Auditory Mismatch Negativity and P300a Elicited by the "Optimal" Multi-feature Paradigm in Early Schizophrenia.

The mismatch negativity (MMN) is an EEG-derived event-related potential (ERP) elicited by any violation of a predicted auditory "rule," regardless of whether one is attending to the stimuli and is thought to reflect updating of the stimulus context. Redirection of attention toward a rare, distracting stimulus event, however, can be measured by the subsequent P3a component of the P300. Chronic schizophrenia patients exhibit robust MMN deficits, as well as reductions in P3a amplitude. While, the substantial literature on the MMN in first-episode and early phase schizophrenia in this population reports reduced amplitudes, there also exist several contradictory studies. Conversely, P3a reduction in this population is relatively consistent, although the literature investigating this is small. The primary goal of this study was to contribute to our understanding of whether auditory change detection mechanisms are altered in early phase schizophrenia and, if so, under what conditions. Event-related potentials elicited by duration, frequency, gap, intensity, and location deviants (as elicited by the "optimal" multi-feature paradigm) were recorded in 14 early phase schizophrenia (EP) patients and 17 healthy controls (HCs). Electrical activity was recorded from 15 scalp electrodes. MMN/P3a amplitudes and latencies for each deviant were compared between groups and were correlated with clinical measures in EPs. There were no significant group differences for MMN amplitudes or latencies, though EPs did exhibit reduced P3a amplitudes to gap and duration deviants. Furthermore, PANSS (Positive and Negative Syndrome Scale) positive symptom scores were correlated with intensity MMN latencies and duration P3a amplitudes in EPs. These findings suggest that MMNs may not be as robustly reduced in early phase schizophrenia (relative to chronic illness), but that alterations may be more likely in patients with increased positive symptomatology. Furthermore, these findings offer further support to previous work suggesting that the understudied P3a may have good complementary utility as a marker of early cortical dysfunction in psychosis.

Alterations of complex mismatch negativity (cMMN) elicited by a two-tone pattern paradigm in early-phase psychosis.

The mismatch negativity (MMN) is a component of the event-related potential (ERP) elicited by a change in auditory stimulation (e.g., the occurrence of a deviant sound that violates the rules or regularities of the preceding stimulus sequence) regardless of whether one is attending to the change or not. As such, the MMN provides a useful index of pre-attentive cognition. While decreases in MMN amplitude are robustly observed in chronic schizophrenia, these deficits are less consistently present at the early phase of the illness. The current study utilizes a two-tone pattern paradigm that requires more complex computations than typical oddball stimulus presentations, which may be more appropriate for elucidating MMN deficits in an early phase psychosis (EP) sample. The stimuli were a standard sequence consisting of two alternating tones with different tonal frequencies (eg. ABABAB…), with MMN-eliciting pattern violations created by repetitions of either the A or the B tone. EEG recordings of 15 EP participants and 12 healthy controls (HCs) were collected. While no between-group differences were observed, MMN amplitudes in the EP group were correlated with positive and negative psychosis symptom scores. Follow-up analysis stratifying EP participants according to illness duration showed a reduced MMN amplitude in EP participants with a longer (2+ years) duration of illness, but not in EP participants who were within the first year of illness. These findings suggest a two-tone pattern paradigm may be useful in characterizing MMN-indexed cortical impairment later in the early phase of the illness, but not at first episode.

Finding the missing-stimulus mismatch negativity (MMN) in early psychosis: altered MMN to violations of an auditory gestalt.

The mismatch negativity (MMN) is an EEG-derived event-related potential (ERP) elicited by any violation of a predicted auditory 'rule', regardless of whether one is attending to the stimuli, and is thought to reflect updating of the stimulus context. Chronic schizophrenia patients exhibit robust MMN deficits, while MMN reduction in first-episode and early phase psychosis is significantly less consistent. Traditional two-tone "oddball" MMN measures of sensory information processing may be considered too simple for use in early phase psychosis in which pathology has not progressed fully, and a paradigm that probes higher order processes may be more appropriate for elucidating auditory change detection deficits. This study investigated whether MMN deficits could be detected in early phase psychosis (EP) patients using an abstract 'missing stimulus' pattern paradigm (Salisbury, 2012). The stimuli were 400 groups of six tones (1000Hz, 50ms duration, 330ms stimulus onset asynchrony), which was presented with an inter-trial interval of 750ms. Occasionally a group contained a deviant, meaning that it was missing either the 4th or 6th tone (50 trials each). EEG recordings of 13 EP patients (≤5year duration of illness) and 15 healthy controls (HC) were collected. Patients and controls did not significantly differ on age or years of education. Analyses of MMN amplitudes elicited by missing stimuli revealed amplitude reductions in EP patients, suggesting that these deficits are present very early in the progression of the illness. While there were no correlations between MMN measures and measures such as duration of illness, medication dosage or age, MMN amplitude reductions were correlated with positive symptomatology (i.e. auditory hallucinations). These findings suggest that MMNs elicited by the 'missing stimulus' paradigm are impaired in psychosis patients early in the progression of illness and that previously reported MMN-indexed deficits related to auditory hallucinations in chronic patients may also be present in EP patients. As such, this paradigm may have promise in identifying early processing deficits in this population.