Specific aims

Our strategy for this project follows a logical structure from experimental data collection that will be used for building mathematical models describing the functional and neurochemical connectome of the disease-state, to experimental model validation in animals and humans, and finally application to therapeutic development.

Working hypotheses:

1 – brain networks mediating pathological drive for alcohol are highly different from a normal mode
2 – that within these differences are access points for therapeutic interventions

Aims:

Aim # 1: To from human and rodent resting-state fMRI experiments on alcoholism-related phenotypes serving as input for modeling and translational analysis
Aim # 2: To of the ‘relapse prone’-state by graph theoretical analysis and identify candidate structures that drive aberrant network states
Aim # 3: To dentified by the graph network models of the ‘relapse prone’-state in a dynamical mathematical model of the rat neurochemical connectome
Aim # 4: To by interfering with the activity of candidate nodes in clinical populations and rodent models
Aim # 5: To to investigate in silico the systemic efficacy of novel treatment approaches for strategies.

Expected Outcome:

The expected outcome is the development of a novel and validated framework based on experimental observation and advanced network modeling that will allow us to evaluate both abstinence and intervention-induced changes on brain connectivity and, most importantly, predict therapeutic interventions to correct aberrant network dynamics.
By assembling the necessary interdisciplinary expertise of leading labs from seven European countries and Israel we will be able to develop theory and experiments in a closed loop to validate the proposed framework. Due to strong preliminary results and outstanding expertise of the participants the chance of success is high and synergies with direct impact on systems medicine are expected.
After finalizing this EU project our validated functional and neurochemical network model will be made public available as a novel world-wide resource for further treatment development.