Timothy K. Murphy

Abnormal auditory pattern perception in schizophrenia

Mismatch negativity (MMN) in response to deviation from physical sound parameters (e.g., pitch, duration) is reduced in individuals with long-term schizophrenia (Sz), suggesting deficits in deviance detection. However, MMN can appear at several time intervals as part of deviance detection. Understanding which part of the processing stream is abnormal in Sz is crucial for understanding MMN pathophysiology. We measured MMN to complex pattern deviants, which have been shown to produce multiple MMNs in healthy controls (HC). Both simple and complex MMNs were recorded from 27 Sz and 27 matched HC. For simple MMN, pitch- and duration-deviants were presented among frequent standard tones. For complex MMN, patterns of five single tones were repeatedly presented, with the occasional deviant group of tones containing an extra sixth tone. Sz showed smaller pitch MMN (p=0.009, ~110ms) and duration MMN (p=0.030, ~170ms) than healthy controls. For complex MMN, there were two deviance-related negativities. The first (~150ms) was not significantly different between HC and SZ. The second was significantly reduced in Sz (p=0.011, ~400ms). The topography of the late complex MMN was consistent with generators in anterior temporal cortex. Worse late MMN in Sz was associated with increased emotional withdrawal, poor attention, lack of spontaneity/conversation, and increased preoccupation. Late MMN blunting in schizophrenia suggests a deficit in later stages of deviance processing. Correlations with negative symptoms measures are preliminary, but suggest that abnormal complex auditory perceptual processes may compound higher-order cognitive and social deficits in the disorder.

Complex mismatch negativity to tone pair deviants in long-term schizophrenia and in the first-episode schizophrenia spectrum

Mismatch negativity (MMN) is an event-related potential to stimulus change. MMN to infrequent deviant tones that differs in a simple physical parameter from repetitive standard tones is reduced in patients with long-term schizophrenia (Sz; d=~1). However, this simple MMN is not uniformly reduced at the first-episode of schizophrenia-spectrum psychosis (FESz; d<0.1 for pitch; <0.4 for duration). Deviant stimuli that violate pattern rules also evoke MMN. This complex MMN is evoked by deviations in the relation of sounds to each other. The simplest pattern involves tone pairs. Although the pitch of first tone in the pair varies, the second tones pitch always follows a rule (e.g., always 3 semitones higher). We measured complex MMN to deviant tone pairs that descended in pitch among standard tone pairs that ascended in pitch, never before examined in Sz or in FESz. Experiment 1 showed significant reductions in complex MMN in 20 Sz compared to 22 matched controls. Experiment 2 replicated smaller complex MMN in a shorter protocol in 24 Sz compared to 21 matched controls, but showed no significant complex MMN reduction in 21 FESz compared to 21 matched controls. Although reduced in Sz, indicating deficits in generation of a simple acoustic pattern rule, the tone pair complex MMN was within normal limits in FESz. This suggests that more complex perceptual pattern analysis processes are, at least partially, still intact at the first break. Future work will determine at what point of pattern complexity subtle auditory perception pathophysiology will be revealed in FESz.

Event-related potentials demonstrate deficits in acoustic segmentation in schizophrenia

Segmentation of the acoustic environment into discrete percepts is an important facet of auditory scene analysis (ASA). Segmentation of auditory stimuli into perceptually meaningful and localizable groups is central to ASA in everyday situations; for example, separation of discrete words from continuous sentences when processing language. This is particularly relevant to schizophrenia, where deficits in perceptual organization have been linked to symptoms and cognitive dysfunction. Here we examined event-related potentials in response to grouped tones to elucidate schizophrenia-related differences in acoustic segmentation. We report for the first time in healthy subjects a sustained potential that begins with group initiation and ends with the last tone of the group. These potentials were reduced in schizophrenia, with the greatest differences in responses to first and final tones. Importantly, reductions in sustained potentials in schizophrenia patients were associated with greater negative symptoms and deficits in IQ, working memory, learning, and social cognition. These results suggest deficits in auditory pattern segmentation in schizophrenia may compound deficits in many higher-order facets of the disorder.

Mismatch Negativity to Pitch Pattern Deviants in Schizophrenia

Simple mismatch negativity (MMN) to infrequent pitch deviants is impaired in individuals with long‐term schizophrenia (Sz). The complex MMN elicited by pattern deviance often manifes is cut from here]‐>ts later after deviant onset than simple MMN and can ascertain deficits in abstracting relationships between stimuli. Sz exhibit reduced complex MMN, but so far this has only been measured when deviance detection relies on a grouping rule. We measured MMN to deviants in pitch‐based rules to see whether MMN is also abnormal in Sz under these conditions. Three experiments were conducted. Twenty‐seven Sz and 28 healthy matched controls (HC) participated in Experiments 1 and 2, and 24 Sz and 26 HC participated in Experiment 3. Experiment 1 was a standard pitch MMN task, and Sz showed the expected MMN reduction (~ 115 ms) in the simple pitch deviant compared to HC. Experiment 2 comprised standard groups of six tones that ascended in pitch, and deviant groups where the last tone descended in pitch. Complex MMN was late (~ 510 ms) and significantly blunted in Sz. Experiment 3 comprised standard groups of 12 tones (six tones ascending in pitch followed by six tones descending in pitch, like a scale), and deviant groups containing two repetitions of six ascending tones (the scale restarted midstream). Complex MMN was also late (~ 460 ms) and significantly blunted in Sz. These results identify a late pitch pattern deviance‐related MMN that is deficient in schizophrenia. This suggests specific deficits in later more complex deviance detection in schizophrenia for abstract patterns.

Reduced auditory segmentation potentials in first-episode schizophrenia

Auditory scene analysis (ASA) dysfunction is likely an important component of the symptomatology of schizophrenia. Auditory object segmentation, the grouping of sequential acoustic elements into temporally-distinct auditory objects, can be assessed with electroencephalography through measurement of the auditory segmentation potential (ASP). Further, N2 responses to the initial and final elements of auditory objects are enhanced relative to medial elements, which may indicate auditory object edge detection (initiation and termination). Both ASP and N2 modulation are impaired in long-term schizophrenia. To determine whether these deficits are present early in disease course, we compared ASP and N2 modulation between individuals at their first episode of psychosis within the schizophrenia spectrum (FE, N=20) and matched healthy controls (N=24). The ASP was reduced by >40% in FE; however, N2 modulation was not statistically different from HC. This suggests that auditory segmentation (ASP) deficits exist at this early stage of schizophrenia, but auditory edge detection (N2 modulation) is relatively intact. In a subset of subjects for whom structural MRIs were available (N=14 per group), ASP sources were localized to midcingulate cortex (MCC) and temporal auditory cortex. Neurophysiological activity in FE was reduced in MCC, an area linked to aberrant perceptual organization, negative symptoms, and cognitive dysfunction in schizophrenia, but not temporal auditory cortex. This study supports the validity of the ASP for measurement of auditory object segmentation and suggests that the ASP may be useful as an early index of schizophrenia-related MCC dysfunction. Further, ASP deficits may serve as a viable biomarker of disease presence.