Although music is ubiquitous in human societies, there are some people for whom music holds no reward value despite normal perceptual ability and preserved reward-related responses in other domains. The study of these individuals with specific musical anhedonia may be crucial to understand better the neural correlates underlying musical reward. Previous neuroimaging studies have shown that musically induced pleasure may arise from the interaction between auditory cortical networks and mesolimbic reward networks. If such interaction is critical for music-induced pleasure to emerge, then those individuals who do not experience it should show alterations in the cortical-mesolimbic response. In the current study, we addressed this question using fMRI in three groups of 15 participants, each with different sensitivity to music reward. We demonstrate that the music anhedonic participants showed selective reduction of activity for music in the nucleus accumbens (NAcc), but normal activation levels for a monetary gambling task. Furthermore, this group also exhibited decreased functional connectivity between the right auditory cortex and ventral striatum (including the NAcc). In contrast, individuals with greater than average response to music showed enhanced connectivity between these structures. Thus, our results suggest that specific musical anhedonia may be associated with a reduction in the interplay between the auditory cortex and the subcortical reward network, indicating a pivotal role of this interaction for the enjoyment of music.Without music, life would be a mistake.Friedrich Nietzsche, Twilight of the Idols T his quote highlights the importance of music for the life of most people. Indeed, although music is not a primary reward (such as food or sex), it is reckoned as one of the most important sources of pleasure in life. Furthermore, music has been present in human societies since prehistory (1), and most of the current literature on music psychology has described it as a universal reward for human beings (2). Its ubiquity and antiquity prove the importance of music in our society (3).Paradoxically, not everybody loves music: A small percentage of healthy individuals do not find music pleasurable, a phenomenon known as specific musical anhedonia (4). A detailed study on this population revealed that this phenomenon cannot be explained by perceptual problems [e.g., hearing impairment or specific impairment in perceptual capabilities, a condition known as amusia (5)] or by general anhedonia (lack of pleasure for all types of rewarding stimuli). When listening to music rated as pleasant by others, people with specific musical anhedonia showed a reduced emotional arousal as indexed by autonomic nervous system activity [in particular, skin conductance response (SCR) and heart rate measurements] compared with people having standard or high sensitivity to music. Notably, they showed normal responses to other types of reward [e.g., money (4)]. Therefore, individuals with specific musical anhedonia represent an idea...