A role for fMRI in optimizing CNS drug development

Key Points Functional MRI (fMRI) has fundamentally changed the way that we can question brain systems because we can see them in action, bringing systems neuroscience to life. fMRI lets neuroscientists visualize the activity of neural networks that underlie human behaviour and development. fMRI is an indirect measure of neural activity that can be used to evaluate disease states as well as drug function in awake humans and animals. Current problems with the translation of animal behaviour (assays) to the human condition might be overcome by using a circuit-based approach to define objective changes in neural systems. fMRI is able to dissect complex brain function in terms of temporally coordinated activation of related neurocircuits rather than dissociated events associated with disparate nuclei. fMRI has given new dimensions to many areas of complex brain function such as pain, sensory systems, psychiatric disorders and their co-morbidity with other central nervous system (CNS) conditions, cognition, language consciousness and neural mechanisms that underlie the developmental plasticity of the brain or its recovery of function after trauma. fMRI can report on the functional neuroanatomy of the brain and, in combination with targeted therapeutic agents, provide novel insights into CNS neuropharmacology that could inform the drug development process from preclinical stages to clinical evaluation. Whole-system effects allow for the evaluation of drug effects or disease states over time, conferring a better understanding of the long-term effects of drugs by objective measures of these circuits. fMRI is a relatively new technology that is now being evaluated for use in drug development. This has generated significant interest from biotech and pharmaceutical companies wishing to decrease the risk of drug development. Borsook et al . examine the potential use of fMRI as a tool to integrate drug development and optimize clinical development and later stage clinical trials. Drug development today needs to balance agility, speed and risk in defining the probability of success for molecules, mechanisms and therapeutic concepts. New techniques in functional magnetic resonance imaging (fMRI) promise to be part of a sequence that could transform drug development for disorders of the central nervous system (CNS) by examining brain systems and their functional activation dynamically. The brain is complex and multiple transmitters and intersecting brain circuits are impli