A meta-analysis and systematic review of single vs. multimodal neuroimaging techniques in the classification of psychosis
Authors: Porter Alexis , Fei Sihan , Damme Katherine S. F. , Nusslock Robin , Gratton Caterina , Mittal Vijay A. 
Published: August 2023

Abstract
Background
Psychotic disorders are characterized by structural and functional abnormalities in brain networks. Neuroimaging techniques map and characterize such abnormalities using unique features (e.g., structural integrity, coactivation). However, it is unclear if a specific method, or a combination of modalities, is particularly effective in identifying differences in brain networks of someone with a psychotic disorder.

Methods
A systematic meta-analysis evaluated machine learning classification of schizophrenia spectrum disorders in comparison to healthy control participants using various neuroimaging modalities (i.e., T1-weighted imaging (T1), diffusion tensor imaging (DTI), resting state functional connectivity (rs-FC), or some combination (multimodal)). Criteria for manuscript inclusion included whole-brain analyses and cross-validation to provide a complete picture regarding the predictive ability of large-scale brain systems in psychosis. For this meta-analysis, we searched Ovid MEDLINE, PubMed, PsychInfo, Google Scholar, and Web of Science published between inception and March 13th 2023. Prediction results were averaged for studies using the same dataset, but parallel analyses were run that included studies with pooled sample across many datasets. We assessed bias through funnel plot asymmetry. A bivariate regression model determined whether differences in imaging modality, demographics, and preprocessing methods moderated classification. Separate models were run for studies with internal prediction (via cross-validation) and external prediction.

Results
93 studies were identified for quantitative review (30 T1, 9 DTI, 40 rs-FC, and 14 multimodal). As a whole, all modalities reliably differentiated those with schizophrenia spectrum disorders from controls (OR = 2.64 (95%CI = 2.33 to 2.95)). However, classification was relatively similar across modalities: no differences were seen across modalities in the classification of independent internal data, and a small advantage was seen for rs-FC studies relative to T1 studies in classification in external datasets. We found large amounts of heterogeneity across results resulting in significant signs of bias in funnel plots and Egger’s tests. Results remained similar, however, when studies were restricted to those with less heterogeneity, with continued small advantages for rs-FC relative to structural measures. Notably, in all cases, no significant differences were seen between multimodal and unimodal approaches, with rs-FC and unimodal studies reporting largely overlapping classification performance. Differences in demographics and analysis or denoising were not associated with changes in classification scores.

Conclusions
The results of this study suggest that neuroimaging approaches have promise in the classification of psychosis. Interestingly, at present most modalities perform similarly in the classification of psychosis, with slight advantages for rs-FC relative to structural modalities in some specific cases. Notably, results differed substantially across studies, with suggestions of biased effect sizes, particularly highlighting the need for more studies using external prediction and large sample sizes. Adopting more rigorous and systematized standards will add significant value toward understanding and treating this critical population.