Neural Compensation Mechanisms of Siblings of Schizophrenia Patients as Revealed by High-Density EEG

Visual backward masking (VBM) deficits are candidate endophenotypes of schizophrenia indexing genetic liability of the disorder. In VBM, a target is followed by a mask that deteriorates target perception. Schizophrenia patients and, to a lesser extent, their unaffected relatives show strong and reproducible VBM deficits. In patients, VBM deficits are associated with strongly decreased amplitudes in the evoked-related potentials (ERPs). Here, to unveil the neural mechanisms of VBM in schizophrenia, circumventing illness-specific confounds, we investigated the electroencephalogram correlates of VBM in unaffected siblings of schizophrenia patients. We tested 110 schizophrenia patients, 60 siblings, and 83 healthy controls. As in previous studies, patients showed strong behavioral deficits and decreased ERP amplitudes compared to controls. Surprisingly, the ERP amplitudes of siblings were even higher than the ones of controls, while their performances were similar. ERP amplitudes in siblings were found to correlate with performance. These results suggest that VBM is deteriorated in patients and siblings. However, siblings, unlike patients, can partially compensate for the deficits by over-activating a network of brain regions.

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

Compensation of visual backward masking deficits in relatives of schizophrenia patients

Patricia Figueiredo, Michael Herzog, Janir Nuno Ramos Antunes Da Cruz, Maya Roinishvili

Visual backward masking (VBM) is a potential endophenotype of schizophrenia reflecting the genetic underpinnings of the disease (Chkonia et al., 2010). Masking deficits are highly correlated with reduced N1 amplitudes as shown by the Global Field Power (GFP; Plomp et al., 2013). Here, we investigated the electrophysiological correlates of VBM in non-affected first-order relatives of schizophrenia patients. We tested a large sample of schizophrenia patients, first-degree relatives and matched healthy controls, 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, followed by a mask. The participants had to discriminate the offset direction by pushing the corresponding button. We had three conditions: target only and two VBM conditions, with long and short inter-stimulus intervals (ISI). Patients’ performance was impaired, while the relatives performed at the same level as the controls. Performance was significantly correlated with the EEG N1 amplitude, as measured by the GFP. Most interestingly, N1 amplitudes were higher in relatives compared to controls for target only and short ISI, while they were lower in patients relative to controls as previously reported (Plomp et al., 2013). For the relatives, N1 amplitudes were at the same level in all conditions; however, for controls and patients, N1 amplitudes increased with task difficult, e.g., amplitudes in the long ISI condition were lower than in short ISI condition. Our results suggest that relatives use a compensation mechanism tuning the brain to maximum performance in VBM. However, as relatives are already at the peak of their activations, increasing task difficulty does not change brain processing.

2016

Visual masking and schizophrenia: enhancement deficit 200 ms after stimulus onset

Ophélie Gladys Favrod, Michael Herzog, Janir Nuno Ramos Antunes Da Cruz, Maya Roinishvili

Masking is strongly deteriorated in schizophrenia patients and to a lesser extent in their healthy relatives. For this reason, masking is a good endophenotype. Here, we show the EEG correlates of masking across the schizophrenia continuum in order to tackle the underlying mechanisms. First, we found that schizophrenia patients have strongly reduced amplitudes, as measured with the Global Field Power (GFP), compared to controls. The reduced amplitudes speak for attention allocation deficits in schizophrenia. Second, patients with first-episodes psychosis have reduced GFP amplitudes compared to controls, but higher amplitudes compared to schizophrenia patients. Their neural correlates are in an intermediate state, indicating a progressive development of the disease through time. In addition, the amplitude remains stable for at least one year, suggesting that serious deficits emerge at a later stage of the disease. Third, healthy participants with high schizotypal traits have reduced GFP amplitudes compared to low schizotypal participants. These deficits are similar to the ones of patients, though strongly attenuated, showing that the mechanism is independent of the individual’s state (health or disease). Fourth, healthy siblings of schizophrenia patients have, surprisingly, higher GFP amplitudes compared to controls. We propose that the siblings use a compensation mechanism to counterbalance for their masking deficits. Finally, patients with the 22q11.2 deletion syndrome have slightly higher GFP amplitudes compared to controls. We speculate it is due to a high co-morbidity. In conclusion, observers with psychosis traits/symptoms have difficulties to enhance faint visual information 200 ms after their onset which explains their lower performance.

2018

EEG microstates and the schizophrenia spectrum: evidence for compensation mechanisms

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

2019