Christian Windischberger was invited by the National Institute of Mental Health (NIMH) to hold a talk on Transcranial Magnetic Stimulation in Health and Disease and the related hardware developments. Our concurrent TMS/fMRI set-up allows the combination of precisely targeted neurostimulation (TMS) with high-sensitivity neuroimaging (fMRI). This promises a tool-driven revolution of TMS, allowing practitioners to individualize treatment for each patient’s need.



Transcranial magnetic stimulation (TMS) has become a promising neuroscientific research tool and in the FDA-approved treatment in major depressive disorder (MDD), however, its neuronal base is not fully understood. This is mainly due to the inherent limitations of the typical TMS / fMRI configurations, what is more important, the low sensitivity and lack of flexibility that conventional MR bird cage coils use. We developed a multi-channel dedicated MR reception coil matrix for 3 Tesla placed below the TMS coil. This configuration allows a flexible positioning while guaranteeing the effectiveness of TMS, a high sensitivity to MRI and the use of sequences parallel / multiband imaging. The flexibility gain due to the new coil can be easily combined with neuronavigation within the MR scanner to allow accurate orientation in the TMS / fMRI experiments. We recently demonstrated the specificity and sensitivity of this novel combined set of coils in stimulation of the motor cortex where localized BOLD changes were found that increase with TMS intensity. To explore the possible extended applications thanks to this new online configuration of TMS / fMRI in combination with advanced imaging and neuronavigation methods, we chose to validate its viability on DLPFC as an area involved in higher order cognitive functions and common stimulation objective for Depression treatment. With this approach, we go beyond observing changes in local activity as a result of TMS by manipulating and imagining brain networks.
In addition, I will present very recent results from two functional connectivity studies on the potential mechanism of rTMS treatment in patients with MDD. In the first study, 60 healthy right-handed subjects underwent rTMS DLPFC in a blind, crossover design controlled by sham. The fMRI images at rest were acquired at 3 Tesla before and twice after the stimulation. In a second independent study, explorations at rest of 30 patients suffering from acute MDD, 32 MDD patients recovered drug-free and 35 healthy control subjects were scanned twice at 7 Tesla with 3 months between scanning sessions. 22 of the 30 patients with acute MDD achieved remission (50% reduction in HAM-D) after 3 months of pharmacotherapy and were included in this analysis. Taken together, these studies show that a single treatment session with rTMS causes a change in connectivity similar to what differentiates patients with MDD even after a successful response to the pharmacotherapy of patients with MDD fully recovered. Therefore, we conclude that the increased connectivity of ACC to DLPFC can act as a marker for the long-term recovery of MDD. We suggest that rTMS over left DLPFC triggers neural processes that are comparable to those responsible for maintaining a stable mental state after recovery from depression.