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Understanding the mechanisms by which intermittent theta burst stimulation (iTBS) protocols exert changes in the default-mode network (DMN) is paramount to develop therapeutically more effective approaches in the future. While a full session (3000 pulses) of 10 Hz repetitive transcranial magnetic stimulation (HF-rTMS) reduces the functional connectivity (FC) of the DMN and the subgenual anterior cingulate cortex, the current understanding of the effects of a single session of iTBS on the DMN in healthy subjects is limited. Here, we use a previously validated target selection approach for an unprecedented investigation into the effects of a single session (1800 pulses) of iTBS over the DMN in healthy controls. Twenty-six healthy subjects participated in a double-blind, crossover, sham-controlled study. After iTBS to the personalized left dorsolateral prefrontal cortex (DLPFC) targets, we investigated the time lapse of effects in the DMN and its relationship to the harm avoidance (HA) personality trait measure (Temperament and Character Inventory/TCI). Approximately 25-30 min after stimulation, we observed reduced FC between the DMN and the rostral and dorsal anterior cingulate cortex (dACC). About 45 min after stimulation the FC of rostral and dACC strongly decreased further, as did the FC of right anterior insula (AI) with the DMN. Also, we report a positive correlation between the FC decrease in the rostral ACC and the HA domain of TCI, indicating that the HA scores can potentially predict iTBS response. Overall, our results show the time lapse by which iTBS at left-DLPFC targets reduces the FC between DMN and the dACC and right AI, regions typically described as nodes of the salience network.

Noninvasive neuromodulation, including repetitive trans-cranial magnetic stimulation (rTMS) and direct current stimulation (tDCS), provides researchers and health care professionals with the ability to gain unique insights into brain functions and treat several neurological and psychiatric conditions. Undeniably, the number of published research and clinical papers on this topic is increasing exponentially. In parallel, several methodological and scientific caveats have emerged in the transcranial stimulation field; these include less robust and reliable effects as well as contradictory clinical findings. These inconsistencies are maybe due to the fact that research exploring the relationship between the methodological aspects and clinical efficacy of rTMS and tDCS is far from conclusive. Hence, additional work is needed to understand the mechanisms underlying the effects of magnetic stimulation and low-intensity transcranial electrical stimulation (TES) in order to optimize dosing, methodological designs, and safety aspects., (© 2019 S. Karger AG, Basel.)

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) delivered to the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment option for treatment resistant depression. However, the underlying mechanisms of a full session of HF-rTMS in healthy volunteers have not yet been described. Here we investigated, with a personalized selection of DLPFC stimulation sites, the effects driven by HF-rTMS in healthy volunteers (n = 23) over the default mode network (DMN) in multiple time windows. After a complete 10 Hz rTMS (3000 pulses) session, we observe a decrease of functional connectivity between the DMN and the subgenual Anterior Cingulate Cortex (sgACC), as well as the ventral striatum (vStr). A negative correlation between the magnitude of this decrease in the right sgACC and the harm avoidance domain measure from the Temperament and Character Inventory was observed. Moreover, we identify that coupling strength of right vStr with the DMN post-stimulation was proportional to a decrease in self-reports of negative mood from the Positive and Negative Affect Schedule. This shows HF-rTMS attenuates perception of negative mood in healthy recipients in agreement with the expected effects in patients. Our study, by using a personalized selection of DLPFC stimulation sites, contributes understanding the effects of a full session of rTMS approved for clinical use in depression over related brain regions in healthy volunteers.