Speech-feature discrimination in children with Asperger syndrome as determined with the multi-feature mismatch negativity paradigm

ObjectiveAsperger syndrome, belonging to the autistic spectrum of disorders, involves deficits in social interaction and prosodic use of language but normal development of formal language abilities. Auditory processing involves both hyper- and hypoactive reactivity to acoustic changes.MethodsResponses composed of mismatch negativity (MMN) and obligatory components were recorded for five types of deviations in syllables (vowel, vowel duration, consonant, syllable frequency, syllable intensity) with the multi-feature paradigm from 8–12-year old children with Asperger syndrome.ResultsChildren with Asperger syndrome had larger MMNs for intensity and smaller MMNs for frequency changes than typically developing children, whereas no MMN group differences were found for the other deviant stimuli. Furthermore, children with Asperger syndrome performed more poorly than controls in Comprehension of Instructions subtest of a language test battery.ConclusionsCortical speech-sound discrimination is aberrant in children with Asperger syndrome. This is evident both as hypersensitive and depressed neural reactions to speech-sound changes, and is associated with features (frequency, intensity) which are relevant for prosodic processing.SignificanceThe multi-feature MMN paradigm, which includes variation and thereby resembles natural speech hearing circumstances, suggests abnormal pattern of speech discrimination in Asperger syndrome, including both hypo- and hypersensitive responses for speech features.     

Attention-dependent allocation of auditory processing resources as measured by mismatch negativity

Mismatch negativity (MMN) is a pre-attentive event-related potential measure of echoic memory. However, recent studies suggest attention-related modulation of MMN. This study investigates duration-elicited MMN in healthy subjects (n = 12) who were performing a visual discrimination task and, subsequently, an auditory discrimination task in a series of increasing task difficulty. MMN amplitude was found to be maximal at centro-frontal electrode sites without hemispheric differences. Comparison of both attend conditions (visual vs. auditory), revealed larger MMN amplitudes at Fz in the visual task without differences across task difficulty. However, significantly smaller MMN in the most demanding auditory condition supports the notion of limited processing capacity whose resources are modulated by attention in response to task requirements.     

The sound of music: differentiating musicians using a fast, musical multi-feature mismatch negativity paradigm

Musicians' skills in auditory processing depend highly on instrument, performance practice, and on level of expertise. Yet, it is not known though whether the style/genre of music might shape auditory processing in the brains of musicians. Here, we aimed at tackling the role of musical style/genre on modulating neural and behavioral responses to changes in musical features. Using a novel, fast and musical sounding multi-feature paradigm, we measured the mismatch negativity (MMN), a pre-attentive brain response, to six types of musical feature change in musicians playing three distinct styles of music (classical, jazz, rock/pop) and in non-musicians. Jazz and classical musicians scored higher in the musical aptitude test than band musicians and non-musicians, especially with regards to tonal abilities. These results were extended by the MMN findings: jazz musicians had larger MMN-amplitude than all other experimental groups across the six different sound features, indicating a greater overall sensitivity to auditory outliers. In particular, we found enhanced processing of pith and sliding up to pitches in jazz musicians only. Furthermore, we observed a more frontal MMN to pitch and location compared to the other deviants in jazz musicians and left lateralization of the MMN to timbre in classical musicians. These findings indicate that the characteristics of the style/genre of music played by musicians influence their perceptual skills and the brain processing of sound features embedded in a musical context. Musicians' brain is hence shaped by the type of training, musical style/genre, and listening experiences.     

Alterations of mismatch negativity (MMN) in schizophrenia patients with auditory hallucinations experiencing acute exacerbation of illness

Auditory verbal hallucinations (AHs), or hearing 'voices', are one of the hallmark symptoms of patients with schizophrenia. The primary objective of this study was to compare hallucinating schizophrenia patients with respect to differences in deviance detection, as indexed by the auditory mismatch negativity (MMN). Patients were recruited during an acute psychotic episode requiring hospitalization, during which time symptoms of psychosis, including auditory hallucinations, are likely to be at their most severe. MMNs to duration, frequency, gap, intensity and location deviants (as elicited by the 'optimal' multi-feature paradigm) were recorded in 12 acutely ill schizophrenia patients (SZ) with persistent AHs and 15 matched healthy controls (HC). Electrical activity was recorded from 32 scalp electrodes. MMN amplitudes and latencies for each deviant were compared between groups and were correlated with trait (PSYRATS) and state measures of AH severity and Positive and Negative Syndrome Scale (PANSS) ratings in SZs. There were significant group differences for duration, gap, intensity and location MMN amplitudes, such that SZs exhibited reduced MMNs compared to HCs. Additionally, gap MMN amplitudes were correlated with measures of hallucinatory state and frequency of AHs, while location MMN was correlated with perceived location of AHs. In summary, this study corroborates previous research reporting a robust duration MMN deficit in schizophrenia, as well as reporting gap, intensity and location MMN deficits in acutely ill schizophrenia patients with persistent AHs. Additionally, MMN amplitudes were correlated with state and trait measures of AHs. These findings offer further support to previous work suggesting that the presence of auditory hallucinations may make a significant contribution to the widely reported MMN deficits in schizophrenia.     

Duration and frequency mismatch negativity in schizophrenia.

OBJECTIVES: The aim of the present study was to elucidate the reasons for apparent inconsistencies in the schizophrenia literature with respect to the mismatch negativity (MMN) waveform of the event-related potential (ERP). While most previous research has shown that MMN is reduced in schizophrenia, there are a small number of studies reporting that frequency MMN is not reduced. METHODS: We recorded ERPs to auditory stimuli with different frequencies and durations from patients with schizophrenia (N = 14) and control subjects (N = 17) of similar age and sex. MMNs to small but discriminable frequency deviants were contrasted with large frequency deviants and duration deviants. RESULTS: Only the MMN to duration deviants was significantly reduced in patients, although there was evidence of a similar trend for large frequency deviants. CONCLUSIONS: The results together with a review of the frequency MMN literature suggest that there are 3 variables which are important in determining whether patients exhibit a reduced MMN to frequency deviants: deviant probability, degree of deviance and interstimulus interval. The results also indicated that patients with schizophrenia may have particular deficits in processing the temporal properties of auditory stimuli. This finding has implications for the pathophysiology of the disorder as time-dependent processing is reliant on the integrity of an extensive network of brain areas consisting of auditory cortex, areas of pre-frontal cortex, the basal ganglia and cerebellum.     

Inhibition in schizophrenia: association with auditory hallucinations

The study investigated whether auditory hallucinations (AH) in schizophrenia are linked to a deficit in inhibition. Two tasks assessing the intentional suppression of cognitive events-the Hayling Sentence Completion Test (HSCT) [Neuropsychologia 34 (1996) 263] and the Inhibition of Currently Irrelevant Memories Task (ICIM) [Nature Neuroscience 2 (1999) 677]-were administered to 42 patients with schizophrenia and 24 normal controls. Presence and severity of symptoms in the patient group were examined using the Positive and Negative Syndrome Scale (PANSS). Patients performed significantly worse on the measures of inhibition compared to controls. More importantly, among patients, significant positive correlations were obtained between an index of AH severity (defined as an increase in frequency of AH on PANSS) and the number of type A errors on the HSCT and errors in the last three runs of the ICIM. An increase in AH severity was, therefore, associated with increasingly impaired control of intentional inhibition. Furthermore, no significant correlations were found between these indices of inhibition and either negative, general or positive symptoms (excluding AH scores).     

The treatment of recurring auditory hallucinations in schizophrenia with rTMS.

BACKGROUND: Auditory hallucinations are a common and disabling problem for many patients with schizophrenia and often fail to respond to optimal antipsychotic therapy. Repetitive transcranial magnetic stimulation (rTMS) has recently been trialled as an alternative treatment option for these patients. These studies have generally been positive, but treatment has only been provided for short periods of time and little is known about the longer-term impact of TMS on the course of hallucinations. METHOD: We describe two cases in which rTMS was provided to patients upon relapse of hallucinations following initial successful rTMS treatment in a clinical trial. RESULTS: A repeat course of rTMS resulted in a marked improvement in the symptoms experienced by these two patients. CONCLUSIONS: rTMS appears to have potential as a long-term treatment for patients with auditory hallucinations, but requires ongoing systematic investigation.     

Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity

The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics (n = 15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics (chi(2) test = 16.13, p < 0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) (r = -0.673, p = 0.008), especially with the hallucinatory behavior subscale (r = -0.677, p = 0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia.     

Temporal resolution in young and elderly subjects as measured by mismatch negativity and a psychoacoustic gap detection task.

OBJECTIVES: The speech understanding difficulties of elderly persons with age-related hearing loss may be related in part to reduced auditory temporal resolution. To investigate the effects of aging on temporal resolution, the electrophysiological and psychoacoustic detection thresholds for a very short silent gap within a pure tone were determined, and the relation between the two test results was examined. METHODS: Behavioral gap detection thresholds were determined in 10 young and 10 elderly normally hearing subjects using an adaptive test procedure. To elicit mismatch negativity (MMN), deviant stimuli with gap durations varying from 6 to 24 ms in 3 ms steps were presented in separate test blocks. RESULTS: There were no significant differences in the psychoacoustic gap detection thresholds between young and elderly subjects. In contrast, longer gaps were needed to elicit MMN in elderly subjects. They also had significantly reduced MMN peak amplitudes, increased MMN peak latencies, a significantly smaller P2 amplitude and longer P2 latency in their responses to the standard stimulus when compared to the same measures in young subjects. CONCLUSIONS: Processing of basic temporal stimulus features in elderly subjects is considerably more reduced at the preattentive level (as indicated by MMN), than when attention is directed to the task (as indicated by the psychoacoustic results).     

The CCK-A receptor gene possibly associated with auditory hallucinations in schizophrenia.

In this study, a PstI polymorphic site with two individual alleles, namely A1 and A2, was identified withinthe boundary between intron 1 and exon 2 of the cholecystokinin (CCK) type A receptor gene. The PstI polymorphic site was used as a genetic marker to study its association with psychotic symptoms in schizophrenia. A significant difference in allelic frequency was found between schizophrenic patients with and without auditory hallucinations(chi(2) = 6.26, df = 1, P = 0.012), and the odds ratio for the allelic association was 2.21 (95% CI 1.18-4.15) with an attributable fraction of 0.1. The frequency of A1-A1 and A1-A2 genotypes showed a significant excess in schizophrenic patients with auditory hallucinations as compared to those without such symptoms (chi(2) = 5.45, df = 1, P = 0.02), and the odds ratio for the genotypic association was 2.27 (95% CI 1. 13-4.57) with an attributable fraction of 0.177. The haplotype-based haplotype relative risk (HHRR) test revealed a significant difference between transmitted and non-transmitted alleles in nuclear families of schizophrenic patients with auditory hallucinations (chi(2) = 4.54, df = 1,P = 0.033) but not in those of schizophrenic patients without them. The present study suggests that the CCK-A receptor gene may be associated with auditory hallucinations in schizophrenia.     

The neurophysiological basis of the auditory continuity illusion: a mismatch negativity study

A sound turned off for a short moment can be perceived as continuous if the silent gap is filled with noise. The neural mechanisms underlying this "continuity illusion" were investigated using the mismatch negativity (MMN), an event-related potential reflecting the perception of a sudden change in an otherwise regular stimulus sequence. The MMN was recorded in four conditions using an oddball paradigm. The standards consisted of 500-Hz, 120-msec tone pips that were either physically continuous (Condition 1) or were interrupted by a 40-msec silent gap (Condition 2). The deviants consisted of the interrupted tone, but with the silent gap filled by a burst of bandpass-filtered noise. The noise either occupied the same frequency region as the tone and elicited the continuity illusion (Conditions 1a and 2a), or occupied a remote frequency region and did not elicit the illusion (Conditions 1b and 2b). We predicted that, if the continuity illusion is determined before MMN generation, then, other things being equal, the MMN should be larger in conditions where the deviants are perceived as continuous and the standards as interrupted or vice versa, than when both were perceived as continuous or both interrupted. Consistent with this prediction, we observed an interaction between standard type and noise frequency region, with the MMN being larger in Condition 1a than in Condition 1b, but smaller in Condition 2a than in Condition 2b. Because the subjects were instructed to ignore the tones and watch a silent movie during the recordings, the results indicate that the continuity illusion can occur outside the focus of attention. Furthermore, the latency of the MMN (less than approximately 200 msec postdeviance onset) places an upper limit on the stage of neural processing responsible for the illusion.     

Specific and unspecific auditory hallucinations in patients with schizophrenia: a magnetoencephalographic study

BACKGROUND/AIMS: Different neuroimaging techniques have indicated that auditory association and language cortices are active in patients with schizophrenia and auditory hallucinations. Auditory verbal hallucinations are thought to arise from a disorder of inner speech, but little is known about their origin. METHODS: Spontaneous magnetoencephalographic (MEG) measurements were recorded with a 74-channel two-sensor system (BIOMAGNES II) in 16 patients with schizophrenia and 8 healthy subjects in frequency ranges from 2 to 6 and 12.5 to 30 Hz. Eight patients had auditory hallucinations during the MEG recordings. RESULTS: The total group of patients with schizophrenia showed a statistically significant elevation of the number of dipoles and dipole density maxima in slow frequency ranges compared to healthy subjects (p <0.001). Significant dipole activities in the fast frequency range were only found during auditory hallucinations (p <0.001). Dipole localization was concentrated in frontal and temporal regions depending on different qualities of hallucinations. In patients with external imperative voices we found a parallel activation of the dorsolateral frontal and temporal cortex. CONCLUSION: We conclude that various auditory hallucinations in schizophrenia are induced by different neuronal activities and may be represented by different cortical regions.     

Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia

BACKGROUND: Mismatch negativity (MMN) specifically the response to tone duration deviants has consistently been shown to be reduced in schizophrenia suggesting dysfunction in auditory sensory memory. As part of a multidimensional approach to the early recognition of psychosis, MMN was investigated as a possible risk factor for later development of psychosis in subjects with a prodromal syndrome. Forty-three prodromal subjects, 31 neuroleptic-free inpatients with schizophrenia and 33 healthy controls were studied. A prodromal state was defined by a cluster 'Cognitive Disturbances' as defined by the 'Bonn Scale for the Assessment of Basic Symptoms' (BSABS), which was found highly predictive of first-episode schizophrenia. To elicit MMN, a three-tone auditory oddball paradigm with 10% 'duration deviants' and 10% 'frequency deviants' was used. RESULTS: MMN amplitudes to tone duration deviants were significantly reduced in the patients with schizophrenia compared to controls. The putatively prodromal subjects also showed a slight, though non-significant reduction of the MMN amplitude that was intermediate between normal controls and patients with schizophrenia, and with a larger within-group variance. CONCLUSION: These results support the view that abnormalities in temporal processing are particularly pronounced in patients with schizophrenia. Prodromal subjects are a heterogeneous group with regard to outcome and time until transition to a first psychotic episode. Follow-up of these putatively prodromal subjects will show whether MMN amplitudes further reduce over time in those developing psychosis and if a reduction is state-dependent.     

Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge

OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.     

Reduced late mismatch negativity and auditory sustained potential to rule‐based patterns in schizophrenia

Complex rule‐based auditory processing is abnormal in individuals with long‐term schizophrenia (SZ), as demonstrated by reduced mismatch negativity (MMN) to deviants in rule‐based patterns and reduced auditory sustained potential (ASP) that appears when grouping tones together. Together, this suggests deficits later in the auditory processing hierarchy in Sz. Here, MMN and ASP were elicited by deviations from a complex zig‐zag pitch pattern that cannot be predicted by simple linear rules. Twenty‐seven SZ and 26 matched healthy controls (HC) participated. Frequent groups of patterns contained eight tones that zig‐zagged in a two‐up one‐down pitch‐based paradigm. There were two deviant patterns: the final tone was either higher in pitch than expected (creating a jump in pitch) or was repeated. Simple MMN to pitch‐deviants among repetitive tones was measured for comparison. Sz exhibited a smaller pitch MMN compared to HC as expected. HC produced a late MMN in response to the repeat and jump‐deviant and a larger ASP to the standard group of tones, all of which were significantly blunted in SZ. In Sz, the amplitude of the late complex MMN was related to neuropsychological functioning, whereas ASP was not. ASP and late MMN did not significantly correlate in HC or in Sz, suggesting that they are not dependent on one another and may originate within distinct processing streams. Together, this suggests multiple deficits later in the auditory sensory‐perceptual hierarchy in Sz, with impairments evident in both segmentation and deviance detection abilities.     

Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations.

BACKGROUND: We used functional magnetic resonance imaging (fMRI) to investigate the frontotemporal disconnection hypothesis of schizophrenia. METHODS: Eight DSM-IV schizophrenia patients and 10 control subjects were studied with fMRI while they thought of the missing last word in 128 visually presented sentences. The fMRI data were analyzed comparing the effect of sentence completion (vs. rest) using a random effects analysis. RESULTS: There were no significant group differences in regional brain responses. Correlation coefficients between left temporal cortex (x = -54, y = -42, z = 3) and left dorsolateral prefrontal cortex (x = -39, y = 12, z = 24) were significantly lower in the schizophrenic group and were negatively correlated with the severity of auditory hallucinations. CONCLUSIONS: Previous demonstrations of hypofrontality in schizophrenia may reflect particular task requirements. Frontotemporal functional connectivity is reduced in schizophrenia and may be associated with auditory hallucinations.     

The relationship of mismatch negativity to quantitative EEG and morphological findings in schizophrenia.

The goal of the present study is to investigate the relationships of mismatch negativity (MMN) to other markers in schizophrenics; Quantitative EEG (QEEG), CT and psychopathological ratings. Thirty unmedicated patients (28.4+/-9.8 y, 20 M) including twenty neuroleptic-naive cases were divided into two groups before treatment; Group A consisted of ten patients with greater MMN amplitudes, while twenty patients with smaller ones were assigned to Group B. In QEEG, Group A showed a closer profile to healthy controls, indicating their function is less distorted. Group B showed greater power in slow wave, slow alpha and fast beta bands. Their greater slow wave may be implicated in cognitive impairment reflected by attenuated MMN as well as greater dilation in lateral ventricles and Sylvian fissures on CT. After pharmacological treatment with conventional neuroleptics, Group A's MMN decreased, whereas that of Group B increased. Furthermore, neuroleptics' EEG-effects observed in Group A were close to the reported profiles of healthy subjects, while those in Group B were distinct from them. Conclusively, MMN might have crucial associations to other measures underlying the brain pathology of schizophrenia. The diagnostic value of MMN as a trait-marker was discussed.     

Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders.

BACKGROUND: One of the most consistent findings in schizophrenia research over the past decade is a reduction in the amplitude of an auditory event-related brain potential known as mismatch negativity (MMN), which is generated whenever a deviant sound occurs in a background of repetitive auditory stimulation. The reduced amplitude of MMN in schizophrenia was first observed for deviant sounds that differ in duration relative to background standard sounds, and similar findings have been observed for sounds that are deviant in frequency. The aim of this study was to determine whether first-degree relatives of schizophrenia patients show a similar reduction in MMN amplitude to duration deviants. METHODS: We measured MMN to duration increments (deviants 100 msec vs. standards 50 msec) in 22 medicated patients with a diagnosis in the schizophrenia spectrum, 17 individuals who were first-degree unaffected relatives of patients, and 21 healthy control subjects. RESULTS: Mismatch negativity amplitude was reduced in patients and relatives compared with control subjects. There were no significant differences between patients and relatives. In contrast, the subsequent positive component, P3a, was larger in relatives compared with patients. CONCLUSIONS: These findings suggest that a reduced MMN amplitude may be an endophenotype marker of the predisposition to schizophrenia.