Is a Paired-Stimuli Configuration Necessary to Obtain Typical Evoked Response Differences in Studies of Psychosis? An MEG Study

Abstract Paired-stimuli (S1-S2) procedures have long been used to assess auditory processing in psychosis. Such studies have shown aberrant evoked responses (ERPs) following long (S1 response) and/or short (S2 response) inter-stimulus intervals. The historical tendency from paired stimuli outcomes in the schizophrenia (SZ) literature is for (i) response to the first stimulus (S1) to be smaller among SZ, and (ii) response to the second stimulus (S2) to be larger among SZ in relation to the size of their S1. An interpretation of these two findings is that SZ have poor auditory response suppression to redundant stimuli (“poor gating”). The present study sought to determine if the reported S1 and S2 effects in SZ (smaller S1 and larger S2 in relation to S1 magnitude) require the paired-stimuli presentation format. Participants (18 schizophrenia and 17 healthy persons) were administered the equivalent of S1 (after a 4.5-sec ISI – “long ISI”) and S2 (after a 500-ms ISI – “short ISI”) stimuli under four conditions (traditional paired long and short, randomly interleaved long and short, block of long, block of short). Neural activity differences were consistent between-groups independent of condition: (i) schizophrenia cases had greater activity in the pre-stimulus to very early post-stimulus period, (ii) healthy persons had greater M100 activity to long ISI stimuli, and (iii) healthy persons had greater activity after the M50/M100 evoked fields (recovery phase) following short ISI stimuli. Simple early auditory processing in psychosis may be largely independent of stimulus presentation condition, an outcome that may help re-frame future translational studies. Traditional paired-stimuli auditory neural response effects may not require the paired-stimuli format.