Meyer-Lindenberg A, Rietschel M. DFG - Deutsche Forschungsgemeinschaft SFB 636: TP B03: Plasticity in prefrontal circuits in the human: Genetic variation, cellular. 01/2012-12/2015.
In the previous funding period, repetitive transcranial magnetic stimulation (rTMS) was shown to induce plasticity in prefrontal circuits for executive function and working memory, and genome-wide significant variants for psychosis were found to impact on these circuits, as well as on prefrontal regulation of the limbic system. In the present project, plasticity in prefrontal circuits will be further dissected by three experiments: (a) a genetic association study examining the effects of genome-wide significant common variants for psychosis on modulation of prefrontal circuit plasticity by rTMS, (b) an experiment in healthy controls relating prefrontal plasticity to a direct cellular assay of synaptic and glutamatergic function by using neuronally-differentiated induced pluripotent stem cells (iPS cells) together with multimodal imaging and rTMS, and (c) an experiment in healthy controls to directly modulate prefrontal circuit (connectivity) features and dependent cognition through real-time-fMRI based neurofeedback. The experiments are independent, but subjects for experiments (b) and (c) will be subsamples of the group investigated in (a) If successful, these experiments will identify genetic variants linking prefrontal plasticity and risk for psychosis, establish a cellular model for systems-level plasticity in humans and provide a first cognitive approach to induce plasticity in connected brain circuits relevant for mental disorders.