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Biomedical subjects

A R Childress

Publications and source records attributed to A R Childress.

At least 19 recordsLinked to original sources

Brain activity during simulated deception: an event-related functional magnetic resonance study.

TheGuilty Knowledge Test (GKT) has been used extensively to model deception. An association between the brain evoked response potentials and lying on the GKT suggests that deception may be associated with changes in other measures of brain activity such as regional blood flow that could be anatomically localized with event-related functional magnetic resonance imaging (fMRI). Blood oxygenation level-dependent fMRI contrasts between deceptive and truthful responses were measured with a 4 Tesla scanner in 18 participants performing the GKT and analyzed using statistical parametric mapping. Increased activity in the anterior cingulate cortex (ACC), the superior frontal gyrus (SFG), and the left premotor, motor, and anterior parietal cortex was specifically associated with deceptive responses. The results indicate that: (a) cognitive differences between deception and truth have neural correlates detectable by fMRI, (b) inhibition of the truthful response may be a basic component of intentional deception, and (c) ACC and SFG are components of the basic neural circuitry for deception.

Adult↗

Three decision-making tasks in cocaine-dependent patients: do they measure the same construct?

AIMS: Substance-abusing populations perform poorly on decision-making tasks related to delay and risk. These tasks include: (1) the Delay Discounting Procedure (DDP), in which choices are made between smaller-sooner and later-larger rewards, (2) the Gambling Task (GT), in which choices are made between alternatives varying in pay-off and punishment, and (3) the Rogers Decision-Making Task (RDMT) in which subjects choose between higher or lower probability gambles. We examine the interrelationship among these tasks. DESIGN: A test battery was created which included the DDP, GT and RDMT, as well as measures of impulsivity, intellectual functioning and drug use. SETTING: Subjects completed the test battery at an outpatient center, prior to beginning 12 weeks of treatment. PARTICIPANTS: Thirty-two treatment-seeking cocaine dependent individuals (primarily African-American males) participated. FINDINGS: Performance on the GT was significantly correlated with performance on the DDP (r = 0.37; p = 0.04). Reaction times on the RDMT correlated with performance on the GT (r = 0.36, p = 0.04) and DDP (r = 0.33, p = 0.07), but actual choices on the RDMT did not (p > 0.9 for both). While no significant relationships were observed between task performance and impulsivity, IQ estimate was positively correlated with both the GT (r = 0.44, p = 0.01) and RDMT (r = 0.41, p = 0.021). Split half reliability data indicated higher reliability when using only data from the latter half of the GT (r = 0.92 vs. r = 0.80). CONCLUSIONS: These data offer preliminary evidence of overlap in the decision-making functioning tapped by these tasks. Possible implications for drug-taking behavior are discussed.

Adult↗

Mood state and recent cocaine use are not associated with levels of cocaine cue reactivity.

Eighty-one cocaine-dependent outpatients were assessed for their reactions to cocaine-related cues in a laboratory setting. All subjects contributed a urine sample prior to the session. Compared with non-drug control cues, the cocaine stimuli produced increases in physiological arousal, self-reports of high, craving, and withdrawal, and self-reports of negative mood. Subjects who tested cocaine-positive on the day of testing differed only in skin resistance responding from those who tested cocaine-negative. Changes in cue-induced physiological and self-report measures were also not associated with between-subject variations in mood as measured by the Profile of Mood States (POMS) questionnaire administered prior to cue assessment. Thus, variations in baseline mood and recent cocaine use history do not introduce an additional source of variability in cue reactivity measurements. However, negative mood states at the start of a session were associated with higher levels of self-reported craving, high, and withdrawal both before and after cue exposure.

Adult↗

Comparing levels of cocaine cue reactivity in male and female outpatients.

Thirty-eight female and 26 male cocaine-dependent outpatients were exposed to cocaine cues in a laboratory setting. Stimuli consisted of an audiotape of patients discussing cocaine use, a videotape of simulated cocaine preparation and use, and the handling of cocaine paraphernalia. Overall, the stimuli produced significant decreases in skin temperature and skin resistance, and significant increases in heart rate, self-reported drug states (high, craving, and withdrawal), and self-reported negative moods. Females were more likely to report increased craving in response to the cues than males, but there were no other gender differences in any of the responses. Levels of reactivity in females were comparable to the results of previous studies with all male samples. These results support the use of a constant set of cues in future treatment studies employing gender-balanced patient samples.

Adult↗

Limbic activation during cue-induced cocaine craving.

OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.

Adult↗

Conditioning factors in drug abuse: can they explain compulsion?

There is a good deal of clinical evidence suggesting that compulsion to resume drug taking is an important part of the addiction syndrome. The symptoms comprising motivation to resume drug use, namely craving and compulsion, have been studied experimentally in human subjects. While much work remains to be done, there is evidence showing that these symptoms are influenced by learning. The research has been guided by animal studies demonstrating that drug effects can be conditioned. Much attention has been directed toward demonstrating the existence of drug conditioning in human addicts and exploring the neurological structures that may underlie such learned responses. We do not yet know the relative importance of learning in the overall phenomenon of relapse, and treatments based on conditioning principles are still under investigation.

Alcohols↗

Failure of ritanserin to block cocaine cue reactivity in humans.

As part of a double-blind placebo-controlled study of the effects of ritanserin on cocaine use and craving, reactivity to cocaine-related events was assessed both before and during medication. Twenty-two patients receiving ritanserin and 23 receiving placebo were exposed to cocaine cues while continuous measures of heart rate, skin temperature, and skin resistance were taken. Self-reports of high, withdrawal, and craving were also collected. The cues produced significant physiological responding as well as significant increases in high and craving during both sessions. Ritanserin reduced cue-elicited decreases in skin temperature, but had no effect on heart rate and skin resistance or on cue-induced high and craving. The results demonstrate that cue reactivity is a robust phenomenon across two assessment sessions but fail to support the use of ritanserin as a means of reducing cue-elicited drug states.

Arousal↗

Role reversals in families of substance misusers: a transgenerational phenomenon.

Fifty adult methadone maintained opiate misusers were seen with their spouse and/or family of origin in outpatient therapy as part of a Veterans Administration Research project supported by NIDA. Family treatment was offered in an attempt to improve and enhance family relationships/social supports and to aid in the decrease or cessation of drug use. In this study, 42 of the 50 patients had parents who were substance misusers. The subjects were evaluated by constructing a Three-Generational Family Tree to define and clarify the nature of problems across the generations. Success or failure was measured by the Addiction Severity Index (ASI) which assessed drug use, problems with family, health, social relationships, legal difficulties, and employment as well as psychiatric symptoms. A recurrent problem of the "absent father" was identified across both generations studied. Thirty of the 50 opiate misusing men had absent fathers (usually due to alcohol or other drug misuse) and 27 of these 30 became absent fathers (also usually due to substance misuse) when they had children of their own. The absence of a father produced major developmental problems seen in these families. Particularly important was the "Parentified Child," forced to prematurely assume adult responsibilities. This age inappropriate role assumption was common in both the patients and their children, and was seen as a contributor to the initiation of drug misuse. A structured clinical intervention is described using the three-generational family tree to bring out these relationship issues, followed by supportive family therapy to restructure wounded family relationships from the family of origin and to bring about appropriate role expectations in the marital families. The findings suggest an improvement in legal difficulties, drug use, and psychiatric symptoms.

Adult↗

Developing treatments that address classical conditioning.

Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classical CRs produced by drugs are complex and bidirectional. There has been progress in classifying and predicting the types of CRs, but little is known of mechanisms. New techniques for understanding brain function, such as microdialysis probes in animals and advanced imaging techniques (positron emission tomography and single photon emission computerized tomography) in human subjects, may be utilized in conditioning paradigms to "open the black box." Because the existence of CRs in drug users is now well established, clinical studies have been instituted to determine whether modification of CRs can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8-week outpatient treatment program.

Animals↗

Cue reactivity and cue reactivity interventions in drug dependence.

Despite a venerable history dating back to Pavlov and countless testimonials from patients such as those in the opening paragraphs of this chapter, there is much that remains to be learned about drug signals and, particularly, about ways of reducing their adverse effects on human drug users. There is a substantial amount of data showing increased craving and signs of physiological arousal to drug-related versus neutral cues in drug users for both drug classes reviewed here. Additional controlled studies will be useful in refining which responses among those studied are, in fact, conditioned in origin and therefore can be subjected reasonably to learning-based interventions. Most attempts to modify cue responsivity for clinical benefit have met with only modest success, and there is ample room for creative, but controlled, treatment-outcome studies. In recent years, several other groups have joined in the effort to understand drug-related cue reactivity, extending the research area to alcohol and nicotine (Monti et al. 1987; Niaura et al. 1988, 1989; Cooney et al. 1984; Hodgson and Rankin 1982; Drummond 1990; Laberg 1990). The interested reader is referred to several additional reviews of cue reactivity and cue exposure research related to alcohol and nicotine (Niaura 1988; Drummond 1990; Laberg 1990), opiates (Powell 1990), opiates and cocaine (Childress et al. 1988b; O'Brien et al. 1990), and all the preceding areas (Rohsenow et al. 1991).

Behavior Therapy↗

Classical conditioning in drug-dependent humans.

Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classically conditioned responses produced by drugs are complex and bi-directional. There has been progress in classifying and predicting the types of conditioned responses, but little is known of mechanisms. New techniques for understanding brain function such as micro-dialysis probes in animals and advanced imaging techniques (PET and SPECT) in human subjects may be utilized in conditioning paradigms to "open the black box." Because the existence of conditioned responses in drug users is now well established, clinical studies have been instituted to determine whether modification of conditioned responses can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8-week outpatient treatment program.

Animals↗

Psychotherapy for cocaine dependence.

Dependence on cocaine is a new disorder for contemporary US clinicians. Until the 1980s sufficient quantities of the drug were not available to produce a true dependence. Thus far the only models for pharmacological intervention involve an interaction between medication and psychotherapy; that is, medication may be able to facilitate a drug-free interval during which time the patient can be engaged in psychotherapy. Psychotherapy programmes for cocaine dependence have generally been modelled on group-oriented treatments of the type used by Alcoholics Anonymous. Controlled studies of therapy programmes for cocaine dependence are currently being conducted and one prospective random-assignment study comparing day hospital and in-patient rehabilitation shows generally good results. Behavioural treatments aimed at reducing or extinguishing conditioned responses in cocaine addicts have also shown efficacy in a controlled study. More general relapse prevention procedures including rehearsal and role-playing are also used in the treatment of cocaine dependence. Combinations of psychotherapy and pharmacotherapy have so far shown the most promise in the treatment of this disorder.

Ambulatory Care↗

Developing and evaluating new treatments for alcoholism and cocaine dependence.

Progress in the treatment of any disorder requires the development of methods for evaluation as well as the development of potentially effective new treatments. In this chapter we briefly describe a new instrument to be used in the measurement of substance abuse treatment, the Treatment Services Review. Some of the potential problems in evaluation research are discussed, such as the tendency for more severely ill patients to be more willing to give up their right to choose treatment and agree to randomization. These unexpected tendencies in study volunteers limit the generalizability of treatment research. Evaluation techniques are illustrated by two studies comparing inpatient and outpatient rehabilitation. The results for both alcohol dependence and cocaine dependence were positive, but there was no evidence of a significant advantage for one treatment environment over the other. This has important implications for program funding. We also describe our search for a new treatment technique based on a conditioning model for cocaine dependence. Pilot studies suggested an improvement in treatment outcome for the patients receiving the experimental treatment, and therefore, a prospective study with random assignment was conducted.

Alcoholism↗

Conditioned responses to cocaine-related stimuli in cocaine abuse patients.

Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine-related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles.

Adult↗

A learning model of addiction.

Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classically conditioned responses produced by drugs are complex and bi-directional. There has been progress in classifying and predicting the types of conditioned responses, but little is known of mechanisms. New techniques for understanding brain function such as micro-dialysis probes in animals and advanced imaging techniques (PET and SPECT) in human subjects may be utilized in conditioning paradigms to "open the black box." Because the existence of conditioned responses in drug users is now well-established, clinical studies have been instituted to determine whether modification of conditioned responses can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8 week outpatient treatment program.

Affect↗