Functional imaging of the brain in the evaluation of drug response and its application to the study of aging

Abstract

Functional neuroimaging techniques including single photon emission computerised tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (FMRI) can provide insight into the functional connectivity of the human brain in both health and disease, including the effects of aging and drugs on brain function. Neuroimaging measurement techniques can either be direct, using radio-specific ligands, or indirect, using the neurophysiological consequences of pharmacological interventions. Both approaches can be combined with sensorimotor or cognitive activation to examine the interaction between the targeted receptor function and the sensorimotor or cognitive process implicit in the study design. Using radionuclides, PET can provide absolute measurement of cerebral blood flow to regions of interest and can measure changes in cerebral metabolism using labelled fluorodeoxyglucose. PET offered the first opportunity to image brain activation caused by a variety of stimuli and hence to measure the effect of drugs on brain activation. PET also enables the study of drug disposition within the brain. SPECT has been used to study relative changes in cerebral blood flow associated with disease processes and also receptor occupancy. FMRI, by contrast, does not involve ionising radiation and has better spatial and temporal resolution. It is still a relatively new technique and limited by its ability to only measure haemodynamic changes through the blood oxygen level-dependent (BOLD) signal. The effects of aging on drug responsiveness and the effects of drug treatment of diseases associated with old age are relatively unexplored areas of functional neuroimaging research.