| Abstract: | Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.Cocaine dependence is a chronically relapsing disorder defined by uncontrolled and compulsive drug use (1). Despite severe negative consequences including disrupted social relationships, loss of employment, and somatic and psychiatric illnesses, an addicted person’s life is often centered around the drug of choice and activities related to it (2). Therefore, drug use is classified as a major social, legal, and public health problem (3). After cannabis, cocaine is the second most prevalent illegal drug in the United States and Europe (4, 5), with a lifetime prevalence among young adults of 6.3% in Europe (15- to 34-y-olds) (4) and 13.3% in the United States (18- to 25-y-olds) (5).Social cognition and social support for drug users are of great clinical relevance, as they have been reported to influence onset of drug use and development of substance use disorders, and treatment success in patients with substance use disorders (6, 7). Impairments in social cognition may augment the risk of social isolation, aggression, and depression, likely supporting the vicious circle of drug use (8). Additionally, impaired social cognition may contribute to the decay of social relationships in addicted patients (9) with negative consequences for treatment success given that higher social support predicted longer abstinence duration (10). Furthermore, no efficient pharmacological treatment for cocaine addiction is currently available (11), and treatment approaches such as cognitive behavioral therapy rely, at least in part, on the emotional responsiveness and social abilities of drug users (12). Previous results suggest that cocaine users (CUs) show impairments in different facets of social cognition, particularly in emotional empathy, mental perspective taking, and emotion recognition in prosody, which are related to deficits in real-life social behavior such as fewer social contacts and more criminal offenses (13, 14). Furthermore, in money distribution games, CUs act more self-servingly and less altruistically than stimulant-naïve controls (15). Volkow et al. (9) postulated that neuroadaptations in the reward systems of drug users (e.g., ventral striatum and orbitofrontal cortex) alter reward processing such that the value of the abused drug is enhanced and concurrently the value of nondrug rewards, including social interaction, is reduced. Consequently, general social competence might become impaired and promote antisocial and criminal behavior. This may explain why social consequences of drug use (e.g., imprisonment or familial problems) do not prompt drug-addicted people to quit using the drug as well as how they contribute to increased drug use and transition from recreational drug use to addiction (9). However, whereas altered processing of monetary rewards has been reported in CUs (16), social reward processing has not been studied yet, neither on the psychological nor the neural level. Therefore, it remains elusive whether CUs (i) show behavioral differences to reward stemming from social interactions and, if so, (ii) which neural adaptations within reward circuitry underlie these potential changes in social interaction behavior.An essential part of social interaction is the phenomenon of “social gaze,” which has two aspects: Gaze can be used by the gazing person as a deictic cue to manipulate the attention of others, and can be read out by observers as a hint toward attentional focus of the gazing person (17). Both aspects can converge in joint attention (JA), which is a central element of social interaction (18) and is established when a person follows the direction of another person’s gaze so that both attend to the same object (19). Engagement in JA is considered to reflect our understanding of another person’s point of view (20). The capacity of JA emerges at 8–12 mo of age (21) and is predictive for later language learning (22) and the development of more advanced social skills such as mental perspective taking (e.g., the attribution of intentions and goals to others, also known as theory of mind) (23). Impaired JA is a core symptom of autism spectrum disorders (24).To test for social gaze differences between CUs and healthy controls (HCs), we applied a paradigm designed to capture the reciprocal and interactive nature of JA (25) (Fig. S1), where participants engage in an online interaction with an anthropomorphic virtual character in real time. Compared with self-initiated nonjoint attention (NJA; i.e., if the counterpart does not follow one’s gaze but rather pays attention to another object), self-initiated JA (i.e., if the counterpart follows one’s own gaze) is perceived as more pleasurable and associated with stronger activation of reward-related brain areas in healthy controls (25). This rewarding nature of JA might underlie the human motivation to engage in the sharing of experiences that emerges in early childhood (22, 25).It has been suggested that changes in social reward processing might underlie alterations in social behavior and cognition in CUs (9). Here we conducted two studies assessing JA processing, which constitutes an elegant approach to investigate basic social interaction patterns related to social reward processing (25), in CUs and stimulant-naïve HCs by means of behavioral, psychophysiological, and functional brain-imaging methods. In study I, a large sample of relatively pure CUs with few psychiatric comorbidities (n = 80) and stimulant-naïve HCs (n = 63) completed an interactive JA task (25) while valence and arousal ratings, error scores, reaction time, and pupil size were obtained. Pupil dilation provides an objective index of affective processing (26, 27). Based on the observations obtained in study I, we further investigated the neural correlates of the blunted emotional response to social gaze in subsamples of 16 CUs and 16 HCs using functional magnetic resonance imaging (fMRI) during an abridged version of the paradigm (study II). We hypothesized that altered emotional responses to JA are accompanied by less pronounced activation in reward-related brain areas of CUs. |
