Cognitive Training Effectiveness on Memory, Executive Functioning, and Processing Speed in Individuals With Substance Use Disorders: A Systematic Review

Background: Cerebral neuroplasticity is compromised due to substance abuse. There is damage to neuronal areas that are involved in memory and executive functioning. Treatments with worse outcomes are often associated with cognitive deficits that have resulted from substance dependence. However, there is evidence that cognitive training can lead to improvements in cognitive functions and can be useful when treating addictions. This systematic review aims to synthesize evidence on the effectiveness of cognitive training in memory, executive functioning, and processing speed in individuals with substance use disorder (SUD). Methods: The Joanna Briggs Institute's PICO strategy was used to develop this systematic literature review. Four databases were searched (PubMed, the Cochrane Library, Web of Science, and PsycINFO) to identify controlled randomized clinical studies and quasi-experimental studies, in English, Portuguese, and Spanish, from 1985 to 2019. The literature found was examined by two independent reviewers, who assessed the quality of studies that met the inclusion criteria. The Cochrane risk-of-bias tool for the randomized controlled trials and the ROBINS-I tool for non-randomized studies were used to assess the risk of bias. In data extraction, the Cochrane Handbook for Systematic Reviews was considered. Results: From a total of 470 studies, 319 were selected for analysis after the elimination of duplicates. According to the inclusion criteria defined, 26 studies were eligible and evaluated. An evaluation was performed considering the participant characteristics, countries, substance type, study and intervention details, and key findings. Of the 26 selected studies, 14 considered only alcoholics, six included participants with various SUD (alcohol and other substances), three exclusively looked into methamphetamine-consuming users and another three into opioid/methadone users. Moreover, 18 studies found some kind of cognitive improvement, with two of these reporting only marginally significant effects. One study found improvements only in measures similar to the training tasks, and two others had ambiguous results. Conclusions: The included studies revealed the benefits of cognitive training with regard to improving cognitive functions in individuals with SUD. Memory was the most scrutinized cognitive function in this type of intervention, and it is also one of the areas most affected by substance use. Systematic Review Registration: [PROSPERO], identifier [CRD42020161039].


INTRODUCTION
Substance abuse is a worldwide problem. It has not only medical, but also social and economic consequences. According to the World Health Organization (2018), it is estimated that 31 million people experience substance use disorders (SUD) and that annually 3.3 million die due to harmful use of alcohol alone. Despite this, presently adequate treatment is only accessible to a minority (Ozgen and Blume, 2019).
Addiction is characterized by a disruption in the brain's reward system cycle, which tends to increase progressively and lead to compulsive consumption of a certain substance, therewith leading to loss of control (Koob and Moal, 1997). Progress in neuroscience has allowed the conceptualization of addiction as a chronic brain disease that comprises several factors, among which are socio-cultural, genetic, and even neurodevelopmental features (Volkow and Morales, 2015). Substance dependence or repeated drug use compromises the neuroplasticity of the brain. Several regions of the brain are impaired due to this consumption, including the neural areas involved in memory (Fernández-Serrano et al., 2011;Sampedro-Piquero et al., 2019) and executive functioning (Fernández-Serrano et al., 2011;Morie et al., 2014). Continued substance use impairs brain function, interfering with self-control and making the subject more sensitive to high stress levels and more prone to the presence of negative mood (Volkow and Morales, 2015). Addiction is also Abbreviations: JBI, Joanna Briggs Institute; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ROBINS-I, Risk of Bias in Nonrandomized Studies -of Interventions; SUD, Substance Use Disorders; WMT, Working Memory Training; WM, Working Memory. characterized by compulsive behaviors (Volkow and Morales, 2015).
When an individual becomes addicted to a particular substance, nerve cells that are located in the brain's reward circuit tend to adapt epigenetically during repeated exposure to the substance in question. These adaptations lead to lasting changes in brain functions, which in turn contribute to dysfunctional behaviors related to the abused substance (Hamilton and Nestler, 2019). In fact, cognitive impairment resulting from substance use is not only common but has been linked to worse treatment outcomes (Sampedro-Piquero et al., 2019).
According to several authors [Vonmoos et al., 2014;see Sampedro-Piquero et al. (2019)], cognitive impairment that results from substance use can be reversed, at least partially, by prolonged drug withdrawal. Abstinence reinforces the neuroplasticity of the brain and, therefore, its regenerative capacity (Sampedro-Piquero et al., 2019). However, others (e.g., Volkow and Morales, 2015;Verdejo-Garcia, 2016) propose that interventions that improve cognitive functioning can contribute to the long-term success of treatment for addiction. Volkow and Morales (2015) go so far as to say that these interventions would be useful even if total abstinence does not occur.
As Hofmann et al. (2012) described, impairment in core executive functions has been linked to poor self-regulation and decision-making. Working memory (WM) impairments, for example, could not only interfere with patient's daily activities (e.g., finding and holding a job) but also impact important clinical variables, such as dropout rates (Rezapour et al., 2016). Such impairments can also make it harder for individuals to correctly evaluate high-risk situations, which may then result in greater difficulties preventing relapse or achieving personal goals (Rochat and Khazaal, 2019). As such, it is not surprising that neurocognitive impairments have been growingly considered as relevant transdiagnostic targets for SUD treatment (Yücel et al., 2019). Interventions that aim to reduce cognitive impairment in these domains, namely cognitive training, could lead to improved treatment outcomes.
There are many types of cognitive training programs, such as working memory training (WMT), executive-functions training, video-game training, and even music and chess instruction (Sala and Gobet, 2019). Working memory training is the most studied type of cognitive training programs (Sala and Gobet, 2019), and its predominance can be explained by the known association between WM and fluid and general intelligence (Salthouse and Pink, 2008). Given its essential role in cognition, it has been believed that WMT could lead to improvements in domaingeneral cognitive skills and, as such, allow for "far-transfer" of training effects. These programs tend to be structured (e.g., number and duration of sessions) and make use of specialized computer software, but they can differ with regards to the specific structure, the chosen tasks (e.g., n-back tasks) and the difficulty level. Executive-functions training programs, similarly to WMT, tend to be structured but propose to focus on more than one cognitive domain. Beyond WM, these programs can also consider training tasks concerning inhibitory control and cognitive flexibility, as well as, reasoning and problem-solving skills (Diamond, 2013). While in WMT, most programs are computerized, in executive-functions training there seems to be a higher heterogeneity with regards to the context and delivery of the chosen tasks (e.g., computer-based tasks, addons to school curriculum, martial arts programs; Diamond, 2013). While WMT and executive-functions training tend to be programs specifically designed with the goal of improving cognitive functioning, it was hypothesized that other, less specific but cognitively demanding activities could have similar benefits. Among them, videogames, music and chess instruction have all received considerable scientific interest and been the subject of several studies (Sala and Gobet, 2019). Despite the diversity of cognitive training programs, overall cognitive training is thought to produce both functional and anatomical changes in the neural system that lead to improvement in cognitive function (Sala and Gobet, 2019).
Although the potential value of improving cognitive functioning in certain populations such as SUD is not disputed, there is disagreement concerning the use of cognitive training for this end. There is an on-going controversy surrounding the effectiveness and clinical relevance of cognitive training that lies on the question: Is it possible for domain-specific tasks and training to impact domain-general cognitive skills? Many studies have cast doubt to the possibility of "far transfer" of any effects resulting from cognitive training (e.g., Melby-Lervåg and Hulme, 2013;Melby-Lervåg et al., 2016;Redick, 2019;Sala and Gobet, 2019), indicating that these effects tend to be short-term and/or training specific, and therefore don't lead to generalized cognitive benefits. Sala and Gobet (2019) go further and argue that when significant effects are observed, they are often associated with limitations in the design of the experiments, such as the lack of an active control group. However, there is the argument that the longevity or "far-transfer" effects of cognitive training could be being masked by the studies' almost exclusive reliance on primary outcomes, as suggested by Brooks et al. (2020) in regards to WMT. These authors also postulate that the current definition of "far-transfer" is too narrow, since it does not consider how cognitive performance (e.g., WM performance) might impact apparently unrelated functions (e.g., impulse control). In fact, in a review of the neural processes of WMT, Brooks et al. (2020), reported that significant neural effects (in frontoparietal and frontostriatal circuitry) could be found, often independently of behavioral changes. Moreover, they reported that alongside neural changes, various neuroimaging studies found "far-transfer" effects of WMT to other un-related cognitive domains.
The on-going debate highlights the importance that more studies be conducted with the aim of reviewing the effectiveness of cognitive training programs on specific contexts and populations, such as SUD.
In the present systematic review, we aim to understand whether cognitive training interventions are effective in improving memory and/or executive functioning in individuals with SUD. In this sense, we intended to synthesize the effectiveness of cognitive training in individuals with SUD with regard to improving memory, executive functioning, and processing speed by answering the following questions: I Is it possible to improve the memory of individuals with SUD through cognitive training programs? II Is it possible to improve the executive functioning of individuals with SUD through cognitive training programs? III What are the most used cognitive training programs in individuals with SUD and what is their effectiveness?

Search Strategy
The protocol for this review was registered and published in the International Prospective Register of Systematic Reviews (PROSPERO) with identification number CRD42020161039. The Population, Intervention, Comparison, and Outcome (PICO) strategy of the Joanna Briggs Institute (JBI; Aromataris and Munn, 2017) was the basis for this systematic literature review. The main objective was to synthesize the effectiveness of cognitive training in individuals with SUD when there are improvements in memory, executive functioning, and processing speed. The research strategy aimed to identify published studies, as well as unpublished studies, written in English, Portuguese, and Spanish, from 1985 to 2019. The selected period was based on the first found article referring to cognitive training in individuals with SUD . It was also intended to include gray literature to limit the bias of the present review.
Initially, a general search was carried out in the JBI Database of Systematic Reviews and Implementation Reports, the Cochrane Database of Systematic Reviews, MEDLINE, Epistemonikos, and PROSPERO to confirm the absence of other systematic literature reviews with the same objectives as the present review. Subsequently, an exhaustive and limited search in four databases was performed, including PubMed, the Cochrane Library, Web of Science, and PsycINFO. Then, the titles were analyzed and the articles were summarized using the search terms.
The search terms originated from DeCS R and Medical Subject Headings (MeSH Browser R ). These were also combined with the Boolean operators, as well as with the elements of the PICO strategy. Below are the keywords used in the search: Lastly, the references of all selected studies were analyzed for the possibility of including new studies. The articles resulting from the bibliographic search, organized according to the steps previously described, were analyzed by two reviewers. First, the titles and abstracts of studies that could possibly be eligible for the literature review were evaluated, followed by the analysis of the full article.

Types of Participants
The present review aimed to select studies that included individuals with SUD, aged ≥ 18 years.

Types of Intervention(s)
In this review were included studies on cognitive training programs focused on memory and/or executive functioning in individuals with SUD. Moreover, since the terms cognitive training, stimulation, and rehabilitation are often confused and used interchangeably in the literature, studies on programs with these designations (i.e., stimulation or rehabilitation) were also considered, provided their characteristics were in line with the description of cognitive training presented below. Cognitive training, which is the focus of the present review, usually entails guided practice on a number of structured tasks that focus on specific cognitive functions (e.g., memory, attention), and can be applied individually or in a group. It is common for tasks to present different levels of difficulty, allowing the selection of the appropriate level for each individual. This type of intervention is grounded on the assumption that regular practice tends to improve or, if improvement is not possible, maintain functioning in a certain cognitive domain, and possibly allow the generalization of cognitive gains over time. As a rule, the results are assessed using cognitive or neuropsychological instruments (Clare and Woods, 2004). Contrastingly, cognitive stimulation generally involves a series of tasks/activities and discussions in a group context, with the intention of improving not only cognitive but also social functioning. This type of approach concerns a generalist method, with no focus on specific cognitive functions, since it is based on the argument that cognitive functions should not be exercised in isolation, but rather combined with other functions (Clare and Woods, 2004). Finally, in cognitive rehabilitation, there is an individualized approach in which the individual, and sometimes their family, helps to establish personally-relevant goals and device appropriate strategies for their particular experience and social context. The focus is on improving the functioning on the everyday context and not on specific cognitive tasks. In this case, neuropsychological tests are not used with the aim of observing improvements in cognitive functions, but rather to substantiate any impact that may result from the changes inherent to the disease in question (Clare and Woods, 2004).

Types of Results
This review aimed to include studies that considered cognitive training programs, namely for (working and long-term) memory, executive functioning (planning, abstract reasoning, cognitive flexibility, and inhibitory control), and processing speed.

Types of Studies
The selected studies were experimental (randomized controlled, and quasi-experimental with a control group) in an adult population, with articles written in English, Spanish, or Portuguese. The studies had to meet the following inclusion criteria: a) a control group that has the same characteristics as the experimental group (individuals with SUD, aged ≥ 18 years); b) pre-and post-test evaluations; c) objective measures to assess memory and/or executive functioning; and d) standardized measures (in the pre-and post-tests) that are not the same or identical to the exercises used in the cognitive training.

Controls
This review included studies with an active or a passive control group. An active control group is identified by the consideration that another type of intervention is performed on the participants, without affecting the variables of interest, such as the same intervention with some changes (alternative intervention) or another type of intervention. In the inactive/passive control group, participants are not subjected to any other type of intervention and/or treatment or alternatively are subjected to standard care (e.g., treatment as usual) or a placebo (Karlsson and Bergmark, 2015;Coughtrey et al., 2018).

Exclusion Criteria
All studies that were not published in English, Spanish, or Portuguese were excluded. Review studies and animal studies were also excluded.

Evaluation of the Methodological Quality of the Studies
The identified articles were independently evaluated by two reviewers, using the standardized JBI instruments. In this context, we used the JBI Critical Appraisal Checklist for Randomized Controlled Trials for randomized controlled trials and the JBI Critical Appraisal Checklist for Quasi-Experimental Studies (non-randomized experimental studies) for quasiexperimental studies (Tufanaru et al., 2017).
To assess the quality of a study, namely the risk of bias, we used the Cochrane risk-of-bias tool for the randomized controlled trials (Higgins et al., 2011). This checklist allowed us to perform a complete assessment of risk of bias that may affect the cumulative evidence of the review. Six bias domains were examined: selection, performance, detection, attrition, reporting, and other biases. The studies were classified as "unclear risk, " "low risk, " and "high risk" in each of the above domains. In turn, for the non-randomized studies, the Risk of Bias in Nonrandomized Studies -of Interventions (ROBINS-I) tool was used (Sterne et al., 2016). The following domains were analyzed: baseline confounding, selection of participants, classification of intervention, deviation from intended intervention, missing data, measurement of outcomes, and selection of reported results. In this case, each study in question was classified as "low risk of bias, " "moderate risk of bias, " "serious risk of bias, " "critical risk of bias, " and "no information." In situations where the reviewers did not reach a consensus on the inclusion or exclusion of a study, a third reviewer intervened. All studies that met the inclusion criteria are included in this review, and any methodological weaknesses present in the selected studies are also discussed.

Data Extraction
Data were extracted considering the Cochrane Handbook for Systematic Reviews . Analysis considered the following items: 1. Countries 2. Substance type 3. Randomization and blindness 4. Cognitive functions 5. Follow-up 6. Outcome measures 7. Characteristics of interventions 8. Key findings The data were extracted by two independent reviewers (TC; ER).

Data Synthesis
Due to the heterogeneity of the data, no meta-analysis was performed. Therefore, a narrative approach was used for data synthesis. There were significant differences between interventions, populations, comparators, and the presentation of outcome results, and thus it was not possible to make a direct comparison regarding the study results. Since statistical pooling was not viable, it was then decided to use tabular and narrative formats to present the results.

Study Selection and Search Results
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart (see Figure 1) shows the studies included and excluded from the present review. Through the research strategies identified above, a total of 467 studies were obtained (54 in PubMed, 124 in Web of Science, 100 in the Cochrane Library, and 189 in PsycINFO) and three studies using other research sources. After the elimination of duplicates, 319 studies remained for analysis. To determine the eligibility of the studies according to the inclusion criteria, their titles and abstracts were analyzed. Fifty studies were considered based on the eligibility criteria; they were analyzed in full by two reviewers (TC; ER). In case of discrepancies, a third reviewer intervened (TA). After this analysis, 24 studies were excluded (see Supplementary Material) and 26 studies met all inclusion criteria. Of the 26 studies included, 25 are controlled randomized clinical studies Yohman et al., 1988;Wetzig and Hardin, 1990;Fals-Stewart and Lucente, 1994;Steingass et al., 1994;Peterson et al., 2002;Goldstein et al., 2005;Fals-Stewart and Lam, 2010;Rupp et al., 2012;Gamito et al., 2013Gamito et al., , 2014Gamito et al., , 2016Gamito et al., , 2017Eack et al., 2015;Rass et al., 2015;Bell et al., 2016Bell et al., , 2017Hendershot et al., 2018;Zhu et al., 2018;Khemiri et al., 2019;Rezapour et al., 2019) and one is quasi-experimental (Hannon et al., 1989). The PRISMA guidelines were used to conduct this systematic literature review. Table 1 summarizes the characteristics of the participants from the 26 included studies. The sample sizes ranged from 12 to 160 participants (with an average of 56.5 participants).

Study Characteristics
The characteristics of the studies (randomization, blindness, control group, and outcome measures) are provided in Table 2.

Characteristics of Interventions
The intervention characteristics (programs, cognitive functions, follow-up, total number of sessions, duration and number of sessions per week, and difficulty level and type of training) are provided in Table 3.

Total Number of Sessions, Duration, and Number of Sessions per Week
One study considered modification of the hierarchical learning intervention (two sessions of 45 min; Wetzig and The memory training program comprised learning and information retrieval tasks, orientation tasks, and exercises to recall recent events for a total of 8 weeks.

Memory training program
Memory 12 months NP NP NP NP NP NP  The experimental group performed several memory training taks, with associated learning tasks, Reality Orientation Training, image recognition, and memory retention tasks for recent events. Hardin, 1990), one used the adaptive Operation Span (OS) and Symmetry Span (SS) tasks in 15 training sessions over <4 weeks (Gunn et al., 2018), one resorted to a cognitive training program of ∼12 training sessions and six memorygame sessions (twice a week training sessions and daily memory games/scanning tasks; Steingass et al., 1994), another applied a Cognitive Enhancement Therapy, with 60 h of training (Eack et al., 2015), and another included the version of the Goldman rehabilitation training (15 sessions of 30 min each, five times a week; Goldstein et al., 2005). One study used a cognitive training program, however the authors did not provide details on the intervention , and another study employed a cognitive rehabilitation program of 48 sessions (50 min each, twice a week; Fals-Stewart and Lucente, 1994). There were also two studies that used specific memory training programs: one included a 32-session memory training program (1 h, four times a week; , and the other a retraining memory program consisting on eight 1-h sessions (Hannon et al., 1989). Finally, Yohman et al. (1988) used a cognitive training program consisting of 20 sessions of ∼30 min each. Considering the 24 studies that provided information on the number of sessions, there was an average of ∼20 training sessions per intervention. However, from the total 18 studies that found some kind of cognitive improvement resulting from the cognitive training, the average number of sessions was slightly superior, at 23 sessions per intervention. The details of the interventions can be found in more detail in Table 3.

Key Findings
Two studies presented somewhat ambiguous results. One study (Eack et al., 2015) reported significant improvement in neurocognition, but described the differences in the areas where the biggest changes were found (processing speed and verbal learning) as failing traditional significant thresholds. Another , reported significant improvements in memory functioning for both the training and active control groups, without presenting data on the statistical comparison between them.
One study (Rass et al., 2015) discriminated results regarding similar and dissimilar measures to the training tasks, reporting improvements in some measures of WM (visuospatial WM and digit span) similar to the training tasks, although no improvements in their dissimilar equivalent.
Finally, the efficacy/effectiveness of cognitive training was not supported in five studies Hannon et al., 1989;Peterson et al., 2002;Brooks et al., 2016Brooks et al., , 2017.  reported that the control and experimental groups showed the same improvement in terms of memory functioning. Hannon et al. (1989) concluded that the obtained results did not show sufficient support to confirm the objective of the study. However, there was still an increase in the Memory Matrix Test between the pre-test and the post-test. Peterson et al. (2002) did not confirm the efficacy of the Computerized Cognitive remediation program. Brooks et al. (2016) found that WM accuracy was improved in the experimental group, but that no near-transfer effects were found (no significant differences in the Trail Making Test). However, the experimental group did show more pronounced neural changes. Similarly, Brooks et al. (2017) reported a learning effect of 35% between pre and post-test, but no significant differences in executive measures (Trail Making Test).

Risk of Bias
In the present literature review, the risk of bias in randomized controlled trials was assessed using the Cochrane Risk of Bias Tool (Higgins et al., 2011). In turn, the non-randomized study (Hannon et al., 1989) was assessed for risk of bias using the ROBINS-I tool (Sterne et al., 2016). Since the methodological details of many of the studies included in the present review were incomplete or not sufficiently detailed (see Supplementary Material), we consider that the risk-of-bias assessment has limitations. However, we observed that the most common possible sources of bias in the randomized controlled trials studies selected for this review refers to the blinding of participants and personnel (performance bias) and blinding of outcome assessment (detection bias). There were also 14 studies in which we were unable to assess the type of concealment performed Yohman et al., 1988;Wetzig and Hardin, 1990;Fals-Stewart and Lucente, 1994;Steingass et al., 1994;Peterson et al., 2002;Goldstein et al., 2005;Fals-Stewart and Lam, 2010;Rupp et al., 2012;Gamito et al., 2013Gamito et al., , 2014Eack et al., 2015;Brooks et al., 2017;Gunn et al., 2018) due to the lack of methodological information (as can be seen Supplementary Material). This lack of information is also a possible source of bias. With reference to low risk of bias, after complete analysis, only two studies (Hendershot et al., 2018;Khemiri et al., 2019) presented a low risk of bias in all the assessment domains (see Supplementary Material).
On the other hand, the quasi-experimental study included (Hannon et al., 1989) in the present review presented a moderated risk of bias on the baseline confounding, selection of participants and selection of reported results. There were also domains (deviation from intended information and missing data) where there can be possible risk of bias due to lack of information provided (see Supplementary Material).
The presented final assessment was discussed between the two reviewers (TC; CC) who examined the discrepancies between the performed evaluations. In situations where the reviewers did not reach a consensus, a third reviewer intervened (TA). The data found highlights selection bias, performance bias and detection bias as risk of bias for the cumulative evidence for the present review.

DISCUSSION
The main goal of the present review was to understand what the state of the art tells us with reference to the effectiveness of cognitive training interventions in improving memory and/or executive functioning in individuals with SUD. Although this review will certainly not resolve the controversy regarding cognitive training, we hope that it will serve as a pertinent contribution to what is, without a doubt, a very important debate.

References
Study aim(s) Key finding(s)  Evaluate long-term memory improvements in participants having as a base an intensive memory rehabilitation program for amnesic alcoholics Both the memory training group and the active control group showed improved memory function in the post-test. There is no information about a statistical comparison between the groups in order to examine possible differences.  Understand whether the memory function can be generalized to other memory functioning tasks and determine the duration of maintenance of the gains in question The control group showed the same benefits in memory performance as the experimental group.
Determine whether the neuropsychological areas involved in patients with alcoholism who undergo cognitive training have improved compared with individuals who have not received any type of training; understand whether other cognitive areas can benefit from training, even if it is specific to a certain area The problem-solving group showed improvements in the results of the problem-solving tests compared with the group that did not receive any training. However, the problem-solving group did not show increase in terms of memory and in perceptual-motor skills. Hannon et al. (1989) Examine the effectiveness of memory retraining in individuals with alcohol problems The results did not show sufficient support to confirm the objective of the study. Only the Memory Matrix Test showed gains between the preand the post-test. Wetzig and Hardin (1990) Understand whether cognitive retraining impacts a sample of individuals with SUD and cognitive impairment Individuals who received remedial training achieved an equal and superior performance on the Wisconsin Card Sorting Test than the general population. Steingass et al. (1994) Determine whether semantically encoded material is favored by the treatment The experimental group that received treatment showed improvements in terms of reproduction of figures and verbal memory.

Fals-Stewart and
Lucente (1994) Based on a cognitive rehabilitation program, evaluate whether there are neuropsychological changes in a sample of individuals with drug use and the presence of cognitive deficits During the first 2 months of treatment, patients who received the cognitive rehabilitation program showed gains in cognitive functioning: Cerebral recovery was faster in these patients. Peterson et al. (2002) Investigate the efficacy of the NeurXerciseTM program, which concerns a computerized cognitive remediation program, within the scope of cognitive recovery The effectiveness of the computerized cognitive remediation program used in the study was not confirmed. There were no statistically significant differences between the group that received the program, the placebo group, and the group without intervention. Goldstein et al. (2005) Investigate the effectiveness of a cognitive training program in order to benefit the cognitive functioning of individuals with alcohol use disorder and comorbidities with other neuropsychiatric disorders, namely in the subacute phase of detoxification There were cognitive increases in the experimental group compared to the placebo group, namely in the conceptual flexibility and attention.

Fals-Stewart and
Lam (2010) Evaluate whether patients in the experimental group who received standard treatment plus computer-assisted cognitive rehabilitation, compared with a control group who received an intensive care program, showed better results in cognitive functioning The group with standard treatment plus computer-assisted cognitive rehabilitation showed a faster overall improvement in cognitive functioning compared to the control group. However, it was not possible to determine whether these improvements were differential for the various cognitive functions. Rupp et al. (2012) Assess whether cognitive remediation therapy during treatment improves cognitive functioning in patients with alcohol use disorder.
The group that received cognitive remediation therapy showed significant increment in memory, executive functioning and care, especially in WM delayed memory and attention (divided attention and alertness). Improvements were also noted in the Mini Mental State Examination and Complex Figure Test indices. Gamito et al. (2013) Evaluate the effect of cognitive stimulation using serious games in a sample of patients with alcohol dependence syndrome There were improvements in the general cognitive functions assessed in all groups. However, there was an improvement in the frontal area in the cognitive functioning of the individuals in the group who received a cognitive stimulation program, using mobile technology. Gamito et al. (2014) Evaluate the cognitive effects in a sample of individuals with alcohol dependence based on a neuropsychological intervention using serious games and mobile technology There was an increase in general cognitive skills, both in the control group and in the experimental group. However, the improvement was more significant in terms of frontal lobe functions in the experimental group. Processing speed was evaluated using two versions of the Color Trail Test (CTT). Although there was a decrease in the error rate and execution time of CTT1 and CTT2, there was no statistically significant interaction in terms of the treatment factor. Eack et al. (2015) Evaluate the efficacy and feasibility of using Cognitive Enhancement Therapy in a sample of patients with schizophrenia and alcohol/cannabis misuse Cognitive Enhancement Therapy was an effective and viable treatment for cognitive impairments in schizophrenic patients with alcohol/cannabis problems. The neurocognitive gains were most evident in verbal learning and processing speed (NIMH MATRICS Consensus Cognitive Battery), although neither showed statistically significant differences.

(Continued)
Frontiers in Psychology | www.frontiersin.org  Rass et al. (2015) Examine whether WMT brings cognitive changes in a sample of methadone maintenance patients.
The experimental group of methadone maintenance patients achieved improvements in some measures of WM after receiving WMT, namely in visuospatial WM and digit span. However, there were no improvements on WM measures dissimilar from the training tasks. Bell et al. (2016) Evaluate the efficacy of cognitive training in memory deficits and verbal learning of older veterans with alcohol use disorder Cognitive training in conjunction with work therapy was effective in ameliorating memory deficits in a sample of individuals with alcohol use disorder. Brooks et al. (2016) Evaluate the effect of standard psychological TAU and adjunct WMT on brain volume in male in-patients receiving treatment for methamphetamine (MA) use.
The control group (TAU) presented larger volume in the bilateral putamen and reduced volume in the left middle temporal gyrus, right post-central gyrus and left insula cortex. The experiemntal group (TAU + WMT) showed more pronounced increases in volume that extended across large areas of the bilateral basal ganglia, along reduced bilateral cerebellar volume. WM accuracy at post-test in the experimental group was associated with larger volume in the right middle frontal cortex and orbitofrontal cortex.While there was an improvement in WM accuracy in the experimental group, no near-transfer effects were found (no changes in the Trail Making Test). Gamito et al. (2016) Evaluate the efficacy of a Cognitive Stimulation Program, using mobile devices, related to the cognitive rehabilitation of recovering alcoholic individuals There was significant benefit in terms of frontal lobe functioning in the experimental group. Bell et al. (2017) Test whether the group of individuals who received cognitive remediation therapy and work therapy showed improvements in neurocognitive functions compared with a group that only received work therapy There were significant differences in the executive functioning indexes in the group that received cognitive remediation therapy and work therapy. There were no statistically significant differences in the rate of change of processing speed between cognitive remediation therapy with work therapy and the work therapy with treatment as usual. Brooks et al. (2017) Evaluate the impact of daily WMT alongside treatment as usual (TAU) on self-report measures of impulsivity and self regulation in patients receiving treatment for methamphetamine (MA) use.
From the experimental group (TAU + WMT), those who engaged in the highest level of training had a learning effect of 35% between pre and post-test, and showed significant changes in self-reported impulsivity and self-regulation scores. There were no significant differences in executive measures (Trail Making Test) between pre and pot-test in the experimental group. Gamito et al. (2017) Analyze the efficacy of cognitive training in the rehabilitation and stimulation of addicts in recovery, based on a serious games approach There was an increase in cognitive functioning in terms of frontal brain functions as well as sustained attention and verbal memory. There were also improvements in decision-making and cognitive flexibility. Gunn et al. (2018) Examine the efficacy a complex WMT program in those with an alcohol use disorder (AUD), as well as predictors of training improvement.
There was significant transfer on two near WM transfer measures (Rotation Span and Auditory Consonant Trigram) at post-test and 30-day follow-up for individuals who completed the WMT, independent of the group (AUD vs. healthy control). There was also evidence of transfer on one moderate transfer task (Running Spatial Span) at post-test, but not on the 30-day follow-up. Hendershot et al. (2018) Assess whether the WMT together with treatment as usual contributes to improvements in executive functioning in the short term There were marginally significant improvements found in the digit span (primary outcome) and in the results of the Cogmed Progress Indicator index (secondary outcome). There were no other secondary outcome improvements to support the efficacy of WMT. Zhu et al. (2018) Understand whether cognitive impairments can be improved based on the Computerized Cognitive Addiction Therapy (CCAT) application Comparing with the control group, the CCAT group had better cognitive performance after 4 weeks of training as well as better performance on impulsive control tasks.
Test the efficacy and viability of a WMT program (computerized) in patients with alcohol use disorder The experimental group saw significant improvements in verbal, but not spacial, WM functioning. No effect of WMT was found on other cognitive functions.
Evaluate the efficacy of a cognitive rehabilitation treatment with a view to improving the neurocognitive functions of individuals with opioid use disorder The group of individuals who received cognitive rehabilitation treatment showed significant improvements in terms of processing speed, WM, and memory span. There was also an increase in these individuals in the switching and learning tests. In turn, these effects were shown to persist for at least 6 months.
hypothesis that cognitive training can be a relevant addition to SUD treatment. Moreover, even though that was not the focus of this review, it is important to note that various studies (even some that did not see significant cognitive improvements; Fals-Stewart and Lucente, 1994;Fals-Stewart and Lam, 2010;Rupp et al., 2012;Eack et al., 2015;Rass et al., 2015;Brooks et al., 2016Brooks et al., , 2017Rezapour et al., 2019) reported a positive impact of cognitive training on clinical and/or SUD variables.

The Impact of Cognitive Training on Memory in SUD
From all cognitive domains, memory was the domain most targeted in the reviewed studies. This is likely explained by the fact that memory is not only one of the areas most affected by substance use, but also one believed to impact treatment outcomes. Significant improvements regarding memory could be found in studies with various SUD populations (i.e., substance of use). When considering overall memory capacity, positive and significant effects were found in participants who consumed both alcohol and other substances (Bell et al., 2016). Concerning WM specifically, significant improvements were shown for both participants who consumed only alcohol (Rupp et al., 2012;Gunn et al., 2018;Khemiri et al., 2019), and those who also used other substances (Hendershot et al., 2018). Khemiri et al. (2019) discriminated between verbal and visuospatial WM, and only found significant changes for the first. Delayed and verbal memory were also studied subdomains, and positive changes in these were found in alcohol-consuming participants (Rupp et al., 2012), and opioid-consuming participants (Gamito et al., 2017).
It is also important to analyse the studies that did not found significant memory improvements following cognitive training. From the studies that showed a clear lack of cognitive improvement after cognitive training, four studies focused on memory Hannon et al., 1989;Brooks et al., 2016Brooks et al., , 2017 with two of those specifically on WM (Brooks et al., 2016(Brooks et al., , 2017, and one considered a number of cognitive functions (e.g., visual-motor coordination, visual-spatial skills) including memory (Peterson et al., 2002). Regarding population, three of these studies explored the effectiveness of cognitive training in alcoholics Hannon et al., 1989;Peterson et al., 2002), and two in methamphetamine users (Brooks et al., 2016(Brooks et al., , 2017. Some of these studies presented significant limitations that may have affected the results, such as small sample size and/or high drop-out rate Peterson et al., 2002), reported possible insensitivity of outcome measures Hannon et al., 1989), and a lack of specificity in the training techniques . Moreover, Peterson et al. (2002), proposed that the lack of baseline cognitive impairment in their study participants may explain theirs result. They pointed out that cognitive training may be more effective on those with at least mild to moderate baseline cognitive impairment, something that would be interesting to consider in future research. Interestingly, two of these studies Hannon et al., 1989) delivered the cognitive training intervention in a group setting. Rass et al. (2015) and Brooks et al. (2016Brooks et al. ( , 2017, presented results that justify a more in-depth look. Rass et al. (2015) had the only study that clearly discriminated results according to the measures' level of similarity to the training tasks. They found that there were significant improvements in some measures of WM similar to the training tasks, but no improvements in dissimilar measures. These results indicate the presence of "near" but not "far transfer" effects, and highlight the root of the ongoing debate about cognitive training effectiveness. Brooks et al. (2016) too found that although WMT did not lead to significant changes in the cognitive measures used (i.e., Trail Making Test), it did increase memory accuracy (in the training tasks). In turn, memory accuracy showed itself to be connected with larger volume in the right middle frontal cortex and orbitofrontal cortex, both regions associated with WM ability and executive functioning. Brooks et al. (2017), found similarly that WMT did not lead to significant improvements in the cognitive measures used (i.e., Trail Making Test), but did lead to a learning effect of 35% and significant changes in self-report measures looking into impulsivity and self-regulation. These results are intriguing and bring up questions about the efficacy of cognitive measures in evaluating potential benefits of WMT, or cognitive training in general, and in adequately assessing "far transfer" effects. In a more recent review study, Brooks et al. (2020) reported that WMT can lead to significant neural effects often in the absence of behavioral changes. Moreover, various neuroimaging studies appeared to have found "far transfer" effects of WMT to other un-related cognitive domains, something that might be harder to measure.

The Impact of Cognitive Training on Executive Functioning and Processing Speed in SUD
Similarly to memory, executive functioning was also studied in different SUD populations (i.e., substance of use). Bell et al. (2017) found significant improvements on neurocognitive measures of executive functioning in participants who consumed both alcohol and other substances following 13 weeks (5 h/week) of cognitive training (both auditory and visual tasks). In line with these findings, Gamito et al. (2017) showed an improvement on the frontal lobe functions of opioid-consuming participants after 10 cognitive training sessions. Concerning mental flexibility specifically, significant improvements were found in alcoholconsuming participants (Gamito et al., 2014). Finally, problemsolving, which is a skill strongly associated with executive functioning, also showed significant positive effects in the same population (Yohman et al., 1988).
In comparison with memory and executive functions, there appears to be a lack of interest in studying the impact of cognitive training on processing speed. From the studies included in the review, only four targeted this cognitive domain (Gamito et al., 2014;Eack et al., 2015;Bell et al., 2017;Rezapour et al., 2019). And, from those, only Rezapour et al. (2019) reported significant improvements in the processing speed of individuals with opioid use disorder who received cognitive training. These improvements persisting for at least 6 months.

Cognitive Training Programs
Cognitive training programs have suffered significant changes over the years as a result of technological advancement. When these programs first started to be used, they were administered with a paper-and-pencil modality, but today most new cognitive training programs created are computer-or even mobile-based. The studies included in this review reflected this tendency, with the majority of cognitive training programs used being computerized (Fals-Stewart and Lucente, 1994;Peterson et al., 2002;Fals-Stewart and Lam, 2010;Rupp et al., 2012;Gamito et al., 2013Gamito et al., , 2014Gamito et al., , 2016Gamito et al., , 2017Eack et al., 2015;Rass et al., 2015;Bell et al., 2016Bell et al., , 2017Brooks et al., 2016Brooks et al., , 2017Gunn et al., 2018;Hendershot et al., 2018;Zhu et al., 2018;Khemiri et al., 2019).
Only five studies declared using paper-and-pencil training programs, and predictably four of those were among the oldest studies included in the review Hannon et al., 1989;Wetzig and Hardin, 1990;Steingass et al., 1994). Interestingly, the fifth study (Rezapour et al., 2019), used the recently developed paper and pencil cognitive rehabilitation package NEuroCOnitiveREhabilitation for Disease of Addiction (NECOREDA).
There is another, more recent, type of cognitive training intervention that we did not considered in this review for lack of any studies that met the inclusion criteria-Virtual Reality programs. These type of interventions have shown promising results in other diseases and/or disorders that involve impairment of cognitive functions (Pedroli et al., 2018). However, to date, most studies that use virtual reality in the scope of SUD seek to understand the relationship between environmental stimuli and drug use (Bordnick et al., 2011;Hone-Blanchet et al., 2014). Indeed, studies that explore virtual reality as a cognitive training tool in SUD are scarce. To our knowledge, only Man (2018) has studied the effectiveness of this type of intervention on the improvement of cognitive functioning in individuals with substance abuse disorders. The results appear promising. As a drastically different form of delivering cognitive training, it is important that more research be conducted to study its effectiveness and compare it to the type of interventions used to date.
It is also important to highlight the diversity of cognitive training programs (e.g., administration, duration, number of sessions, and hours of training) and populations (i.e., substance of use, time of abstinence) included in the reviewed studies. This heterogeneity, along with the lack of detailed information about the used interventions found in many studies, prevented us from analyzing the results more in-depth and from evaluating the real impact of these variables, for example on effect size. It also made it impossible to generalize about the improvements obtained in cognitive functions for the general population with SUD.
Finally, the lack of concealment concerning the researchers in most of the included studies in the present review stands out, along with the fact that some studies failed to provide information regarding the methodology used for concealment of the participants.

CONCLUSIONS
Overall, this review found that the majority of the included studies reported cognitive improvements following cognitive training, including in two of our main domains of interestmemory and executive functioning. In addition, various studies also found that cognitive training led to significant changes in clinical (e.g., treatment engagement) and SUD variables (e.g., substance use, relapse rate), even though the mechanisms behind these improvements are not completely understood.
Although the results appear promising, the heterogeneity among the studies regarding the type of cognitive training program used and the population studied demands further and more careful research. To this end, future studies should explore the comparative effectiveness of similar cognitive training programs on different SUD populations. Moreover, they should also study the impact of structural variables (such overall duration, number of sessions, and hours of training), on the effectiveness of the programs. This data would be relevant to understand the feasibility (and cost-benefit) of integrating these type of interventions in different clinical settings.
Concerning the controversy about the generalization (or lack thereof) of cognitive gains from cognitive training, we support those who have suggested that many of the studies conducted to date have been too narrow in their approach. We believe future research into cognitive training effectiveness may gain from broadening the concepts of "far-transfer, " as well as from considering multiple forms of assessment (e.g., cognitive tests, neuroimaging, and self-report questionnaires) when measuring potential effects.
It is becoming clear that, if we want to bring clarity to the discussion surrounding the effectiveness of cognitive training, we should not only start asking more nuanced questions, but also considering that the answers may likewise be more complex.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.

AUTHOR CONTRIBUTIONS
TC, MP, and MD contributed to the conception and design of the study, constant revision, wrote the article, which was critically revised by all the other authors, and revised the manuscript critically for relevant intellectual content. TC and ER conducted the literature search, selection, data extraction, and analysis. TC and CC conducted the assessment of study quality. Disagreements were resolved by TA. TC, ER, and CC revised the last version of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

FUNDING
This work was funded by Portuguese national funds provided by Fundação para a Ciência e a Tecnologia (FCT) (UIDB/05704/2020). The research center, ciTechCare, provided the necessary funds to cover the open access publication fees.