Theory of mind and schizophrenia: a positron emission tomography study of medication-free patients

Abstract

Background: "Theory of mind" (TOM) refers to the ability to attribute mental states (ie, beliefs and goals) to one's self and others and to recognize that behaviors are guided by these mental states. This capacity, critical for social competence, is impaired in schizophrenia. We undertook a study of TOM in a group of patients with schizophrenia and healthy controls.

Method: We used positron emission tomography to identify the neural circuits recruited during a verbal task that required participants to attribute mental states to a character in a story of their creation. The comparison task consisted of reading aloud a neutral story, controlling for the speech component of the task.

Results: Patients and controls generated the same percentage of TOM utterances. However, the two groups had markedly different patterns of brain activation. Compared with controls, patients had a lower blood flow in multiple regions in the left hemisphere including the frontal and visual association cortices, posterior hippocampus, and insula. The flow was also lower in contralateral areas in the lateral cerebellum and vermis, thalamus, and posterior insula. On the other hand, the flow was higher in the patients predominantly in the right hemisphere, including multiple frontal and parietal regions, insula, visual association cortex, and pulvinar.

Discussion: The areas of lower flow are consistent with previous studies indicating impairment in recruiting cortical-cerebellar circuitry in schizophrenia. The areas of higher flow may reflect a need to draw on the right hemisphere to compensate for deficits in left hemisphere networks that include frontal cortex, anterior cingulate, cerebellum, and thalamus.

Fig. 1.

This figure shows brain regions recruited differently by the 2 study groups based on between-group randomization analysis comparing the theory of mind minus the Read Story subtraction in both groups (patients with schizophrenia – healthy individuals). Orientation is radiological convention. Four different sets of images have been selected in order to illustrate the location of peaks. Three orthogonal views are shown, with transaxial at the top, sagittal in the middle, and coronal on the bottom. Green crosshairs are used to show the location of the slice. Statistical maps of the PET data, showing regions that are differentially activated, are superimposed on a composite MR image derived by averaging the MR scans from the subjects. Two types of statistical maps are provided. The “peak map” (left side of image) shows the small areas where all contiguous voxels exceed the predefined threshold for statistical significance (P < .005). The “t map” (right side of image) shows the value of t for all voxels in the image and provides a general overview of the landscape of changes in regional cerebral blood flow (rCBF). Areas of higher rCBF appear in yellow, while those of lower rCBF are in blue. For each slice (axial, sagittal, and coronal planes), the green crosshairs show the location of the 2 other slices, and the intersection of the crosshairs indicates the pixel with the highest t value within the area marked by the crosshairs. In (A), an area of decreased flow in the left and right orbitofrontal area (BA 11) can be seen in the sagittal view. In (B), an area of lower rCBF in the left hippocampus is seen at the intersection of the crosshairs in all 3 planes. In (C), an area of lower rCBF in the left lingual gyrus (BA 18) shows all 3 planes; an area of decreased flow is also seen in the dorsomedial nucleus of the thalamus. In (D), in the transaxial view, a large area of lower rCBF is also seen in the cerebellum.

Fig. 2.

Several areas of higher regional cerebral blood flow (rCBF) (in yellow) in patients with schizophrenia are shown. In the axial plane, an area in the calcarine fissure (BA 17) and one in the right frontal area (BA 32/10/47/11) are seen. In addition, a left frontal area (BA 9/46) in the sagittal plane and another area in the thalamus in the frontal plane exhibit a higher rCBF in the patients. Finally, 3 regions of higher rCBF show in yellow: a right thalamic (Pulvinar) area in the sagittal view and a right cerebellar and a right superior parietal (BA 7) area in the frontal plane.