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

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.

Brain Mechanisms Underlying the Subjective Experience of Remembering

“…One's cultural background may additionally influence the way that memories are reconstructed: for instance, individuals from East Asian and Western cultures differ in the way that they incorporate contextual and self-relevant details in memory (reviewed by Gutchess & Huff 2016), suggesting a basis for cultural differences in the subjective experience of memory. Conversely, the link discussed above between paracingulate sulcus reductions and hallucinations in schizophrenia has been found to generalize across patients from Australia, the United Kingdom, and China (Garrison et al 2015;Rollins et al 2020).…”

“…People with schizophrenia are often impaired on reality monitoring tasks (Bentall et al 1991;Brébion et al 2000), tending to misattribute imagined stimuli as real (Stephane et al 2010;Vinogradov et al 1997), an effect that is associated with reduced activity in anterior prefrontal cortex (Garrison et al 2017;Vinogradov et al 2008). Moreover, the occurrence of hallucinations in people with schizophrenia can be predicted on the basis of paracingulate sulcus length, with sulcal reductions in individuals with a history of hallucinations compared with those who received their diagnosis based on other symptoms (Garrison et al 2015;Rollins et al 2020) (Figure 3D).…”

Sexually dimorphic neuroanatomical differences relate to ASD-relevant behavioral outcomes in a maternal autoantibody mouse model

“…detailed in Supplementary Table 2. Following cluster assignment, correlation values for each brain region within a cluster were then averaged, similar to that described previously [13]. Mean correlation values were then compared between treatment conditions and sex using Kruskal-Wallis non-parametric testing, with corrections for multiple comparisons using a two-stage step-up FDR method at a level of 5%.…”

Revisiting the Morphology and Classification of the Paracingulate Gyrus with Commentaries on Ambiguous Cases

“…Another brain area associated with hallucinations is the superior temporal sulcus. For example, a reduced depth of this sulcus is observed in patients with auditory hallucinations [36]. Some studies revealed that focal decreased gyrification might lead to hallucinations, but also global reduction of this process might play an important role [36,37].…”

“…For example, a reduced depth of this sulcus is observed in patients with auditory hallucinations [36]. Some studies revealed that focal decreased gyrification might lead to hallucinations, but also global reduction of this process might play an important role [36,37]. Decreased cortical folding was also observed in patients with obsessive-compulsive disorder (OCD).…”