Orbitofrontal cortex hypergyrification in hallucinating schizophrenia patients: surface ratio as a promising brain biomarker

BackgroundThere has been increasing interest in the study of brain gyrification in schizophrenia since it may provide additional useful information on the cytoarchitecture and connectivity of the brain. Various methods have been developed to estimate brain gyrification that, so far, have yielded mixed and inconclusive results in schizophrenia studies. To the best of our knowledge, an alternative method to compute brain gyrification, known as surface ratio (SR), has not yet been applied to a schizophrenia sample. Our aim in this study was to assess whether SR could provide new insights on the brain structure of schizophrenia patients and the severity of symptoms. We also computed a more established brain gyrification measure, namely absolute mean curvature (AMC), for comparison. MethodWe processed and analyzed a total of 63 magnetic resonance images, 25 from schizophrenia patients with treatment-resistant auditory verbal hallucinations (SCH-H), 18 from schizophrenia patients without hallucinations (SCH-NH), and 20 from healthy controls (HC). We estimated brain gyrification with SR and AMC employing CAT software. ResultsThe SR measure mainly revealed that SCH-H patients had a more folded orbitofrontal cortex than SCH-NH patients and HC. Gyrification in this region was also negatively associated with positive symptoms, specifically with the delusions and conceptual disorganization items, only in the SCH-H group. Conversely, SCH-NH and HC showed more SR than SCH-H in other frontal areas. As for the AMC measure, we identified two areas where HC showed more gyrification than SCH-H patients, but no relationships arose with symptoms. DiscussionWe hypothesize that the hypergyrification of the orbitofrontal cortex displayed by SCH-H patients, as captured by the SR measure, suggests aberrant and/or excessive wiring in these patients, which in turn could give rise to auditory verbal hallucinations. Alternatively, we comment on potential compensatory mechanisms that may better explain the negative association between orbitofrontal gyrification and positive symptomatology. Importantly, the estimation of brain gyrification with the SR measure seems to capture the most relevant differences and associations, making it a promising biomarker in schizophrenia research.