Research report
Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers

https://doi.org/10.1016/j.cogbrainres.2004.12.010Get rights and content

Abstract

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (≥3 months) and healthy controls who underwent positron emission tomography scans with H215O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.

Introduction

Risky decision making is a primary characteristic of drug abuse and addiction, often cited as both an antecedent [6], [21], [46], [53], [54], [98], [99] and a consequence of illicit drug use [8], [9], [81], [93]. A defining characteristic of risky decision making is the failure to avoid an imminent threat or negative consequence by shifting to a “safer” strategy. Such a shift may either result in the simple avoidance of penalty or increased likelihood of reward. Persistent risky decision making can therefore often lead to harm. While the mechanisms that underlie this tendency are unknown, there is evidence that some risk-taking individuals, also characterized as sensation or novelty-seekers, derive arousal that they perceive as pleasurable from engaging in risky behavior [16], [96]. Curiously, some individuals repeatedly engage in risky decision making, despite the negative consequences. There is also evidence that risk taking may be associated with increased sensitivity to reward and a corresponding relative insensitivity to penalty [11], [12], [39]. Deficits in executive cognitive functions (ECF) that modulate impulse control, conflict/error monitoring, and goal-driven behaviors may contribute to such risky behavior.

Such traits and cognitive deficits describe the behavior of drug abusers and addicts [10], [14], [28], [61]. Under experimental conditions, drug abusers select risky choices that involve potential to obtain a large reward but also an even greater potential for higher penalty more often than people who do not abuse drugs [7], [51], [87]. Contributing factors may be heightened sensitivity to reward and relative insensitivity to negative consequences in drug abusers, favoring reward-approach behaviors over pain-avoidance behaviors [7], [39], [84].

Most studies have not differentiated between the causes and effects of drug use with respect to its relationship with various cognitive functions (e.g., working memory, attention, problem solving, etc.), including risky decision making. While there is evidence that traits such as novelty-seeking, approach behaviors, impulsivity, and poor decision making are precursors to drug abuse [3], [4], [5], [45], [95], chronic drug use may also exacerbate existing deficits in decision making or give rise to them [42], [52], [58], [74], [86], compromising the ability to execute conservative judgments. The present study does not attempt to isolate cause from consequence in view of the fact that, regardless of the origins of risky decision making, this trait may undermine treatment efforts [1]. Thus, it would be beneficial to identify the neural underpinnings that subserve high-risk behaviors that may influence the propensity for drug abuse and relapse.

Section snippets

Neuroanatomy of risky decision making

Recent neuroimaging studies implicate the orbitofrontal cortex (OFC) in drug abuse [15], [19], [36], [50], [66], [71] and behaviors or diagnoses, such as impulsivity, ADHD, aggression, and poor decision-making ability [17], [35], [103], which are related to drug abuse. Rogers et al. [88] developed a cognitive task, the Rogers Decision-Making Task (RDMT), to assess impairments in decision making as reflected in risk-taking behaviors. Healthy control subjects performing the RDMT exhibited

Task pretesting and selection

In phase 1 of this study (reported elsewhere; [39]), four ECF tasks and one emotional regulation task were pretested on a sample of 41 drug abusers abstinent for a minimum of 3 months and control subjects without a history of drug abuse. Tasks were selected on the basis of ECF dimensions thought to be conceptually related to drug abuse, including impulsivity, sensitivity to consequences, attention, decision making, and emotional regulation. The purpose of this pretest was to identify those two

Subjects

The Institutional Review Boards of both the Research Triangle Institute and the National Institute on Drug Abuse Intramural Research Program approved the study protocol. Thirteen abstinent drug abusers and 14 control subjects (21–35 years of age) participated after providing written informed consent and were compensated for their time. For both groups, individuals under the age of 21 years and over 35 years were excluded to avoid effects of age on cognitive parameters [63]. The following

Participant screening

Participants initially visited the NIDA Intramural Research Program for a medical examination including a neurological exam, urine toxicology screen, pregnancy test for women, and cardiac evaluation. Extensive psychiatric, behavioral, and psychological testing was also conducted, including the Diagnostic Interview Schedule (DSM-IV criteria) [2], demographic questionnaire, Addiction Severity Inventory (ASI) [73], Symptom Checklist 90 Revised (SCL-90-R) [29], Psychopathy Checklist-Screening

Image processing

PET scanning and reconstruction procedures were the same as those employed by Bolla et al. [19] and Ernst et al. [34]. Briefly, scans were acquired on a Siemens ECAT EXACT HR+ in 3D mode. Images were reconstructed by applying corrections for attenuation and scatter using a Hann filter (cutoff frequency = 0.5 cycles/pixel) and filtered back projection algorithm. The image resolution following reconstruction was 6.52 and 7.16 mm in the x and y transverse planes, respectively, at the center of the

Cognitive group comparisons

Performance on the entire task of 75 trials (including the embedded sequence of 21 trials) with the exception of neutral risk scenarios (i.e., equal number of yellow and value boxes and equal point value, 5 trials) was used in the analysis of task performance. Risky choices are defined both as low probability options, referred to as risk level (yellow choices in trials with one or two yellow boxes), and as the odds of either winning or losing a large amount (60, 70, 80, and 90 points), referred

Overall performance

Across the entire set of task trails (i.e., not restricted to the embedded sequence), drug abusers made significantly more risky choices (mean percent = 41; percent SD = 10) as compared to controls (mean percent = 31; percent SD = 10) (F = 4.4, df = 1,25; P < 0.05) (Fig. 2).

The following subsections more closely evaluate the specific effect of risk and of consequences (i.e., reward) on performance.

Effect of degree of risk

There was a main effect of the risk condition in that both groups selected significantly fewer

Discussion

This study investigated differences between abstinent drug abusers and healthy controls in the functional anatomic correlates of a complex decision-making process involving risk. Abstinent drug abusers showed significant differences in both task performance and task-related neuronal activation compared to controls. These findings are consistent with numerous studies of risky decision making in normals and brain-damaged patients which show that performance on similar decision-making tasks is

Acknowledgments

Funding for this study was provided by the Office of National Drug Control Policy (#DABT63-00-C-1014).

This project was initiated while EDL and SJG were members of the NIDA Intramural Research Program.

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