A functional MRI study of Theory of Mind in euthymic bipolar disorder patients

OBJECTIVES: To determine the neural responses invoked in Theory of Mind (ToM) in euthymic bipolar patients as compared with healthy subjects. METHODS: This study examined 20 euthymic bipolar patients (11 males and 9 females) and 20 suitably matched healthy subjects using functional magnetic resonance imaging (fMRI) while subjects were engaged in a ToM task. Within-scanner eye movements were monitored to ensure task engagement. The activation paradigm involved observing ToM and random-motion animated sequences in a block design. Both within group (ToM versus random motion) and random effects between group analyses were performed on fMRI data using the BrainVoyager software package. Demographic and clinical data, along with subject ratings of fMRI stimuli, were collated and analysed. RESULTS: Patients were compromised in their ability to appropriately rate the ToM stimuli and assess them for intention as compared to healthy subjects. This was reflected in the fact that patients had few within-group significant activations in response to ToM animated sequences, namely, the left anterior cingulate, and precuneus and cuneus bilaterally. In contrast, robust activations in response to ToM animated sequences in healthy subjects were widespread and involved regions recognized for mental state reasoning, in particular the insula, inferior frontal, supramarginal and angular gyri, and temporal cortex. The between-group random effects analysis exclusively favoured the healthy subjects, with many activations occurring in regions overlapping with those found in the within-group analyses. CONCLUSIONS: The findings of this novel neuroimaging study suggest that in a social context, euthymic bipolar patients, though seemingly well and capable of engaging aspects of ToM, are perhaps constrained in their ability to mentalize fully, and furthermore cannot reliably adopt an alternate cognitive perspective when appropriate. Impairment of this capacity, though subtle, may in effect compromise their ability to understand the emotions and intentions of others, and also may limit appreciation of their own illness and symptoms. Such a deficit in bipolar disorder perhaps impacts upon interpersonal relationships and adversely affects social cognition and clinical functioning. The potential implications of this putative mentalizing compromise in euthymic patients with bipolar disorder are substantial, both for the individual and for understanding the neural substrate of the illness, and therefore warrant further investigation.