Auditory event-related potentials and alpha oscillations in the psychosis prodrome: Neuronal generator patterns during a novelty oddball task

Abstract

Prior research suggests that event-related potentials (ERP) obtained during active and passive auditory paradigms, which have demonstrated abnormal neurocognitive function in schizophrenia, may provide helpful tools in predicting transition to psychosis. In addition to ERP measures, reduced modulations of EEG alpha, reflecting top-down control required to inhibit irrelevant information, have revealed attentional deficits in schizophrenia and its prodromal stage. Employing a three-stimulus novelty oddball task, nose-referenced 48-channel ERPs were recorded from 22 clinical high-risk (CHR) patients and 20 healthy controls detecting target tones (12% probability, 500 Hz; button press) among nontargets (76%, 350 Hz) and novel sounds (12%). After current source density (CSD) transformation of EEG epochs (−200 to 1000 ms), event-related spectral perturbations were obtained for each site up to 30 Hz and 800 ms after stimulus onset, and simplified by unrestricted time-frequency (TF) principal components analysis (PCA). Alpha event-related desynchronization (ERD) as measured by TF factor 610–9 (spectral peak latency at 610 ms and 9 Hz; 31.9% variance) was prominent over right posterior regions for targets, and markedly reduced in CHR patients compared to controls, particularly in three patients who later developed psychosis. In contrast, low-frequency event-related synchronization (ERS) distinctly linked to novels (260–1; 16.0%; mid-frontal) and N1 sink across conditions (130–1; 3.4%; centro-temporoparietal) did not differ between groups. Analogous time-domain CSD-ERP measures (temporal PCA), consisting of N1 sink, novelty mismatch negativity (MMN), novelty vertex source, novelty P3, P3b, and frontal response negativity, were robust and closely comparable between groups. Novelty MMN at FCz was, however, absent in the three converters. In agreement with prior findings, alpha ERD and MMN may hold particular promise for predicting transition to psychosis among CHR patients.

Hemifield-dependent N1 and event-related theta/delta oscillations: An unbiased comparison of surface Laplacian and common EEG reference choices

“…While changes in neural oscillations are concealed by the ERP averaging process, a time-frequency decomposition of the single trials used to compute ERPs allows the quantification of event-related spectral changes over time (e.g., Makeig, 1993; Pfurtschneller and Lopes da Silva, 1999; Herrmann et al, 2014). To the extent that event-related oscillations contribute locally to the generation of N1pc, we hypothesize similar hemifield-dependent asymmetric EROs, presumably involving low frequencies in the theta and delta range, as previously observed for an auditory N1 (Kayser et al, 2014). Thus, a secondary goal was to study the association between theta/delta EROs and visual N1pc.…”

“…Principal components analysis (PCA) was used to determine the common sources of variance of the time domain (i.e., waveforms between −100 and 1000 ms) and time-frequency domain (i.e., 30-by-82 ERSP matrices) data (Kayser and Tenke, 2003; Kayser et al, 2014). To warrant a single PCA decomposition across all data transformations, all five data transformations were first rescaled to the same covariance structure within each domain by using the Eigenvalues of the covariance matrix (i.e., computing the ratio relative to the square root of the sum of the diagonal elements).…”

“…Consistent with our prior research, we employed a comprehensive approach for ERP and ERO analysis, which uses principal components analysis (PCA) to yield data-driven component estimates (e.g., Donchin and Heffley, 1978; Kayser and Tenke, 2003; Kayser et al, 2014; Tenke and Kayser, 2005). To further avoid any a priori assumptions typically required for statistical analysis, including independence of observations, normal distribution, homogeneity of variances, and preassigning scalp sites to a repeated measures ANOVA design, topographic differences between hemifields were evaluated for each data transformation by means of unbiased randomization tests (e.g., Maris, 2004; Kayser et al, 2007, 2013).…”

Neural mechanisms of mismatch negativity (MMN) dysfunction in schizophrenia

“…64 ). By contrast, we 34 and others 35,36,65 have linked MMN deficits to impaired theta-frequency response, and underlying NMDAR dysfunction in rodent 66,67 and primate 28 models. At the local circuit level, theta rhythms are tied to interactions involving non-PV cells, especially somatostatintype inhibitory interneurons 6,29,68 .…”

“…We 34 and others 35,36 have previously linked MMN dysfunction in schizophrenia primarily to impaired theta frequency response. In the present study we investigate alpha-frequency activation to standard stimuli as well.…”