Transcranial magnetic stimulation of the prefrontal cortex of drug-resistant depressive patients: Where and how should we stimulate?
In humans, transcranial magnetic stimulation (TMS) is an effective method for brain stimulation without the need for surgery. This method involves application of magnetic pulses to the brain, by passing high currents via an electromagnetic coil placed over the intact scalp. TMS can induce an effective electrical field in specific brain areas that produces action potential and localized activation. Repeated brain stimulation using this method is being applied to study and treat various clinical conditions such as depression and schizophrenia. The standard coils used for TMS induce stimulation only in the superficial layers of the cortex under the windings of the coil. In order to allow stimulation of deeper brain regions and eventually to target the brain reward system directly, we have developed deep TMS (dTMS) coils, which enable direct stimulation of much deeper brain regions based on spatial summation. A comparative trial in healthy volunteers demonstrated that this coil (termed the H-coil) allows effective stimulation of much deeper brain regions than the standard coils (Zangen et al., 2005). Following studies demonstrated the safety and the cognitive effects of the H-coils in healthy volunteers. Recently we completed the first study comparing the effectiveness of various versions of the H-coil in drug-resistant depressive patients (Figure). We are also studying stimulation paradigms and the effectiveness of deep TMS in addiction. These studies are performed in collaboration with several clinical centers. Consistently with our animal studies using brain stimulation in the CMS model, we found in two different human studies, that deep transcranial stimulation of the prefrontal cortex exerts a potent antidepressant effects on patients who did not respond previously to antidepressant drugs. As presented in the figure below, the antidepressant effect was dependant on the stimulation area (determined by the version of the H-coil and the intensity used). We hope that these studies will enrich our understanding of the pathophysiology of psychiatric disorders and will be of paramount importance in designing novel treatments for depression, addiction and perhaps other disorders associated with neuroplasticity in deep brain regions.
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