated MMN amplitudes to speech stimuli, but there was no significant difference between the two diagnostic subgroups. MMN to tone stimuli did not differ between the groups. Children with SLI made more errors in the discrimination task, but discrimination scores did not correlate with MMN amplitudes. The present data suggest that children with SLI show a specific deficit in automatic discrimination of CV syllables differing in place of articulation, whereas the processing of simple tone differences seems to be unimpaired.     

The discrimination of and orienting to speech and non-speech sounds in children with autism

The present study aimed to find out how different stages of cortical auditory processing (sound encoding, discrimination, and orienting) are affected in children with autism. To this end, auditory event-related potentials (ERP) were studied in 15 children with autism and their controls. Their responses were recorded for pitch, duration, and vowel changes in speech stimuli, and for corresponding changes in the non-speech counterparts of the stimuli, while the children watched silent videos and ignored the stimuli. The responses to sound repetition were diminished in amplitude in the children with autism, reflecting impaired sound encoding. The mismatch negativity (MMN), an ERP indexing sound discrimination, was enhanced in the children with autism as far as pitch changes were concerned. This is consistent with earlier studies reporting auditory hypersensitivity and good pitch-processing abilities, as well as with theories proposing enhanced perception of local stimulus features in individuals with autism. The discrimination of duration changes was impaired in these children, however. Finally, involuntary orienting to sound changes, as reflected by the P3a ERP, was more impaired for speech than non-speech sounds in the children with autism, suggesting deficits particularly in social orienting. This has been proposed to be one of the earliest symptoms to emerge, with pervasive effects on later development.     

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

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

Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia

Feature-specific stimulus discrimination related to short-term auditory sensory memory can be studied electrophysiologically using a specific event-related potential (ERP) component termed mismatch negativity (MMN), which is generated in the auditory cortex, indexing automatic comparison of the existing memory trace to incoming novel stimuli. Previous results with electroencephalography (EEG) and magnetoencephalography (MEG) suggest that schizophrenia patients have attenuated MMN response and that preattentive auditory processing preceding MMN appears to be functionally asymmetric in schizophrenia. Here we studied parallel MMN activity of the hemispheres using a whole-head MEG by presenting stimulus blocks consisting of frequent standard and infrequent deviant tones to 15 schizophrenia patients and 19 healthy control subjects. Auditory evoked fields (AEFs) were recorded simultaneously over both auditory cortices. The equivalent current dipole (ECD) modeling revealed that patients had significant MMNm reduction (magnetic counterpart of MMN) in both temporal lobes. In addition, patients had significantly delayed MMNm in the left but not in the right hemisphere to ipsilateral auditory stimuli. These results suggest that patients with schizophrenia have impaired auditory processing in the temporal lobes underlying preattentive stimulus discrimination that is also selectively delayed in the left hemisphere.     

Age-related change in neural processing of time-dependent stimulus features

Aging is associated with changes in automatic processing of task-irrelevant stimuli, and this may lead to functional disturbances including repeated orienting to nonnovel events and distraction from task. The effect of age on automatic processing of time-dependent stimulus features was investigated by measurement of the auditory mismatch negativity (MMN) in younger (18-23) and older (55-85) adults. Amplitude of MMN recorded during a paradigm involving low-probability deviation in interstimulus interval (from 500 ms to 250 ms) was found to be reduced in the older group at fronto-central sites. This effect was paralleled by, and correlated to, decreased sensory gating efficiency for component N1 recorded during a separate paradigm involving alternate presentation of auditory stimuli at long (9 s) and short (0.5 s) interstimulus intervals. Further, MMN amplitude was correlated to behavioral performance on a small subset of neuropsychological tests, including the Rey Auditory Verbal Learning Test, within a group of healthy older adults. The results support the hypothesis that aging is associated with declines in automatic processing of time-dependent stimulus features, and this is related to cognitive function. These conclusions are considered in the context of age-related declines in prefrontal cortex function and associated increases in susceptibility to task-irrelevant stimuli.     

Mismatch negativity in schizophrenia: a meta-analysis

BACKGROUND: Mismatch negativity (MMN) is an auditory event-related potential that provides an index of automatic context-dependent information processing and auditory sensory memory. Many studies have reported abnormalities in the generation of MMN in schizophrenia. The objective of this study was to assess the magnitude of this deficit and associated factors. METHOD: Studies of MMN in schizophrenia were identified and included in a meta-analysis to estimate the mean effect size. Effects of duration of illness, gender ratio, age of patients, type of MMN (duration versus frequency MMN) and characteristics of the test paradigms (deviant probability, magnitude of standard-deviant difference) on effect size were assessed. RESULTS: Of 62 identified studies 32 met our inclusion criteria. The mean effect size was 0.99 (95% confidence intervals: 0.79, 1.29). Overall, no specific factor was significantly associated with MMN deficits, although MMN to stimuli differing in duration appeared more impaired in schizophrenia than MMN to frequency deviants. In addition, effect sizes of frequency MMN were significantly correlated with duration of illness. CONCLUSIONS: MMN deficits are a robust feature in chronic schizophrenia and indicate abnormalities in automatic context-dependent auditory information processing and auditory sensory memory in these patients. Reports of normal MMN in first-episode schizophrenia and the association of deficits in frequency MMN with illness duration suggest that MMN may index ongoing neuropathological changes in the auditory cortex in schizophrenia.     

Altered responses to tone and phoneme mismatch in kindergartners at familial dyslexia risk

Differences in automatic auditory processing between kindergartners with (n = 31) and without (n = 29) familial dyslexia risk were investigated using frequency and phoneme mismatch negativity (MMN) paradigms with small deviance and short intervals. During an early mismatch response segment children at risk tended to have more mid-frontal positivity than controls, especially to phoneme deviance. Significant group differences were found in the late MMN segment, where the mismatch response of children at risk was attenuated to frequency deviance and less left lateralised to phoneme deviance. This indicates deviant automatic processing of phoneme and simple tone deviance in children at risk. These differences might be just related to the dyslexia risk or more specifically to future reading difficulties and thus be useful for early recognition of dyslexia.     

Atypical attention to voice in toddlers and pre-schoolers with autism spectrum disorder is related to unimpaired cognitive abilities. An ERP study

BackgroundSound perception in autism spectrum disorder (ASD) is usually at typical levels, even when auditory stimuli carry a social value, as it is the case for speech. Nevertheless, orienting to sounds in a speech context might be atypical in some individuals with ASD, which in ERP studies is reflected by a diminished P3a component. As P3 values and cognitive abilities seem to be inversely related under some circumstances, the current study investigates whether diminished attentional orienting to sounds in speech is equally observable in children with ASD with and without developmental delay (DD).MethodChildren with typical development (TD, n = 17) or ASD, with or without comorbid DD (ASD/DD, n = 22, and ASD/noDD, n = 12), aged 1.5 through 4 years took part in a passive auditory oddball task while EEG data were recorded. The paradigm consisted in the presentation of two deviant stimuli (one vowel sound and one complex tone) either in a speech or in a non-speech context.ResultsWe found overall more negative MMN voltages in both ASD groups compared to TD. For P3a mean voltages, we found an attenuated response in children ASD/noDD when deviant tones were presented in speech, but not in other conditions. Children with ASD/DD did not differ from TD in P3a mean voltages.ConclusionAtypical speech sound processing might be more accentuated in children with ASD/noDD than in their peers with comorbid DD. This finding is interpreted within the theoretical framework of neural adaptation.     

Candidate Electrophysiological Endophenotypes of Hyper-Reactivity to Change in Autism

Although resistance to change is a main feature of autism, the brain processes underlying this aspect of the disorder remain poorly understood. The aims of this study were to examine neural basis of auditory change-detection in children with autism spectrum disorders (ASD; N = 27) through electrophysiological patterns (MMN, P3a) and to test whether these are quantitatively related to intolerance of change (using the BSE-R scale). ASD displayed significantly shorter MMN latency and larger P3a than controls, indicating a greater tendency to switch attention to deviant events. These electrophysiological abnormalities were significantly more marked in children who displayed greater difficulties in tolerating change. The atypical neurophysiological mechanism of change perception identified might thus be associated with one of the hallmark behavioural manifestations of autism.     

Mismatch negativity in socially withdrawn children.

BACKGROUND: Individual differences in auditory processing have been associated with social withdrawal, introversion, and other forms of dysfunction in social engagement. The goal of this study was to investigate the characteristics of an electrophysiologic response that is seen to index early cortical auditory processing (mismatch negativity, MMN) among socially withdrawn and more sociable control children. METHODS: Auditory event-related potentials to standard and deviant tone stimuli were computed for 23 socially withdrawn children and 22 control subjects. We calculated MMN difference waveforms for frontal, central, and parietal electrode sites. RESULTS: Socially withdrawn children had smaller MMN amplitude and longer MMN latencies compared with more sociable control children. CONCLUSION: The findings point to the involvement of individual differences in early cortical auditory processing in childhood social withdrawal. Reduced MMN amplitude and delayed latency may index a component of social withdrawal seen in socially withdrawn children and in depressed and schizophrenic patients. The existence of a secondary MMN generator in the frontal cortex may provide a link between the hypothesized frontal lobe involvement in childhood social withdrawal, schizophrenia, and depression and the MMN reductions seen in these conditions.     

The mismatch negativity (MMN) response to complex tones and spoken words in individuals with aphasia

Background: The mismatch negativity (MMN) is a fronto-centrally distributed event-related potential (ERP) that is elicited by any discriminable auditory change. It is an ideal neurophysiological tool for measuring the auditory processing skills of individuals with aphasia because it can be elicited even in the absence of attention. Previous MMN studies have shown that acoustic processing of tone or pitch deviance is relatively preserved in aphasia, whereas the basic acoustic processing of speech stimuli can be impaired (e.g., auditory discrimination). However, no MMN study has yet investigated the higher levels of auditory processing, such as language-specific phonological and/or lexical processing, in individuals with aphasia. Aims: The aim of the current study was to investigate the MMN responses of normal and language-disordered subjects to tone stimuli and speech stimuli that incorporate the basic auditory processing (acoustic, acoustic-phonetic) levels of non-speech and speech sound processing, and also the language-specific phonological and lexical levels of spoken word processing. Furthermore, this study aimed to correlate the aphasic MMN data with language performance on a variety of tasks specifically targeted at the different levels of spoken word processing. Methods & Procedures: Six adults with aphasia (71.7 years ±3.0) and six healthy age-, gender-, and education-matched controls (72.2 years ±5.4) participated in the study. All subjects were right-handed and native speakers of English. Each subject was presented with complex harmonic tone stimuli, differing in pitch or duration, and consonant-vowel (CV) speech stimuli (non-word /de:/ versus real word /deI/). The probability of the deviant for each tone or speech contrast was 10%. The subjects were also presented with the same stimuli in behavioural discrimination tasks, and were administered a language assessment battery to measure their auditory comprehension skills. Outcomes & Results: The aphasic subjects demonstrated attenuated MMN responses to complex tone duration deviance and to speech stimuli (words and non-words), and their responses to the frequency, duration, and real word deviant stimuli were found to strongly correlate with performance on the auditory comprehension section of the Western Aphasia Battery (WAB). Furthermore, deficits in attentional lexical decision skills demonstrated by the aphasic subjects correlated with a word-related enhancement demonstrated during the automatic MMN paradigm, providing evidence to support the “word advantage effect”, thought to reflect the activation of language-specific memory traces in the brain for words. Conclusions: These results indicate that the MMN may be used as a technique for investigating general and more specific auditory comprehension skills of individuals with aphasia, using speech and/or non-speech stimuli, independent of the individual's attention. The combined use of the objective MMN technique and current clinical language assessments may result in improved rehabilitative management of aphasic individuals.     

Atypical perceptual and neural processing of emotional prosodic changes in children with autism spectrum disorders

Objective

The present study explored the processing of emotional speech prosody in school-aged children with autism spectrum disorders (ASD) but without marked language impairments (children with ASD [no LI]).

Auditory event related potentials in children with peripheral hearing loss

ObjectiveThe aim of the study was to investigate the neurophysiological responses in children with hearing loss.MethodsCortical auditory evoked potentials and Mismatch Negativity (MMN) Responses were recorded in 40 children, 9–12 years old: 12 with hearing loss, 12 with central auditory processing disorder (CAPD) and 16 with normal hearing. Passive oddball paradigms were used with nonverbal and verbal stimuli.ResultsFor P1, no significant group differences were observed. A significant reduction in N2 amplitude with all stimuli was observed in the group of children with hearing loss compared to the results of those with normal hearing. N2 results did not reveal any significant differences between the group of children with hearing loss and the children with CAPD. MMN amplitude indicated a trend toward larger MMN amplitude among the group of children with hearing loss compared to the value of those of children with CAPD.ConclusionsAbnormal N2 characteristics could be a manifestation of a specific signature in children with hearing loss. This cortical response could be considered as a neurophysiologic marker of central auditory processing deficits in these children.SignificanceResults suggest maturational delays and/or deficits in central auditory processing in children with hearing loss.     

A modified oddball paradigm "cross-modal delayed response" and the research on mismatch negativity

A modified oddball paradigm was developed to facilitate the focus of attention and to minimize target effects on deviant-related components of auditory and visual event-related potentials (ERPs) elicited with long interstimulus intervals. Subjects were required to focus on either the visual or auditory stimulus in each stimulus block. Deviant-related components were obtained by subtracting ERPs of the standard stimulus from that of the deviant stimulus for each modality with each stimulus condition. Results showed that auditory mismatch negativity (MMN) and a visual early deviant related negativity (DRN1) were elicited both when stimuli were attended and unattended. In contrast, N2b and P3 were produced only under the attended condition. In comparison of attended MMN and unattended MMN at three time windows (100-150 ms, 150-200 ms, and 200-250 ms) of MMN zone, different scalp distributions were shown, depending on the time windows. This result suggests that the attended auditory MMN is a mixed wave, consisting of genuine MMN, N2b, and possible P165. The effect of attention on MMN may stem from the contamination of these overlapping components. With the present paradigm, at least three sensory memory traces have to be maintained simultaneously in multiple sensory modalities to support automatic processing.     

Differentiation of negative event-related potentials in an auditory discrimination task.

Several different negative potentials elicited in auditory perceptual tasks make spatially and temporally overlapping contributions to the scalp-recorded event-related potential. Frequent non-target tones in a 2-stimulus oddball pitch discrimination task, when compared with the same stimuli in ignore or simple reaction time conditions, elicit a negative deflection with two peaks (NA1 and NA2) differing in their latency and topography from the exogenous N92-P156 deflections. Oddball tones, when compared with the frequent ones, elicit mismatch negativity (MMN) in both ignore and discrimination conditions; MMN displays a frontocentral-posterolateral polarity inversion. In the discrimination condition, MMN is followed by N2 and P3b; the former has a more central amplitude maximum than MMN, and no posterolateral polarity inversion. When the pitch discrimination task was made more difficult, there was no effect on NA1 or NA2, but the latency of MMN, N2, P3b, and reaction time all increased in parallel. It is hypothesized that MMN reflects the outcome of an automatic mismatch detection process, and that the subsequent processing of targets is related to the event of mismatch detection.     

Grammar processing outside the focus of attention: an MEG study

To address the cerebral processing of grammar, we used whole-head high-density magnetoencephalography to record the brain's magnetic fields elicited by grammatically correct and incorrect auditory stimuli in the absence of directed attention to the stimulation. The stimuli were minimal short phrases of the Finnish language differing only in one single phoneme (word-final inflectional affix), which rendered them as either grammatical or ungrammatical. Acoustic and lexical differences were controlled for by using an orthogonal design in which the phoneme's effect on grammaticality was inverted. We found that occasional syntactically incorrect stimuli elicited larger mismatch negativity (MMN) responses than correct phrases. The MMN was earlier proposed as an index of preattentive automatic speech processing. Therefore, its modulation by grammaticality under nonattend conditions suggests that early syntax processing in the human brain may take place outside the focus of attention. Source analysis (single-dipole models and minimum-norm current estimates) indicated grammaticality dependent differential activation of the left superior temporal cortex suggesting that this brain structure may play an important role in such automatic grammar processing.     

The Modality Shift Experiment in Adults and Children with High Functioning Autism

This study used the modality shift experiment, a relatively simple reaction time measure to visual and auditory stimuli, to examine attentional shifting within and across modalities in 33 children and 42 adults with high-functioning autism as compared to matched numbers of age- and ability-matched typical controls. An exaggerated “modality shift effect” relative to the TD children occurred for the children with autism in conditions involving the reaction time when shifting from sound to light but not from light to sound. No exaggerated MSE was found for the adults with autism; rather, their responses were characterized by a generalized slowness relative to the adults with TD. These results suggest a lag in maturational development in autism in basic information processing mechanisms.