 Based on the fundamental principle of the biophysical transduction of physiological signals to magnetic resonance MR imaging and spectroscopic signals, advanced techniques will be developed to measure the activity, metabolism, structure, and biochemistry of the brain. The development of these techniques typically includes the following steps: 1 proof-of-concept computer simulations, 2 implementation of the imaging concept with an MRI scanner and phantoms, 3 feasibility testing on control subjects, and 4 evaluation of the sensitivity and specificity of these techniques in detecting functional changes modulated by task performance, contrast agent injection, CO2 administration, CO2 administration, or transcranial magnetic stimulation evaluation of these techniques in detecting functional andor structural alterations of the brain related to a specific disease. 