Background Huntington’s disease (HD) can be associated with impairments in theory of mind: the ability to reason about mental states. Deficits in the ability to reflect on and interpret one’s own emotional experience (ie alexithymia) can also be present in HD.

Aims We investigated the neural correlates of empathy in HD by contrasting neural activity to photographs of faces when participants were reasoning about mental versus physical states. We also examined whether neural responses were related to alexithymia ratings.

Method 32 HD gene carriers and 28 matched healthy controls underwent fMRI during the Reading the Mind in the Eyes Task, which involves matching complex mental states (e.g. pensive) to photographs of eyes. For the comparison condition, participants matched ages (eg 45) to the same stimuli. Assessments also included an alexithymia scale which measures the ability to reflect on, interpret and express emotional experiences.

Results When compared to controls, patients exhibited higher ratings of alexithymia, and were impaired at judging mental state, but not age. Differential activity was apparent in areas including frontal and temporal-occipital cortex, anterior cingulate and insula during mental state judgments, and in precuneus and inferior frontal gyrus during age judgments. Contrasting these conditions revealed that the empathy element of the task was associated with reduced activity within left middle frontal gyrus and posterior supramarginal gyrus in HD. Studies implicate these brain regions in attention orienting and switching between first and third person perspective. Alexithymia ratings covaried with activity in the right caudate and anterior cingulate during the empathy task.

Conclusions In HD, a combination of frontal and inferior parietal dysfunction may impair the perspective taking processes required for empathy. Anterior cingulate dysfunction may contribute to both alexithymia and impairments in mentalising.