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Spatially Covarying Patterns of Gray Matter Volume and Concentration Highlight Distinct Regions in Schizophrenia

ABSTRACT: Introduction: Individuals with schizophrenia have consistent gray matter reduction throughout the cortex when compared to healthy individuals. However, the reduction patterns vary based on the quantity (concentration or volume) utilized by study. The objective of this study was to identify commonalities between gray matter concentration and gray matter volume effects in schizophrenia. Methods: We performed both univariate and multivariate analyses of case/control effects on 145 gray matter images from 66 participants with schizophrenia and 79 healthy controls, and processed to compare the concentration and volume estimates. Results: Diagnosis effects in the univariate analysis showed similar areas of volume and concentration reductions in the insula, occipitotemporal gyrus, temporopolar area, and fusiform gyrus. In the multivariate analysis, healthy controls had greater gray matter volume and concentration additionally in the superior temporal gyrus, prefrontal cortex, cerebellum, calcarine, and thalamus. In the univariate analyses there was moderate overlap between gray matter concentration and volume across the entire cortex (r = 0.56, p = 0.02). The multivariate analyses revealed only low overlap across most brain patterns, with the largest correlation (r = 0.37) found in the cerebellum and vermis. Conclusions: Individuals with schizophrenia showed reduced gray matter volume and concentration in previously identified areas of the prefrontal cortex, cerebellum, and thalamus. However, there were only moderate correlations across the cortex when examining the different gray matter quantities. Although these two quantities are related, concentration and volume do not show identical results, and therefore, should not be used interchangeably in the literature.

SUBMITTER: Rootes-Murdy K

PROVIDER: S-EPMC8551386 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDespite decades of research, there is continued uncertainty regarding whether autism is associated with a specific profile of gray matter (GM) structure. This inconsistency may stem from the widespread use of voxel-based morphometry (VBM) methods that combine indices of GM density and GM volume. If GM density or volume, but not both, prove different in autism, the traditional VBM approach of combining the two indices may obscure the difference. The present study measures GM density and volume separately to examine whether autism is associated with alterations in GM volume, density, or both.MethodsDifferences in MRI-based GM density and volume were examined in 6-25 year-olds with a diagnosis of autism spectrum disorder (n = 213, 80.8% male, IQ 47-154) and a typically developing (TD) sample (n = 190, 71.6% male, IQ 67-155). High-resolution T1-weighted anatomical images were collected on a single MRI scanner. Regional density and volume were estimated via whole-brain parcellation comprised of 1625 parcels. Parcel-wise analyses were conducted using generalized additive models while controlling the false discovery rate (FDR, q < 0.05). Volume differences in the 68-region Desikan-Killiany atlas derived from Freesurfer were also examined, to establish the generalizability of findings across methods.ResultsNo density differences were observed between the autistic and TD groups, either in individual parcels or whole brain mean density. Increased volume was observed in autism compared to the TD group when controlling for Age, Sex, and IQ, both at the level of the whole brain (total volume) and in 45 parcels (2.8% of total parcels). Parcels with greater volume included inferior, middle, and superior temporal gyrus, inferior and superior frontal gyrus, precuneus, and fusiform gyrus. Converging evidence from a standard Freesurfer pipeline also identified greater volume in a number of overlapping regions.LimitationsThe method for determining "density" is not a direct measure of neuronal density, and this study cannot reveal underlying cellular differences. While this study represents possibly the largest single-site sample of its kind, it is underpowered to detect very small differences.ConclusionsThese results provide compelling evidence that autism is associated with regional GM volumetric differences, which are more prominent than density differences. This underscores the importance of examining volume and density separately, and suggests that direct measures of volume (e.g. region-of-interest or tensor-based morphometry approaches) may be more sensitive to autism-relevant differences in neuroanatomy than concentration/density-based approaches.

Project description:Widespread cortical gray matter alternations in people with schizophrenia are correlated with both psychotic symptoms and cognitive/behavioral abnormalities, including the impairments of exploratory eye movement (EEM). Particularly, the loss of gray matter density is specifically related to deficits of the responsive search score (RSS) of EEM in schizophrenia. It is unknown, however, whether the schizophrenia-related RSS deficits are associated with certain psychotic symptoms, such as hallucinations.In 33 participants with schizophrenia, the measurement of EEM, assessment of the hallucination severity using Positive and Negative Syndrome Scale (PANSS) and a voxel-based morphometric analysis of cortical gray matter volume (GMV) were conducted to investigate the relationships between the RSS of EEM, symptom severity, and GMV. In 29 matched healthy controls, the measurement of EEM and a voxel-based morphometric analysis of cortical GMV were also conducted to investigate the relationship between the RSS of EEM and GMV.In participants with schizophrenia, the hallucination severity was significantly negatively correlated with both the RSS and the GMV of a large number of brain regions in the frontal, temporal, parietal, orbitofrontal, calcarine, cingulate, and insular cortices, and rolandic operculum, hippocampus, parahippocampal gyrus, and thalamus. Also in participants with schizophrenia, the RSS was significantly positively correlated with the GMV in the left supplementary motor area (SMA), left superior frontal cortex (SFG), bilateral precentral gyri, bilateral postcentral gyri, and bilateral middle frontal cortices. More importantly, the GMV of the SMA, SFG, and precentral gyrus in the left hemisphere was not only significantly negatively correlated with the hallucination severity but also significantly positively correlated with the RSS. No significant correlation could be revealed between the RSS and the GMV of any brain regions in healthy controls.There was a significantly negative association between the hallucination severity and the RSS of EEM, suggesting that the RSS may be a potential biomarker for predicting the hallucination severity of schizophrenia. Also, the GMV of the left SMA, SFG, and precentral gyrus may be the common substrates underlying both hallucination induction and the RSS in people with schizophrenia.

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Spatially Covarying Patterns of Gray Matter Volume and Concentration Highlight Distinct Regions in Schizophrenia

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