Noninvasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation or transcranial direct and alternating current stimulation, are advocated as measures to enable causal inference in cognitive neuroscience experiments. Transcending the limitations of purely correlative neuroimaging measures and experimental sensory stimulation, they allow to experimentally manipulate brain activity and study its consequences for perception, cognition, and eventually, behavior. Although this is true in principle, particular caution is advised when interpreting brain stimulation experiments in a causal manner. Research hypotheses are often oversimplified, disregarding the underlying (implicitly assumed) complex chain of causation, namely, that the stimulation technique has to generate an electric field in the brain tissue, which then evokes or modulates neuronal activity both locally in the target region and in connected remote sites of the network, which in consequence affects the cognitive function of interest and eventually results in a change of the behavioral measure. Importantly, every link in this causal chain of effects can be confounded by several factors that have to be experimentally eliminated or controlled to attribute the observed results to their assumed cause. This is complicated by the fact that many of the mediating and confounding variables are not directly observable and dose–response relationships are often nonlinear. We will walk the reader through the chain of causation for a generic cognitive neuroscience NIBS study, discuss possible confounds, and advise appropriate control conditions. If crucial assumptions are explicitly tested (where possible) and confounds are experimentally well controlled, NIBS can indeed reveal cause–effect relationships in cognitive neuroscience studies.

Previous studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal modeling to investigate effective connectivity between premotor areas during overt repetition of words and pseudowords presented in both the auditory and visual modalities. Regions involved in phonological aspects of language production were identified as those where regional increases in the BOLD signal were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection.