Addiction Research: Recent Insights into the Cognitive Neuroscience and Functioning

Assistant Professor, Department of Psychology and Biomedical Research Imaging Center,
University of North Carolina, Chapel Hill

First published in Psychiatry Weekly, Volume 3, Issue 16, on April 28, 2008

This interview was conducted on March 28, 2008 by Lonnie Stoltzfoos

The majority of addiction research taking place today involves animal models—animals used to model some aspect of addictive behavior or brain response to drugs of abuse. “We have learned a tremendous amount from animal model studies,” says Dr. Charlotte Boettiger. “Unfortunately, most of the drugs identified in animal studies as potential therapeutic medicines for addiction fail in clinical trials, which implies the need to understand better how drugs work in human subjects prior to clinical trials.”

Dr. Boettiger underscores the need for more mainstream, accessible addiction treatments, given the significant, widely dispersed effects that addictions have on society. “There are data indicating that over 50% of US adults claim to have a close family member who is an alcoholic, and ~24% of US children live with an alcoholic family member. Overall, ~10% of the US population is directly engaged in substance use.”

Brain Function in Addiction

It has been a long-standing, rather obvious, observation that addictive disorders are characterized by executive impairment—or the loss of executive control. Accordingly, Dr. Boettiger remarks that her research focus is “to try to understand at a very detailed level the executive function abnormalities that are associated with addictive behavior, and to then try to understand how we might ameliorate those abnormalities. At this time, very few studies have been done into the cognitive neuroscience of this issue.”

How this plays out practically is by attempting to isolate particular aspects of executive function to determine the neurobiology of those functions and in what way, or ways, those functions are abnormal in people with addictive disorders. In addition to pharmacologic interventions, Dr. Boettiger is interested in identifying the brain mechanisms of behavioral therapies designed to help shift executive functioning into normal range.

“A good deal of research focuses on trying to manipulate processes of reward, based on the theory that perhaps people are addicts because they’re hypersensitive to reward,” explains Dr. Boettiger. “I think that we may have more success trying to manipulate aspects of behavioral control. That is, it may be more useful to devise treatments that improve addicts’ ability to control themselves, rather than to manipulate their sensitivity to reward. Blunting response to reward might be one way to promote abstinence, but perhaps not the best solution.”

A recent study by Boettiger and colleagues assessed brain activity underlying decisions between different rewards in abstinent alcoholics as well as people with no history of substance abuse. The participants were asked to decide on smaller amounts of money available immediately versus larger amounts of money available at a delay. Choices varied in terms of the amount of money, delay time, and the difference between the two amounts. All told, participants made hundreds of different decisions during the analysis.

“What we found, robustly, is that abstinent alcoholics consistently choose the immediate reward more frequently than people without a history of drug or alcohol abuse,” says Dr. Boettiger. “This finding could not be attributed to socioeconomic status, IQ, or education level—things one might expect to contribute to that kind of decision making.”

The average length of sobriety for the experimental group was ~2.5 years, although several outliers had been sober for decades. It is suggested that impulsivity, such as the kind Boettiger and colleagues assessed, is a character trait that predates alcohol abuse, but there are very few clinical data exploring this question.

“We do not know whether immediate reward bias precedes or follows addictive behavior, but there is one possible clue,” Dr. Boettiger explains. “We collected DNA material from these same participants and tested their genotype at one particular site in the COMT gene, which produces an enzyme that controls the level of dopamine in the cortex—especially the frontal cortex.”

The COMT gene, and the particular site in the COMT gene, have both been reasonably well studied. There are two common flavors of this gene, and they are pretty evenly distributed across the population. Approximately one-third of our subjects had two copies of one flavor, resulting in low frontal dopamine, about a third had two copies of the other flavor, resulting in relatively higher frontal dopamine, and the other third had one copy of each, resulting in an intermediate level of frontal dopamine. This distribution of genotypes across the population is consistent with that observed by many different groups.

“We found that people who have the genotype that leads to a low level of frontal dopamine tended to choose the immediate reward more often than the other groups,” Dr. Boettiger recounts, “and that tendency was independent of their alcohol abuse history.”

Another important area of cognitive research—one that Boettiger and colleagues place specific emphasis upon—is what they call “abnormal attention to addiction-related information.” Many different groups around the world have reported an abnormal fixation with stimuli related to one’s particular addiction, which makes this trait appear as a commonality—if not universal feature—across many different types of addictions and in different cultures. The level of resulting attention bias to addiction-related stimuli predicts relapse liability. The specter of relapse liability tied to this issue implies its potent clinical relevance.

“We are designing paradigms right now, and my postdoctoral fellow, Dr. Vicki Chanon, is in the pilot stages of testing subjects to identify whether this is an abnormal capture of attention by these stimuli, or whether these stimuli are better able to hold attention once they gain it,” Dr. Boettiger explains. “We are using two different types of paths to assess that issue in individual people, and we will soon gather fMRI data to hopefully identify what brain abnormalities are associated with that attentional bias.”

Pharmacologic Treatment in Addictions

From the results of the attentional bias study, Boettiger and colleagues hope to identify any medications that may dampen such biases. The use of medications in addiction treatment are still rare, however. Only 5 medications have been FDA-approved for addiction—aside from nicotine addiction—with no medications approved for stimulant abuse. In her own work, Dr. Boettiger places emphasis on exploring two specific aspects of medications: identifying what a drug is doing cognitively, and finding a way to predict how it affects the cognitive behavior of different people. “Perhaps then we can discover who is a better candidate for one drug compared to another, and to identify known people for whom it does work, and why,” she explains.

Conclusion

“Understanding the frontal lobe will be part of the secret in helping to understand addiction,” Dr. Boettiger says. “This is an area of the brain that is most elaborated in humans—compared to other animals—so our understanding of it can be uniquely advanced by studying it in people, and the cognitive neuroscience techniques developed over the past 15 years are finally giving us a chance to do so.”

Disclosure: Dr. Boettiger reports no affiliations with, or financial interests in, any organization that may pose a conflict of interest.