Both resting state functional magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS) are increasingly popular techniques that can be used to non-invasively measure brain connectivity in human subjects. TMS shows additional promise as a method to manipulate brain connectivity. In this review we discuss how these two complimentary tools can be combined to optimally study brain connectivity and manipulate distributed brain networks. Important clinical applications include using resting state fcMRI to guide target selection for TMS and using TMS to modulate pathological network interactions identified with resting state fcMRI. The combination of TMS and resting state fcMRI has the potential to accelerate the translation of both techniques into the clinical realm and promises a new approach to the diagnosis and treatment of neurological and psychiatric diseases that demonstrate network pathology.

Intrinsic activity in the brain is organized into networks. Although constrained by their anatomical connections, functional correlations between nodes of these networks reorganize dynamically. Dynamic organization implies that couplings between network nodes can be reconfigured to support processing demands. To explore such reconfigurations, we combined repetitive transcranial magnetic stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical activity in one node of the default network, and assessed the effect of this upon functional correlations throughout the network. Two different frequencies of rTMS to the same default network node (the left posterior inferior parietal lobule, lpIPL) induced two topographically distinct changes in functional connectivity. High-frequency rTMS to lpIPL decreased functional correlations between cortical default network nodes, but not between these nodes and the hippocampal formation. In contrast, low frequency rTMS to lpIPL did not alter connectivity between cortical default network nodes, but increased functional correlations between lpIPL and the hippocampal formation. These results suggest that the default network is composed of (at least) two subsystems. More broadly, the finding that two rTMS stimulation regimens to the same default network node have distinct effects reveals that this node is embedded within a network that possesses multiple, functionally distinct relationships among its distributed partners.network dynamics | resting-state functional MRI | hippocampus | medial prefrontal cortex I ntrinsic activity in the brain is organized into networks (1). Functional connectivity MRI (fcMRI) analyses have used spontaneous low-frequency oscillations in the blood oxygenation level-dependent (BOLD) signal to show that nodes within these networks are functionally correlated with one another (2; for reviews see refs. 3 and 4). Although intrinsic brain networks are constrained by an anatomical skeleton, the strength of functional connectivity between network regions is dynamic (1, 5, 6). Consequently, there is growing interest in characterizing how networks of brain regions dynamically change their couplings to form multiple possible functional configurations.Transcranial magnetic stimulation (TMS) affords an opportunity to explore such alternative configurations by modulating intrinsic activity networks. Repetitive TMS (rTMS) alters local cortical activation in a temporally sustained fashion (7,8), and permits the targeting of predetermined cortical regions. rTMS is particularly well suited to study changes across cortical networks (9, 10). Local stimulation to an accessible network node can propagate, via transsynaptic means, to distal but interconnected nodes with high spatial specificity (11,12). This approach allows for causality to be inferred between the applied stimulation and the observed changes in network connectivity.The default network is comprised of a set of distributed brain regions, including the medial prefrontal cortex (mPFC), the pos...