OTHER IMAGING STUDIES IN COCAINE USE DISORDERS
Computed Tomography (CT)
The popularity of CT in addiction research has diminished considerably because of its resolution power and the risk of ionizing radiation. In 1991, a planimetric CT study found significant cerebral atrophy among 35 habitual cocaine abusers as compared to 16 self-reported first-time users and 54 control subjects.
Magnetic Resonance Imaging (MRI)
MRI is a noninvasive imaging modality that is based on the physical properties of water in the tissues. The MRI is not associated with health concerns related to ionizing radiation. female pink viagra
MRI studies during acute cocaine infusion. Recently, Bartzokis and colleagues conducted a clinical trial that involved 11 patients who were acutely administered with cocaine and studied with MRI. The study reported a positive correlation between the frontal and temporal cortical volumes and euphoric effects of cocaine.
MRI studies during early cocaine abstinence. The 2002 MRI study by Bartzokis and colleagues examined 37 male cocaine-dependent patients who were recently admitted for cocaine treatment and 52 healthy controls. The study found some evidence of brain maturation arrest (absence of white-matter expansion) among chronic cocaine users but not among the control subjects. The limitations of this study included subject selection. The subjects were predominantly men aged 19-47 years, with 43% reporting ongoing or prior alcohol abuse.
Franklin and colleagues used the technique of voxel-based morphometry to examine 13 recent cocaine users and 16 cocaine-naive individuals. The cocaine users reported an average of 13-year history of cocaine use and an average of 15-day cocaine use in the 30 days prior the study. The whole-brain analysis revealed a decreased gray matter density in the medial orbitofrontal, anterior cingulate, insular and superior temporal cortices in cocaine-dependent subjects as compared with control subjects. Interestingly, no white-matter differences were reported.
The Tl-weighted MRI study by Matochik and coworkers was driven by the hypothesis of a region of interest based their PET study They scanned 14 cocaine abusers who were abstinent for 20 days and 11 in the nondrug-using comparison group. The average duration of cocaine use was about eight years and the frequency of use was at least four times per month. The study found a statistically significant frontal cortical tissue loss among abstinent cocaine users as compared to nondrug-using control subjects. Intriguingly, no frontal cortex white-matter differences were noted. The investigators suggested that these brain alterations were probably induced by cocaine.
MRI studies during prolonged cocaine abstinence. Strickland and coworkers have used MRI to study cocaine-using individuals who were abstinent for six months and found no abnormalities. Chang and colleagues studied African-American multiple-substance-abusing men with cocaine as their drug of choice (n=26). The duration of cocaine use was about seven years and the last use was 47 months. Although the MRI study found no changes, the proton magnetic resonance spectroscopy revealed biochemical changes suggestive of lost neuronal cell integrity. The result of this study may not be general-izable to patients with CUDs alone.
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Diffusion Tensor Imaging (DTI)
The DTI is utilized to study the integrity of axon-al microstructure and is based on directional flow properties of water in the axons. Lim and colleagues evaluated cocaine abusers using the DTI and noted significant white-matter loss in the frontal lobe, implying a possible link between deranged connectivity and craving and decision-making deficits in these individuals. More DTI studies are needed to resolve the issue of white-matter loss in CUDs.
MRI Imaging of Cocaine Users Performing Cognitive Tasks
Fein and coworkers have compared prefrontal cortical volume reduction in 20 normal control subjects, 17 cocaine-only and 29 cocaine-alcohol subjects. The drug using subjects were abstinent for six weeks. Although the drug-using patients showed no
Table 3. CUDs: initial clinical assessment
History (psychiatric, medical and neurologic) Drug and sexual history Physical, including neurologic examination Laboratory screens
Neuropsychologic Testing (see text)
Rating Scales and Inventories
group differences, the observed frontal cortex changes correlated with impaired cognitive performances, indicating that brain function may be affected by changes in frontal cortex volume associated with cocaine dependence with or without alcohol dependence. altace blood pressure
Kaufman and colleagues used MRI to test the hypothesis of inhibitory dyscontrol in CUDs. The study found that activity in the anterior cingulate was significantly reduced during the go-no-go test, a test of response inhibition, implying that the anterior cingulate may be a treatment target in CUDs.
Positron Emission Tomographic (PET) Imaging
PET imaging has revolutionized research in psychiatry by making in vivo visualization possible at molecular level. The PET combines the CT and nuclear scanning and involves an intravenous injection of a radioactive tracer that emits a radioactive substance. The PET cameras are used to record the signals emitted by the tracer. The PET cameras are expensive and their reimbursement remains a major issue.
PET studies during acute cocaine infusion. Volkow and coworkers investigated the molecular substrates of cocaine euphoria using PET imaging. They reported that the subjective effects of cocaine at doses commonly used in humans (0.3-0.6 mg/kg) were significantly correlated with the level and rate of dopamine transporter occupancy. cialis soft tabs
PET studies during early cocaine abstinence. In a series of seminal PET studies, Volkow and colleagues have elucidated the role of frontal lobe in CUDs. The early studies revealed decrements in prefrontal blood flow during acute withdrawal as well as alterations in postsynaptic dopamine receptor availability in long-term cocaine users. Subsequent studies revealed that brain metabolism in CUDs was time-dependent and regional, with higher activity in the basal ganglia and orbitofrontal cortex within the first week, but not within 2-4 weeks among the cocaine-withdrawn subjects as compared to the nondrug-using controls.
PET studies during prolonged abstinence. Using an expanded time frame, Volkow and colleagues found no global differences in the brain metabolism between the cocaine users and the control subjects following 1-6 weeks of abstinence and again following about three months of verified abstinence. However, the left frontal cortex was significantly lower in cocaine users even at four months of abstinence. These results have been replicated and confirmed in persistent cocaine abusers and appeared to link compulsive drug use to the frontal lobe’s failure to exert executive control over brain regions involved in drive and emotion and indicated a possible role for pharmaceutical augmentation of frontal lobe in CUDs.
Recently, Bolla and colleagues used functional PET imaging to examine 13 abstinent cocaine abusers and 13 control subjects who were required to perform the Iowa Gambling Task, a test of decision-making. The patients were studied following an average of 25 days of monitored abstinence and showed a significantly impaired activation of the orbitofrontal cortex as compared to the control subjects, which suggested possible deficits in working memory and planning. buy revatio
Imagining Studies in Cocaine Craving
Imaging studies of brain substrates in cocaine craving have also been insightful regarding the neurobiology of CUDs. The studies have used paradigms, such as external cues in videotapes or internal cues in script-guided imagery. The external models have relied on videotapes of cocaine cues or some versions of emotion face assessment task. Interestingly enough, studies that used external cues, but not the study that used imagery, revealed greater prefrontal cortex activation in cocaine abusers than in control subjects. In their study, Wexler and colleagues used cocaine-cue videotapes to illustrate regional activations in the amygdala, subcallosal gyrus, nucleus accumbens and anterior cingulate cortex in cocaine abusers but not in control subjects.
Furthermore, functional brain imaging appears to support a role for the frontal cortex, and cerebellar and limbic structures in the neural activity in cocaine craving. In their [F18] fluorodeoxyglucose (FDG) PET study of cue-induced craving, Wang and coworkers showed that cocaine theme interview, but not the neutral interview, produced activations in the orbitofrontal and left insular cortex.
The accumulating evidence supports a role for limbic neuronal hyperexcitability in cocaine craving. For example, reexposure to drug cues resulted in an increased activation in the amygdala among cocaine-using individuals as well as decrements in activation in the prefrontal cortex. This appears to indicate that the amygdala might be ineffectively inhibited by the frontal lobe in cue-induced craving, suggesting an important treatment target.
Taken together, the brain imaging studies suggest that CUDs are associated with functional, structural, cellular and molecular alterations. Cocaine use appears to induce regional brain dysfunction in the prefrontal cortex (executive), anterior cingulate cortex (internal monitoring of performance, error detection and performance adjustment) and the basal ganglia (movement and cognition). In addition, suboptimal inhibitory control of the amygdala by the prefrontal cortex may have a role in cocaine craving.