Pathological gambling, currently classified as an impulse control disorder in the DSM-IV, has been regarded as a ‘behavioral addiction’ by many researchers 
and is expected to be incorporated in the new DSM-V under the new category of “Addiction and Related Disorders”. The disorder is characterized by loss of control over gambling behavior and continuation of gambling regardless of negative consequences. Despite the phenomenological evidence of abnormalities in a variety of cognitive and motivational functions in problem gambling and its neural mechanisms 
, studies addressing both functional systems simultaneously are lacking. This limits our understanding of the interplay between these systems in problem gambling, which is needed to further elucidate the etiology of this disorder.
Adequate behavior requires continuous coordination between initiation and inhibition of actions, the latter being particularly important when sudden changes in the situation call for a cancellation of planned or ongoing behavior. The cognitive executive process of response inhibition is responsible for interruption of ongoing behavior and depends on the right inferior frontal cortex (IFC; especially the frontal operculum extending into the insula), the superior frontal cortex (SFC) and the medial frontal cortex (MFC; particularly the pre-supplementary motor areas) 
. Evidence from functional magnetic resonance imaging (fMRI) studies in healthy adults indicates that affective information has a regulatory role in goal directed behavior through reciprocal interactions between dorsal “executive”
and ventral “affective” processing systems
. Several studies have revealed that this interaction between prefrontal cognitive control regions and limbic affective processing areas is critically involved in regulating attention and response selection in the presence of affective information 
In addictive disorders, including pathological gambling, there is evidence that both affective and motivational systems are more sensitive to addiction relevant material. For example, studies have shown that addiction related cues attract more attention than other salient stimuli, a phenomenon known as “attentional bias” 
. In problematic gamblers, enhanced brain responsiveness towards gambling related cues (“cue reactivity”) has also been found in brain areas related to motivational processing and cognitive control (amygdala, basal ganglia, ventrolateral prefrontal cortex and dorsolateral prefrontal cortex) 
. The incentive sensitization
theory introduced by Robinson and Berridge 
explains attentional bias and cue reactivity as the result of sensitization of the mesocorticolimbic system following repeated exposure to addictive stimuli, associated with incentive salience to reward-associated stimuli and drug wanting. In addition, diminished executive functions such as disadvantageous choice behavior and diminished response inhibition have been reported in problem gamblers 
, and has been associated with an attenuated BOLD response in the ventrolateral prefrontal cortex in problem gamblers compared to controls 
. However, it is unclear whether the nature and extent of interactions between the ventral “affective”
and dorsal “executive” processing systems
in problematic gamblers differ from those in healthy controls.
In a previous fMRI study 
, we investigated the influence of affective stimuli (positive, negative and gambling related pictures) on response inhibition in problematic gamblers (PRGs) and healthy controls (HCs) during an affective Go-NoGo task. When presented with neutral pictures, response inhibition in PRGs was associated with more DLPFC and ACC activation, similar accuracy and slower reaction times compared to HCs. Stronger activation of DLPFC and ACC in combination with slower reaction times suggested a compensatory response and higher effort in PRGs to achieve the same accuracy as HCs. Interestingly, when an affective condition was introduced in the Go-NoGo task, PRGs were more accurate than HCs at response inhibition when confronted with gambling related and positive pictures and showed less activation of the relevant brain circuits, whereas negative pictures led to better task performance in both groups.
The facilitation of inhibition in PRGs compared to HCs when confronted with gambling and positive stimuli could be interpreted within the “dual process and competition” framework regarding the interaction between motivational and cognitive functioning 
. This model posits that affective stimuli influence competition for cognitive resources both at a perceptual and executive level. Thus, salience of affective stimuli will result in extra attention. This may facilitate task performance, such as discrimination or response inhibition tasks, but salient stimuli may also become overwhelming, and result in an overload of attentional resources and diminished cognitive control 
. The finding that gambling related and positive pictures facilitated task performance more in PRGs than HCs indicates that increased attention towards these stimuli may have facilitated attentional network processing in PRGs compared to HCs.
From these results, it becomes clear that the interaction between cognitive and motivational brain areas may be crucial for a better understanding of the influence of salient stimuli on (the neural mechanisms of) cognitive control in PRGs. In this report, we present a new analysis of previously published fMRI data 
using a functional connectivity technique, generalized Psycho-Physiological Interactions (gPPI; 
), which allows us to investigate the effect of affective stimuli on functional connectivity patterns during response inhibition in PRGs and HCs. Two relevant seed regions were chosen: (1) the right inferior frontal cortex (rIFC) for its crucial role in response inhibition 
, and (2) the left caudate for its role in the coding of affectively relevant stimuli 
. We decided to use the term functional connectivity instead of effective connectivity 
because PPI cannot be used to infer the directionality of the connection, so that we cannot state that the caudate/IFC affects other regions and vice versa.
First, we tested the general hypothesis that increased connectivity between the sub-regions of the dorsal executive system is associated with higher task accuracy, i.e., adequate response inhibition in both PRGs and HCs. This hypothesis is based on previous research showing a positive relation between task performance and functional connectivity with the task related network 
. For example, in a study on response inhibition using a stop signal task, psychophysiological interaction analyses showed that, successful stops evoked greater effective connectivity between the IFC and pre-supplementary motor areas than stop errors 
. Therefore we hypothesized that better task accuracy, i.e. better response inhibition, would be related to higher connectivity within the dorsal frontal system. Second, we tested the hypothesis that in the neutral condition, functional connectivity between the right IFC and other sub-regions of the dorsal executive system is stronger in HCs than in PRGs, based upon our previous findings of more efficient task performance in HCs compared to PRGs 
. Given the findings of enhanced activation of the reward and motivational brain system in gamblers toward gambling stimuli 
, our third hypothesis was that gambling related stimuli will enhance functional connectivity between the ventral affective and the dorsal executive systems during response inhibition more in PRGs than in HCs. Finally, we explored group by condition interaction effects and the modulatory effect of positive and negative affective stimuli on functional connectivity during inhibition trials in PRGs and HCs.