Disruption of spatiotemporal coordination as an early marker of schizophrenia: a translational study of the role of frontotemporal interaction (NU22-04-00526)
Basic informations
Investigator: RNDr. Tereza Nekovářová, PhD.
Main recipient: Institute of Physiology (IPHYS) of the Czech Academy of Sciences (CAS)
Co-recipient: National Institute of Mental Health (NIMH)
Research period: 1/5/2022 – 31/12/2025
Total budget: 13,715,000 CZK
NIMH budget: 8,278,000 CZK
Supported by: Czech Health Research Council (AZV ČR)
Annotation
Schizophrenia is a serious neuropsychiatric disorder of neurodevelopmental origin, which manifests with positive symptoms, negative symptoms, and cognitive deficits. It severely affects patients´ quality of life and daily abilities and provides a reliable predictor of long-term functioning and therapeutic outcome. Besides disruptions of attention and working and spatial memory, changes in the temporal perception in the domain of interval timing (estimating second- and minute-intervals) are also consistently found in schizophrenia. Regarding the neural substrate, a significant disruption of the interaction between the frontal and temporal lobes, especially the prefrontal cortex and hippocampus. This translational project will aim at the scientifically up-to-date question of the role of this crosstalk in spatial and temporal cognition and spatiotemporal integration, the latter proposed as a core deficit both of frontotemporal disconnection and schizophrenia, which can serve as a more reliable predictor of therapeutic outcome and patient´s recovery. The project will employ advanced techniques of selective micro-inactivations, chemogenetics, electrophysiology, and sophisticated behavioral testing, and relate disrupted frontotemporal crosstalk to the dysfunctioning spatiotemporal integration at the levels of an animal model of psychosis and human subjects with first-episode schizophrenia. It will also specify the yet elusive role of inhibitory interneurons in these processes. The results will provide applied points of depart for predicting the therapeutic response and valuably extend knowledge of the pathophysiology of this debilitating disease. The project will combine the most up-to-date knowledge from preclinical and clinical research of schizophrenia and substantially improve the diagnostic and long-term outcome of this disorder.substantially improve the diagnostic and long-term outcome of this disorder.