Introduction: The last decade has witnessed a growing interest in human social cognition. Social neuroscience has differentiated at least two functions and the respective neural networks that support successful interaction: a network that allows for affect sharing (empathizing) and underlies the understanding of others’ affective states and a network that enables the inference of thoughts, beliefs, and goals and underlies understanding others’ mental states (Theory of Mind (ToM)). Empathy paradigms have mainly focused on witnessing pain or suffering and have revealed increased activation in the anterior insula (AI) and the anterior midcingulate cortex (aMCC) [1]. ToM tasks typically involve inferring others’ thoughts or intentions and induce increased activation in the temporoparietal junction (TPJ), the temporal poles and the dorsomedial prefrontal cortex (dmPFC) [2]. Although these different routes of social cognition show differential time courses during development [3] and are differentially impaired in psychopathology [4], these routes usually interact in healthy brains. So far, fMRI paradigms are lacking, which can reliably dissociate mentalizing and empathizing routes within a single person. The aim of the present study was to develop and validate an fMRI task in which demands on the affective and the cognitive social cognition route are manipulated independently and that therefore allows the investigation of their interaction as well as differential impairment. Methods: We developed the EmpaToM, a 30 minute paradigm presenting participants with naturalistic video stimuli (~15 seconds) in which people recount auto-biographical episodes that are either emotionally negative (e.g. loss of a loved one) or neutral (control condition; e.g., commuting to work). Each video is followed by ratings of affect and of empathic concern. Subsequently, specific questions about the content of the video are probing either ToM (questions about the mental states of people in the video) or no ToM (control condition; factual reasoning). The task, hence, follows a 2 (negative emotional load versus no emotional load) x 2 (ToM requirements versus factual reasoning) factorial design. In a first validation study, 19 participants were tested in the EmpaToM and classical tasks measuring empathy (the Social Video Task (SoVT) [5]) and ToM [2] (3T Siemens Verio Scanner; TR = 2000; TE =; 37 slices (2 mm)). Results: Viewing negative emotional compared to neutral videos increased activation in a distinct network including the bilateral AI and aMCC. This empathy network overlapped with activity elicited by the SoVT [5] and coordinates derived from a meta-analysis on empathy for pain paradigms [1]. Affect ratings and emotional concern ratings after the emotionally negative videos were correlated with the IRI subscale ‘empathic concern’ and with SoVT concern ratings. Furthermore, activity in the aMCC and right AI was parametrically modulated by the subjective rating of negative emotion experienced after each video. Contrasting ToM- and factual reasoning during the questions activated the well-described network including bilateral TPJ, temporal poles and mPFC. Again, these clusters largely overlapped with a classical false-belief ToM-task [2]. A subsequent study with 200 participants replicated these patterns. Conclusions: The present results confirm that the EmpaTom is able to reliably identify and separate the networks underlying our abilities to empathize (affective route) and to mentalize (cognitive route) within individuals and one task. This makes the EmpaToM a suitable task for the efficient differentiation of empathy and ToM related networks and for investigating their interaction. The EmpaToM could be of tremendous use for both the comprehensive characterization of different types of deficits in psychopathology as well as for the measurement of differential training effects and interventions both on the level of behavior and brain functioning. References [1] Lamm, C., Decety, J., & Singer, T. (2011). ‘Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain’, NeuroImage, vol. 54, pp. 2492-2502. [2] Dodell-Feder, D., Koster-Hale, J., Bedny, M., Saxe, R. (2011). ‘fMRI item analysis in a theory of mind task’, Neuroimage, vol. 55, pp. 705-12. [3] Singer, T. (2006). ‘The neuronal basis and ontogeny of empathy and mind reading: Review of literature and implications for future research’, Neuroscience & Biobehavioral Reviews, vol. 30, pp. 855-863. [4] Bird, G., Silani, G., Brindley, R., White, S., Frith, U., & Singer, T. (2010). ‘Empathic brain responses in insula are modulated by levels of alexithymia but not autism’, vol., 133, pp. 1515-1525. [5] Klimecki, O.M., Leiberg, S., Lamm, C., & Singer, T. 2013). ‚Functional Neural Plasticity and Associated Changes in Positive Affect After Compassion Training’. Cerebral Cortex, vol. 23, pp. 1552-1561.