In addition to reward system dysfunction, a prominent symptom of PG is the strong urge to gamble, which often leads to a relapse in gambling behavior. Although craving and cue reactivity have been extensively studied with neuroimaging techniques in SUDs, only a few studies in PG have been published.
The first fMRI study on gambling urges was published in 2003 [12
]. While viewing a gambling video designed to evoke emotional and motivational antecedents to gambling (actors who mimicked emotional [eg, happy, angry] situations followed by the actor describing driving to and walking through a casino and the feeling of gambling), participants were asked to press a button when they experienced gambling urges. During such episodes of increased craving, the PG group (n
10) showed less activation in the cingulate gyrus, (orbito)frontal cortex, caudate, basal ganglia, and thalamic areas compared with the NC group (n
11). Recently, the authors reanalyzed their 2003 data to determine whether motivational processing in pathological gamblers (n
10) and cocaine users (n
9) differed from that of recreational gamblers (n
11) and NCs (n
6) not using cocaine [13
]. Viewing of addiction-related scenarios compared with neutral scenarios resulted in increased activity in the ventral and dorsal anterior cingulate cortex and right inferior parietal lobule, with relatively decreased activity in pathological gamblers compared with recreational gamblers, and relatively increased activity in cocaine users compared with NCs. These findings therefore indicate opposite effects in individuals with an SUD compared with those with a behavioral addiction.
In contrast, an fMRI cue reactivity study by Crockford et al. [14
] found a higher BOLD response in the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus, medial frontal gyrus, left parahippocampal region, and left occipital cortex in response to gambling stimuli in pathological gamblers (n
10) compared with NCs (n
11). In addition, the dorsal visual processing stream was activated in pathological gamblers when they were viewing gambling movies, whereas the ventral visual stream was activated in controls when they viewed these movies. The authors argued that brain regions activated in pathological gamblers compared with NCs predominantly involved regions associated with the DLPFC network, which is associated with conditional responses.
In a recent study, Goudriaan et al. [15
] showed similar cue reactivity-related brain activations as reported by Crockford et al. [14
] in pathological gamblers (n
17) compared with NCs (n
17). In this fMRI study, participants viewed gambling pictures and neutral pictures while being scanned. When viewing gambling pictures versus neutral pictures, higher bilateral parahippocampal gyrus, right amygdala, and right DLPFC activity was found in problem gamblers relative to NCs. Furthermore, a positive relationship was found between subjective craving for gambling after scanning in problem gamblers and BOLD activation in the ventrolateral prefrontal cortex, left anterior insula, and left caudate head when viewing gambling pictures versus neutral pictures.
Finally, in a recent gambling paradigm study, 12 problems gamblers and 12 frequent (nonproblem) gamblers were asked to play a blackjack gambling game while fMRI scans were obtained [16
]. The game consisted of trials with a high risk of losing and trials with a low risk of losing. Problem gamblers showed a signal increase in thalamic, inferior frontal, and superior temporal regions during high-risk trials and a signal decrease in these regions during low-risk trials, whereas the opposite pattern was observed in frequent gamblers. Miedl and colleagues [16
] argued that the frontal-parietal activation pattern noted during high-risk trials compared with low-risk trials in problem gamblers reflects a cue-induced addiction memory network that is triggered by gambling-related cues. They suggested that high-risk situations might serve as an addiction cue in problem gamblers, whereas the low-risk situation signifies a “safe” hit in frequent gamblers. Interestingly, problem gamblers showed higher activity in dorsolateral prefrontal and parietal lobes compared with frequent gamblers while winning as compared with losing money, a network generally associated with executive function. However, activity patterns in limbic regions while winning compared with losing money were similar, which is at odds with earlier findings of reward processing in the studies by Reuter et al. [6
] and de Ruiter et al. [7
•]. Differences in the employed paradigms could explain the dissimilarities between these studies: whereas in the blackjack paradigm of Miedl and colleagues [16
], the winning result had to be calculated by the participants (calculating the card values) before they realized that a win or loss was experienced, in the studies by Reuter et al. [6
] and de Ruiter et al. [7
•], wins or losses were displayed on the screen and thus experienced immediately. Therefore, in the study by Miedl et al. [16
], the relatively high stimulus complexity and cognitive elements in reward and loss experiencing may have influenced reward processing and diminished the potential to find group differences.
Thus, cue reactivity studies in PG have so far reported conflicting results. It should be noted, however, that the findings of Potenza et al. [12
] are difficult to interpret because of the complex emotional movies used to elicit craving for gambling. On the other hand, the increased activity in response to gambling cues in the prefrontal cortex, parahippocampal regions, and occipital cortex reported by Crockford et al. [14
], Goudriaan et al. [15
], and Miedl et al. [16
] is consistent with results from cue reactivity paradigms in SUD studies [17
]. However, in contrast to SUD studies, enhanced limbic activation during cue reactivity paradigms in gambling was only reported in one of the gambling cue reactivity studies [15
]. Future research should focus on the type of stimuli that elicit the most powerful cue reactivity (eg, pictures vs movies). One aspect that may diminish the power to detect differences in cue reactivity in PG studies as opposed to SUD studies is that gambling may involve a diversity of gambling activities (eg, blackjack, slot machines, horse racing), whereas cue reactivity to a substance is more specific for the targeted substance (eg, cocaine, marijuana) and may therefore elicit limbic brain activity in most SUD participants. Selecting specific gambling types for cue reactivity stimuli and limiting participant inclusion to a specific gambling pathology may result in a better matching of cues and PG pathology and thus result in more robust brain activations in response to cues in PG.