The EEG multiverse of schizophrenia.

Research on schizophrenia typically focuses on one paradigm for which clear-cut differences between patients and controls are established. Great efforts are made to understand the underlying genetical, neurophysiological, and cognitive mechanisms, which eventually may explain the clinical outcome. One tacit assumption of these "deep rooting" approaches is that paradigms tap into common and representative aspects of the disorder. Here, we analyzed the resting-state electroencephalogram (EEG) of 121 schizophrenia patients and 75 controls. Using multiple signal processing methods, we extracted 194 EEG features. Sixty-nine out of the 194 EEG features showed a significant difference between patients and controls, indicating that these features detect an important aspect of schizophrenia. Surprisingly, the correlations between these features were very low. We discuss several explanations to our results and propose that complementing "deep" with "shallow" rooting approaches might help in understanding the underlying mechanisms of the disorder.

Embedded figures in schizophrenia: A main deficit but no specificity.

Visual deficits are core deficits of schizophrenia. Classically, deficits are determined with demanding psychophysical tasks requiring fine-grained spatial or temporal resolution. Less is known about holistic processing. Here, we employed the Leuven Embedded Figures Test (L-EFT) measuring classic aspects of Gestalt processing. A target shape is embedded in a context and observers have to detect as quickly as possible in which display the target is embedded. Targets vary in closure, symmetry, complexity, and good continuation. In all conditions, schizophrenia patients had longer RTs compared to controls and depressive patients and to a lesser extent compared to their siblings. There was no interaction suggesting that, once the main deficit of schizophrenia patients is discarded, there are no further deficits in Gestalt perception between the groups. This result is in line with a growing line of research showing that when schizophrenia patients are given sufficient time to accomplish the task, they perform as well as controls.

Electrophysiological correlates of visual backward masking in patients with bipolar disorder.

In visual backward masking (VBM), a target is followed by a mask that decreases target discriminability. Schizophrenia patients (SZ) show strong and reproducible masking impairments, which are associated with reduced EEG amplitudes. Patients with bipolar disorder (BP) show masking deficits, too. Here, we investigated the neural EEG correlates of VBM in BP. 122 SZ, 94 unaffected controls, and 38 BP joined a standard VBM experiment. 123 SZ, 94 unaffected controls and 16 BP joined a corresponding EEG experiment, analyzed in terms of global field power. As in previous studies, SZ and BP show strong masking deficits. Importantly and similarly to SZ, BP show decreased global field power amplitudes at approximately 200 ms after the target onset, compared to controls. These results suggest that VBM deficits are not specific for schizophrenia but for a broader range of functional psychoses. Potentially, both SZ and BP show deficient target enhancement.

EEG microstates are a candidate endophenotype for schizophrenia.

Electroencephalogram microstates are recurrent scalp potential configurations that remain stable for around 90 ms. The dynamics of two of the four canonical classes of microstates, commonly labeled as C and D, have been suggested as a potential endophenotype for schizophrenia. For endophenotypes, unaffected relatives of patients must show abnormalities compared to controls. Here, we examined microstate dynamics in resting-state recordings of unaffected siblings of patients with schizophrenia, patients with schizophrenia, healthy controls, and patients with first episodes of psychosis (FEP). Patients with schizophrenia and their siblings showed increased presence of microstate class C and decreased presence of microstate class D compared to controls. No difference was found between FEP and chronic patients. Our findings suggest that the dynamics of microstate classes C and D are a candidate endophenotype for schizophrenia.

Risk prediction error signaling: A two-component response?

Organisms use rewards to navigate and adapt to (uncertain) environments. Error-based learning about rewards is supported by the dopaminergic system, which is thought to signal reward prediction errors to make adjustments to past predictions. More recently, the phasic dopamine response was suggested to have two components: the first rapid component is thought to signal the detection of a potentially rewarding stimulus; the second, slightly later component characterizes the stimulus by its reward prediction error. Error-based learning signals have also been found for risk. However, whether the neural generators of these signals employ a two-component coding scheme like the dopaminergic system is unknown. Here, using human high density EEG, we ask whether risk learning, or more generally speaking surprise-based learning under uncertainty, is similarly comprised of two temporally dissociable components. Using a simple card game, we show that the risk prediction error is reflected in the amplitude of the P3b component. This P3b modulation is preceded by an earlier component, that is modulated by the stimulus salience. Source analyses are compatible with the idea that both the early salience signal and the later risk prediction error signal are generated in insular, frontal, and temporal cortex. The identified sources are parts of the risk processing network that receives input from noradrenergic cells in the locus coeruleus. Finally, the P3b amplitude modulation is mirrored by an analogous modulation of pupil size, which is consistent with the idea that both the P3b and pupil size indirectly reflect locus coeruleus activity.

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.

Electrophysiological correlates of visual backward masking in patients with major depressive disorder.

Depression and schizophrenia are two psychiatric diseases with high co-morbidity. For this reason, it is important to find sensitive endophenotypes, which may disentangle the two disorders. The Shine-Through paradigm, a visual backward masking task, is a potential endophenotype for schizophrenia. Masking is strongly deteriorated in schizophrenia patients, which is reflected in reduced EEG amplitudes. Here, we tested whether masking deficits and associated EEG changes are also found in patients with major depressive disorder. First, we replicated previous findings showing that depressive patients exhibit, at most, only weak masking deficits. Second, we found that the EEG amplitudes of depressive patients were reduced compared to controls and slightly increased compared to schizophrenia patients. As a secondary analysis, we compared the performance in the masking paradigm with three cognitive tasks, namely: the Wisconsin card sorting test, a verbal fluency test and a degraded continuous performance test. Performance in all but the verbal fluency test could discriminate schizophrenia from depression.

Electrophysiological correlates of visual backward masking in patients with first episode psychosis.

Visual backward masking is strongly impaired in patients with schizophrenia. Masking deficits have been proposed as potential endophenotypes of schizophrenia. Masking performance deficits manifest as strongly reduced amplitudes in the electroencephalogram (EEG). In order to fulfill the criteria of an endophenotype, masking deficits should not vary substantially across time and should be present at the first psychotic event. To verify whether these conditions are met for visual backward masking, we tested patients with first episode psychosis (n = 21) in a longitudinal study. Patients were tested with visual backward masking and EEG three times every six months over a period of one year. We found that the EEG amplitudes of patients with first episode psychosis were higher as compared to those of patients with schizophrenia but lower as compared to those of unaffected controls. More interestingly, we found that the EEG amplitudes of patients with first episode psychosis remained stable over the course of one year. Since chronic schizophrenia patients have strongly reduced amplitudes, we speculate that the neural correlates of masking deficits (EEG amplitudes) continue to decrease as the disease progresses.

Rethinking Body Ownership in Schizophrenia: Experimental and Meta-analytical Approaches Show no Evidence for Deficits.

Schizophrenia is a severe psychiatric disorder, in which patients experience an abnormal sense of self. While deficits in sensorimotor self-representation (agency) are well documented in schizophrenia, less is known about other aspects of bodily self-representation (body ownership). Here, we tested a large cohort (N = 59) of chronic schizophrenia patients and matched controls (N = 30) on a well-established body illusion paradigm, the Full Body Illusion (FBI). In this paradigm, changes in body ownership are induced through prolonged multisensory stimulation, in which participants are stroked on their back while seeing the stroking on the back of a virtual body. When the felt and seen stroking are synchronous, participants typically feel higher identification with the seen body as well as a drift in self-location towards it. However, when the stroking is asynchronous, no such changes occur. Our results show no evidence for abnormal body ownership in schizophrenia patients. A meta-analysis of previous work corroborates this result. Thus, while schizophrenia patients may be impaired in the sense of agency, their multisensory bodily self-representation, as tested here, seems to be unaffected by the illness.

Electrophysiological correlates of visual backward masking in high schizotypic personality traits participants.

Visual backward masking is strongly deteriorated in patients with schizophrenia. Masking deficits are associated with strongly reduced amplitudes of the global field power in the EEG. Healthy participants who scored high in cognitive disorganization (a schizotypic trait) were impaired in backward masking compared to participants who scored low. Here, we show that the global field power is also reduced in healthy participants scoring high (n=25) as compared to low (n=20) in cognitive disorganization, though quantitatively less pronounced than in patients (n=10). These results point to similar mechanisms underlying visual backward masking deficits along the schizophrenia spectrum.