Non-invasive brain stimulation targets and approaches to modulate gambling-related decisions: A systematic review.

INTRODUCTION: Despite intense neuroscience research on the neurobiological underpinnings of Gambling Disorder (GD) and gambling-related decision-making, effective treatments targeting these dysfunctions are still lacking. Non Invasive Brain Stimulation (NIBS) techniques, such as transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS), selectively modulate activity of brain circuits and have the potential to reverse alterations sustaining GD symptoms. Therefore, the aim of this systematic review was to determine the impact of different NIBS interventions on gambling-related decision processes. METHODS: We conducted a comprehensive and translational search in three online databases (MEDLINE via PubMed, Scopus, Web of Science), in accordance with the PRISMA guidelines. We included studies applying neuromodulation (TMS, tDCS) techniques in GD patients or assessing gambling-related decision-making in healthy subjects. In addition, we explored the potential impact of NIBS in drug-induced GD (e.g., Parkinson's Disease). RESULTS: Twenty-seven studies have been included. We summarized results to detect the impact of different targets and stimulation/inhibition protocols in terms of gambling-related decision-making. The majority of both tDCS and TMS studies targeted the dorsolateral prefrontal cortex. Although heterogeneous in protocols and parameters, results from tDCS and TMS studies converge in indicating that the stimulation (instead of inhibition) of prefrontal regions could be beneficial to contrast dysfunctional gambling-related decision processes. CONCLUSION: NIBS interventions show promise to be further tested in controlled clinical settings for the treatment of behavioral addictions. Further studies are also necessary to investigate connectivity changes and laterality issues (unilateral versus bilateral; left versus right) of NIBS application in GD.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Distinct Response Inhibition Patterns in Obsessive Compulsive Disorder Patients and Pathological Gamblers.

Background: Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are common disorders. The cognitive models of OCD and PG focus on abnormalities in response inhibition. Although, these functions have been studied in different PG and OCD samples, no study has compared the response inhibition in both. Methods: Medication-naïve OCD (n = 61) and PG subjects (n = 109) and healthy controls (n = 131) performed CPT and Go/NoGo tasks. Results: Compared to healthy controls (HC), PG and OCD groups underperformed on speed and exhibited larger time variability on the CPT and Go/NoGo task. Only in OCD patients, a positive correlation between omission errors and response time (RT) was observed in the CPT. At the Go/NoGo task, a negative correlation between false alarms and RT (a fast-errors trade-off) was significant only in the PG group. The HC group had greater sensitivity values (d') than the OCD and PG groups in the Go/NoGo task. The PG group displayed lower d' values and more conservative response criterion in the CPT. In addition, only the OCD group expressed a high switching cost compared to both the PG and HC groups in terms of the RT and d' values. Conclusions: Both the PG and OCD groups demonstrated impaired response inhibition compared to the HC group. On several measures, the OCD and PG groups showed comparable impairments, and in others these were distinct. Thus, it appears that distinct neurocognitive patterns are involved in performance of the CPT and the Go/NoGo tasks among OCD and PG subjects whose cognitive status is currently under intensive investigation.

The role of gender in association between inhibition capacities and risky decision making.

BACKGROUND: Research on the association between decision making and inhibition abilities has exhibited fundamental controversies. Some authors claim that inhibition abilities are an integral part of the decision-making process, whereas others suggest that the decision-making process does not operate in close association with inhibition abilities. Can gender explain variations in risky decisions via inhibition influences? PURPOSE: The purpose of the present study was to explore the associations between response inhibition, reflection inhibition, interference inhibition, and decision-making processes in men and women. METHODS: To this end, 46 women and 46 men were assessed by the Go/NoGo task, a measure of response inhibition, by the Matching Familiar Figure Test, a measure of reflection inhibition; and by the Stroop task, a measure of interference inhibition. RESULTS: No differences were detected in these measures between groups. The net score of the performance on the last section of the Iowa Gambling Task choices did not correlate with the inhibition measures in the two groups. We did not discover any significant main effects of gender on the association between these measures. CONCLUSION: These findings do not support the hypothesis that risky decisions are due to impaired inhibitory control. Further studies are needed to identify the cognitive mechanisms involved in the tendency to make risky decisions.

Ability to use the wait-and-see strategy in pathological gamblers.

Pathological gamblers (PGs) perform differently on neurocognitive tests than do healthy controls (HC). The aim of this study was to assess "waiting ability" - a major components of inhibition control-using a modified Stop Signal Task (SST) in a population of male PGs (N=55), and HCs (N=53). Results indicated no differences between PGs and HCs in reaction times, intra-individual response variability, or number of false alarms and misses. In conclusion, PGs were not impaired in their ability to manipulate their on-line response strategy during the experimental task and were instead able to change their strategy to decrease the number of false alarms. However, much more empirical and theoretical work needs to be carried out in order to understand the key neural basis of impulsivity among PGs.

Four-year follow-up study of pharmacological treatment in pathological gamblers.

OBJECTIVE: In the past decade, we have witnessed the emergence of pharmacological treatments for pathological gambling with some success but many question marks. We aimed to explore pharmacological treatments that have been previously explored with some success, with the intent of comparing their efficacy and pave the way to larger placebo-controlled trials. METHODS: In this study, we allocated 78 patients to 4 different types of psychotropic medications: naltrexone, topiramate, bupropion, and escitalopram. We treated patients for more than 2 years, with additional 2-year follow-ups without medication. The sample was evaluated using the 21-item Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Global Assessment of Functioning, and the Visual Analog Scale to measure general well-being before enrollment as well as at 1 month, 6 months, 24 months, and 48 months after beginning medication treatment. RESULTS: During the first 2 years of treatment, 34 patients dropped out, with one more dropping out during the additional 2 years of follow-up. Significant improvement on all rating scales was seen in all groups after 2 years, except HAMD in the group that received topiramate. We found the naltrexone-treated group of patients to have a statistically significant lower dropout rate compared with other groups, statistically significant lower HAMD scores in comparison to the group treated with bupropion, statistically significant lower Hamilton Anxiety Rating Scale score compared to the groups treated with escitalopram and topiramate, and significantly higher Visual Analog Scale scores compared to the groups treated with bupropion and topiramate. CONCLUSIONS: Pathological gambling is essentially a biopsychological disorder that may be attenuated provided that patients adhere to medication. In our study, among 4 medications with different mechanisms of action, naltrexone was found to be the most effective. Placebo-controlled studies involving large numbers of subjects are required before naltrexone's efficacy can be established.

Football gambling three arm-controlled study: gamblers, amateurs and laypersons.

BACKGROUND: Football (soccer) betting, as a strategic form of betting, became one of the favorite wagers for pathological gamblers. Previous studies demonstrated the psychological and biological significance of the 'illusion of control' (personal control) and 'near miss' results in gambling. In our study, we explored whether knowledge and expertise of pathological sports gamblers can ensure a successful bet. SAMPLE AND METHODS: Participants were divided into three groups of individuals - pathological gamblers, amateurs and laypersons - and were asked to predict in advance the general result and the exact result of football matches in the European Champions League Round of 16. RESULTS: The 165 participants included 53 pathological sports gamblers (52 males and 1 female), 78 laypersons (45 females and 33 males) and 34 amateurs (all males). After a thorough statistical analysis, we found no significant differences between the groups, no matter what kind of previous knowledge they had acquired. CONCLUSION: This study demonstrates that the 'illusion of control' of pathological gamblers, attained by knowledge of the game and its latest data and information (especially in a strategic gamble as football betting), has no factual background. Moreover, our study demonstrates without a doubt that there is no significant difference between the male pathological sports gamblers group and the male/female laypersons group.

Deep transcranial magnetic stimulation for the treatment of pathological gambling.

Five pathological gamblers received deep transcranial magnetic stimulation (DTMS). Evaluations included rating scales and collateral anamnesis. Despite initial improvement in ratings, collateral anamnesis demonstrated failure to respond. DTMS to the pre-frontal cortex using an H1 coil was an ineffective treatment. Our study is preliminary, and additional studies are required.

Tricotillomania: pathopsychology theories and treatment possibilities.

The phenomenon of hair pulling has been recognized for centuries, yet the true prevalence of trichotillomania (TTM) is largely unknown and the topic has been sparsely studied. TTM is classified as an impulse-control disorder despite much debate about its etiology. In this review we summarize the different hypotheses, including impulse-control disorders, obsessive-compulsive disorders, behavioral problems and addiction, and the appropriate treatment methods. The combination of selective serotonin reuptake inhibitors and antipsychotic medications are shown to be most effective. Treatment with anti-addiction drugs seems relevant. Further research is needed to increase our knowledge regarding the etiology of TTM.

Acamprosate and Baclofen were Not Effective in the Treatment of Pathological Gambling: Preliminary Blind Rater Comparison Study.

OBJECTIVES: Pathological gambling (PG) is a highly prevalent and disabling impulse control disorder. A range of psychopharmacological options are available for the treatment of PG, including selective serotonin reuptake inhibitors, opioid receptor antagonists, anti-addiction drugs, and mood stabilizers. In our preliminary study, we examined the efficacy of two anti-addiction drugs, baclofen and acamprosate, in the treatment of PG. MATERIALS AND METHODS: Seventeen male gamblers were randomly divided into two groups. Each group received one of the two drugs without being blind to treatment. All patients underwent a comprehensive psychiatric diagnostic evaluation and completed a series of semi-structured interviews. During the 6-months of study, monthly evaluations were carried out to assess improvement and relapses. Relapse was defined as recurrent gambling behavior. RESULTS: None of the 17 patients reached the 6-months abstinence. One patient receiving baclofen sustained abstinence for 4 months. Fourteen patients succeeded in sustaining abstinence for 1-3 months. Two patients stopped attending monthly evaluations. CONCLUSION: Baclofen and acamprosate did not prove efficient in treating pathological gamblers.

Risk-taking decisions in pathological gamblers is not a result of their impaired inhibition ability.

This work investigates whether inhibition impairments influence the decision making process in pathological gamblers (PGs). The PG (N=51) subjects performed the Iowa Gambling Task (IGT as the measure of the decision making process) and two tests of inhibition: the Stroop (interference inhibition), and the Go/NoGo (response inhibition), and were compared with demographically matched healthy subjects (N=57). Performance in the IGT block 1 and block 2 did not differ between the groups, but the differences between the PGs and healthy controls began to be significant in block 3, block 4 and block 5. PGs learned the IGT task more slowly than the healthy controls and had non-optimal outcomes (more disadvantageous choices). Impaired IGT performance in PGs was not related to an inhibition ability measured by the Stroop (interference response time) and the Go/NoGo (number of commission errors) parameters. Further controlled studies with neuroimaging techniques may help to clarify the particular brain mechanisms underlying the impaired decision making process in PGs.

Alternation learning in pathological gamblers: an fMRI Study.

OBJECTIVES: We have previously reported that pathological gamblers have impaired performance on the Stroop color word naming task, go-no-go task and speed accuracy tradeoff performance, tasks used to assess executive function and interference control. The aim of the present neuroimaging study was to explore the relationship between frontal cortex function and gambling severity in pathological gamblers. MATERIALS AND METHODS: Functional MRI (fMRI) was used to estimate brain activity of ten male medication-free pathological gamblers during performance of an alternation learning task. Performance of this task has been shown to depend on the function of regions in the frontal cortex. RESULTS: The executive functions needed to perform the alternation learning task were expressed as brain activation in lateral and medial frontal as well as parietal and occipital regions. By correlating the level of local brain activation to task performance, parietal regions and lateral frontal and orbitofrontal regions were demonstrated. A higher score in SOGS was associated with intrusion on the task-specific activation in the left hemisphere, to some extant in parietal regions and even more pronouncedly in left frontal and orbitofrontal regions. CONCLUSIONS: Our preliminary data suggests that pathological gambling may be characterized by specific neuro-cognitive changes related to the frontal cortex.

Response to deep TMS in depressive patients with previous electroconvulsive treatment.

BACKGROUND: The efficacy of transcranial magnetic stimulation (TMS) in the treatment of major depression has already been shown. Novel TMS coils allowing stimulation of deeper brain regions have recently been developed and studied. OBJECTIVE: Our study is aimed at exploring the possible efficacy of deep TMS in patients with resistant depression, who previously underwent electroconvalsive therapy (ECT). METHODS: Using Brainsway's deep TMS H1 coil, six patients who previously underwent ECT, were treated with 120% power of the motor threshold at a frequency of 20 Hz. Patients underwent five sessions per week, up to 4 weeks. Before the study, patients were evaluated using the Hamilton depression rating scale (HDRS, 24 items), the Hamilton anxiety scale, and the Beck depression inventory and were again evaluated after 5, 10, 15, and 20 daily treatments. Response to treatment was considered a reduction in the HDRS of at least 50%, and remission was considered a reduction of the HDRS-24 below 10 points. RESULTS: Two of six patients responded to the treatment with deep TMS, including one who achieved full remission. CONCLUSIONS: Our results suggest the possibility of a subpopulation of depressed patients who may benefit from deep TMS treatment, including patients who did not respond to ECT previously. However, the power of the study is small and similar larger samples are needed.

Pathological gambling: an impulse control disorder? Measurement of impulsivity using neurocognitive tests.

Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) and in the ICD-10 (International Classification of Disease) as an impulse control disorder. The association between impulsivity and pathological gambling remains a matter of debate: some researchers find high levels of impulsivity within pathological gamblers, others report no difference compared to controls, and yet others even suggest that it is lower. In this review we examine the relationship between pathological gambling and impulsivity assessed by various neurocognitive tests. These tests--the Stroop task, the Stop Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the Wisconsin Card Sorting Test, the Tower of London test, and the Continuous Performance Test--demonstrated less impulsivity in gambling behavior. The differences in performance between pathological gamblers and healthy controls on the neurocognitive tasks could be due to addictive behavior features rather than impulsive behavior.

Speed-accuracy tradeoff in decision-making performance among pathological gamblers.

BACKGROUND: Pathological gambling is classified as an impulse control disorder in the DSM-IV-TR; however, few studies have investigated the relationship between gambling behavior and impulsive decision-making in time-non-limited situations. METHODS: The subjects performed the Matching Familiar Figures Test (MFFT). The MFFT investigated the reflection-impulsivity dimension in pathological gamblers (n = 82) and demographically matched healthy subjects (n = 82). RESULTS: Our study demonstrated that pathological gamblers had a significantly higher rate of errors than healthy controls (p = 0.01) but were not different in terms of response time (p = 0.49). We found a similar power of correlation between the number of errors and response time in both pathological gamblers and controls. We may conclude that impaired performance of our pathological gamblers as compared to controls in a situation without time limit pressure cannot be explained by a trade-off of greater speed at the cost of less accuracy. CONCLUSIONS: The results of our study showed that pathological gamblers tend to make more errors but do not exhibit quicker responses as compared to the control group. Diminished MFFT performance in pathological gamblers as compared to controls supports findings of previous studies which show that pathological gamblers have impaired decision-making. Further controlled studies with a larger sample size which examine MFFT performance in pathological gamblers are necessary to confirm our results.

[Depressive disorders in elderly: treatment possibilities rather than pharmacotherapy].

Treatment of depression is one of the most challenging issues in adult populations. In adults, response rates to classic treatments are lower than expected. The effectiveness of different treatment strategies could be related to age, sex and physical conditions of the patients. The side-effect profile in adult population affects pharmacological interventions. The aim of this review is to present the non-pharmacological treatment strategies in the adult population. However, possible treatment strategies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS) were less frequently studied in this population. ECT was found to be the most effective treatment procedure for depression of adults. There were only a few double-blind sham (placebo) controlled studies with demonstrated effectiveness of TMS. DBS lacks double-blind studies of this invasive treatment method. ECT seems to be the gold standard for the treatment of resistant patients in this population but the side-effect profile of ECT in this sensitive population will be discussed. Double-blind sham controlled studies with larger samples are necessary to confirm preliminary results with TMS and DBS.

Mood disorders in elderly population: neurostimulative treatment possibilities.

Treatment of mood disorders is one of the most challenging territories in elderly. Effectiveness of different treatment strategies could be related to age, sex and physical conditions. The side effect profile in this population also affects pharmacological interventions. Our review includes the neurostimulative treatment strategies in elderly. However, possible treatment strategies such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) were less studied in elderly. ECT was found to be an effective treatment procedure in mood disorders. Few double-blind sham controlled studies were conducted and demonstrated effectiveness of TMS. DBS has lack of double-blind studies. ECT seems to be the golden standard for the treatment resistant elderly patients, yet side effect profile of ECT in elderly will be discussed. Double -blind sham controlled studies with larger samples are necessary to confirm preliminary results with transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST) and VNS, DBS.

Go-no-go performance in pathological gamblers.

Previous neuropsychological studies demonstrated various deficits of impulse control in pathological gamblers (PGs). However, there are limited data available on response-inhibition impairment among PGs. The present study attempted to assess response inhibition in untreated PGs (N=83), in comparison with normal subjects (N=84). Go/no-go and target-detection conditions of a computerized task were used as a measure of response-inhibition ability. A repeated measures analysis of covariance (ANCOVA-RM) was used with response time, variability of response time, and number of false alarms and misses as dependent measures; group (PG and controls) as the between-subjects measure; condition (target detection or go/no-go) and time slice (first and second in each condition) as repeated measures within-subject factors; and educational level as a covariate. Our results showed that PGs were significantly more impaired in both target detection and go/no-go task performance than controls. The PGs had significantly more false alarms and misses than controls, and they were slower and less consistent in their responses.

Pathological gambling: an update on neuropathophysiology and pharmacotherapy.

Neurobiological research has shown the potential involvement of serotonergic, dopaminergic and opioid dysfunction in the pathophysiology of pathological gambling. In this review, we present current theories of the neuropathology of pathological gambling, paying particular attention to the role of the neural circuitry underlying motivation, reward, decision-making and impulsivity. This review also presents a literature review of current pharmacological treatment strategies for pathological gambling, such as selective serotonin reuptake inhibitors (SSRIs), opioid receptor antagonists, anti-addiction drugs and mood stabilizers, and also discusses the role of nonpharmacological interventions.A hypothetical model of the clinical subtypes of pathological gambling is presented, e.g. the impulsive subtype, the obsessive-compulsive subtype and the addictive subtype. This model attempts to integrate current knowledge in the field of pathological gambling regarding neuropathology, psychiatric co-morbidity, family history, genetics, course of illness, gender and response to pharmacological treatment. Finally, it is proposed that the existence of possible clinical subtypes of pathological gambling may provide a potential framework for matching the various subtypes with specific pharmacotherapies.