P300 response modulation reflects breaches of non-probabilistic expectations

In oddball paradigms, infrequent stimuli elicit larger P300 event related potentials (ERPs) than frequent ones. One hypothesis is that P300 modulations reflect the degree of “surprise” associated with unexpected stimuli. That is the P300 represents how unlikely the stimulus is and this signal is then used to update the observer’s expectations. It could be hypothesized that P300 is modulated by any factor affecting an observer’s expectations, not only target probability. Alternatively, the P300 may reflect an evaluative process engaged whenever a discrepancy between task context and sensory inputs arises, irrespective of the latter probability. In previous ERP studies, stimulus probability was often the only determinant of task set confounding the effects of stimulus probability and set stimulus discrepancy. In this study, we used a speeded luminance detection task. The target was preceded by a central cue that predicted its location. The probability that the target was valid, i.e. would appear at the cued location was manipulated by varying the reliability of the cue. Reaction times were modulated by probabilistic expectations based on cue reliability and target validity while P300 was affected by target validity only. We conclude that increased P300 amplitude reflects primarily breaches of non-probabilistic expectations, rather than target probability

Towards Clinically Relevant Oculomotor Biomarkers in Early Schizophrenia

In recent years, psychiatric research has focused on the evaluation and implementation of biomarkers in the clinical praxis. Oculomotor function deviances are among the most consistent and replicable cognitive deficits in schizophrenia and have been suggested as viable candidates for biomarkers. In this narrative review, we focus on oculomotor function in first-episode psychosis, recent onset schizophrenia as well as individuals at high risk for developing psychosis. We critically discuss the evidence for the possible utilization of oculomotor function measures as diagnostic, susceptibility, predictive, monitoring, and prognostic biomarkers for these conditions. Based on the current state of research we conclude that there are not sufficient data to unequivocally support the use of oculomotor function measures as biomarkers in schizophrenia

Arm movement metrics influence saccade metrics when looking and pointing towards a memorized target location

Abstract Saccades are known to influence subsequent arm movements. There is less information to suggest that the characteristics of saccades depend on the reaching movements they accompany. To explore this issue, we studied the systematic errors of saccades generated by two adult female Rhesus monkeys (Macaca Mulata), which were trained to perform center-out saccades and reaching arm movements to the memorized location of targets. The mean error of saccades executed in isolation differed significantly from that of saccades that were executed towards the same target location and accompanied a reaching movement. This difference was observed in both animals whether they used their right or left arm, whether the size of the movement was equal to 10 or 15 degrees and whether there was no delay or a 3 s delay between the extinction of a visual target and the cue to move. Moreover, the endpoints of saccades and those of the arm-reaching movements in the reaching task were significantly correlated. These data suggest that signals specifying the metrics of limb movements influence those specifying the metrics of preceding saccades at a programming stage

The dissociating effects of fear and disgust on multisensory integration in autism: evidence from evoked potentials

BackgroundDeficits in Multisensory Integration (MSI) in ASD have been reported repeatedly and have been suggested to be caused by altered long-range connectivity. Here we investigate behavioral and ERP correlates of MSI in ASD using ecologically valid videos of emotional expressions.MethodsIn the present study, we set out to investigate the electrophysiological correlates of audiovisual MSI in young autistic and neurotypical adolescents. We employed dynamic stimuli of high ecological validity (500 ms clips produced by actors) that depicted fear or disgust in unimodal (visual and auditory), and bimodal (audiovisual) conditions.ResultsWe report robust MSI effects at both the behavioral and electrophysiological levels and pronounced differences between autistic and neurotypical participants. Specifically, neurotypical controls showed robust behavioral MSI for both emotions as seen through a significant speed-up of bimodal response time (RT), confirmed by Miller’s Race Model Inequality (RMI), with greater MSI effects for fear than disgust. Adolescents with ASD, by contrast, showed behavioral MSI only for fear. At the electrophysiological level, the bimodal condition as compared to the unimodal conditions reduced the amplitudes of the visual P100 and auditory P200 and increased the amplitude of the visual N170 regardless of group. Furthermore, a cluster-based analysis across all electrodes revealed that adolescents with ASD showed an overall delayed and spatially constrained MSI effect compared to controls.ConclusionGiven that the variables we measured reflect attention, our findings suggest that MSI can be modulated by the differential effects on attention that fear and disgust produce. We also argue that the MSI deficits seen in autistic individuals can be compensated for at later processing stages by (a) the attention-orienting effects of fear, at the behavioral level, and (b) at the electrophysiological level via increased attentional effort

Modelling reaction time distribution of fast decision tasks in schizophrenia: Evidence for novel candidate endophenotypes

Increased reaction time (RT) and variability of RT in fast decision tasks is observed in patients with schizophrenia and their first degree relatives. This study used modelling of the RT distribution with the aim of identifying novel candidate endophenotypes for schizophrenia. 20 patients with schizophrenia, 15 siblings of patients and 25 healthy controls performed an oddball task of varying working memory load. Increases in mean and standard deviation (SD) of RT were observed for both patients and siblings compared to controls and they were again independent of working memory load. Ex-Gaussian modelling of the RT distribution confirmed that parameters mu, sigma and tau increased significantly in patients and siblings compared to controls. The Drift Diffusion Model was applied on RT distributions. A decrease in the diffusion drift rate (v) modeling the accumulation of evidence for reaching the decision to choose one stimulus over the other, was observed in patients and siblings compared to controls. The mean time of the non-decisional sensorimotor processes (t0) and it's variance (st0) was also increased in patients and siblings compared to controls. In conclusion modeling of the RT distribution revealed novel potential cognitive endophenotypes in the quest of heritable risk factors for schizophrenia

Pleiotropic meta-analysis of cognition, education, and schizophrenia differentiates roles of early neurodevelopmental and adult synaptic pathways

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness