Brain-Behavior Associations: From Discovery to Clinical Application

Modern neuroimaging techniques have enabled great strides in understanding how the brain gives rise to behavior. While uncovering relationships between neural systems and psychiatric illnesses offers great promise for improving patient outcomes, current therapeutic approaches that utilize brain-behavior associations remain largely experimental and have seen limited integration into routine clinical practice. In this review, we outline key challenges and opportunities across 3 main stages in the brain-behavior therapeutic development cycle: identification, interpretation, and implementation. First, we discuss several experimental and technical considerations when elucidating associations between the brain (regions, networks, dynamics, etc.) and clinically relevant behaviors, with an emphasis on multimodal imaging and novel psychometric approaches. Next, we explore the complexities of interpreting brain-behavior relationships to glean mechanistic insights for therapeutic development. These include modeling considerations, causal inference, and contending with weak associations. Finally, we discuss the barriers facing clinical implementation spanning technical, political, and ethical dimensions. By laying out what we consider to be the critical challenges impeding therapeutic development from start to finish, alongside the potential opportunities to address them, we hope to accelerate the progression of brain-behavior associations through identification, interpretation, and implementation, culminating in new impactful methods for treating psychiatric illnesses.