Research using latent variable models demonstrates that pre-attentive measures of early auditory processing (EAP) and cognition may initiate a cascading effect on daily functioning in schizophrenia. However, such models fail to account for relationships among individual measures of cognition and EAP, thereby limiting their utility. Hence, EAP and cognition may function as complementary and interacting measures of brain function rather than independent stages of information processing. Here, we apply a data-driven approach to identifying directional relationships among neurophysiologic and cognitive variables.

Using data from the Consortium on the Genetics of Schizophrenia 2, we estimated Gaussian Graphical Models and Bayesian networks to examine undirected and directed connections between measures of EAP, including mismatch negativity and P3a, and cognition in 663 outpatients with schizophrenia and 630 control participants.

Chain structures emerged among EAP and attention/vigilance measures in schizophrenia and control groups. Concerning differences between the groups, object memory was an influential variable in schizophrenia upon which other cognitive domains depended, and working memory was an influential variable in controls.

Measures of EAP and attention/vigilance are conditionally independent of other cognitive domains that were used in this study. Findings also revealed additional causal assumptions among measures of cognition that could help guide statistical control and ultimately help identify early-stage targets or surrogate endpoints in schizophrenia.

Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR).

Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC).

The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP.

Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied.

A total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression.

MMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(β) = 2.100, 95% confidence interval (CI) 1.104–3.993, p = 0.024] and nonremission in CHR individuals [Exp(β) = 1.898, 95% CI 1.065–3.374, p = 0.030].

These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.

Obsessive-compulsive disorder (OCD) patients with poor response to serotonin reuptake inhibitors (SRIs) may have dysfunction involving other neurotransmitters, including glutamate. Mismatch negativity (MMN), an event-related potential dependent on glutamatergic functioning, has not been studied in the adult OCD population and SRI non-responders.

To compare the amplitude of MMN between OCD subjects who have responded(R) and not responded(NR) to SRIs, with healthy volunteers(HV).

MMN was measured in 15 OCD subjects fulfilling DSM-IV criteria (8 non-responders and 7 responders) and 22 healthy volunteers. Auditory MMN was measured using a multi-feature paradigm consisting of two variants each in frequency, duration, and intensity domains. EEG was recorded using 64 channel electrodes at 1000Hz. Epochs of 700 ms were extracted for each stimulus. MMN was evaluated as peak difference between the deviant and standard stimulus. MMN amplitudes at Fz were used for comparison between the groups using Kruskal-Wallis test followed by posthoc analysis, with significance set at p<0.05.

There was no significant difference in age/gender distribution between the three groups and duration of illness between the two OCD groups. There was a significant difference in MMN amplitude of a frequency deviant between the three groups (H=7.312,P=0.026). Post-hoc pairwise analyses revealed a significant reduction in MMN amplitude in NRs as compared to the HV group (H=10.9,P=0.04).

The results are suggestive of glutamatergic dysfunction in OCD subjects with poor response to SRIs. The findings have to be replicated in larger samples employing other paradigms to evaluate glutamatergic functioning and have future potential in understanding treatment response to SRIs.

Individuals with attention-deficit hyperactivity disorder (ADHD) often display over-response to stimuli that are irrelevant to the ongoing task, and their attentional abilities disproportionately worsen in the presence of competing stimuli. Auditory event-related potentials (ERPs) such as mismatch negativity (MMN) and P3a using the passive oddball paradigm have been studied in children and adolescents with ADHD. Still, there is no such data for adults with ADHD. This study aimed to compare the MMN and P3a and their clinical and neurocognitive correlations between drug-naive adults with ADHD and control adults.

We recruited 52 adults with ADHD (26.5 ± 6.2 years), and 62 age-matched controls (25.6 ± 5.6 years). They received the psychiatric interviews, auditory ERP, the Conners' continuous performance test (CCPT), and the Cambridge gambling test (CGT). They also completed the questionnaires about ADHD symptoms and real-world executive functions. MMN and P3a were assessed during a passive duration-deviant auditory oddball paradigm from the midline electrodes Cz.

Adults with ADHD demonstrated smaller Cz MMN amplitude, more severe ADHD symptoms, poorer attention profiles (CCPT), and a wide range of executive dysfunctions than controls. As for the correlates, Cz peak amplitude of MMN correlated with inattention symptoms, executive dysfunctions, attentional vigilance (CCPT), and decision-making (CGT) in ADHD adults but only with decision-making in controls.

Our findings that smaller amplitude of MMN and its differential associated pattern with inattention, real-world executive dysfunction, and decision-making, in drug-naive adults with ADHD from adult controls, provide evidence to support the potential electrophysiological biomarker for adult ADHD.

Deficits of mismatch negativity (MMN) in schizophrenia and individuals at risk for psychosis have been replicated many times. Several studies have also demonstrated the occurrence of subclinical psychotic symptoms within the general population. However, none has yet investigated MMN in individuals from the general population who report subclinical psychotic symptoms.

The MMN to duration-, frequency-, and intensity deviants was recorded in 217 nonclinical individuals classified into a control group (n = 72) and three subclinical groups: paranoid (n = 44), psychotic (n = 51), and mixed paranoid-psychotic (n = 50). Amplitudes of MMN at frontocentral electrodes were referenced to average. Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among groups.

We found no significant differences in MMN amplitudes of surface electrodes. However, significant differences in MMN generation among the four groups were revealed at the frontal source for duration-deviant stimuli (P = 0.01). We also detected a trend-level difference (P = 0.05) in MMN activity among those groups for frequency deviants at the frontal source.

Individuals from the general population who report psychotic symptoms are a heterogeneous group. However, alterations exist in their frontal MMN activity. This increased activity might be an indicator of more sensitive perception regarding changes in the environment for individuals with subclinical psychotic symptoms.

Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).

Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.

Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.

MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.

Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls.

A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment.

Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up.

The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

The purpose of this study was to investigate whether the effects of quetiapine on abnormalities of early auditory processing in patients with schizophrenia were reflected by mismatch negativity (MMN).

Subjects were 23 patients with schizophrenia and 23 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 4-week and after 8-week treatments with quetiapine. Auditory stimuli for event-related potentials consisted of 100 ms/1000 Hz standards, intermixed with 100 ms/1500 Hz frequency deviants and 250 ms/ 1000 Hz duration deviants. A stimulus onset asynchrony of each was 300 ms. Electroencephalograph was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from those elicited by frequency- or duration-deviant stimuli.

Quetiapine decreased all PANSS scores. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure analysis of variance with sessions (i.e. baseline and 4- and 8-week treatments) and MMN type (frequency versus duration) as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes (for MMN type: F = 0.704, df = 1, p = 0.403; for MMN type × session: F = 0.299, df = 2, p = 0.796). Session main effect was significant (F = 3.576, df = 2, p = 0.031). Least square difference tests showed significant differences between MMN amplitudes at 8 weeks and those at both baseline (p = 0.025) and 4 weeks (p = 0.020). MMN amplitudes at 8 weeks were higher than those at baseline.

Quetiapine improved the amplitudes of MMN after the 8-week treatment. MMN offers objective evidence that treatment with the quetiapine may ameliorate preattentive deficits in schizophrenia.