Attenuated mismatch negativity in patients with first-episode antipsychotic-naive schizophrenia using a source-resolved method

Abstract

Background Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method. Method Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location. Results No scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls ( p = 0.01), as was P3a at the superior frontal cortex (p = 0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons. Conclusion Attenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method.

Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia

“…As opposed to MMN amplitudes, no significant differences were observed in MMN latencies across groups either across deviant types (F (2,99) = 0.44, p = 0.65) or for any of the deviant types independently (all p > 0.2) (Table 2). As expected, there was a highly significant latency variation by deviant type (F (4,96) = 85.4, p < 0.0001) but no significant interaction with group (F (8,192) = 147, p = 0.17). The order of latencies was location < pitch < FM < duration < intensity, with significant differences between in repeated contrast testing (all p < 0.001).…”

“…Deficits in MMN generation in Sz are associated with impaired activation of superior temporal auditory cortex as reflected in both ERP source localization ( 8 , 9 ) and fMRI ( 10 , 11 ) studies, as well as reduced activation of subcortical regions such as inferior colliculus and thalamus ( 12 ). During MMN paradigms, activation is also observed within prefrontal cortex and a salience network that includes insula and anterior cingulate cortex ( 9 , 11 , 13 ).…”

Impairment of novelty-related theta oscillations and P3a in never medicated first-episode psychosis patients

“…Reduced amplitude of this ERP has been consistently reported in ultra-high risk for psychosis (UHR), first-episode psychosis (FEP), and chronic schizophrenia patients, with most of the research being performed with medicated patients under passive conditions 8 – 15 . Two reports described reduced P3a using active paradigms in medicated patients 16 , 17 , and three studies showed P3a deficits in unmedicated patients under passive tasks 18 – 20 . Nevertheless, to our knowledge, no reports of P3a obtained with active paradigms in unmedicated patients have been performed (for a review on these studies see Justo-Guillén et al 5 ).…”

A machine-learning framework for robust and reliable prediction of short- and long-term treatment response in initially antipsychotic-naïve schizophrenia patients based on multimodal neuropsychiatric data

“…Already at the onset of disease, schizophrenia patients display abnormalities in neuroanatomical 3,4 , electrophysiological 5,6 , and cognitive measures 7 . Changes are subtle and only apparent on the group level, and antipsychotic medication as well as duration of illness are potential confounders 8,9 .…”