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Objectives: Smooth pursuit eye movement deficits are an established psychosis biomarker across schizophrenia, schizoaffective and psychotic bipolar disorder (BPwP). Whether smooth pursuit deficits are also seen in bipolar disorder without psychosis (BPwoP) is unclear. Here we present data from the Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP) study comparing bipolar patients with and without psychotic features. Methods: Probands with BPwP (N = 49) and BPwoP (N = 36), and healthy controls (HC, N = 71) performed eye tracking tasks designed to evaluate specific sensorimotor components relevant for pursuit initiation and pursuit maintenance. Results: While BPwoP did not differ from either BPwP or HC on initial eye acceleration, they performed significantly better than BPwP on early (P <.01) and predictive (P =.02) pursuit maintenance measures, both without differing from HC. BPwP were impaired compared to HC on initial eye acceleration, and on early and predictive pursuit maintenance (all P <.01). In contrast to the three pursuit measures, BPwP and BPwoP were both impaired on general neurocognitive assessments in relation to HC (both P <.001), without a significant difference between the two bipolar patient groups. Conclusions: Our findings support the model that impairments of sensorimotor and cognitive processing as required for early and later predictive smooth pursuit maintenance are relatively specific to those bipolar patients with a history of psychosis. This suggests that the neural circuitry for developing feed‐forward predictive models for accurate pursuit maintenance is associated with the occurrence of psychotic features in bipolar patients. In contrast, generalized neuropsychological impairments did not differentiate the two bipolar patient groups. [ABSTRACT FROM AUTHOR]

Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs. [ABSTRACT FROM AUTHOR]

Saccadic tasks are widely used to study cognitive processes, effects of pharmacological treatments, and mechanisms underlying psychiatric disorders. In genetic studies, it is assumed that saccadic endophenotypes are traits. While internal consistency and temporal stability of saccadic performance is high for most of the measures, the magnitude of underlying trait components has not been estimated, and influences of situational aspects and person by situation interactions have not been investigated. To do so, 68 healthy participants performed prosaccades, antisaccades, and memory-guided saccades on three occasions at weekly intervals at the same time of day. Latent state-trait modeling was applied to estimate the proportions of variance reflecting stable trait components, situational influences, and Person × Situation interaction effects. Mean variables for all saccadic tasks showed high to excellent reliabilities. Intraindividual standard deviations were found to be slightly less reliable. Importantly, an average of 60% of variance of a single measurement was explained by trans-situationally stable person effects, while situation aspects and interactions between person and situation were found to play a negligible role. We conclude that saccadic variables, in standard laboratory settings, represent highly reliable measures that are largely unaffected by situational influences. Extending previous reliability studies, these findings clearly demonstrate the trait-like nature of these measures and support their role as endophenotypes. [ABSTRACT FROM AUTHOR]

Translational biomarkers, such as prepulse inhibition (PPI) of the acoustic startle response, are playing an increasingly important role in the development of antipsychotic drugs for schizophrenia and related conditions. However, attempts to reliably induce a PPI deficit by psychotomimetic drugs have not been successful, leaving an unmet need for a cross-species psychosis model sensitive to this widely studied surrogate treatment target. Sleep deprivation (SD) might be such a model as it has previously been shown to induce PPI deficits in rats, which could be selectively prevented with antipsychotic but not anxiolytic or antidepressant compounds. Here, in a first proof-of-concept study we tested whether SD induces a deficit in PPI and an increase in psychosis-like symptoms in healthy humans. In two counterbalanced sessions, acoustic PPI and self-reported psychosis-like symptoms (Psychotomimetic States Inventory) were measured in 24 healthy human volunteers after a normal night's sleep and after a night of total SD. SD decreased PPI (p = 0.001) without affecting the magnitude or habituation of the startle response (all p > 0.13). SD also induced perceptual distortions, cognitive disorganization, and anhedonia (all p < 0.02). Thus, extending previous rodent work, we conclude that SD, in combination with the PPI biomarker, might be a promising translational surrogate model for psychosis as this method represents a possibility to partially and reversibly mimic the pathogenesis of psychotic states. [ABSTRACT FROM AUTHOR]

Several times per minute, blinks introduce abrupt changes to the visual input. Here, we use scene cuts in Hollywood movies to model such changes and investigate how they affect our visual behaviour. Specifically, we studied the time course of saccades and blinks after scene cuts in the studyforrest data set [Henke et al., 2016] which comprises of data from 30 subjects watching the Forrest Gump movie and includes manually annotated scene cuts. Blinks and saccades were automatically detected with the sp_tool [Agtzidis et al., 2016], which achieves close to human performance. For our analysis we used the original positions of the 868 abrupt movie cuts together with a randomly shuffled representation of those as baseline. The used metric was the timing of the first event after a scene cut. Our results show that both saccades and blinks are similarly affected by scene cuts, but the time course differs for the two event types. In both cases, cuts initially lead to an inhibitory period, with a processing latency of about 100ms for saccades and 250ms for blinks. After about 40ms, an excitatory period leads to an increased number of saccades to reorient the gaze on the new stimulus content for about 300ms. For blinks, a less pronounced excitation-after-inhibition occurs after about 250ms and lasts for about a second. Afterwards, both blink and saccade rates return to normal. To summarize, we here described the time course of the visual system's information maximization strategy in response to a change in the visual input. [ABSTRACT FROM AUTHOR]