Effects of Transcranial Direct Current Stimulation (tDCS) over dlPFC and over vmPFC in the behavior in a risky decision-making task

Universidade do Minho Escola de Psicologia Filipa Azevedo Dantas Effects of Transcranial Direct Current Stimulation (tDCS) over dlPFC and over vmPFC in the Behavior in a Risky Decision-Making Task outubro de 2022 Effects of Transcranial Direct Current Stimulation (tDCS) over dlPFC and over vmPFC in the Behavior in a Risky Decision-Making Task Filipa Dantas UMinho | 2022 Universidade do Minho Escola de Psicologia outubro de 2022 Filipa Azevedo Dantas Effects of Transcranial Direct Current Stimulation (tDCS) over dlPFC and over vmPFC in the Behavior in a Risky DecisionMaking Task Dissertação de M estrado Mestrado Integrado em Psicologia Trabalho efetuado sob a orientação de Professor Doutor Pedro Moreira Professora Doutora Sandra Carvalho ii DIREITOS DE AUTOR E CONDIÇÕES DE UTILIZAÇÃO DO TRABALHO POR TERCEIROS Este é um trabalho académico que pode ser utilizado por terceiros desde que respeitadas as regras e boas práticas internacionalmente aceites, no que concerne aos direitos de autor e direitos conexos. Assim, o presente trabalho pode ser utilizado nos termos previstos na licença abaixo indicada. Caso o utilizador necessite de permissão para poder fazer um uso do trabalho em condições não previstas no licenciamento indicado, deverá contactar o autor, através do RepositóriUM da Universidade do Minho. Licença concedida aos utilizadores deste trabalho Atribuição-NãoComercial-SemDerivações CC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/ iii Agradecimentos Já Aristóteles dizia que “o ser humano é um ser social” porque necessita dos outros membros da espécie para sobreviver e prosperar. Assim, não podia deixar de expressar a minha profunda gratidão para com todos aqueles que contribuíram para que o momento em que estou a escrever estes Agradecimentos chegasse. Em primeiro lugar, quero agradecer a todos os responsáveis e envolvidos na elaboração deste trabalho: quero agradecer à Universidade do Minho, à Escola de Psicologia, aos meus orientadores na dissertação, Professor Doutor Pedro Moreira e Professora Doutora Sandra Carvalho. Quero agradecer à minha família, por estar sempre disponível para mim e para me ouvir e entender os meus desabafos quando a carga de trabalho ao longo deste período difícil aumentava ou simplesmente eu perdia as minhas estribeiras. Em especial à minha irmã, que, também minha companheira de casa, teve de aturar todos os meus dramas. Também aos meus bichinhos de estimação, que souberam consolar-me e animar-me em todas as horas, como sempre. Um agradecimento especial às minhas melhores amigas, Márcia e Diana, colegas de curso, companheiras de percurso, amigas do coração e, acredito eu, parceiras de vida. (Com elas compartilhei todo este melodrama/ comédia dramática.) Sei que são aquelas que eu levarei comigo para as próximas experiências que a vida me reservar, e no geral para o que estiver por vir. iv STATEMENT OF INTEGRITY I hereby declare having conducted this academic work with integrity. I confirm that I have not used plagiarism or any form of undue use of information or falsification of results along the process leading to its elaboration. I further declare that I have fully acknowledged the Code of Ethical Conduct of the University of Minho. Braga, 17th October de 2022 (Filipa Azevedo Dantas) v Efeitos da Estimulação por Corrente Direta Transcraniana (tDCS) sobre o dlPFC e sobre o vmPFC no Comportamento numa Tarefa de Tomada de Decisão de Risco Resumo A tomada de decisão é um comportamento complexo, que compreende múltiplos componentes. A tomada de decisão arriscada tem ganho particular atenção, porque diariamente tomamos decisões sob algum grau de risco e conhecer o que nos torna propensos ao risco pode ajudar a prever essas decisões. As emoções influenciam a tomada de decisão de uma forma regular e previsível (Keltner & Lerner, 2010), portanto é pertinente explorar a capacidade de a modular. Estando os córtices pré-frontal dorsolateral e ventromedial implicados neste processo (Nejati et al., 2021), uma estratégia seria aplicar tDCS sobre estas regiões. Avaliámos os efeitos da tDCS anodal sobre os córtices pré-frontal dorsolateral e ventromedial na modulação da tomada de decisão arriscada, durante uma Balloon Analogue Risk Task (BART Automática e BART Manual) em 32 voluntários saudáveis (idades entre 18 e 25 anos). Hipotetizámos que todos os indivíduos manifestariam uma preferência por decisões pouco arriscadas, na sessão ativa comparativamente com a sham. Foi realizada uma ANOVA mista para cada uma das métricas da BART, seguida de testes-t amostras-emparelhadas (ou testes de Wilcoxon) para diferenças entre grupos. Os resultados não revelaram diferenças estatisticamente significativas entre as sessões sham e activa em nenhuma das métricas da BART. Palavras-Chave: Tomada de Decisão de Risco, Córtex Pré-frontal Dorsolateral, Córtex Pré-frontal Ventromedial, Estimulação por Corrente Direta Transcraniana, Balloon Analogue Risk Task vi Effects of Transcranial Direct Current Stimulation (tDCS) over dlPFC and over vmPFC in the Behavior in a Risky Decision-Making Task Abstract Decision-making is a complex behavior that comprises multiple component processes. Risky decision-making has been gaining particular attention as daily we need to make decisions under some degree of risk and knowing what makes us prone to risk may help us predict our decisions. As individuals make decisions in a regular and predictable manner when driven by emotions (Keltner & Lerner, 2010), it is pertinent to explore the capability of modulating decision-making. Since the dorsolateral and the ventromedial prefrontal cortices have been implicated in decision-making (Nejati et al., 2021), a useful strategy would be to apply tDCS over these regions. We aimed to evaluate the effects of anodal tDCS over vmPFC and over dlPFC on the modulation of risky decision-making during a Balloon Analogue Risk Task (BART; Automatic BART and Manual BART) in 32 healthy volunteers (ages between 18 and 25). We hypothesized that all individuals would reveal a preference for low-risk decisions in the active comparatively to the sham session. A mixed-design ANOVA was run for both BART metrics, followed by pairedsamples t-tests (or Wilcoxon test) to analyze differences between groups. Results revealed no statistically significant differences between the sham and active sessions in none of the BART metrics. Keywords: Risky Decision-Making, Dorsolateral Prefrontal Cortex, Ventromedial Prefrontal Cortex, Transcranial Direct Current Stimulation, Balloon Analogue Risk Task Index Introduction ....................................................................................................................... 8 1. State of the art .................................................................................................................... 8 1.1. Decision-Making ................................................................................................................................. 8 1.2. Risky Decision-Making ........................................................................................................................ 8 1.3. Decision-Making in the Brain ............................................................................................................... 9 1.4. Neuromodulation Decision-Making ..................................................................................................... 10 2. Goals ................................................................................................................................. 11 Method ............................................................................................................................ 12 1. Sample .............................................................................................................................. 12 2. Instruments ...................................................................................................................... 12 2.1. Balloon Analogue Risk Task (BART) .................................................................................................... 12 2.2. Self-report questionnaires .................................................................................................................. 15 2.3. Go/No-Go ........................................................................................................................................ 16 3. Experimental design ......................................................................................................... 17 4. Procedure ......................................................................................................................... 17 5.1. BART data ....................................................................................................................................... 18 5.2. Go/No-Go data ................................................................................................................................. 19 5.3. Self-report questionnaires data .......................................................................................................... 19 Results ............................................................................................................................. 20 1. Behavioral results: BART .................................................................................................. 20 2. Manipulation Check: Go/No-Go Task ................................................................................ 22 3. Self-report questionnaires data ........................................................................................ 25 Discussion ....................................................................................................................... 27 1. Future directions .............................................................................................................. 29 Appendix A ....................................................................................................................... 38 Appendix B ....................................................................................................................... 39 14 The instructions given to the participants were the same as in the other format of the experience except for the explanation of how they should respond to pump the balloons. As we intended to reduce any bias that we could predict to the minimum, we used two formats of the BART – the original format from Lejuez et al. (2002), or Manual BART, and the one proposed by Pleskac et al. (2008), or Automatic BART. Both formats of the task were created using PsychoPy (3.0). Illustrations of both formats used are presented in Figures 1 and 2 below. Figure 1 Schema of the Manual BART Figure 2 Schema of the Automatic BART 15 2.2. Self-report questionnaires Considering the role of impulsivity in risky decision-making (Megías-Robles et al., 2022) and its association with dlPFC and vmPFC functioning, participants will be characterized with a widely used measure of impulsivity - Barratt Impulsivity Scale. Peculiarities in inhibitory control processes of individuals were assessed through the application of the BIS/BAS, which measures the reactivity of inhibition and activation systems. The SAM scale provided information about the emotional processing component of the decision. In similar logic, the PANAS was applied to assess changes in mood associated either with tDCS active stimulation or with the performance of the BART. Behavioral Inhibition System and Behavioral Approach System Scale (BIS/BAS) The BIS/BAS has four scales: one for the Behavioural Inhibition System and three for the Behavioural Approach System (BASD, BAS-RR, BAS-FS). Internal consistencies of the subscales are satisfactory – Cronbach’s alpha is .83 for the BIS subscale and .082 for the BAS composite. Barratt’s Impulsivity Scale (BIS-11) The BIS-11 is a 30-item self-report instrument with a four-point scale that appears to be the gold standard for measuring impulsivity. It has been used to explore the social consequences and behavioral correlates of individual differences in impulsivity (Carlson, Johnson, & Jacobs, 2010). In this investigation, Cronbach’s alpha for the 2nd order factors is: .73 for the Attentional, .77 for Motor and .81 for Nonplanning. Impulsive Behavior Scale – Portuguese Version (UPPS-P) UPPS-P is a 59-item self-report scale (Lynam et al., 2006) that assesses impulsivity as a multi-dimensional construct. It comprises the dimensions: Negative Urgency (i.e., the tendency to act rashly under extreme negative emotions); Lack of Premeditation (i.e., the tendency to act without thinking); Lack of Perseverance (i.e., the inability to remain focused on a task); Sensation Seeking (i.e., a tendency to seek out novel and thrilling experiences); Positive Urgency (i.e., the tendency to act rashly under extreme positive emotions; Whiteside & Lynam, 2001). In this investigation, Cronbach’s alpha of UPPS’ dimensions ranges from .84 to .94. Self-Assessment Manikin Scale (SAM) SAM is a non-verbal picture-oriented questionnaire containing three single-item scales that directly measure: the valence of the response (from positive to negative), arousal (from high to low), and perceptions of dominance/control (from high to low) associated a person’s affective reaction to a wide variety of stimuli. Cronbach’s alpha ranges from .63 to .98. 16 Positive Affect and Negative Affect Scale (PANAS) The adapted version of PANAS for the Portuguese population is a scale formed of 10 items about positive affect plus 10 items about negative affect. To fill it, participants must rate the extent to which they experience each within a specified period on a five-point scale, with higher scores indicating higher PA or NA levels. Cronbach's alpha is .86 for the PA subscale and .89 for the NA one. Three additional questionnaires will be applied. The Edinburgh Handedness Inventory (EHI) will be completed at the beginning of the first session to assess participants’ laterality and bridge the need for homogeneity between participants in this feature. The Visual Analog Scale (VAS) will be completed preand post-stimulation to control for potential adverse effects of the stimulation. Moreover, a blinding questionnaire will be completed at the end of each session to assess the blinding procedure's efficacy. Edinburgh Handedness Inventory (EHI) EHI measures hand preference for common manual tasks. To accomplish this, participants must rate 10 statements on the use of the right or left hand when performing a specific action. Scores range from -100 to +100 for left and right-handed, respectively. To be included, participants had to punctuate above 70. Visual Analogue Scale (VAS) The VAS is a 10-item continuous scale that measures potential adverse effects of tDCS. Participants are screened for: tiredness, anxiety, sadness, restlessness, drowsiness, itch, headache, another pain, tingle, and metallic taste. Blinding Questionnaire A blinding questionnaire asks participants to indicate if they think tDCS intervention was active, sham, or do not know the answer, and to mention how confident they feel about their response. 2.3. Go/No-Go In order to do a manipulation check of the effect of the stimulation from tDCS participants also completed a control task at the end of the main task (BART) and before the post-stimulation questionnaires in both experimental sessions. Inhibitory control refers to the capacity of interrupting a tendency action. A recent meta-analysis (Schroeder et al., 2020) that explored the effects of tDCS on inhibitory control demonstrated the existence of a small but significant moderating effect of tDCS on inhibitory control in single-session studies. Once we applied tDCS to increase the neural activity in dlPFC and in vmPFC, which, as we have seen, play 17 roles in impulsivity, application of a task that assesses inhibitory control seemed optimal for manipulation check purposes. The Go/No-Go paradigm is one of the most used (Wessel, 2018). The Go/No-Go task we used here consisted of the sequential presentation of 120 trials represented by black tell screens with only a draw of a white square (30/120) or circumference (90/120) in it. Participants were instructed to click on the “Space” key if they saw a circle on the black screen and not to click on any key and just wait for the experience to move on to the next trial if they saw a square. Each trial was preceded by a cross fixation cross with variable durations and had a duration of 2000 milliseconds, except the ones in which the participant clicked on the “Space” key, which terminated that trial immediately and moved on to the next one. The task was created and presented using E-Prime 3.0 software (Psychology Software Tools, Pittsburgh, PA). 3. Experimental design Since the goal of this study is to analyze and compare the impact of anodal tDCS over vmPFC and dlPFC to sham stimulation, there will be two groups: one will receive anodal tDCS stimulation over vmPFC in one session and sham stimulation in another, and the other will receive anodal tDCS over dlPFC in one session and sham in the other. Each participant will complete two sessions, separated by a minimum of two days washout period – in one session they will receive anodal stimulation, and, in the other, they will receive sham (intrasubject variable). Participants will differ by stimulation condition, i.e., by the fact that they will be stimulated on the vmPFC or the dlPFC (inter-subject variable). In the end, each participant will receive anodal stimulation in one session (either on vmPFC or on dlPFC) and sham stimulation in another. 4. Procedure Participants were contacted by e-mail, requisites for participation were confirmed, study procedures were explained, and the experimental sessions were scheduled. Participants completed some of the self-report questionnaires (EHI, tDCS Feasibility, BIS/BAS, BIS-11) before the first session to accelerate the process. On the first session, participants signed the informed consent form, completed the rest of the self-report questionnaires, and were attributed to one of the two conditions, using Simple Random Sampling. 18 Direct electrical current was delivered using a Magstim Eldith DC Stimulator Plus (Neuroconn, DE) using two rubber electrodes enclosed in saline-soaked sponges. tDCS montage followed the 10-20 EEG system. In the active session of dlPFC group, participants received left anodal/ right cathodal or right anodal/ left cathodal dlPFC tDCS (randomized). To stimulate the left dlPFC, the anode electrode was placed over F3 and the cathode over F4; to stimulate the right dlPFC, polarity was reversed. In the active session of the vmPFC stimulation condition, the anode was placed over Fpz and the cathode over Cz. In the sham session of both conditions, montage was the same as in the respective active condition. A typical and safe stimulation protocol of 2mA with a 30ms ramp-in and ramp-out period was delivered. Stimulation began 5 minutes prior to the BART and lasted for the remaining 20 minutes for active sessions. For sham sessions, the current had an intensity of 2mA as well, but it was turned off after 30 seconds. Participants felt an initial itching but did not receive active current for the rest of the stimulation period. All subjects were blind to tDCS intervention. While the BIS and the BIS/BAS instruments measure trait characteristics, and thus are stable and not prone to fluctuation as a function of one active session of tDCS, the SAM and the PANAS assess states, they are relatively volatile, and therefore susceptible to observable changes in their scores derived from stimulation. As such, these questionnaires were completed again at the end of each session. Also, in the preand post-stimulation assessments, participants were screened for potential adverse effects of tDCS using a continuous VAS. At the end of each session, the blinding procedure's efficacy was assessed with a blinding questionnaire. 5. Data analysis strategy All statistical analyses were done using software JASP (0.16.03). 5.1. BART data Risk-taking behavior was measured through the average number of adjusted pumps from the Manual BART (which considers only the trials in which the balloon did not explode) and the average number of pumps from the Automatic BART (which allows us to consider all trials without a bias towards lower numbers of pumps). 19 In order to scan for possible statistically significant (SS) differences in the BART metrics between the sham session and the active session in both groups, we first ran a mixed-design analysis of variance model, i.e., a mixed-design ANOVA model. In statistics, this model is used to test for differences between two or more independent groups whilst subjecting participants to repeated measures. In this case, the between-subjects variable is the stimulation site (vmPFC or dlPFC) and the within-subjects variable is the stimulation type (sham and active). Then, to specifically evaluate the impact of modulating vmPFC and modulating dlPFC on the BART metrics, we needed to compare BART metrics from active tDCS with those resulting from sham tDCS, in a within-subject design, using paired samples t-tests (active vmPFC versus sham and active dlPFC versus sham). In cases where the normality of the distribution did not verify, we used a nonparametric alternative, the Wilcoxon test. The statistical analyses considered the Adjusted Mean Score from the Manual BART and the Average Number of Pumps from the Automatic BART. 5.2. Go/No-Go data Analysis of the results of the Go/No-Go task was done through the computation of the D’Prime, a variable derived from signal detection theory and is thought to represent a person's ability to detect a target from among distracters, thus considering the proportion of targets to nontargets (Bodnar et al., 2007). A higher D’ means a better performance at the task; in this case: a higher accuracy, with a reduced proportion of misses and false alarms. To analyze the impact of stimulation by tDCS in inhibitory control, we ran a Pearson’s correlation test for the D’Prime score between the sham session and the active session, for both stimulation groups (distributions’ normality verified). 5.3. Self-report questionnaires data The VAS informed about possible negative outcomes from tDCS (descriptive statistical data at Appendix A). For the Blinding Questionnaire, responses’ frequency for “the guessing item”, i.e., indicating whether they thought that session had been active, sham or if they did not know, was calculated, per group, and per session (Appendix B). The BIS/BAS, BIS-11 and UPPS-P were applied once, and the SAM and PANAS were applied at the beginning and at the end of each session. Considering that the tDCS montages used are thought to 20 modulate impulsivity and inhibitory control processes, as well as to interfere with emotional and rational factors of decision-making, it seemed pertinent to investigate possible associations between participants’ performance on both formats of the BART, in the active and/or sham sessions and their scores on the self-report questionnaires that aimed to access these precise constructs. As such, Pearson or Spearman correlation tests (depending on whether normality of the distributions was verified or not, respectively) were run for the scores on the BIS/BAS, BIS-11, and UPPSP and the four metrics obtained from the BART – MANUAL_Sham, AUTO_Sham, MANUAL_Active, AUTO_Active. Pearson’s or Spearman’s correlation tests were also run for the scores on the Sam and the PANAS in the sham and active sessions and participants’ performance on the BART metrics. Paired-samples t-tests, or the Wilcoxon test (when normality assumption did not verify), were run to detect SS differences between scores on the self-report questionnaires pre and post stimulation in both sessions. Results 1. Behavioral results: BART Descriptive statistics of the main metrics of the study, i.e., the metrics produced by the BART, in the active and in the sham session of both groups are presented in Table 1. The mixed-design ANOVA model ran for the average number of pumps from the Automatic BART revealed no significant main effect of Stimulation Type (F(1, 30)=0.319, p=0.576, h2=0.003) and no SS interaction effect Stimulation Type*Stimulation Site (F(1, 30)=0.222, p=0.641, h2=0.002). A SS main effect of Stimulation Site was not found either (F(1, 30)=0.103, p=0.751, h2=0.003). Although no SS results were found by the mixed-design ANOVA for the average number of pumps from the Automatic BART, the descriptive plot seems to suggest a tendency (Figure 1). While in the sham session the average number of pumps is evidently lower in the dlPFC stimulation group than in the vmPFC one, in the active session there is an accentuated decrease in the average number of pumps in the vmPFC stimulation group whereas in the dlPFC it remains almost the same. In order to assess the SS of this difference in the average number of pumps between the sham and active sessions in the vmPFC group, a paired-samples t-test was applied. The results yielded no SS differences (W(1, 16)=83.000, p=0.782, rrb=0.085). 21 The mixed-design ANOVA ran on the adjusted mean score from the Manual BART revealed no SS main effect of Stimulation Type (F(1, 30)=0.199, p=0.659, h2<0.001) and no SS interaction effect Stimulation Type*Stimulation Site (F(1, 30)=1.069, p=0.309, h2=0.003). An SS main effect of Stimulation Site was not found either (F(1, 30)=0.009, p=0.923, h2<0.001). Once again, despite the non-SS results obtained on the mixed-design ANOVA for the adjusted mean score from the Manual BART, a tendency is evidenced by the descriptive plot (Figure 2). The adjusted mean score is lower on the sham session for the vmPFC stimulation group than for the dlPFC stimulation group. On the other hand, on the active session, the adjusted mean score decreases for the dlPFC stimulation group whereas the one for the vmPFC stimulation group notably increases. Thus, in the active session, contrary to what is seen in the sham session, the adjusted mean score is higher for the vmPFC stimulation group than for the dlPFC one. To evaluate the statistical significance of this change in the adjusted mean score for the active compared to the sham session, in the vmPFC stimulation group, a paired-samples t-test was further applied. No SS differences were found (t(1, 16)=-1.108, p=0.284, Cohen’s d = -0.269). Similarly, a paired-samples t-test was run for the adjusted mean score in the active and in the sham session for the dlPFC stimulation group and, once more, no SS differences were encountered (t(1, 14)=0.392, p=0.701, Cohen’s d = 0.101). Table 1 Descriptive Statistics of the Main Metrics of the BART, in the Sham and the Active Sessions of the dlPFC and the vmPFC Groups N Mean Std. Deviation Shapiro-Wilk P-value of Shapiro-Wilk AUTO_Sham_dlPFC 15 42.033 12.167 0.978 0.954 AUTO_Sham_vmPFC 17 44.271 12.954 0.973 0.873 AUTO_Active_dlPFC 15 41.827 13.057 0.968 0.834 AUTO_Active_vmPFC 17 41.976 10.720 0.972 0.853 MANUAL_Sham_dlPFC 15 41.487 12.535 0.980 0.969 MANUAL_Sham_vmPFC 17 39.851 11.979 0.954 0.528 MANUAL_Active_dlPFC 15 40.788 12.828 0.961 0.713 MANUAL_Active_vmPFC 17 41.609 12.063 0.953 0.498 22 Figure 3 Descriptive plots of the Automatic BART Figure 4 Descriptive plots of the Manual BART 2. Manipulation Check: Go/No-Go Task tDCS effects on inhibitory control were analyzed through the D’Prime metric of the Go/No-Go task. The descriptive statistics of this metric can be found in Tables 2 and 3. Normality test of Shapiro-Wilk ran for the dlPFC group did not indicate a deviation from normality (p=0.989). The paired-samples t-test ran for the D’Prime metric of the sham sessions and for the D’Prime metric of the active sessions, in the dlPFC stimulation group revealed no statistically significant differences ( t(1, 14)=-0.033, p=0.974 , Cohen’s d = 0.133 ). The test of normality of Shapiro-Wilk ran for the vmPFC 23 stimulation group did not suggest a deviation from normality (p=0.929). The paired-samples t-test ran for the D’Prime metric in this group yielded no SS results either ( t(1, 16)=1.139, p=0.276 , Cohen’s d = 0.276). Although no SS differences were found between the D’Prime of the active and D’Prime of the sham session, in both groups, the correspondent descriptive plots seem to present a trend. While a tendency towards a decrease in the D’Prime metric from the sham to the active session in the vmPFC group can be observed (Figure 6), there does not seem to be a difference in the dlPFC group (Figure 5). Table 2 Descriptive Statistics of the Metrics Extracted from the Go/No-Go Task, in the dlPFC Stimulation Group, in the Sham and in the Active Session Mean Std. Deviation ShapiroWilk P-value of ShapiroWilk Acc (NoGo)_Sham 0.831 0.155 0.909 0.132 ACC (Go)_Sham 0.996 0.007 0.608 < .001 Acc (NoGo corrected: 1-1/2*N = 0,983)_Sham 0.827 0.151 0.893 0.075 Omission errors (1 - Acc Go)_Sham 0.004 0.007 0.611 < .001 Omission errors (corrected 1/2*N = 0,005)_Sham 0.008 0.005 0.580 < .001 d'_Sham 3.625 0.792 0.940 0.386 Acc (NoGo)_Active 0.820 0.159 0.865 0.029 ACC (Go)_Active 0.997 0.009 0.398 < .001 Acc (NoGo corrected: 1-1/2*N = 0,983)_Active 0.823 0.161 0.848 0.016 Omission errors (1 - Acc Go)_Active 0.003 0.009 0.385 < .001 Omission errors (corrected 1/2*N = 0,005)_Active 0.007 0.008 0.370 < .001 d'_Active 3.629 0.839 0.915 0.159 Table 3 Descriptive Statistics of the Metrics Extracted from the Go/No-Go Task, in the vmPFC Stimulation Group, in the Sham and in the Active Session Mean Std. Deviation ShapiroWilk P-value of ShapiroWilk Acc (NoGo)_Sham 0.831 0.121 0.947 0.406 ACC (Go)_Sham 0.997 0.007 0.571 < .001 Acc (NoGo corrected: 1-1/2*N = 0,983)_Sham 0.829 0.118 0.935 0.264 Omission errors (1 - Acc Go)_Sham 0.003 0.007 0.569 < .001 Omission errors (corrected 1/2*N = 0,005)_Sham 0.007 0.005 0.543 < .001 d'_Sham 3.572 0.596 0.978 0.934 30 investigations trying to accomplish what we tried to accomplish here could add experimental condition with different protocols for the stimulation of the dlPFC (unilateral dlPFC, bilateral, right cathode/left anode and left cathode/right anode); this way, the ideal protocol for modulating risk-taking behavior could be discriminated. It would also be also worth adding neuromodulation techniques with a higher spatial precision, such as High-Definition tDCS, in order to avoid shunting effects. 2. Conclusion The results obtained did not allow us to confirm our hypotheses, but there are some relevant conclusions to be drawn. Attending to the sample size setback we had, vmPFC remains, in our view, a good candidate for a region to modulate using tDCS. Regarding dlPFC-related results, they sure are congruent with the previous literature insofar as they added to the existent notion that there is still no consistent evidence about the precise way in which this region’s activity affects the process of decision-making under risk. First, it is imperative that an investigation that compiles different stimulation protocols into different experimental conditions is developed in order to clarify dlPFC’s role on these processes, as well as the optimal stimulation parameters to use when aiming to modulate them. Exploring more spatially precise neuromodulation techniques should be considered. Only afterwards can we know how therapies and treatments for increased impulsivity or deficits in inhibitory control should be designed. 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Behavioural Brain Research , 400 , 113044. https://doi.org/10.1016/j.bbr.2020.113044 38 Appendix A Table A1 Means and Standard Deviations of the VAS items, per session, in the dlPFC stimulation group Table A2 Means and Standard Deviations of the VAS items, per session, in the vmPFC stimulation group Session Sham Active Pre Post Pre Post M SD M SD M SD M SD Tiredness 4,267 2,154 3,667 2,059 3,667 2,35 2,6 1,999 Anxiety 2,333 2,257 1,533 1,959 2,133 2,2 1,733 1,831 Sadness 1,533 1,552 0,867 1,187 1,933 2,344 1,2 1,612 Restlessness 2,2 2,274 1,6 2,098 2,067 1,751 1,733 2,187 Drowsiness 3,467 2,8 4 2,673 3,533 2,446 2,4 2,501 Itch 0,4 0,828 1 1,254 0,533 0,99 2,533 2,475 Headache 0,6 1,404 0,933 1,668 0,667 1,589 0,8 1,146 Another Pain 0,533 1,356 0,467 1,06 0,467 1,246 0,333 0,816 Tingle 0,467 1,302 0,533 1,125 0,267 0,799 1,6 1,805 Metallic Taste 0 0 0 0 0,067 0,258 0 0 Session Sham Active Pre Post Pre Post M SD M SD M SD M SD Tiredness 5,235 2,796 4,529 2,478 4,353 103,882 4,412 152,118 Anxiety 1,882 1,833 2,118 2,421 2,353 51,882 0,941 32,941 Sadness 0,765 0,97 0,176 0,529 0,706 13,529 0,118 1,765 Restlessness 1,118 1,576 1,941 2,561 2,706 109,529 1,706 85,529 Drowsiness 4,765 2,884 3,941 2,926 4,059 168,941 4,235 211,059 Itch 0,353 0,862 1,176 2,007 0,471 18,235 2,353 151,882 Headache 0,412 1,064 0,647 1,115 1,059 30,941 1,412 46,118 Another Pain 1,118 1,996 0,706 1,532 0,706 21,529 0,529 14,235 Tingle 0 0 0,412 0,87 0,235 15,059 2,353 149,882 Metallic Taste 0,059 0,243 0 0 0 0 0,176 8,471 39 Appendix B Frequencies of “Sham”, “Active” and “I don’t know” answers, per stimulation group, and per session Stimulation Group dlPFC vmPFC Sham Active Sham Active "Sham" answers 0.2 0.133 0.294 0.294 "Active" answers 0.8 0.866 0.588 0.647 "I don't know" answers 0 0 0.118 0.059