Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia

Colleen P E Rollins,Raymond C K Chan,Duo Wang,Bill Deakin,Chao Yan,Maite Arribas,Junwei Yang,John Suckling,Rachel Upthegrove,Jane R Garrison,Arnaud Cachia,Graham K Murray,Zhi Li,Jon S Simons,Aida Seyedsalehi,Zheng-Hui Yi,Pietro Liò

doi:10.1038/s41398-020-01075-y

Abstract

All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.

Highlights

All perception is a construct of the brain
Bearing in mind that sulcal patterns are established during gestation and are fixed across the first decades of life, our results indicate a structural risk factor for hallucinations arising in early life that we suspect is sensitive to subsequent life experiences and culturally-acquired expectations that are known to color hallucination content
We first replicated the association of reduced left paracingulate sulcus (PCS) length with hallucinations in two independent samples representing British and Han Chinese ethnicities, collectively comprising a larger sample than previously studied

Summary

Introduction

All perception is a construct of the brain. Sensory constructions emerge without origin in the physical world and are experienced as hallucinations. Hallucinations occur transdiagnosticallly, cross-culturally, and in all sensory modalities[4,5]. Our prior work established the role of cingulate and temporal lobe sulcal topology, products of early neurodevelopment[7], in reality monitoring and the experience of hallucinations associated with schizophrenia[8,9,10,11], suggesting that variants in fetal brain development might confer later vulnerability to hallucinations. The characteristic morphological features of the brain’s surface emerge in a specific order during the perinatal period, with the primary convolutions occurring in the second trimester, and dramatic growth of sulci and gyri in Rollins et al Translational Psychiatry (2020)10:387

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Conclusion