Visual masking in Schizophrenia: an endophenotype and its neural correlates

Objective: In visual backward masking, a target is followed by a mask, which deteriorates performance on the target. Masking is a very sensitive endophenotype for schizophrenia. Patients and their siblings (to a lesser extent) show strong performance deficits. Here, we investigate EEG correlates of masking across the schizophrenia continuum. Method: We measured high-density EEG, while performing a masking task. We report the Global Field Power (GFP), which is the standard deviation across all electrodes. Results: First, schizophrenia patients (n=90) have strongly reduced GFP amplitudes as compared to controls (n=76). The reduced amplitudes imply an attention allocation deficit in schizophrenia associated with the cholinergic system. Second, patients with first episodes psychosis (n=21) have reduced GFP amplitudes when compared to controls (n=20), but higher amplitudes when compared to schizophrenia patients (n=22). The neural correlates are in an intermediate state, implying a progressive development of the disease through time. In addition, the amplitudes remain stable for at least one year (n=11), suggesting that further deficits emerge slowly over time. Third, healthy participants with high schizotypal traits (n=25) have reduced GFP amplitudes compared to low schizotypal participants (n=20). These deficits are similar to the ones of patients, though strongly attenuated, showing that the mechanism is independent of the state of an individual (i.e., health or disease). Fourth, healthy relatives of schizophrenia patients (n=55) have higher GFP amplitudes compared to controls. We propose that the relatives use a compensation mechanism to counterbalance for their masking deficits. Finally, patients with the 22q11.2 deletion syndrome (n=19), who have a 30% risk for schizophrenia, have slightly higher GFP amplitudes when compared to controls (n=18). Conclusion: Observers with psychosis related traits or symptoms have difficulties to enhance faint visual information 200 ms after onset which explains their lower performance in visual backward masking.

Electrophysiological correlates of visual backward masking in the schizophrenia continuum

Ophélie Gladys Favrod

In visual backward masking (VBM), a target is followed by a mask. Over the past decade, a VBM task, called the Shine-Through paradigm (ST), has been shown to be a very sensitive endophenotype of schizophrenia. In the present thesis, the electrophysiological correlates (EEG) of this endophenotype are investigated. Patients with schizophrenia show strongly reduced amplitudes of the Global Field Power (GFP, standard deviation across all electrodes of the EEG) 200 ms after target onset. Here, I show, first, that patients with first episode psychosis also have masking deficits and that the associated EEG amplitudes are between those of controls and patients with schizophrenia. In detail, when the task is challenging the neural correlates are similar to patients with schizophrenia and when the task is easy the neural correlates are similar to controls. This result suggests that patients with first episode psychosis are in an intermediate state where the disease is not fully developed yet. In addition, the neural signature is stable over at least one year meaning that the fully developed deficits must occur over durations longer than one year. Second, I show that healthy participants with high schizotypal traits, in particular scoring high in the cognitive disorganization dimension, also have GFP amplitude reductions 200 ms after target onset compared to participants with low schizotypal traits. Quantitatively, the difference between high and low scoring participants is much smaller than between patients and controls. Nonetheless, the result shows that deficits are qualitatively similar along the schizophrenia continuum even in a non-clinical population. Third, patients with 22q11 deletions syndrome, who also suffer from psychosis in 30% of the cases, do not show masking deficits. Deficits were expected but potentially because of high co-morbidity with other disorders, I did not find the same neural signature. Fourth, patients with major depressive disorder are not impaired in the ST, however, their neural correlates are lower compared to controls, though not as low as schizophrenia patients. This is surprising given the good behavioral performance. Despite the GFP reduction, the neural signature of depressive patients differs from the one of schizophrenia patients. They do not show the amplitude increment as a function of task difficulty seen in controls, siblings of patients with schizophrenia, and patients with schizophrenia. Finally, I describe preliminary results from on-going studies on healthy aging, autism and bipolarity. The objective is to make all populations fit in a unified framework.

EPFL2019

EEG microstates and the schizophrenia spectrum: evidence for compensation mechanisms

Ophélie Gladys Favrod, Patricia Figueiredo, Michael Herzog, Christine Mohr, Maya Roinishvili

Introduction: Electroencephalogram (EEG) microstates are on-going scalp potential configurations that remain stable for around 80 ms (1). Four recurrent and dominant classes of microstates (labeled A-D) are observed in resting-state EEG, explaining around 65-84 % of the global variance of the data (2). Several studies have reported abnormalities in the dynamics of EEG microstates in schizophrenia patients (3). Similar abnormalities have also been observed in adolescents with 22q11.2 deletion syndrome, a population that has a 30% risk of developing psychosis (4). These results prompted researchers to suggest that the abnormal dynamics of EEG microstates is a potential endophenotype for schizophrenia. For endophenotypes, it is important that unaffected relatives also show the abnormal dynamics (5). To the best of our knowledge, no study analyzed the resting dynamics of these four EEG microstate classes in relatives of schizophrenia patients. Methods: We examined 5 minutes resting-state EEG data of 260 participants collected across experiments, and we estimated the dynamics of the four canonical EEG microstates using Cartool (6). In experiment 1, to investigate whether unaffected siblings of schizophrenia patients show EEG microstates abnormalities, we tested 38 unaffected siblings of schizophrenia patients, 89 schizophrenia patients, and 69 healthy controls. In experiment 2, to assess whether these abnormalities are also present in people with high schizotypal traits, we tested 42 healthy students scoring either high (n=22) or low (n=20) in schizotypal traits. In experiment 3, to investigate whether microstates abnormalities are already present at the beginning of the disorder, we tested 22 patients with first episodes of psychosis (FEP). We also tested the FEP patients two more times throughout one year to assess whether the microstates dynamics change with disease progression. For each group of participants, we identified four microstates classes and labeled them A-D according to their similarities to the previously reported microstate class topographies (2). For each subject, three per-class microstate parameters were computed: mean duration (in ms), time coverage (in %), and frequency of occurrence (occurrence). Results: In line with previous studies, schizophrenia patients showed increased presence of the microstate class C and decreased presence of the microstate class D compared to controls (Figure 1). Siblings showed similar patterns of microstates classes C and D as patients. Surprisingly, siblings showed increased presence of the microstate class B compared to patients and controls. A similar result was also found in students scoring high in schizotypal traits compared to the ones scoring low (Figure 2). No difference was found between FEP and matched chronic patients. Moreover, the microstates dynamics remained stable throughout one year. Conclusions: Our findings suggest that the dynamics of resting-state EEG microstates not only meet most of the requirements for an endophenotype for schizophrenia (5), particularly classes C and D, but they also reveal a potential compensation mechanism that unaffected siblings and healthy people with high schizotypal traits have that might prevent them to develop the disorder. We associate this compensation mechanism with the increased presence of microstate class B. Only little is known about microstate class B. It has been related to the resting-state visual network in fMRI (7), and in healthy participants it is the shortest and least frequent microstate from adolescence on (8, 9). This suggests that the temporal dynamics of microstate class B might be an early marker to discriminate people that are at risk to develop schizophrenia from people that might compensate for their vulnerability.

2019

EEG microstates and the schizophrenia spectrum: evidence for compensation mechanisms

Ophélie Gladys Favrod, Patricia Figueiredo, Michael Herzog, Christine Mohr, Maya Roinishvili

2019

Electrophysiological correlates of visual backward masking in the schizophrenia continuum

Ophélie Gladys Favrod

EPFL2019