Default mode network alterations after intermittent theta burst stimulation in healthy subjects

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.

Theta Burst Transcranial Magnetic Stimulation of Fronto-Parietal Networks: Modulation by Mental State

“…For example, dlPFC stimulation has been observed to induce changes in a limbic anteriorcingulate network [104]. More intriguingly, a single session of iTBS to the dlPFC in healthy subjects has been shown to reduce default mode connectivity at the rostral-dorsal anterior cingulate gyrus [105], a finding we will seek to replicate. We are using two-sided tests, because unpredicted results have been described in the literature, where inhibitory cTBS has resulted in increased perfusion [42], and increased connectivity [44], and excitatory 5 Hz TMS to dlPFC demonstrated reduced BOLD activation [106].…”

Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders

“…Our finding of decreased corticolimbic rsFC after iTBS parallel results from previous studies showing that targeted prefrontal stimulation reduced both within- and between-networks connectivity (40). Specifically, active iTBS compared to sham has been shown to decrease the connectivity between DLPFC and insula (26), and between the DLPFC and nodes of the default mode network (25), both in healthy volunteers. Importantly, recent research has suggested that iTBS efficacy in patients with several psychiatric disorders may depend upon ‘normalization’ of pathologically increased connectivity (41).…”

“…Targeting the left dorsolateral prefrontal cortex (DLPFC) via excitatory rTMS and iTBS has been shown to improve emotion processing in both healthy and patient populations, by inhibiting negative bias and increasing response for positive stimuli (20)(21)(22), while right-sided prefrontal stimulation is associated with increased right amygdala activation and enhanced attentional allocation to threatening stimuli (23,24). Furthermore, it has been reported that left prefrontal iTBS also decreases functional connectivity between DLPFC and limbic regions (25,26), which is increased in individuals with FMD (8).…”

Subject-specific whole-brain parcellations of nodes and boundaries are modulated differently under 10Hz rTMS

“…Repetitive transcranial magnetic stimulation (rTMS) has become a popular method for the non-invasive modulation of brain function (George et al, 1999). Recent neuroimaging studies have shown that functional changes induced by rTMS in a localized cortical region lead to selective and distinct modulation of activity and functional connectivity both within and between large-scale brain networks (Cocchi et al, 2015; Eldaief et al, 2011; Sale et al, 2015; Singh et al, 2020, 2019; Valchev et al, 2015; Watanabe et al, 2014). The mechanisms by which rTMS induces network modulations are still not well understood.…”