Functional Imaging of Craving : Part 4

by National Institute of Health

(Page 4 of 6)

To identify brain regions involved in craving, Hommer and colleagues determined changes in glucose metabolism following injection of mCPP or an inactive saline solution using FDG PET. In all cases the placebo was always administered first, followed by mCPP 60 minutes later. Although other studies have found that mCPP can elicit both a desire to drink and subjective effects similar to alcohol intoxication among alcoholics, none of the alcoholics in this study (who were in the PET scanner when being assessed) expressed any increase in desire to drink or experienced any alcohollike effects. In fact, neither alcoholics nor control subjects reported any significant subjective effects following mCPP administration other than a mild increase in anxiety. Both groups, however, exhibited increases in brain glucose metabolism. Among the control subjects, the increases occurred in the following brain regions: Two ridges (gyri) on the surface of the orbital cortex (the right medial and posterior orbital gyrus). The cerebellar4 hemispheres on both sides of the brain (bilaterally), the left nucleus accumbens, the head of the caudate nucleus bilaterally. Two groups of neurons located bilaterally in the thalamus (the anterior and medial dorsal nuclei of the thalamus), the dorsolateral prefrontal cortex, the left insular cortex. A gyrus on the temporal cortex located at the side of the brain (the left middle temporal gyrus). A gyrus on the cingulate cortex (the posterior cingulate gyrus).

Among the alcoholic subjects, mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate gyrus than it did in the nonalcoholics. Conversely, the alcoholics showed a smaller area of mCPP-induced activation in the thalamus compared with the healthy volunteers, almost no activation in the orbital cortices, and no activation in the head of the caudate nucleus and the dorsolateral prefrontal cortex.

These results indicate that among nonalcoholics, treatment with a substance that induces or mimics serotonin release (a serotonergic challenge) activates striatal-thalamic circuits involving the orbital and dorsolateral prefrontal cortices and that these responses are reduced, or blunted, among alcoholics. Unfortunately, the relevance of these findings for identifying brain regions involved in craving remains unclear. The brain regions activated by mCPP in nonalcoholics include the parts of the striatum, thalamus, and cortex that have been implicated in mediating craving for alcohol by Modell and colleagues. Conversely, alcoholics showed a blunted response to mCPP in these regions. The findings could indicate that the difficulties alcoholics experience with craving and with controlling their alcohol intake are associated with lowerthan- normal activity in this circuit. In the absence of studies demonstrating a link between subjective craving and the function of striato-thalamic and orbitofrontal circuits, however, this model for the functional neuroanatomy of craving remains speculative.

Craving Studies in Cocaine Abusers

In contrast to the few imaging studies conducted on alcohol craving, six studies have investigated craving for cocaine. Three of those studies used drug-related cues to elicit craving for cocaine, and three studies used drug administration (one study used cocaine itself and two studies used the chemical methylphenidate [Ritalin®]). Grant and colleagues used FDG PET to compare brain glucose metabolism in 13 nontreatment- seeking cocaine abusers and 5 control subjects. The two scanning sessions, separated by 1 week, took place while the subject viewed videotapes of objects associated with cocaine use or objects used in crafts. An ROI analysis demonstrated that among the control subjects, no significant differences in brain glucose metabolism existed in response to the two sets of cues. Among the cocaine abusers, however, brain metabolism increased significantly in response to the cocaine-related cues in several regions of the cortex, including the medial orbital, dorsolateral prefrontal, and medial temporal (including the amygdala) cortices as well as other cortical regions.5 No significant changes in brain metabolism occurred in the basal ganglia or thalamus. In addition, the subjects' self-ratings of craving showed a significant positive correlation with metabolism in the dorsolateral prefrontal cortex and the medial temporal cortex.

Recently Childress and colleagues reported the results of an 15O PET study of cocaine craving that included 14 treatment-seeking cocaine abusers and 6 non-cocaine-abusing control subjects. The investigators performed six sequential scans on each subject, both during rest periods and while the subjects were watching cocainerelated and non-cocaine-related videotapes. Using ROI analysis the study demonstrated that in the cocaine abusers, but not in the control subjects, cocaine craving elicited by the videotapes resulted in increased blood flow in the amygdala and anterior cingulate cortex and decreased blood flow in the caudate nucleus and in the globus pallidus, which connects the striatum and the thalamus.

The videotapes that Childress and colleagues used to elicit cocaine craving also were used in an fMRI study of six cocaine abusers (whose treatment status was not specified) and six control subjects. The study was designed to determine whether the changes observed in the two previously described studies also could be demonstrated using fMRI. To this end the investigators used a ROI analysis of 10 brain regions that had been identified in the other two studies as being responsive to cocaine craving. Among those regions, however, only the anterior cingulate gyrus and the left dorsolateral prefrontal cortices were activated in the cocaine abusers, and only the results for the anterior cingulate gyrus reached statistical significance.

Another fMRI study of cocaine craving used cocaine administration to induce both euphoria and craving in 10 nontreatment- seeking cocaine abusers. The study included no control subjects. Cocaine administration induced BOLD-signal increases in a large number of limbic and other brain regions, whereas a saline solution caused only small changes in the BOLD signals measured in the lateral prefrontal and temporo-occipital cortices. The largest increases following cocaine administration occurred in the region of the nucleus accumbens, caudate nucleus, thalamus, and anterior cingulate and insular cortices, as well as in a few other brain regions.6 In the amygdala the BOLD signal decreased in response to cocaine administration.

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