technetium-tc-99m-exametazime and Cocaine-Related-Disorders

Previous studies have shown that cocaine abusers have cerebral perfusion deficits that may diminish cognitive functioning. This study examined whether cocaine-dependent patients have perfusion abnormalities associated with poor decision-making ability as measured by the Iowa Gambling Task (IGT).. Seventeen abstinent cocaine-dependent patients were administered the IGT after completion of resting 99mTc-HMPAO single-photon emission computed tomography (SPECT).. Better IGT performance was negatively correlated with perfusion within the anterior cingulate gyrus, middle frontal gyrus, medial frontal gyrus, and superior frontal gyrus. The time to complete card selections was positively correlated with the severity of impairment.. Resting hyperperfusion in brain regions previously implicated in decision making and response inhibition was associated with worse IGT scores. Impaired performance was related to a greater amount of time taken for card selections, suggesting that reduced ability was due to cognitive factors other than an impulsive response pattern.

Topics: Adult; Brain Mapping; Cerebral Cortex; Cerebrovascular Circulation; Cocaine-Related Disorders; Decision Making; Female; Gambling; Humans; Male; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Amygdala; Anesthetics, Local; Brain; Brain Stem; Cerebrovascular Circulation; Cocaine-Related Disorders; Humans; Injections, Intravenous; Male; Procaine; Radiopharmaceuticals; Regional Blood Flow; Single-Blind Method; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self-administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched healthy control participants. Differences between early- (first use before 20 years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine-addicted and control participants were observed following ondansetron relative to saline. Early-onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late-onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/hippocampal gyrus. Early-onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late-onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine-addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol-dependent patients.

Topics: Adult; Age of Onset; Case-Control Studies; Cerebrovascular Circulation; Cocaine-Related Disorders; Female; Functional Neuroimaging; Hippocampus; Humans; Male; Ondansetron; Parahippocampal Gyrus; Personality Inventory; Radiopharmaceuticals; Receptors, Serotonin, 5-HT3; Regional Blood Flow; Serotonin Antagonists; Sodium Chloride; Subthalamic Nucleus; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Young Adult

The orbitofrontal cortex (OFC) is crucial for the inhibition of extraneous stimuli, evaluation of aversive information and emotional regulation-all behaviors impaired in cocaine addiction. Previous studies suggest that cocaine-addicted subjects have decreased basal activity in the OFC. In this study, we examined regional cerebral blood flow (rCBF) during a saline infusion in two independent populations of abstinent cocaine- (and mostly nicotine-) addicted (n=33 and 26) and healthy control (n=35 and 20) men and women. Isolated rCBF decreases (P<0.001) were observed in the left caudolateral OFC, as well as left superior temporal cortex, in cocaine-addicted subjects relative to controls in both cohorts and bilaterally in the combined cohort. An anatomically defined region of the caudolateral OFC showed similar findings and were evident in both male and female addicted subjects. The reliability of these findings across two cohorts reveals a functional disruption in the lateral OFC, a brain region implicated in the evaluation of behavior-terminating stimuli. This may contribute to an addicted individual's persistent drug use despite negative consequences.

Topics: Adult; Case-Control Studies; Cerebrovascular Circulation; Cocaine-Related Disorders; Cohort Studies; Female; Frontal Lobe; Humans; Male; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Fifty abstinent cocaine-dependent patients and 20 healthy controls were evaluated with 99mTc-HMPAO SPECT to examine gender differences in perfusion. Group contrasts with statistical parametric mapping revealed male and female patients exhibited not only different regions, but different types of perfusion abnormality, including decreased perfusion in the anterior cingulate/frontal regions among cocaine-dependent men, and increased perfusion in the posterior cingulate of cocaine-dependent women. The findings suggested that cocaine-dependent men have perfusion deficits previously associated with cocaine withdrawal and impaired response inhibition, whereas, cocaine-dependent women demonstrated perfusion abnormalities consistent with heightened stress responsivity and worse treatment outcome. The possibility of different neural mechanisms underlying relapse in men and women, and the implications for utilizing specialized treatments are discussed.

Topics: Adult; Brain; Cerebrovascular Circulation; Cocaine-Related Disorders; Female; Humans; Male; Radiopharmaceuticals; Regional Blood Flow; Sex Characteristics; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Cerebral perfusion abnormalities and neuropsychological impairment are common sequelae of chronic cocaine abuse. While perfusion abnormalities have been shown to relate to cognitive deficits in this substance abuse population, the relationship between cognitive performance and the magnitude of perfusion abnormality has yet to be fully determined.. Thirty-seven abstinent cocaine abusers and 13 normal controls were administered resting 99m-Tc-HMPAO single photon emission computed tomography (SPECT) scans followed by a neuropsychological assessment battery tapping executive skills, attention, memory, and motor performance. Statistical parametric mapping (SPM99) techniques were used to analyze the SPECT data to detect significant regional perfusion abnormalities in the cocaine group relative to normal controls, and resulting abnormal SPECT counts were employed for comparison with the assessment measures to examine the relationship between cocaine-induced perfusion abnormalities and cognitive performance.. SPECT data analysis revealed significant regional perfusion abnormalities in the cocaine abuse sample relative to controls and significant differences in neuropsychological functioning on measures of executive functioning, complex attention, memory, and manual dexterity. For chronic cocaine abusers, however, within-group comparisons of the magnitude of abnormal perfusion and neuropsychological performance were largely nonsignificant, with the exception of complex attention and motor speed.. Perfusion abnormalities and neuropsychological impairments readily distinguished cocaine abusers from normal controls. However, when the magnitude of cocaine-induced perfusion abnormalities is examined in relation to cognitive performance, motor speed and complex attention appear to be the best behaviorial indicants of the severity of perfusion dysfunction within this substance abuse population.

Topics: Adolescent; Adult; Cerebral Cortex; Cocaine; Cocaine-Related Disorders; Cognition Disorders; Female; Humans; Image Processing, Computer-Assisted; Male; Neuropsychological Tests; Psychometrics; Reference Values; Regional Blood Flow; Reproducibility of Results; Substance Withdrawal Syndrome; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Orbitofrontal cortex regional cerebral blood flow (rCBF) is lower in cocaine-dependent subjects than in non-cocaine-dependent subjects. Performance on the Gambling Task, a test of decision making, is a putative correlate of orbitofrontal cortex activity and is reportedly impaired in drug-dependent subjects. The authors tested the hypothesis that lower Gambling Task scores would be associated with lower resting orbitofrontal cortex rCBF in cocaine-dependent subjects.. Fifteen healthy comparison subjects and 13 abstinent cocaine-dependent subjects underwent resting single photon emission computed tomography to measure rCBF, after which they completed the Gambling Task.. Resting anterior cingulate and left dorsolateral prefrontal cortex rCBF significantly correlated with performance on the Gambling Task, but orbitofrontal cortex rCBF did not. Left dorsolateral prefrontal cortex rCBF was lower in the cocaine-dependent subjects than in the comparison subjects.. Resting anterior cingulate and dorsolateral prefrontal cortex rCBF is significantly related to decision making, as assessed by the Gambling Task.

Topics: Adult; Cerebral Cortex; Cerebrovascular Circulation; Cocaine-Related Disorders; Female; Gambling; Gyrus Cinguli; Humans; Male; Middle Aged; Psychomotor Performance; Radiopharmaceuticals; Rest; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Cocaine abuse has been associated with widely distributed areas of significant cerebral blood flow (CBF) reductions or hypo-perfusion as well as CBF hyper-perfusion, but these perfusion abnormalities have not been examined using newer technologies such as statistical parametric mapping (SPM). These areas of abnormal CBF may be more likely among those who abuse cocaine and alcohol together.. Using SPECT with HMPAO for CBF we compared proportional scaling (PS) to histogram normalization (HEQ) in SPM among 20 controls and 32 recently abstinent cocaine abusers. We then separated the cocaine abusers into two groups (12 cocaine plus alcohol abusers and 20 cocaine alone abusers) and compared both groups to the 20 controls for brain areas of hypo- and hyper-perfusion.. Sensitivity to hypo-perfusion was greater with HEQ than PS. Hypo-perfused areas were more likely in the 12 alcohol plus cocaine abusers than in the 20 cocaine alone abusers or 20 controls, and hyper-perfused areas were significantly more likely among the cocaine abusers than controls. The type of CBF abnormality varied by brain location with hypo-perfusion significantly more likely in occipital and temporal cortex or cerebellum and hyper-perfusion more likely in frontal and parietal cortex.. These abnormalities in brain perfusion are consistent with previous non-SPM approaches that showed more hypo-perfusion in cocaine abusers than controls and appear to reflect vasospasm and potential compensations in cerebral blood flow.

Topics: Adult; Alcoholism; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cocaine-Related Disorders; Female; Humans; Male; Radiopharmaceuticals; Sampling Studies; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.

Topics: Adult; Alcoholism; Cerebral Cortex; Cerebrovascular Circulation; Cocaine-Related Disorders; Female; Humans; Image Interpretation, Computer-Assisted; Male; Methamphetamine; Middle Aged; Radiopharmaceuticals; Substance-Related Disorders; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Nuclear medicine studies found decreased regional cerebral blood flow (rCBF) in the cortex and deep gray matter of cocaine users. Perfusion magnetic resonance imaging (MRI), a non-radioactive technique, has not been applied to evaluate persistent rCBF abnormalities. Twenty-five abstinent cocaine users and 15 healthy subjects without a history of drug use were examined with perfusion MRI, using dynamic bolus-tracking, and single photon emission computed tomography (SPECT), using 133Xe-calibrated 99mTc-HMPAO. After coregistration of SPECT with MRI, the relative rCBF (from perfusion MRI and SPECT) and absolute rCBF (from SPECT) were determined in 10 brain regions in each hemisphere. There was a statistically significant interaction between drug use and brain region on SPECT alone (relative and absolute rCBF), and on SPECT and perfusion MRI combined, but not on perfusion MRI alone. There also was a significant interaction among gender, drug use, and brain region. Compared to the control subjects, cocaine users showed increased rCBF in the frontal white matter (+8.6%, P=0.02) and in the globus pallidus (+6.3%, P=0.05), and decreased rCBF in the putamen (-3.9%, P=0.04) and the temporal cortex (-2.4%, P=0.02). SPECT and perfusion MRI detect a regional pattern of rCBF abnormalities in cocaine users that is consistent across the two methods. The hypoperfusion in the cortex and deep gray matter of the cocaine users is consistent with previous results. The increased rCBF in the white matter of cocaine users may be due to the presence of reactive glia.

Topics: Adolescent; Adult; Brain; Cocaine-Related Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon