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Biomedical subjects

Anna Rose Childress

Publications and source records attributed to Anna Rose Childress.

7 recordsLinked to original sources

Telling truth from lie in individual subjects with fast event-related fMRI.

Deception is a clinically important behavior with poorly understood neurobiological correlates. Published functional MRI (fMRI) data on the brain activity during deception indicates that, on a multisubject group level, lie is distinguished from truth by increased prefrontal and parietal activity. These findings are theoretically important; however, their applied value will be determined by the accuracy of the discrimination between single deceptive and truthful responses in individual subjects. This study presents the first quantitative estimate of the accuracy of fMRI in conjunction with a formal forced-choice paradigm in detecting deception in individual subjects. We used a paradigm balancing the salience of the target cues to elicit deceptive and truthful responses and determined the accuracy of this model in the classification of single lie and truth events. The relative salience of the task cues affected the net activation associated with lie in the superior medial and inferolateral prefrontal cortices. Lie was discriminated from truth on a single-event level with an accuracy of 78%, while the predictive ability expressed as the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 85%. Our findings confirm that fMRI, in conjunction with a carefully controlled query procedure, could be used to detect deception in individual subjects. Salience of the task cues is a potential confounding factor in the fMRI pattern attributed to deception in forced choice deception paradigms.

Adolescent↗

Retrospective study: influence of menstrual cycle on cue-induced cigarette craving.

Cigarettes acquire reinforcing properties from nicotine and from cues associated with their intake. However, smoking in males and females may be reinforced differentially. Smoking in females is posited to be influenced more by cues whereas male smoking is influenced predominantly by the direct pharmacological actions of nicotine in the brain. Menstrual cycle phase may contribute to some of the sex differences observed in smokers. We hypothesized that females may report more intense craving to smoking cue exposure than males and, further, that female craving scores may be influenced by menstrual cycle phase. Thus, we reexamined previously collected cue exposure data with respect to sex and cycle phase. Self-report measures were collected from subjects prior to and immediately following exposure to visual smoking stimuli. The study included 69 male and 41 female treatment-seeking subjects who smoked more than 15 cigarettes per day for more than 10 years. Females were grouped according to cycle phase. Of the female subjects, 17 were classified as follicular phase females (FFemales) and 24 were classified as luteal phase females (LFemales). Change scores were calculated from the subjective data collected before and after stimulus presentation. Contrary to our hypothesis, overall, males and all females did not differ in their level of cue-induced craving; however, when females were separated into groups by cycle phase, FFemales reported significantly less craving than either males or LFemales (p<.05). The suppressed craving response in FFemales suggests an influence of cycle phase on cue-induced craving.

Cues↗

A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients.

The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50-70 mg/day) and either DM (n=10) or placebo (n=5) during the 12-day active medication phase of the study. DM participants received doses of 120, 240, and 480 mg/day in increasing order (4 days each). DM at high doses caused mild elevations of heart rate, blood pressure, temperature, and plasma bromide. However, none of these effects was clinically significant. DM caused no significant changes in respiration, pupil diameter, or subjective drug effects measured by standard scales. Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs. 21), but these effects were not clinically serious. The most commonly reported side effects were sleepiness and drowsiness. Several participants reported intoxicating effects at the highest dose. Overall, DM was well-tolerated by the methadone-maintained opiate-dependent subjects studied here. These results support the further exploration of DM as an adjunct medication during methadone replacement therapy.

Adult↗

Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients.

BACKGROUND: Structural deficiencies within limbic and prefrontal regions may contribute to the characteristic drug-seeking and drug-taking behaviors that prevail in persons dependent on cocaine. To date, a focal structural analysis of the brains of cocaine patients has not been undertaken. METHODS: We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of cocaine-dependent (n = 13) and cocaine-naive individuals (n = 16) to assess differences between the two groups in gray and white matter concentration. RESULTS: We report a decrease in gray matter concentration in the ventromedial orbitofrontal, anterior cingulate, anteroventral insular, and superior temporal cortices of cocaine patients in comparison to controls (p <.01 corrected for multiple comparisons). The average percentage decrease in gray matter concentration within a region ranged from 5% to 11%. White matter concentration did not differ between groups. CONCLUSIONS: We conclude that the brains of cocaine patients are structurally dissimilar from those of nondrug-using controls. The differences were detected in regions involved in decision-making, behavioral inhibition and assignation of emotional valence to environmental stimuli and, hence, may contribute to some of the behavioral deficits characteristic of chronic cocaine users.

Adult↗

Brain metabolic changes during cigarette craving.

BACKGROUND: In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. METHODS: Twenty heavy smokers (who smoked > or =20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18-fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). RESULTS: From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. CONCLUSIONS: Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

Adult↗

A potential role for GABA(B) agonists in the treatment of psychostimulant addiction.

AIMS: Here we briefly review the preclinical and clinical evidence that gamma-aminobutyric acid (GABA(B)) agonists may be useful in the treatment of cocaine addiction. An extensive series of studies in rats has demonstrated that baclofen and other GABA(B) agonists reduce cocaine self-administration in an apparently specific manner. METHODS: A number of schedules of reinforcement, including fixed-ratio, progressive-ratio and discrete trials procedures, have been used to model various aspects of cocaine reinforcement and addiction. RESULTS: The results show that systemic pretreatment with baclofen can reduce cocaine intake at doses that do not affect responding for other positive reinforcers, such as food. Direct intracerebral injections of baclofen into the ventral tegmental area also produce a specific reduction in cocaine self-administration, suggesting that an inhibition of dopaminergic neurons may be responsible for the effect. Recent clinical evidence and case reports indicate some therapeutic value for baclofen in controlling cocaine intake and craving, although the evidence from controlled clinical trials has been less than convincing. Perhaps the most intriguing data come from human imaging studies, wherein cocaine addicts report increased cocaine craving and activation of orbital-frontal cortex, anterior cingulate and amygdala when shown videotapes of drug paraphernalia and other addicts taking cocaine. The craving is reduced and the limbic activation is eliminated in cocaine-dependent patients who had been taking baclofen (10-20 mg twice daily) for 7-10 days. CONCLUSIONS: Systematic clinical studies of GABA(B) agonists are needed to determine the extent to which these drugs might serve as tools to promote abstinence in cocaine users seeking treatment for their addiction. Several areas must still be addressed, including potential side-effects that may limit compliance and whether GABA(B) agonists interfere with other, non-drug-related behaviours.

Animals↗