This study has several limitations. learn more There is a need to further substantiate the validity and limitations of the mentalising paradigm as applied to music, and the relation between elementary emotion processing and the attribution of more complex or ambiguous affective states to music. There is no universally agreed ‘lexicon’ of musical emotions and more information is needed about musical mentalising in the healthy brain. Mentalising in music should

ideally be studied in the context of a comprehensive assessment of mentalising abilities in different modalities; this would enable evaluation of the specificity and sensitivity of the music-associated deficit. In a related vein, it would be relevant to manipulate musical stimulus parameters such as familiarity, valence and complexity as well as perceptual characteristics to assess the extent to which these may modulate mentalising on musical stimuli. From a clinical perspective, there is a need for detailed neuropathological correlation in bvFTD populations, both to establish disease associations and to correlate behavioural deficits

with histopathological features. It would, for example, be intriguing to evaluate the role of Von Economo neurons in this very specifically human ability (Seeley et al., 2012). In addition, the promise of early disease detection requires further substantiation of the timing of development of mentalising deficits in the course of bvFTD evolution. CDK inhibitor It would be of great interest, for example, to establish whether such deficits (and particularly, deficits of more abstract ToM processes, such as those embodied in music) might lead other features in presymptomatic carriers of mutations causing bvFTD. This will require longitudinal study of individuals affected and at-risk Thiamet G of developing bvFTD. Taking these caveats into account, the present findings provide evidence that music can represent surrogate mental states and that the ability to construct such mental representations is impaired

in bvFTD. The findings have potential implications for our understanding of the biology of this disease and human social cognition more broadly. LED, CJM, SJC and JDW were each involved in designing and conducting the study, and in drafting and critically revising the manuscript. LED collected and analysed the data and CJM also provided technical assistance with the neuroimaging analysis. AB and RO created the stimulus sets, collected pilot data and were involved in drafting the manuscript. HLG assisted with collection of neuropsychological data and was involved in drafting the manuscript. JN designed and supervised the statistical analysis and was involved in drafting the manuscript. LED, CJM, HLG, SJC and JDW receive salary and research support from the Medical Research Council, Alzheimer Research UK and the Wellcome Trust.