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.

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.

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.

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.

Efectividad de las ondas de choque de baja intensidad (LIWS) en varones con disfunción eréctil (DE) no respondedores a IPDE5. Estudio piloto / Effectiveness of low-intensity extracorporeal shock wave therapy on patients with Erectile Dysfunction (ED) who have failed to respond to PDE5i therapy. A pilot study

Las LISW son una novedosa modalidad de tratamiento en pacientes con disfunción eréctil (DE). Objetivo: Evaluar la efectividad y seguridad de las LISW en varones con DE no respondedores a IPDE5. Método: Estudio naturalístico, prospectivo, longitudinal, observacional que incluyo una población de 25 pacientes no respondedores a dosis máxima de IPDE5. El tratamiento consistió en aplicar 20000 LISW durante 4 semanas (4 sesiones). En cada sesión el paciente recibió 5000 ondas de choque de 0,09 mJ/mm2. 1800 aplicadas en el pene (900 en cada cuerpo cavernoso) y 3200 en el periné (1600 en la raíz derecha e izquierda cavernosa). Durante el tratamiento y fases de seguimiento se mantuvo igual dosis de IPDE5 como venía siendo tratado. Los cambios sobre la erección fueron evaluados utilizando el Índice Internacional de la Función Eréctil-6 (IIEF-6) y las preguntas 2 y 3 del Perfil de Encuentro Sexual (SEP). Complementariamente se agregó una pregunta sobre eficacia global del tratamiento (GAQ). Consideramos respondedor al paciente que mejoraba significativamente los 3 parámetros de rigidez y que respondiera afirmativamente a la GAQ, 3 meses pos-tratamiento. Fueron aplicadas variables de cálculo para considerar una significancia estadística con una p< 0,05. Resultados: El 80% de los pacientes (20/25) completaron el estudio. La mediana de la edad fue de 63 años. Cinco fueron excluidos del análisis por perdida de seguimiento. Del grupo evaluado, 12 (60%) mejoraron los 3 parámetros de erección y respondieron afirmativamente a la GAQ. El incremento promedio del IIEF-6 fue de 9 puntos. Ningún evento adverso fue reportado. Conclusiones: LISW en varones con DE no respondedores a IPDE5 fue eficiente y seguro, restaurando la respuesta a los IPDE5 en más de la mitad de los pacientes. Estudios multicéntricos, controlados y con mayor número de pacientes confirmaran el beneficio de esta nueva línea de tratamiento

Low-intensity extracorporeal shock wave therapy (LIESWT) of the penis has recently emerged as a promising modality in the treatment of ED. Objetives: The objective of this paper is to assess the effectiveness and safety of LIESWT on patients with ED who have failed to respond to PDE5i treatment. Methods: Open label, prospective, longitudinal observational study. The study involved an uncontrolled population of 25 patients. The treatment consisted in applying 20,000 shock waves during a period of four weeks. In each session the patient received 5000 shock waves of 0.09 mJ/mm2: 1800 were applied on the penis (900 on each corpus cavernosum), and 3200 were applied on the perineum (1600 on each crus). During the active treatment and follow-up phases, all patients remained on their regular high on demand or once-a-day dose PDE5i schedules. Main Outcome Measures: Effectiveness was assessed by IIEF-6, SEP2, SEP3 and GAQ. Patients were considered to be responders whenever they improved on all three erection assessment parameters and respond positively to the GAQ at three months post-treatment. Adverse events were recorded. Statistical variables were applied and findings were considered to be statistically significant whenever the P value was < 0.05. Results: Eighty percent (median age 63) of the patients (20/25) completed the study. Five patients were lost to follow-up and were excluded from the analysis. Sixty percent (60%) of the patients responded to the treatment, improved the 3 efficacy evaluating parameters and responded positively to the GAQ. The increase in mean IIEF-6 score was of 9 points after the third posttreatment month. There were no patients reporting treatment-related adverse events. Conclusions: LIESWT for men with ED and that are PDE5i non-responders was safe and effective and restoring PDE5i response in more than 50% of patients. A large-scale multicenter study is required to determine the benefits of this treatment for ED

Invadopodia, regulation, and assembly in cancer cell invasion.

The occurrence of invadopodia has been, since its characterization, a hallmark of cancerous cell invasion and metastasis. These structures are now the subject of a controversy concerning their cellular function, molecular regulation, and assembly. The terms invadopodia and podosomes have been used interchangeably since their discovery back in 1980. Since then, these phenotypes are now more established and accepted by the scientific community as vital structures for 3D cancer cell motility. Many characteristics relating to invadopodia and podosomes have been elucidated, which might prove these structures as good targets for metastasis treatment. In this review, we briefly review the actin reorganization process needed in most types of cancer cell motility. We also review the important characteristics of invadopodia, including molecular components, assembly, markers, and the signaling pathways, providing a comprehensive model for invadopodia regulation.

StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion.

Breast cancer is one of the most commonly diagnosed cancers in women around the world. In general, the more aggressive the tumor, the more rapidly it grows and the more likely it metastasizes. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in breast cancer cell motility and metastasis. The switch between active GTP-bound and inactive GDP-bound state is regulated by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and guanine-nucleotide dissociation inhibitors (GDIs). We studied the role of StarD13, a recently identified Rho-GAP that specifically inhibits the function of RhoA and Cdc42. We aimed to investigate its role in breast cancer proliferation and metastasis. The levels of expression of this Rho-GAP in tumor tissues of different grades were assayed using immunohistochemistry. We observed that, while the level of StarD13 expression decreases in cancer tissues compared to normal tissues, it increases as the grade of the tumor increased. This was consistent with the fact that although StarD13 was indeed a tumor suppressor in our breast cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell motility. In fact, StarD13 knockdown resulted in an inhibition of cell motility and cells were not able to detach their tail and move forward. Our study describes, for the first time, a tumor suppressor that plays a positive role in cancer motility.

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.

Interplay between apoptosis and autophagy, a challenging puzzle: new perspectives on antitumor chemotherapies.

Autophagy is a mechanism of protection against various forms of human diseases, such as cancer, in which autophagy seems to have an extremely complex role. In cancer, there is evidence that autophagy may be oncogenic in some contexts, whereas in others it clearly contributes to tumor suppression. In addition, studies have demonstrated the existence of a complex relationship between autophagy and cell death, determining whether a cell will live or die in response to anticancer therapies. Nevertheless, we still need to complete the autophagy-apoptosis puzzle in the tumor context to better address appropriate chemotherapy protocols with autophagy modulators. Generally, tumor cell resistance to anticancer induced-apoptosis can be overcome by autophagy inhibition. However, when an extensive autophagic stimulus is activated, autophagic cell death is observed. In this review, we discuss some details of autophagy and its relationship with tumor progression or suppression, as well as role of autophagy-apoptosis in cancer treatments.

Myopia for the future or hypersensitivity to reward? Age-related changes in decision making on the Iowa Gambling Task.

It has been shown that older adults perform less well than younger adults on the Iowa Gambling Task (IGT), a real-world type decision-making task that factors together reward, punishment, and uncertainty. To explore the reasons behind this age-related decrement, we administered to an adult life span sample of 265 healthy participants (Mdn age = 62.00 +/- 16.17 years; range [23-88]) 2 versions of the IGT, which have different contingencies for successful performance: A'B'C'D' requires choosing lower immediate reward (paired with lower delayed punishment); E'F'G'H' requires choosing higher immediate punishment (paired with higher delayed reward). There was a significant negative correlation between age and performance on the A'B'C'D' version of the IGT (r = -.16, p = .01), while there was essentially no correlation between age and performance on the E'F'G'H' version (r = -.07, p = .24). In addition, the rate of impaired performance in older participants was significantly higher for the A'B'C'D' version (23%) compared with the E'F'G'H' version (13%). A parsimonious account of these findings is an age-related increase in hypersensitivity to reward, whereby the decisions of older adults are disproportionately influenced by prospects of receiving reward, irrespective of the presence or degree of punishment.

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.

Impulsive behavior in adults with attention deficit/ hyperactivity disorder: characterization of attentional, motor and cognitive impulsiveness.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by inattention and/or hyperactivity/impulsivity. Impulsivity persists in adults with ADHD and might be the basis of much of the impairment observed in the daily lives of such individuals. The objective of this study was to address the presence, and more importantly, the three dimensions of impulsivity: attentional, non-planning and motor, in how they may relate to neuropsychological mechanisms of impulse control. We studied a sample of 50 adults with ADHD and 51 healthy comparison controls using the Barratt Impulsivity Scale Version 11 (BIS), and neuropsychological tasks, namely the Continuous Performance Task (CPT-II) and the Iowa Gambling Task (IGT). The ADHD group showed more signs of impulsivity on the three dimensions of BIS, committed more errors of omission and commission on the CPT-II, and made more disadvantageous choices on the IGT. These results support the existence of deficits related to three components of impulsivity: motor, cognitive, and attentional among adults with ADHD. Most importantly, this study also highlights the complementary nature of self-report questionnaires and neuropsychological tasks in the assessment of impulsivity in ADHD adults.

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.

Réplica. Mecanismos cerebrales implicados en la toma de decisiones / Reply. The brain mechanisms involved in making decisions

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[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.

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

Objetivo. Revisar los estudios sobre los mecanismos cerebrales de la toma de decisiones en el marco de la hipótesis del marcador somático y basados experimentalmente en el empleo dela tarea de apuestas de Iowa (Iowa Gambling Task). Desarrollo. Se presenta la teoría del marcador somático y las características de la citada tarea de toma de decisiones y otras relacionadas. A continuación, se revisan los principales estudios llevados a cabo en personas con lesión cerebral y los procedentes de sujetos normales, con el empleo de neuroimagen funcional, que han hecho posible la identificación de las estructuras neurales implicadas en la toma de decisiones en humanos. Conclusiones. La principal región implicada es la corteza prefrontal ventromedial, donde se produce la integración de la información sensorial, amnésica y emocional necesaria para la tarea. Otras estructuras que intervienen en diferentes procesos relevantes para la toma de decisiones serían la amígdala (procesamiento y codificación de la señal emocional y su asociación con estímulos contextuales) y la corteza cingulada (monitorización del proceso e inhibición de respuesta, especialmente en situaciones de incertidumbre). La corteza prefrontal dorso lateral también participaría en este proceso debido a la necesaria activación de la memoria de trabajo en la toma de decisiones, en especial cuando la tarea es compleja (AU)

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 indecision 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 (AU)

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.