Abstract
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.
Highlights
The large variability of responses to the FDA-approved10 Hz repetitive transcranial magnetic stimulation protocol for the treatment of depression has led to a world-wide demand for better techniques or improved protocols
It is important to note that when comparing the default-mode network (DMN) only across real intermittent theta burst stimulation (iTBS) resting state functional MRI (rsfMRI) sessions without sham correction, we see the same regions decoupling from the DMN (Supplementary Fig. 1), except by smaller medial prefrontal cortex (mPFC) and larger right anterior insula (AI) blobs in the R2 rsfMRI
After left dorsolateral prefrontal cortex (DLPFC) stimulation (Fig. 2b) we see a decrease in the functional connectivity of the DMN, mainly with the rostral anterior cingulate cortex (rACC) and dorsal anterior cingulate cortex (dACC) during the R2 rsfMRI window (Fig. 3 A1-A2, about 27–32 min after stimulation)
Summary
The large variability of responses to the FDA-approved10 Hz repetitive transcranial magnetic stimulation (rTMS) protocol for the treatment of depression has led to a world-wide demand for better techniques or improved protocols. Brain connectivity changes underlying the effects of intermittent theta burst stimulation (iTBS) delivered at the left dorsolateral prefrontal cortex (DLPFC) remain unexplored. The TBS protocol was developed to mimic rodent[6,7] and human hippocampal activity[8], where a combination of gamma-frequency spike patterns superimposed on theta rhythms[9] was found. It involves application of a burst of three TMS pulses every 20 ms (50 Hz), which is repeated five times per second (5 Hz)[10,11]. When delivered continuously (continuous TBS–cTBS) for 40 s, it results
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