Synaptic and cellular events: the last frontier?

The use of functional magnetic resonance imaging (fMRI) to follow random or serial sequences of neural activity is explored and illustrated with examples that include auditory hallucinations and a short-term memory paradigm. Despite the availability of ultra-high-speed fMRI sequences, the inherent latency of the haemodynamic response limits the time resolution of fMRI studies. To access finer time-scales, it can be combined with electromagnetic techniques (MEG or EEG). Functional magnetic resonance spectroscopy (MRS) studies, in which infusion of [1-(13)C]glucose enables rates of the tricarboxylic acid cycle to be determined, demonstrates substantial (50%) increases in this flux on visual activation. Not only does this provide a quantitative estimate of the energy cost of brain activation, it also shows that the extra glucose is consumed essentially oxidatively. In the same studies, measurements of the rate of glutamine synthesis, enable the rate of recycling of neurotransmitter glutamate to be estimated.