Tost H. BMBF - Bundesministerium für Bildung und Forschung 01GQ1102: Multimodal neuroimaging of frontal striatal plasticity in humans: biomarkers, genetic mechanisms, disease vulnerability and neurochemical modulatin. 04/2011-03/2016.
This grant examines previously unknown aspects of frontal-striatal plasticity, a crucial mechanism for the experience-dependent modification of brain circuits that is frequently disturbed in schizophrenia. This work is expected to advance our current neuroscientific knowledge on frontal-striatal plasticity and identify new genetic and neural systems-level biomarkers for plasticity disturbance and schizophrenia with high clinical potential. Over seven studies, the functional, structural and biochemical correlates of frontal-striatal plasticity will be quantified in vivo using multimodal magnetic resonance imaging (MRI) and established behavioral paradigms allowing for a robust induction of short- and long-term neural adaptation processes (Studies 1 und 2). The potential of these measures as biomarkers for disease vulnerability and severity is subsequently examined in neuroleptics-naïve patients with schizophrenia and their unaffected first-grade relatives (Study 3). The dopaminergic and glutamatergic mechanisms that modulate these processes will be examined using pharmaco-neuroimaging (Study 4). By combining neuroimaging and molecular genetics, the effects of important risk variants on frontal-striatal plasticity will be examined. Apart from the analysis of disease- and plasticity-related candidate genes (Studies 5 and 6) genome-wide association studies (GWAS) will be used to identify previously unknown risk variants (study 7).