Empathy relies on distinct but interacting processes for representing others’ states and regulating self-oriented affect. Neuroimaging studies implicate the right temporoparietal junction (rTPJ) in perspective-taking and the left dorsolateral prefrontal cortex (lDLPFC) in emotion regulation, yet causal evidence from neuromodulation remains limited. This study compared the effects of rTPJ- and lDLPFC-targeted transcranial direct current stimulation (tDCS) on empathy across multiple contexts and modalities.

In Study 1, participants performed a static pain empathy task following anodal or sham tDCS over the rTPJ or lDLPFC, with electroencephalography recorded. In Study 2, participants viewed autobiographical videos depicting positive, negative, and neutral events before and after stimulation, while heart rate variability (HRV) was assessed. Machine learning-based decoding integrated behavioral and physiological data to evaluate the ‘readability’ of empathic states.

rTPJ-tDCS enhanced cognitive empathy across tasks, increasing empathic ratings and late positive potential amplitudes in the pain empathy task, and enhancing the subjective sense of content and emotion understanding in the video task. lDLPFC-tDCS selectively increased HRV in the video task, consistent with greater autonomic flexibility, without altering explicit ratings. Decoding analyses converged with these findings: rTPJ stimulation increased classification accuracy of targets’ emotional states, indicating stronger alignment between empathic responses and others’ emotional cues, whereas lDLPFC stimulation reduced accuracy, suggesting regulation-related attenuation of overt emotional signals.

These findings provide causal evidence for rTPJ supporting cross-context cognitive empathy and lDLPFC modulating autonomic regulation. Multi-context, multimodal assessment delineated distinct target-specific profiles, informing precision neuromodulation strategies for empathy-related deficits and regulation needs.