Auditory steady-state EEG response across the schizo-bipolar spectrum

Abstract

Deviant auditory steady-state responses (aSSRs) in the gamma range (30-90 Hz) may be translational biomarkers for schizophrenia (SZ). This study tests whether aSSR deviations are (i) specific to SZ across the psychosis dimension, (ii) specific to particular frequency bands, and (iii) present in bipolar I disorder without psychosis (BDNP).

Methods: Beta (20-), low- (40-), and high-gamma (80-Hz) aSSRs were measured with EEG and compared across 113 SZ, 105 schizoaffective disorder (SAD), 99 bipolar disorder with psychosis (BDP), 68 BDNP, and 137 healthy comparison subjects (HC). Standard aSSR measures (single-trial power [STP] and inter-trial phase coherence [ITC]), as well as evoked responses to stimulus onsets/offsets and pre-stimulus power, were quantified. Multivariate canonical discriminant analysis was used to summarize variables that efficiently and maximally differentiated groups.

Results: (i) Psychosis groups showed reduced responses on ITC 20 Hz, STP/ITC 40 Hz, STP/ITC 80 Hz, indicating dimensional reductions in aSSR across the psychosis spectrum not specific to aSSR frequency. For the 40- and 80-Hz ITCs there was greater reduction in SZ compared to SAD, possibly indexing cortical disruptions linked to psychosis without mood symptoms. (ii) All probands had elevated pre-stimulus power, possibly compromising neural entrainment to the steady-state stimuli. (iii) Onset/Offset and 80 Hz ITC responses were most important for group discrimination and showed dimensional reduction across the schizo-bipolar spectrum.

Conclusions: Deviant aSSRs were found across the schizo-bipolar spectrum at multiple frequencies with psychosis status and severity linked to greatest reductions at low and high gamma.

Keywords: Auditory steady-state response; Bipolar disorder; EEG biomarkers; Gamma oscillations; Psychosis; Schizophrenia.

Conflict of interest statement

Disclosures and Conflict of Interest:

DA Parker, JP Hamm, JE McDowell, SK Keedy, ES Gershon, EI Ivleva, GD Pearlson, MS Keshavan, and JA Sweeney report no financial interests or potential conflicts of interest. BA Clementz has served as a consultant for Astellas. Dr. Tamminga is a Deputy Editor of the Journal. She has served as an ad Hoc Consultant to Astellas, and Eli Lilly Pharmaceuticles, a consultant for Kaye Scholer LLC and TAISHO Pharmaceutical Co LTD and is on the Advisory Board for Intra-cellular Therapies (ITI, Inc.); She has served as an unpaid volunteer at The Brain & Behavior Foundation (Council Member), Institute of Medicine (Council Member), Lieber Institute (Scientific Advisory Board), and NAMI (Council Member).

Copyright © 2019 Elsevier B.V. All rights reserved.

Figures

Figure 1:. Evoked Power.

Evoked Power (dB) response averaged over all trial-types and all subjects using peak central-frontal sensors. Red Box indicate areas used for onset (3–9 Hz; 50–300 ms) and offset (3–9 Hz; 1550–1800 ms) evoked response analysis. Topographies of each steady-state stimulation frequencies averaged over all trial-types and all subjects from onset of stimulus to offset (0–1500 ms). Bottom topography is the average of both the onset and offset response periods.

Figure 2:

PCA scores derived from the unadjusted single-trial power from the pre-stimulus period (−500–0ms), the onset (3–9 Hz; 50–300 ms) and offset (3–9 Hz; 1550–1800 ms) evoked response and the Steady-State response at 20, 40 and 80 Hz, resulting in unique 7 components by group. See supplemental tables 6, 7 and 8 for PCA weights. HC, Healthy Comparison subjects (n=137); SZ, probands with schizophrenia (n=113); SAD, probands with schizoaffective disorder (n=105); BDP, probands with bipolar disorder I with psychosis (n=99); BDNP, probands with bipolar disorder I without psychosis (n=68). Error bars=SEM. Full orthogonal contrast results can be found in supplemental table 9.

Figure 3:

Canonical Variate. Show a dimensional pattern of severity of psychopathology. The variate correlated strongest with the onset and offset PCA component and the 80 Hz ITC PCA component. HC, Healthy Comparison subjects (n=137); SZ, probands with schizophrenia (n=113); SAD, probands with schizoaffective disorder (n=105); BDP, probands with bipolar disorder I with psychosis (n=99); BDNP, probands with bipolar disorder I without psychosis (n=68). Error bars=SEM. *p