Interactions between affective and cognitive processing systems in problematic gamblers: a functional connectivity study

Background: Motivational and cognitive abnormalities are frequently reported in pathological gambling. However, studies simultaneously investigating motivational and cognitive processing in problem gamblers are lacking, limiting our understanding of the interplay between these systems in problematic gambling. Studies in non-clinical samples indicate that interactions between dorsal “executive” and ventral “affective” processing systems are necessary for adequate responses in various emotive situations. Methods: We conducted a Psycho-Physiological Interaction (PPI) analysis to assess the influence of affective stimuli on changes in functional connectivity associated with response inhibition in 16 treatment seeking problem gamblers (PRGs) and 15 healthy controls (HCs) using an affective Go-NoGo fMRI paradigm including neutral, gambling-related, positive and negative pictures as neutral and affective conditions. Results: Accuracy of task performance during neutral inhibition trials was positively correlated with functional connectivity between regions belonging to the dorsal executive system. During affective (gambling, positive and negative) inhibition trials, accuracy of task performance was positively correlated with functional connectivity within sub-regions of the dorsal executive system as well as with functional connectivity between the regions of the dorsal executive system and the ventral affective system. Group interactions showed that during neutral inhibition, HCs exhibited more functional connectivity between the right inferior frontal cortex (IFC) and other dorsal executive brain areas (superior frontal, middle frontal and anterior cingulate cortex) than PRGs. In contrast, during inhibition in the gambling and positive condition, PRGs compared to HCs showed greater functional connectivity between the right IFC/left caudate and the dorsal executive system. The negative condition showed an enhanced functional connectivity in HCs compared to PRGs between sub-regions belonging to the motor preparation circuit (supplementary motor cortex and putamen), whereas PRGs compared to HCs showed more functional connectivity between sub-regions of the dorsal executive system (anterior cingulate, superior frontal cortex, middle frontal cortex). Conclusions: Gambling-related and positive affective stimuli lead to enhanced functional connectivity between the ventral affective system and the dorsal executive system in PRGs compared to HCs, suggesting bottom-up facilitation of the dorsal executive system, resulting in better task performance in PRGs during gambling and positive inhibition trials. Interactions between affective and cognitive processing systems Introduction Pathological gambling, currently classified as an impulse control disorder in the DSM-IV, has been regarded as a “behavioural addiction’ by many researchers (Holden, 2001; Petry, 2006; Potenza, 2006) and is expected to be incorporated in the new DSM-V under the new category of “Addiction and Related Disorders” (American Psychiatric Association, 2010). The disorder is characterized by loss of control over gambling behaviour 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 (for a review see; van Holst et al., 2010), 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 aetiology of this disorder. Adequate behaviour 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 behaviour. The cognitive executive process of response inhibition is responsible for interruption of ongoing behaviour and depends on the right inferior frontal cortex (IFG; especially the frontal operculum extending into the insula), the superior frontal cortex (SFC) and the medial frontal cortex (MFC; particularly the presupplementary motor areas) (Aron et al., 2007; Aron, 2007; for recent reviews see Chambers et al., 2009; Chen et al., 2009; Li et al., 2006; Picton et al., 2007). Evidence from functional magnetic resonance imaging (fMRI) studies in healthy adults indicates that affective information has a regulatory role in goal directed behaviour through reciprocal interactions between dorsal “executive” and ventral “affective” processing systems (Dolcos and McCarthy, 2006; Northoff et al., 2004; Ochsner et al., 2009; Phillips et al., 2003). 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 (Dolcos and McCarthy, 2006; Ochsner et al., 2009; Ochsner and Gross, 2005; Schulz et al., 2009). 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” (Boyer and Dickerson, 2003; for a review see Field and Cox, 2008; McCusker and Gettings, 1997). In problem gambling, 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) (Crockford et al., 2005; Goudriaan et al., 2010). The incentive sensitization theory introduced by Robinson and Berridge (1993) explains attentional bias and cue reactivity as the result of sensitisation 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 behaviour and diminished response inhibition have been reported in problem gamblers (Goudriaan et al., 2006a; Goudriaan et al., 2008; Kertzman et al., 2006; Kertzman et al., 2008), and has been associated with an attenuated BOLD response in the ventrolateral prefrontal cortex in problem gamblers compared to controls (Potenza et al., 2003; Tanabe et al., 2007). 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 (van Holst et al., 2011, submitted) we investigated the influence of affective stimuli (positive, negative and gambling related pictures) on response