Effectiveness of Cognitive Training for School-Aged Children and Adolescents With Attention Deficit/Hyperactivity Disorder: A Systematic Review

Problems with executive functions (EF) are hallmark characteristics of Attention Deficit/Hyperactivity Disorder (ADHD). Therefore, this review analyzed the efficacy of cognitive training for EF in reducing ADHD symptomatology and improving educational, interpersonal, and occupational outcomes in children and adolescents with this disorder. A systematic search, using a PICO (population/participant, intervention/indicator, comparator/control, outcome) framework was carried out. From 2008 to 2018, resorting to EBSCOhost, the following databases were searched: Academic Search Complete, ERIC, MEDLINE with Full Text, PsycARTICLES, PsycINFO, and Psychology and Behavioral Sciences Collection. Twenty-two studies were included in this review. Of the 18 studies that reported performance-based measures of EF, 13 found improvements and five did not. Overall, 17 studies showed positive transfer effects on ADHD symptomatology, EF, academic improvement, reduced off-task behavior, and/or enhanced social skills. Of the nine studies that performed follow-up sessions, seven concluded that the treatment effects were maintained over time. In sum, results showed that cognitive training can be an effective intervention for children and adolescents with ADHD and might be a complementary treatment option for this disorder.

processes develop throughout childhood and adolescence and are invaluable to the cognitive, behavioral, emotional, and social functioning of the individual (Anderson, 2002), originating a variety of difficulties when impaired (Brown, 2013).
Consequently, EF has been broadly investigated in individuals with ADHD and, even though results have been incongruous, studies showed poor performance of children with ADHD on EF tasks when compared to typically developing peers (e.g., Nigg et al., 2002;Willcutt et al., 2005). For instance, a metaanalytic review composed of 83 studies evaluated the validity of the EF theory in this population and observed that children with ADHD display significant deficits in inhibitory control, vigilance, working memory, and planning (Willcutt et al., 2005). A few studies also found difficulties in processing speed (Nigg et al., 2002;Lawrence et al., 2004;Pasini et al., 2007;Yáñez-Téllez et al., 2012), cognitive flexibility (Lawrence et al., 2004;Geurts et al., 2005;Yáñez-Téllez et al., 2012), and sustained attention (Nigg et al., 2002;Trani et al., 2011;Yáñez-Téllez et al., 2012). Thus, problems with EF seem to be hallmark characteristics of this disorder.
Treatment options for ADHD are limited and, frequently, involve the prescription of psychostimulant medication as a first line treatment (Yildiz et al., 2011). Improvements in behavior, attention, interpersonal interactions, cognition (Biederman and Spencer, 2008), and EF (e.g., Barnett et al., 2001;Swanson et al., 2011) reinforce the short-term efficacy of psychostimulant medication, of which methylphenidate and dextroamphetamine are the most prescribed (Rabipour and Raz, 2012). Nevertheless, the limitations of such medication (e.g., short-term effects, unknown long-term effects, sideeffects such as insomnia and lack of appetite) prompt parents and professionals to look for another treatment options (Rabipour and Raz, 2012). Thus, efforts have been made to develop non-pharmacological interventions that decrease ADHD symptomatology, and cognitive training has been considered a potential intervention. As reported by Vinogradov et al. (2012), due to brain plasticity, cognitive training can strengthen and develop essential brain networks and underlying cognitive processes by exposing the brain to well-defined learning tasks, resulting in more adaptive behaviors across contexts.
The tasks presented in cognitive training interventions vary extensively, are usually conferred as games, and can be presented through a computer or pen and paper format, aiming to improve a plethora of abilities such as working memory, attention, inhibitory control, planning, and cognitive flexibility. As it is important to keep the child engaged, motivated, and practicing at a level that is in accordance with or slightly above their current abilities (Diamond, 2012;Rapport et al., 2013), this training is usually adaptive (i.e., the difficulty of the task is adjusted to the performance of the child; Rapport et al., 2013). Thus, it has been proposed that cognitive training can reduce ADHD symptomatology and improve functioning by addressing the neuropsychological deficits thought to mediate its pathophysiology (Cortese et al., 2015).
A meta-analytic review carried out by Cortese et al. (2015) examined the effects of cognitive training on ADHD symptomatology, neuropsychological deficits, and academic skills in children and adolescents with ADHD. The authors concluded that there were significant effects of training on ADHD symptoms when considering unblinded raters. Yet, these results were drastically reduced when analyses were limited to trials with active control groups or where raters were blind to treatment conditions. Additionally, significant performance improvements in objective measures of visual and verbal working memory were reported, while there were no effects on inhibition or attention. However, these effects of training on working memory did not extend to academic outcomes. Other reviews found similar results (e.g., Karch et al., 2013;Rapport et al., 2013;Sonuga-Barke et al., 2013). However, the majority of the studies included in these previous reviews focused on a single EF, such as working memory, inhibitory, and attention (or a combination of these). Given that children with ADHD display a diverse set of EF deficits, and training multiple EF might be a more effective strategy than focusing on a single EF domain (Dovis et al., 2015), a systematic literature review focusing on the training of multiple EF domains is lacking.
As it has been proposed that cognitive training for improving executive functioning can reduce ADHD symptomatology (e.g., Cortese et al., 2015), our main aim is to update and extend the findings of previous systematic reviews and meta-analyses, characterizing the current literature on cognitive training interventions for EF in children and adolescents diagnosed with ADHD. We, thus, examine the outcomes within the included studies to determine the efficacy of cognitive training assessed by performance-based measures of EF and behavioral/EF questionnaires. Additionally, we intended to evaluate the transfer effects (i.e., generalization of training effects to other nontrained tasks) and possible maintenance of gains reported in each study. As such, we developed the following research question using the PICO framework: In children and adolescents with ADHD, is cognitive training for EF, compared to other types of intervention, typically developing controls, or placebo, effective in developing executive functioning, reducing symptomatology, and improving educational, interpersonal and/or occupational outcomes? (cf. Table 1).

Search Strategy
The systematic literature search was conducted between January and February 2018, resorting to EBSCOhost   (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018), the keywords executive function * OR executive functioning AND cognitive training OR intervention * AND Attention Deficit Hyperactivity Disorder OR ADHD were used to conduct the search. Every reference was, then, conveyed to Mendeley and Rayyan, a website developed to assist systematic review authors to perform study selection (Ouzzani et al., 2016), and duplicates were removed. Every study was initially identified by title and abstract, according to the inclusion criteria. Figure 1 details the process of study selection.

Inclusion and Exclusion Criteria
In order to be included in this review, studies had to: (1) include children with ADHD aged 3-14 years; (2) include a cognitive intervention/training focusing on one or more components of EF; (3) include an active and/or a passive control condition; (4) include measures of EF, ADHD symptomatology, academic achievement and/or interpersonal relationship quality as outcomes; and (5) be published in English.
Studies were not excluded if children presented comorbid diagnoses or maintained the course of pharmacological treatment during interventions.
After screening each study by title and abstract, the full texts were analyzed and included if they fulfilled the stipulated criteria. Two additional studies (Green et al., 2012;Johnstone et al., 2012) were hand-searched and included in this review.

Risk of Bias (Quality) Assessment
In order to assess the risk of bias of the included studies, the Cochrane Collaboration tools were used, namely the RoB 2.0 (Sterne et al., 2019) for the randomized trials and the ROBINS-I (Sterne et al., 2016) for the non-randomized trials. The RoB 2.0 assesses five domains of bias, specifically: (1) bias due to randomization, (2) bias due to deviations from intended intervention, (3) bias due to missing data, (4) bias due to outcome measurement, and (5) bias due to selection of reported result. The ROBINS-I, one the other hand, assesses: (1) bias due to confounding, (2) bias due to selection of participants, (3) bias in classification of interventions, (4) bias due to deviation from intended intervention, (5) bias due to missing data, (6) bias in measurement of outcomes, and (7) bias in selection of the reported result. Risk of bias was independently assessed by AV and MF and disagreements were resolved through discussion.

Data Extraction
Data obtained from each study encompassed sample characteristics, study design, settings, intervention materials, outcome measures, and main findings.

Trial Flow
A total of 739 articles were identified from the databases using the search strategy previously reported. Two additional references were hand-searched and included in this review. Two hundred and twenty-four duplicates were removed, and 517 articles were assessed by title and abstract. Of these, 463 reports were excluded since they did not fulfill the predetermined criteria. Hence, 54 papers were included and their full-text analyzed, of which 22 met inclusion criteria. Again, in Figure 1, the study selection process is presented in a PRISMA flow diagram (Moher et al., 2009). Frontiers in Psychology | www.frontiersin.org

General Study Characteristics
The age range of the participants included in each study varied extensively and most of the studies analyzed children aged between 3 and 12 years old (cf. Table 2).
Sample groups were composed by children diagnosed with ADHD and their typically developing peers. Twelve studies included samples of participants with no comorbidities and seven studies included children with comorbid diagnosis such as Opposition Defiant Disorder (ODD), Conduct Disorder (CD), Learning Disabilities (LD), Anxiety and/or Tics, Mood Disorders, Phobias and/or Elimination Disorders. Three studies did not FIGURE 4 | Risk of bias summary for all non-randomized trials included. detail whether they included or excluded participants with comorbidities (cf. Table 2).
Regarding research design, 10 studies were randomized controlled trials, eight were randomized trials, two were open-label/open-trial designs, and two were non-randomized controlled trials (cf. Table 2). In regard to control groups, three of these studies compared the performance of the experimental groups only with active control groups (i.e., medication, nonadaptive training, different intervention) and 14 included passive control groups (i.e., waitlist, healthy control group, normal school activities, treatment as usual) (cf. Table 2). Furthermore, to assess outcomes, eight studies included informants blind to study conditions (i.e., uninformed regarding which people belong to a particular group). One study included only blinded teachers (Beck et al., 2010) and three included blinded classroom observers (Green et al., 2012;Steiner et al., 2014;Minder et al., 2018). In three studies all informants were blind, either parents, teachers, and/or clinicians (van Dongen-Boomsma et al., 2014;Dovis et al., 2015;Bigorra et al., 2016). Lastly, one study used blind clinician assessments (Tamm and Nakonezny, 2015) and another blinded researchers and participants (Green et al., 2012). The remainder fourteen studies used unblinded informants.
Seven studies included in this review were carried out in the USA and 10 in Europe. Two studies were carried out in China, one in Brazil, one in Iran, and one in Australia (cf. Table 2). Eight interventions were conducted at home, six took place in school settings, and four in clinical settings. One study was carried out both in school and clinical settings (Minder et al., 2018). This information was not explicitly stated in three studies. When interventions took place at home, parents where usually the ones providing support during sessions. At school, the intervention was either delivered by teachers, clinicians, or trained research assistants. In regard to the clinical setting, most of the programs were employed by clinicians, but it was not possible to gather precise information in three of these investigations.
Nine of the 22 included studies were published between 2010 and 2014, while five studies were published in 2015, two in 2016, three in 2017, and three in 2018 (cf. Table 2).
Regarding the computerized training, the majority of the studies employed some variation of the Cogmed software. Additional websites and software encompass the Persian software of working memory training, Project: Evo, Braingame Brian, CogniPlus, the Brain Train website, and others. Further programs and activities, without computerized characteristics, feature the activities presented in the manual published by Caponi and collaborators, the OutSMARTers program, PIAFEx, a training program based on Dawson and Guare's training of executive skills for children, and other activities. One study did not specify the training program used during the intervention but provided some insights about its characteristics .

Targets of Intervention
As previously stated, there is no universally accepted definition of EF and, therefore, there is no agreement concerning the elements incorporated in this construct. Consequently, there is extensive variability in the domains of intervention across studies, and, in total, 16 EF were considered. Five of these 16 domains were targeted more frequently, specifically: attention (n = 8), inhibition (n = 8), working memory (n = 16), planning (n = 3), and cognitive flexibility (n = 4). Other components of executive functioning addressed by interventions incorporate organization, processing speed, short-term memory, self/emotional regulation, time management, and theory of mind (cf.

Outcome Measures
A variety of measures were used across studies to measure EF, as detailed in Table 3. These measures can be subdivided into two categories: (1) performance-based neuropsychological measures (i.e., computer-oriented or pen-paper tasks) and (2) behavioral and EF questionnaires (under the perspective of parents, teachers, clinicians and/or significant others).
Within the 22 studies, 44 performance-based measures were used to assess particular aspects of EF. Of these 44 measures, 10 were adopted in three or more studies, respectively: (1) Conners' Continuous Performance Test, (2) Trail Making Test,  Furthermore, within the 20 ratings employed, five were widely used across studies, specifically: (1) Behavior Rating Inventory of Executive Functions, (2) Conners' Rating Scales, (3) Swanson, Nolan, and Pelham Questionnaire−4th edition, (4) Strengths and Difficulties Questionnaire, and (5) ADHD Rating Scale-IV.
Of these 22 studies, 13 did not analyze the possible maintenance of gains through follow-up sessions. Of the nine studies that performed follow-up sessions, seven concluded that the gains observed at the end of the intervention were maintained throughout time (Beck et al., 2010;Johnstone et al., 2012;Egeland et al., 2013;van der Oord et al., 2014;van der Donk et al., 2015;Bigorra et al., 2016;Hannesdottir et al., 2017).
In order to assess if study design had implications in the results obtained across studies, a qualitative comparison of the results obtained in randomized (n = 18) vs. non-randomized (n = 4) trials was conducted. On one hand, randomized studies reported, more often than non-randomized trials, improvements in ratings (≃33 vs. ≃25%) as well as in performance-based measures and ratings combined (≃33 vs. ≃25%). On the other hand, nonrandomized trials reported improvements only in performancebased measures more frequently than randomized studies (≃50 vs. ≃22%).
As previously reported, seven studies contemplated in this review included samples of children with comorbid diagnoses. A qualitative comparison of the results obtained by these studies showed that, comparatively to studies that included children with an ADHD diagnosis only, a higher proportion of studies with included comorbid diagnoses reached improvements in ratings (≃43 vs. ≃25%) and performance-based measures in combination with ratings (≃43 vs. ≃25%). Also, in samples without comorbid diagnoses, improvements were found more frequently only in performance-based measures (≃42%).

DISCUSSION
The first aim of this study was to update and extend the findings of previous reviews, characterizing the current literature on cognitive training interventions for EF in children and adolescents diagnosed with ADHD between 3 and 14 years of age. A total of 741 articles were identified and, after duplicates removal, 517 articles were analyzed. Twenty-two studies were eligible for inclusion. Regarding the characteristics of the included studies, it is useful to highlight important methodological features. Studies tend to include individuals diagnosed with ADHD and other comorbid disorders (i.e., ODD, CD, LD, Anxiety and/or Tics, Mood Disorders, Phobias, and/or Elimination Disorders). Regarding research designs, the majority of the included studies were randomized trials, but a few non-randomized studies were also included as they fulfilled the pre-established inclusion criteria. Also, although all studies included control groups, unblinded outcomes assessments were performed frequently. Most of the research was conducted in USA and Europe in home, school, and/or clinical settings. Regarding intervention programs, computerized but also noncomputerized programs were frequently employed. The most frequent EF domains targeted by interventions were attention, inhibition, working memory, planning, and cognitive flexibility.
Our second aim was to assess whether cognitive training was effective in ADHD as evaluated by performance-based measures of EF and/or behavioral/EF questionnaires. Results showed that most of the studies that used performance-based measures  For simple EF tasks (e.g., sustained attention and inhibition), the experimental group had the same results as the active stimulant medication group. However, for a number of complex EFs (e.g., verbal and visuospatial short-term memory and non-verbal reasoning), the experimental group showed better results than the active stimulant medication and placebo groups. The experimental group showed better results on parent ratings of overall ADHD symptoms, inattention, initiation, planning/organization, and working memory than the waitlist control group. The experimental group improved significantly more than the control group on parent ratings of the metacognition index (i.e., the child's ability to monitor, initiate, plan, organize, and sustain future-oriented problem solving in working memory). Also, the experimental group improved significantly more than the control group on teacher ratings of the metacognitive index, initiation, working memory, monitoring, and shifting. Also, for the experimental group compared to the control group there were significant improvements in performance-based measures of EF, ADHD symptoms, and functional impairment. The experimental group showed better results than the control group in performance-based measures of working memory and other neuropsychological measures. Effects were not found for inattention and hyperactivity problems rated by teachers and parents. The experimental group showed more improvements than the control group on performance-based measures of attention, working memory, and inhibition than the control group, especially among children with greater symptom severity and impaired attention.
6 Dovis et al. (2015) Corsi Block Tapping Test Forward: η 2 p = 0.16 Backward: η 2 p = 0.09 Only children in the full-active condition (where working memory, inhibition, and cognitive flexibility were trained) compared to a partially-active condition (where only inhibition and cognitive flexibility were trained) and to a placebo condition showed better results on measures of visuospatial short-term memory and working memory. The experimental group presented better results than the control group only in processing speed. Reading and mathematics were improved in the experimental group, changes in ADHD symptom rating scales were not visible. In addition, the improvements in reading scores remained significant 8 months later. The experimental group presented reductions in off-task ADHD-associated behaviors after training. Improvements in working memory performance-based measures were also found. No significant improvements were found on parent rating scales.

(Continued)
Frontiers in Psychology | www.frontiersin.org Compared to a waitlist control group, the experimental group (OutSMARTers Program) showed a reduction of ADHD symptomatology, improved social skills and better emotion regulation according to parents. No improvements were found on performance-based measures. No differences were found between the experimental and a parent training group, as both groups showed some improvement. These improvements were still visible 3 months later. Both experimental groups (cognitive training vs. neurofeedback) improved in ratings of ADHD symptomatology and executive functions according to parents and teachers and off-task behavior as reported by blinded raters. An effect of training was found for cognitive training only on inattention symptoms rated by parents.
13 Qian et al. (2017) -After the intervention, children in the experimental group were rated by parents as displaying improved executive functioning, diminished ADHD symptomatology, reduced risk-tasking behaviors and enhanced academic performance. Despite these improvements, the experimental group was still distinguishable from the healthy control group in almost all variables.
14 Re et al. (2015) Walk-No walk: η 2 p = 0.27 MF-14 (errors): η 2 p = 0.37 Children with ADHD presented better performance in tasks assessing attention, inhibition, and working memory. Improvements in children with typical development who attended the training were also found. Both parents and teachers' ratings of ADHD symptomatology improved for the experimental and control groups.
15 Shuai et al. (2017) -The experimental group presented better performance in neuropsychological tests after the intervention, with improvements in processing speed, inhibition, shifting, working memory, and planning. Results from parent rating scales showed reduced ADHD symptomatology and behavioral problems as well as improved executive functioning and academic performance. At post-test, there were no significant differences between the ADHD and healthy control groups.
16 Steiner et al. (2014) -Only children who attended the neurofeedback intervention showed significant improvement in ratings of attention, executive functioning and off-task behavior compared with those in the control and cognitive training conditions. The experimental group showed better results on parent ratings of ADHD symptomatology as well as on the metacognition index and total score of the BRIEF compared to a waitlist control group. These effects maintained stable at the 9-week follow-up and improvements on inhibition were found. Teacher ratings showed no effects of training at post-test but revealed improvements from pre-test to follow-up on ADHD symptomatology.

22
van Dongen-Boomsma et al. (2014) -No significant treatment effect was found on the outcome measures applied. The experimental and placebo groups did not differ at the end of the intervention on behavioral symptoms, neurocognitive performance, executive and global functioning.
Frontiers in Psychology | www.frontiersin.org demonstrated efficacy in improving one or more domains of EF in children and adolescents. Study design appears to have implications in the results obtained across studies, as a qualitative comparison of the results obtained in randomized and nonrandomized trials showed that randomized studies reported, more often than non-randomized trials, improvements in ratings as well as in performance-based measures and ratings combined. Conversely, non-randomized trials reported improvements only in performance-based measures more frequently than randomized studies. Furthermore, we intended to evaluate the transfer of gains (i.e., the generalization of training effects to other nontrained tasks). Regarding these transfer effects, research has shown decreases in parent and/or teacher ratings of ADHD symptomatology, social skills improvements, and reductions in EF dysfunction in daily life. Additionally, improvements in academic performance and reduced off-task behavior (i.e., task disengagement to engage in unrelated behaviors) were reported. In spite of these results showing that cognitive training can be an effective intervention for children and adolescents with ADHD, our conclusions should be interpreted considering limitations of the included studies as discussed below.
As previously mentioned, several studies integrated in this review included participants with associated comorbidities. In fact, Efron et al. (2016) found that in a sample of 132 diagnosed children, aged 4-7 years, 39% had one comorbidity and 37% had more than one comorbidity. According to the authors, ODD (53%), Anxiety Disorder (23.5%), LD (15.9%), and Language Disorder (14.4%) were the most common comorbidities across individuals with ADHD. Similar results have been reported by Reale et al. (2017). The authors found that of the 1,919 subjects evaluated, 66% had at least one comorbid diagnosis, while only 34% presented just ADHD. Among the most common comorbid diagnosis were LD (56%), Sleep Disorders (23%), ODD (20%), and Anxiety Disorders (12%). Therefore, it is clear that the majority of children diagnosed with ADHD have, at least, one comorbid disorder.
The comparison of the results obtained by the included studies in this review demonstrated that a higher proportion of studies that included comorbid diagnoses reached improvements in ratings and performance-based measures in combination with ratings. Contrarily, in samples without comorbid diagnoses, improvements were found more frequently only in performancebased measures. These results suggest that, for children with comorbidities, improvements perceived by informants in daily life were more frequent. In fact, as discussed by Diamond (2012), children with greater difficulties on executive functioning may benefit the most from any intervention focusing on its training. As children with comorbid diagnoses usually present with higher levels of symptomatology and EF problems, they may have more room for improvement than children presenting with one single diagnosis (Flook et al., 2010). As such, individuals with different comorbidities may respond differently to specific treatments, have differing clinical correlates, and/or demonstrate unique clinical outcomes what might influence results obtained across studies. So, additional studies should group ADHD individuals into more homogenous subgroups based on comorbid patterns.
Regarding control groups, in order to consider that differences between the groups may be accounted to effects of the intervention, researchers should compare the performance of an experimental group and a control group that "accounts for improvements caused by factors other than the treatment" (i.e., an active control group; Boot et al., 2013). In line with these theoretical assumptions, assessing the efficacy of interventions by comparing the performance between a treated group and a non-treated group (i.e., treatment as usual, waitlist, typical development) would not be appropriate since both groups have different expectations (Boot et al., 2013), influencing results on outcome measurements. In fact, of the studies included in this review, three reported active control groups and five used both active and passive control groups. Nevertheless, the majority of the comparison groups were passive (n = 14), and these considerations should be taken into account while interpreting these results.
Another limitation of most of the studies conducted is the lack of transfer effects when the efficacy of the intervention is assessed by blinded raters. Even though this was confirmed across the majority of studies that included unblinded informants, positive results should also be highlighted. Beck et al. (2010) and Bigorra et al. (2016) assessed treatment efficacy through blinded raters and found significant results. Beck et al. (2010) found slight improvements in the initiate scale of the BRIEF-Teacher Form, even though these only approached significance. Bigorra et al. (2016) found significant improvements in several subscales of the BRIEF-Teacher and Parent Forms, with small to large effect sizes. The authors also found significant improvements in ADHD symptoms according to both teachers and parents. These results show that blind raters are able to detect changes in everyday situations following cognitive training interventions. Nevertheless, more studies using blind raters are needed in order to provide a better understanding of the effects of cognitive training.
For future studies, there are a number of additional issues that researchers must address to support empirical evidence for the implementation of EF training as a complementary intervention for individuals with ADHD. Specifically, a welldesigned intervention should (a) randomize participants into the experimental and control groups; (b) match participants in variables that might account for differences between groups other than the treatment (e.g., age, comorbidity); (c) control for participants and informants expectations through blinding and assessment of expectations prior to the beginning of the intervention to control for possible placebo effects; (d) compare the performance of the experimental group to both active and passive control groups; and (e) use both performancebased measures and ratings of EF and behavior to assess the interventions' efficacy.
Notwithstanding, this review represents an important contribution as it includes a wider range of studies (i.e., different designs and interventions), having important clinical and educational implications, as it demonstrates the feasibility and positive effects of conducting EF training with children and adolescents with ADHD in a variety of contexts.
In sum, our results showed that cognitive training can be an effective intervention for children and adolescents with ADHD and might be considered a complement of psychostimulant medication. Nonetheless, conclusions should be interpreted with caution due to important methodological limitations. However, the available evidence certainly justifies the allocation of resources to evaluate the efficacy of EF interventions, since they carry the promise of reducing ADHD symptomatology and improving academic, interpersonal, and occupational outcomes.

AUTHOR CONTRIBUTIONS
AV and MF contributed to the conception and design of the work. AV prepared the first draft of the manuscript.
MF revised the manuscript critically for important intellectual content. MF and SV revised the last version of the manuscript.