Background Huntington's disease patients’ social conduct is altered and there is frequently severe breakdown in interpersonal relationships. Patients are often described as self-centred, lacking in sympathy and empathy, and mentally inflexible, sometimes with fixed ideas, which may not be consistent with the prevailing view or available evidence.

Aims We assessed the brain mechanisms related to the appraisal of emotional cues of another person in connection with contextual cues.

Methods We used H2O15 position emission tomography in a paradigm of face to face social interaction supposed to cause an empathic response to evaluate the modulation of cerebral blood flow related to the appraisal of empathy.

Results The results showed that patients had a deficit of activation in the temporal pole and of inhibition in the anterior cingulate cortex and the orbitofrontal cortex, demonstrating a lack of association between the emotion expressed by the virtual partner and the emotional context, and also a deficit of inhibition of behavioural response in the case of inappropriate social behaviours. In the spouses’ group, cerebral activation seemed to be midway between that of the patient and the control group in the anterior cingulate cortex and the left temporoparietal junction.

Conclusions The results of this study make it clear that Huntington's disease patients demonstrate functional changes in empathy and perspective taking related regions when appraisal of emotional and contextual cues is requested. In contrast, decision making and behavioural response structures (OFC and ACC) were more activated in patients, probably reflecting a lack of inhibition in these regions. Nevertheless, compensatory processes may have taken place to counteract the difficulty of making emotion/context association by mentalising processes, and their underlying brain structure, that is self-representation and inference/false indication detection supported by the precuneus and the left TPJ, respectively.