Non-invasive brain stimulation is a promising approach to study the causal relationship between brain function and behavior. However, it is difficult to interpret behavioral null results as dynamic brain network changes have the potential to prevent stimulation from affecting behavior, ultimately compensating for the stimulation. The present study investigated local and remote changes in brain activity via functional magnetic resonance imaging (fMRI) after offline disruption of the inferior parietal lobule (IPL) or the vertex in human participants via 1 Hz repetitive transcranial magnetic stimulation (rTMS). Since the IPL acts as a multimodal hub of several networks, we implemented two experimental conditions in order to robustly engage task-positive networks, such as the fronto-parietal control network (on-task condition) and the default mode network (off-task condition). The condition-dependent neural after-effects following rTMS applied to the IPL were dynamic in affecting post-rTMS BOLD activity depending on the exact time-window. More specifically, we found that 1 Hz rTMS applied to the right IPL led to a delayed activity increase in both, the stimulated and the contralateral IPL, as well as in other brain regions of a task-positive network. This was markedly more pronounced in the on-task condition suggesting a condition-related delayed upregulation. Thus together, our results revealed a dynamic compensatory reorganization including upregulation and intra-network compensation which may explain mixed findings after low-frequency offline TMS.

Learning the contingencies between a situational context (S), one's own responses (R), and their outcomes (O) and selecting responses according to their anticipated outcomes is the basis of a goal-directed behavior. Previous imaging studies found the angular gyrus (AG) to be correlated to both the representation of R-O associations and outcome-based response selection. Based on this correlational relationship, we investigated the causal link between AG function and goal-directed behavior in offline and online transcranial magnetic stimulation (TMS) experiments. To this end, we employed an experimental R-O compatibility paradigm testing outcome anticipation during response selection and S-R-O knowledge to probe S-R-O learning. In Experiment 1, we applied 1-Hz rTMS offline to the AG or the vertex before participants performed the experimental tasks. In Experiment 2, we applied online 10-Hz pulse trains to the AG or used sham stimulation during an early action selection stage in half of the trials. In both experiments, the R-O compatibility effect was unaltered when response selection was outcome-based, suggesting no causal role of the AG in outcome anticipation during response selection. However, in both experiments, groups with AG stimulation showed significantly modulated knowledge of S-R-O associations in a posttest. Additionally, in an explorative analysis, we found an induced R-O compatibility effect later in the experiment when response selection was guided by stimulus–response rules, suggesting reduced selectivity of outcome anticipation. We discuss possible compensatory behavioral and brain mechanism as well as specific TMS-related methodical considerations demonstrating important implications for further studies investigating cognitive function by means of TMS.

Both active response execution and passive listening to verbal codes (a form of instruction) in single prime trials lead to item-specific repetition priming effects when stimuli re-occur in single probe trials. This holds for task-specific classification (stimulus–classification, SC priming, e.g., apple–small) and action (stimulus–action, SA priming, e.g., apple–right key press). To address the influence of expectation on item-specific SC and SA associations, we tested if item-specific SC and SA priming effects were modulated by the instructed probability of re-encountering individual SC or SA mappings (25% vs. 75% instructed switch probability). Importantly, the experienced item-specific switch probability was always 50%. In Experiment 1 (N = 78), item-specific SA/SC switch  expectations affected SA, but not SC priming effects exclusively following active response execution. Experiment 2 (N = 40) was designed to emphasize SA priming by only including item-specific SC repetitions. This yielded stronger SA priming for 25% vs. 75% expected switch probability, both following response execution as in Experiment 1 and also following verbally coded SA associations. Together, these results suggest that SA priming effects, that is, the encoding and retrieval of SA associations, is modulated by item-specific switch expectation. Importantly, this expectation effect cannot be explained by item-specific associative learning mechanisms, as stimuli were primed and probed only once and participants experienced item-specific repetitions/switches equally often across stimuli independent of instructed switch probabilities. This corroborates and extends previous results by showing that SA priming effects are modulated by  expectation not only based on experienced item-specific switch probabilities, but also on mere instruction.