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Functional Imaging of Craving Functional Imaging of Craving Daniel W. Hommer, M.D. To visualize brain activity associated with mental states, such as craving for alcohol and other drugs (AODs), researchers have begun to use functional imaging techniques. Three commonly used techniques are single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Studies using these three approaches have been reviewed in order to evaluate the validity of a proposed model of the brain regions involved in alcoholism and the craving for alcohol. This model suggests a central role for a connected group of brain regions that include the basal ganglia, thalamus, and orbital cortex. A study using SPECT technology in alcoholics, however, found altered brain activity in only some of those regions during craving. Additional studies in alcoholics, as well as cocaine users, identified several other brain regions whose activities appeared to change in response to craving. These studies have led to the development of a revised model of brain regions involved in craving for AODs. Numerous questions remain, however, that must be answered before the brain areas involved in craving can be identified conclusively. KEY WORDS: AOD (alcohol and other drug) craving; single photon emission computed tomography; positron emission tomography; magnetic resonance imaging; brain imaging; blood flow measurement; cocaine; brain; basal ganglia; limbic system; brain function; neurotransmission; dopamine; glucose metabolism; literature review rimates, including humans, are neurochemical processes in specific brain tions already exist between the inside visual animals—that is, they like regions (i.e., brain states). Although and the outside of a resting or inactive Pto see things—giving rise to the one cannot see mental states, one can neuron, the process of moving addi- adage “seeing is believing.” One cannot generate images that help visualize the tional ions to generate a nerve signal see thoughts, feelings, or mental states, intensity and location of physiological requires energy. In the brain, this energy however, whether one’s own or those processes associated with brain states. is supplied by the brain’s metabolism of of other people. One can only perceive At the most basic level, the physio- the sugar glucose, which is delivered these states either directly, in one’s own logical processes underlying brain states to the brain through the bloodstream. consciousness, or indirectly, through involve changes in and the maintenance Accordingly, when a certain brain the reports and behavior of other people. of differences in the concentrations of “Craving” is a term derived from pop- molecules that carry electrical charges ular psychology that is used to describe (i.e., ions) across the membrane form- DANIEL W. H OMMER, M.D., is chief of one of these mental states—namely, the ing the boundary of each nerve cell, or the Section of Brain Electrophysiology intense desire for a certain object or neuron. Changes in the concentrations and Imaging, Laboratory of Clinical experience (e.g., alcohol or other drugs of various ions inside and outside of the Studies, Division of Intramural Clinical [AODs]). cell serve as signals that can be trans- and Biological Research, at the National Cognitive neuroscience postulates mitted from one neuron to another. Institute on Alcohol Abuse and Alcoholism, that mental states are the product of Because differences in ion concentra- Bethesda, Maryland. Vol. 23, No. 3, 1999 187 region is actively involved in the gener- to be detected or quantified accurately people engaged in an activity unrelated ation of mental states, the energy by simple visual inspection. Therefore, to drinking. At least in theory, the only requirements of that region increase a new image representing the differ- difference between the mental states and, consequently, so does the blood ences between the two original images evoked by the two videos would be flow there. By measuring blood flow or (i.e., a difference image) is created using that one video would induce a desire to glucose metabolism (a process known computerized analysis. This can be done drink, and the other video would not. as functional brain imaging), one can because each image is made up of small Thus, the difference image produced in determine which brain areas are most units, or pixels, each of which repre- this experiment would represent the active during a particular brain state. sents a small brain area. For each pixel blood flow or glucose metabolism asso- This article reviews the small num- the blood-flow or glucose-metabolism ciated with alcohol craving. However, ber of studies that have applied func- researchers cannot be absolutely certain tional brain imaging to investigating that any differences between the brain brain states associated with craving for states induced by the two videos would AODs, particularly alcohol and cocaine. By measuring result only from the presence or absence It includes studies on cocaine craving of craving. Other influences not related because (1) to date, only two studies blood flow or glucose to craving, such as differences between have attempted to image craving for the two videos with regard to their alcohol, and (2) the brain states associ- metabolism, one can visual properties (e.g., color and move- ated with craving may be similar for all determine which brain ment), also may affect the difference AODs. The article first describes the image. Consequently, it is important three most commonly used functional areas are most active that investigators try to minimize dif- imaging techniques. It then introduces during a particular ferences between the stimuli used to a preliminary model of the functional evoke the desired brain states other anatomy of craving to provide a frame- brain state. than the one difference that they are work for understanding the studies on attempting to visualize. craving conducted among alcoholics and cocaine abusers. After comparing value in the first image is “subtracted” Single Photon Emission the results of studies that examine the from the value in the corresponding Computed Tomography preliminary model, the article discusses pixel in the second image. For example, future directions in the functional assume that the blood flow in a given SPECT is the oldest functional imaging imaging of craving. pixel is low in the first brain state (e.g., technique and generally provides images no craving) and is assigned a value of 2 with the lowest resolution, although on a scale from 0 to 10. In the second newer SPECT equipment provides Methods of Functional brain state (e.g., craving), the blood flow images with significantly greater detail. Brain Imaging in the same pixel is high (i.e., is assigned With this approach, the subject is injected a value of 9). Thus, in the difference with a weakly radioactive tracer—usu- Currently three major techniques are image, this pixel will have a blood flow ally 99mtechnetium-hexamethylpropy- used to visualize the brain activity asso- value of 7, representing a relatively large lene-amineoxide (99mTc-HMPAO)— ciated with various mental states: single difference between the two brain states. to measure blood flow. This technique photon emission computed tomography This subtraction process is performed allows the investigator to visualize the (SPECT), positron emission tomogra- for all pixels in the images, generating blood flow distribution within the phy (PET), and functional magnetic an image that represents the extent of brain during the first 1 or 2 minutes resonance imaging (fMRI). Each tech- changes in blood flow between the two after 99mTc-HMPAO injection. The nique involves measuring local changes brain states being assessed. Statistical major advantage of this approach is in cerebral1 blood flow or metabolism. analysis of several difference images that it is more widely available and To that end, researchers usually obtain then allows the identification of the much less expensive than other imag- at least two separate images representing brain regions whose activities vary most ing techniques, such as PET. two different states of the brain regions strongly between the two brain states. SPECT also has substantial disadvan- of interest. In theory, one could just visu- The key to this approach is to select tages, however. The biggest disadvan- ally compare the two images to identify tasks that will induce brain states that tage is that because 99mTc-HMPAO brain regions in which brain activity differ only with regard to the mental decays slowly (i.e., has a long half-life), differs depending on mental state. In state being investigated. In a study of the two images needed to produce a many cases, however, the differences alcohol craving, for example, investiga- difference image must be recorded sev- between the two images are too subtle tors might have alcoholics watch two eral days apart, leading to two practical different videotapes: One video might problems. First, each time a subject is 1For definitions of this and other technical terms show people drinking alcoholic beverages, placed in the machine (i.e., the scanner) used in this article, see the glossary, p. 196. whereas the other video might show that measures the radioactivity and 188 Alcohol Research & Health Functional Imaging of Craving generates the image, his or her posi- eration of more accurate images com- already delivered its oxygen to the tis- tioning will be slightly different. This pared with 15O PET. A disadvantage sues (i.e., deoxygenated hemoglobin). inconsistency complicates the genera- of the prolonged measurement period This fMRI approach is based on the tion of an accurate difference image, needed to generate one image, how- fact that oxygenated and deoxygenated because the two original images must ever, is that FDG PET allows the gen- hemoglobin differ slightly in their mag- be aligned so that their size, shape, and eration of only one pair of images, and netic properties, resulting in the emis- orientation match perfectly.
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