Orbitofrontal volume deficit in schizophrenia and thought disorder

Abstract

Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse 'positive formal thought disorder' (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.

Fig. 1

Orbitofrontal subregions and sulcogyral pattern. (A) Orbitofrontal subregions defined by sulci. The Middle Orbital Gyrus (MiOG) defined by us is located between olfactory sulcus medially and lateral orbital sulcus and circular insular sulcus laterally. (B) Sulcogyral pattern within orbitofrontal region. Type I expression is the most frequent and Type III expression is the least frequent. Abbreviations: GR = Gyrus Rectus; MiOG = Middle Orbital Gyri; LOG = Lateral Orbital Gyrus; Olf = olfactory sulcus; MOS = medial orbital sulcus (−r: rostral, −c: caudal); TOS = transverse orbital sulcus; LOS = lateral orbital sulcus (−r: rostral, −c: caudal); IOS = intermediate orbital sulcus (−m: medial, −l: lateral); POS = posterior orbital sulcus; Fr = sulcus fragmentosus. Figures were adapted and modified from a previous paper by Chiavaras and Petrides (see M.M. Chiavaras and M. Petrides. Orbitofrontal sulci of the human and macaque monkey brain. J Comp Neurol 2000; 422: 35–54; reprinted with permission of Wiley-Liss, Inc., a subsidiary of John Wiley & Sons, Inc.).

Fig. 2

MR Images of three orbitofrontal subregions. (A) 3D reconstruction of the three orbitofrontal subregion ROI superimposed on axial SPGR image: Gyrus Rectus (GR; left: blue, right: green); Middle Orbital Gyri (MiOG; left: brown, right: red); and Lateral Orbital Gyrus (LOG; left: purple, right: light green). (B) Orbitofrontal ROIs in axial and coronal planes of SPGR images. Color coding as in (A). See method section for their boundary definition.

Fig. 3

OFC volume comparison. Relative Volume = [Absolute Volume (cm³)/Intra-Cranial Contents Volume (cm³)] × 100 (%). Bars indicate means. Probabilities are from independent-samples t-tests. Note bilateral MiOG differences. Abbreviations: SZ = schizophrenia; HC = healthy control.

Fig. 4

MiOG volume and sulcogyral pattern. Middle Orbital Gyri (MiOG) volumes are not different among the three sulcogyral patterns within each group.

Fig. 5

MiOG probability map comparison. Probability maps of the Middle Orbital Gyri (MiOG) are compared between the schizophrenia and HC groups. The t-map indicates where t-level of schizophrenia <HC at the P0.0001 level (t₄₆ = 4.38). The left anterior OFC (area 11) shows a robust group difference.

Fig. 6

Iowa GamblingTask. Panel A. The schizophrenia group (SZ, red squares) shows poorer performance in Iowa GamblingTask (IGT) as compared to healthy control group (HC, blue triangles). Panel B. IGT performance over time divided into five periods of consecutive 20 trials. At trials 1–20, the gambling scores are almost the same, while groups clearly differ in the gambling score thereafter (trials 21 to 100) with poorer performance in the SZ group.

Fig. 7

Clinical/cognitive correlation analysis. In the schizophrenia group (red squares), smaller left MiOG volumes are associated with more severe positive formal thought disorder. Longer duration of the illness from the first hospitalization for psychosis is associated with smaller MiOG volume. In the control group (blue triangles), larger right MiOG volumes are independently associated with better performance in Iowa Gambling Task and higher IQ.