COMMENTARY
Social cognition in cocaine addiction Antonio Verdejo-Garcia^ School of Psychological Sciences, Monash University Melbourne, VIC 3800, Australia
We humans have a hiologically hased need to form intimate personal relationships and large social networks. Social honding is evolutionarily adaptive and powerfully rewarding, whereas social isolation often results in emotional pain and harmful hehavior. However, the longing for social honding can be dampened in some mental disorders. Cocaine addiction is a potentially chronic condition associated with social isolation and breach of social rules. At the same time, successfully recovered addicts often refer to social emotions as momentous drivers for their recovery (e.g., "could not put up with my family feeling embarrassed ahout me"). Despite its relevance, the cognitive deficits underlying social deterioration and the neural systems involved in social interaction and/or disnipfion have barely heen explored in the context of addiction. In PNAS, Preller et al. (1) address these issues and demonstrate that individuals with cocaine dependence have hlunted reward response to mutual social interactions, as manifested hy flattened feelings of pleasantness, narrowed changes in pupu size, and reduced orhitofrontal cortex signal to joint gaze relative to nonjoint gaze interactions vis-à-vis with an anthropomorphic avatar (Fig. lA). In agreement with the notion that we are hardwired to forming hoth intimate and large social networks, the activation of the orhitofrontal cortex, the key hrain region for representation and weighing of reward value, was associated with the actual size of the social network of study participants (Fig. IS). Therefore, the findings from Preller et al. compeUingly suggest that cocaine addiction is associated with dampened reward response to social interaction, which ultimately impacts the richness of cocaine users' social connections.
(striatum, medial prefrontal cortex, and posterior cingulate cortex) in response to drug stimuli, coupled with significantly decreased activations in the same regions in response to sexual stimuli or monetary offers (3-5). Using an analogy, in the "addicted brain stock market," drug stocks would be continually overrated, and all competitors steadily underrated. This uneven value ultimately feedbacks value-based decisionmaking systems (the previously mentioned orbitofrontal cortex being the fundamental decision center) (6, 7), which are misled to prioritize drug seeking over natural reinforcers or related long-term goals (e.g., staying healthy or saving money) (8). The study by Preller et al. experimentally demonstrates that cocaine-dependent individuals not only underrate natural personal reinforcers hut also social interactions. Continuing with the previous rationale, underrated social interactions would similarly feedhack value-based decision-making systems (9), explaining why social bonds and social rules may lose their power to regulate behavior in cocaine-dependent users (Fig. lC). As a result, the prospect of social well-being (family réintégration and building or rebuilding of friendships) or tlie threat of social breach (harm to others and violation of law) would be less influential to guiding decisions in cocaine-dependent individuals.
The study of Preller et al. also reveals that the basic deficit behind abnormal social interaction in cocaine users is emotional. Cocaine users (unlike, for example, individuals with autism spectrum disorders) could competendy generate social interactions with their counterparts, without delays and without errors. However, they missed the bulk of These findings hlend in and enrich funda- the emotion (in this case, reward) normally mental assumptions of addiction neurosci- attached to the reciprocal social experience. ence models. The prevailing view is that We obtained simuar conclusions from a neusuhstance-related disorders represent an im- roimaging study in which a group of cocaine balance hetween the exaggerated value given users was challenged with a different type of to drugs (even after loss of originally strong social interaction task, namely moral düemrewarding effects) and the devalued appeal of mas (e.g., "would you throw a dying person a range of natural reinforcers, from food to into the sea tofloata lifeboat full of survivors?"). sex or money (2). Various neuroimaging The social decisions of cocaine users were studies have demonstrated that cocaine- generally sound and comparable to those of dependent users show increased activations controls; both groups frequently endorsed in the main regions of the hrain reward system deontological or no responses. However, the 2406-2407
| PNAS | February 18, 2014
| vol. I l l
| no. 7
Ú Joint> Non-joint
Fig. 1 . (fi) (Left) Main conditions of the social gaze task: joint attention (the participant and the avatar direct gaze in the same direction) and nonjoint attention (the participant and the avatar direct gaze in opposite directions), (Right) Cocaine users, compared with controls, showed blunted emotional response to joint vs. nonjoint attention, as manifested across multimodal measures: subjective ratings (flattened pleasantness scores on manikin analog scales), bodily indices (narrowed changes in pupil size), and brain signal (reduced orbitofrontal cortex activation). Cocaine users also experienced abnormally increased arousal (represented in the manikin's body) to joint relative to nonjoint attention. (B) Correlation between orbitofrontal cortex signal to joint vs. nonjoint attention and the size of participants' reai-life socia networks. (C) Different value representations feedback orbitofrontal cortex decision-making systems. In cocaine users, blunted representations of social reward (red callout) coupled with heightened representations of drug reward (green callout) may persistently bias decisionmaking systems toward cocaine use.
analyses of brain activations showed that whue pondering moral dilemmas, cocaine users, in contrast to controls, had significantly blunted activafion in a set of brain regions primarily involved in emofion generafion and representation, including the anterior cingulate cortex, the Ínsula, and the midbrain periaqueductal gray (10). Both these findings can be viewed
Author contributions: A.V.-G. wrote the paper. The author declares no conflict of interest. See companion article on page 2842. 'E-mail: [email protected].
www.pnas.org/cgi/doi/10.1073/pnas.1324287111
as suggestive of the existence of a basic emotional deficit impacting soeial eognition in cocaine addiction: Cocaine users can cognitively address social interaction tasks but fail to flilly experience the positive or negative emotions that soeial scenarios would typically generate. Mechanistically, it has been proposed that this deficit may be accounted by either dispositional or drug-induced difficulties to trigger or to perceive the somatic markers (bodily based emotional drivers) that evolutionarily signal the most advantageous outcomes for our decisions, including those driven to secure soeial bonding (11). To briefly illustrate this point: If during a drug-seeking opportunity the emotional signals attaehed to the prospect of letting down family and fiiends arose (e.g., feelings of embarrassment), the ehances of seeking drugs would decrease. On the other hand, if these social emotional signals were not powerfiJ enough, even if the cognitive prospect of letting people down is evoked, the chances of seeking drugs would increase. The findings of Preller et al. also bring back the relevance of social reward for addiction recovery. The link between decreased brain reward systems volume and response to social interaction and the size of soeial networks (1, 12) on addiction treatment outcomes (13) clearly advocates for nurturing of community engagement and soeial networking during cocaine addiction treatment. The most supported evidencebased intervention for cocaine addiction is contingency management, which is based on exchange of cocaine abstinence checks for personally relevant rewards (e.g., money vouchers) (14). The current findings emphasize the need to enhance this approach \'ia soeial (reciprocal interaction based) rewards. Preclinical evidence suggests these dyadic interactions can actually work as a competent alternative reward to cocaine (15). Moreover, there is a dearth of evidence-based pharmacological treatments for cocaine addiction. Clinical trials have focused on psyehostimulant substitution drugs, anti-impulsivity drugs, and cognitive enhancers, but none of them
Verdejo-Garcia
have yielded compelling outcomes (16, 17). In this regard, the current findings suggest the need to explore the novel pathway of soeial interaction boosters; for example, oxytocin has shown to increase the reward signal
toward soeial cues in experimental studies (18). Overall, it is important to note that even the best possible behavioral or pharmacological interventions could only taekle drug use for limited time periods, whereas normalization of soeial bonding-derived rewards can strengthen resilience against drug intake in a longer-term perspective. Last but not least, the study of Preller et al. raises intriguing questions for future research. A paramount question is whether soeial
reward deficits are a cause or a consequence of cocaine addietion. This very same laboratory has provided preliminary evidenee regarding this question, showing that social decision-making deficits occur in both recreational and dependent cocaine users (19), therefore suggesting social deficits are a vulnerability factor for cocaine addiction. However, it is also well known that cocaine detrimentally impacts orbitofrontal cortex functions (20), such that even recreational exposure to cocaine may impair or worsen the orbitofrontal ability to properly weigh up social bonds and social rules. Longitudinal studies are warranted to address this fascinating issue. Along the same lines, it would be relevant to determine whether social reward deficits are cocaine specific or a general characteristic of addiction or, more specifically, may these basic deficits discriminate between addictions inherently linked to major social issues vs. addictions without inherent soeial complications, such as smoking?
1 Preller KH. et al. (2014) Functional changes of the reward system underlie blunted response to social gaze in cocaine users. Proc Nati Acad Sei USA 111:2842-2847. 2 Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobioiogical basis: Neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159(10):1642-1652. 3 Asensio S, et al. (2010) Altered neural response of the appetitive emotional system in cocaine addiction: An tMRI Study. Addict Bioi 15(4):504-516. 4 Garavan H, et at (2000) Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli. Aw J Psychiatry 157(11 ): 1789-1798. 5 Goldstein RZ, et al. (2007) Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? >im./ Psychiatry 164(1):43-51. 6 Fellows LK (2011) Orbitofrontal contributions to value-based decision making: Evidence from humans with frontal lobe damage. Arm N Y Acad Sei 1239:51-58. 7 Levy DJ, Glimcher PVii (2012) The root of all value: A neural common currency for choice. Curr Opin Neurobioi 22(6): 1027-1038. 8 Bechara A (2005) Decision making, impulse control and loss of willpower to resist drugs: A neurocognitive perspective. Nat Neurosci 8(11):1458-1463. 9 Azzi JC, Sirigu A, Duhamel JR (2012) Modulation of value representation by social context in the primate orbitofrontal cortex. Proc Nati Acad Sei USA 1O9(6):2126-2131. 10 Verdejo-Garcia A, et ai. (2012) Funaional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects
[published online ahead of print July 11, 2012]. Addict Biol, 10.1111/j.1369-1600.2012.00472.x. 11 Verdejo-Garcia A, Bechara A (2009) A somatic marker theory of addiction. Neuropharmacobgy 56(Suppl l):48-62. 12 Lewis PA, Rezaie R, Brown R, Roberts N, Dunbar Rl (2011) Ventromediai prefrontal volume predicts understanding of others and social network size. Neuroimage 57(4):1624-1629. 13 Kaskutas LA. Bond J, Humphreys K (2002) Social networks as mediators of the effect of Alcoholics Anonymous. Addiction 97(7): 891-900. 1 4 Dutra L, et al. (2008) A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry 165(2): 179-187. 15 Zernig G, Kummer KK, Prast JM (2013) Dyadic social interaction as an alternative reward to cocaine. Front Psychiatry 4:100. 16 Castells X, et al. (2010) Efficacy of psychostimulant drugs for cocaine dependence. Cochrane Database Syst Rev (2):CD007380. 17 Sofuoglu M, DeVito EE, Waters AJ, earroii KM (2013) Cognitive enhancement as a treatment for drug addictions. Neuropharmacoiogy 64:452-463 18 Groppe SE, et ai. (2013) Oxytocin infiuences processing of sociaiiy reievant cues in the ventrai tegmentai area of the human brain. Biol Psychiatry 74(3): 172-179. 19 Hulka LM, et al. (2013) Altered sociai and non-social decisionmaking in recreational and dependent cocaine users [published online ahead of print July 22, 2013]. Psychol Med, 10.1017/ S0033291713001839. 2 0 Lucantonio F, Stainaker TA, Shaham Y, Niv Y, Schoenbaum G (2012) The impact of orbitofrontai dysfunction on cocaine addiction, «oí Neurosci 15(3):358-366.
A paramount question is whether social reward deficits are a cause or a consequence of cocaine addiction.
PNAS I February 18.2014
| vol. 111 ¡ no. 7 | 2407
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academies Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Social cognition in cocaine addiction Antonio Verdejo-Garcia^ School of Psychological Sciences, Monash University Melbourne, VIC 3800, Australia
We humans have a hiologically hased need to form intimate personal relationships and large social networks. Social honding is evolutionarily adaptive and powerfully rewarding, whereas social isolation often results in emotional pain and harmful hehavior. However, the longing for social honding can be dampened in some mental disorders. Cocaine addiction is a potentially chronic condition associated with social isolation and breach of social rules. At the same time, successfully recovered addicts often refer to social emotions as momentous drivers for their recovery (e.g., "could not put up with my family feeling embarrassed ahout me"). Despite its relevance, the cognitive deficits underlying social deterioration and the neural systems involved in social interaction and/or disnipfion have barely heen explored in the context of addiction. In PNAS, Preller et al. (1) address these issues and demonstrate that individuals with cocaine dependence have hlunted reward response to mutual social interactions, as manifested hy flattened feelings of pleasantness, narrowed changes in pupu size, and reduced orhitofrontal cortex signal to joint gaze relative to nonjoint gaze interactions vis-à-vis with an anthropomorphic avatar (Fig. lA). In agreement with the notion that we are hardwired to forming hoth intimate and large social networks, the activation of the orhitofrontal cortex, the key hrain region for representation and weighing of reward value, was associated with the actual size of the social network of study participants (Fig. IS). Therefore, the findings from Preller et al. compeUingly suggest that cocaine addiction is associated with dampened reward response to social interaction, which ultimately impacts the richness of cocaine users' social connections.
(striatum, medial prefrontal cortex, and posterior cingulate cortex) in response to drug stimuli, coupled with significantly decreased activations in the same regions in response to sexual stimuli or monetary offers (3-5). Using an analogy, in the "addicted brain stock market," drug stocks would be continually overrated, and all competitors steadily underrated. This uneven value ultimately feedbacks value-based decisionmaking systems (the previously mentioned orbitofrontal cortex being the fundamental decision center) (6, 7), which are misled to prioritize drug seeking over natural reinforcers or related long-term goals (e.g., staying healthy or saving money) (8). The study by Preller et al. experimentally demonstrates that cocaine-dependent individuals not only underrate natural personal reinforcers hut also social interactions. Continuing with the previous rationale, underrated social interactions would similarly feedhack value-based decision-making systems (9), explaining why social bonds and social rules may lose their power to regulate behavior in cocaine-dependent users (Fig. lC). As a result, the prospect of social well-being (family réintégration and building or rebuilding of friendships) or tlie threat of social breach (harm to others and violation of law) would be less influential to guiding decisions in cocaine-dependent individuals.
The study of Preller et al. also reveals that the basic deficit behind abnormal social interaction in cocaine users is emotional. Cocaine users (unlike, for example, individuals with autism spectrum disorders) could competendy generate social interactions with their counterparts, without delays and without errors. However, they missed the bulk of These findings hlend in and enrich funda- the emotion (in this case, reward) normally mental assumptions of addiction neurosci- attached to the reciprocal social experience. ence models. The prevailing view is that We obtained simuar conclusions from a neusuhstance-related disorders represent an im- roimaging study in which a group of cocaine balance hetween the exaggerated value given users was challenged with a different type of to drugs (even after loss of originally strong social interaction task, namely moral düemrewarding effects) and the devalued appeal of mas (e.g., "would you throw a dying person a range of natural reinforcers, from food to into the sea tofloata lifeboat full of survivors?"). sex or money (2). Various neuroimaging The social decisions of cocaine users were studies have demonstrated that cocaine- generally sound and comparable to those of dependent users show increased activations controls; both groups frequently endorsed in the main regions of the hrain reward system deontological or no responses. However, the 2406-2407
| PNAS | February 18, 2014
| vol. I l l
| no. 7
Ú Joint> Non-joint
Fig. 1 . (fi) (Left) Main conditions of the social gaze task: joint attention (the participant and the avatar direct gaze in the same direction) and nonjoint attention (the participant and the avatar direct gaze in opposite directions), (Right) Cocaine users, compared with controls, showed blunted emotional response to joint vs. nonjoint attention, as manifested across multimodal measures: subjective ratings (flattened pleasantness scores on manikin analog scales), bodily indices (narrowed changes in pupil size), and brain signal (reduced orbitofrontal cortex activation). Cocaine users also experienced abnormally increased arousal (represented in the manikin's body) to joint relative to nonjoint attention. (B) Correlation between orbitofrontal cortex signal to joint vs. nonjoint attention and the size of participants' reai-life socia networks. (C) Different value representations feedback orbitofrontal cortex decision-making systems. In cocaine users, blunted representations of social reward (red callout) coupled with heightened representations of drug reward (green callout) may persistently bias decisionmaking systems toward cocaine use.
analyses of brain activations showed that whue pondering moral dilemmas, cocaine users, in contrast to controls, had significantly blunted activafion in a set of brain regions primarily involved in emofion generafion and representation, including the anterior cingulate cortex, the Ínsula, and the midbrain periaqueductal gray (10). Both these findings can be viewed
Author contributions: A.V.-G. wrote the paper. The author declares no conflict of interest. See companion article on page 2842. 'E-mail: [email protected].
www.pnas.org/cgi/doi/10.1073/pnas.1324287111
as suggestive of the existence of a basic emotional deficit impacting soeial eognition in cocaine addiction: Cocaine users can cognitively address social interaction tasks but fail to flilly experience the positive or negative emotions that soeial scenarios would typically generate. Mechanistically, it has been proposed that this deficit may be accounted by either dispositional or drug-induced difficulties to trigger or to perceive the somatic markers (bodily based emotional drivers) that evolutionarily signal the most advantageous outcomes for our decisions, including those driven to secure soeial bonding (11). To briefly illustrate this point: If during a drug-seeking opportunity the emotional signals attaehed to the prospect of letting down family and fiiends arose (e.g., feelings of embarrassment), the ehances of seeking drugs would decrease. On the other hand, if these social emotional signals were not powerfiJ enough, even if the cognitive prospect of letting people down is evoked, the chances of seeking drugs would increase. The findings of Preller et al. also bring back the relevance of social reward for addiction recovery. The link between decreased brain reward systems volume and response to social interaction and the size of soeial networks (1, 12) on addiction treatment outcomes (13) clearly advocates for nurturing of community engagement and soeial networking during cocaine addiction treatment. The most supported evidencebased intervention for cocaine addiction is contingency management, which is based on exchange of cocaine abstinence checks for personally relevant rewards (e.g., money vouchers) (14). The current findings emphasize the need to enhance this approach \'ia soeial (reciprocal interaction based) rewards. Preclinical evidence suggests these dyadic interactions can actually work as a competent alternative reward to cocaine (15). Moreover, there is a dearth of evidence-based pharmacological treatments for cocaine addiction. Clinical trials have focused on psyehostimulant substitution drugs, anti-impulsivity drugs, and cognitive enhancers, but none of them
Verdejo-Garcia
have yielded compelling outcomes (16, 17). In this regard, the current findings suggest the need to explore the novel pathway of soeial interaction boosters; for example, oxytocin has shown to increase the reward signal
toward soeial cues in experimental studies (18). Overall, it is important to note that even the best possible behavioral or pharmacological interventions could only taekle drug use for limited time periods, whereas normalization of soeial bonding-derived rewards can strengthen resilience against drug intake in a longer-term perspective. Last but not least, the study of Preller et al. raises intriguing questions for future research. A paramount question is whether soeial
reward deficits are a cause or a consequence of cocaine addietion. This very same laboratory has provided preliminary evidenee regarding this question, showing that social decision-making deficits occur in both recreational and dependent cocaine users (19), therefore suggesting social deficits are a vulnerability factor for cocaine addiction. However, it is also well known that cocaine detrimentally impacts orbitofrontal cortex functions (20), such that even recreational exposure to cocaine may impair or worsen the orbitofrontal ability to properly weigh up social bonds and social rules. Longitudinal studies are warranted to address this fascinating issue. Along the same lines, it would be relevant to determine whether social reward deficits are cocaine specific or a general characteristic of addiction or, more specifically, may these basic deficits discriminate between addictions inherently linked to major social issues vs. addictions without inherent soeial complications, such as smoking?
1 Preller KH. et al. (2014) Functional changes of the reward system underlie blunted response to social gaze in cocaine users. Proc Nati Acad Sei USA 111:2842-2847. 2 Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobioiogical basis: Neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159(10):1642-1652. 3 Asensio S, et al. (2010) Altered neural response of the appetitive emotional system in cocaine addiction: An tMRI Study. Addict Bioi 15(4):504-516. 4 Garavan H, et at (2000) Cue-induced cocaine craving: Neuroanatomical specificity for drug users and drug stimuli. Aw J Psychiatry 157(11 ): 1789-1798. 5 Goldstein RZ, et al. (2007) Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? >im./ Psychiatry 164(1):43-51. 6 Fellows LK (2011) Orbitofrontal contributions to value-based decision making: Evidence from humans with frontal lobe damage. Arm N Y Acad Sei 1239:51-58. 7 Levy DJ, Glimcher PVii (2012) The root of all value: A neural common currency for choice. Curr Opin Neurobioi 22(6): 1027-1038. 8 Bechara A (2005) Decision making, impulse control and loss of willpower to resist drugs: A neurocognitive perspective. Nat Neurosci 8(11):1458-1463. 9 Azzi JC, Sirigu A, Duhamel JR (2012) Modulation of value representation by social context in the primate orbitofrontal cortex. Proc Nati Acad Sei USA 1O9(6):2126-2131. 10 Verdejo-Garcia A, et ai. (2012) Funaional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects
[published online ahead of print July 11, 2012]. Addict Biol, 10.1111/j.1369-1600.2012.00472.x. 11 Verdejo-Garcia A, Bechara A (2009) A somatic marker theory of addiction. Neuropharmacobgy 56(Suppl l):48-62. 12 Lewis PA, Rezaie R, Brown R, Roberts N, Dunbar Rl (2011) Ventromediai prefrontal volume predicts understanding of others and social network size. Neuroimage 57(4):1624-1629. 13 Kaskutas LA. Bond J, Humphreys K (2002) Social networks as mediators of the effect of Alcoholics Anonymous. Addiction 97(7): 891-900. 1 4 Dutra L, et al. (2008) A meta-analytic review of psychosocial interventions for substance use disorders. Am J Psychiatry 165(2): 179-187. 15 Zernig G, Kummer KK, Prast JM (2013) Dyadic social interaction as an alternative reward to cocaine. Front Psychiatry 4:100. 16 Castells X, et al. (2010) Efficacy of psychostimulant drugs for cocaine dependence. Cochrane Database Syst Rev (2):CD007380. 17 Sofuoglu M, DeVito EE, Waters AJ, earroii KM (2013) Cognitive enhancement as a treatment for drug addictions. Neuropharmacoiogy 64:452-463 18 Groppe SE, et ai. (2013) Oxytocin infiuences processing of sociaiiy reievant cues in the ventrai tegmentai area of the human brain. Biol Psychiatry 74(3): 172-179. 19 Hulka LM, et al. (2013) Altered sociai and non-social decisionmaking in recreational and dependent cocaine users [published online ahead of print July 22, 2013]. Psychol Med, 10.1017/ S0033291713001839. 2 0 Lucantonio F, Stainaker TA, Shaham Y, Niv Y, Schoenbaum G (2012) The impact of orbitofrontai dysfunction on cocaine addiction, «oí Neurosci 15(3):358-366.
A paramount question is whether social reward deficits are a cause or a consequence of cocaine addiction.
PNAS I February 18.2014
| vol. 111 ¡ no. 7 | 2407
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academies Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
