Noninvasive Brain Stimulation and Neuroimaging: Novel Ways of Assessing Causal Relationships in Brain Networks

The behavioral consequences of TMS offer potential insight into both the neural underpinnings of cognitive processes in the brain (Pascual-Leone et al., 2000; Cowey and Walsh, 2001; Miniussi et al., 2010) and the mechanisms of action of TMS itself (Bestmann et al., 2008b; Reithler et al., 2011). In this chapter, we review how the combination of TMS and neuroimaging has led to the formulation of novel and testable hypotheses about the functioning of distributed brain networks in vivo in the human brain. We focus on studies that have tested the effect of TMS on functional magnetic resonance imaging (fMRI) or electroencephalographic (EEG) correlates of behavior and discuss how TMS-induced functional changes may relate to behavioral changes induced by TMS. We outline examples of work that have led to specific predictions about TMS actions and then review how these predictions were tested by combining TMS with neuroimaging. Finally, we discuss how these “stimulateand-record” approaches (Paus, 2005) have advanced our understanding of brainbehavior relationships. Our chapter illustrates how concurrent recordings of brain signals during TMS have afforded increasingly refined hypotheses about how TMS interacts with networks in the human brain. Such understanding is paramount for adequate interpretation of TMS effects, for testing novel hypotheses on how functional interactions among cortical and subcortical brain regions support and enable perception and cognition, and for optimizing potential clinical applications of neurostimulation. The latter is of particular importance in light of the vast number of TMS parameters, which can be potentially exploited for translational goals.