Although the exact mechanism by which synaptic processes cause metabolic and vascular changes is not well-understood, the empirical relationship between these parameters is very reliable. PET is one of the techniques that has exploited this empirical relationship to image neural activity of the human brain in vivo. In PET, participants are injected with (or in some cases breathe) a radioactively labeled compound (e.g., one containing nC, 15O, 18f, or N). These compounds reach the brain about 20 sec after administration. When the isotope decays, it emits positrons that travel a short distance (a few millimeters on average, depending on the compound) until they encounter an electron; at this point they annihilate each other, producing two high-energy photons traveling 180° apart along a single line. The PET detectors (rings of ''scintillation detectors'' arrayed in parallel planes) record the near-simultaneous arrival of photons along a single line and employ the difference in arrival time to compute exactly where along the line the photons were produced. A three-dimensional image is then created on the basis of this information.

The relationship between local neural activity and regional glucose metabolism has been used in PET studies employing 18F-fluorodeoxyglucose (18F-DG), which is metabolized only partially (unlike glucose 6-phosphate), and more of it accumulates intracellularly when the local metabolic rate is greater. By employing 18F-DG, it is possible to visualize brain regions containing neural populations that were metabolically active during the period between tracer injection and detection of the radioactive decay. Because of the long half-life of 18F-DG (about 2 hr; recall that a half-life is the time required for one-half the radiation to decay), this technique has been employed to study phenomena with very slow time courses, such as sleep. To study faster phenomena, such as perception and attention, better temporal resolution is required. H^O, with its half-life of about 2 min, became the most widely used tracer for these types of studies. The short half-life allows the administration of multiple experimental conditions in the same session. Because H^O accumulates locally, with linear increases relative to rCBF, it is possible to measure rCBF (which is tightly coupled with synaptic activity) without the need to measure the time course of radioactivity by arterial blood sampling.

1. Analysis of PET Data

Typical preprocessing stages in the analysis of PET data include the removal of global fluctuations in rCBF (i.e., changes in rCBF that occur over the entire brain), spatial smoothing (i.e., averaging of information from adjacent voxels to reduce the noise and increase the signal), and spatial normalization to correct for brain shape differences between individuals, after which statistical tests are applied, typically on a voxel-by-voxel basis. The simplest method consists of normalizing and subtracting two images acquired during the administration of two conditions and then looking for values significantly different from zero. What counts as ''active,'' thus, depends on the statistical threshold used. Furthermore, the same issues regarding multiple comparisons described for the EEG and MEG techniques apply here. A commonly adopted approach consists of creating a "statistical parametric map'' (SPM) from the single-voxel tests and computing corrected probability values for single voxels and clusters of voxels, such that the overall probability of obtaining significant differences by chance alone remains within acceptable limits. The resulting maps indicate the loci where one condition evoked more activation than another; these maps are sometimes overlaid onto high-resolution images of a standard brain obtained with magnetic resonance imaging.

2. Summary of Advantages and Disadvantages of PET

Currently, a major strength of PET for cognitive studies is that it can provide absolute measures of rCBF, which are much more difficult to obtain with other techniques. Such measures are particularly useful in individual differences studies that focus on the correlation between performance and brain activation. Another major strength of PET that is particularly important in the clinical domain is the possibility of mapping the distribution of particular receptors in the brain by using appropriate

"radio-ligands." These radioactive chemicals mimic various neurotransmitters and are lodged in receptors that typically accept such neurotransmitters. Thus, it is possible to map the distribution of receptors by noting where these chemicals come to reside after they are administered. The major disadvantages of PET are that it is very expensive (partly because the radioactive tracers need to be manufactured on the spot), is invasive, and has relatively poor temporal resolution (it requires at least 40 sec to obtain an image).

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