In this project, we will evaluate the deficits in spatial navigation in schizophrenia patients and in an animal model of schizophrenia-like behavior by a set of real-space tests for the animals and in virtual analogies of these tasks for patients and control subjects. We will include patients hospitalized after the first attack, with stable symptoms, immediately prior to or after discharge. Results of the tests will be considered with regard to medication and symptoms, correlated with neuropsychological tests and compared to a group of matched healthy subjects. The project will also study novel cognitive tests for the animal model, i.e. reversal and working memory paradigms in two spatial tasks. Comparison of results in animals and patients with schizophrenia will determine similarities in cognitive traits between species and therefore validate these tests in model animals. Beside scientific papers, this project will establish a pilot norm of performance in a novel set of spatio-cognitive tests.

V rámci řešení projektu bude sledován deficit prostorové navigace u pacientů se schizofrenií a animálního modelu schizofrenního chování, a to sadou prostorových testů v reálné podobě u zvířat a ve virtuální analogii u pacientů a kontrolních subjektů. Zařazeni budou pacienti hospitalizovaní po proběhlé atace, se stabilní symptomatologií, těsně před nebo po propuštění. Výsledky pacientů budou posuzovány na základě předepsané léčby a symptomatiky, korelovány se standardními neuropsychiatrickými testy, a dále srovnány s kontrolní skupinou zdravých dobrovolníků. V rámci projektu proběhne rovněž studium nových testů pro animální model, především paradigmatu přeučení a pracovní paměti ve dvou prostorových úlohách. Srovnáním výsledků prostorových testů schizofrenních pacientů s animálním modelem schizofrenie bude možné stanovit podobnost jejich chování a tak validizovat tyto testy u modelových zvířat. Kromě vědeckých publikací tak bude výsledkem studie pilotní norma výkonu v sadě prostorově-kognitivních úloh.

• MeSH
• hlodavci MeSH
• kognitivní poruchy diagnóza   MeSH
• lidé MeSH
• modely u zvířat MeSH
• neuropsychologické testy MeSH
• prostorová navigace MeSH
• prostorové chování MeSH
• psychiatrické posuzovací škály MeSH
• receptory N-methyl-D-aspartátu MeSH
• reverzní učení MeSH
• schizofrenie diagnóza   patofyziologie   MeSH
• škály posuzující chování MeSH
• software MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• fyziologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

OBJECTIVES: Deficit in visuospatial functions can influence both simple and complex daily life activities. Despite the fact that visuospatial deficit was reported in schizophrenia, research on visuospatial functions as an independent entity is limited. Our study aims to elucidate the impact of visuospatial deficit in comparison with verbal deficit on global functioning and quality of life in the first psychotic episode of schizophrenia spectrum disorder (FES). The significance of clinical symptoms and antipsychotic medication was also studied. METHODS: Thirty-six FES patients and a matched group of healthy controls (HC group) were assessed with a neuropsychological battery focused on visuospatial (VIS) and verbal (VERB) functions. Using multiple regression analysis, we evaluated the cumulative effect of VERB and VIS functions, psychiatric symptoms (PANSS) and antipsychotic medication on global functioning (GAF) and quality of life (WHOQOL-BREF) in the FES group. RESULTS: The FES group demonstrated significant impairment both in VIS and VERB cognitive abilities compared to the HC group. Antipsychotic medication did not significantly affect either VIS or VERB functioning. PANSS was not related to cognitive functioning, apart from the Trail Making Test B. In the FES group, the GAF score was significantly affected by the severity of positive symptoms and VERB functioning, explaining together 60% of GAF variability. The severity of negative and positive symptoms affected only the Physical health domain of WHOQOL-BREF. The degree of VERB deficit was associated with both Physical and Psychological health. Although we did not find any relation between VIS functioning, GAF, and WHOQOL-BREF, a paradoxical finding emerged in the Environment quality domain, where a worse quality of the environment was associated with better VIS functioning. CONCLUSIONS: Our results suggest that the deficit in VIS functions is an integral part of cognitive deficit in schizophrenia spectrum disorders, rather than a side effect of symptomatology or antipsychotic medication. Moreover, VERB functioning was a better predictor of GAF and WHOQOL-BREF than VIS functioning. Given the findings of negative or missing effect of VIS deficit on WHOQOL-BREF and GAF, the accuracy of these measures in evaluating the impact of global cognitive deficit on everyday life in schizophrenia could be questioned.

• Publikační typ
• časopisecké články MeSH

Schizophrenia is a devastating disorder affecting 1 % of the world's population. An important role in the study of this disease is played by animal models. Since there is evidence that acute psychotic episodes can have consequences on later cognitive functioning, the present study has investigated the effects of a single systemic application of higher doses of (+)MK-801 (3 mg/kg and 5 mg/kg) to adult male Long-Evans rats from the Institute's breeding colony on delayed testing in the active place avoidance task with reversal on the Carousel (a rotating arena). Besides significant mortality due to the injections, a disruption of procedural functions in active place avoidance, after the dose 5 mg/kg was observed. It was concluded that Long-Evans rats from our breeding colony do not represent a suitable biomodel for studying the effects of single high-dose NMDA antagonists.

• MeSH
• antagonisté excitačních aminokyselin aplikace a dávkování   toxicita   MeSH
• dizocilpinmaleát aplikace a dávkování   toxicita   MeSH
• kognitivní poruchy chemicky indukované   psychologie   MeSH
• krysa rodu rattus MeSH
• potkani Long-Evans MeSH
• psychomotorický výkon účinky léků   MeSH
• reverzní učení účinky léků   MeSH
• toxické psychózy psychologie   MeSH
• učení vyhýbat se účinky léků   MeSH
• úniková reakce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Bilingualism (BL) is increasing around the world. Although BL has been shown to have a broad impact-both positive and negative-on language and cognitive functioning, cognitive models and standards are mainly based on monolinguals. If we take cognitive performance of monolinguals as a standard, then the performance of bilinguals might not be accurately estimated. The assessment of cognitive functions is an important part of both the diagnostic process and further treatment in neurological and neuropsychiatric patients. In order to identify the presence or absence of cognitive deficit in bilingual patients, it will be important to determine the positive and/or negative impact of BL properties on measured cognitive performance. However, research of the impact of BL on cognitive performance in neuropsychiatric patients is limited. This article aims to compare the influence of the language (dominant-L1, second-L2) used for assessment of verbal cognitive performance in two cases of bilingual neuropsychiatric patients (English/Czech). Despite the fact that the two cases have different diagnoses, similarities in working memory and verbal learning profiles for L1 and L2 were present in both patients. We expected L1 to have higher performance in all measures when compared with L2. This assumption was partially confirmed. As expected, verbal working memory performance was better when assessed in L1. In contrast, verbal learning showed the same or better performance in L2 when compared with L1. Verbal fluency and immediate recall results were comparable in both languages. In conclusion, the language of administration partially influenced verbal performance of bilingual patients. Whether the language itself influenced low performance in a given language or it was a result of a deficit requires further research. According to our results, we suggest that an assessment in both languages needs to be a component of reasonable cognitive assessment of bilingual patients.

• MeSH
• dospělí MeSH
• duševní poruchy diagnóza   MeSH
• kognice * MeSH
• krátkodobá paměť * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mnohojazyčnost * MeSH
• neuropsychologické testy MeSH
• verbální učení * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• NMDA receptory, excitotoxicita,
• MeSH
• dlouhodobá paměť * MeSH
• dlouhodobá potenciace fyziologie   MeSH
• ionotropní glutamátové receptory fyziologie   MeSH
• krátkodobá paměť fyziologie   MeSH
• kyselina glutamová * fyziologie   škodlivé účinky   MeSH
• lidé MeSH
• neurotoxiny MeSH
• neurotransmiterové látky fyziologie   MeSH
• paměť fyziologie   MeSH
• receptory metabotropního glutamátu fyziologie   MeSH
• receptory N-methyl-D-aspartátu * fyziologie   nedostatek   MeSH
• schizofrenie * etiologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Nogo-A protein is an important inhibitor of axonal growth, which also regulates neuronal plasticity in the CNS. Mutations in the gene encoding Nogo-A or abnormalities in Nogo-A expression are linked to neuropsychiatric disorders such as schizophrenia. The present study assesses the impact of constitutively reduced expression of Nogo-A on place navigation in a novel transgenic rat model. Two spatial paradigms were used: (1) A battery of tests in the Carousel maze requiring continuous processing of spatial information with increasing demands for the segregation of reference frames and behavioral flexibility and (2) a delayed-matching-to-place version of the Morris water maze (MWM), which requires place navigation and is sensitive to deficits in one-trial-encoded place representation. The Carousel maze testing revealed a subtle but significant impairment in management of reference frames. Matching-to-place learning in the Morris water maze was unaffected, suggesting an intact representation of an unmarked goal. Our results show that Nogo-A deficiency leads to cognitive deficit in processing of the reference frames. Such a deficit may be the result of neuro-developmental alterations resulting from Nogo-A deficiency.

• MeSH
• bludiště - učení fyziologie   MeSH
• down regulace * MeSH
• genový knockdown MeSH
• krysa rodu rattus MeSH
• myelinové proteiny genetika   metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• potkani transgenní MeSH
• prostorové chování fyziologie   MeSH
• učení vyhýbat se fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction.

• Publikační typ
• časopisecké články MeSH

The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.

• Publikační typ
• časopisecké články MeSH

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.

• Publikační typ
• časopisecké články MeSH

Dopamine plays a role in generating flexible adaptive responses in changing environments. Chronic administration of D2-like agonist quinpirole (QNP) induces behavioral sensitization and stereotypical behaviors reminiscent of obsessive-compulsive disorder (OCD). Some of these symptoms persist even after QNP discontinuation. In QNP-sensitization, perseverative behavior has often been implicated. To test the effect of QNP-sensitization on reversal learning and its association with perseveration we selected an aversively motivated hippocampus-dependent task, active place avoidance on a Carousel. Performance was measured as the number of entrances into a to-be-avoided sector (errors). We tested separately QNP-sensitized rats in QNP-drugged and QNP-undrugged state in acquisition and reversal tasks on the Carousel. In acquisition learning there were no significant differences between groups and their respective controls. In reversal, QNP-sensitized drugged rats showed a robust but transient increase in number of errors compared to controls. QNP-sensitized rats in an undrugged state were not overtly different from the control animals but displayed an altered learning manifested by more errors at the beginning compensated by quicker learning in the second session compared to control animals. Importantly, performance was not associated with perseveration in neither QNP-sensitized drugged nor QNP-sensitized undrugged animals. The present results show that chronic QNP treatment induces robust reversal learning deficit only when the substance is continuously administered, and suggest that QNP animal model of OCD is also feasible model of cognitive alterations in this disorder.

• Publikační typ
• časopisecké články MeSH