Abnormal cortical folding patterns within Broca's area in schizophrenia: evidence from structural MRI

Abstract

We compared cortical folding patterns between patients with schizophrenia and demographically-matched healthy controls in prefrontal and temporal regions of interest. Using the Freesurfer (http://surfer.nmr.mgh.harvard.edu) cortical surface-based reconstruction methodology, we indirectly ascertained cortical displacement and convolution, together, by measuring the degree of metric distortion required to optimally register cortical folding patterns to an average template. An area within the pars triangularis of the left inferior frontal gyrus (Broca's area) showed significantly reduced metric distortion in the patient group relative to the control group (p=0.0352). We discuss these findings in relation to the neurodevelopmental hypothesis and language dysfunction in schizophrenia.

Figure 1

Cortical reconstruction. A given subject brain represented here by a 3D pial surface reconstruction (a) was transformed into gray matter/white matter interface surface (b), inflated (c) and transformed again into a spherical surface (d). Gyri and sulci are represented in light gray and dark gray colors, respectively.

Figure 2

Spherical registration and metric distortion. Spheres (a, d) and (b, e) are reconstructed brain surfaces from a control subject and a schizophrenia patient, respectively. A subject sphere was registered to the average subject template sphere (c) using a non-linear warping algorithm. The metric distortion required to correctly align gyri (light gray) and sulci (dark gray) was a direct reflection of the cortical folding distortions and convolutions between a subject sphere and the template average. Outlines of the central sulcus (CS, light green), intraparietal sulcus (IPS, light blue), Sylvian fissure (SF, yellow) and superior temporal sulcus (STS, magenta) based on the average subject template sphere (c) are overlaid on the subject spheres before and after registration to illustrate the process.

Figure 3

Cortical folding variability in Broca's area (pOr, pTr, pOp), dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG). This illustrates the individual cortical folding variability of these ROI's between two control subjects (a, b) and two schizophrenia patients (c, d) in a pial surface reconstruction of brain image volumes. In the spherical registration of these subjects to an average subject template, the metric distortion required for optimal alignment is a reflection individual cortical displacement and convolution.

Figure 4

Composite surface representation of statistically significant clusters of metric distortion in the (a) left and (b) right hemispheres that survived multiple comparisons correction in the pars orbitals (pOr), pars triangulars (pTr), pars opercularis (pOp), dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) ROI's. One blue-cyan cluster in the left pTr survived multiple comparisons correction. Statistical analysis was performed using a General Linear Model (GLM) and corrected for multiple comparisons using the Monte Carlo permutation method. Color bar represents statistical significance for the maxima p-value of the coordinate vertices located within the significant clusters of metric distortion: control subjects > schizophrenia patients (0.1 control subjects (0.1