Figure 1.

Schematic relations between the signal (S) obtained in functional imaging experiments and mental processes (M). In the usual experimental plan and interpretation, based on psychology, a direct relationship between S and M is assumed, as represented by the upper pathway. The definition of M is based on psychology, while the imaging experiment serves to localize and quantitate the brain activity identified with the process. The lower pathway, Neuroscience, assumes that M has a molecular and cellular basis, which is broken into three steps leading to S. The signal, S, in fMRI or PET experiments, is primarily a measure of the neurophysiological parameters (NP) of cerebral metabolic rate of glucose consumption (CMRglc), cerebral metabolic rate of oxygen consumption (CMRO₂) or CBF. PET methods have been developed for measuring each of these three parameters separately, while fMRI signals respond to differences in the changes of CBF and CMRO₂, whose quantitative relationships are being investigated. CMRO₂ and CMRglc measure cerebral energy consumption, while ΔCMRO₂ and ΔCMRglc measure its increment. The relation between (NP) the neurophysiological measure of energy consumption and neuronal activity (N) has been clarified by the ¹³C MRS experiments (8–10). These recent findings allow measurements of S to be converted into measures of N, which places us squarely facing the unsolved “hard” problem of neuroscience, i.e., what is the relationship between M and N?