The field of brain imaging has benefited from enormous technological advances over the past 25 years. There is rapid progress in the application of magnetic resonance imaging (MRI) for functional imaging (fMRI) and positron emission tomography (PET) for biochemical imaging. Imaging techniques enable us to assess the properties of brain tissue and to obtain information of how the brain works across scales from the systems level to the molecular level. These assessments and imaging modalities include:(i) Brain morphology and tissue composition: computerized axial tomography (CAT) and MRI.(ii) Electrical and magnetic signals which result from the communication between cells and hence can be used to assess regional brain activation: electroencephalography (EEG) and magnetoencephalography (MEG).(iii) Biochemical components of neurotransmission which provide information on neuronal activity and communication: PET, single-photon emission computed tomography (SPECT), and magnetic resonance spectroscopy (MRS).(iv) Physiological processes which provide information on tissue energy requirements and cerebral blood flow and hence can be used to assess regional brain function: fMRI, PET, SPECT, dynamic CAT.

The sensitivity and specificity for different parameters defines the unique properties as well as the limitations of each imaging modality. For applied research it is thus important to compare one with another with respect to spatial resolution, temporal resolution, sensitivity, and biochemical specificity (Table 1). fMRI has the highest spatial resolution of the imaging technologies that are used for functional mapping of the human brain (1–3). The resolution is significantly better than that of PET and does not require ionizing radiation. This is advantageous because the regional representation in cortex involves areas that are smaller than the current resolution of most PET scanners, and multiple studies can be done in the same subject without the limitation of radiation exposure (Fig. 1). However, compared with PET, the technique is limited by the lack of absolute quantitation. It is generally believed that the activation signal which is generated from fMRI is due to differences in magnetic properties of oxygenated versus deoxygenated hemoglobin (BOLD contrast). During activation of a brain region, there is an excess of arterial blood delivered into the area with concomitant changes in the ratio of deoxyhemoglobin to oxyhemoglobin. It has still not been clarified whether this relative excess of oxyhemoglobin in the activated region is due to perfusion of nonactivated adjacent areas or to excess oxygenation in the activated area secondary to anaerobic glycolysis. However, because functional processes in brain occur at the millisecond range, whereas hemodynamic changes