Visual backward masking and the schizophrenia spectrum: EEG correlates

Schizophrenia is a heterogeneous disease strongly influenced by genetic factors. We have previously shown that visual backward masking (VBM) is a very sensitive endophenotype of schizophrenia (Chkonia et al., 2010). Importantly, not only patients but also unaffected relatives and healthy students with schizotypal traits show masking deficits (Cappe, Herzog, Herzig, Brand, & Mohr, 2012; Chkonia et al., 2010). Here, we investigate the neurophysiological correlates of VBM as measured by EEG across the schizophrenia spectrum. We tested 93 schizophrenia patients, 55 non-affected first-degree relatives, 76 matched healthy controls, as well as 20 first-episode psychotic patients, and 53 healthy students with schizotypal traits, in a VBM paradigm while recording the electroencephalography (EEG). In our VBM paradigm: a vernier target, i.e. two vertical bars that are slightly offset in the horizontal direction, is presented; after the target, a mask follows; the observers have to discriminate the offset direction by pushing the corresponding button. Two VBM conditions (long and short inter-stimulus intervals (ISI)) were randomly presented with target only and mask only conditions. The EEG was recorded and the amplitude of N1 peak in response to each condition was quantified. When only the mask is presented, EEG responses are roughly comparable between the populations. However, for the three conditions with the target, we found altered N1 amplitudes in all populations of the schizophrenia spectrum: (a) In schizophrenia patients: strongly reduced N1 amplitudes associated with behavioural deficits, when compared to controls (Plomp et al., 2013). (b) In first-episode patients: reduced N1 amplitudes when compared to controls, but higher when compared with schizophrenia patients. In order to track the progress of the EEG correlates, we followed up patients every 6 months and tested them 3 times. Preliminary results suggest that N1 amplitudes remain stable across time. (c) In students with high schizotypal traits, i.e., cognitive disorganization (CogDis): reduced N1 amplitudes compared to low schizotypal students (Favrod et al., under review). These deficits are similar to those of patients but to a lesser extend, suggesting CogDis as a risk factor for psychosis. (d) In relatives of schizophrenia patients: higher N1 amplitudes compared to controls. We propose that relatives use a compensation mechanism, tuning their brain to maximum performance to potentially counterbalance for their masking deficits. Conclusions: We found EEG correlates of VBM deficits across all populations of the schizophrenia spectrum. Since our genetic studies point to an association between abnormalities in the cholinergic system and VBM in schizophrenia (Bakanidze et al., 2013), and the cholinergic system plays a role in boosting faint sensory information, related to selective attention, we propose that VBM impairments across the schizophrenia spectrum are not caused by visual deficits per se but are related to general dysfunctions of attention and the cholinergic system reflected in lower neural activity. These findings therefore close the loop between genetics, neural processing and behavior.