Maya Roinishvili

The shine-through masking paradigm is a potential endophenotype of schizophrenia.

Background To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. Methodology/Principal Findings We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. Conclusions/Significance The shine-through paradigm is a potential endophenotype.

Electrophysiological Evidence for Ventral Stream Deficits in Schizophrenia Patients

Schizophrenic patients suffer from many deficits including visual, attentional, and cognitive ones. Visual deficits are of particular interest because they are at the fore-end of information processing and can provide clear examples of interactions between sensory, perceptual, and higher cognitive functions. Visual deficits in schizophrenic patients are often attributed to impairments in the dorsal (where) rather than the ventral (what) stream of visual processing. We used a visual-masking paradigm in which patients and matched controls discriminated small vernier offsets. We analyzed the evoked electroencephalography (EEG) responses and applied distributed electrical source imaging techniques to estimate activity differences between conditions and groups throughout the brain. Compared with controls, patients showed strongly reduced discrimination accuracy, confirming previous work. The behavioral deficits corresponded to pronounced decreases in the evoked EEG response at around 200 ms after stimulus onset. At this latency, patients showed decreased activity for targets in left parietal cortex (dorsal stream), but the decrease was most pronounced in lateral occipital cortex (in the ventral stream). These deficiencies occurred at latencies that reflect object processing and fine shape discriminations. We relate the reduced ventral stream activity to deficient top-down processing of target stimuli and provide a framework for relating the commonly observed dorsal stream deficiencies with the currently observed ventral stream deficiencies.

Association of the Nicotinic Receptor α7 Subunit Gene (CHRNA7) with Schizophrenia and Visual Backward Masking.

The nicotinic system is involved in the pathophysiology of schizophrenia. However, very little is known about its genetic basis and how it relates to clinical symptoms and potentially pharmacological intervention. Here, we investigated five single nucleotide polymorphisms (SNPs) [rs3826029] [rs2337506] [rs982574] [rs904952] [rs2337980] of the cholinergic nicotinic receptor gene, alpha 7 subunit (CHRNA7) and their association to schizophrenia. We found an association with rs904952 (p = 0.009) in a German sample of 224 schizophrenic patients and 224 healthy control subjects. The same trend was shown in an independent Georgian sample of 50 schizophrenic patients, 57 first order unaffected relatives, and 51 healthy controls. In addition, visual backward masking (VBM), a sensitive test for early visual information processing, was assessed in the Georgian sample. In line with prior studies, VBM performance deficits were much more pronounced in schizophrenic patients and their unaffected relatives compared to healthy controls (schizophrenic patients: 156 ms; unaffected relatives: 60 ms; healthy controls: 33 ms). VBM was strongly correlated with SNP rs904952 (H[2] = 7.3, p = 0.026). Our results further support the notion that changes in the nicotinic system are involved in schizophrenia and open the avenue for pharmacological intervention.

Schizophrenia and visual backward masking: a general deficit of target enhancement

The obvious symptoms of schizophrenia are of cognitive and psychopathological nature. However, schizophrenia affects also visual processing which becomes particularly evident when stimuli are presented for short durations and are followed by a masking stimulus. Visual deficits are of great interest because they might be related to the genetic variations underlying the disease (endophenotype concept). Visual masking deficits are usually attributed to specific dysfunctions of the visual system such as a hypo- or hyper-active magnocellular system. Here, we propose that visual deficits are a manifestation of a general deficit related to the enhancement of weak neural signals as occurring in all other sorts of information processing. We summarize previous findings with the shine-through masking paradigm where a shortly presented vernier target is followed by a masking grating. The mask deteriorates visual processing of schizophrenic patients by almost an order of magnitude compared to healthy controls. We propose that these deficits are caused by dysfunctions of attention and the cholinergic system leading to weak neural activity corresponding to the vernier. High density electrophysiological recordings (EEG) show that indeed neural activity is strongly reduced in schizophrenic patients which we attribute to the lack of vernier enhancement. When only the masking grating is presented, EEG responses are roughly comparable between patients and control. Our hypothesis is supported by findings relating visual masking to genetic deviants of the nicotinic α7 receptor (CHRNA7).

Combining vernier acuity and visual backward masking as a sensitive test for visual temporal deficits in aging research.

Performance in many everyday situations slows down when age increases. The causes of slowing down may be found on any stage of information processing. Here, we show that the combination of a vernier acuity task and the shine-through backward masking paradigm is a good paradigm to determine temporal processing deficits. The paradigm is relatively robust to optical blur and unlikely affected by motor dysfunctions. Strong masking deficits are found from an age of about 50 years on.

Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express the same deviant patterns of resting state EEG microstates: A candidate endophenotype of schizophrenia

Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80 ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia.

The McCollough Effect and Facial Emotion Discrimination in Patients With Schizophrenia and Their Unaffected Relatives

Abnormalities in visual processing have been found consistently in schizophrenia patients, including deficits in early visual processing, perceptual organization, and facial emotion recognition. There is however no consensus as to whether these abnormalities represent heritable illness traits and what their contribution is to psychopathology. Fifty patients with schizophrenia, 61 of their first-degree healthy relatives, and 50 psychiatrically healthy volunteers were tested with regard to facial affect (FA) discrimination and susceptibility to develop the color-contingent illusion [the McCollough Effect (ME)]. Both patients and relatives demonstrated significantly lower accuracy in FA discrimination compared with controls. There was also a significant effect of familiality: Participants from the same families had more similar accuracy scores than those who belonged to different families. Experiments with the ME showed that schizophrenia patients required longer time to develop the illusion than relatives and controls, which indicated poor visual adaptation in schizophrenia. Relatives were marginally slower than controls. There was no significant association between the measures of FA discrimination accuracy and ME in any of the participant groups. Facial emotion discrimination was associated with the degree of interpersonal problems, as measured by the Schizotypal Personality Questionnaire in relatives and healthy volunteers, whereas the ME was associated with the perceptual-cognitive symptoms of schizotypy and positive symptoms of schizophrenia. Our results support the heritability of FA discrimination deficits as a trait and indicate visual adaptation abnormalities in schizophrenia, which are symptom related.

Patients with functional psychoses show similar visual backward masking deficits

Recent genetic, behavioral, and clinical studies suggest that functional psychoses (schizophrenia, bipolar disorder, schizoaffective disorder), previously thought to be distinct from each other, may belong to one continuum. The shine-through masking paradigm is a potential endophenotype of schizophrenia with high sensitivity and specificity for discriminating between patients, their clinically unaffected relatives, and healthy controls. Hence, if schizophrenia, bipolar disorder and schizoaffective disorder belong to one common disease, strong masking deficits are expected to occur in all three diseases whereas no masking deficits are expected for abstinent alcoholic or depressive patients. Indeed, we found masking to be much stronger in psychotic patients compared to controls and to depressive patients and abstinent alcoholics, who performed on similar levels.

Contextual suppression and protection in schizophrenic patients

IntroductionContextual processing is often strongly deteriorated in schizophrenic patients as found, for example, in higher cognitive as well as lower visual paradigms. In visual detection tasks, impoverished contextual facilitation was attributed to aberrant excitatory neural circuits. On the other hand, we found contextual suppression, possibly related to neural inhibition, to be fast and intact in a visual backward masking task. Here, we combine a suppressive with a “protective” paradigm to further our understanding of the contextual deficiencies of schizophrenic patients in visual information processing.MethodsTwenty three schizophrenic patients and 18 healthy controls were asked to discriminate the offset direction of a vernier target, which was followed by one of a variety of masks for several stimulus onset asynchronies (SOAs).ResultsAs in previous studies, patients needed clearly longer SOAs than controls. However, when longer SOAs were taken into account, increases as well as decreases in backward mask strength had comparable effects in patients and controls.ConclusionsFrom these results, we suggest that complex spatial processing is fast and intact in schizophrenic patients.

First-order relatives of schizophrenic patients are not impaired in the Continuous Performance Test

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been reportedly proposed as an endophenotype of schizophrenia. One requirement for an endophenotype is that unaffected first-order relatives must show deteriorated performance compared to healthy controls. We investigated 56 schizophrenic patients, 33 nonaffected first-order relatives, and 36 healthy controls in a degraded and an undegraded version of the CPT of the AX type. Performance of relatives and controls was roughly identical whereas schizophrenic patients performed worse right from the beginning. These results add further evidence that a deficit in the CPT performance is not an endophenotype of schizophrenia in accordance with previous studies.