Update on the efficacy of cognitive rehabilitation following moderate to severe traumatic brain injury: a scoping review

  • Adeline Julien
    Corresponding author: Adeline Julien Département de neurologie, Unité de neuropsychologie clinique, CHU de Toulouse, Place du Dr Baylac, 31059 Toulouse cedex.
    Department of Neurology, Toulouse University Hospital, place du Dr Baylac, 31059 Toulouse cedex, France

    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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  • Lola Danet
    Department of Neurology, Toulouse University Hospital, place du Dr Baylac, 31059 Toulouse cedex, France

    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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  • Mallaury Loisel
    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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  • David Brauge
    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France

    University Sports Clinic, Toulouse University Hospital, place du Dr Baylac, 31059 Toulouse cedex, France
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  • Jérémie Pariente
    Department of Neurology, Toulouse University Hospital, place du Dr Baylac, 31059 Toulouse cedex, France

    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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  • Patrice Péran
    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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  • Mélanie Planton
    Department of Neurology, Toulouse University Hospital, place du Dr Baylac, 31059 Toulouse cedex, France

    Toulouse Neuroimaging Center, Université de Toulouse, Inserm, UPS, place du Dr Baylac, 31059 Toulouse cedex, France
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Open AccessPublished:July 30, 2022DOI:



      : To identify, categorize and analyze the methodological issues of cognitive rehabilitation of patients with moderate to severe traumatic brain injury and its efficacy.

      Data sources

      : Pubmed and PsycINFO were searched for studies published between 2015 and 2021 using keywords for cognitive intervention and traumatic brain injury.

      Study selection

      : Two independent reviewers selected articles concerning cognitive rehabilitation for adults with traumatic brain injury. Of 458 studies, 97 full text articles were assessed and 46 met the inclusion criteria.

      Data extraction

      : Data were analyzed by one reviewer according to criteria concerning the methodological quality of studies.

      Data synthesis

      : Results showed a large scope of 7 cognitive domains targeted by interventions, delivered mostly in individual sessions (83%) with an integrative cognitive approach (48%). Neuroimaging tools as a measure of outcome remained scarce, featuring in only 20% of studies. Forty-three studies reported significant effects of cognitive rehabilitation, among which 7 fulfilled a high methodological level of evidence.


      : Advances and shortcomings in cognitive rehabilitation have both been highlighted and led us to develop methodological key points for future studies. The choice of outcome measures, the selection of control interventions and the use of combined rehabilitation should be investigated in further studies.


      List of abbreviations:

      CRTF (cognitive rehabilitation task force), DAI (diffuse axonal injury), DMN (default mode network), EEG (electroencephalography), ECN (executive control network), fMRI (functional magnetic resonance imaging), GAS (goal attainment scaling), GMT (goal management training), ITT (intention to treat), MET (multiple errands tests), NIBS (non-invasive brain stimulation), rTMS (repeated transcranial magnetic stimulation), RCT (randomized controlled trial), SCED (single-case experimental design), tDCS (transcranial direct current stimulation), TBI (traumatic brain injury), WM (working memory)
      Cognitive disorders after a traumatic brain injury (TBI) have been well described over the last decades. Long-term memory, attention, processing speed, executive functions and self-awareness disorders are frequent and related to the high frequency of temporal and frontal lesions 1. Cognitive sequelae commonly persist several years after a moderate to severe TBI 2,3, impacting vocational integration and quality of life 4,5. Cognitive rehabilitation aims to decrease acquired neurocognitive impairment and disability using various and complementary approaches 6. Interventions could aim to train or strengthen impaired cognitive functions and/or to implement compensatory mechanisms in addition to external aids 6. Metacognitive strategies are also trained in order to facilitate the transfer to different environmental contexts 7–9.
      Over the last years, the literature has provided quantitative data about cognitive rehabilitation after TBI, leading to a better understanding of the underlying cerebral mechanisms and the development of new interventions. Results were reported across reviews, systematic reviews, meta-analyses and scoping reviews. The most consequent systematic review was conducted by the Cognitive Rehabilitation Task Force (CRTF) of the American Congress of Rehabilitation Medicine 10. Since 2000, Cicerone and colleagues have published 4 successive systematic reviews on the cognitive rehabilitation of patients with TBI or stroke and established evidence-based clinical recommendations 6,10–12. Four hundred ninety-one studies have now been reviewed and classified according to the level of evidence, including 109 studies in class I, 68 in class II and 314 in class III. For each cognitive domain, Cicerone et al. 10 provided several levels of recommendations: Practice Standards, Practice Guidelines and Practice Options. Practice Standards, derived from the strongest evidence, have been identified for treatment of attention deficits, left visual neglect, apraxia, mild memory impairments, language and social communication deficits, mild to moderate executive functions deficits and holistic neuropsychological rehabilitation. They concluded that future research could investigate the impact of individual characteristics, especially the role of psychological insight, residual cognitive reserve and the presence of associated psychiatric comorbidities. They also recommended including the frequency and intensity of cognitive rehabilitation as covariates in statistical models. Furthermore, several scoping reviews addressed complementary aspects of TBI, such as societal dimensions 13–15, neurological and neuropsychological patterns 16–18, psychological conditions associated with TBI 19, delivery mode of rehabilitation 20,21 and state of scientific research on clinical rehabilitation 22,23. Two scoping reviews have reported the effects of cognitive rehabilitation 24,25 on two very specific approaches that focused on driving rehabilitation 25 and the use of repeated transcranial magnetic stimulation on cognitive functioning 24.
      The literature about cognitive rehabilitation following TBI is vast. Reviews on this subject usually analyze the content of rehabilitation to derive recommendations for clinical practice. Here, we chose to focus on methodological criteria to determine the level of scientific evidence of these studies. The most recent substantial systematic review on this subject includes published articles up to 2014 10. In this paper, we aimed to review the scope of interventions in cognitive rehabilitation since 2015. Moreover, we chose to select studies including only patients with TBI and to exclude the stroke population in order to limit the heterogeneity of the underlying physiopathology of cognitive disorders. We also excluded the mild TBI population because the functional and cognitive outcomes differ from moderate to severe TBI 26. Scoping review was an appropriate approach to map the scope and nature of research in cognitive rehabilitation after TBI, summarize research findings and identify gaps in the existing literature. In order to guide our search, we addressed four main questions: (i) Which cognitive domains does cognitive rehabilitation focus on? (ii) What are the characteristics of interventions in cognitive rehabilitation? (iii) What are the outcome measures used by authors? (iv) What is the efficacy of cognitive rehabilitation?


      The scoping review was based on the framework developed by Arksey & O'Malley 27 including the successive stages described below.

      Search strategy

      A systematic search of publications listed in the Pubmed (via Medline) and PsycINFO databases was conducted in August 2021 using the keywords “cognitive rehabilitation” (OR “cognitive remediation,” “cognitive intervention,” “cognitive training,” “cognitive treatment”) AND “traumatic brain injury.” The following terms were excluded from the systematic search: “children,” “pediatric,” “concussion,” “mild” and “animal.” The scope of the search went from January 1, 2015, to July 31, 2021.

      Inclusion and exclusion criteria

      Inclusion criteria were: (i) studies including adults or adolescents, no younger than 15 years old, with moderate to severe TBI. The Mayo Classification System criteria were used to define moderate to severe TBI: loss of consciousness lasting 30 minutes or more and/or post-traumatic anterograde amnesia lasting 24 hours or more and/or worst Glasgow Coma Scale score less than 13 in the first 24 hours and/or imaging evidence of intracranial pathology (intracerebral hematoma, subarachnoid hemorrhage, cerebral contusion, etc…) 28. We also reported for each article if brain lesions were identified by authors through computed tomography / magnetic resonance scanning (Table 1). In a context of mixed samples including several acquired brain injuries, moderate to severe TBI should be the most represented group; (ii) patients had to be included at least 3 months after the onset; (iii) interventions had to investigate the rehabilitation of cognitive functions; (iv) effects of cognitive rehabilitation had to be documented by quantitative or qualitative comparisons throughout follow-up; (v) interventions had to be conducted in a rehabilitation center, ambulatory care or at home.
      Table 1Summary of reviewed studies on cognitive rehabilitation post-traumatic brain injury
      Executive functions


      level of evidence

      Cognitive rehabilitation characteristics

      DesignIntervention characteristicsNeuropsychological outcome measuresSignificant main results
      Cho et al. 70

      Class III
      3 TBI, including 2 severe TBI

      Ages: 24, 51 and 52 years old
      60 minutes

      1 per week

      Over 6 weeks

      Total of 6 sessions
      Intra-individual comparison: help-seeking scores before vs. after CR.Group sessions

      NICE training protocol (Noticing you have a problem, Identifying the information you need for help, Compensatory strategies, Evaluating progress): Intervention protocol targeting help-seeking behaviors during wayfinding.

      Ecological executive assessment (Executive function route-finding task).

      Structured role-plays with a four-point social behavior rating scale.
      - Absence of statistical analysis -

      Improvements for all three patients of ecological measures and structured role-plays.
      Constandinidou et al. 62

      Class II
      15 moderate to severe TBI

      Age: 28.13 (9.21)
      60 minutes

      2 to 4 per week

      10-12 weeks

      Average total of 27 sessions
      Intergroup comparison:

      Categorization performance (CP) training in young adults with TBI vs. CP training in young healthy adults vs. CP training in older adults vs. no training in healthy older adults.
      Individual sessions

      Categorization performance training.

      Two categorization tests designed for this study.

      Scores on executive function, visuospatial, memory, working memory and language tests.

      Improvement in CP for all treated groups.

      No intergroup differences.
      Elbogen et al. 51

      Class I
      112 TBI with PTSD,

      including 57% moderate to severe TBI

      Age: 36.52 (8.42)
      60-90 minutes

      3 home visits at 0, 2, 4 months

      Over 6 months
      Intergroup comparison: CR with a cognitive application for life management (CALM) vs. active control intervention including psychoeducation.Individual sessions

      CALM: Goal management training plus mobile devices and attentional control.

      Scores on executive functions tests.

      Emotional and behavioral questionnaires.

      No improvement on executive performance.

      Improvement on behavioral, emotional and PTSD symptoms.

      Emmanouel et al. 52

      Class I
      18 brain-injured patients, including 11 moderate to severe TBI ‡

      Severity: Period of loss of consciousness ranging from 12 to 33 days

      Age: 35 (9)
      30 minutes

      3 to 4 per week

      Total of 11 sessions
      Intergroup comparison: CR combining goal management training (GMT) + working memory training (WMT) vs. control intervention including GMT only.Individual sessions

      Goal management training combined with working memory Training.

      Experimental tasks: Multistep everyday tasks.

      Scores on executive function, memory, working memory and language tests.

      Executive ecological assessment.

      Executive functioning questionnaires (self- and relative-reports).

      Improvements on multistep everyday tasks for the intervention group compared to the control group (medium to large effect sizes).

      No interaction effects between treatment and time for all other neuropsychological measures.
      Goodwin et al. 73

      Class III
      66 ABI patients, including 50 traumatic injuries (46 closed head injuries and 4 open head injuries)

      Age: 31.6 (11.75)

      Intensive phase: 4 full days a week

      Over 12 weeks

      Re-integration phase: 2 or 3 full days a week

      Over 12 weeks

      Total of 24 sessions

      Intra-individual comparison:

      Dysexecutive scores before vs. after CR.
      Individual and group sessions

      Holistic neuropsychological rehabilitation including 2 phases:

      - Intensive phase: education, practical tasks, facilitated discussion and homework.

      - Re-integration phase.
      Executive functioning and behavioral questionnaire (self- and relative-reports).Lower number of self-reported and relative-reported dysexecutive symptoms.
      Gracey et al. 54

      Class I
      59 acquired non-progressive brain injuries, including 27 patients with TBI

      Severity obtained for 55% of TBI participants: 41% severe, 7% moderate, 7% mild

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 47.79 (14.72)

      Max. mean age: 49.76 (12.94)

      90 to 120 minutes

      Total number of sessions varied depending on the abilities of the participant
      Longitudinal intergroup comparison - Cross-over design: Assisted intention monitoring vs. control intervention (information and games).Individual sessions

      Assisted intention monitoring (AIM): Brief GMT combined with periodic SMS text messages.

      Proportion of daily intentions achieved by participant.

      Improvement of achievement intentions after the intervention phase compared to the control condition (medium effect sizes).
      Hart et al. 55

      Class I
      8 moderate to severe TBI

      Age: 23.8 (4.3)
      8 weeks

      No more details
      Intergroup comparison: Goal intention intervention (with text messaging) vs. active control group (who received unspecific text messages).Individual sessions

      Goal intention intervention: Implementation of intentions with reminder messages.

      Assessment of emotional function, social participation and goal attainment scaling scores.Improvement for the experimental group on self- and relative-reports for social participation and social relation compared to control group (medium to large effect sizes).
      Powell et al. 57

      Class I
      23 ABI (including 14 motor vehicle crashes, 1 fall and 2 assaults)

      No information regarding severity

      Age: 44 (15)

      60 minutes

      Over 8 weeks

      Total of 6 sessions

      Intra-individual comparison: problem solving, self-efficacy and life satisfaction self-report scores before vs. after CR.Individual sessions

      Implementation of web-based program (Prosolv program) for problem solving in daily life.

      Self-report questionnaires on problem solving, self-efficacy and life satisfaction scores.No difference

      Siponkoski et al. 44

      Class I
      40 moderate to severe TBI

      Age: 41.3 (13.3)
      60 minutes

      2 times per week

      Over 3 months

      Total of 20 sessions
      Longitudinal intergroup comparison - Cross-over design:

      intervention phase vs. control phase (standard care).
      Individual sessions

      Neurological music therapy: intervention adapted from 2 existing music therapies (functionally oriented music therapy and music-supported training).

      Scores on executive function, memory, attention and reasoning tests.Improvement of cognitive functioning in the AB group.

      Increase in gray matter volume (right inferior frontal gyrus) in both groups during intervention and control periods.

      Vander Linden et al. 45

      Class III
      16 moderate to severe TBI ‡

      Age: 15 years 8 months (1 year 7 months)
      40 minutes

      5 per week

      Over 8 weeks

      Total of 40 sessions

      Intergroup comparison: changes in gray matter volume in regions of interest related to executive functions after cognitive training vs. changes in gray matter volume in control regions.Individual sessions

      Brain games software: Home-based cognitive training program targeting executive functions and attention.
      Scores on working memory, executive function, attention and processing speed tests.No difference on frontal gray matter volume after training.

      Significant negative correlation between changes in processing speed score and gray matter volume of putamen area.

      Vander Linden et al. 65

      Class II
      16 moderate to severe TBI ‡

      Age: 15 years 8 months (1 year 7 months)
      40 minutes

      5 per week

      Over 8 weeks

      Total of 40 sessions

      Intergroup comparison: computerized cognitive training vs. healthy control group (no training).Individual sessions

      Brain games software: Home-based cognitive training program targeting executive functions and attention.
      Scores on working memory, executive functions, attention and processing speed tests.

      Executive functioning and behavioral questionnaires (relative-report).
      At 6-month follow-up, lower effect from training on executive functions was found in adolescents with diffuse axonal injuries in the deep brain nuclei compared to adolescents without diffuse axonal injuries in this area.

      Verhelst et al. 76

      Class III
      5 moderate to severe TBIs ‡

      Age: 16 (9 months)

      40 minutes

      5 per week

      Over 8 weeks

      Total of 40 sessions
      Intra-individual comparison: executive performances before and after CR.Individual sessions

      Brain games software: Home-based cognitive training program targeting executive functions and attention.

      Scores on attention, working memory and executive function tests.

      Executive functioning and behavioral questionnaires (self- and relative-reports).
      Small to large effect size of intervention on all neuropsychological measures.

      Results maintained or increased at 6-month follow-up.

      Verhelst et al. 46

      Class II
      16 moderate to severe TBIs ‡

      Age: 15 (1.8)
      40 minutes

      5 per week

      Over 8 weeks

      Total of 40 sessions
      Intergroup comparison:

      white matter changes in TBI patient group vs. healthy control group.
      Individual sessions

      Brain games software: Home-based cognitive training program targeting executive functions and attention.

      Scores on attention, working memory and executive function tests.

      Executive functioning and behavioral questionnaires (self- and relative-reports).
      Time X

      group interaction effects on one attention score and on one executive function score (small to moderate effect sizes).
      Arroyo-Ferrer et al. 40

      Class III
      20-year-old man with TBI ‡

      Axonal damage was diagnosed using MRI

      45 minutes

      4 sessions per week

      Over 6 weeks

      Total of 16 sessions
      Case reportIndividual sessions

      EEG-based neurofeedback (EEG-NFB) intervention targeting inhibition of theta frequency band in frontal areas during exercises in virtual environments.

      Neuropsychological intervention aiming attention, executive functions and working memory.

      Scores on executive function, memory, attention and visuospatial ability tests.Improvement of visuospatial abilities, attention and executive functions after EEG-NFB intervention compared to after neuropsychological intervention.

      Correlative quantitative EEG changes were found.

      Dundon et al.38

      Class I
      26 TBI

      Information regarding regions of damage for 23/26 participants.

      Age: 37.3 (9.98)

      Not detailedIntergroup comparison:

      adaptive training group vs. non-adaptive training group vs. no training control group.
      Individual sessions

      Dichotic listening training task.

      Scores on attention and memory tests.

      Self-report questionnaires of global cognitive disorders.
      Improvement with both trainings on cognitive variables.

      Interaction between group and time was not significant.
      Dymowski et al.63

      Class II
      3 severe TBI ‡

      Ages: 21, 27 and 53
      60 minutes

      2-3 per week

      Over 12 to 16 weeks

      Total of 9 sessions

      Single case design repeated across subjects:

      baseline phase vs. attention training phase, and attention training phase vs. individualized strategies training phase.
      Individual sessions

      Computerized attention training: Attention process training 3 (APT-3)

      Scores on processing speed and attention tests.

      Questionnaire of attentional complaint (self- and relative-reports).
      Improvement in speed processing scores after attentional training and strategy learning.
      Fitzgerald et al.53

      Class I
      11 moderate to severe TBI ‡

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 27.2 (5.6)

      Max. mean age: 33.78 (13.33)

      40 minutes

      2 per week

      Over 4 weeks

      Total of 8 sessions
      Intergroup comparison: error awareness training vs. no feedback group.Individual sessions

      Computer-based intervention program for improving error awareness: participants received feedback on errors.

      Specific task about error awareness.

      Scores on global functioning, executive function and attention tests.

      Self- and relative-reports on dysexecutive questionnaires.

      Improvement of error awareness scores (large effect size in the experimental group).

      No change in group who did not receive feedback.
      McDonald et al. 36

      Class I
      72 TBI: 36 mild,

      8 complicated mild,

      8 moderate,

      23 severe

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 37.2 (12.0)

      Max. mean age: 43.1 (12.3)
      50 minutes

      2 per week

      Over 4 weeks

      Total of 8 sessions
      Intergroup comparison: cognitive behavioral therapy vs. repetitive cognitive tasks combined with methylphenidate or placebo.Individual sessions

      Memory and attention adaptation training (MAAT): metacognitive intervention.

      Attention builders training (ABT): Repetitive cognitive tasks.

      Scores on memory, attention, executive function and processing speed tests.Improvement in scores for learning, working

      memory and divided attention after combined MAAT/ methylphenidate intervention.

      Better memory improvement scores after MAAT compared to ABT intervention.

      Sacco et al. 34

      Class I
      32 severe TBI

      Age: 37.7 (10.4)
      60 minutes (including 20 min tDCS + 40 min cognitive rehabilitation)

      Twice per day

      Over 5 days

      Total of 10 sessions
      Intergroup comparison: real tDCS group vs. placebo tDCS group.Individual sessions

      Computerized rehabilitation of divided attention combined with unilateral or bilateral tDCS on dorsolateral prefrontal cortex (depending on the hemispheric lesion distribution for each patient), 20 min 2mA.

      Scores on visuospatial, semantic

      fluency, divided attention, working memory and long-term

      memory tests.
      Improvement in divided attention score in experimental group.

      No change over the pretreatment phase and within the control group.

      Reorganization of neuronal activations on fMRI.

      Vakili et al. 58

      Class I
      31 TBI

      Average length of post-traumatic amnesia (days):

      intervention group: 41.87 (43.87)

      control group: 43.64 (35.64)

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 27.73 (11.43)

      Max. mean age: 28.63 (6.54)

      2 hours

      Once a week

      Over 8 weeks

      Total of 8 sessions
      Intergroup comparison:

      video games group vs. passive control group (usual care).
      Group sessions

      Sessions combined “Medal of Honor: Rising Sun” games on PlayStation 2 (first-person shooter action video game) and psychoeducation program with compensatory strategies.

      Game performance on Playstation 2.

      Attentional blink task.

      Scores on attention tests.

      Self-report questionnaires of quality of life, self-efficacy and executive functioning.
      Improvements in game performance, attentional blink and attentional task, implying processing speed.

      No change in behavioral and self-efficacy scales scores.
      Jones et al.48

      Class I
      15 ABI, including

      9 moderate to severe TBI

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 51.9 (11.02)

      Max. mean age: 55.4 (10.54)

      45 minutes

      1 session per week

      Over 3 weeks

      Total of 3 sessions
      Intergroup comparison:

      music attention control training group (MACT) vs. attention process training (APT)
      Individual sessions

      music attention control training (MACT): Structured music-based auditory training exercises to practice attention functions.

      APT: Computer-based tasks to address focused, sustained, selective, alternating and divided attention.
      Scores on attention and executive tests.

      Improvements in one of the three attention and executive tests (TMT B) after the intervention for the MACT group compared to the APT group.
      Chiaravalotti et al. 42

      Class I
      18 TBI: 3 mild,

      3 moderate,

      12 severe

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 42.22 (14.12)

      Max. mean age: 45.78 (10.53)

      45 to 60 minutes

      Twice per week

      Over 5 weeks

      Total 10 sessions
      Intergroup comparison:

      treatment group vs. placebo control group (memory exercises but not exposed to critical components of training).
      Individual sessions

      Modified story memory technique,

      involving the training of mental imagery and the use of the source/context of learned information.

      BOLD signal on fMRI, word learning task and word recognition task.

      Scores on memory tests.
      Improvement in prose recall compared to

      placebo group.

      fMRI: Changes in activation in executive control network and default mode network (Bonferroni correction).
      Chiaravallotti et al. 49

      Class I
      69 moderate to severe TBI

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 37.17 (11.24)

      Max. mean age:

      40.68 (11.28)
      45 to 60 minutes

      Twice per week

      Over 5 weeks

      Total 10 sessions
      Intergroup comparison: treatment group vs. placebo control group (non-training-oriented tasks).Individual sessions

      Modified story memory technique,

      involving the training of mental imagery and the use of the source/context of learned information.

      Scores on memory tests.

      Ecological scores on the Rivermead Behavioural Memory Test.

      Cognitive and behavioral executive questionnaires (self- and relative-reports).
      Improvement in prose recall compared to

      placebo group (medium effect size).


      treatment effect on standardized memory scores.

      Improvement on Rivermead Behavioural Memory Test in the experimental group compared to placebo group.

      Hara et al. 33

      Class III
      67-year-old man who sustained a diffuse

      axonal injury ‡
      6 per week

      Over 2 weeks

      Total of 12 sessions
      Case reportIndividual sessions

      rTMS (2400 pulses once a day)

      combined with CR (training program focused on memory and attention disorders).
      Scores on memory, attention and executive function tests.

      Everyday memory assessment scores on Rivermead Behavioural Memory Test.
      - Absence of statistical analysis -

      2-point gain on the MMSE.
      Lesniak et al. 61

      Class I
      65 ABI including

      30 TBIs,

      27 CVAs,

      4 encephalitis.

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 39.6 (15)

      Max. mean age:

      42.2 (14)

      60 minutes

      5 per week

      Over 3 weeks

      Total 15 sessions
      Intergroup comparison: individual therapy group vs. group therapy group vs. no therapy group.Individual and group sessions

      Increased awareness of memory deficits and learning of global strategies for everyday memory.

      Scores on memory tests.

      Ecological memory scores (RBMT).

      Self-report of everyday memory complaint.
      No difference between groups.

      In individual therapy group, significant improvements on computerized memory, attention and working memory tests.

      In group therapy group, decrease of memory failures in daily life (relatives-report).

      Lesniak et al. 74

      Class III
      15 moderate to severe TBI ‡

      Age: 26.2 (7.6)
      5 individual and

      5 group sessions per week

      Over 3 weeks

      Total of 30 sessions
      Intergroup comparison:

      comprehensive therapeutic program vs. waiting list control condition.
      Group and group sessions

      Group sessions: Internal memory strategy training and implementation of external aids. Discussion about memory problems and their respective compensatory strategies.

      Individual sessions: exercises using memory strategies on Rehacom software.
      Scores on episodic memory, working memory and attention tests.

      Self- and relative-reports on cognitive measures.
      Improvement of cognitive scores (small to moderate effect sizes).

      Improvement on self- and relative-report measures.

      Gains maintained at 4-month follow-up.

      Raskin et al. 75

      Class III

      moderate to severe TBI

      Age: 42.11 (13.21)
      60 minutes

      1 or 2 per week

      Over 6 months

      Total of sessions not specified
      Longitudinal intergroup comparison - Cross-over design:

      active treatment condition vs. no treatment phase at baseline and at 1-year follow-up.
      Individual sessions

      Metacognitive technique using mental imagery.

      Prospective memory scores.

      Scores on attention, retrospective memory and executive function tests.

      Self-report questionnaires about prospective memory, everyday memory and quality of life.
      Improvement of prospective memory measure after active treatment phase only.

      Improvement on self-report questionnaire for everyday memory.

      Improvement maintained at 1-year follow-up for all previous results.
      Global training
      Buccellato et al. 69

      Class III
      21 ABI, including 62% mild to severe TBI

      Age: 41 (13.38)
      30 to 40 minutes

      3 per week

      Over 6 weeks

      Total of 18 sessions
      Longitudinal comparison - Cross-over within-subjects design:

      Global cognitive training phase with the Brainer Virtual Rehabilitation software vs.

      standard-of-care therapies phase.
      Individual sessions

      Virtual reality training using Bright Brainer Virtual Rehabilitation software (global cognitive training).
      Scores on sustained attention, processing speed, working memory and visuospatial tests.

      Neurobehavioral symptoms inventory and mood questionnaire.

      No significant difference between phases.
      De la Rosa-Arredondo et al.66

      Class III
      26-year-old woman with severe TBI ‡1 time per week

      Over 24 weeks

      Total of 24 sessions
      Case reportIndividual sessions

      CR including two phases of 12 weeks:

      Phase 1 targeted sustained and selective attention and visuospatial abilities.

      Phase 2 focused on memory and executive functions.
      Scores on attention, working memory, memory, visuospatial and abstract reasoning tests.- Absence of statistical analysis -

      Improvement in selective attention, verbal fluency, visuospatial ability and executive function scores.

      De Luca et al. 50

      Class I
      100 mild to moderate TBI

      Brain lesion site specified

      Age: 39.9 (10.1)
      60 minutes

      3 times per week

      Over 8 weeks

      Total of 24 sessions
      Intergroup comparison:

      Virtual reality training group vs. traditional CR group.
      Individual sessions

      Semi-immersive virtual reality using Nirvana BTs-N software, targeting attention, executive function and visuospatial training.
      Scores on global scale, executive functions and attention tests.Improvements on cognitive and mood scores for both traditional and virtual reality training.

      Improvements on cognitive flexibility for virtual reality training.

      Eilam-Stock et al. 35

      Class III
      29-year-old man with a moderate TBI30 minutes per day

      (including initial safety checks and 20 minutes of tDCS combined with cognitive training)

      5 times per week

      Over 4 weeks

      Total of 20 sessions
      Case reportIndividual sessions

      Computerized CR with BrainHQ program (attention, processing speed, executive functions and working memory) combined with tDCS (anodal electrode on the left DLPFC and a cathodal electrode on the right DLPFC, 20 min 2 mA).

      Scores on attention, working memory, processing speed, executive function and memory tests.

      Mood, sleep, pain and fatigue self-report scales.
      - Absence of statistical analysis -

      Improvement in several cognitive domains: attention, working memory, processing speed and semantic fluency.

      Improvement in emotional functioning: mood, sleep and fatigue.

      Hwang et al.56

      Class I
      96 TBI

      No classification of severity.

      49% of participants with positive CT scan findings

      Age: Detailed for each group. Not for total sample.

      Min. mean age: 65.8 (10.7)

      Max. mean age:

      68.1 (11.4)
      Once a week

      Over 6 months

      Total of sessions not specified
      Intergroup comparison:

      computerized cognitive training (CCT) group or tai chi (TC) group vs. usual care group.
      Individual sessions

      Computerized cognitive training using Rehacom software (attention, memory, speed of processing, executive functioning).

      Scores on global cognitive scales and executive function tests.Improvement on attention, memory scales and global cognitive scale scores after the intervention for the CCT group compared to usual care.

      No difference at 6-month follow-up.

      Improvement on conceptualization scores and global cognitive scale for the TC group compared to usual care.

      Differences between CCT and TC were not investigated.

      Kanchan et al. 39

      Class II
      10 moderate to severe TBI

      Age: 20-40
      45 min

      1 to 5 times per week

      Over 6 months

      Total of session not specified
      Intergroup comparison:

      cognitive training vs. passive control group (no training).

      Individual sessions

      Brainwave-R software: cognitive strategies and techniques for brain injury rehabilitation (attention, visual processing, information processing, memory, executive functions).

      Scores on cognitive battery (Luria Nebraska Neuropsychological Battery Adults - Form I).Improvement for all impaired cognitive areas in the experimental group.

      Differences between experimental group and passive control group after training.

      Kumar et al. 32

      Class III
      34-year-old woman with severe TBI ‡2 hours

      3 per week

      Over 2 months

      Total of 18 sessions
      Case reportIndividual sessions

      Immersive environment (coffeehouse) targeting practice job activities, which involved motor, social and cognitive skills.
      Score on executive function tests.

      Self-report quality of life.
      - Absence of statistical analysis-Improvement on TMT B score after intervention compared to baseline.

      Maggio et al. 64

      Class II
      56 TBI ‡

      Information regarding brain lesion sites

      Age: 35.5 (5.3)

      30 minutes

      5 times per week

      Over 8 weeks

      Total of 40 sessions
      Intergroup comparison:

      Lokomat training with virtual reality vs. Lokomat without virtual reality.
      Individual sessions

      Lokomat training with or without virtual reality.
      Score on general cognitive status, frontal ability and attention tests.Improvements on global cognitive scores, executive and attention scores for the experimental group.
      Pinard et al. 37

      Class III
      3 severe TBI

      Ages ranged between 39 and 57 years
      Over 15 months

      Length varied for each user

      Total session not detailed
      Case reportIndividual sessions

      Implementation and training to use a cognitive assistive technology for meal preparation called COOK (Cognitive Orthosis for coOKing).

      Qualitative scores of numbers of meals prepared per week with the stove, number of warnings, number of interventions of security modules.- Absence of statistical analysis -

      For two of three participants, increased number of meals prepared per week.

      Ramanathan et al. 47

      Class III
      54-year-old man with severe TBI ‡2.5 hours per day

      4 times per week

      Over 3 weeks

      Total of 12 sessions
      Case reportIndividual sessions

      CR including attention and

      prospective memory training and metacognitive strategy instructions.
      Scores on executive functions, attention and communication tests.

      Self-report of quality of life.

      Improvement on executive and attentional scores and quality of life scale.

      Cerebral activation task: Increased activation in middle and inferior frontal gyrus and superior temporal gyrus.

      Resting state: greater functional integration of frontal and parietal cortices, visual and auditory association areas and portions of the cerebellar vermis.

      Structural (DTI-measured FA; p < 0.01 uncorrected): increased FA in white matter tracts throughout the brain. Especially in tracts serving the prefrontal, occipito-parietal and temporal association cortices and cerebellum.
      Valimaki et al. 59

      Class I
      90 TBI ‡

      Severity defined with the presence of intracranial injury and sequelae of injuries to the head (ICD-10)

      Age: 41

      30 minutes per day

      Over 8 weeks

      Total of 8 sessions
      Intergroup comparison:

      Rehabilitation gaming group vs. entertainment gaming (PlayStation 3) group vs. passive control group (no gaming).
      Individual sessions

      Rehabilitation gaming with Cognifit software (cognitive training platform with three categories of exercises: memory, spatial and mental planning).

      Scores on processing speed, visuomotor tasks, attention, executive functions and working memory tests.

      Executive self-report questionnaire.
      No difference between the three groups.
      Wu et al. 43

      Class III
      50-year-old man, TBI with multiple

      contusions and lacerations, diffuse axonal injury and scattered

      cerebral hemorrhages ‡
      30 minutes

      5 times per week

      Over 1 month

      Total of sessions not specified
      Case reportIndividual sessions

      Comprehensive multifaced intervention including computer-assisted cognitive impairment rehabilitation system targeting memory, attention and visuospatial defects.
      Score on general cognitive status.- Absence of statistical analysis -

      Global improvement of cognitive performance.

      DTI neuroimaging:

      Number and length of callosal fiber bundle increased, especially for fibers connecting the bilateral hemispheres.
      Douglas et al. 71

      Class III
      13 severe TBI

      Age: 35.2 (9.3)
      Twice per week

      Over 6 weeks

      Total of 12 sessions
      Intra-individual comparison: communication scores before vs. after intervention vs. 3-month follow-up.

      Individual sessions and with communication partner

      CommCope-I program: Communication-specific coping intervention.

      Communication specific coping scores.

      Scores on functional communication abilities scale.
      Improvements in communication-specific coping strategies scores (moderate to medium effect sizes).

      Improvements in functional communication scores (moderate effect size).

      Improvements on stress scores (moderate effect size).
      Bosco et al. 68

      Class III
      19 severe TBI

      Age: 38.5 (10.8)
      1.5 hours

      Twice per week

      Over 12 weeks

      Total of 24 sessions
      Longitudinal comparison - Cross-over within-subjects design:

      Cognitive pragmatic treatment vs. unspecific activities phase.
      Group sessions

      Cognitive pragmatic treatment: rehabilitation training program for communicative-pragmatic abilities.

      Scores on attention, memory, executive function and logical reasoning tests.

      Scores on theory of mind test.

      Scores on communicative pragmatic tests.

      Scores on functional communication abilities scale.
      Overall improvement in pragmatic scores.

      Scores remained stables at 3-month follow–up.
      Gabbatore et al. 72

      Class III
      15 severe TBI ‡

      Age: 36.7 (8.73)
      1.5 hours

      Twice per week

      Over 12 weeks

      Total of 24 sessions

      Longitudinal comparison - Cross-over within-subjects design:

      Cognitive pragmatic treatment vs.

      unspecific activities phase.
      Group sessions

      Cognitive pragmatic treatment: Rehabilitation training program for communicative-pragmatic abilities.

      Scores on attention, memory, executive function and language tests.

      Scores on communicative pragmatic tests.

      Scores on theory of mind test.

      Improvement in comprehension and production scores.

      Improvement in long-term verbal memory and cognitive flexibility.
      Sacco et al. 41

      Class III
      8 severe TBI

      Age: 36.37 (8.6)
      1.5 hours

      Twice per week

      Over 12 weeks

      Total of 24 sessions
      Longitudinal comparison - Cross-over within-subjects design:

      Cognitive pragmatic treatment vs. unspecific activities phase.
      Group sessions

      Cognitive pragmatic treatment: Rehabilitation training program for communicative-pragmatic abilities.

      Scores on communicative pragmatic tests.

      Improvement in comprehension and production scores.

      Social Cognition
      Westerhof-Evers et al. 60

      Class I
      61 moderate to severe TBI

      Age: 43.2 (13)
      60 minutes

      1 or 2 per week

      Total of 16 to 20 sessions
      Intergroup comparison:

      social cognition and emotional regulation protocol training vs. active control treatment (computerized cognitive training).
      Individual sessions

      T-ScEmo protocol including 3 modules (i, enhancing emotion perception, ii, perspective taking and theory of mind, iii, basic and goal-directed social behavior).

      Scores on social cognition tests.

      Scores on attention and executive function tests.

      Self- and relative- reports: dysexecutive symptoms, social monitoring, empathy.
      Improvement for the experimental group on facial affect recognition, theory of mind compared to the control group.

      Improvement in relative-reported empathic behavior, and societal participation.

      Topographic orientation
      Boccia et al.67

      Class III
      49-year-old man with extensive head trauma and a coma (period of 1 week) ‡Over 8 weeks

      No information regarding intensity

      Case reportIndividual session

      Imagery-based treatment including two phases (i, imagery training in order to rapidly generate mental images, ii, generating and retrieving mental images).
      Scores on working memory, cognitive map test and 3D mental rotation tests.

      Ecological navigational tasks in real environment.
      Improvement of topographic skills and episodic memory scores.
      Verbal auditory perception
      Kim et al.31

      Class III
      65-year-old patient with TBI ‡

      Information about lesion area
      Over 2 months

      No information regarding intensity

      Case reportIndividual sessions

      Speech therapy and cognitive rehabilitation (cognitive domains not specified).
      Scores on global cognitive scale and aphasia test.Improved isolated-word verbal comprehension.

      No change in sentence comprehension.
      * Participants: n, TBI severity, mean age in years (SD)
      ✝ Cognitive rehabilitation characteristics: Length for each session; intensity (e.g. number of cognitive rehabilitation sessions per week and number of weeks), total of sessions.
      ‡ Brain lesions were identified by authors through computed tomography / magnetic resonance scanning for all included patients.
      ABI: acquired brain injury
      BOLD: blood-oxygen-level dependent
      CR: cognitive rehabilitation
      CT scan: computed tomography scan
      CVA: cerebral vascular accidents
      DTI: diffusion tensor imaging
      FA: fractional anisotropy
      ICD: international classification of diseases
      MMSE: mini mental state examination
      PTSD: post-traumatic stress disorder
      Reviews and study protocols were excluded from this research, as were those not written in the English language. Then, for all citations, two authors (AJ, ML) conducted an abstract review and excluded articles that did not meet the eligibility criteria. All remaining citations underwent a full text review.

      Data analysis

      For each of the four research questions, criteria of analysis were defined and collected in order to classify the characteristics and level of evidence of the reviewed studies.

      Cognitive domains targeted by cognitive rehabilitation

      All cognitive functions targeted by rehabilitation were listed. When several cognitive functions were trained, we registered all of them. We consider interventions to be “global training” interventions when they focused on three or more cognitive functions, or when the aim was defined with the generic term “cognitive skills.”

      Characteristics of cognitive rehabilitation

      Types of cognitive rehabilitation were divided into three categories of interventions. Cognitive training was defined as repetitive exercises without any explicit mention of metacognitive strategy training. Integrative cognitive intervention referred to interventions that explicitly combined the training of cognitive functions and metacognitive strategies. Finally, external aids training corresponded to the use of external compensatory mechanisms such as notebooks, cell phone applications and alarms.
      We also identified combined approaches, which referred to cognitive rehabilitation associated with other interventions like pharmacotherapy or non-invasive brain stimulation (NIBS).
      Three other parameters of cognitive interventions were analyzed: the delivery mode including group versus individual sessions, the length and the intensity. Length was studied by distinguishing very short (1 week or less), short (1 week to 1 month), moderate (1 to 3 months) and high (more than 3 months) duration. Intensity was classified as low (1 session per week), moderate (2 sessions per week) or high (3 or more sessions per week).

      Behavioral examination and neuroimaging as outcome measures

      Concerning behavioral outcome measures, four types of assessment were distinguished: (i) neuropsychological examination including standardized neuropsychological tests; (ii) ecological neuropsychological examination including standardized tests and/or experimental ecological tasks with reference to daily life situations; (iii) self-reporting of cognitive complaints, social participation in everyday activities and quality of life; (iv) relative-reporting of patient's difficulties in daily life. We also counted the number of these types of assessment for each study in order to attest to the exhaustiveness of the assessment.
      Neuroimaging outcome measures were classified as structural and/or functional imaging and/or electroencephalography (EEG).

      Efficacy of cognitive rehabilitation

      The efficacy of cognitive rehabilitation was analyzed according to three main criteria and associated sub-criteria detailed below. A coding grill was used for the extraction of these methodological criteria.
      The outcome measures were the first criteria. We first pointed out the results showing a significant improvement in at least one of the outcome measures defined by the authors. Quantitative and qualitative improvements were coded when collected. Second, if a significant and/or clinically relevant change was reported, we distinguished whether it was in the primary or secondary outcome measures.
      The internal validity of reviewed studies was assessed as secondary criteria, based on the classification used by Cicerone et al. in systematic reviews 6. According to this classification, studies were classified as class I when they were well designed, prospective, randomized controlled trials. Class II referred to prospective, nonrandomized cohort studies, retrospective, non-randomized case-control studies or multiple baseline studies that allowed a direct comparison between treatment conditions. Class III included clinical series without concurrent controls or single-subjects designs. In a second step, we also detailed the control group design, distinguishing active, passive or no control group. We considered it an active control group when patients participated in usual care or unspecific activities. A passive control group referred to a waiting list or a no-treatment phase.
      The statistical analysis was the third criteria. As proposed by Cicerone et al. 29, comparisons of between-group treatment conditions were considered as a higher level of methodological quality compared to within-group comparisons. We also identified whether or not the authors applied an intention-to-treat (ITT) analysis. Finally, we analyzed whether the effect size and measures of variability such as confidence intervals were reported.

      Charting the data

      In accordance with the PRISMA-Scr guidelines 30, a flow diagram was used in order to illustrate study selection (Figure 1). The level of evidence for the efficacy of cognitive rehabilitation was also charted (Figure 2). Figure 2 details the number of studies that met each pre-cited methodological criterion and associated sub-criteria. For each study, the key characteristics of TBI participants, cognitive rehabilitation, experimental design, intervention, neuropsychological outcome measures and significant main results were collected and summarized in Table 1.
      Figure 1:
      Figure 1Flow diagram for the scoping review process with PRISMA-Scr guidelines.
      Figure 2:
      Figure 2Flow diagram for the level of evidence in the efficacy of cognitive rehabilitation in the reviewed studies.


      Between January 2015 and July 2021, 458 studies were published in the Pubmed (via Medline) and PsycINFO databases. We found 31 duplicates across the two databases and removed them (Figure 1). Four hundred twenty-seven records were reviewed by title and abstract and 330 were excluded based on the inclusion and exclusion criteria. Ninety-seven articles were assessed by full text review. In the end, 46 studies were included in the scoping review.

      Cognitive domains targeted by cognitive rehabilitation

      The results showed a large scope of 7 cognitive functions targeted by interventions: executive functions (n=14, 30%), attention (n=14, 30%), memory (n=7, 15%), communication (n=4, 9%), social cognition (n=1, 2%), topographic orientation (n=1, 2%) and verbal auditory perception (n=1, 2%). Global training was proposed in 12 out of the 46 studies (26%).

      Characteristics of cognitive rehabilitation

      Type of cognitive interventions

      In this review, integrative cognitive interventions concerned 48% of studies (n=22), cognitive training was reported in 37% of studies (n=17) and external aids training was described in 11% (n=5). Two studies (4%) did not detail the type of intervention 31,32. The effects of combined interventions were examined in 4 studies 33–36, in which cognitive rehabilitation was associated with pharmacotherapy 36, repetitive transcranial magnetic stimulation (rTMS) 33 or transcranial direct current stimulation (tDCS) 34,35.

      Methodological parameters of cognitive rehabilitation

      Among the 46 reviewed studies, we showed that individual sessions were used in 83% of the studies (n= 38), whereas group sessions were only used in 11% (n=5). Six percent (n=3) of the studies combined individual and group sessions.
      Furthermore, the length of interventions was heterogeneous, ranging from 5 days 34 to 15 months 37. Fifty-four percent of studies (n=25) proposed an intervention which lasted between 1 and 3 months. Shorter interventions lasting 1 week to 1 month were found in 24% of studies (n=11). Finally, cognitive rehabilitation interventions including a duration of less than 1 week or longer than 3 months were found in 1 (2%) and 8 studies (18%), respectively. In one study (2%), this methodological feature was not detailed 38.
      Concerning the intensity of interventions, 26% of the reviewed studies (n=12) proposed two sessions per week and 44% (n=20) proposed three or more sessions per week. Conversely, 11% (n=5) included only one session per week. In one study, the intensity was variable and progressively decreased among each phase of cognitive rehabilitation 39. Finally, 17% (n=8) did not describe this methodological point.
      Our results indicated that 9 out of the 46 studies (20%) did not detail both the length and intensity of the interventions. Among studies that detailed length and intensity, the most common design combined 3 or more sessions per week over 1 to 3 months and was found, in this scoping review, in 10 studies.

      Behavioral examination and neuroimaging as outcome measures

      The effects of cognitive rehabilitation were mostly measured with standardized neuropsychological tests in 41 out of the 46 studies (89%). Ecological neuropsychological examination was used in 35% of studies (n=16). Fifty percent (n=23) included a self-report questionnaire, whereby cognitive complaint was assessed in 16 studies (70%) and quality of life was measured in 7 studies (30%). Finally, reporting by relatives was used in 35% of studies (n=16).
      Thirty-seven percent of studies (n=17) used one of these 4 types of measures, 28% of studies (n= 13) used 2 types of measures and 24% (n=11) used 3 types of measures. In contrast, 11% of studies (n=5) proposed an exhaustive evaluation with these 4 types of measures.
      Neuroimaging outcome measures used as brain markers of cognitive rehabilitation were reported in 20% (n=9) of studies, whereas EEG was performed in only two studies 38,40. More specifically, resting state functional magnetic resonance imaging (fMRI) 41, regional cerebral blood flow 33 and brain activation during an fMRI cognitive task 34,42 were analyzed in 4 studies. Structural MRI data were reported in 4 studies 43–46 . Only one paper combined diffusion tensor imaging, attention-related fMRI and resting-state fMRI sequences 47.

      Efficacy of cognitive rehabilitation

      According to Cicerone's criteria for evidence-based classes 6, 41% (n= 19) 34,36,38,42,44,48–61 of reviewed studies were classified as class I, 13% (n=6) 39,46,62–65 as class II and 46% (n= 21) 31–33,35,37,40,41,43,45,47,66–76 as class III.
      Ninety-three percent of studies reported significant cognitive improvement on at least one outcome measure, among which 19 studies described clinical improvement on the primary outcome independently of statistical change (Figure 2). Within these studies, 10 were classified as class I and involved an active control group 34,36,42,44,48,49,52–54,56. Then, with regard to statistical analysis, these 10 studies applied between-groups comparisons to assess the efficacy of treatment, among which 7 used an intention-to-treat analysis (15% of reviewed studies) 34,42,44,49,52,53,56. Medium to large effect sizes were reported in 5 out of these 7 studies 44,49,52,53,56 and the confidence interval was reported in only one out of these 7 studies 49.


      This scoping review was conducted starting with 2015, after the most recent systematic review 10, in order to identify and characterize studies evaluating cognitive rehabilitation following a moderate to severe TBI, to summarize the cognitive approach used and the domains investigated and to analyze their efficacy.
      Memory, attention and executive functions were most often targeted in individual sessions adopting an integrative cognitive approach. Cognitive interventions were mainly temporally distributed with 3 or more sessions per week over 1 to 3 months. One or two behavioral outcome measures were mostly preferred by authors to assess the efficacy of intervention, while neuroimaging outcome measures were rarely used. The review found clinically significant effects of cognitive rehabilitation after a moderate to severe TBI in a very large part of reviewed studies (93%), among which 41% described an improvement on the primary outcome measure. The high number of positive published results could be the sign of a publication bias according to Dwan and colleagues’ conclusions in 2013 77. Nevertheless, when methodological criteria for the level of evidence were controlled (outcome measures, internal validity and statistical analysis) a significant decrease was observed, from 93% to 15%. This significant decrease is unsatisfactory and highlights the methodological requirements for future studies. Challenges in TBI rehabilitation imply that cognitive interventions must be based on a robust experimental design to prove their efficacy and to replicate the findings on which recommendations for clinical practice could be finally derived. Therefore, this scoping review provides a complementary approach to prior systematic reviews 6,10–12 by identifying five key methodological points.

      Specific experimental designs for cognitive rehabilitation of TBI patients

      In this scoping review, 41% of reviewed studies were classified as class I. This result highlights a continuing upward trend of randomized controlled trials in cognitive rehabilitation. Indeed, Cicerone et al. reported a percentage of class I studies ranged from 17%6,12 to 20% 11 until 2008, which increased to 36% between 2009 and 2014. RCTs were crucial for evidence-based studies but not always relevant in rehabilitation practice, where double blind was sometimes not feasible 11 because the therapist was systematically aware of the hypothesis underlying the contents of intervention. Furthermore, experimental and control groups have to share common methodological parameters such as delivery mode, length and intensity of rehabilitation to allow between-groups comparisons 78. A major advance in the literature is the presence of an active control group to attest to the specificity of the experimental intervention and to rule out the nonspecific effects of global cognitive stimulation, such as treatment effect, motivational or novelty effect and Hawthorne effect 78. Statistically, the efficacy of interventions cannot be only demonstrated using within-group analysis. Improvements must be specific to the experimental intervention and thereby confirmed with between-group comparisons. Effect sizes, rarely presented in reviewed studies, are also a supplementary indicator of the efficacy of cognitive interventions and should be systematically added in the future. All these methodological points were controlled in one study 49, in which the authors investigated the added effects of psychoeducation and metacognitive strategy training in an experimental group compared to an active control group with cognitive rehabilitation including non-training-oriented tasks, with a positive effect for patients. Finally, a challenge for further group studies may be the individualization of the cognitive intervention regarding cognitive profiles and complaints in order to compensate for the clinical heterogeneity of TBI. Two main solutions could be proposed for greater methodological relevance. The first is to constitute toolboxes for each cognitive domain, including standardized exercises with increasing levels of difficulty, like those developed by Visch-Brink et al. 79 and Van Rijn et al. 80 in aphasia therapy 81. For a single cognitive function rehabilitated, the therapist will be able to choose the modalities of presentation of the most relevant exercise to work on. The second solution is the use of single-case experimental design (SCED). Multiple baseline design includes a small number of patients (i.e. classically at least 3 participants), has high feasibility and allows for an individualized approach. The high level of evidence of SCED lies in the repeated measurements performed during the baseline and intervention phases in order to control for intra-individual variance. The participant corresponds to their own control, comparing their performance at the baseline and after the intervention. Visual and statistical analysis are used to measure the efficacy of intervention 63,82–84.

      Combined cognitive interventions as an attractive perspective

      Combined interventions are interesting to potentiate significant individual benefits of each therapy on cognitive functioning and to promote the generalization of improvements to daily functioning. Regarding the results of the present scoping review, combination may be considered at three levels: within interventions, between delivery modes of interventions and between interventions.
      Forty-eight percent of the reviewed studies used integrative rehabilitation combining both cognitive and metacognitive training. For example, Emmanouel et al. 52, in a randomized controlled trial of 18 TBI patients, showed the benefits of goal management training associated with working memory training (GMT + WM group) in comparison with an isolated WM group on multistep everyday tasks and ecological executive measures, with small to large effects sizes for the combined approach.
      The second level of combination was between group and individual sessions. Even if, in this scoping review, results showed that individual interventions remained the majority (83%), a combined approach of these two delivery modes was proposed in 3 studies, but its specific benefits were not analyzed 61,73,74 .
      The third level concerned the use of combined interventions. Only 4 studies proposed combined rehabilitation with pharmacotherapy 36 or NIBS 33–35. The heterogeneous designs and the low statistical power of these studies call for replication.

      Specific effects of length and intensity of cognitive rehabilitation

      The main temporality reported by this scoping review included a moderate duration (i.e. ranging between 1 and 3 months) with a high intensity (i.e. 3 or more sessions per week). This choice seems related to clinical relevance and feasibility in clinical research protocols. As mentioned by Cicerone et al. 10, the intensity and length of the cognitive interventions must be studied in order to determine their respective contribution to the efficacy of the rehabilitation and thus have to be integrated into statistical models. None of these two parameters were analyzed across all reviewed studies. Furthermore, Chiaravalotti et al. 49 have investigated the use of monthly booster sessions proposed over 5 months, after memory training with 10 sessions over 5 weeks. These focused on applying trained memory strategies in daily life. Although the authors reported no effect of these booster sessions during follow-up, it seems very useful to check the implementation and efficacy of trained cognitive strategies in daily living.
      In addition to length and intensity parameters, future studies should investigate the severity of cognitive impairment at inclusion, the delay from the injury or fatigability as contributing variables in determining the dynamic of the intervention.

      Selection of outcome measures as a key experimental point

      The choice of outcome measures is a key methodological point as well as the categorization into classes I to III for evidence-based medicine. Assessment using standardized neuropsychological examination was the most frequently reported (89%), followed by self-report questionnaires (50%), ecological neuropsychological assessment (35%) and relative-report questionnaires (35%). An exhaustive neuropsychological examination of all cognitive domains could contribute to demonstrating the benefits of therapy on trained as well as on untrained functions. Moreover, after a wash-out period, a follow-up assessment may show maintained benefits of rehabilitation. However, it has been well described that standardized pencil-paper neuropsychological performance test could not exactly reflect those obtained in daily contexts, especially in executive functions assessment 85. In this way, an ecological cognitive assessment could be a sensitive measure to predict real-life performance 86. Ecological tests such as the Test of Everyday Attention 87 or the Rivermead Behavioral Memory Test 88 were frequently proposed in the reviewed studies but remained in non-ecological environments and encompassed a restricted representation of daily life tasks. Conversely, the Multiple Errands Test (MET) 85, which was not reported here, implies daily life activities, takes place outside of the rehabilitation sites and offers a more sensitive image of executive disorders 85. MET should be combined with person-centered assessment to improve the clinical relevance of the evaluation. The Goal Attainment Scaling (GAS) 89, derived from occupational therapy, makes it possible to set personalized goals with the patient as well as 5 levels of predicted attainment for a sensitive evaluation of progress 90.
      In the scoping review, two authors developed ecological experimental tasks to assess the effect of executive rehabilitation. Emmanouel et al. 52 proposed multistep daily activities such as sending a text message or buy an airplane ticket. The number of correct steps was counted and compared among parallel scripts before and after cognitive rehabilitation. After sessions of goal management training, Gracey et al. 54 defined with each participant several daily life intentions, such as making sure their mobile phone is with them, charged and switched on. The daily proportion of intentions achieved by patients was studied.
      Finally, several studies used cognitive complaint and quality of life questionnaires to investigate views of patients and their family in addition to the standardized neuropsychological examination. After cognitive rehabilitation, these reports provided an update on the cognitive complaint and metacognitive abilities.
      Exhaustiveness and specificity of assessment constitutes a methodological key point contributing to the level of evidence of interventions. Complete outcome measures (i.e. standardized examination, ecological assessment, self- and relative-reports) were reported in only 5 studies 49,52,60,61,63.

      Multiple contributions of neuroimaging in cognitive interventions

      Magnetic resonance imaging was used in 20% of reviewed studies. The use of neuroimaging tools still remained scarce in recent years, which is in agreement with Galetto and Sacco 91, who reported only 11 studies between 1985 and 2016 that used neuroimaging techniques to attest to neuroplastic changes after cognitive rehabilitation in TBI. For instance, Chiaravalotti et al. 42 reported BOLD signal changes during word learning and recognition tasks, with patterns of increased and decreased cerebral activation in the frontal and parietal lobes after 10 sessions of memory rehabilitation. Some authors have suggested a disengagement of the executive control network (ECN) and an activation of the default mode network (DMN) after cognitive rehabilitation to explain cognitive improvement, suggesting that memory tasks became less cognitively demanding after cognitive rehabilitation. Nevertheless, no details were given about cognitive scores on task-related functional activation.
      Brain imaging constituted a promising method but further research is needed to identify potential contributions. Structural and functional MRI continue to contribute to a better understanding of TBI physiopathology. These techniques illustrate the brain reorganization and the dynamics of plasticity mechanisms that could be associated with short and long-term cognitive changes.
      Brain imaging may also participate in the identification of potential modulators of recovery trajectories after TBI 92 such as brain reserve, including measures of specific patterns of gray matter volume, cortical thickness, synaptic integrity or white matter microstructural properties. Neuroimaging could make multiple contributions but at this time its use as a measure of the efficacy of an intervention should be done in combination with cognitive measures.

      Study limitations

      A few main limitations were identified in the scoping review. The first concerned the search strategy, which focused on only two databases and did not include the gray literature. As reported, the impact of publication biases could contribute to an inaccurate picture of the literature on cognitive rehabilitation. Second, only one reviewer performed data extraction and analysis. While we made efforts to define criteria precisely to assess the methodological quality of the reviewed studies, there may be subjective interpretation involved in this process.


      This scoping review highlights the persistent and growing interest in cognitive rehabilitation with major methodological improvements in the design of studies for moderate to severe TBI since 2015. In consequence, this led to higher number of studies that show an improvement in the primary outcome measures after cognitive rehabilitation. Our findings make it possible to identify three methodological criteria and sub-criteria for determining the level of evidence of cognitive interventions and could be used in future studies. Our approach is complementary to the prior systematic reviews 6,10–12 which were mainly focused on the content of interventions. Methodological efforts must be continued, and combined interventions studies must be proposed. Individualized cognitive rehabilitation also remains a challenge. Outcome measures must be well selected, including neuropsychological tests in ecological and non-ecological environments, patient- and relative-reports. Rehabilitation of social cognition and emotion regulation should be better investigated. The results of this scoping review now need to be confronted with systematic reviews and meta-analyses.


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