Applications of fMRI in translational medicine and clinical practice

Functional MRI (fMRI) has had a major impact in cognitive neuroscience. It now has promising applications in clinical and translational medicine.fMRI can assess changes in relative blood oxygenation accompanying increased blood flow in regions of the brain that are active while a task (for example, hand movement) is performed. The most well-established clinical application of fMRI is for presurgical mapping; this guides a neurosurgeon to spare brain tissue that, if injured, would cause new clinical deficits or limit good recovery.In combination with simultaneously acquired electroencephalography (EEG), fMRI can image blood oxygenation state changes that accompany spontaneously generated changes in brain state in order to localize the source of seizure-inducing activity in epilepsy. The spatial definition of MRI allows this to be done at a much higher resolution than with EEG alone.A frontier area for fMRI is in the identification of neurophysiologically based intermediate phenotypes in ways that can characterize even disorders that do not show structural changes in the brain. Recent applications suggest that functional intermediate phenotypes could better define heterogeneity in psychotic and affective disorders, and could be used to predict treatment outcomes.In some instances, intermediate phenotypes that are heritable are endophenotypes. Because endophenotypes can be determined by smaller numbers of genes than conventional clinical phenotypes, in some cases plausible allelic associations have been identified with sample sizes smaller than those required in usual association studies.By defining functional anatomy that is related to behavioural or perceptual states, fMRI can also help to directly understand the genesis of symptoms. For example, fMRI dissection of the subjective experience of pain into anatomically distinct activities of different functional systems provides a rationale for treatment approaches that are based on the modulation of different, interacting pathways.Applications of fMRI as a pharmacodynamic (or pharmacokinetic) measure (pharmacological fMRI or phMRI) suggest that it might assume an important role in drug development. There are already several examples in which fMRI has been shown to be sensitive to change after a therapeutic intervention.However, there remain practical problems that need to be resolved before fMRI can be used routinely. Signal changes are small, there are many confounds affecting the signal-to-noise ratio and the underlying physiological response itself is highly variable.The promise of this new technique is substantial, but it is clear that the widespread introduction of clinical fMRI will demand new skills and working methods in clinical neuroradiology if this promise is to be delivered.