Parahippocampal area three gray matter is reduced in first‐episode schizophrenia spectrum: Discovery and replication samples

Abstract

Early course schizophrenia is associated with reduced gray matter. The specific structures affected first and how deficits impact symptoms and cognition remain unresolved. We used the Human Connectome Project multimodal parcellation (HCP‐MMP) to precisely identify cortical areas and investigate thickness abnormalities in discovery and replication samples of first‐episode schizophrenia spectrum individuals (FESz). In the discovery sample, T1w scans were acquired from 31 FESz and 31 matched healthy controls (HC). Thickness was calculated for 360 regions in Freesurfer. In the replication sample, high‐resolution T1w, T2w, and BOLD‐rest scans were acquired from 23 FESz and 32 HC and processed with HCP protocols. Thickness was calculated for regions significant in the discovery sample. After FDR correction (q < .05), left and right parahippocampal area 3 (PHA3) were significantly thinner in FESz. In the replication sample, bilateral PHA3 were again thinner in FESz (q < .05). Exploratory correlation analyses revealed left PHA3 was positively associated with hallucinations and right PHA3 was positively associated with processing speed, working memory, and verbal learning. The novel use of the HCP‐MMP in two independent FESz samples revealed thinner bilateral PHA3, suggesting this byway between cortical and limbic processing is a critical site of pathology near the emergence of psychosis.

Identification of texture MRI brain abnormalities on first-episode psychosis and clinical high-risk subjects using explainable artificial intelligence

“…In other regions such as the insular or cingulate cortex, gray matter loss in CHR-T has also been reported to exceed that of CHR_NT [ 75 ]. The structural alterations reported in previous studies are in line with the identified regions in the current analysis, such as temporal regions [ 76 ]; frontal cortex [ 77 – 79 ]; thalamus [ 72 ]; insula [ 80 ]; hippocampus and caudate nucleus [ 81 , 82 ]; pallidum, putamen [ 83 ]; parahippocampus [ 83 , 84 ]; and lingual cortex [ 85 ]. White matter: There is accumulating evidence of compromised white matter function leading to abnormalities in synchronization and connectivity in patients with schizophrenia [ 86 ], the most widely used measure being fractional anisotropy (FA) assessed with diffusion tensor imaging (DTI).…”

“…In other regions such as the insular or cingulate cortex, gray matter loss in CHR-T has also been reported to exceed that of CHR_NT [ 75 ]. The structural alterations reported in previous studies are in line with the identified regions in the current analysis, such as temporal regions [ 76 ]; frontal cortex [ 77 – 79 ]; thalamus [ 72 ]; insula [ 80 ]; hippocampus and caudate nucleus [ 81 , 82 ]; pallidum, putamen [ 83 ]; parahippocampus [ 83 , 84 ]; and lingual cortex [ 85 ].…”

Altered Coupling of Cerebral Blood Flow and Functional Connectivity Strength in First-Episode Schizophrenia Patients With Auditory Verbal Hallucinations

“…Further analysis based on ROI showed that these areas of AVH patients have higher CBF and lower FCS than HC ( Supplementary Figure 8 ). Many structural ( Onitsuka et al, 2004 ; Cui et al, 2018 ; Curtis et al, 2021 ), functional neuroimaging ( Allen et al, 2008 ), and circuit studies ( Benetti et al, 2015 ; Huang et al, 2019 ; Ren et al, 2021 ) have indicated that the left STG, particularly the primary and association auditory cortex, and the left MTG, play a key role in the etiology of AVHs. The STG on the left mainly deals with the perception of “speech,” that is, understanding the phonetic and semantic features of the speech content ( Modinos et al, 2013 ) and auditory feedback processing originating from the cerebellum ( Christoffels et al, 2007 ).…”

Dysconnection and cognition in schizophrenia: a spectral dynamic causal modeling study

“…Structurally, both the PHG and ITG regions have been reported to have less gray matter volume in SZ patients than in HCs (Curtis et al, 2021;Zhuo et al, 2017). According to (Curtis et al, 2021), the thinner gray matter in the PHG of first episode SZ patients correlates with their hallucinations, processing speed, working memory, and verbal learning. Functionally, (Diederen et al, 2010) showed that auditory verbal hallucinations in SZ patients are consistently preceded by deactivation of the PHG.…”

“…The third contributing variable to the connection-cognition CCA model was the effective connection from PHG to ITG, in the COG network. Structurally, both the PHG and ITG regions have been reported to have less gray matter volume in SZ patients than in HCs (Curtis et al, 2021;Zhuo et al, 2017). According to (Curtis et al, 2021), the thinner gray matter in the PHG of first episode SZ patients correlates with their hallucinations, processing speed, working memory, and verbal learning.…”