Effects of repetitive transcranial magnetic stimulation on resting-state connectivity: A systematic review

Abstract

The brain is organized into networks that reorganize dynamically in response to cognitive demands and exogenous stimuli. In recent years, repetitive transcranial magnetic stimulation (rTMS) has gained increasing use as a noninvasive means to modulate cortical physiology, with effects both proximal to the stimulation site and in distal areas that are intrinsically connected to the proximal target. In light of these network-level neuromodulatory effects, there has been a rapid growth in studies attempting to leverage information about network connectivity to improve neuromodulatory control and intervention outcomes. However, the mechanisms-of-action of rTMS on network-level effects remain poorly understood and is based primarily on heuristics from proximal stimulation findings. To help bridge this gap, the current paper presents a systematic review of 33 rTMS studies with baseline and post-rTMS measures of fMRI resting-state functional connectivity (RSFC). Literature synthesis revealed variability across studies in stimulation parameters, studied populations, and connectivity analysis methodology. Despite this variability, it is observed that active rTMS induces significant changes on RSFC, but the prevalent low-frequency-inhibition/high-frequency-facilitation heuristic endorsed for proximal rTMS effects does not fully describe distal connectivity findings. This review also points towards other important considerations, including that the majority of rTMS-induced changes were found outside the stimulated functional network, suggesting that rTMS effects tend to spread across networks. Future studies may therefore wish to adopt conventions and systematic frameworks, such as the Yeo functional connectivity parcellation atlas adopted here, to better characterize network-level effect that contribute to the efficacy of these rapidly developing noninvasive interventions.

Keywords: Distal effects; Network neuroscience; Repetitive transcranial magnetic stimulation; Resting-state functional connectivity.

Fig. 1.

Study Characteristics of Reviewed Literature. a) Cumulative number of published articles across years. b) Proportion of patients and healthy volunteers. c) Distribution of stimulated networks with DM: default mode, FL: fronto limbic SM: somato motor, VA: ventral attention, O: others, and study-specific networks. d) Method of determining TMS targeting with aMRI: anatomical MRI, and fMRI functional MRI. e) rTMS frequencies for conventional single frequency and patterned protocols. f) Stimulation intensities relative to motor threshold (resting motor threshold: 90%; or active motor threshold: 7.5% of the included studies).

Fig. 2.

rTMS-induced changes in RSFC by resting-state functional networks for each type of stimulation protocol separated into conventional inhibitory/excitatory and periodic versus patterned pulse sequences (Periodic conventionally inhibitory: 1Hz, Periodic conventionally excitatory: 5,10, and 20Hz; Patterned conventionally inhibitory: cTBS and iQPS; Patterned conventionally excitatory: iTBS and eQPS). The starting point of each arrow indicates the stimulated network, and the head of each arrow represents a network where corresponding rTMS-induced changes were observed. The thickness of the arrow indicates the number of studies finding the same result (e.g., FL-DM is thicker as 4 studies were associated with changes between these networks). Blue arrows indicate increased RSFC after rTMS, and red arrows indicate decreased RSFC.