Cognitive, Clinical, and Neural Aspects of Drug Addiction

By Ahmed Moustafa

Drug addictions are often difficult to treat. The most successful treatments begin with studying why individuals become addicted to drugs and how to change their thinking and behaviour. Cognitive, Clinical, and Neural Aspects of Drug Addiction focuses on the theories that cause drug addiction, including avoidance behavior, self-medication, reward sensitization, behavioral inhibition and impulsivity. Dr. Moustafa takes this book one step further by reviewing the psychological and neural causes of relapse including the role of stress, anxiety and depression. By examining both the causes of drug addiction and relapse, this book will help clinicians create individualized treatment options for patients suffering from drug addiction.

• Identifies key factors contributing to addiction, including stress, anxiety and depression
• Reviews inhibition and impulsivity in drug use
• Assesses the cognitive underpinnings of behavioral choices in addiction
• Discusses the argument of self-medication vs. reward sensitization
• Examines the psychological causes of why patients relapse

• Language: English
• Publisher: Academic Press
• Release date: Jan 10, 2020
• ISBN: 9780128169803

Ahmed Moustafa

Dr. Ahmed Moustafa is a Professor of Psychology and Computational Modeling at School of Psychology, Bond University, Gold Coast, Queensland, Australia. Prior to moving to Bond University, Ahmed was an associate professor in Psychology and Neuroscience at Marcs Institute for Brain, Behavior, and Development & School of Psychology, Western Sydney University. Ahmed is trained in computer science, psychology, neuroscience, and cognitive science. His early training took place at Cairo University in mathematics and computer science. Before joining Western Sydney University as a lab director, Ahmed spent 11 years in America working on several psychology and neuroscience projects. Ahmed conducts research on computational and neuropsychological studies of addiction, schizophrenia, Parkinson’s disease, PTSD, depression, Alzheimer’s disease. He has published over 240 papers in high-ranking journals including Science, PNAS, Journal of Neuroscience, Brain, Neuroscience and Biobehavioral Reviews, Nature (Parkinson’s disease), Neuron, among others. Ahmed has obtained grant funding from Australia, USA, Qatar, UAE, Turkey, and other countries. Ahmed has recently published ten books: (1) Computational models of brain and behavior; (2) Social Cognition in Psychosis, (3) computational Neuroscience Models of the Basal Ganglia, (4) Cognitive, Clinical, and Neural Aspects of Drug Addiction; (5) The Nature of Depression: An updated review; (6) Big data in psychiatry and neurology; (7) Alzheimer’s Disease: Understanding Biomarkers, Big Data, and Therapy. Elsevier; (8) Cognitive and Behavioral Dysfunction in Schizophrenia; (9) Female Pioneers from Ancient Egypt and the Middle East; and (10) Mental health effects of COVID-19. In the last 10 years, Ahmed has published collaboratively with 71 colleagues, has more than 510 co-authors, from 35 institutions in 14 countries. Ahmed is now Editor-in-Chief of Discover Psychology, a new journal by Springer Nature.

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Baetu.

Part I

Cognitive and learning aspects of drug addiction

Chapter 1

Executive functioning and substance use disorders

Bruno Kluwe-Schiavona; Breno Sanvicente-Vieirab; Thiago Wendt Violab; Ahmed A. Moustafac    a Experimental and Clinical Pharmacopsychology Laboratory, Department of Psychiatry, Psychotherapy, and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland

b Developmental Cognitive Neuroscience Laboratory, Faculty of Psychology, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

c Marcs Institute for Brain, Behaviour, and Development and School of Psychology, Western Sydney University, Penrith, NSW, Australia

Abstract

Executive functioning has been extensively studied over the past six decades and can be defined as a dynamic multifaceted construct that includes different but intercorrelated processes that aimed to self-regulate stress and cognitive engagement, enabling individuals to learn by experience. Substance-related disorders (SUD) are mainly characterized as a chronic self-regulatory disease where individuals engage in reward-seeking situations despite of the adverse consequences, shifting from impulsive to compulsive drug-seeking behaviors. It has been suggested that SUD are related to the failure to balance cognitive engagement (e.g., self-control, behavior inhibition, cognitive flexibility) over stressful demands (e.g., craving or coping with daily-stressful events). This imbalance leads to alterations on the main processes of decision-making (i.e. representation of adaptive behaviors, valuation of choices, goal-oriented action selection, feedback processing and updating), which are related to changes in both cortical and subcortical neural structures. This book chapter firstly highlight the concept of executive functioning and discuss how SUD are related to alterations in brain structures usually associated with executive performance. Additionally, we describe recent evidence on the role of dopaminergic system and how SUD can be described as a biopsychosocial executive functioning disorder.

Keywords

Addiction; Substance use; Drug abuse; Executive function; Cognition; Decision-making

The concept of executive functioning

Executive functioning has been extensively studied in prior psychological research over the past six decades. Some of the key studies in this area include those of the British experimental psychologist Donald E. Broadbent (1926–93) and the American psychologist Michael I. Posner (1936–) on attentional processing, and the studies of the Russian neuropsychologist Alexander Luria (1902–77) regarding the frontal lobes and the hierarchical organization of brain functioning (Freeman, 1967; Luria, 1965, 1970). What do these authors have in common? Broadly speaking, their work highlighted a variety of behaviors that were accepted to be driven by high-order cognitive processes and lately become to be known, for instance, as inhibitory control, attention shifting, working memory, goal-directed behavior, and strategic planning. Although several executive functioning models and theories have emerged since then (Goldstein, Naglieri, Princiotta, & Otero, 2014), such idea remains, and executive functioning has become a multifaceted mental concept that includes more than 30 different components (Barkley, 2012), in which the prefrontal cortex (PFC) and its related structures are still the main neuroanatomical counterpart.

The hierarchical framework of executive functioning and the PFC has its roots on two main fields. Based on a neuroscience view, the role of the PFC in executive functioning emerged with observations of patients who had suffered frontal lobe lesions becoming unable to manipulate, integrate, and respond to internal and external stimulus. In other words, these patients seem to have lost the capacity of prospecting future actions and making reasonable decisions as before, showing difficulties in moderating social behavior and, ultimately, changing their usual personality expression in detriment of impulsive and disinhibit traits (Harlow, 1868). Based a psychological view, the role of PFC in executives functioning was intimately related to the cognitive revolution in the 1950s as an attempt to understand how information is processed by the mind. In this regard, several experimental models on information processing emerged to explain selective attention and multistore memory processes (e.g. the bottleneck theory of attention and the three-component model). These models, however, were not able to explain how information is deliberatively selected or inhibited during demanding tasks and, therefore, the concept of cognitive control was introduced to fulfil this gap (Goldstein et al., 2014), while concurrently phenomenologically explaining behavior attributed to the PFC.

With the advent of functional imaging techniques and neuroscience, the exclusive role of the PFC becomes a matter of ongoing debate over the last 20 years (Kluwe-Schiavon, Viola, Sanvicente-Vieira, Malloy-Diniz, & Grassi-Oliveira, 2016; Miyake et al., 2000), but it has been accepted that the participation of the frontal lobes in virtually any ‘executive process’ is probably a necessary, but largely insufficient, requirement (Alvarez & Emory, 2006). Thus, as described by the Alvarez and Emory (2006), executive functioning involves the coordination of activity among diffuse anatomical and functional brain areas, with the frontal lobes associated with executive functioning sensitivity, rather than specificity. The idea that PFC might contribute to executive functioning is vastly well-accepted, since it has been shown that executive functioning skills reach their peak at age 20–29, in association with the constant myelination of neurons in the prefrontal cortex (Best & Miller, 2010). Such finding also contributes to elucidate another debate, supporting the idea that executive functioning constitutes related, but distinct, multifaceted processes, instead of one single underlying ability that can explain all the components (Jurado & Rosselli, 2007).

The self-regulatory model the Lezak’s four-component conceptual model (Lesak, 1982) and the three component conceptual model of Diamond (Diamond, 2013), are some of the most influential multifaceted models of executive functioning. Barkley (2001) focused on the evolutionary role of executive functioning and social contexts, and according to him, it serves to shift the control of behavior from the immediate context, social others, and the temporal now to self-regulation by internal representations regarding the hypothetical social future. More than that, Barkley pinpoints that executive functioning may have evolved to solve some social adaptive problems such as reciprocal altruism or selfish cooperation, highlighting the crucial role of self-regulation. On the other hand, Lezak proposed simple, but pragmatic, framework where volition, planning, purposeful action, and effective performance are the main core executive functioning processes that enable a person to engage successfully in independent, purposive, and self-serving behavior. This model is broadly used by clinicians and researchers, since it allows us to identify and assess its components. Along the same lines, Diamond (2013) suggested that executive functioning can be described as a family of top-down mental processes recruited when automatic, instinct or intuition would be insufficient to cope with an ongoing demand, emphasizing its role as a self-regulatory process, which is in agreement with Barkley’s model. According to Diamond (2013), the main functions are behavioral/cognitive inhibition (including selective attention), working memory, and cognitive flexibility. Several other models have also been reported in the literature. For example, the Miyake and Friedman’s model is based on latent variable analysis that suggested both the unity and diversity aspects of executive functioning, emphasizing updating, inhibition, and shifting as it processes (Miyake et al., 2000); or the dual-processing frameworks and its branches that have been extensively used to differentiate emotional hot processes from rational cold processes and to describe cognitive changes associated with psychiatric disorders and/or neurodevelopment (Kahneman, 2003, 2011; Noël, Brevers, & Bechara, 2013; Zelazo & Carlson, 2012).

Nevertheless, in this chapter, rather than describing different models, we will assume that executive functioning is a dynamic multifaceted construct that, consequently, includes different but intercorrelated processes that aimed to self-regulate (or balance) stress and cognitive engagement, enabling individuals to learn by experience inasmuch as they internalize efficient behaviors and use such information to prospect a set of new behaviors and their most likely consequences (Kluwe-Schiavon, Viola, Sanvicente-Vieira, Malloy-Diniz, & Grassi-Oliveira, 2016). Such broad perspective allows us to go beyond the discussion on which specific executive functioning component some neuropsychological test is depicting, by understanding that any highly complex behavior, such as decision-making and theory of mind, demands an efficient executive functioning performance. Here, therefore, we will discuss how substance related disorders (SUD) might impair executive functioning over a series of different perspectives.

Substance use disorders and executive dysfunction

Nonetheless, one may ask, why should we look for specific deficits of executive functioning associated with addictive disorders? Initially, it is widely well-known that addictive disorders are clinically characterized as the compulsive engagement in rewarding stimuli despite the adverse consequences. Hence, non-substance related or behavioral addictions refer to compulsive engagement in rewarding behaviors, for instance, sex, gambling, video-game or internet, and shopping. Here, we will focus on SUD, which refer to a pattern of substance consumption in which the user consumes the substance in quantities or with methods which are harmful to themselves or others. Therefore, phenomenologically speaking, one could characterize SUD as a chronic decision-making and self-regulatory disease, since both the onset of substance use and the maintenance of additive behaviors are characterized by the failure of balancing highly stressful demands (e.g. craving or coping with daily-stressful events) and cognitive/behaviors inhibition, culminating on the engagement in rewarding drug-seeking behaviors despite their adverse consequences (George & Koob, 2010). This understanding is strengthened by studies that suggest that critical cortical and subcortical neural structures related to executive functioning performance are gradually compromised in these pathologies, increasing the frequency of impulsive and compulsive search for the substance (Goldstein & Volkow, 2011; Peterson & Welsh, 2014).

As it is not yet clear what the conceptual borders that distinguish the conceptual definitions of executive functioning and decision-making or how worthful such conceptual differentiation would be, to approach how SUD are related to executive functioning alterations based on the broad executive functioning perspective we assumed, we will also accept that decision-making processes (representation of choices and valuation processing, action selection, outcome evaluation and updating) (Rangel, Camerer, & Montague, 2008), may demand the core executive functioning processes, such as planning, set-shifting, inhibition of non-adaptive choice selection and updating. Therefore, as mentioned above, the coordination of all these processes (e.g. valuation processing, action selection, outcome evaluation and updating) is not mainly done by the PFC, although the PFC plays a crucial role on their efficiency. For instance, two meta-analyses revealed that SUD patients have functional alterations in brain structures highly associated to planning and representation of options, such as the ventral striatum and the anterior cingulate cortex (ACC) (Kuhn & Gallinat, 2011). The ACC lies in a unique position in the brain, connecting the emotional limbic system and the cognitive PFC, being associated to the ability to control and manage uncomfortable emotions (Stevens, Hurley, & Taber, 2011). In addition, not only because its spatial position, but also because its functions, the ACC plays role in shifting between salience and control networks (Menon & Uddin, 2010). The salience network relates to implicit processing and identification of relevant stimuli and events while the control network relates to explicit executive processing. Although it is not totally clear, together with the insula, the ACC is hypothesized to play as a gatekeeper, implicitly selecting important stimuli for attention and explicitly avoiding irrelevant information (Menon & Uddin, 2010).

Positron emission tomography (PET) studies showed that the right dorsal ACC dopamine neurotransmission—critical for the rewarding effects of drugs and the key neurotransmitter involved in several addiction models (Bickel et al., 2018)—increases significantly during the performance of certain executive processes, such as conflict monitoring and set-shifting (Abenavoli, Greenberg, & Bierman, 2017). Using a unique hair toxicology approach to objectively characterize substance use over the past 6 months and proton magnetic resonance spectroscopy (H-MRS), Hulka et al. (2014) revealed that higher cocaine hair concentrations were associated with lower glutamine ratios in the ACC, indicating that cocaine can be related to changes in glutamate cycling and functional alteration of this brain region. Thus, in a decision-making perspective, it has been hypothesized that the ACC alterations observed in people with SUD are associated with a failure to exert control over the selection of the appropriate behaviors when facing a long and possibly uncertain sequence of actions (Peoples, 2002). More than that, changes in the activity of the ACC, together with the insular cortex may explain, for example, the difficulty of chronic users in representing more adaptive and functional options to replace drug-seeking behaviors, especially during periods of stress, withdrawal symptoms, or severe fissures (Naqvi & Bechara, 2010).

The valuation of choices is a decision-making process that can be closely related to cognitive flexibility and set shifting, as it is crucial for setting goals. In decision behavior theory, we say that during the valuation phase people will attribute a subjective value (known as expected utility) to those options that were previously identified (i.e. represented) and, afterwards, these values will be compared to each other, triggering the behavior of chosen the highest rated option. Interestingly, evidence shows that individuals with SUD are less sensitive to the valuation processing of potentially positive (e.g., earning more money on the task) or potentially negative (e.g., the physical and emotional impact of their use) outcomes in daily life situations (Konova et al., 2012). However, the valuation phase is not directly associated with PFC structures, but mainly to subcortical structures such as the nucleus accumbens (NAc) and the amygdala (Gilman et al., 2014).

If the NAc can be described as the centre of the pleasure and reward learning, the amygdala can be described as the centre of fear and aversive conditioning in the brain. From a cognitive neuroscience perspective based on a decision behavior theory, we can say that the amygdala encodes and responds to risks and the magnitude of losses. In this regard, some studies have shown that cannabis dependent users have a lower volume of NAc when compared to non-users (Yucel et al., 2008), and that even recreational marijuana users may present morphological and volumetric abnormalities in both NAc and amygdala compared to non-users (Gilman et al., 2014), wherein some of these changes being observable already in adolescent users (Padula, McQueeny, Lisdahl, Price, & Tapert, 2015). In a recent study, Augier et al. (2018) showed that animals that chose alcohol over a high-value alternative (rewarding concentration of the non-caloric sweetener saccharin) despite adverse consequences have lower expression of a specific GABA transporter (GAT-3) in the amygdala. The authors went further, showing that increased GABAergic tone in the amygdala due to reduced GABA uptake by GAT-3 transporters contributes to behaviors that are key for alcohol addiction, advocating for a causal contribution of neuroadaptations on the amygdala to the development of alcohol addiction (Augier et al., 2018).

Such studies highlight the role of different neurotransmitters on SUD, complementing the understanding of it with new theories and hypotheses (Bickel et al., 2018). However, the mesolimbic and the mesocortical projections from ventral tegmental area (VTA) into the basal ganglia and the PFC, respectively, make these regions the highest concentrations of dopamine within the brain and crucial for the valuation of rewarding stimuli and learning. Therefore, before describing how SUD are related to alterations on action selection and motivation, and feedback processing and updating, a brief note about the dopaminergic system and it relations with executive functioning is necessary.

The role of dopamine in executive dysfunction in SUD

A common characteristic of addictive drugs is their capacity to reinforce behavior and to act as powerful rewards when these substances reach the central nervous system. The simple notion that drugs of abuse produce rewarding and reinforcing effects in the brain has been elegantly demonstrated in animal self-administration studies. In this regard, cocaine, amphetamine, nicotine, opiates, cannabis and alcohol have the ability to enhance endogenous DA neurotransmission, primarily in the NAc, that consequently leads to enhanced stimulation of DA receptors located on medium spiny neurons (Asensio et al., 2010; Galaj, Ewing, & Ranaldi, 2018; Kalivas & Volkow, 2005; Satel et al., 1991; Yap & Miczek, 2008). To be noted, the NAc is a core region of the brain’s reward system, which is an evolutionarily conserved brain network that underlies basic motivational processes activated by survival- and reproduction-related stimuli (McClure & Bickel, 2014).

Paradigms such as the delay discounting, which is a robust neuropsychological task, has been successfully converted to use in rodent studies (Tedford, Persons, & Napier, 2015), and it has been the basis of some important studies that explored the relation between dopamine, decision-making and executive functioning. The basic premise of the delay discounting task is to choose between obtaining an immediate reward of lesser value in relation to the waiting required to obtain a reward of highest value (Pine, Shiner, Seymour, & Dolan, 2010). In rodents, this task is performed in operant conditioning chamber, allowing the animal to choose between two rewarding options: a single sugar pellet with no presentation delay, or three sugar pellets with a delay interval between 10 and 60 s (Saddoris et al., 2015).

In a remarkable set of experiments, one recent study demonstrated the role of dopaminergic neurotransmission in mesocorticolimbic pathways, defining its causal role for inhibitory control in reward-related situations (Saddoris et al., 2015). Initially, bilateral cannulas were implanted into the NAc of adult rats, and, using fast-scan cyclic voltammetry technology, dopamine release levels were recorded with a time accuracy of millisecond. Before reward collection, particularly during the expectation and anticipation of obtaining a reward, animals had a very high dopaminergic release in the NAc, and such release was even more intense in view of the expectation of obtaining the highest reward. Subsequently, the authors investigated the role of dopaminergic stimulation via the implantation of optogenetic cannulae in the NAc, which allows for a precise and dynamic control of a signaling pathway. They observed that the increase in dopamine release artificially, particularly during the anticipation period, induced rats to choose the highest reward regardless of how long they had to wait for it. Therefore, these experiments provided evidence that cues that predict a reinforcing stimulus during the delay discounting task also modulated extra synaptic dopamine concentrations in the NAc, energizing motivation and modulating decision-making (Volkow, Wise, & Baler, 2017). More than that, it was shown that dopamine has an important role on inhibitory control during decision-making processes.

This mechanism is also implicated in the neurobiology of how drugs of abuse trigger strong behavioral and psychological responses immediately after exposure to drug-related cues. Stimuli (including contextual or environmental) associated with the drug effects become conditioned and, with repeated co-exposure, will trigger dopamine neuronal firing in the NAc. This increased dopaminergic signaling that follows exposure to drug-related cues ensures that an individual will have the necessary motivation to engage in drug-seeking behaviors (Volkow & Morales, 2015). However, neuroplastic changes in midbrain dopamine neurons associated with chronic drug exposure may also result in less inhibitory control, which is extremely necessary to cope with the craving elicited by drug or reward-related cues (Volkow et al., 2017).

These observations led researches to establish a critical role for dopamine during valuation processing, since dopamine release before a goal-directed behavior is a key mechanisms underlying action selection that drives an individual to choose a given option/behavior associated with a potential outcome (Volkow et al., 2017). More than that, altered dopaminergic signaling has been directly related to impulsivity and impairments in executive functioning and decision-making among people with SUD (McClure & Bickel, 2014). For instance, impulsivity in the delay discounting task was observed among individuals who are drug dependents, as well as in those individuals at a high-risk of developing SUD during early stages of drug use behavior (Bickel, Koffarnus, Moody, & Wilson, 2014; Hulka et al., 2014). However, the complexities of the behavioral and neurobiological factors underlying SUD created enormous challenges in efforts to develop effective pharmacological treatments targeting dopaminergic signaling. In this regard, traditional approaches that have focused on blocking selective dopaminergic receptors provided encouraging results in animal models of addiction, but the clinical utility of these agents has been limited due to the side effects they might produce (Galaj et al., 2018).

Action selection, feedback processing and updating

Once the individual has identified a number of options and assigned a subjective value to them, the PFC and its substructures (ventromedial portion, vmPFC, dorsolateral portion, dlPFC, and orbitofrontal cortex, OFC) integrate all information, inhibit inappropriate behaviors and drive goal-oriented ones. Accordingly, a study investigating the neural network involved in the transformation of stimulus values into motor responses found that in healthy individuals the magnitude of costs and benefits are computed in both the vmPFC and the dlPFC and that the resulting signaling of this comparison modulates the activity of the motor cortex and the cerebellum (Wunderlich, Rangel, & O’Doherty, 2009), suggesting that the resulting signaling might be related to motivation and volition. In addition, it is largely accepted that the dlPFC is strongly associated to behavioral inhibition and that this process is independent of the participant’s conscious evaluation of the situation they are judging (Büchel et al., 2017). Remarkably, such independency is often reported by individuals with SUD, who usually report not being able to inhibit substance-seeking behaviors despite of being aware of the risks involved. Usually, behavioral disinhibition is observed during delayed gratification tasks in which individuals must inhibit the behavior of choosing an immediate but low value reward in detriment of a late, but higher value reward. Not surprisingly, several studies already show that people with SUD and non-substance related disorders perform worse than people with no SUD (Alvarez & Emory, 2006; Amlung, Vedelago, Acker, Balodis, & MacKillop, 2017; MacKillop et al., 2011). Cocaine-dependent patients who underwent repeated sessions of high-frequency transcranial magnetic stimulation (TMS) in the right dlPFC (which leads to an excitatory effect of this region) had significant reductions in craving and a lower relapse rates when compared to a placebo control group (Terraneo et al., 2016).

As we mentioned above, the concepts of executive functioning also comprise the idea that individuals must be able to learn by experience, in such way that feedback processing and updating are central aspects of many executive functioning models. In this regard, many studies have been using neuropsychological paradigms, such as the Iowa Gambling Task (IGT) (Bechara, Damasio, & Damasio, 2000) to investigate feedback processing and implicit probabilistic learning (Ekhtiari, Victor, & Paulus, 2017). The IGT is a card game that assesses the ability to evaluate immediate gains over long-term losses. In this sense, individuals are instructed that the object of the task is to accumulate as much money as possible by picking one card at a time from any of four decks (A, B, C, and D) until the instruction is given to stop. The task ends when the individual has chosen 100 cards. However, the card decks differ along three dimensions: the immediate gain, the expected long-term gain and the schedule of penalties. All the cards from Decks A and B yield a larger short-term reward ($100 per card) than cards from Decks C and D ($50 per card). Certain cards in all of the decks also carry a penalty, and the accumulated penalties in Decks A and B are larger than in Decks C and D. Over the long run, continued choice from either Deck C or D leads to a net gain ($250/10 cards), whereas choice from either Deck A or B leads to a net loss ($250/10 cards). Therefore, Decks A and B are considered disadvantageous decks, while decks C and D are considered advantageous (Grant, Contoreggi, & London, 2000). The inspiring work done by Bechara et al. (2000) identified the first clues regarding how the human brain performs and mediates the processes of judgment and decision-making, given some important insights on how impairments in these processes might lead to impulsive behaviors. By using the IGT, the authors demonstrated that patients with PFC lesions, particularly in the vmPFC, had poor performance in this task, depicted by frequent choices of cards that generated high reward monetary values, but in the long run, resulted in consistent monetary losses (Verdejo-García & Bechara, 2009).

In the early 2000s, one of the first investigations with the IGT and with individuals with SUD was published (Grant et al., 2000). In this study, 30 polysubstance dependents were compared to a comparison group of 24 individuals who did not use illicit drugs of abuse. Individuals with SUD performed much more poorly on the IGT (net score = 10.2) than controls (net score = 26.0). Therefore, these authors have showed that drug dependents are more likely to make maladaptive decisions in the IGT that result in long-term losses exceeding short-term gains; and they may continue to choose cards from the low yield decks in the IGT because they underestimate the magnitude of their losses occurring over an extended period. These findings contributed to the hypothesis that dysfunctional PFC underlies a kind of myopia for the future in people with SUD, and this may be one of the principle mechanisms underlying the transition from casual substance taking to compulsive and uncontrollable behavior (Bechara & Damasio, 2002; Verdejo-García, Bechara, Recknor, & Pérez-García, 2006).

Moreover, this pattern of altered decision-making and PFC functionality was not restricted to neurological conditions but was also evident in psychiatric disorders such as SUD. Remarkably, these results were further replicated using samples including individuals with addiction to smoked/snorted cocaine, cannabis, alcohol or opiate (Bolla, Eldreth, Matochik, & Cadet, 2005; Pirastu et al., 2006; Viola et al., 2012), and the disadvantageous choices on the IGT were associated with higher levels of social dysfunction in people with SUD, suggesting the ecological validity of the IGT for real-life decision-making situations (Cunha, Bechara, de Andrade, & Nicastri, 2011). The IGT has become one of the most used tasks to measure feedback processing, decision-making and, therefore, executive functioning in SUD (Kovacs, Richman, Janka, Maraz, & Ando, 2017), suggesting that impaired performance in this task can be explained, in part, by alterations in the vmPFC that might impair the integration of NAc and amygdala signaling (Basten, Biele, Heekeren, & Fiebach, 2010). Moreover, recent evidence demonstrated that the NAc is also involved with the performance in the classic decision-making paradigm, the IGT (Grassi et al., 2018), once more advocating for the dynamic nature of executive functioning involving the coordination of activity among diffuse neural structures.

Recently, another neuropsychological task has been used to investigate explicit feedback processing on SUD. The Columbia Card Task, CCT, (Figner, Mackinlay, Wilkening, & Weber, 2009) is another card game where participants face a deck with 32 facedown cards. In each trial, participants are informed about how many loss cards are on the deck, the value amount of losing cards and the value amount of the winning cards. Considering this information, participants are asked to choose how many cards they want, seeking the best possible score at the end of the trial. The task is composed by two versions, the no-feedback condition and the feedback condition. In the feedback condition, participants had to choose cards one-by-one until they decided that it was too risky to continue. When selected, the card is signaled as an unknown card until participants voluntarily decide to end the round, and then the cards are turned over according to the order in which they were chosen. In the no-feedback condition, participants have to select the number of cards (from 0 to 32) that they would choose. However, cards are randomly selected by the computer and no-feedback is given until the end of the task (composed by 24 rounds). Because the CCT displays all the information, allowing participants to estimate the risks involved, it can be considered as a decision under risk task with explicit information; differently from the IGT in which participants are not informed on the risks involved and must implicitly learn by association which ones are the best decks.

A study with crack-cocaine dependent users showed that women with SUD perform worse than women without SUD, but similar as adolescents, on the no-feedback condition of the CCT. Interesting, when the feedback was provided, women with SUD showed a reduction of risk-taking behavior, performing similar as women without SUD (Kluwe-Schiavon, Viola, Sanvicente-Vieira, Pezzi, & Grassi-Oliveira, 2016). In another study, we investigated the influences of feedback processing and attention to environmental contingencies on risk-taking in heroin-dependent individuals. However, in contrast with previous findings, this study revealed that heroin-dependent patients pay less attention to environmental contingencies during risk-taking than controls, suggesting either that heroin-dependent patients display different risk -taking behavior to cocaine-dependent individuals, or an influence of opioid replacement therapy on behavior (Saleme et al., 2018). Based on such difference, future studies can specifically investigate how different SUD may affect learning from feedback on risk decision-making scenarios.

SUD, a biopsychosocial executive functioning disorder

Above, we have discussed how different neurobiological mechanisms play a central role in orchestrating executive functioning changes on SUD. In this sense, it is clear that besides the structural and the functional changes in the brain, there are many social and psychological characteristics that are related to SUD and alterations on executive functioning performance. For instance, excessive use of stimulants, such as cocaine, is functionally and clinically associated with impairments in every-day life, in form of health problems, disability, and failure to meet major responsibilities at work, school, or home (Volkow, Baler, & Goldstein, 2011).

As occasional drug use progresses into addictive behavior, individuals typically become increasingly impaired in their ability to function socially (Augier et al., 2018; Heilig, Epstein, Nader, & Shaham, 2016). Those impairments result in social marginalization and exclusion, which is associated with further substance-seeking behaviors (Heilig et al., 2016). Other real-life impairments that reported negative associations between executive functioning and measures of social adjustment, particularly related to family and finances, meaning that as much more executive functioning impairments, more financial and family problems may occur (Cunha et al., 2011). Thus, impairments in abilities such as theory of mind—which is a complex social ability related to understanding what other people is thinking about based on contextual information (e.g., face expression, speech, previous knowledge)—relate to higher symptoms and worse SUD profile (Hulka, Preller, Vonmoos, Broicher, & Quednow, 2013; Preller et al., 2014; Sanvicente-Vieira, Kluwe-Schiavon, Corcoran, & Grassi-Oliveira,