No association between symptom severity and MMN impairment in schizophrenia: A meta-analytic approach.

The mismatch negativity (MMN) is an event-related potential that is consistently attenuated in people with schizophrenia. Within the predictive coding model of psychosis, MMN impairment is thought to reflect the same prediction failures that are also thought to underlie the development and crystallization of delusions and hallucinations. However, the true relationship between symptom severity and MMN impairment across studies has not yet been established. The present meta-analysis used meta-regressions to examine the relationship between MMN impairment (quantified as Hedges' g) and PANSS positive and negative symptom totals across 62 and 68 samples, respectively. Furthermore, we examined the relationship between MMN impairment and group differences in educational achievement (n = 47 samples), cognitive ability (n = 36 samples), and age (n = 86 samples). Overall, we found no significant associations between MMN impairment and symptom severity (p's > 0.50); however, we did observe a trend-level association between MMN impairment and lower education (p = 0.07) and a significant association with older age (p < 0.01) in the schizophrenia patient group. Taken together, these results challenge a simple predictive coding model of psychosis, and suggest that MMN impairment may be more closely associated with premorbid functioning than with the expression of psychotic symptoms.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia.

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia.SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia.

A Meta-Analysis of Mismatch Negativity in Schizophrenia: From Clinical Risk to Disease Specificity and Progression.

BACKGROUND: The observation that mismatch negativity (MMN) is consistently impaired in schizophrenia has generated considerable interest in the use of this biomarker as an index of disease risk and progression. Despite such enthusiasm, a number of issues remain unresolved regarding the nature of MMN impairment. The present study expands upon an earlier meta-analysis of MMN impairment in schizophrenia by examining impairment across a range of clinical presentations, as well as across experimental parameters. METHODS: One hundred one samples of schizophrenia patients were included in the present study, including first-episode (n = 13), chronic (n = 13), and mixed-stage (n = 75) samples. Additionally, MMN was examined in three related conditions: bipolar disorder (n = 9), unaffected first-degree relatives (n = 8), and clinical high risk (n = 16). RESULTS: We found that MMN impairment 1) likely reflects a vulnerability to disease progression in clinical high-risk populations rather than a genetic risk for the condition; 2) is largely unrelated to duration of illness after the first few years of illness, indicating that impairment is not progressive throughout the life span; 3) is present in bipolar disorder, albeit to a lesser degree than in schizophrenia; and 4) is not modulated by experimental parameters such as magnitude of change between standard and deviant tones or frequency of deviant tones but may be modulated by attentional demands. CONCLUSIONS: Such findings lay the foundation for a better understanding of the nature of MMN impairment in schizophrenia, as well as its potential as a clinically useful biomarker.