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

Abstract

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.

Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia

“…A more recent study, however, found no significant MMN deficit to 800 µs ITD deviants in Sz when these were intermixed with other deviants in an optimal, multi-feature paradigm. However, the study also did not find deficits in other MMN types (38).…”

“…In Sz and CHR, the vast majority of studies have been performed using pitch and duration deviants, which are easiest to generate and manipulate parametrically, and which show subtle differences in terms of sensitivity to patient type (6,45). Here, we additionally evaluated integrity of location MMN generation, which has been studied in only a few prior Sz studies (37,38,40), and has not previously been investigated in CHR. As observed here (Table 2), location MMN has shorter onset latency than other deviant types, suggesting deviance detection even within subcortical components of the central auditory pathway.…”

“…To date, a limited number of studies have investigated localization ability and location MMN generation in Sz (37,38). In two prior studies, we have observed intercorrelations between impaired localization ability and severity of both thought disorder and auditory verbal hallucinations (AVH), such that severity of AVH correlated with paradoxically preserved MMN to right hemifield stimuli and severity of thought disorder correlated significantly with impaired spatial location ability to right hemifield stimuli (39,40).…”

The Neuronal Basis of Predictive Coding Along the Auditory Pathway: From the Subcortical Roots to Cortical Deviance Detection

“…The computational feature behind deviance detection is currently thought to be foundation and trigger of higher order cognitive functions (Näätänen, Astikainen, Ruusuvirta, & Huotilainen, 2010) such as attention (Fritz, Elhilali, David, & Shamma, 2007; Sussman, Winkler, & Wang, 2003) and memory (Bartha-Doering, Deuster, Giordano, am Zehnhoff-Dinnesen, & Dobel, 2015; Ranganath & Rainer, 2003). Consequently, it is not surprising that MMN is not only disrupted in patients suffering from neurodevelopmental and psychiatric conditions, with a characteristically prominent reduction in schizophrenia (Baldeweg, Klugman, Gruzelier, & Hirsch, 2004; Damaso, Michie, & Todd, 2015; Ells et al., 2018; Fisher et al., 2018; Haigh et al., 2017; Javitt & Sweet, 2015; Joshi et al., 2018; Kantrowitz, Swerdlow, Dunn, & Vinogradov, 2018; Koshiyama et al., 2018; Näätänen & Kähkönen, 2009; Todd, Harms, Schall, & Michie, 2013), but also altered in other pathologies such as Parkinson’s disease (Brønnick, Nordby, Larsen, & Aarsland, 2010; Heldmann et al., 2017; Minks et al., 2014; Pekkonen, Jousmäki, Reinikainen, & Partanen, 1995; Seer, Lange, Georgiev, Jahanshahi, & Kopp, 2016; Solís-Vivanco et al., 2011), Alzheimer’s disease (Idrizbegovic, Hederstierna, & Rosenhall, 2016; Jiang et al., 2017; Papadaniil et al., 2016; Pekkonen, 2000; Pekkonen, Hirvonen, Jääskeläinen, Kaakkola, & Huttunen, 2001; Tsolaki et al., 2017), autism spectrum disorders (Goris et al., 2018; Hudac et al., 2018; Schwartz, Shinn-Cunningham, & Tager-Flusberg, 2018; Vlaskamp et al., 2017), and language impairments (Davids et al., 2011; Kujala & Leminen, 2017). Because of this, MMN has become a central tool in cognitive and clinical neuroscience (Bartha-Doering et al., 2015; Kujala, Tervaniemi, & Schröger, 2007; Näätänen, Paavilainen, Rinne, & Alho, 2007; Näätän...…”

MMN and P3a Elicited by a Novelty Oddball Paradigm Are Not Reduced in Early-Phase Psychosis

“…Additional factors such as symptomotology [17,22,26], social and occupational function (as discussed above) [11,12], gray matter deficits [13], or duration of illness [28,29] should be taken into account in addition to a reduced MMN waveform. P3a also holds promise as a biomarker for schizophrenia; several studies reported reduced amplitudes compared to controls [25,[57][58][59][60]. As with MMN, the type of deviant used appears to impact the reliability of finding a reduced P3a amplitude, and additional factors (such as symptomology and functionability) have influence and should be considered alongside waveform reduction in establishing a biomarker.…”