Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study

Abstract

IntroductionSchizophrenia is regarded as a disorder of connectivity associated with neurodevelopmental abnormality.1 Despite accumulating evidence for disturbances in functional connectivity, 2 it is unclear how these findings are related to defective cortical development.Developmental aberrations can affect several characteristic anatomic features of the grey matter surface. Cortical development is constrained by the need to develop a cost-efficient wiring scheme wherein signal transmission is quick and effective 3 and by the limitations on the total brain size partly to facilitate parturition. 4,5 This is facilitated by a substantial expansion of surface area along with a high degree of cortical folding despite a relatively minor gain in cortical thickness during evolutionary development. 6 This remarkable dissociation between thickness and surface area persists in adult human brains. 7Axonal connections in the developing brain are considered to be one of several factors that influence the morphology of the cortical surface. 8 In particular, a widely accepted model of cortical morphogenesis suggests that the appearance of cortical convolutions is dependent on the underlying neuronal connectivity.9 Disturbances in regional cortical gyrification can be a surrogate marker for disruptions in neuronal connectivity during development. 9,10Most studies examining neuroanatomical changes in patients with schizophrenia have employed voxel-based morphometry (VBM) and report consistent volume reduction bilaterally in the insula and anterior cingulate cortex (ACC). Compared with the number of studies investigating volumetric defects, relatively few studies have attempted to locate gyrification defects within the entire cortex in patients with schizophrenia (see White and Hilgetag 10 for a detailed review). Most previous investigations have quantified differences in gyrification at preselected regions of interest (ROI), Background: Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in connectivity at an early period of cortical maturation can result in widespread defects in gyrification. Investigating the anatomic distribution of gyrification defects can provide important information about neurodevelopment in patients with schizophrenia. Methods: We undertook an automated surface-based morphometric assessment of gyrification on 3-dimensionally reconstructed cortical surfaces across multiple vertices that cover the entire cortex. We used a sample from our previous research of 57 patients (50 men) with schizophrenia and 41 controls (39 men) in whom we had tested a specific hypothesis regarding presence of both hypoand hypergyria in the prefrontal cortex using a frontal region-of-interest approach. Results: Regions with significant reductions in gyrification (hypogyria) were seen predominantly in the left hemisphere, involving the insula and several regions of the multimodal association cortex. Although the prefrontal hypergyria documented ea...

Reduced brain cortical folding in schizophrenia revealed in two independent samples

“…Our finding of reduced gyrification in left pericentral and right temporo-occipital cortex is partly convergent with two previous studies using the automated lGI method in patients with adolescent onset (Palaniyappan et al, 2013a) and adult onset schizophrenia (Palaniyappan and Liddle, 2012). Hypogyria in bilateral insular, left frontal and right temporal regions have been linked to lack of response to antipsychotic medication in first-episode psychosis patients (Palaniyappan et al, 2013b).…”

“…Higher GI in prefrontal cortex has been found among high-risk patients who later developed schizophrenia compared to those who did not (Harris et al, 2004(Harris et al, , 2007. Studies using the automated lGI method have shown reduced folding in the right prefrontal cortex among patients with adolescent onset (Janssen et al, 2009) and adult onset schizophrenia (Palaniyappan et al, 2011), and reduced folding in the left insula and medial parieto-occipital cortex in adult onset schizophrenia (Palaniyappan and Liddle, 2012).…”

Increased gyrification in schizophrenia and non affective first episode of psychosis

“…However, other studies reported hypogiria or preserved GI in the PFC of patients with schizophrenia (Bonnici et al, 2007;Cachia et al, 2007;Kulynych et al, 1997;Mancini-Marie et al, 2015;McIntosh et al, 2009;Nesvag et al, 2014;Palaniyappan and Liddle, 2012;Palaniyappan et al, 2011;Tepest et al, 2013;Highley et al, 2003). Possible explanations for these contrasting results could be related to the relative small sample size or to the presence of discrepancy between males and females within the patients or the control group.…”

“…Nonetheless, the evidence reporting the role of prefrontal cortical folding in schizophrenia have led to contrasting results (White and Hilgetag, 2011). Indeed, although PFC hypergyria has been reported in patients suffering from schizophrenia (Falkai et al, 2007;Vogeley et al, 2001;Nenadic et al, 2015), other authors have, in contrast, reported hypogyria (Bonnici et al, 2007;Cachia et al, 2007;Kulynych et al, 1997;Mancini-Marie et al, 2015;McIntosh et al, 2009;Nesvag et al, 2014;Palaniyappan et al, 2011;Palaniyappan and Liddle, 2012;Tepest et al, 2013) or no abnormalities (Highley et al, 2003). Similarly, the same mixed picture have been reported in first-episode patients with schizophrenia (Narr et al, 2004;Janssen et al, 2014;Wiegand et al, 2005), while only one study has investigated cortical gyrification in non-affective first-episode psychosis (FEP-NA) (Palaniyappan et al, 2013), showing hypogyria in the PFC.…”

Diagnostic Discontinuity in Psychosis: A Combined Study of Cortical Gyrification and Functional Connectivity

“…In a different sample of subjects, we have previously shown that both increased and decreased gyrification in schizophrenia are observable at this threshold. 31 …”