Competing Motivations: Proactive Response Inhibition Toward Addiction-Related Stimuli in Quitting-Motivated Individuals.

We examined whether addiction-related cues impact proactive inhibition (the restraint of actions in preparation for stopping) in individuals who are motivated to quit gambling or cannabis use. In Study 1, treatment-seeking individuals with cannabis use disorder and matched controls performed a stop-signal task that required them to inhibit categorizing cannabis or neutral pictures, and within varying levels of stop-signal probability. In Study 2, two groups of individuals, who applied to a voluntary self-exclusion program toward gambling, performed the stop-task following relaxation or gambling craving induction, with results compared to non-gamblers. Study 1 showed that despite being less efficient in proactive inhibition, individuals with cannabis use disorder exhibited heightened proactive inhibition toward cannabis cues. In Study 2, proactive inhibition toward gambling cues was heightened in gamblers after craving, but the degree of proactive adjustment decreased as a function of induced changes in gambling-related motivation. Present findings demonstrate that exposure to addiction-related cues can modulate proactive inhibition in individuals who are motivated to restrict their addictive behaviors.

The regulation of RhoA at focal adhesions by StarD13 is important for astrocytoma cell motility.

Malignant astrocytomas are highly invasive into adjacent and distant regions of the normal brain. Rho GTPases are small monomeric G proteins that play important roles in cytoskeleton rearrangement, cell motility, and tumor invasion. In the present study, we show that the knock down of StarD13, a GTPase activating protein (GAP) for RhoA and Cdc42, inhibits astrocytoma cell migration through modulating focal adhesion dynamics and cell adhesion. This effect is mediated by the resulting constitutive activation of RhoA and the subsequent indirect inhibition of Rac. Using Total Internal Reflection Fluorescence (TIRF)-based Förster Resonance Energy Transfer (FRET), we show that RhoA activity localizes with focal adhesions at the basal surface of astrocytoma cells. Moreover, the knock down of StarD13 inhibits the cycling of RhoA activation at the rear edge of cells, which makes them defective in retracting their tail. This study highlights the importance of the regulation of RhoA activity in focal adhesions of astrocytoma cells and establishes StarD13 as a GAP playing a major role in this process.

Deciding advantageously before knowing the advantageous strategy.

Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded by a nonconscious biasing step that uses neural systems other than those that support declarative knowledge. Normal participants and patients with prefrontal damage and decision-making defects performed a gambling task in which behavioral, psychophysiological, and self-account measures were obtained in parallel. Normals began to choose advantageously before they realized which strategy worked best, whereas prefrontal patients continued to choose disadvantageously even after they knew the correct strategy. Moreover, normals began to generate anticipatory skin conductance responses (SCRs) whenever they pondered a choice that turned out to be risky, before they knew explicitly that it was a risky choice, whereas patients never developed anticipatory SCRs, although some eventually realized which choices were risky. The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does. Without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.

Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

Poor decision making among older adults is related to elevated levels of neuroticism.

BACKGROUND: A well-studied index of reasoning and decision making is the Iowa Gambling Task (IGT). The IGT possesses many features important to medical decision making, such as weighing risks and benefits, dealing with unknown outcomes, and making decisions under uncertainty. PURPOSE: There exists a great deal of individual variability on the IGT, particularly among older adults, and the present study examines the role of personality in IGT performance. We explored which of the five-factor model of personality traits were predictive of decision-making performance, after controlling for relevant demographic variables. METHODS: One hundred and fifty-two healthy cognitively intact adults (aged 26-85) were individually administered the IGT and the NEO Five-Factory Inventory. RESULTS: In the older adults, but not the younger, higher NEO neuroticism was associated with poorer IGT performance. CONCLUSIONS: Our findings are discussed in the context of how stress may impact cognitive performance and cause dysfunction of neural systems in the brain important for decision making.

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Subcortical and cortical brain activity during the feeling of self-generated emotions.

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

Effects of anticipatory stress on decision making in a gambling task.

Recent research has highlighted the fact that emotion that is intrinsic to a task benefits decision making. The authors tested the converse hypothesis, that unrelated emotion disrupts decision making. Participants played the Iowa Gambling Task, during which only experimental participants anticipated giving a public speech (A. Bechara, D. Tranel, & H. Damasio, 2000). Experimental participants who were anticipating the speech learned the contingencies of the choices more slowly, and there was a gender interaction later in the game, with stressed female participants having more explicit knowledge and more advantageous performance and stressed male participants having poorer explicit knowledge and less advantageous performance. Effects of anticipatory stress on decision making are complex and depend on both the nature of the task and the individual.

Neural correlates of the impact of prior outcomes on subsequent monetary decision-making in frequent poker players.

Individuals have a tendency to be more risky in their choices after having experienced a monetary loss, than after a reward. Here, we examined whether prior outcomes influence differently the patterns of neural activity of individuals who are used to taking monetary risk, namely poker players. High-frequency poker players and non-gamblers were scanned while performing a controlled task that allowed measuring the effect of prior outcomes on subsequent decisions. Both non-gamblers and poker players took more risks after losing a gamble than after winning one. Neuroimaging data revealed that non-gamblers exhibited higher brain activation than poker players when pondering a decision after losing, as compared to after winning. The opposite was found in poker players. This differential pattern of activation was observed in brain regions involved in high-order motor processes (the dorsal premotor cortex). These results suggest that gambling habits introduce significant changes in action preparation during decision-making following wins and losses.

Neural correlates of proactive and reactive motor response inhibition of gambling stimuli in frequent gamblers.

We used functional magnetic resonance imaging to examine whether motivational-salient cues could exert a differential impact on proactive (the restrain of actions in preparation for stopping) and reactive (outright stopping) inhibition. Fourteen high-frequency poker players, and 14 matched non-gambler controls, performed a modified version of the stop-signal paradigm, which required participants to inhibit categorization of poker or neutral pictures. The probability that a stop-signal occurs (0%, 17%, 25%, 33%) was manipulated across blocks of trials, as indicated by the color of the computer screen. Behavioral analyses revealed that poker players were faster than controls in categorizing pictures across all levels of proactive motor response inhibition (go trials). Brain imaging analyses highlighted higher dorsal anterior cingulate cortex activation in poker players, as compared to controls, during reactive inhibition. These findings suggest that, due to their faster rates of stimulus discrimination, poker players might have recruited more cognitive resources than controls when required to stop their response (reactive inhibition). Nevertheless, no main effect of stimulus type was found, on either proactive or reactive inhibition. Additional studies are, therefore, needed in order to confirm that investigating the dynamics between reactive and proactive inhibition offers a discriminative analysis of inhibitory control toward motivational-salient cues.

The Iowa Gambling Task and the somatic marker hypothesis: some questions and answers.

A recent study by Maia and McClelland on participants' knowledge in the Iowa Gambling Task suggests a different interpretation for an experiment we reported in 1997. The authors use their results to question the evidence for the somatic marker hypothesis. Here we consider whether the authors' conclusions are justified.

Cognitive function and mood in MDMA/THC users, THC users and non-drug using controls.

Repeated ecstasy (MDMA) use is reported to impair cognition and cause increased feelings of depression and anxiety. Yet, many relevant studies have failed to control for use of drugs other than MDMA, especially marijuana (THC). To address these confounding effects we compared behavioural performance of 11 MDMA/THC users, 15 THC users and 15 non-drug users matched for age and intellect. We tested the hypothesis that reported feelings of depression and anxiety and cognitive impairment (memory, executive function and decision making) are more severe in MDMA/THC users than in THC users. MDMA/THC users reported more intense feelings of depression and anxiety than THC users and non-drug users. Memory function was impaired in both groups of drug users. MDMA/THC users showed slower psychomotor speed and less mental flexibility than non-drug users. THC users exhibited less mental flexibility and performed worse on the decision making task compared to non-drug users but these functions were similar to those in MDMA/THC users. It was concluded that MDMA use is associated with increased feelings of depression and anxiety compared to THC users and non-drug users. THC users were impaired in some cognitive abilities to the same degree as MDMA/THC users, suggesting that some cognitive impairment attributed to MDMA is more likely due to concurrent THC use.

Emotion, decision-making and substance dependence: a somatic-marker model of addiction.

Similar to patients with orbitofrontal cortex lesions, substance dependent individuals (SDI) show signs of impairments in decision-making, characterised by a tendency to choose the immediate reward at the expense of severe negative future consequences. The somatic-marker hypothesis proposes that decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between abnormalities in experiencing emotions in SDI, and their severe impairments in decision-making in real-life. Growing evidence from neuroscientific studies suggests that core aspects of substance addiction may be explained in terms of abnormal emotional guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in SDI. Combined neuropsychological and physiological assessment has demonstrated that the poorer decision-making of SDI is associated with altered reactions to reward and punishing events. Imaging studies have shown that impaired decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, including the ventromedial cortex, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker model of addiction.

[Brain mechanisms involved in decision-making]. / Mecanismos cerebrales de la toma de decisiones.

AIM: To review the studies on brain mechanisms in decision making within the framework of the somatic marker hypothesis, and based on experiments employing the Iowa Gambling Task. DEVELOPMENT: An overview of the somatic marker hypothesis is presented together with the review of the main results obtained from research in brain damaged patients, and normal subjects with functional neuroimaging studies, that have led to the identification of the neural structures involved in decision making in humans. CONCLUSIONS: The main region involved in decision making is the ventromedial prefrontal cortex, that integrates sensory, mnesic and emotional information relevant to the task. Other structures intervening in the various relevant processes in decision making are the amygdala (processing and encoding of the emotional signal and its association with contextual stimuli) and the cingulate cortex (process monitoring and response inhibition, especially in situations of uncertainty). The prefrontal dorsolateral cortex would also be involved through the necessary activation of the working memory in the decision making process, especially in the case of complex tasks.

Satisfaction assessment with malleable prosthetic implant of Spectra (AMS) and Genesis (Coloplast) models.

The malleable prosthetic implant is widely accepted among patients and physicians owing to a lower degree of surgical complexity, its rare mechanic failures and lower cost. We have compared the degree of satisfaction with malleable prosthetic implant in 60 patients, 36 with Spectra (AMS) and 24 with Genesis (Coloplast). For assessment purposes, we implemented the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) satisfaction questionnaire adapted for penile prosthetic implants. The mean age and follow-up was 61.7 years (31-82) and 19.9 months (1-61), respectively. Mean EDITS scores did not indicate superiority of one implant over the other, overall satisfaction index being 77.1% and 75.6% for Genesis and Spectra prosthesis, respectively (P=0.4970). Our results revealed that these two models of malleable prostheses present a high level of satisfaction and confirm that the malleable prosthetic implant is an excellent option to treat patients with ED refractory to medical treatment.

The ability to decide advantageously declines prematurely in some normal older persons.

The prefrontal region of the brain, including the ventromedial sector which supports reasoning and decision-making, may undergo disproportionate aging in some older persons, but the empirical evidence is decidedly mixed. To help resolve this, we tested 80 neurologically and psychiatrically healthy Younger (aged 26-55) and Older (aged 56-85) adults on a "Gambling Task", which provides a close analog to real-world decision-making by factoring in reward, punishment, and unpredictability, yielding a sensitive index of ventromedial prefrontal function. A subset of the Older group manifested a decision-making impairment on the Gambling Task, in spite of otherwise intact cognitive functioning. This finding raises the possibility of disproportionate aging of the ventromedial prefrontal cortex in these individuals. Our finding has important societal and public policy implications (e.g., choosing medical care, allocating personal wealth), and may also help explain why many older individuals are targeted by and susceptible to fraudulent advertising.

Impaired perception of self-motion (heading) in abstinent ecstasy and marijuana users.

RATIONALE: Illicit drug use can increase driver crash risk due to loss of control over vehicle trajectory. This study asks, does recreational use of +/-3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) and tetrahydrocannabinol (THC; marijuana) impair cognitive processes that help direct our safe movement through the world? OBJECTIVE: This study assesses the residual effects of combined MDMA/THC use, and of THC use alone, upon perceived trajectory of travel. METHODS: Perception of self-motion, or heading, from optical flow patterns was assessed using stimuli comprising random dot ground planes presented at three different densities and eight heading angles (1, 2, 4 and 8 degrees to the left or right). On each trial, subjects reported if direction of travel was to the left or the right. RESULTS: Results showed impairments in both drug groups, with the MDMA/THC group performing the worst. CONCLUSIONS: The finding that these psychoactive agents adversely affect heading perception, even in recently abstinent users, raises potential concerns about MDMA use and driving ability.

Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers.

A decision-making instrument known as the "gambling task" was used, which has been shown to be sensitive to the decision-making impairment of patients with bilateral lesions of the ventromedial prefrontal cortex (VM). Three groups of subjects were tested, substance dependent individuals (SD) (n=41), normal controls (n=40), and VM patients (n=5). All SD met the DSM-IV criteria for dependence, with either alcohol or stimulants (metamphetamine or cocaine) as the primary substance of choice. The results revealed a significant impairment in the performance of SD relative to normal controls. A significantly high proportion of SD (61 vs. only 32.5% of normal controls) performed within the range of the VM patients, while the rest performed within the range of normal controls. General demographic factors such as age, sex, and level of education could not explain these differences in performance. As well, differences in performance were not explained by intelligence (IQ), memory, or performance on standard executive function/frontal lobe tests. Performance on the gambling task was best predicted by a combination of factors, including duration of abstinence, years of abuse, relapses and times in treatment, and the ability to hold gainful employment. The results support the hypothesis that impairment in decision-making linked to a dysfunctional VM cortex is associated with at least a sub-group of SD.

Insensitivity to future consequences following damage to human prefrontal cortex.

Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes.