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.

Universal Patterns in Color-Emotion Associations Are Further Shaped by Linguistic and Geographic Proximity.

Many of us "see red," "feel blue," or "turn green with envy." Are such color-emotion associations fundamental to our shared cognitive architecture, or are they cultural creations learned through our languages and traditions? To answer these questions, we tested emotional associations of colors in 4,598 participants from 30 nations speaking 22 native languages. Participants associated 20 emotion concepts with 12 color terms. Pattern-similarity analyses revealed universal color-emotion associations (average similarity coefficient r = .88). However, local differences were also apparent. A machine-learning algorithm revealed that nation predicted color-emotion associations above and beyond those observed universally. Similarity was greater when nations were linguistically or geographically close. This study highlights robust universal color-emotion associations, further modulated by linguistic and geographic factors. These results pose further theoretical and empirical questions about the affective properties of color and may inform practice in applied domains, such as well-being and design.

Impact of subjective sleep quality on objective measures of neurocognitive dysfunction in patients with major depressive disorder.

Background: Sleep disturbances are prevalent in major depressive disorder (MDD). MDD and sleep disturbances are both linked to cognitive impairments. Studies exploring the mechanisms and impact of sleep disturbances on neurocognitive functioning in depressed patients are lacking and proper assessment and therapeutic interventions for sleep disturbances are not part of clinical management of MDD. Aim: We investigated the association between subjective sleep quality and neurocognitive dysfunction in patients with MDD. Materials and Methods: Patients with moderate MDD episode were matched and assigned to two groups with poor and good sleep quality. We used Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. To measure frontotemporally mediated cognitive functioning, following tests were administered: Wisconsin Card Sorting Test (WCST) and degraded continuous performance test (CPT-DS). Two-tailed independent samples t tests or Mann-Whitney U tests and Pearson's correlation coefficient were performed for the statistical analysis of sleep latency, sleep duration, overall sleep quality, CPT d' value, WCST correct answers, errors, and perseverative errors. Results: Participants with MDD and poor sleep quality performed worse on cognitive tests compared to patients with MDD and good sleep quality. Scores of subjective sleep on PSQI positively correlated with WCST errors (r (60) =0.8883 P = .001) and negatively correlated with WCST correct answers (r (60) = -.869 P = .001) and measures of CPT-DS d' value (r (60) = -.9355 P = .001). Conclusions: Poor sleep quality, notably sleep duration and sleep latency, worsens the neurocognitive impairments of MDD patients. As these impairments are found to be associated with treatment outcomes, sleep disturbances should be additionally assessed and treated in MDD episode.

Intact Serial Dependence in Schizophrenia: Evidence from an Orientation Adjustment Task.

BACKGROUND AND HYPOTHESIS: For a long time, it was proposed that schizophrenia (SCZ) patients rely more on sensory input and less on prior information, potentially leading to reduced serial dependence-ie, a reduced influence of prior stimuli in perceptual tasks. However, existing evidence is constrained to a few paradigms, and whether reduced serial dependence reflects a general characteristic of the disease remains unclear. STUDY DESIGN: We investigated serial dependence in 26 SCZ patients and 27 healthy controls (CNT) to evaluate the influence of prior stimuli in a classic visual orientation adjustment task, a paradigm not previously tested in this context. STUDY RESULTS: As expected, the CNT group exhibited clear serial dependence, with systematic biases toward the orientation of stimuli shown in the preceding trials. Serial dependence in SCZ patients was largely comparable to that in the CNT group. CONCLUSIONS: These findings challenge the prevailing notion of reduced serial dependence in SCZ, suggesting that observed differences between healthy CNT and patients may depend on aspects of perceptual or cognitive processing that are currently not understood.

Intact and deficient contextual processing in schizophrenia patients.

Schizophrenia patients are known to have deficits in contextual vision. However, results are often very mixed. In some paradigms, patients do not take the context into account and, hence, perform more veridically than healthy controls. In other paradigms, context deteriorates performance much more strongly in patients compared to healthy controls. These mixed results may be explained by differences in the paradigms as well as by small or biased samples, given the large heterogeneity of patients' deficits. Here, we show that mixed results may also come from idiosyncrasies of the stimuli used because in variants of the same visual paradigm, tested with the same participants, we found intact and deficient processing.

Visual masking deficits in schizophrenia: a view into the genetics of the disease through an endophenotype.

Schizophrenia is a severe psychiatric disorder determined by a complex mixture of genetic and environmental factors. To better understand the contributions of human genetic variations to schizophrenia, we performed a genome-wide association study (GWAS) of a highly sensitive endophenotype. In this visual masking endophenotype, two vertical bars, slightly shifted in the horizontal direction, are briefly presented (vernier offset). Participants are asked to indicate the offset direction of the bars (either left or right). The bars are followed by a grating mask, which makes the task both spatially and temporally challenging. The inter-stimulus interval (ISI) between the vernier and the mask was determined in 206 patients with schizophrenia, 109 first-order relatives, and 143 controls. Usually, in GWAS studies, patients are compared to controls (i.e., a binary task) without considering the large differences in performance between patients and controls, as it occurs in many paradigms. The masking task allows for a particularly powerful analysis because the differences in ISI within the patient population are large. We genotyped all participants and searched for associations between human polymorphisms and the masking endophenotype using a linear mixed model. We did not identify any genome-wide significant associations (p < 5 × 10-8), indicating that common variants with strong effects are unlikely to contribute to the large inter-group differences in visual masking. However, we found significant differences in polygenetic risk scores (PRS) between patients and controls, and relatives and controls.

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.

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.

Schizophrenia patients using atypical medication perform better in visual tasks than patients using typical medication.

Schizophrenia (SCZ) patients show deficits in many domains, including cognition and perception. However, results are often mixed. One reason for mixed results may be differences in medication. Very little is known about the role of medication in visual processing. Here, we investigated the effects of typical vs. atypical medication on contrast sensitivity (spatial frequencies ranging from 0.2 to 20 cycles per degree), vernier acuity, and visual backward masking. From a large pool of patients, we selected 50 patients (Study 1, conducted in Brazil) and 97 patients (Study 2, conducted in Georgia) taking either only typical or atypical medication. Patients with atypical medication performed significantly better than patients with typical medication for contrast sensitivity, vernier duration, and backward masking. As a secondary result, we found similar, but not significant, trends for the cognitive tasks (Stroop, Flanker, Trail-Making Test-B, Wisconsin Card Sorting Test and Continuous Performance Test) in the same patients. No correlations were found between demographics, psychopathology, chlorpromazine equivalents and visual processing. A conclusion of our study is that one needs to be careful comparing studies when medication is not comparable.

Sex-related differences in vision are heterogeneous.

Despite well-established sex differences for cognition, audition, and somatosensation, few studies have investigated whether there are also sex differences in visual perception. We report the results of fifteen perceptual measures (such as visual acuity, visual backward masking, contrast detection threshold or motion detection) for a cohort of over 800 participants. On six of the fifteen tests, males significantly outperformed females. On no test did females significantly outperform males. Given this heterogeneity of the sex effects, it is unlikely that the sex differences are due to any single mechanism. A practical consequence of the results is that it is important to control for sex in vision research, and that findings of sex differences for cognitive measures using visually based tasks should confirm that their results cannot be explained by baseline sex differences in visual perception.

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.

Is the perception of illusions abnormal in schizophrenia?

There seems to be no common factor for visual perception, i.e., performance in visual tasks correlates only weakly with each other. Similar results were found with visual illusions. One may expect common visual factors for individuals suffering from pathologies that alter brain functioning, such as schizophrenia. For example, patients who are more severely affected by the disease, e.g., stronger positive symptoms, may show increased illusion magnitudes. Here, in the first experiment, we used a battery of seven visual illusions and a mental imagery questionnaire. Illusion magnitudes for the seven illusions did not differ significantly between the patients and controls. In addition, correlations between the different illusions and mental imagery were low. In the second experiment, we tested 59 patients (mostly outpatients) with ten visual illusions. As for the first experiment, patients and controls showed similar susceptibility to all but one visual illusion. Moreover, there were no significant correlations between different illusions, symptoms, or medication type. Thus, it seems that perception of visual illusions is mostly intact in schizophrenia.

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.

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.

Local versus global and retinotopic versus non-retinotopic motion processing in schizophrenia patients.

Schizophrenia impairs cognitive functions as much as perception. For example, patients perceive global motion in random dot kinematograms less strongly, because, as it is argued, the integration of the dots into a single Gestalt is complex and therefore deteriorated. Similarly, the perception of apparent motion is impaired, because filling-in of the illusory trajectory requires complex processing. Here, we investigated very complex motion processing using the Ternus-Pikler display. First, we tested whether the perception of global apparent motion is impaired in schizophrenia patients compared to healthy controls. The task requires both the grouping of multiple elements into a coherent Gestalt and the filling-in of its illusory motion trajectory. Second, we tested the perception of rotation in the same stimulus, which in addition requires the computation of non-retinotopic motion. Contrary to earlier studies, patients were not impaired in either task and even tended to perform better than controls. The results suggest that complex visual processing itself is not impaired in schizophrenia patients.

Crowding, grouping, and gain control in schizophrenia.

Visual paradigms are versatile tools to investigate the pathophysiology of schizophrenia. Contextual modulation refers to a class of paradigms where a target is flanked by neighbouring elements, which either deteriorate or facilitate target perception. It is often proposed that contextual modulation is weakened in schizophrenia compared to controls, with facilitating contexts being less facilitating and deteriorating contexts being less deteriorating. However, results are mixed. In addition, facilitating and deteriorating effects are usually determined in different paradigms, making comparisons difficult. Here, we used a crowding paradigm in which both facilitation and deterioration effects can be determined all together. We found a main effect of group, i.e., patients performed worse in all conditions compared to controls. However, when we discounted for this main effect, facilitation and deterioration were well comparable to controls. Our results indicate that contextual modulation can be intact in schizophrenia patients.

Does chronic nicotine consumption influence visual backward masking in schizophrenia and schizotypy?

Nicotine consumption is higher for people within the schizophrenia spectrum compared to controls. This observation supports the self-medication hypothesis, that nicotine relieves symptoms in, for example, schizophrenia patients. We tested whether performance in an endophenotype of schizophrenia (visual backward masking, VBM) is modulated by nicotine consumption in i) smoking and non-smoking schizophrenia patients, their first-degree relatives, and age-matched controls, ii) non-smoking and smoking university students, and iii) non-smoking, early and late onset nicotine smokers. Overall, our results confirmed that VBM deficits are an endophenotype of schizophrenia, i.e., deficits were highest in patients, followed by their relatives, students scoring high in Cognitive Disorganisation, and controls. Moreover, we found i) beneficial effects of chronic nicotine consumption on VBM performance, in particular with increasing age, and ii) little impact of clinical status alone or in interaction with nicotine consumption on VBM performance. Given the younger age of undergraduate students (up to 30 years) versus controls and patients (up to 66 years), we propose that age-dependent VBM deficits emerge when schizotypy effects are targeted in populations of a larger age range, but that nicotine consumption might counteract these deficits (supporting the self-medication hypothesis).