Mentalizing in preclinical Huntington's disease: an fMRI study using cartoon picture stories

Huntington's disease (HD) is an autosomal dominant degenerative brain disorder that is characterized by motor, cognitive and affective symptoms. Previous research has shown that patients with HD, similar to patients with schizophrenia, are impaired in their ability to appreciate the mental states of others. Functional brain imaging studies have shown that patients with schizophrenia underactivate the neural network involved in mentalizing, and that deviant patterns of brain activation are also present in individuals at high risk of developing a psychotic disorder. Accordingly, the present study sought to examine the brain activation in premanifest mutation carriers for HD. Thirty premanifest mutation carriers (13 males) defined by a positive gene test and absence of unequivocal HD symptoms ("pre-HD") performed a cartoon mentalizing task during functional brain imaging. For comparison, a group of 26 healthy controls took part in the study. BOLD responses revealed that pre-HD subjects activated the mentalizing network comprising prefrontal, temporoparietal and parietal brain regions during task performance. A comparison between pre-HD patients and healthy controls revealed no significant activation differences. Premanifest mutation carriers of HD activated the neural network involved in mentalizing similar to healthy control subjects. This suggests that impaired mentalizing emerges with the clinical manifestation of the disease, but is not necessarily part of the pre-manifest stage.