Distance disintegration characterizes node-level topological dysfunctions in cocaine addiction.

Previous investigations have used global graph theory measures in order to disentangle the complexity of the neural reorganizations occurring in cocaine use disorder (CUD). However, how these global topological alterations map into individual brain network areas remains unknown. In this study, we used resting state functional magnetic resonance imaging (fMRI) data to investigate node-level topological dysfunctions in CUD. The sample was composed of 32 individuals with CUD and 32 healthy controls, matched in age, years of education and intellectual functioning. Graph theory measures of optimal connectivity distance, node strength, nodal efficiency and clustering coefficient were estimated in each participant using voxel-wise functional connectivity connectomes. CUD individuals as compared with healthy controls showed higher optimal connectivity distances in ventral striatum, insula, cerebellum, temporal cortex, lateral orbitofrontal cortex, middle frontal cortex and left hippocampus. Furthermore, clinical measures quantifying severity of dependence were positively related with optimal connectivity distances in the right rolandic operculum and the right lateral orbitofrontal cortex, whereas length of abstinence was negatively associated with optimal connectivity distances in the right temporal pole and the left insula. Our results reveal a topological distancing of cognitive and affective related areas in addiction, suggesting an overall reduction in the communication capacity of these regions.

Motivational factors modulate left frontoparietal network during cognitive control in cocaine addiction.

Cocaine addiction is characterized by alterations in motivational and cognitive processes involved in goal-directed behavior. Recent studies have shown that addictive behaviors can be attributed to alterations in the activity of large functional networks. The aim of this study was to investigate how cocaine addiction affected the left frontoparietal network during goal-directed behavior in a stop-signal task (SST) with reward contingencies by correct task performance. Twenty-eight healthy controls (HC) and 30 abstinent cocaine-dependent patients (ACD) performed SST with monetary reward contingencies while undergoing a functional magnetic resonance imaging scan. The results showed that the left frontoparietal network (FPN) displayed an effect of cocaine addiction depending on reward contingencies rather than inhibition accuracy; and, second, we observed a negative correlation between dependence severity and the modulation of the left FPN network by the monetary reward in ACD. These findings highlight the role of the left FPN in the motivational effects of cocaine dependence.

Left frontoparietal network activity is modulated by drug stimuli in cocaine addiction.

Cocaine addicts present reduced activity in the left frontoparietal network, a brain network associated with cognitive control, during the processing of non-drug reward related stimuli (Costumero et al., Addiction Biology 22:479-489, 2015). However, the involvement of this network in drug-related stimuli processing remains unclear. Here, fifteen cocaine-dependent men and fifteen healthy matched controls viewed cocaine-related, erotic, aversive, and neutral pictures during an fMRI session. Group independent component analysis was then performed to investigate how functional networks were modulated by the different emotional images. The results showed that the cocaine-dependent group showed stronger left frontoparietal network activity during the processing of cocaine-related pictures than the control group. Furthermore, the activity of this network during cocaine image processing was positively associated with the years of cocaine use in addicted subjects. In conclusion, our results indicate that the left frontoparietal network is affected in cocaine-dependent men, and may be related to the cognitive control deficits shown in addiction.

Reduced activity in functional networks during reward processing is modulated by abstinence in cocaine addicts.

Cocaine addiction is characterized by alterations in motivational and cognitive processes. Recent studies have shown that some alterations present in cocaine users may be related to the activity of large functional networks. The aim of this study was to investigate how these functional networks are modulated by non-drug rewarding stimuli in cocaine-dependent individuals. Twenty abstinent cocaine-dependent and 21 healthy matched male controls viewed erotic and neutral pictures while undergoing a functional magnetic resonance imaging scan. Group independent component analysis was then performed in order to investigate how functional networks were modulated by reward in cocaine addicts. The results showed that cocaine addicts, compared with healthy controls, displayed diminished modulation of the left frontoparietal network in response to erotic pictures, specifically when they were unpredicted. Additionally, a positive correlation between the length of cocaine abstinence and the modulation of the left frontoparietal network by unpredicted erotic images was found. In agreement with current addiction models, our results suggest that cocaine addiction contributes to reduce sensitivity to rewarding stimuli and that abstinence may mitigate this effect.

Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts.

The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake. We examine how the magnitude of the reward affects goal-directed processes in healthy control (HC) subjects and abstinent cocaine dependent (ACD) patients by using functional magnetic resonance imaging (fMRI) during a counting Stroop task with blocked levels of monetary incentives of different magnitudes (€0, €0.01, €0.5, €1 or €1.5). Our results showed that increasing reward magnitude enhances (1) performance facilitation in both groups; (2) left dorsolateral prefrontal cortex (DLPFC) activity in HC and left superior occipital cortex activity in ACD; and (3) left DLPFC and left putamen connectivity in ACD compared to HC. Moreover, we observed that (4) dorsal striatal and pallidum activity was associated with craving and addiction severity during the parametric increases in the monetary reward. In conclusion, the brain response to gradients in monetary value was different in HC and ACD, but both groups showed improved task performance due to the possibility of obtaining greater monetary rewards.

Inferior frontal cortex activity is modulated by reward sensitivity and performance variability.

High reward sensitivity has been linked with motivational and cognitive disorders related with prefrontal and striatal brain function during inhibitory control. However, few studies have analyzed the interaction among reward sensitivity, task performance and neural activity. Participants (N=57) underwent fMRI while performing a Go/No-go task with Frequent-go (77.5%), Infrequent-go (11.25%) and No-go (11.25%) stimuli. Task-associated activity was found in inhibition-related brain regions, with different activity patterns for right and left inferior frontal gyri (IFG): right IFG responded more strongly to No-go stimuli, while left IFG responded similarly to all infrequent stimuli. Reward sensitivity correlated with omission errors in Go trials and reaction time (RT) variability, and with increased activity in right and left IFG for No-go and Infrequent-go stimuli compared with Frequent-go. Bilateral IFG activity was associated with RT variability, with reward sensitivity mediating this association. These results suggest that reward sensitivity modulates behavior and brain function during executive control.

BAS-drive trait modulates dorsomedial striatum activity during reward response-outcome associations.

According to the Reinforcement Sensitivity Theory, behavioral studies have found that individuals with stronger reward sensitivity easily detect cues of reward and establish faster associations between instrumental responses and reward. Neuroimaging studies have shown that processing anticipatory cues of reward is accompanied by stronger ventral striatum activity in individuals with stronger reward sensitivity. Even though establishing response-outcome contingencies has been consistently associated with dorsal striatum, individual differences in this process are poorly understood. Here, we aimed to study the relation between reward sensitivity and brain activity while processing response-reward contingencies. Forty-five participants completed the BIS/BAS questionnaire and performed a gambling task paradigm in which they received monetary rewards or punishments. Overall, our task replicated previous results that have related processing high reward outcomes with activation of striatum and medial frontal areas, whereas processing high punishment outcomes was associated with stronger activity in insula and middle cingulate. As expected, the individual differences in the activity of dorsomedial striatum correlated positively with BAS-Drive. Our results agree with previous studies that have related the dorsomedial striatum with instrumental performance, and suggest that the individual differences in this area may form part of the neural substrate responsible for modulating instrumental conditioning by reward sensitivity.

Characterizing individual differences in reward sensitivity from the brain networks involved in response inhibition.

A "disinhibited" cognitive profile has been proposed for individuals with high reward sensitivity, characterized by increased engagement in goal-directed responses and reduced processing of negative or unexpected cues, which impairs adequate behavioral regulation after feedback in these individuals. This pattern is manifested through deficits in inhibitory control and/or increases in RT variability. In the present work, we aimed to test whether this profile is associated with the activity of functional networks during a stop-signal task using independent component analysis (ICA). Sixty-one participants underwent fMRI while performing a stop-signal task, during which a manual response had to be inhibited. ICA was used to mainly replicate the functional networks involved in the task (Zhang and Li, 2012): two motor networks involved in the go response, the left and right fronto-parietal networks for stopping, a midline error-processing network, and the default-mode network (DMN), which was further subdivided into its anterior and posterior parts. Reward sensitivity was mainly associated with greater activity of motor networks, reduced activity in the midline network during correct stop trials and, behaviorally, increased RT variability. All these variables explained 36% of variance of the SR scores. This pattern of associations suggests that reward sensitivity involves greater motor engagement in the dominant response, more distractibility and reduced processing of salient or unexpected events, which may lead to disinhibited behavior.

Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

Reward anticipation enhances brain activation during response inhibition.

The chance to achieve a reward starts up the required neurobehavioral mechanisms to adapt our thoughts and actions in order to accomplish our objective. However, reward does not equally reinforce everybody but depends on interindividual motivational dispositions. Thus, immediate reward contingencies can modulate the cognitive process required for goal achievement, while individual differences in personality can affect this modulation. We aimed to test the interaction between inhibition-related brain response and motivational processing in a stop signal task by reward anticipation and whether individual differences in sensitivity to reward (SR) modulate such interaction. We analyzed the cognitive-motivational interaction between the brain pattern activation of the regions involved in correct and incorrect response inhibition and the association between such brain activations and SR scores. We also analyzed the behavioral effects of reward on both reaction times for the "go" trials before and after correct and incorrect inhibition in order to test error prediction performance and postinhibition adjustment. Our results show enhanced activation during response inhibition under reward contingencies in frontal, parietal, and subcortical areas. Moreover, activation of the right insula and the left putamen positively correlates with the SR scores. Finally, the possibility of reward outcome affects not only response inhibition performance (e.g., reducing stop signal reaction time), but also error prediction performance and postinhibition adjustment. Therefore, reward contingencies improve behavioral performance and enhance brain activation during response inhibition, and SR is related to brain activation. Our results suggest the conditions and factors that subserve cognitive control strategies in cognitive motivational interactions during response inhibition.

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success.

Reward sensitivity is associated with brain activity during erotic stimulus processing.

The behavioral approach system (BAS) from Gray's reinforcement sensitivity theory is a neurobehavioral system involved in the processing of rewarding stimuli that has been related to dopaminergic brain areas. Gray's theory hypothesizes that the functioning of reward brain areas is modulated by BAS-related traits. To test this hypothesis, we performed an fMRI study where participants viewed erotic and neutral pictures, and cues that predicted their appearance. Forty-five heterosexual men completed the Sensitivity to Reward scale (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire) to measure BAS-related traits. Results showed that Sensitivity to Reward scores correlated positively with brain activity during reactivity to erotic pictures in the left orbitofrontal cortex, left insula, and right ventral striatum. These results demonstrated a relationship between the BAS and reward sensitivity during the processing of erotic stimuli, filling the gap of previous reports that identified the dopaminergic system as a neural substrate for the BAS during the processing of other rewarding stimuli such as money and food.