Skip to main content
PMC home page
PLOS ONE logoLink to PLOS ONE
. 2020 Jul 9;15(7):e0235510. doi: 10.1371/journal.pone.0235510

Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized controlled trials

Rodrigo Fernández López 1,*,#, Adoración Antolí 1,2,#
Editor: Jose A Muñoz-Moreno3
PMCID: PMC7347178  PMID: 32645046

Abstract

Introduction

Acquired brain injury (ABI) leads to cognitive deficits in a great variety of cognitive functions. Interventions aimed at reducing such deficits include the use of computer-based cognitive interventions. The present work synthetizes and quantitively analyses the effect of computer-based cognitive interventions in ABI.

Methods

PubMed, Scopus, Web of Science, ProQuest and Ovid databases were searched for randomized controlled trials (RCT) addressing this issue. A total number of 8 randomized-controlled trials were included for systematic review and meta-analysis. Univariate meta-analyses were conducted for every cognitive function, producing aggregates when a study contributed more than one effect size per cognitive domain.

Results

Random-effects meta-analyses showed an improvement of Visual and Verbal working memory, while other domains like Attention, Processing speed, Executive functions and Memory were not benefited by the interventions.

Conclusions

Computer-based cognitive interventions might be a beneficial intervention for ABI population to improve Visual and Verbal working memory, although no effect was found in other cognitive domains. Implications and possible future directions of the research are discussed.

Introduction

Acquired brain injury (ABI) can lead to deficits in attention, memory, executive functions and processing speed. Approximately, 50–60% of traumatic brain injury (TBI) patients manifest memory and attention problems, and 30% of the patients require assistance in the activities of daily living [1]. On the other hand, between 70–96% of stroke patients have cognitive impairment to some degree [2]. These deficits can lead to a loss of functional independence [3] and disability [4]. ABI represents a major global health burden. Estimated costs for stoke and TBI were EUR 97.1 billion in Europe [5] and USD 221 billion in the United States [6].

Cognitive intervention refers to the provision of neuropsychological interventions aimed at rehabilitating, restoring or compensating neurocognitive impairments after ABI. The interest in cognitive rehabilitation has increased over the years [7] and there are considerable efforts in the search of evidence-based interventions [8] for ABI patients. Computer-based cognitive interventions are potentially an important tool for the rehabilitation of neurocognitive impairments. Theoretically, computer-based cognitive interventions can be sensitive to the user performance and adapt in real time the level of difficulty or the nature of the task. Additionally, they present advantages over classical cognitive interventions, allowing the standardization of the intervention and providing performance data to both the user and the professional, which can help to adapt the intervention to the patient’s needs. Computer-based cognitive interventions are usually based on direct cognitive training of the different cognitive domains. Cognitive interventions can be multi-domain or single-domain. Multi-domain interventions target several different cognitive domains (e.g. memory, executive functions and working memory) throughout the duration of the intervention. On the other hand, single-domain interventions focus in the training of a single cognitive domain along the whole process. Some of these computer-based interventions can be carried out by the patient alone or with the therapist involved. Computer-based programs can be used in addition with other compensatory techniques such as strategy training in order to improve the performance of the patients in the given task.

Several meta-analyses have addressed the efficacy of computer-based cognitive interventions in Dementia [9, 10], Mild Cognitive Impairment (MCI) [11] and healthy population [12]. Although the trials included in these studies had methodological problems that could be improved, they showed a general positive small effect on cognition. Previous systematic reviews in mild traumatic brain injury [13], stroke [14] and ABI [15] population suggest that computer-based cognitive interventions might be effective, although the current available evidence is weak and methodologically flawed. To date, no meta-analysis has been performed on computer-based cognitive interventions for ABI.

Thus, the objective of this study is to systematically review and meta-analyze randomized controlled trials (RCT) that study the effect of computerized cognitive interventions for ABI in the different cognitive domains.

Methods

This study was conducted following the recommendations of Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines [16] (see S1 Table). The review and meta-analysis protocol (#CRD42019138833) was pre-registered with PROSPERO International Prospective Register of Systematic Reviews. All the data and R code used in this study can be freely accessed and consulted at: https://osf.io/9r3ks/?view_only=145ae9c0bbb8418796832ea1d73f28d0

Eligibility criteria

Inclusion criteria were as follows [1] randomized-controlled trials, [2] active or passive control group, [3] acquired brain injury population, [4] intervention aimed at improving cognition [5] use of computer-based intervention, [6] evaluation of cognition using standardized tests immediately post-intervention and [7] pre-post design.

Exclusion criteria were as follows [1] non-randomized trials, [2] uncontrolled trials, [3] trials with inadequate control group (e.g. comparing standard cognitive intervention vs computer-based), [4] participants with neurodegenerative conditions, [5] participants with neurodevelopmental disorders, [7] absence of cognitive assessment, [8] testing was not done immediately after intervention and [9] insufficient data to estimate effect size.

Information sources

We conducted a search in PubMed, Scopus, ProQuest, Ovid and Web of Science databases. We also consulted references from studies and accessed Google Scholar database. The latest search was carried out in September 2019 without any time or language restriction.

Search strategy

The search equation applied to all the databases was: ("cognitive intervention" OR "cognitive training" OR “cognitive stimulation” OR "cognitive remediation" OR "cognitive rehabilitation" OR "neuropsychological intervention" OR "attention training" OR "memory training" OR "executive function* training" OR “flexibility training” OR "processing speed training" OR "working memory training" OR "brain training" OR “brain games” OR "reasoning training" OR "mental training" OR "neurocognitive training") AND ("computer-based" OR "computerized" OR "videogame" OR "computer game") AND ("acquired brain injury" OR "traumatic brain injury" OR”stroke” OR “brain injuries” OR “cerebrovascular disorders”).

The search terms were developed collaboratively by the two review authors (RFL, Rodrigo Fernández López and AAC, Adoración Antolí Cabrera).

Selection process

Eligibility was assessed by RFL following the exclusion and inclusion criteria. After the electronic search and duplicate removal, article titles and abstracts were screened. The full-text articles that met initial eligibility criteria were assessed for a final determination of eligibility by the two review authors independently. When a disagreement occurred, the decision was made by consensus. When there was insufficient information to assess eligibility (e.g. unclear control group), the authors were contacted for further information.

Data collection process

A spreadsheet was created containing the main coded variables for the study. The items coded for each effect size were [1] demographics (e.g., %female, age), [2] type of ABI (e.g., stroke, traumatic brain injury, mixed), [3] intervention domain (e.g., working memory, memory, executive functions, processing speed, attention), [4] intervention duration, dosage and characteristics, [5] control group design (i.e., passive or active) and [6] neuropsychological assessment (e.g., digit span forward, trail making test, WAIS sub-tests). When necessary data to estimate effect size was missing, study authors were contacted via e-mail. When study authors did not answer within one month, a second e-mail was sent asking for the data. A total number of 6 authors were contacted via e-mail, of which 2 authors responded. Of those 2 authors, one author was not able to access the data we were requesting, and the other author did not send us the data.

Intervention domains and outcome measures were coded according to previous works [17, 18] that categorize the data into cognitive domains based on the description of the intervention and assessment on each study.

Summary measures

Effect sizes were calculated as standardized mean differences (SMD) with a 95% confidence interval (CI) using the Hedge’s g estimator. To estimate effect size and variance, the formula for pre-post study designs with a control group proposed by Morris [19] was used. Positive values are interpreted as an improvement on the cognitive function of the experimental group compared to the control group. When an outcome measure reflected improvement by scoring less (e.g., reaction times), the g values were inverted. According to Cohen’s criteria, values of 0.2–0.5 are interpreted as small effect, 0.5–0.8 as medium effect, and >0.8 as large effect.

Synthesis of results

A random-effects model was assumed following the recommendations of Borenstein et al. [20] given the heterogeneity between the samples and the neuropsychological tests. The Sidik-Jonkman estimator of variance was used to conduct the random-effects model, since it has been found that it is a good estimator when heterogeneity variance is large [21].

When a study included more than one post-treatment measures, we only calculated the effect size for the measure closer in time to the end of the intervention. When there were more than one valid control group, we combined the groups into a single following the recommendations in the Chapter 7 of the Cochrane Handbook [22].

When a study reported multiple outcome measures for the same cognitive function, aggregates were generated using de Agg function of the MAD package in R [23] as suggested by Borenstein et al. [20] to avoid violating the assumptions of independence. The correlation between outcomes was set at 0.5 by default. For each cognitive function, univariate meta-analyses and forest plots were calculated using the metaphor package for R [24] and the p-value significance was set at < .05.

The heterogeneity of the effect sizes of the studies was assessed using the Cochrane’s Q statistic, the τ2 and the I2. I2 was interpreted according to Higgins et al. [25], where I2 = 25% means low heterogeneity, I2 = 50% means medium heterogeneity and I2 = 75% means high heterogeneity. Due to the low number of studies included in the analysis (k<10), funnel plot and meta-regression analyses were not calculated following the recommendations of the Cochrane Handbook [22, 26].

Risk of bias in individual studies

Risk of bias was assessed using the Cochrane Risk of Bias Tool for experimental studies and the guidelines in Chapter 8 of the Cochrane Handbook [22] by RFL. When there was uncertainty in the coding of risk of bias, the two review authors decided by consensus.

Results

Study selection

Initial search in databases returned 3181 records and 3 records were identified from other sources. After removal of duplicates, 3095 unique records remained. These records were screened by RFL by reading the title and abstract, obtaining a total of 3048 excluded records and 37 included records to assess for full-text eligibility. After full-text assessing, 8 studies were included for quantitative analyses and systematic review. The selection process and the reasons for exclusion are summarized in the PRISMA flowchart in Fig 1.

Fig 1. PRISMA flowchart of the studies included in the systematic review and meta-analysis.

Fig 1

Open in a new tab

Study characteristics

Table 1 summarizes the study characteristics of the trials selected for the meta-analysis, including author, year, N, population, age, sex, intervention domain, intervention format, intervention method, and type of control group. Other relevant characteristics of the interventions provided are detailed in Table 2.

Table 1. Summary of study and intervention characteristics.

Author Year N Population Age Sex%female Intervention domain Interventionformat Interventionmethod Control
Åkerlund et al. [27] 2013 45 ABI 47.70 (11.27) 49.0 Working memory Individual Cognitive training (Cogmed) Usual care
Cho, Kim & Jung [28] 2015 25 Stroke 61.92 (5.78) 36.0 Attention Individual Cognitive training (RehaCom) Usual care
Lin et al. [29] 2014 34 Stroke 62.82 (5.77) 41.2 Executive function Individual Cognitive traning (Rehacom) Passive group
Man et al. [30] 2006 48 ABI 45.13 (19.96) 38.0 Problem-Solving Individual Cognitive training and strategy training Passive group
Piovesana et al. [31] 2017 57 TBI 11.88 (2.48) 48.3 Multi-domain Individual Cognitive training (Mitii) Usual care
Van de Ven et al. [32] 2017 97 Stroke 59.45 (8.67) 30.7 Multi-domain Individual Cognitive training (BrainGymmer) Active and passive control group
Westerbeg et al. [33] 2007 18 Stroke 54 (7.70) 33.3 Working memory Individual Cognitive training (RoboMemo) Passive group
Yoo et al. [34] 2015 46 Stroke 54.75 (8.40) 63.0 Multi-domain Individual Cognitive training (RehaCom) Usual care
Open in a new tab

Table 2. Relevant characteristics of the computer-based cognitive interventions.

Author Date Duration of intervention (hours) Frequency (Sessions/week) Length of session (min) Number of sessions Setting Time since injury (months) Therapist during intervention
Åkerlund et al. [27] 2013 15 5 30–45 25 Outpatient 33.18 (25.42) No (feedback provided once a week)
Cho, Kim & Jung [28] 2015 15 5 30 30 Inpatient 5.67 (2.23) Yes
Lin et al. [29] 2014 60 6 60 60 Outpatient 7.49 (0.69) Yes
Man et al. [30] 2006 15 1 45 20 Home 44.79 (47.19) Yes
Piovesana et al. [31] 2017 17.57 NR NR NR Home NR No (feedback provided once a week)
van de Ven et al. [32] 2017 29 5 30 58 Home 28.52 (15.71) No (feedback provided once a week)
Westerbeg et al. [33] 2007 13.3 NR 40 23 Home 20.11 (6) No (feedback provided once a week)
Yoo et al. [34] 2015 12.5 5 30 25 Inpatient 11.26 (6.83) NR
Open in a new tab

The included studies resulted in a total of 370 participants (M = 46.25, SD = 24.19). There was heterogeneity in terms of age (M = 50.41, SD = 16.45), and there was general consistency in the sex of the participants (% females, M = 42.44, SD = 10.6). Stroke was the most common condition in the participants (k = 5), followed by mixed samples of TBI and Stroke (k = 2) and TBI alone (k = 1). In relation to the type of intervention, all the included studies provided individual cognitive interventions (k = 8). The targeted cognitive domains were different between trials, being the multi-domain interventions the most common ones (k = 4), followed by single-domain interventions in working memory (k = 2), attention (k = 1) and problem solving (k = 1).

Trials can use different types of control groups. Active control group refers to the provision of another intervention to the control group that is known to not affect the variables being assessed. On the other hand, passive groups do not participate in any kind of intervention. Additionally, there is another kind of control group in which the usual care of the setting is provided (e.g. Physical rehabilitation) without the intervention given to the experimental group. The most common control group was usual care (k = 4), followed by passive groups (k = 3) and active control group (k = 1).

Regarding the neuropsychological assessment, there was a high heterogeneity, with different studies providing several effect sizes for the same cognitive domain and several trials providing no effect size for some of them. See S1 Table for a detailed table containing all the tests used for every cognitive function by the studies included in the meta-analysis.

There was substantial variability in the duration of the interventions provided (hours, M = 22.17, SD = 15.11). While most trials provided interventions in the range of 10–20 hours (k = 6), others reached 29 hours (k = 1) and 60 hours (k = 1). The same happens with the number of sessions provided to the participants (M = 34.43, SD = 15.79), ranging from 20 to 30 sessions for the studies that provide less hours (k = 6) and58 to 60 (k = 2) for longer ones In terms of frequency, the most common was 5 sessions per week (k = 4), followed by 6 sessions per week (k = 1) and 1 session per week (k = 1). Note that Piovesana et al. [28] and Westerberg et al. [30] do not report frequency because patients were able to self-manage the amount of sessions per week. Regarding the length of sessions (M = 38.93, SD = 10.16), most of the studies are in the range of 30–45 minutes (k = 6), while only one trial provides 60 minutes (k = 1). The most common setting in which the interventions took place was at home (k = 4), while other trials were performed in an outpatient setting (k = 2) or in an inpatient setting (k = 2). In the trials included, 3 of them had a therapist providing the intervention, while in 4 studies the intervention was completed by the patient alone with weekly feedback from the therapist.

There was considerably variability in the time since injury presented by the patients (M = 23.36, SD = 26.56). The most usual time since injury is less than 12 months (k = 3). There were trials in the range of 12 to 24 months (k = 1) and 24 to 36 months (k = 2), up to more than 36 months (k = 1).

Risk of bias in individual studies

The details of the risk of bias assessment can be seen in Fig 2 and Fig 3. Generally, a good methodological quality is assumed given that all the included studies are RCTs. However, the most common methodological flaw that the studies presented was a lack of the description of the randomization process and the absence of allocation concealment. Additionally, there was a lack of blinding for participants and neuropsychological assessors. Most trials did not report a planned protocol for the study (e.g. Pre-registration), which could lead to selective reporting of the outcome measures or deviations from the intended intentions. Due to the low number of studies included, moderator analyses based on the methodological quality of the studies could were not performed.

Fig 2. Risk of bias assessment of individual studies included in the meta-analysis.

Fig 2

Open in a new tab

Fig 3. Risk of bias assessment across the studies included in the meta-analysis by the Cochrane risk of bias tool.

Fig 3

Open in a new tab

Represented in the X axis are the percentages of studies for every risk of bias domain.

Synthesis of results

Separate univariate meta-analyses were performed for every cognitive domain addressed by the studies. Forest plots of statistically significant cognitive domains are depicted in Fig 4 and Fig 5. The forest plots of non-significant outcomes can be seen at S1 File. In general, all the cognitive functions showed a positive effect of the cognitive intervention of the study participants, although not all of them reached statistical significance. The cognitive domains that showed a significant improvement were: Verbal working memory (SMD = 0.486, 95% CI [0.034, 0.938], p = 0.035, small effect) and Visual working memory (SMD = 0.543, 95% CI [0.189, 0.897], p < 0.01, medium effect).

Fig 4. Forest plot for the Verbal working memory cognitive domain.

Fig 4

Open in a new tab

Fig 5. Forest plot for the Visual working memory cognitive domain.

Fig 5

Open in a new tab

The outcome domains that did not reach statistical significance were Attention (SMD = 0.282, 95% CI [-0.123, 0.687], p = 0.172), Flexibility (SMD = 0.036, 95% CI [-0.220, 0.294], p = 0.778), General cognition (SMD = 0.130, 95% CI [-0.267, 0.529], p = 0.519), Inhibition (SMD = 0.258, 95% CI [-0.124, 0.641], p = 0.186), Processing speed (SMD = 0.163, 95% CI [-0.091, 0.418], p = 0.207), Reasoning (SMD = 0.161, 95% CI[-0.139, 0.461], p = 0.293), Verbal memory (SMD = 0.305, 95% CI [-0.336, 0.945], p = 0.351) and Visual memory (SMD = 1.370, 95% CI [-0.886, 3.626], p = 0.234).

Due to the low number of studies, I2 was used as the main heterogeneity estimator, since it is not sensitive to the number of trials included. However, the Cochrane’s Q statistic yields similar results. High heterogeneity was found in Verbal memory and Visual memory (I2 > 75%). The cognitive domains that showed a moderate heterogeneity were Attention, Reasoning, Verbal working memory and Visual working memory (75% > I2 > 25%). A low heterogeneity was found in Flexibility, General cognition, Inhibition and Processing speed (I2 < 25%).

Meta-analysis could not be performed on Verbal fluency because it was assessed only by 1 study [29] in which they reported no statistical significance, which is in line with the aggregate in that cognitive function (Hedge’s g = 0.04) that yields no effect.

Discussion

The aim of the current study was to assess the effects of computer-based cognitive interventions in the cognitive functioning of ABI patients. To our knowledge, this is the first meta-analysis addressing this topic. The main finding of this study is that Visual and Verbal working memory are improved immediately after computer-based cognitive intervention in ABI population, while other cognitive functions like Attention, Reasoning, Processing speed, Inhibition, Flexibility and Visual and Verbal memory do not seem to improve.

In general, there was a low heterogeneity given the low number of studies included and the difference between the tests used and the population characteristics, which makes the findings more robust.

These findings are in line with previous works in ABI population. Fetta, Starkweather & Jill [13] conducted a systematic review on computer-based cognitive intervention in mild traumatic brain injury population. The authors concluded that there is weak evidence of improvement in working memory after intervention. Working memory is known to be one of the cognitive domains that benefits the more from direct training [35]. However, it has been argued that this improvement lacks generalization to other aspects of cognition and daily living [36, 34], although evidence in computer-based cognitive training from studies that could not be included in the present work due to insufficient data [37, 38], suggest that this training might be beneficial on self-reported occupational performance and dealing with cognitive fatigue.

On the other hand, these results are partially different from the systematic review performed on computer-based cognitive interventions for Attention and Executive functions in ABI [15] population. The authors found that most trials showed a positive effect, which was not replicated in the present work. The main reason might be that when only RCTs are included, the effect on those cognitive domains is non-significant. Virk et al. [39] performed a meta-analysis that found no effect of cognitive remediation in most of attentional deficits after ABI. The main reason of this lack of effect is probably because attention improves better when cognitive remediation is provided together with metacognitive and compensatory strategies [8], while most of the included studies in this work provide cognitive remediation alone.

These results are also in line with a previous systematic review in stroke population [14] that found no evidence of improvement in executive functions after computer-based cognitive intervention. Evidence suggests that metacognitive strategy training and self-regulation is the best intervention for such deficits, while cognitive training remains a second option [8, 40, 41]. No effect is also found in Verbal and Visual memory, which are better suited for external and internal compensatory strategies and instructional techniques rather than cognitive training [42–44].

Processing speed results are in contrast with the findings of studies done in elder healthy [45] and MCI population [46] that show a significant improvement right after training. This may point that ABI patients are more resistant to processing speed rehabilitation, and the evidence suggests that a compensatory approach such as Time Pressure Management [47] is more suited to this kind of population.

Finally, General cognition might not benefit from computer-based cognitive intervention. However, only 2 effect sizes contributed to that domain, and no standard tests of generalized usage such as Montreal Cognitive Assessment and Mini-Mental State Examination were used in the included studies. Considering that most of the cognitive domains did not benefit from computer-based cognitive intervention, it is to be expected that General cognition does not either, although studies in healthy and MCI show a small improvement on overall cognition [46]. More RCTs using General cognition scales are needed to clarify if General cognition benefits from computer-based cognitive interventions.

Limitations

The main limitation of the present work is the low number of the included studies. Although the fact that they are RCTs provides robustness to the results, many of the planned analyses in the protocol could not be performed. Meta-regression analyses would have provided valuable information, such as what kind of population benefits more from the intervention (e.g. Stroke vs TBI), what kind of interventions produce better results (e.g. Multi-domain vs Single-Domain), the effects of passive vs active control groups, the effect that study quality has on the final results, the generalization of the cognitive improvements on real-life setting or a transfer effect to other cognitive domains. The intervention characteristics, such as hours of intervention and number of sessions could not be explored as moderators either, which would have provided valuable information since it is has not been addressed in ABI population, with studies suggesting that shorter and less frequent sessions are more effective in healthy people [47] and MCI patients [46]. Funnel plot would have allowed us to examine the publication bias of the studies selected, although given that many of them are have small sample sizes and report non-significant outcomes, it may not be a major issue in this particular topic.

Conclusions and future directions

Computer-based cognitive interventions that were included in the present work are beneficial for Verbal and Visual working memory immediately after intervention in ABI, although no effect was found in the rest of the cognitive domains addressed. There is a need for more high-quality RCTs investigating possible moderators for a successful rehabilitation. The implementation of long-term and daily living measures is necessary for future trials, since evidence of lasting results and generalization is lacking. Other kinds of cognitive interventions that do not imply direct training were rarely used by the studies included. It would be of great interest to try to combine compensatory strategy training or instructional techniques with computer-based cognitive training, as Man et al. [30] did, to see if there is a bigger effect in the outcomes studied.

Efforts should be made to decrease the risk of bias, since most of the reviewed studies were at risk, especially due to the absence of proper randomization procedures and allocation concealment. Additionally, pre-registration should be considered to avoid selective reporting of outcomes.

Supporting information

S1 Table. PRISMA checklist.

(DOC)

Click here for additional data file. (65.5KB, doc)
S2 Table. Tests used by the included studies to assess the cognitive domains.

When more than one test measured the same function, aggregates were produced for the independent meta-analyses.

(DOCX)

Click here for additional data file. (19.3KB, docx)
S1 File. Forest plots and heterogeneity tests of non-significant cognitive domains.

(DOCX)

Click here for additional data file. (143.3KB, docx)

Data Availability

All the study data and R code are publicly available at: https://osf.io/9r3ks/?view_only=145ae9c0bbb8418796832ea1d73f28d0 and full report of non-included analyses can be found in Supporting Information files within the manuscript.

Funding Statement

This work was supported by funds from the Andalusian Regional Government (Spain) (PIN-0072-2016), (UCO-FEDER 18 REF. 1265277 MD A1), and the University of Córdoba (Spain) (PPG2018-UCOSOCIAL-11) to AA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

  • 1.Ponsford JL, Downing MG, Olver J, Ponsford M, Acher R, Carty M, et al. Longitudinal Follow-Up of Patients with Traumatic Brain Injury: Outcome at Two, Five, and Ten Years Post-Injury. Journal of Neurotrauma. 2014;31(1):64–77. 10.1089/neu.2013.2997 [DOI] [PubMed] [Google Scholar]
  • 2.Sun J-H, Tan L, Yu J-T. Post-stroke cognitive impairment: epidemiology, mechanisms and management. Annals of Translational Medicine. 2014;2(8):16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Dikmen SS, Machamer JE, Powell JM, Temkin NR. Outcome 3 to 5 Years After Moderate to Severe Traumatic Brain Injury. 2003;84:9. [DOI] [PubMed] [Google Scholar]
  • 4.Park YH, Jang J-W, Park SY, Wang MJ, Lim J-S, Baek MJ, et al. Executive Function as a Strong Predictor of Recovery from Disability in Patients with Acute Stroke: A Preliminary Study. Journal of Stroke and Cerebrovascular Diseases. 2015;24(3):554–61. 10.1016/j.jstrokecerebrovasdis.2014.09.033 [DOI] [PubMed] [Google Scholar]
  • 5.Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, et al. Cost of disorders of the brain in Europe 2010. European Neuropsychopharmacology. 2011;21(10):718–79. 10.1016/j.euroneuro.2011.08.008 [DOI] [PubMed] [Google Scholar]
  • 6.Orman JAL, Kraus JF, Zaloshnja E, Miller T. Epidemiology In: Silver JM, McAllister TW, Yudofsky SC editor(s). Textbook of Traumatic Brain Injury. 2nd Edition Washington, DC: American Psychiatric Publishing, 2011 [Google Scholar]
  • 7.Dams-O’Connor K, Gordon WA. Role and Impact of Cognitive Rehabilitation. Psychiatric Clinics of North America. 2010;33(4):893–904. 10.1016/j.psc.2010.08.002 [DOI] [PubMed] [Google Scholar]
  • 8.Cicerone KD, Goldin Y, Ganci K, Rosenbaum A, Wethe JV, Langenbahn DM, et al. Evidence-Based Cognitive Rehabilitation: Systematic Review of the Literature From 2009 Through 2014. Archives of Physical Medicine and Rehabilitation. 2019;100(8):1515–33. 10.1016/j.apmr.2019.02.011 [DOI] [PubMed] [Google Scholar]
  • 9.García-Casal JA, Loizeau A, Csipke E, Franco-Martín M, Perea-Bartolomé MV, Orrell M. Computer-based cognitive interventions for people living with dementia: a systematic literature review and meta-analysis. Aging & Mental Health. 2017;21(5):454–67. [DOI] [PubMed] [Google Scholar]
  • 10.Hill NTM, Mowszowski L, Naismith SL, Chadwick VL, Valenzuela M, Lampit A. Computerized Cognitive Training in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis. AJP. 2017;174(4):329–40. [DOI] [PubMed] [Google Scholar]
  • 11.Zhang H, Huntley J, Bhome R, Holmes B, Cahill J, Gould RL, et al. Effect of computerised cognitive training on cognitive outcomes in mild cognitive impairment: a systematic review and meta-analysis. BMJ Open. 2019;9(8):e027062 10.1136/bmjopen-2018-027062 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Gates NJ, Rutjes AWS, Di Nisio M, Karim S, Chong LY, March E, et al. Computerised cognitive training for maintaining cognitive function in cognitively healthy people in late life. Cochrane Database of Systematic Reviews 2019, Issue 3. Art. No.: CD012277. 10.1002/14651858.CD012277.pub2 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Fetta J, Starkweather A, Gill JM. Computer-Based Cognitive Rehabilitation Interventions for Traumatic Brain Injury: A Critical Review of the Literature. Journal of Neuroscience Nursing. 2017;49(4):235–40. 10.1097/JNN.0000000000000298 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.van de Ven RM, Murre JMJ, Veltman DJ, Schmand BA. Computer-based cognitive training for executive functions after stroke: A systematic review. Frontiers in Human Neuroscience. 2016; 10 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Bogdanova Y, Yee MK, Ho VT, Cicerone KD. Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review. Journal of Head Trauma Rehabilitation. 2016;31(6):419–33. 10.1097/HTR.0000000000000203 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Medicine. 2009;6(7):6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Román-Caballero R, Arnedo M, Triviño M, Lupiáñez J. Musical practice as an enhancer of cognitive function in healthy aging—A systematic review and meta-analysis. Torun S, editor. PLoS ONE. 2018;13(11):e0207957 10.1371/journal.pone.0207957 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Sherman DS, Mauser J, Nuno M, Sherzai D. The Efficacy of Cognitive Intervention in Mild Cognitive Impairment (MCI): a Meta-Analysis of Outcomes on Neuropsychological Measures. Neuropsychol Rev. 2017;27(4):440–84. 10.1007/s11065-017-9363-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Morris SB. Estimating Effect Sizes From Pretest-Posttest-Control Group Designs. Organizational Research Methods. 2008;11(2):364–86. [Google Scholar]
  • 20.Borenstein M, Hedges L V, Higgins JPT, Rothstein HR. Introduction to meta-analysis. New York, NY, USA: John Wiley & Sons, Ltd; 2009. [Google Scholar]
  • 21.Sidik K, Jonkman JN. A comparison of heterogeneity variance estimators in combining results of studies. Statist Med. 2007;26(9):1964–81. [DOI] [PubMed] [Google Scholar]
  • 22.Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. 2011. http://handbook-5-1.cochrane.org/ [Google Scholar]
  • 23.Del Re AC, Hoyt WT. MAd: Meta-Analysis with Mean Differences. R package version 0.8–2. 2014; https://cran.r-project.org/package=MAd [Google Scholar]
  • 24.Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010; 36(3): 1–48. http://www.jstatsoft.org/v36/i03/ [Google Scholar]
  • 25.Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. 10.1136/bmj.327.7414.557 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Lau J, Ioannidis JPA, Terrin N, Schmid CH, Olkin I. The case of the misleading funnel plot. BMJ. 2006;333(7568):597–600. 10.1136/bmj.333.7568.597 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Åkerlund E, Esbjörnsson E, Sunnerhagen KS, Björkdahl A. Can computerized working memory training improve impaired working memory, cognition and psychological health? Brain Injury. 2013;27(13–14):1649–57. 10.3109/02699052.2013.830195 [DOI] [PubMed] [Google Scholar]
  • 28.Cho H-Y, Kim K-T, Jung J-H. Effects of computer assisted cognitive rehabilitation on brain wave, memory and attention of stroke patients: a randomized control trial. J Phys Ther Sci. 2015;27(4):1029–32. 10.1589/jpts.27.1029 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Lin Z, Tao J, Gao Y, Yin D, Chen A, Chen L. Analysis of central mechanism of cognitive training on cognitive impairment after stroke: Resting-state functional magnetic resonance imaging study. J Int Med Res. 2014;42(3):659–68. 10.1177/0300060513505809 [DOI] [PubMed] [Google Scholar]
  • 30.Man DWK, Soong WYL, Tam SF, Hui-Chan CWY. A randomized clinical trial study on the effectiveness of a tele-analogy-based problem-solving programme for people with acquired brain injury (ABI). NRE.;21(3):205–17. [PubMed] [Google Scholar]
  • 31.Piovesana A, Ross S, Lloyd O, Whittingham K, Ziviani J, Ware RS, et al. A randomised controlled trial of a web-based multi-modal therapy program to improve executive functioning in children and adolescents with acquired brain injury. Clin Rehabil. 2017;31(10):1351–63. 10.1177/0269215517695373 [DOI] [PubMed] [Google Scholar]
  • 32.van de Ven RM, Buitenweg JIV, Schmand B, Veltman DJ, Aaronson JA, Nijboer TCW, et al. Brain training improves recovery after stroke but waiting list improves equally: A multicenter randomized controlled trial of a computer-based cognitive flexibility training. Quinn TJ, editor. PLoS ONE. 2017;12(3):e0172993 10.1371/journal.pone.0172993 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Westerberg H, Jacobaeus H, Hirvikoski T, Clevberger P, Östensson M-L, Bartfai A, et al. Computerized working memory training after stroke–A pilot study. Brain Injury. 2007;21(1):21–9. 10.1080/02699050601148726 [DOI] [PubMed] [Google Scholar]
  • 34.Yoo C, Yong M, Chung J, Yang Y. Effect of computerized cognitive rehabilitation program on cognitive function and activities of living in stroke patients. J Phys Ther Sci. 2015;27(8):2487–9. 10.1589/jpts.27.2487 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Spencer-Smith M, Klingberg T. Benefits of a Working Memory Training Program for Inattention in Daily Life: A Systematic Review and Meta-Analysis. Rypma B, editor. PLoS ONE. 2015;10(3):e0119522 10.1371/journal.pone.0119522 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Melby-Lervåg M, Redick TS, Hulme C. Working Memory Training Does Not Improve Performance on Measures of Intelligence or Other Measures of “Far Transfer”: Evidence From a Meta-Analytic Review. Perspect Psychol Sci. 2016;11(4):512–34. 10.1177/1745691616635612 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Björkdahl A, Åkerlund E, Svensson S, Esbjörnsson E. A randomized study of computerized working memory training and effects on functioning in everyday life for patients with brain injury. Brain Injury. 2013;27(13–14):1658–65. 10.3109/02699052.2013.830196 [DOI] [PubMed] [Google Scholar]
  • 38.Lundqvist A, Grundström K, Samuelsson K, Rönnberg J. Computerized training of working memory in a group of patients suffering from acquired brain injury. Brain Injury. 2010;24(10):1173–83. 10.3109/02699052.2010.498007 [DOI] [PubMed] [Google Scholar]
  • 39.Virk S, Williams T, Brunsdon R, Suh F, Morrow A. Cognitive remediation of attention deficits following acquired brain injury: A systematic review and meta-analysis. NRE. 2015;36(3):367–77. [DOI] [PubMed] [Google Scholar]
  • 40.McEwen S, Polatajko H, Baum C, Rios J, Cirone D, Doherty M, et al. Combined Cognitive-Strategy and Task-Specific Training Improve Transfer to Untrained Activities in Subacute Stroke: An Exploratory Randomized Controlled Trial. Neurorehabil Neural Repair. 2015;29(6):526–536. 10.1177/1545968314558602 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Polatajko HJ, McEwen SE, Ryan JD, Baum CM. Pilot Randomized Controlled Trial Investigating Cognitive Strategy Use to Improve Goal Performance After Stroke. American Journal of Occupational Therapy. 2012;66(1):104–9. 10.5014/ajot.2012.001784 [DOI] [PubMed] [Google Scholar]
  • 42.Ehlhardt LA, Sohlberg MM, Kennedy M, Coelho C, Ylvisaker M, Turkstra L, et al. Evidence-based practice guidelines for instructing individuals with neurogenic memory impairments: What have we learned in the past 20 years? Neuropsychological Rehabilitation. 2008;18(3):300–42. 10.1080/09602010701733190 [DOI] [PubMed] [Google Scholar]
  • 43.Mahan S, Rous R, Adlam A. Systematic Review of Neuropsychological Rehabilitation for Prospective Memory Deficits as a Consequence of Acquired Brain Injury. J Int Neuropsychol Soc. 2017;23(3):254–65. [DOI] [PubMed] [Google Scholar]
  • 44.Rebok GW, Ball K, Guey LT, Jones RN, Kim H-Y, King JW, et al. Ten-Year Effects of the Advanced Cognitive Training for Independent and Vital Elderly Cognitive Training Trial on Cognition and Everyday Functioning in Older Adults. J Am Geriatr Soc. 2014;62(1):16–24. 10.1111/jgs.12607 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Mewborn CM, Lindbergh CA, Stephen Miller L. Cognitive Interventions for Cognitively Healthy, Mildly Impaired, and Mixed Samples of Older Adults: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials. Neuropsychol Rev. 2017;27(4):403–39. 10.1007/s11065-017-9350-8 [DOI] [PubMed] [Google Scholar]
  • 46.Winkens I, Van Heugten CM, Wade DT, Habets EJ, Fasotti L. Efficacy of Time Pressure Management in Stroke Patients With Slowed Information Processing: A Randomized Controlled Trial. Archives of Physical Medicine and Rehabilitation. octubre de 2009;90(10):1672–9. [DOI] [PubMed] [Google Scholar]
  • 47.Lampit A, Hallock H, Valenzuela M. Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers. Gandy S, editor. PLoS Med. 2014;11(11):e1001756 10.1371/journal.pmed.1001756 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Jose A Muñoz-Moreno

25 Mar 2020

PONE-D-20-03777

Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized controlled trials

PLOS ONE

Dear Mr. Fernández López,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Reviewers have provided queries on this manuscript with several questions arising. They include a better description of the interventions performed and the main variables considered, and improvement of the introduction and discussion sections. Changes should be applied in text before the acceptation of the work.

We would appreciate receiving your revised manuscript by May 09 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Jose A. Muñoz-Moreno, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please ensure that you have discussed how your submission relates to and advances upon the following publication:

https://pubmed.ncbi.nlm.nih.gov/28661947

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Manuscript #: PONE-D-20-03777

Title: Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized controlled trials

Thank you for the opportunity to read this manuscript. The purpose of this paper was to conduct a systematic review and metanalysis of RCTs that used computer-based cognitive interventions for persons with acquired brain injury.

Abstract: The abstract overall is clear and concise.

Introduction: The second paragraph of the introduction requires some expansion for the reader. The sentence, “The impact of cognitive rehabilitation has increased over the years…..” needs some further explanation to what that impact is. Is it better for the patient outcomes? Is it being used more?

A definition of the what types of computer-based interventions would also be helpful. There are interventions on the computer that still require a therapist to be involved in the session and make decisions about advancing (such as the Attention Process Training) and there are others that the computer automatically advances the difficulty based on performance. Are all of these included in the review?

Methods:

Regarding the eligibility criteria. Were studies only included if they studied adults or were pediatric populations considered as well?

The search strategy and statistical analysis plan described is adequate for the purposes of this paper.

Results:

The description of the demographics at the top of page 10 should be reworded. “There was heterogeneity in terms of age…..although there was a general consistency in the sex of the participants”. Although does not seem to be the correct word. The authors should note that the higher percentage of males in a TBI population is consistent with other statistics published.

Later in the first paragraph on page 10, the authors describe the various types of trials as multi-domain, working memory………The control groups were usual care, passive and active.” As a reader, I’d like to know more about what these trials mean. Explain the difference between multi-domain and the single domains. What do those interventions look like? Examples would be helpful. The same with the control groups, description of what usual care entailed and what passive and active controls were used would be helpful.

Additional information that was not provided but is necessary includes the setting the RCTs were conducted in. Were these studies in an outpatient setting, acute inpatient rehab, etc? If the studies reviewed reported time since injury to start of intervention that is also an important variable that should be reported.

In the 3rd paragraph on page 10, the authors describe the variation in duration of the interventions provided. Additional information that would be helpful for the reader is the average length for each session and the frequency the sessions were provided.

Discussion and Conclusions: The authors state on page 14 that general cognition may not benefit from cognitive training. This needs to be clarified, do you mean any cognitive training or specifically the computerized cognitive training addressed in this paper? This clarification needs to be addressed throughout the 2nd paragraph on page 14.

Figures and Tables: In Figure 1, the box describing records excluded. The fourth bullet point indicates no intervention in cognitive functions. Should this be no computerized cognitive intervention?

Table 1. For the reporting of age, either a range of standard deviation from each study would be helpful. Also, more information about the interventions such as, length and frequency of each session, where interventions were delivered and were other interventions with a therapist also delivered with these computerized interventions?

Figure 2 More explanation of the figure and what it means is needed.

In general, as a reader of this paper, I wanted to see more explanation of the computerized interventions and how they were delivered. I also wanted to see more information about the outcome measures that were used.

Reviewer #2: The authors conducted a systematic review and meta-analysis of RCTs that assessed Computer-based cognitive interventions in acquired brain injury – which included patients who have suffered a TBI and/or stroke. This is a well written and easy to read manuscript. The tables and flow chart is well done. I have a few items that I would like the authors to address/expand on.

Introduction

1. The authors write “The impact of cognitive rehabilitation has increased over the years (7) and there are considerable efforts in the search of evidence-based interventions (8) for ABI patients.” The authors should briefly expand further on the phrase “impact” – what exactly do they mean by this?

2. The authors write “In order to provide an optimal intervention for every patient, the use of computer-based interventions has increased.” This is an assumption that unless can be backed up, should be re-writteen

3. The authors write “Computer-based cognitive interventions are most commonly provided with the use of tools such as Rehacom and Cogmed, which are based on cognitive training of the different cognitive domains.” I recommend not highlighting any specific company unless the authors can back up that these two companies are factually “most commonly” used.

Discussion

4. The authors write “However, it has been argued that this improvement lacks generalization to other aspects of cognition and daily living (33), although evidence in computer-based cognitive training from studies that could not be included in the present work (34, 35) suggest that this training might be beneficial on daily activities and dealing with cognitive fatigue.” The authors should expand on this (i) Specifically state that none of the reviewed article assessed daily activities and (ii) state why 34 and 35 could not be included

5. The Limitations flow into the ‘suggestions for future research’. This should be separate.

Conclusions

6. The authors conclude “The Computer-based cognitive training is a beneficial intervention for Verbal and Visual working memory after ABI, although no effect was found in the rest of the cognitive domains addressed.” Please rephase this in the context of the studies examined (i) Computer-based cognitive training that --fall within the design parameters summarized here – is a beneficial intervention (ii) benefits occurs ‘immediately’ after intervention.

General

7. There is a 2016 systematic review “Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review by Bogdanova, Cicerone et al. that was not mentioned by the authors. Please appropriately include this review in both the introduction and discussion.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 9;15(7):e0235510. doi: 10.1371/journal.pone.0235510.r002

Author response to Decision Letter 0

30 Apr 2020

Response to reviewers

Dear Dr. Jose A. Muñoz-Moreno,

thank you for allowing us to submit a revised draft of our work “Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized-controlled trials” and for taking the time to review and comment it for improvements. We tried our best to reflect the changes suggested by editor and reviewers. We are grateful to reviewers and editor for their helpful feedback on the work.

Here we response point by point all the points made by reviewers and editor. Please note that when we point the specific location of the changes, we refer to the manuscript with track changes file.

Comments from editor

Editor: “1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.”

Response: We found some mistakes in the text style so we changed them according to the requirements. However, we did not find any mistake in file naming after careful examination of the templates. If editor could point out the specific mistake in file naming, we would correct it as soon as possible.

Editor: “Please ensure that you have discussed how your submission relates to and advances upon the following publication: https://pubmed.ncbi.nlm.nih.gov/28661947”

Response: We did as suggested and included this publication in the introduction and discussion. This change can be seen in page 4, second paragraph, line 80-82 and third paragraph of page 16, line 294-297.

Comments from reviewer 1

Reviewer 1:” The second paragraph of the introduction requires some expansion for the reader. The sentence, “The impact of cognitive rehabilitation has increased over the years…..” needs some further explanation to what that impact is. Is it better for the patient outcomes? Is it being used more?”

Response: We agree with reviewer 1 in relation to the word “impact”. It is not clear. We wanted to point that this kind of intervention has gained attention in the literature, so we rephrased it to make it clear, instead of using “impact”. This change can be seen in page 3, second paragraph, line 56.

Reviewer1:” A definition of the what types of computer-based interventions would also be helpful. There are interventions on the computer that still require a therapist to be involved in the session and make decisions about advancing (such as the Attention Process Training) and there are others that the computer automatically advances the difficulty based on performance. Are all of these included in the review?”

Response: Reviewer 1 asked us to provide a definition for the different kinds of computer-based interventions. We think it is a good idea, so we included a brief definition. We included information about the therapist being involved during intervention. We would also like to confirm that all the interventions that Reviewer 1 mentions are included in the review. Changes can be seen in the end of page 3 and the first paragraph of page 4, line 66-75

Reviewer 1: “Regarding the eligibility criteria. Were studies only included if they studied adults or were pediatric populations considered as well?”

Response: We decided not to include age limitation for the analysis as long as subjects do not present neurodevelopmental disorders. The trial with the youngest population included adolescents and children around 10-12 years, so we decided it could be useful for the inclusion.

Reviewer 1: “The description of the demographics at the top of page 10 should be reworded. “There was heterogeneity in terms of age…..although there was a general consistency in the sex of the participants”. Although does not seem to be the correct word. The authors should note that the higher percentage of males in a TBI population is consistent with other statistics published.”

Response: Reviewer 1 make an excellent point. We changed the phrasing to make it clear that these results are in line with previous evidence. This change can be seen in page 12, first paragraph, line 200.

Reviewer 1:” Later in the first paragraph on page 10, the authors describe the various types of trials as multi-domain, working memory………The control groups were usual care, passive and active.” As a reader, I’d like to know more about what these trials mean. Explain the difference between multi-domain and the single domains. What do those interventions look like? Examples would be helpful. The same with the control groups, description of what usual care entailed and what passive and active controls were used would be helpful.

Additional information that was not provided but is necessary includes the setting the RCTs were conducted in. Were these studies in an outpatient setting, acute inpatient rehab, etc? If the studies reviewed reported time since injury to start of intervention that is also an important variable that should be reported.

In the 3rd paragraph on page 10, the authors describe the variation in duration of the interventions provided. Additional information that would be helpful for the reader is the average length for each session and the frequency the sessions were provided.”

Response: We agree with reviewer 1, so we included a brief definition of what multi-domain and single-domain interventions are (end of page 3 and the first paragraph of page 4, line 66-75) and what the different kind of control groups looks like (page 12, second paragraph, line 208-213). We also added information about length and frequency (first paragraph of page 13). Additionally, we decided to include a second table to summarize more information about the RCTs, such as setting, time since injury, frequency and length of intervention (Page 11, Table 2 and page 13, line 229-237).

Reviewer 1: “Discussion and Conclusions: The authors state on page 14 that general cognition may not benefit from cognitive training. This needs to be clarified, do you mean any cognitive training or specifically the computerized cognitive training addressed in this paper? This clarification needs to be addressed throughout the 2nd paragraph on page 14.”

Response: We intended to mean computerized cognitive training, but we can see it is confusing the way it is redacted. We changed it to reflect that it is specifically computerized cognitive training from our results. This change can be found in last paragraph of page 17.

Reviewer 1:”Figures and Tables: In Figure 1, the box describing records excluded. The fourth bullet point indicates no intervention in cognitive functions. Should this be no computerized cognitive intervention?”

Response: We agree. We intended to mean computer-based cognitive intervention, so we changed it to be more accurate. Change can be found in Fig 1.

Reviewer 1: “Table 1. For the reporting of age, either a range of standard deviation from each study would be helpful. Also, more information about the interventions such as, length and frequency of each session, where interventions were delivered and were other interventions with a therapist also delivered with these computerized interventions?”

Response: We agree. We included the standard deviations in the age columns, and we also included an additional table with the required information. Please note that when taking into account standard deviations, mean age differs slightly from the previous ones. Changes can be found in Table 1, Table 2 and first paragraph of page 13.

Reviewer 1:” Figure 2 More explanation of the figure and what it means is needed.”

Response: We added some information to make it clear. However, due to the low number of studies, maybe this figure can be confusing. If reviewers find it not to be useful, we can consider deleting it. The change can be found in line 250-252 of page 14.

Comments from reviewer 2

Reviewer 2: “The authors write “The impact of cognitive rehabilitation has increased over the years (7) and there are considerable efforts in the search of evidence-based interventions (8) for ABI patients.” The authors should briefly expand further on the phrase “impact” – what exactly do they mean by this?”

We agree with Reviewer 2. As we responded to Reviewer 1, the phrasing is misleading and we changed it to reflect that it has gained attention in the literature. This change can be seen in page 3, second paragraph, line 56.

Reviewer 2:”The authors write “In order to provide an optimal intervention for every patient, the use of computer-based interventions has increased.” This is an assumption that unless can be backed up, should be re-written”

Response: We also agree with Reviewer 2 that the phrasing in “In order to provide an optimal intervention for every patient, the use of computer-based interventions has increased” is not optimal, and we changed it to reflect that it has potential but has not proven to be better yet. Change can be found in page 3, second paragraph, line 59-60

Reviewer 2:”The authors write “Computer-based cognitive interventions are most commonly provided with the use of tools such as Rehacom and Cogmed, which are based on cognitive training of the different cognitive domains.” I recommend not highlighting any specific company unless the authors can back up that these two companies are factually “most commonly” used.”

Response: We agree with Reviewer 2, using the brand names of the programs might not be the best idea, so we changed it to a simple description with no names in it. Change can be found in page 3, second paragraph, line 65-66.

Reviewer 2:” The authors write “However, it has been argued that this improvement lacks generalization to other aspects of cognition and daily living (33), although evidence in computer-based cognitive training from studies that could not be included in the present work (34, 35) suggest that this training might be beneficial on daily activities and dealing with cognitive fatigue.” The authors should expand on this (i) Specifically state that none of the reviewed article assessed daily activities and (ii) state why 34 and 35 could not be included”

Response: We agree that the writing is confusing and can lead to misunderstanding. We re-phrased it to make it clearer and give the information asked and added new information from a trial that was included in the analysis. Change can be found in page 16, second paragraph, line 300-303.

Reviewer 2: “The Limitations flow into the ‘suggestions for future research’. This should be separate.”

Response: We agree, so we separated it as suggested by reviewer 2. This change can be found in the last paragraph of page 18.

Reviewer 2: “The authors conclude “The Computer-based cognitive training is a beneficial intervention for Verbal and Visual working memory after ABI, although no effect was found in the rest of the cognitive domains addressed.” Please rephase this in the context of the studies examined (i) Computer-based cognitive training that --fall within the design parameters summarized here – is a beneficial intervention (ii) benefits occurs ‘immediately’ after intervention.”

Response: We agree that the original phrasing can be misleading. We changed it to reflect what reviewer 2 suggested, being the wording now more accurate and clearer. Changes can be found in last paragraph of page 15, line 288 and first 2 lines of last paragraph of page 18.

Reviewer 2: “There is a 2016 systematic review “Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review by Bogdanova, Cicerone et al. that was not mentioned by the authors. Please appropriately include this review in both the introduction and discussion.”

Response: Thanks for pointing this out. We modified the introduction and discussion to include the paper suggested and we discussed how it relates to the present work. This change can be found in second paragraph of page 4, line 79-82 and last paragraph of page 16, line 304-308.

Additional clarifications

In the process of introducing the changes suggested by reviewers, we noticed some minor mistakes that we corrected in the manuscript:

• In addition to the studies that we discussed by suggestion of editor and Reviewer 2, we included a systematic review of computer-based cognitive interventions in stroke population by Van de ven et al. (2016) in our work.

• Regarding the hours of intervention and the number of sessions in Piovesana et al (2017) and Westerberg et al (2007), we originally reported a bigger number of hours and sessions than what the actually provided. The reason we made a mistake is because their protocol describes a potential amount of sessions and hours, which is what we originally used for the table. After careful examination, we noticed that they point the actual number of sessions and hours that were provided, which differ from the planned ones. The revised manuscript is already corrected.

• When assessing Risk of bias in Fig 2, we noticed that Van de ven et al. (2017) shows as unclear risk of bias in the randomization process. However, we believe their work has a low risk of bias in that topic. We originally conceived it that way, but we made a mistake when including the information in the excel table. We properly corrected it.

• We want to point out that we updated the funding statement because we got the new included funding recently. We can still assure that the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

We look forward to responding any other question or comments that editor or reviewers may have.

Sincerely,

Rodrigo Fernández López.

Decision Letter 1

Jose A Muñoz-Moreno

17 Jun 2020

Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized controlled trials

PONE-D-20-03777R1

Dear Dr. Fernández López,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Jose A. Muñoz-Moreno, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

We are sorry about the delay in our final decision. COVID-19 crisis is being a hard time for all of us. Reviewers are thankful for the thoughtful responses to their comments and we think the manuscript is convenient now for publication.

Acceptance letter

Jose A Muñoz-Moreno

23 Jun 2020

PONE-D-20-03777R1

Computer-based cognitive interventions in acquired brain injury: A systematic review and meta-analysis of randomized controlled trials

Dear Dr. Fernández López:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Jose A. Muñoz-Moreno

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Table. PRISMA checklist.

    (DOC)

    Click here for additional data file. (65.5KB, doc)
    S2 Table. Tests used by the included studies to assess the cognitive domains.

    When more than one test measured the same function, aggregates were produced for the independent meta-analyses.

    (DOCX)

    Click here for additional data file. (19.3KB, docx)
    S1 File. Forest plots and heterogeneity tests of non-significant cognitive domains.

    (DOCX)

    Click here for additional data file. (143.3KB, docx)

    Data Availability Statement

    All the study data and R code are publicly available at: https://osf.io/9r3ks/?view_only=145ae9c0bbb8418796832ea1d73f28d0 and full report of non-included analyses can be found in Supporting Information files within the manuscript.

    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES