Smoking Addiction Linked to Abnormal Cue Reactivity and Diminished Error Processing

Caroline Helwick

August 31, 2010

August 31, 2010 (Amsterdam, The Netherlands) — More evidence has emerged to show that abnormal cue reactivity is an underlying mechanism for behavioral and substance-related addictions and diminished ability to "process errors" may also be involved in nicotine dependence.

The studies, both conducted in The Netherlands, were reported at the 23rd European College of Neuropsychopharmacology Congress.

Smoking and Gambling

Abnormal cue reactivity was validated by functional magnetic resonance imaging (MRI) in a study from the University of Amsterdam, reported by Anna E. Goudriaan, MD. The study involved 17 treatment-seeking nonsmoking problem gamblers, 18 nongambling heavy smokers, and 17 nongambling and nonsmoking healthy controls. The subjects were shown gambling, smoking-related, and neutral pictures in a 2-choice response task while undergoing functional MRI. They were also administered gambling and smoking urge questionnaires.

"We were examining how problem gamblers in treatment react to gambling cues, whether their neural responses were comparable to smokers and substance abusers," Dr. Goudriaan explained.

She and her colleagues observed increased regional responsiveness to gambling pictures in occipitotemporal areas, posterior cingulated cortex, and parahippocampal gyrus — regions linked to visual processing, emotion-motivation. and attentional-control. This reactivity also reflects similar neural mechanisms underlying cue reactivity in substance dependence. Subjective craving in the gamblers correlated positively with brain activation in the left ventrolateral prefrontal cortex and left insula.

While gambling is considered an impulse control disorder, this finding supports the perception of it as an addiction.

"The pathological gamblers showed activation in areas related to reward processing and impulsivity, comparable to what is seen in substance-dependent persons," she said. "This activation is positively related to gambling urges. The brain circuitry that is involved in craving is similar to substance abuse. While gambling is considered an impulse control disorder, this finding supports the perception of it as an addiction."

The heavy smokers' reaction to smoking cues was not different from healthy controls or gamblers; however, smokers with higher nicotine dependence scores (mean Fagerstrom Test score, 5.4) showed higher brain activation in ventromedial prefrontal cortex, rostral anterior cingulated cortex, insula, and middle/superior temporal gyrus while watching smoking-related pictures (relative to neutral pictures) than the subgroup with lower nicotine dependence scores (mean score, 2.9) and nonsmoking controls. Higher smoking urge was associated with increased activity in reward and emotion-related brain areas.

"Future research needs to establish whether the long-term effects of gambling cues on brain activation in problem gamblers in treatment are related to relapse," she added.

Smokers Lack Error Recognition

In a separate study from Erasmus University Rotterdam's Institute of Psychology in The Netherlands, researchers showed that deficits in error processing may contribute to the inability to stop smoking despite negative consequences. This characteristic was observed during smoking cue exposure at both the behavioral and electrophysiologic level, Maartje Luijten, MSc, reported at the meeting.

"I call it the 'oops response,' such as when you recognize you've made a mistake," said Ms. Luijten in an interview. "This response is less pronounced in smokers."

The diminished processing error is related to impulsivity, she added. "The more impulsive you are, the less likely you are to have the 'oops' reaction. Because adequate error processing is required to adapt behavior properly, reduced error processing may contribute to the development and maintenance of additive behaviors."

I call it the 'oops response,' such as when you recognize you've made a mistake. This response is less pronounced in smokers.

The study investigated error processing deficits in smokers given conditioned smoking cues. At the same time, error processing was measured electrophysiologically with 2 event-related potentials (ERPs) that corresponded to error-related negativity (which reflects automatic and initial error processing) and error positivity (assumed to be related to the motivational significance attributed to the error).

ERPs were measured during the performance of an adapted Eriksen flanker task during which participants were exposed to smoking-related and neutral pictures. The task is a visual experiment where participants are expected to respond to a centered and directed item that is surrounded by distracting symbols and that judges reaction time and accuracy. The researchers also assessed impulsivity, nicotine dependence, and nicotine craving.

The cohort included 13 smokers (mean age, 21 years) who smoked at least 10 cigarettes a day (mean, 17 cigarettes) and 14 nonsmoking controls. The mean age of both groups was 21 years.

The smokers and nonsmoking controls made a comparable number of errors on the task, but nonsmokers exhibited diminished posterror processing during smoking cue exposure; that is, they were less likely to recognize the mistakes they made. Decreased error-related negativity and error positivity amplitudes in smokers were accompanied by diminished error processing.

In addition, impulsivity in both smokers and nonsmokers was directly related to reduced amplitude of error-related negativity on the ERPs, as was level of nicotine dependence in the smokers.

"What this means is that in performing the task the smokers did not monitor their errors and process mistakes as well as nonsmokers," she said. "And on a simple electrophysiological reaction test, smokers' brain activation was much less pronounced than nonsmokers. This may mean that smokers don't care so much about doing things that are not good for them, ie, continuing to smoke. They are not as likely to recognize this as a mistake."

Adding to the Evidence

Marcus Munafò, PhD, an addiction expert from the Department of Experimental Psychology at the University of Bristol, United Kingdom, commented that these studies add to a growing awareness of enhanced cue reactivity and impulsivity in addiction.

"There is a lot of literature on the extent to which smoking cues distract smokers, alcohol cues distract drinkers, and so on vs neutral cues," Dr. Munafò told Medscape Medical News. "One of the features of this is their inability to suppress those distractions and that is a newer area of interest.

"These data fit with this concept," he added. "When the inability to suppress an urge is diminished, a person is more likely to engage in some behavior. Error processing, which is related to impulsivity, fits within this context. Such studies may eventually give us pharmacologic targets and support for behavioral therapy that would enhance the ability to suppress urges."

Dr. Goudriaan, Ms. Luitjen, and Dr. Munafò have disclosed no relevant financial relationships.

23rd European College of Neuropsychopharmacology (ECNP) Congress: Abstracts P.6.f.001 and P.6.e.006. Presented August 29, 2010.

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