Mental health diseases such as depression are a major burden on society and new treatment options are strongly needed. One strategic goal of NIMH is to develop novel therapies based on discoveries in neuroscience. TMS is a non-invasive neuromodulation technique that can directly interfere with brain activity. TMS is FDA-approved for depression treatment, however, shows mixed efficacy. Thus, improved stimulation protocols would have a major impact in providing better treatments for depression and other brain diseases associated with alterations in cortical excitability (e.g., autism, schizophrenia). Here, we propose to develop a multiscale model of rTMS that will combine electric field simulations with neuron models and molecular simulations of intracellular calcium. Accompanying experiments in in-vitro slice preparations will be used to validate model predictions.

The proposed project is a first important step towards biology-driven, computer-assisted personalized rTMS therapies to promote beneficial neural plasticity. Moreover, our molecular approach provides the perspective in testing synergistic effects of pharmacological interventions and rTMS-based therapies, which may be instrumental in informing future clinical trials to tackle mental health disease.