Multivariate brain-behaviour associations in psychiatric disorders.

Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.

Translating research findings into clinical practice: a systematic and critical review of neuroimaging-based clinical tools for brain disorders.

A pivotal aim of psychiatric and neurological research is to promote the translation of the findings into clinical practice to improve diagnostic and prognostic assessment of individual patients. Structural neuroimaging holds much promise, with neuroanatomical measures accounting for up to 40% of the variance in clinical outcome. Building on these findings, a number of imaging-based clinical tools have been developed to make diagnostic and prognostic inferences about individual patients from their structural Magnetic Resonance Imaging scans. This systematic review describes and compares the technical characteristics of the available tools, with the aim to assess their translational potential into real-world clinical settings. The results reveal that a total of eight tools. All of these were specifically developed for neurological disorders, and as such are not suitable for application to psychiatric disorders. Furthermore, most of the tools were trained and validated in a single dataset, which can result in poor generalizability, or using a small number of individuals, which can cause overoptimistic results. In addition, all of the tools rely on two strategies to detect brain abnormalities in single individuals, one based on univariate comparison, and the other based on multivariate machine-learning algorithms. We discuss current barriers to the adoption of these tools in clinical practice and propose a checklist of pivotal characteristics that should be included in an "ideal" neuroimaging-based clinical tool for brain disorders.