A virtual reality task based on animal research – spatial learning and memory in patients after the first episode of schizophrenia

Abstract

Objectives: Cognitive deficit is considered to be a characteristic feature of schizophrenia disorder. A similar cognitive dysfunction was demonstrated in animal models of schizophrenia. However, the poor comparability of methods used to assess cognition in animals and humans could be responsible for low predictive validity of current animal models. In order to assess spatial abilities in schizophrenia and compare our results with the data obtained in animal models, we designed a virtual analog of the Morris water maze (MWM), the virtual Four Goals Navigation (vFGN) task.Methods: Twenty-nine patients after the first psychotic episode with schizophrenia symptoms and a matched group of healthy volunteers performed the vFGN task. They were required to find and remember four hidden goal positions in an enclosed virtual arena. The task consisted of two parts. The Reference memory (RM) session with a stable goal position was designed to test spatial learning. The Delayed-matching-to-place (DMP) session presented a modified working memory protocol designed to test the ability to remember a sequence of three hidden goal positions.Results: Data obtained in the RM session show impaired spatial learning in schizophrenia patients compared to the healthy controls in pointing and navigation accuracy. The DMP session showed impaired spatial memory in schizophrenia during the recall of spatial sequence and a similar deficit in spatial bias in the probe trials. The pointing accuracy and the quadrant preference showed higher sensitivity toward the cognitive deficit than the navigation accuracy. Direct navigation to the goal was affected by sex and age of the tested subjects. The age affected spatial performance only in healthy controls.Conclusions: Despite some limitations of the study, our results correspond well with the previous studies in animal models of schizophrenia and support the decline of spatial cognition in schizophrenia, indicating the usefulness of the vFGN task in comparative research.

A new human delayed‐matching‐to‐place test in a virtual environment reverse‐translated from the rodent watermaze paradigm: Characterization of performance measures and sex differences

“…Moreover, the only spatial cues were three landmarks within the circular testing arena, whereas in the rodent paradigm the cues for goal localization are outside the pool, and the size of the goal locations made up 10% of the whole testing arena, making goal localization substantially easier than in the rodent task, where the goal locations occupies <1% of the pool area. Overall, while the study by Fajnerová et al () support the feasibility of a human DMP test, the differences outlined above limit direct comparability to the rodent paradigm.…”

“…The incremental watermaze paradigm has been reverse‐translated into human paradigms, in which participants are required to find a hidden goal in a real or virtual environment. Performance on these incremental watermaze task analogues is impaired in patients with hippocampal damage (Astur, Taylor, Mamelak, Philpott, & Sutherland, ; Barkas et al, ; Goodrich‐Hunsaker, Livingstone, Skelton, & Hopkins, ; Nedelska et al, ), and has been used to probe impaired hippocampal function in various human conditions, including schizophrenia (Fajnerová et al, ; Folley, Astur, Jagannathan, Calhoun, & Pearlson, ; Hanlon et al, ; Rodriguez, ), clinical and nonclinical age‐related decline (Daugherty et al, ; Daugherty, Bender, Yuan, & Raz, ; Driscoll, Hamilton, Yeo, Brooks, & Sutherland, ; Gazova et al, ; Hort et al, ), as well as to characterize the development of hippocampal place memory in children (Balcomb, Newcombe, & Ferrara, ).…”

Hippocampal Neural Disinhibition Causes Attentional and Memory Deficits

“…The 5CSRT and DMP tests have high validity to measure deficits in attention and memory relevant to clinical disorders, with related human paradigms -continuous performance tests and place learning tests in analogues of the watermaze, respectively -revealing marked deficits in schizophrenia and age-related cognitive decline (Chudasama and Robbins 2006;Hort et al 2007;Lustig et al 2013;Romberg et al 2013;Fajnerova et al 2014). Our present findings in rats suggest that hippocampal neural disinhbition contributes to clinically relevant attentional and memory deficits.…”

“…To test for memory deficits, we used the watermaze delayed-matching-to-place (DMP) task, which requires rats to learn rapidly (within one trial) new place information every day and is highly dependent on hippocampal function (Steele and Morris 1999;Bast et al 2009;Pezze and Bast 2012), including function of the temporal to intermediate hippocampus (presumably because these regions feature functional connectivity to frontal and subcortical sites necessary to translate hippocampal learning into performance; Bast et al 2009;Bast 2011). The task resembles the everyday problem of remembering new places and routes, and similar human tests using virtual or real-space analogues of the watermaze reveal marked deficits in schizophrenia and age-related cognitive decline (Hort et al 2007;Fajnerova et al . For comparison and to identify behaviorally effective doses without gross sensorimotor effects, we first examined effects on locomotor activity and startle prepulse inhibition (PPI), with locomotor hyperactivity and PPI disruption also being widely-used psychosis-related indices (Bast and Feldon 2003;Swerdlow et al 2008).…”

Cognitive deficits in schizophrenia and other neuropsychiatric disorders: Convergence of preclinical and clinical evidence

“…Three intriguing papers (Zawadzki et al, 2013;Fajnerová et al, 2014;Ledoux et al, 2014) report preclinical and clinical evidence for brain correlates of cognitive deficits in schizophrenia. An interesting hypothesis was presented by Nekovarova et al (2014a) who proposed a translation of findings from animal studies into clinical symptoms of schizophrenia.…”