Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neuro circuitry in unipolar depression

For nearly two decades now, transcranial magnetic stimulation (TMS) has been available as a noninvasive clinical tool to treat patients suffering from major depression. In this period, a bulk of animal and human studies examined TMS parameters to improve clinical outcome. However, the neurobiological mechanisms underlying mood changes remain an important focus of research. In addition to having an effect on neuroendocrinological processes, neurotransmitter systems, and neurotrophic factors, TMS may not only affect the stimulated cortical regions, but also those connected to them. Therefore, we will review current human data on possible neurobiological mechanisms of repetitive (r) TMS implicated in the deregulated neurocircuitry present in unipolar depression. Furthermore, as the rTMS application can be considered as a "top-down" neuronal intervention, we will focus on the neuronal pathways linked with the stimulated area and we will present an integrative model of action.