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Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test-retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time-frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test-retest reliability while ITC had poor to fair test-retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test-retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies. [ABSTRACT FROM AUTHOR]

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia patients show widespread deficits in neurocognitive, clinical, and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are robust translational biomarkers associated with schizophrenia and associated with cognitive dysfunction, negative symptom severity, and psychosocial disability. Although these biomarkers are conceptually linked as measures of early auditory information processing, it is unclear whether MMN and gamma-band ASSR account for shared vs. non-shared variance in cognitive, clinical, and psychosocial functioning.Methods: Multiple regression analyses with MMN, gamma-band ASSR, and clinical measures were performed in large cohorts of schizophrenia outpatients (N = 428) and healthy comparison subjects (N = 283).Results: Reduced MMN (d = 0.67), gamma-band ASSR (d = -0.40), and lower cognitive function were confirmed in schizophrenia patients. Regression analyses revealed that reduced MMN amplitude showed unique associations with lower verbal learning and negative symptoms, reduced gamma-band ASSR showed a unique association with working memory deficits, and both reduced MMN amplitude and reduced gamma-band ASSR showed an association with daily functioning impairment in schizophrenia patients.Conclusion: MMN and ASSR measures are non-redundant and complementary measures of early auditory information processing that are associated with important domains of functioning. Studies are needed to clarify the neural substrates of MMN and gamma-band ASSR to improve our understanding of the pathophysiology of schizophrenia and accelerate their use in the development of novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Mismatch negativity (MMN) is a candidate biomarker for early stages of psychosis. Although an association among duration MMN (dMMN), cognitive deficits, and functional outcome in chronic schizophrenia has been shown by a large-scale study, the effects of deviant type and clinical stages have not been investigated.Methods: We investigated the relationships among dMMN, frequency MMN (fMMN), global functioning, and cognitive function in early stages of psychosis. The participants included 26 individuals with recent-onset schizophrenia (ROSZ), 30 individuals with ultra-high risk (UHR), and 20 healthy controls.Results: The correlational analyses revealed that dMMN amplitude, which was impaired in the ROSZ group compared to the healthy controls, correlated with global functioning (Global Assessment of Functioning-Functioning scale) in the ROSZ (r=-0.45) and UHR (r=-0.37) groups. The amplitude of fMMN, which did not differ among the groups, correlated with working memory (r=-0.57) only in the ROSZ group. The path analyses indicated that dMMN had a direct effect on global functioning in the ROSZ and UHR groups while fMMN had a direct effect on working memory only in the ROSZ group.Conclusions: Our findings suggested that the association between MMN and global functioning was specific to the duration deviant and was already present in early stages of psychosis. These findings confirm the usefulness of dMMN as a biological marker of early psychosis to guide treatment interventions. [ABSTRACT FROM AUTHOR]

Background: There is evidence to suggest that people with established psychotic disorders show impairments in the mismatch negativity induced by a frequency-deviant sound (fMMN), and that these impairments worsen with the deterioration of psychotic symptoms. This study aimed to test whether individuals at ultra-high risk (UHR) for psychosis show pre-morbid impairments in fMMN, and if so, whether fMMN continues to deteriorate with transition to psychosis.Method: fMMN was recorded in a cohort of UHR individuals (n=42) and compared to healthy controls (n=29). Of the 27 UHR participants who returned for a second EEG session, six participants had transitioned to psychosis by 12-month follow-up (UHR-T) and were compared to the 21 participants who did not transition (UHR-NT).Results: fMMN amplitude was significantly reduced, relative to healthy controls, in the UHR cohort. Furthermore, UHR-T individuals showed a significant decrease in fMMN amplitude over the period from baseline to post-transition; this reduction was not observed in UHR-NT.Conclusions: These results suggest that fMMN is abnormal in UHR individuals, as has repeatedly been found previously in people with established psychotic disorders. The finding that fMMN impairment worsens with transition to psychosis is consistent with the staging model of psychosis; however, caution must be taken in interpreting these findings, given the extremely small sample size of the UHR-T group. [ABSTRACT FROM AUTHOR]

One of the most robust electrophysiological features of schizophrenia is reduced mismatch negativity, a component of the event related potential (ERP) induced by rare and unexpected stimuli in an otherwise regular pattern. Emerging evidence suggests that mismatch negativity (MMN) is not the only ERP index of deviance detection in the mammalian brain and that sensitivity to deviant sounds in a regular background can be observed at earlier latencies in both the human and rodent brain. Pharmacological studies in humans and rodents have previously found that MMN reductions similar to those seen in schizophrenia can be elicited by N-methyl-d-aspartate (NMDA) receptor antagonism, an observation in agreement with the hypothesised role of NMDA receptor hypofunction in schizophrenia pathogenesis. However, it is not known how NMDA receptor antagonism affects early deviance detection responses. Here, we show that NMDA antagonism impacts both early and late deviance detection responses. By recording EEG in awake, freely-moving rats in a drug-free condition and after varying doses of NMDA receptor antagonist MK-801, we found the hypothesised reduction of deviance detection for a late, negative potential (N55). However, the amplitude of an early component, P13, as well as deviance detection evident in the same component, were increased by NMDA receptor antagonism. These findings indicate that late deviance detection in rats is similar to human MMN, but the surprising effect of MK-801 in increasing ERP amplitudes as well as deviance detection at earlier latencies suggests that future studies in humans should examine ERPs over early latencies in schizophrenia and after NMDA antagonism. [ABSTRACT FROM AUTHOR]

Abstract: Background: A shorter duration of untreated psychosis in patients with schizophrenia results in better symptomatic and functional outcomes. Therefore, identifying biological markers in the early stages of psychosis is an important step toward early detection and intervention. Mismatch negativity (MMN) and P3a are leading candidate biomarkers. MMN measures differ in their sensitivity to varying deviants. However, this has not been fully addressed in assessing the early stages of psychosis. In the current study, we examined MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. To our knowledge, this is the first study that examined both MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. Methods: Participants consisted of 20 patients with first episode schizophrenia (FES), 21 ultra-high risk (UHR) individuals, and 22 healthy controls (HC). We measured dMMN/dP3a and fMMN/fP3a ERP components by means of a 64 electrodes-cap for EEG recording, and we used two-tone auditory oddball paradigms with 2000 stimuli. Results: The amplitude of dMMN was significantly reduced in FES and UHR compared to HC. The amplitude of fMMN showed no significant difference among the three groups. The amplitudes of dP3a and fP3a were significantly reduced in FES and UHR compared to HC. Conclusion: These findings suggest that dMMN may have higher sensitivity than fMMN whereas dP3a and fP3a may have similar sensitivity in the early stages of psychosis. [Copyright &y& Elsevier]

Abstract: Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode. [Copyright &y& Elsevier]

Cognitive impairment in schizophrenia is an important predictor of clinical and social outcome. In this preliminary study, the correlation between cognitive status and deficits in mismatch negativity (MMN) generation was explored. The MMN response to tone duration deviants was recorded using a new stimulation protocol with continuously changing (‘roving’) standard stimuli in order to measure the effect of standard repetitions on MMN (memory trace effect). Cognitive status of the patient group (n=28) was assessed using neuropsychological screening. Healthy participants (n=20) served as age-matched comparison group.In patients, MMN amplitude in frontal electrodes as well as the MMN memory trace effect was diminished compared to controls. While both measures were inversely related to patient''s age and disease severity, only the MMN memory trace effect was robustly correlated with the degree of neuropsychological impairment. This suggests that ERP measures of auditory system adaptability more appropriately characterise the pathophysiological processes underlying cognitive impairment in schizophrenia than static measures of ERP magnitude. [Copyright &y& Elsevier]

Schizophrenia is associated with dysfunction in language processing. At the earliest stage of language processing, dysfunction of categorical perception of speech sounds in schizophrenia has been demonstrated in a behavioral task. The aim of this study was to assess automatic categorical perception of speech sounds as reflected by event-related changes in magnetic field power in schizophrenia. Using a whole-head magnetoencephalographic recording, the magnetic counterpart of mismatch negativity (MMNm) elicited by a phonetic change was evaluated in 16 right-handed patients with chronic schizophrenia and in 19 age-, sex-, and parental socioeconomic status-matched normal control subjects. Three types of MMNm (MMNm in response to a duration decrement of pure-tone stimuli; a vowel within-category change [duration decrement of Japanese vowel /a/]; vowel across-category change [Japanese vowel /a/ versus /o/]) were recorded. While the schizophrenia group showed an overall reduction in magnetic field power of MMNm, a trend was found toward more distinct abnormalities under the condition of vowel across-category change than under that of duration decrement of a vowel or tone. The patient group did not show abnormal asymmetries of MMNm power under any of the conditions. This study provides physiological evidence for impaired categorical perception of speech sounds in the bilateral auditory cortex in schizophrenia. The language-related dysfunction in schizophrenic patients may be present at the early stage of auditory processing of relatively simple stimuli such as phonemes, and not just at stages involving higher order semantic processes. [Copyright &y& Elsevier]