Project Overview
This project investigates how the disruption of spatiotemporal coordination – the brain’s ability to integrate space and time – may serve as an early biomarker of schizophrenia. Schizophrenia is a severe psychiatric disorder marked not only by hallucinations and delusions but also by profound cognitive impairments. Among these, distortions in time perception and spatial orientation represent fundamental disruptions of mental processes that may contribute to the fragmentation of self-experience.
The research focuses on the role of frontotemporal connectivity and parvalbumin-positive (PV+) interneurons in the perception of time and the coordination of spatial and temporal information. By combining preclinical and clinical approaches, the project aims to uncover the neural mechanisms underlying these deficits and their relationship to the core symptoms of schizophrenia.
Scientific Aims
- Identify disruptions of spatiotemporal coordination in patients with first-episode schizophrenia compared to healthy controls.
- Examine the causal role of frontotemporal synchrony, using animal models of psychosis and advanced electrophysiological recordings.
- Investigate PV+ interneurons as potential modulators of temporal accuracy and network synchrony, using chemogenetic manipulations.
- Correlate frontotemporal connectivity with cognitive performance, linking EEG signatures to time estimation and spatial navigation tasks.
- Develop translational tasks in both rodents and humans to bridge findings across levels – from neuronal oscillations to behavioral performance.
Methods
The project integrates:
- Clinical studies: testing schizophrenia patients and matched healthy volunteers in tasks assessing time estimation, sequential timing, and spatiotemporal integration. Psychometric scales and EEG recordings are used to link symptom severity with neural signatures of timing deficits.
- Preclinical models: employing rodent models of psychosis (e.g., MK-801 administration) to probe deficits in interval timing and spatiotemporal navigation. Chemogenetic tools (DREADDs) are applied to selectively manipulate PV+ interneurons and assess their role in temporal coding and gamma/theta oscillations.
- Electrophysiology and behavioral assays: simultaneous recording of hippocampal and prefrontal activity during cognitive tasks, with a focus on cross-frequency coupling as a neural correlate of time perception accuracy.
Expected Contributions
- Fundamental insight into how disrupted spatiotemporal processing contributes to schizophrenia.
- Identification of biomarkers linking frontotemporal dysfunction to cognitive disorganization.
- Novel translational approaches, bridging cellular mechanisms and clinical symptoms.
- Foundations for targeted interventions, supporting the development of treatments aimed at cognitive deficits in schizophrenia – a domain still lacking effective therapies
