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Neural drivers of functional disconnectivity in brain disorders

A rapidly expanding approach to understanding neural organization is to map patterns of spontaneous neural activity as an index of functional communication and connectivity across brain regions. Fostered by the advent of neuroimag... see more

31/12/2024

IIT

1M€

Project Budget: 1M€

Project leader

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2024-12-31

ERC-2018-STG: ERC Starting Grant Scope:Objectives

I+D

Cerrada does 7 years

0% 100% 100%

characteristics of the participant

Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

Private Information

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

IIT

1.50M€ | Leader

IZAR CUTTING TOOLS

201.28K€ | participant

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Project duration: 73 months Date Start: 2018-11-08
End date: 2024-12-31

Project leader

FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 1M€

participation deadline Sin fecha límite de participación.

Project description A rapidly expanding approach to understanding neural organization is to map patterns of spontaneous neural activity as an index of functional communication and connectivity across brain regions. Fostered by the advent of neuroimaging methods like resting-state fMRI (rsfMRI), this approach has revealed that functional connectivity is almost invariably disrupted in severe psychiatric disorders, such as autism or schizophrenia. However, the neural basis of such functional disconnectivity remains mysterious. What drives brain-wide functional synchronization? And are there shared pathophysiological mechanisms leading to impaired large-scale neural coupling? This project aims to elucidate the neural drivers of macroscale functional connectivity, as well as its breakdown in brain connectopathies. To achieve this goal, I propose a multi-scale perturbational approach to establish causal relationships between specific neural events and brain-wide functional connectivity via a novel combination of rsfMRI and advanced neural manipulations and recordings in the awake mouse. By directionally silencing functional hubs as well as more peripheral cortical regions, I will provide a hierarchical description of spontaneous network organization that will uncover regional substrates vulnerable to network disruption. I will also manipulate physiologically-distinct excitatory or inhibitory populations to probe a unifying mechanistic link between excitatory/inhibitory imbalances and aberrant functional connectivity. Finally, to account for the hallmark co-occurrence of synaptic deficits and functional disconnectivity in developmental disorders, I will link cellular mechanisms of synaptic plasticity and learning to the generation of canonical and aberrant spontaneous activity patterns. These studies will pave the way to a back-translation of aberrant functional connectivity into interpretable neurophysiological events and models that can help understand, diagnose or treat brain disorders.

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