Prefrontal cortex activity is reduced in gambling and nongambling substance users during decision-making

Abstract

Objective: Poor decision-making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision-making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance-dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance-dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems.

Method: 18 controls, 14 substance-dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT.

Result: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision-making. Controls showed the greatest activity, followed by SDPG, followed by SD.

Conclusion: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision-making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance-dependent individuals.

Figure 1

Performance on modified Iowa Gambling Task. All participants increased net score over time consistent with learning. Controls and SDPG had higher net scores than SD, but the difference was not statistically significant (data are mean ± SEM).

Figure 2

Second level analysis of brain regions active during decision‐making compared with no‐decision making. Statistical maps were corrected for multiple comparisons using family‐wise‐error and were set at a threshold P < 0.005.

Figure 3

Second level ANCOVA statistical maps showing brain regions significantly different across three groups during decision‐making were ventral medial prefrontal, right superior frontal, right frontopolar and were set at threshold F > 6 (P < 0.005). Images are shown in radiological convention (right is on the left). Education and IQ were entered as covariates.

Figure 4

Size of fMRI effect during decision‐making for ventral medial frontal and right orbitofrontal regions (MNI coordinates shown) was largest in controls, followed by SDPG, followed by SD. Data represent size of fMRI effect (β) for individuals. Data were analyzed using ANOVA and post‐hoc Tukey's, controlling for education and IQ.

Figure 5

Second level event‐related analysis of brain activity during the experience of winning or losing. Medial inferior orbitofrontal regions (BA 25 (10, 14, −20) and BA 32 (16, 34, −6)) were more active during wins versus losses, whereas lateral inferior orbitofrontal regions (BA 47/12 (34, 20, −16) were more active during losses versus wins. Superior medial frontal (BA 9 (0, 52, 38)) was also more active during losses vs. wins. Color bar corresponds to t‐value.