Reduced auditory segmentation potentials in first-episode schizophrenia
Introduction
Perceptual deficits have been recognized as a hallmark of schizophrenia since the initial classification of the disorder by Kraepelin > 100 years ago (Kraepelin, 1987). They are present before emergence of psychotic symptoms (Cornblatt and Erlenmeyer-Kimling, 1985, Davidson et al., 1999), persist throughout life (Rund, 1998), and are related to functional outcome (Niendam et al., 2006, Uhlhaas and Silverstein, 2005). Neurophysiology of auditory perceptual deficits in schizophrenia has traditionally been characterized by reduced auditory event-related potentials (ERPs), such as P50 and N100 (Javitt, 2009), and reductions in mismatch negativity (MMN), which has been linked to functional outcome and disease burden (Klosterkötter et al., 2001, Light and Braff, 2005). MMN appears with the presentation of stimuli that deviate from an established/predicted pattern of physical sound characteristics such as pitch and duration, independent of attention to the stimuli being presented. MMN reductions have been heavily studied over the past 20 years, and converging evidence suggests that reductions in the MMN develop over the disease course in schizophrenia. Yet, deficits in MMN responses to pitch changes are not identified at first psychotic episode in schizophrenia (Haigh et al., 2017). It is thus unclear if pitch MMN is suitable as a pre-psychosis biomarker of disease presence. However, deficits in MMN response to deviation from temporal expectancy (i.e. tone duration) seem to be somewhat more reliable at first psychotic episode, suggesting that deficits in predictive modeling of temporal parameters may suffer prior to deficits in modeling of frequency (Haigh et al., 2017). In recent years, more complex auditory perceptual paradigms have been investigated in an attempt to identify such a biomarker. For example, MMN can be detected in response to deviation from complex pattern rules, such as changes in the number of tones (Haigh et al., 2016, Rudolph et al., 2015, Salisbury, 2012), or pitch relationships between tones (Saarinen et al., 1992, Zuijen et al., 2004). Importantly, this type of deviance detection relies on the perceptual organization of auditory patterns in the auditory scene. To detect complex pattern deviance, the brain must first identify relationships among pattern elements and segment the auditory scene into distinct auditory objects. Representations of auditory objects are then used as a predictive model to be validated or revised upon presentation of subsequent auditory objects. More generally, auditory objects are important for downstream processing of auditory information in association with the other senses, and for guiding behavior (Nelken et al., 2014).
The process of segmenting the auditory scene into discrete auditory objects, termed auditory scene analysis (ASA), is a late perceptual process accomplished through segregation of multiple sound sources, integration of concomitant acoustic elements, and grouping of patterned auditory sequences into auditory objects (Bregman, 1994). All of these facets are disrupted in long-term schizophrenia, as demonstrated by studies of auditory stream segregation (Ramage et al., 2012, Silverstein et al., 1996, Weintraub et al., 2012) and acoustic pattern segmentation based on rhythmic regularities (Coffman et al., 2016). Using ERPs, we recently identified two reliable neurophysiological correlates of auditory object segmentation in subjects passively listening to acoustic patterns. First, N2 amplitude is greater (more negative) in response to initial and final sequence elements compared to medial elements of the auditory object (Coffman et al., 2016). The N2 is an ERP occurring approximately 200 ms after stimulus onset that traditionally reflects stimulus classification. In the context of acoustic pattern segmentation, N2 amplitude modulation for initial and final elements of the auditory object may reflect the identification of object initiation and termination/closure, termed auditory object “edge” detection by Chait et al. (2008). Second, healthy subjects show a reliable sustained ERP in response to groups/patterns of auditory stimuli that persists for the duration of the pattern before returning to baseline shortly thereafter (Coffman et al., 2016). This response, which we now label the auditory segmentation potential (ASP), is correlated with auditory edge detection (N2 modulation) and intellectual function (IQ) (Coffman et al., 2016). We hypothesize that the ASP represents the segmentation of auditory objects from patterned acoustic stimuli in the auditory scene, and that deficits in this response will be identifiable early in the disease course, at first episode of psychosis.
The ASP is closely related to other auditory-evoked sustained responses that have been previously identified. Sustained potentials in response to long-duration single tones were among the earliest auditory-evoked potentials to be identified (Köhler et al., 1952). These responses occur when tone duration is longer than 600 ms, and normally co-occur with onset and offset potentials (N1/P2 complex) that track the edges of the auditory tone burst (Picton et al., 1978a, Picton et al., 1978b). Interestingly, sustained potentials elicited by long-duration tones are facilitated if participants are instructed to attend the duration, but not the intensity or warble of the tones, suggesting a role in temporal expectancy (Picton et al., 1978b). Further, sustained potentials/fields have also been identified in response to abutting short-duration tone pips, and these potentials/fields are enhanced when regular frequency patterns are presented (Auksztulewicz et al., 2017, Barascud et al., 2016, Southwell et al., 2017). The ASP is similar to these previously-identified sustained responses in that (1) the ASP is generated in response to auditory objects with long duration, but the stimuli used to elicit the ASP are not themselves sustained, and (2) it is generated in response to predictable patterns of stimulation, but the tone pip sequences used to generate the ASP are not abutting. Rather, stimuli presented with long (280 ms) inter-stimulus interval (ISI) and even longer (750 ms) inter-trial interval (ITI), giving the perception of temporally-discrete groups of temporally-distinct tones.
We previously reported reductions of the ASP and the initial/final tone N2 response in schizophrenia in two experiments of sequential auditory pattern perception (Coffman et al., 2016). Here, we extend these findings by examining the neurophysiology of auditory pattern perception in individuals at their first episode of schizophrenia-spectrum psychosis. Further, we implemented an auditory pattern task in this study that is of significantly shorter duration compared to our previous experiments and utilizes patterns that are recognizable only by temporal regularity and not by frequency pattern. This abbreviated auditory pattern task was used in order to improve the clinical utility of the neurophysiological responses identified here as tools for early identification of auditory perceptual deficits. Further, we collected structural MRI in a subset of participants to afford distributed source modeling of the ASP based on individual realistic head models.
Section snippets
Participants
Participants included 20 individuals within six months of their initial contact with clinical services for help seeking at their first episode of psychosis within the schizophrenia spectrum (FE) and 24 healthy control subjects. T1-weighted structural MRIs were acquired for 14 FE and 14 controls, permitting analysis of cortical source activity. In both the overall sample and the smaller subsample of subjects with available MRIs, groups were matched for age, gender, IQ, and parental social
Results
Sensor-level ASP amplitude was reduced by 43% (0.8 SD) in FE compared to controls (FE: − 0.61 ± 0.13 μV; controls: − 1.04 ± 0.12 μV; F(1,42) = 6.20; p = 0.017; Fig. 1A and B). There were no other main effects or interactions for sensor-level comparisons of ASP amplitude. At the cortical surface, ASP sources were identified in auditory cortex and MCC, bilaterally (Fig. 2). Statistical comparisons of ASP source amplitudes revealed a significant interaction of group and source location (F(1,26) = 5.78; p =
Discussion
Auditory object segmentation responses were identified in healthy controls, with larger N2 responses to initial and final tones compared to intermediate tones, and an ASP that persisted for the duration of the object. In our previous series of experiments, we identified deficits in these neurophysiological indices of auditory object segmentation in long-term schizophrenia (Coffman et al., 2016). Here, we have extended these findings to individuals who are > 13 years earlier in the course of the
Role of the funding source
The NIH played no role in the collection or analysis of data or in the preparation of this manuscript.
Contributors
DFS designed the study and wrote the protocol. BAC, JL, and TKM performed the statistical analyses. BAC, DFS, and SMH interpreted findings. BAC wrote the first draft of the paper. All authors contributed to the critical revision of the manuscript and approved the final version.
Conflicts of interest
All other authors declare that they have no conflicts of interest.
Acknowledgements
Supported by NIH (R01 MH094328) to DFS. We thank K. Ward, the faculty and staff of the WPIC Psychosis Recruitment and Assessment Core, the Conte Center for Translational Mental Health Research (P50 MH103204, David Lewis, MD, Director), and the University of Pittsburgh Clinical Translational Science Institute (UL1 RR024153, Steven E. Reis, MD) for their assistance in recruitment, diagnostic and psychopathological assessments, and neuropsychological evaluations.
References (40)
- et al.
Auditory temporal edge detection in human auditory cortex
Brain Res.
(2008) - et al.
Event-related potentials demonstrate deficits in acoustic segmentation in schizophrenia
Schizophr. Res.
(2016) - et al.
Cortical surface-based analysis: I. Segmentation and surface reconstruction
NeuroImage
(1999) - et al.
Dynamic statistical parametric mapping: combining fMRI and MEG for high-resolution imaging of cortical activity
Neuron
(2000) - et al.
EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis
J. Neurosci. Methods
(2004) - et al.
MNE software for processing MEG and EEG data
NeuroImage
(2014) - et al.
Abnormal auditory pattern perception in schizophrenia
Schizophr. Res.
(2016) - et al.
Assessing and improving the spatial accuracy in MEG source localization by depth-weighted minimum-norm estimates
NeuroImage
(2006) - et al.
Neurocognitive performance and functional disability in the psychosis prodrome
Schizophr. Res.
(2006) - et al.
Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia
Schizophr. Res.
(2013)
Human auditory sustained potentials. II. Stimulus relationships
Electroencephalogr. Clin. Neurophysiol.
Human auditory sustained potentials. I. The nature of the response
Electroencephalogr. Clin. Neurophysiol.
Evidence for stimulus-general impairments on auditory stream segregation tasks in schizophrenia
J. Psychiatr. Res.
Finding the missing-stimulus mismatch negativity (MMN) in early psychosis: altered MMN to violations of an auditory gestalt
Schizophr. Res.
The cumulative effects of predictability on synaptic gain in the auditory processing stream
J. Neurosci.
Brain responses in humans reveal ideal observer-like sensitivity to complex acoustic patterns
Proc. Natl. Acad. Sci.
Auditory Scene Analysis: The Perceptual Organization of Sound
Global attentional deviance as a marker of risk for schizophrenia: specificity and predictive validity
J. Abnorm. Psychol.
Consistent resting-state networks across healthy subjects
Proc. Natl. Acad. Sci.
Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents
Am. J. Psychiatry
Cited by (5)
Individual-specific characterization of event-related hemodynamic responses during an auditory task: An exploratory study
2023, Behavioural Brain ResearchCitation Excerpt :Capturing the cortical correlates of auditory processing has improved the understanding of the mechanisms of normal auditory processing [1–3] and altered cortical processing in a number of conditions, including dyslexia [4,5], schizophrenia [6,7], central auditory processing disorder [8], and autism spectrum disorder [9,10].
The role of auditory source and action representations in segmenting experience into events
2024, Nature Reviews PsychologyWorking memory and sensory memory in subclinical high schizotypy: An avenue for understanding schizophrenia?
2023, European Journal of NeuroscienceHyper-Sensitivity to Pitch and Poorer Prosody Processing in Adults With Autism: An ERP Study
2022, Frontiers in Psychiatry