"Where do auditory hallucinations come from?"--a brain morphometry study of schizophrenia patients with inner or outer space hallucinations

Abstract

Auditory verbal hallucinations are a cardinal symptom of schizophrenia. Bleuler and Kraepelin distinguished 2 main classes of hallucinations: hallucinations heard outside the head (outer space, or external, hallucinations) and hallucinations heard inside the head (inner space, or internal, hallucinations). This distinction has been confirmed by recent phenomenological studies that identified 3 independent dimensions in auditory hallucinations: language complexity, self-other misattribution, and spatial location. Brain imaging studies in schizophrenia patients with auditory hallucinations have already investigated language complexity and self-other misattribution, but the neural substrate of hallucination spatial location remains unknown. Magnetic resonance images of 45 right-handed patients with schizophrenia and persistent auditory hallucinations and 20 healthy right-handed subjects were acquired. Two homogeneous subgroups of patients were defined based on the hallucination spatial location: patients with only outer space hallucinations (N=12) and patients with only inner space hallucinations (N=15). Between-group differences were then assessed using 2 complementary brain morphometry approaches: voxel-based morphometry and sulcus-based morphometry. Convergent anatomical differences were detected between the patient subgroups in the right temporoparietal junction (rTPJ). In comparison to healthy subjects, opposite deviations in white matter volumes and sulcus displacements were found in patients with inner space hallucination and patients with outer space hallucination. The current results indicate that spatial location of auditory hallucinations is associated with the rTPJ anatomy, a key region of the "where" auditory pathway. The detected tilt in the sulcal junction suggests deviations during early brain maturation, when the superior temporal sulcus and its anterior terminal branch appear and merge.

Fig. 1.

White Matter Volume in the Right Temporoparietal Junction and Spatial Location of Hallucinations. (Up) White matter volume decrease in patients with outer space hallucinations in comparison to patients with inner space hallucinations (red: P corrected < .05; yellow: P uncorrected < .001, for illustration purpose). (Down) Box plot of white matter volumes at cluster voxel maximum (Talairach x, y, z = [54, −37, 13]) controlled for age and gender (pink: patients with outer space hallucinations, green: healthy controls, blue: patients with inner space hallucinations). **P corrected < .05 (whole-brain analysis); *P corrected < .05 (small volume correction with the cluster of the contrast “inner space vs outer space” as mask).

Fig. 2.

Anterior-Posterior Variability of the Right Superior Temporal Sulcus (STS) and Its Anterior Branch (Also Called Angular Sulcus) in Schizophrenia Patients. Individual segmented sulci of patients with outer space hallucinations (pink) and inner space hallucinations (blue) were superimposed on a Montreal Neurological Institute (MNI) referential. (Left) The patient group sulci are shown on an individual's reconstructed right hemisphere cortex surface. (Right) The data are superimposed on the MRI of a subject from the study, at an axial slice (z = 13) where the maximum of voxel-based morphomery difference (x, y, z = [54, −37, 13]) was observed. Note the incomplete overlap between subgroups.

Fig. 3.

Local Displacement of the Right Superior Temporal Sulcus and its Branch in Schizophrenia Patients and Healthy Subjects. In each axial z-slice, the position of the sulcus barycentre was averaged separately for patients with outer space hallucinations (pink spheres), patients with inner space hallucinations (blue spheres), and healthy subjects (green spheres). The yellow region indicates the VBM cluster where white matter volume was reduced in patients with outer space hallucinations in comparison to those with inner space hallucinations (P < .001, uncorrected for multiple testing for ease of visualization). These data are shown on a 3D reconstruction of one individual's right superior temporal sulcus and its branch (light gray). Around the junction between the right superior temporal sulcus and its branch (black arrow), the outer space hallucination subgroup showed an anterior displacement of barycentres, and the inner space hallucination subgroup a posterior displacement of barycentres, in comparison to the healthy group. This is also illustrated by the boxplot of the sulcus barycentre y coordinates (z = 13) in outer space hallucination subgroup, inner space hallucination subgroup, and healthy group. *P < .05.