Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions

Abstract

Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case‐control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data‐driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case‐control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.

Brain network functional connectivity changes in long illness duration chronic schizophrenia

“…The human brain has a cortical stratification mechanism that extends from the primary sensory system to the higher cognitive function system, which helps the human brain process different domains of functions (such as sensory and cognitive processes) separately. In addition, the brain network can be dynamically configured and interacted to achieve more complex mental activities ( 37 ).…”

Magnetic Resonance Imaging (MRI) Insights into Brain Morphology and Connectivity Disruptions in Schizophrenia

“…MRI techniques elucidate disruptions in connectivity networks, such as the default mode network, contributing to a better understanding of how connectivity abnormalities relate to cognitive deficits in schizophrenia [3].…”

On the Road to Individualizing Pharmacotherapy for Adolescents and Adults with Schizophrenia – Results from an Expert Consensus Following the Delphi Method

“…Nevertheless, such measurable indicators of underlying biological processes or states have the potential to improve diagnostic accuracy, predict treatment response, and deepen understanding of the underlying neurobiological mechanisms associated with the disorder. Therefore, augmenting the field of psychiatry, which relies mostly on self-reports, informant reports, interviews and behavioral observation, by linking these data points to biological assessments [31][32][33][34][35][36][37][38] is an aspirational goal that needs to be pursued further. However, while some genetic, immunological, clinical, and neuroimaging biomarkers have shown potential, particularly in the areas of predicting conversion to psychosis and treatment response, discontinuation, and relapse risk, no single biomarker has been able to achieve disease-or https://doi.org/10.2147/NDT.S456163…”