- Several psychiatric disorders involve impaired excitability and function of reward-related circuitries. Repeated stimulation of these circuitries can enhance neuroplasticity and induce long-lasting alterations in excitability and function, thereby becoming a novel therapeutic approach. Our animal studies revealed that multiple sessions of localized stimulation of the prefrontal cortex unilaterally or bilaterally can alter molecular and behavioral features of depression or addiction, respectively. In order to affect the relevant circuitries without a surgery, we have designed special transcranial magnetic stimulation (TMS) coils that enable stimulation of deeper and larger regions relative to those directly affected by standard TMS. These coils, termed H-coils, were tested for their safety and ability to reach deeper brain regions, and evaluation of their antidepressant potential when applied over the prefrontal cortex of medication-resistant depressive patients showed high rates of remission in a large multi-center study. The therapeutic potential of other versions of the H-coils are evaluated in several psychiatric disorders including addiction. We have recently completed a study in heavy smokers in which the effectiveness of several stimulation parameters were evaluated in combination with or without cue-induced craving. It was found that high-frequency stimulation of the prefrontal cortex and the insular cortex combined with craving induction causes significant lasting reductions in cigarette consumption, urine cotinine levels and cigarette craving. Such effect was not observed when stimulation did not follow psychological activation of craving or when stimulation was applied at low frequency. The choice of coil and target in TMS studies may be critical in both psychiatric and basic brain research. The ability to induce direct stimulation of deeper brain regions opens a wide range of therapeutic and research options. Optimization of stimulation parameters requires further investigation into mechanisms utilizing imaging and electrophysiological techniques.