Paracingulate sulcus morphology is associated with hallucinations in the human brain

Abstract

Hallucinations are common in psychiatric disorders, and are also experienced by many individuals who are not mentally ill. Here, in 153 participants, we investigate brain structural markers that predict the occurrence of hallucinations by comparing patients with schizophrenia who have experienced hallucinations against patients who have not, matched on a number of demographic and clinical variables. Using both newly validated visual classification techniques and automated, data-driven methods, hallucinations were associated with specific brain morphology differences in the paracingulate sulcus, a fold in the medial prefrontal cortex, with a 1 cm reduction in sulcal length increasing the likelihood of hallucinations by 19.9%, regardless of the sensory modality in which they were experienced. The findings suggest a specific morphological basis for a pervasive feature of typical and atypical human experience.

Figure 1. PCS measurement for two example images.

The paracingulate sulcus (PCS), marked in red, lies dorsal and parallel to the cingulate sulcus (CS), itself dorsal to the corpus callosum. (a) In this image, the PCS is continuous and is measured from its origin in the first quadrant (indicated by the cross-hairs at y=0 and z=0) to its end. (b) In this example, the PCS appears less distinct; it is measured from the point at which it runs in a posterior direction, dorsal to the cingulate sulcus.

Figure 2. PCS length by group.

(a) Total PCS length across both hemispheres. (b) PCS length in the left hemisphere. (c) PCS length in the right hemisphere. ***P<0.001, **P<0.01, *P<0.05. Error bars represent standard error of the mean. Controls: 40 healthy control subjects; no hallucinations: 34 patients with schizophrenia who had not experienced hallucinations; hallucinations: 79 patients with schizophrenia who experienced hallucinations in any modality.

Figure 3. Whole-brain cortical gyrification differences as a function of hallucination status.

(a) mPFC regions surrounding the PCS exhibiting significantly reduced gyrification in 79 patients who experienced hallucinations compared with 34 patients without hallucinations, rendered on a canonical pial cortical surface, viewed from the midline. (b) Local gyrification index in regions surrounding the PCS significantly differentiates patients with schizophrenia as a function of hallucination status, t(111)=2.165, P=0.033, d=0.448. Error bars represent standard error of the mean.

Figure 4. Grey matter volume differences measured with voxel-based morphometry.

(a) Significantly greater grey matter volume in 79 patients who experienced hallucinations than in 34 patients without hallucinations in the mPFC region of interest in the vicinity of the anterior PCS (circled), rendered on an inflated canonical cortical surface, viewed from the front. (b) Grey matter volume in PCS region significantly differentiates patients with schizophrenia as a function of hallucination status, Z=2.82; P=0.036 (small volume corrected). Error bars represent standard error of the mean.