6. Cognition Interventions Post Acquired Brain Injury
Abbreviations
ABI Acquired Brain Injury
APT Attention Process Training
CES Cranial Electrotherapy Stimulation
GH Growth Hormone
Met Methionine Allele
PASAT Paced Auditory Serial Addition Task
PDA Personal Digital Assistant
PTA Post Traumatic Amnesia
RCT Randomized Controlled Trial
TBI Traumatic Brain Injury
TPM Time Pressure Management
Val Valine Allele
Key Points
Although attention training programs in general improve attention scores, the level of structure in these programs does not appear to influence the success of the intervention.
Dual-task training has been shown to improve measures of attention to the extent that the ABI population does not significantly differ from healthy controls, however it is undetermined if the strength of these effects compared to non-dual-task training are greater.
Computer-based interventions are no more effective than no intervention in improving measures of attention and concentration post ABI.
Repetitive virtual reality tasks which include repetition are effective in improving attention and concentration in ABI populations.
Goal management training is effective in assisting those who sustain an ABI learning to manage life goals through improved attention.
Therapies which focus on emotional regulation or mindfulness do not appear to be effective at improving attention post ABI.
In order to determine if attentional training is effective in improving attention post-ABI standardized protocols must be developed to allow between study comparisons.
Tasks that involve mathematical skills may be effective at improving attention post-ABI.
Cognitive rehabilitation therapy is not likely to remediate attentional deficits in ABI populations.
Transcranial direct current stimulation may be effective in remediating attentional deficits when combined with computer assisted training in ABI populations.
Donepezil can help improve attention in individuals with ABI.
The effectiveness of methylphenidate treatment to improve cognitive impairment following brain injury is unclear.
Methylphenidate is effective in improving reaction time for working memory.
Response to methylphenidate may depend on genotype.
Bromocriptine might improve executive function, but not memory, attention, or reading ability in patients post TBI.
Cerebrolysin may be beneficial for the improvement of clinical outcome and cognitive functioning following brain injury; however, controlled trials are needed to further evaluate its efficacy.
Rivastigmine may not be effective in treating attention deficits post-ABI.
Pager and voice-organizer programs may improve a patient’s ability to complete tasks post TBI.
Personal digital assistant (PDA) devices are superior to paper-based interventions at improving memory and task completion post TBI; specially when introduced using systematic instructions and in combination with occupational therapy. Patients who have used previous memory aids might benefit from this intervention the most.
Text message prompts sent to a patient’s smartphone, when used alone or in combination with other memory-improvement therapies, likely improve task completion post TBI. However, risk exists of device dependency exists.
A television assisted prompting (TAP) program may be superior to other methods of memory prompting in patients post TBI.
Automated prompting systems, such as Guide (audio-verbal interactive micro-prompting system) and a computerized tracking system, can reduce the amount of prompts needed from support staff to patients to complete tasks post TBI.
Calendars may be effective tools for improving memory and task completion post ABI.
The use of a diary may help to improve memory and task completion post ABI, but more so if diary training is combined with self-instructional training.
Virtual reality programs may enhance the recovery of memory, learning, but there is currently limited evidence supporting the use of virtual reality programs.
Memory-retraining programs appear effective, particularly for functional recovery although performance on specific tests of memory may or may not change.
Specific computer-based softwares seem to be effective for improving memory post-ABI.
Computer-based interventions may be as effective as therapist administered interventions.
Emotional self-regulation therapy may be effective for improving specific elements of memory.
Recall and recognition of words can be enhanced by using a spaced learning condition.
Cranial electrotherapy stimulation is likely not effective at enhancing memory and recall abilities following TBI.
Donepezil likely improves attention and memory following TBI.
There is conflicting evidence that methylphenidate administration post TBI improves attention, memory, concentration and processing speed.
Response to methylphenidate likely varies depending on genotype at the catechol-O-methyltransferase (COMT) gene.
Sertraline has not been shown to improve learning, or memory within the first 12 months post TBI, and may be associated with side effects.
Amantadine might not be effective at improving learning and memory deficits post TBI.
Pramiracetam might improve memory in males post TBI; however, additional studies are required.
Physostigmine likely improves long-term memory in men with TBI.
Bromocriptine may improve dual task performance and motivational deficits but its effect on memory is controversial. More research is needed before the benefits of using bromocriptine to enhance learning and memory deficits are required.
Cerebrolysin may be beneficial for the improvement of clinical outcome and cognitive functioning following brain injury; however, controlled trials are needed to further evaluate its efficacy.
The administration of recombinant human Growth Hormone (rhGH) is likely not different than placebo at improving executive functioning, memory, or learning in patients post TBI; however certain aspects of patient quality of life may be improved.
The administration of recombinant human Growth Hormone (rhGH) might be superior at improving intelligence and cognition in patients with a growth hormone deficiency, versus those who do not, post TBI. Molecular markers of growth however may not be different post treatment between groups.
Rivastigmine may not be effective in treating memory deficits post-ABI.
Targeted hypnosis may improve memory, attention, and cognitive function in patients post TBI or stroke; however, only as long as the intervention is being administered.
Attention improvement interventions may be superior to non-specific cognitive or education programs at improving memory and attention in patients post TBI.
A comprehensive cognitive treatment strategy is likely superior to a computerized training package at improving task initiation and completion in patients post TBI; this intervention may also improve cerebral blood flow.
It is unclear whether virtual-reality training is superior to conventional training at improving cognitive and executive function outcomes post TBI. Conflicting evidence exists, and further studies are required.
Computer or smartphone software programs (BrainHQ, Parrot Software, ProSolv app) may not be superior to common interventions at improving memory, attention, and problem-solving skills in patients post TBI.
Goal management training may superior to motor skills training at improving every day skills (meal preparation), but not intelligence or neuropsychological outcomes in patients post TBI.
It is unclear whether goal oriented interventions delivered in a group setting are more successful than educational interventions at improving cognitive and executive function post ABI. However, no detrimental effects have been found with the intervention.
Emotional regulation interventions delivered in a group setting may improve executive function in patients post TBI; however, it is unclear if it is superior at doing so compared to conventional cognitive remediation.
It is unclear whether cognitive interventions (such as the Metacognitive Strategy
Instruction program) improves language ability, and executive/ cognitive function in patients post TBI.
Remedial occupational therapy is likely superior to adaptive occupational therapy at improving general cognitive functioning in patients post TBI.
Low intensity outpatient cognitive rehabilitation might improve goal attainment and cognitive function in patients post ABI.
Donepezil might improve attention, learning and short-term memory following TBI; however, side effects may incur from its use.
The effectiveness of methylphenidate treatment to improve cognitive impairment following brain injury is unclear. Further studies with larger populations are required.
Sertraline has not been shown to improve cognitive functioning within the first 12 months post TBI, and may be associated with side effects.
Amantadine might not be effective at improving attention and memory deficits post TBI. Its impact on executive functioning should be studied further.
Bromocriptine may improve some executive cognitive functions such as dual task performance and motivational deficits. More research is needed before the benefits of using bromocriptine to enhance cognitive functioning are known.
The administration of recombinant human Growth Hormone (rhGH) is likely not different than placebo at improving executive functioning, memory, or learning in patients post TBI; however certain aspects of patient quality of life may be improved.
The administration of recombinant human Growth Hormone (rhGH) might be superior at improving intelligence and cognition in patients with a growth hormone deficiency, versus those who do not, post TBI. Molecular markers of growth however may not be different post treatment between groups.
Rivastigmine may not be effective in treating memory deficits post-ABI.
Introduction
Cognitive dysfunction is a common symptom of acquired brain injury (ABI) which can negatively affect many areas of cognition such as attention, memory, executive function, learning, and social cognition. Each of these cognitive functions represents a unique area of cognition which allows individuals to execute activities of daily living. Cognitive impairment can be caused not only by the initial trauma, but also by secondary inflammation or insult. Compared to mild traumatic brain injury (TBI), moderate/severe TBI is associated with more severe and persistent cognitive deficits, with about 65% of patients reporting long-term cognitive problems (Rabinowitz & Levin, 2014). The effects of TBI on overall cognitive functioning vary depending on the time post injury (Schretlen & Shapiro, 2003). Even with good medical prognosis, cognitive ability remains one of the best predictors of successful return to work and independent living (Brain Injury Medicine, pp 990). With the diverse nature of the brain there are a multitude of ways that each trauma can impact cognition. As a result, there are a variety of interventions available to clinicians to help rehabilitate cognitive function post ABI. In Ontario, the mean direct per-patient medical costs in the first follow-up year after ABI was $32 132 for TBI and $38 018 for non-traumatic brain injury. (Chen et al., 2012).
The broadest categories of cognitive interventions can be classified as pharmacological and non-pharmacological. Pharmacological interventions use medication in an attempt to remediate cognitive deficits. These types of medications usually moderate neurotransmitters in the brain which regulate cognitive functions. By influencing the concentration and absorption of either excitatory or inhibitory neurotransmitters these medications are able to affect memory, attention, and social behaviours (Brain Injury Medicine, pp 1205). Non-pharmacological interventions span a broader spectrum and can include anything from physical exercise to memory programs with assistive technology. However, there are multiple challenges when evaluating the effectiveness of cognitive interventions. First, there is no consensus regarding a definition of attention; currently, it is used as a general construct. Attention can be further broken down into sub types (sustained, divided, focused, selective, vigilance, speed of information processing), however this is not always reflected in the literature. Second, researchers and clinicians may use different measures when reporting outcomes, making comparisons between interventions difficult. Third, a study may use the same outcome measures repeatedly, thereby confounding practice and treatment effects (e.g., Paced Auditory Serial Attention Task (PASAT)). Finally, studies may not consider or account for the rate of spontaneous recovery following brain injury (i.e., would participants naturally show recovery of function in the absence of treatment?). For these reasons, assessing the efficacy of interventions for cognitive rehabilitation is more challenging compared to other modules due to the heterogeneous presentation and assessment of cognitive deficits..
This module reviews the available evidence related to interventions for cognitive rehabilitation following ABI. Studies that specifically deal with cognitive-communication deficits are discussed in module 7.
6.2 Remediation of Attention, Concentration, and Information Processing Speed
Although there is no specific agreement on the definition of attention, it is usually measured using externally directed tests, such as instructing participants to focus their attention on a sequence of stimuli or attenuating to a particular stimulus.
In general, TBI populations demonstrate significant deficits compared to control populations. Dymowski et al. (2015) showed that mild to severe TBI participants performed significantly worse on speed of information processing tasks compared to a healthy control group.
Dockree et al. (2006) and Hasegawa and Hoshiyama (2009) found that TBI patients made significantly more errors than their non-TBI counterparts on dual task experiments for sustained attention. However, a case series by Foley et al. (2010) found that level of injury severity as measured by the Glasgow Coma Scale or PTA did not play a role in who performed poorly on the dual task assignment given to participants. They found that only 27% of TBI study participants performed below the cut-off for normal performance.
Two studies assessing the reaction times of individuals demonstrated that those with a TBI were found to have slower reaction times than individuals who had not sustained a TBI (Azouvi et al., 2004; Stuss et al., 1989). Results of the visual analogue scale also indicated that mental effort was higher for those with a TBI than for the controls. The results of this study confirmed what previous studies had found: those with a TBI have greater difficulty when dealing with two simultaneous tasks (Azouvi et al., 2004).
In order to better understand the mechanism by which cognitive interventions can improve attention, concentration, and information processing, there needs to be a consensus as to the definition of specific cognitive processes, such as attention.
6.2.1 Non-Pharmacological Interventions
6.2.1.1 Drill & Practice
Key Points
Although attention training programs in general improve attention scores, the level of structure in these programs does not appear to influence the success of the intervention.
The following studies examined the influence of “drill & practice” exercises (either computerized and/or paper-and-pencil) on attentional functioning. Drill and practice training aims to improve attention through repetitive training of specific tasks involving attention.
Evidence Table(s)
Discussion
Conclusions
There is level 3 evidence that attention processing training may improve attention compared to visual search training in ABI populations.
6.2.1.2 Dual-Task Training
Key Points
Discussion
Conclusions
6.2.1.3 Computer-Based Interventions
Key Points
Repetitive virtual reality tasks which include repetition are effective in improving attention and concentration in ABI populations.
Discussion
Repetition of tasks in virtual reality improved performance, both in terms of speed and accuracy (Dvorkin et al., 2013; Gerber et al., 2014). Gentle nudges corrected behaviour better than break-through or no feedback (Dvorkin et al., 2013). However, repetition of the Stroop test in different virtual reality environments showed limited improvement in performance on those specific tests (Dahdah et al., 2017). A virtual reality exercise program demonstrated significant benefits in reaction times but not attention after intervention; more high quality research is needed to confirm the efficacy of virtual reality exercise (Grealy et al., 1999).
Conclusions
There is level 4 evidence that attention performance can be improved in ABI populations through repetition of tasks, either through computer-based or virtual reality environments.
6.2.1.4 Attention Training Programs
Key Points
Therapies which focus on emotional regulation or mindfulness do not appear to be effective at improving attention post ABI.
In order to determine if attentional training is effective in improving attention post-ABI standardized protocols must be developed to allow between study comparisons.
Tasks that involve mathematical skills may be effective at improving attention post-ABI.
Cognitive rehabilitation therapy is not likely to remediate attentional deficits in ABI populations.
Cicerone et al. (2005) recommended strategy training for persons with TBI for improving deficits of attention. It should be noted, however, that there was insufficient evidence to distinguish the effectiveness of specific attention training during acute stage rehabilitation from improvements made from spontaneous recovery or from more general cognitive interventions (Cicerone et al., 2005).
Evidence Table(s)
Discussion
A recent RCT (Dundon et al., 2015) examined the effect of adaptive training on dichotic listening tasks and attention, interestingly the adaptive training group had significantly higher scores on the listening task compared to non-adaptive training group, however, the non-adaptive training group surpassed the adaptive training group in test of everyday attention scores.
Emotional regulation was also examined as a potential intervention for the remediation of attention post-ABI (Cantor et al., 2014). However, this treatment was not seen to be effective in the recovery of attention, other significant effects on executive functioning from this study are discussed further in section 6.4.1.1. Another study which focused specifically on mindfulness (McHugh and Wood, 2013) found that mindful focused training significantly improved participant’s ability to correctly select stimuli compared to controls.
Fasotti et al. (2000) assessed the effectiveness of time pressure management (TPM) training compared to concentration training in patients with slowed processing speed as a result of traumatic brain injury. Though both groups showed improvements on information intake task performance, no significant differences between groups were observed even though specific time pressure management strategies were learned by the experimental group (Fasotti et al., 2000).
Taking focused training a step further, many studies examined the effects goal training or cognitive training (Boman et al., 2004; Chen et al., 2012; Laatsch et al., 1999; Novakovic-Agopian et al., 2011; Sohlberg et al., 2000). Physiologically cognitive rehabilitation therapy resulted in an increase in cerebral blood flow during treatment in the experimental group (Laatsch et al., 1999), as well as the experimental group reporting greater improvements in productivity. Levine et al. (2000) completed an RCT comparing a group of patients taking goal management training strategies, to a control group who were exposed to only motor skills training. The treatment group improved on paper and pencil everyday tasks as well as meal preparation, which the authors used as an example of a task heavily reliant on self-regulation. A pre-post study (Boman et al., 2004) found that cognitive training for three weeks significantly improved attention task scores compared to pre-test scores. One study did demonstrate that cognitive training (although beneficial) may not be more beneficial than other interventions such as educational training with respect to processing speed (Chen et al., 2011). In this study both groups significantly improved in attention directed goal completion. Another study comparing the effects of attentional training with another intervention (in this case physical exercise), found that there was no significant difference between groups post-intervention, but there was a within subjects effect such that both groups reported significantly less cognitive failures (McMillan et al., 2002). Novakovic-Agonian et al. (2011), found similar results in an RCT crossover where participants were assigned to received goal-training followed by education or the reverse. The goal training first group saw a significant improvement in sustained attention compared to the education-first group, additionally the goal training first group maintained their gains over 10 weeks. When it comes to attention process training, that was also shown to have greater results in attention remediation compared to education (Sohlberg er al., 2000). One study examined the effects of a memory training program on attention, to positive results. Hellgren et al. (2015), found that a memory training program was successful in improving attentional scores on the Paced-Auditory Serial Attention Test, as well as further enhancing memory in general which is discussed later on in the chapter.
The inconsistencies between studies may be due to a lack of standardized goal management training or attention process training protocols. The lack of a consensus on the definition of certain cognitive processes appears to be reflected in the interventions used to attempt to rehabilitate these deficits. Unfortunately, this decreases the ability to compare studies on a more specific level, however, general conclusions can still be made that specific training programs which intend to increase attentional capacity are effective, to what extent they are more beneficial than other training programs needs to be addressed in the future through comparative methodologies. Only one study (Serino et al., 2007) described the specific task which was successful in improving attention. This cognitive task involved mental addition in combination with two other standardized tasks and was an effective strategy for improving attention.
Conclusions
There is level 1b evidence that emotional regulation therapy is not effective in treating attentional disorders compared to waitlist controls in ABI populations.
There is level 2 evidence that mindfulness training compared to no intervention may improve an individual’s ability to correctly reject inappropriate stimuli post ABI.
There is level 2 evidence to suggest goal management training, when compared to education, may be effective at improving attention in post-ABI individuals.
There is level 2 evidence that goal management training is more effective in remediating task completion times than motor skill training, however is not more effective in treating attention deficits, in post-ABI individuals.
There is conflicting (level 2) evidence that attentional control or processing training may not significantly improve attention in post-ABI individuals compared to control training.
There is level 4 evidence that summation tasks may be effective at improving attention in individuals post ABI.
There is level 4 evidence that a working memory training program may remediate attention in post-ABI individuals.
There is level 4 evidence that cognitive rehabilitation therapy may not be effective for improving attention post-ABI.
6.2.1.5 Transcranial Direct Current Stimulation
Key Points
Evidence Table(s)
Discussion
Conclusions
6.2.2 Pharmacological Interventions
6.2.2.1 Donepezil
Key Points
Discussion
Conclusions
6.2.2.2 Methylphenidate
Key Points
Methylphenidate is effective in improving reaction time for working memory.
Response to methylphenidate may depend on genotype.
Evidence Table(s)
Discussion
Speech et al. (1993) conducted a double blind placebo controlled trial evaluating the effects of methylphenidate following closed head injury. In contrast to the results noted by Whyte et al. (2004) and Plenger et al. (1996), methylphenidate did not demonstrate significant differences compared to placebo on measures of attention, information processing speed, or learning. Kim et al. (2006) examined the effects of a single-dose treatment of methylphenidate and, although a trend was found in favour of improved working and visuospatial memory for the treatment group, these results did not reach significance. Recently, Kim et al. (2012) found that reaction time improved significantly while on the methylphenidate. This is in line with Willmott and Ponsford (2009) who found that administering methylphenidate to a group of patients during inpatient rehabilitation, did significantly improve the speed of information processing. Conflicting results continue to be reported, as two high-quality RCTs reached different conclusions regarding methylphenidate use. While Dymowski et al. (2017) noted no improvements in any measures of attention and mental processing, Zhang and Wang (2017) noted improvements in reaction time, arithmetic tests, and even mental health outcomes after intervention by methylphenidate.
In a recent RCT conducted by Willmott et al. (2013), the authors hypothesized that an individuals’ response to methylphenidate depends on their genotype. More specifically, that individuals possessing the methionine (Met) allele at the catechol-O-methyltransferase (COMT) gene would confer greater response to methylphenidate compared to those with the valine (Val) allele. While both Met/Met and Val/Val carriers performed more poorly in various attentional tasks compared to healthy controls, Met/Met carriers did show greater improvements in strategic control in attention than Val/Val carriers. As well, the authors were able to identify one significant drug and genetic interaction between Met/Met carriers and performance on the Symbol Digit Modalities Test (SDMT). These findings suggest Met/Met carriers may in fact be more responsive to methylphenidate than individuals with the Val genotype. However, further studies are needed to draw firm conclusions.
Conclusions
There is level 1a evidence that methylphenidate improves reaction time of working memory compared to placebo in individuals post ABI.
6.2.2.3 Bromocriptine
Key Points
Evidence Table(s)
Discussion
Although McDowell et al. (1998) demonstrated some benefits following administration of bromocriptine, there was only a single administration of bromocriptine and the dose was considerably lower than that given by Whyte et al. (2008). Spontaneous recovery may have been a factor leading to the improved abilities in individuals receiving a single dose (2.5 mg daily) of the medication; however, study results did not answer this question. Results from Whyte et al. (2008) noted that the placebo group demonstrated better (although not significant) trends in improvement on the various tasks administered.
Conclusions
There is level 2 evidence that bromocriptine improves attention, compared to placebo post ABI.
6.2.2.4 Cerebrolysin
Key Points
Evidence Table(s)
Discussion
Conclusions
6.2.2.5 Acetylcholinesterase Inhibitors
Key Points
Discussion
Conclusions
6.2.2.6 Growth Hormone (GH) Replacement Therapy
6.3 Remediation of Learning and Memory Deficits
Cicerone et al. (2000) reviewed 42 studies examining the effectiveness of various interventions to improve memory impairment following stroke and TBI. In 2005 and again in 2011, Cicerone and colleagues updated their original review (2005; 2011). It should be noted that studies were not included in our review if the population did not comprise of more than 50% brain-injured patients, or if the sample size (n) was less than 3. As well only those studies dealing with moderate-to-severe brain-injured individuals were included in this review.
Cappa and colleagues (2005) reviewed various strategies used to improve memory deficits without the use of electronic devices, external aids were judged to be “possibly effective.” Specific learning strategies (e.g. errorless learning) were found to be “probably effective” depending upon the task used, the type of memory involved and the severity of impairment.
6.3.1 Non-Pharmacological Interventions
6.3.1.1 Assistive Devices
6.3.1.1.1 External Technology Aids
Key Points
Personal digital assistant (PDA) devices are superior to paper-based interventions at improving memory and task completion post TBI; specially when introduced using systematic instructions and in combination with occupational therapy. Patients who have used previous memory aids might benefit from this intervention the most.
Text message prompts sent to a patient’s smartphone, when used alone or in combination with other memory-improvement therapies, likely improve task completion post TBI. However, risk exists of device dependency exists.
A television assisted prompting (TAP) program may be superior to other methods of memory prompting in patients post TBI.
Automated prompting systems, such as Guide (audio-verbal interactive micro-prompting system) and a computerized tracking system, can reduce the amount of prompts needed from support staff to patients to complete tasks post TBI.
Cicerone et al. (2000) recommended that the use of memory notebooks or other external aids “may be considered for persons with moderate to severe memory impairments after TBI (and) should directly apply to functional activities, rather than as an attempt to improve memory function per se.”
Evidence Table(s)
Discussion
Voice organizers have also been shown to improve goal execution. In a study by Kim et al. (2000), 12 TBI patients were given palmtop computers programmed with scheduling software capable of generating audible reminder cues. Patient feedback suggested that the use of the palmtop computer was beneficial for their rehabilitation, and over half of the patients continued to use the device even after the conclusion of the study. In addition, one case series (van den Broek et al., 2000) and one RCT (Hart et al., 2002) found that voice organizers helped to improve recall of previously identified goals.
With advances in technology, more sophisticated organizers integrating these tools into personal digital assistants (PDAs) have also been studied. Patients accustomed to using memory aids were more likely to make use of computerized organizers (Wright et al., 2001b). Dowds et al. (2011) found that two different PDAs improved task completion rates compared to a paper-based schedule book, while Lannin et al. (2014) found that the use of a PDA in addition to conventional occupational therapy significantly reduced memory failures and forgetting. However, the variety of available electronic organizers and learning curve for use prevent clear conclusions across studies. An RCT by Powell et al. (2012) demonstrated the importance of systematic instruction, as they compared direct instructions to conventional, trial and error patient learning on a PDA. Those receiving systematic instruction were superior in the number and speed of correct PDA tasks compared to conventional trial and error learning group. No differences were found between groups based on PDA input (physical vs touch-screen keyboard), provided the three core memory aides of appointment diary, notebook, and to-do list were maintained (Wright et al., 2001a).
Smartphones represent a relatively new area of accessible technology and provide the user with many benefits. Smartphones are already designed to send notifications about their use, as well as multiple companies design apps for each phone brand interface allowing individuals to keep their current devices and still access helpful applications. The most common advantages to smartphones are reminders/alarms and ability to combine a calendar, tasks list, contacts, mail, and phone on one device. Disadvantages included the reduction of battery life and risk of dependency on the assistive device, however these are minor inconveniences in comparison to the reported improvement in memory in some patients (Evald, 2015).The increasing availability of smartphones also creates the ability to enhance current therapies with text messages. A case series by Fish et al. (2007) demonstrated that participants could be trained to associate a text message with stopping and thinking about what needed to be done, with participants more likely to remember the instruction to call the investigators when texted the message “STOP”. Gracey et al. (2017) also found that goal management training could be supplemented with text messages for improving achievement of everyday intentions, with individuals who received text prompt more likely to succeed in their goals compared to those not receiving prompts. This effect was not observable once the texts had stopped to both groups.
External memory aids can also be incorporated into an individual’s home or work environment. Lemoncello et al. (2011) developed a television assisted prompting (TAP) system that provided reminders of events to be completed through the television screen. This crossover RCT found that compared to traditional methods (paper planner, cell phones or computers), participants using the TAP system completed significantly more tasks (Lemoncello et al., 2011).
These external aids can also be adapted for use in an inpatient settings. O’Neill et al. (2017) developed an audio-verbal interactive micro-prompting system, Guide, designed to emulate the verbal prompts and questions provided by caregivers or support workers. The number of support workers prompts needed during their morning routine was reduced, even though there were no significant differences between groups in terms of the number of errors and satisfaction scores (O’Neill et al., 2017). An acute rehabilitation unit also showed efficacy for a computerized tracking system designed to locate patients and send reminders when patients moved in the wrong direction for appointments (Burke et al., 2001). By reducing the number of staff prompts needed, these systems can increase patient independence and help free up support personnel for other tasks.
Conclusions
There is level 4 evidence that voice organizer programs are effective at improving recall of goals, and are found to be effective by patients post TBI.
There is level 2 evidence that personal digital assistants (PDAs) are superior to a paper-based schedule book at improving task completion rates post TBI.
There is level 1b evidence that the use of a personal digital assistant (PDA) in combination with conventional occupational therapy is superior to occupational therapy alone at improving memory in patients post TBI.
There is level 1b evidence that use of a personal digital assistant (PDA) after receiving systematic instructions is superior to PDA trial and error learning at improving the number and speed of correct tasks post TBI.
There is level 4 evidence that conventional or touch-screen personal digital assistant (PDA) use are similar at improving memory post TBI.
There is level 1b evidence that reminder text messages sent to patients through their smartphones, whether alone or in combination with goal management training, may improve goal completion post TBI.
There is level 2 evidence that a television assisted prompting (TAP) system is superior to traditional methods of memory prompting (paper planners, cell phones, computers) at improving the amount of completed tasks post TBI.
There is level 1b evidence that the audio-verbal interactive micro-prompting system, Guide, can reduce the amount of support-staff prompts needed for the patient to complete a task post TBI.
There is level 4 evidence that a computerized tracking system that sends reminders to patients when they are moving in the wrong direction reduces the amount of support-staff prompts needed for patients to complete a task post TBI.
6.3.1.1.2 External Passive Techology or Non-Technology Aids
Key Points
The use of a diary may help to improve memory and task completion post ABI, but more so if diary training is combined with self-instructional training.
In recent years, clinicians have recommended the use of computers as an efficacious tool in cognitive rehabilitation. A systematic review identified 23 studies that demonstrated computerized cognitive interventions were effective for improvement of attention and executive functions (Bogdanova et al., 2016).
Discussion
Conclusions
There is level 2 evidence that the presence of a calendar may not improve orientation post ABI.
There is level 2 evidence that diary training in combination with self-instructional training may be more effective than diary training alone at improving memory and task completion post ABI.
6.3.1.1.3 Virtual Reality
Key Points
Evidence Table(s)
Discussion
In terms of cognitive functioning, two RCTs found that training in a virtual environment did not show significantly more improvement than general cognitive re-training or psychoeducation groups on executive functioning outcomes (Jacoby et al., 2013; Man et al., 2013). One RCT focusing on vocational problem-solving skills (Man et al., 2013)identified significant improvements in both VR intervention and conventional psychoeducation control groups, but no differences between groups for cognitive or vocational outcomes except on WCST % errors and % conceptual level response (Man et al., 2013).
Yip and Man (2013) found that a non-immersive prospective memory VR training program significantly improved some memory outcomes compared to a control with regular activities, suggesting larger scale trials may be needed to fully assess the effect. Virtual reality in combination with exercise has also been found to improve performance on learning and memory tasks (Grealy et al., 1999). (Man et al., 2013)
Conclusions
There is level 2 evidence that virtual reality training alone may be promising for improving memory outcomes, and has a positive impact on visual and verbal learning when in combination with exercise.
6.3.1.2 Internal Memory Strategies
Key Points
Discussion
Twum and Parente (1994) randomly assigned 60 patients with a TBI into one of 4 groups (one control and three mnemonic strategy groups) counterbalanced. The researches demonstrated improved performance for subjects who were taught a strategy (either verbal labeling or visual imagery) while learning paired-associations. Treatment groups showed greater efficiency in learning and greater delayed recall information.
Thoene and Glisky (1995) using a case series design also showed enhanced performance following the use of a mnemonic strategy (verbal elaboration and visual imagery) compared to vanishing cues and/or video presentation during paired associations.
Goldstein et al. (1996) evaluated a visual-imagery technique “Ridicuously Imaged Story” technique in training severely brain injured individuals to learn and recall lengthy word lists. Participants were asked to read a story where 20 words are presented in bold-face and subjects were instructed to remember the bold-face words for later recall. If subjects could not recall all the words they were provided with (1) the part of the story in which the word appeared and if that didn’t aid recall, they were then provided with (2) a category cue for the word. It should be noted that in both studies reviewed, a number of their subject pool (N=10) came from a previous study (Goldstein et al., 1988). Goldstein et al. (1996) evaluated whether there were differences between a computerized and non-computerized version of “Ridicuously Imaged Story” and another visual imagery technique (Pictorial Imagery). Results indicated that although the computerized versions resulted in a slightly better performance on learning trials, the difference was non-significant.
By using the various visual imagery techniques to aid learning and recall, researchers have demonstrated that increasing the saliency of features encoded, results in an increase in the amount recalled. Milder et al. (1998) examined performance on a name learning task by increasing the meaningfulness of people’s names with various strategies (e.g. when learning a new name-face association try to think of an occupation or object with the same name or a famous person with a similar name etc). When subjects (13 severely TBI versus 13 matched controls) were tested on 3 different memory tasks, results indicated a significant difference following training, more so for the control group than the TBI group. Also, learning procedures were more effective on one task (where subjects were required to learn the name-occupation-and town) compared to the other two tasks (famous-faces or name learning).
In a 4 year follow up study, to one conducted by Berg and colleagues, Milder et al. (1995) found the effects at 4 months were no longer evident at 4 years (all groups were equivalent). In the original study, Berg et al. (1991) demonstrated that severely brain injured patients demonstrated improved effects on objective measures of memory at 4 months following training in a strategy-use group compared to a pseudo-treatment and a no treatment control group. In the strategy group, individuals were taught general cognitive principles of memory functioning and aids (i.e., internal and external strategies were taught and practiced). In contrast, the pseudo-treatment group practiced memory games and tasks with no explanation.
How individuals learn (i.e., encode) information will determine to a large extent what is later recalled. Twum and Parente (1994) demonstrated that if an active strategy (either verbal labeling for visual information or visual imagery for verbal information) is taught to individuals while learning the paired associations, learning and recall is enhanced (i.e., fewer trials needed to reach criterion during learning and improved recall following a delay). Tailby and Haslam (2003) also examined how learning can improve or limit later recall of information. They had 24 ABI subjects matched on basis of age, gender, premorbid and current intellectual status divided into 3 groups based on performance of verbal memory (mild, moderate & severe). Each group (n=8) was randomly assigned to one of 3 learning conditions: errorless learning, self-generated; errorless learning, experimenter generated; and errorful learning. Results showed that regardless of severity level, subject recalled more information in the errorless learning conditions (with self-generated superior to experimenter generated) than in the errorful learning condition.
Constantinidou and Neils (1995) examined the effects of stimulus modality on verbal learning of patients with moderate-to-severe closed head injury and a matched control group. Results indicated that when information is presented visually (with and/or without auditory presentation of names) more information is learned than when information is presented within the auditory modality alone. As expected, patients learn new information at a significantly slower rate compared to controls.
It is generally thought that while patients are experiencing post-traumatic amnesia (PTA), they are not able to learn and retain new information, and as a result, cognitive rehabilitation is usually postponed until PTA has resolved. This tends to be true if using tasks of explicit or declarative learning and recall. Two studies were reviewed that reported that PTA patients were capable of learning and retaining new information when task demands were dependent on implicit/procedural learning. Glisky and Delaney (1996) evaluated implicit memory (priming using a stem completion task) and the use of vanishing cues when learning semantic information in a small number of patients with a TBI (n=8 & 4) who were still experiencing PTA and a matched control group. Findings revealed that learning and recall of information (once PTA has resolved) had occurred, albeit at reduced levels compared to controls. Ewert et al. (1989) also demonstrated procedural learning and retention in a group of 16 severely closed head injured participants and matched controls.
Conclusions
6.3.1.3 Learning and Memory Training Programs
Key Points
Specific computer-based softwares seem to be effective for improving memory post-ABI.
Computer-based interventions may be as effective as therapist administered interventions.
Emotional self-regulation therapy may be effective for improving specific elements of memory.
Recall and recognition of words can be enhanced by using a spaced learning condition.
Evidence Table(s)
Discussion
Chiaravalloti et al. (2016) compared the efficacy of the modified Short Memory Technique to conventional therapy for the improvement of memory post TBI. Amongst the memory assessments quantified, significant improvements were seen only in two specific categories; the Memory Assessment Scale- Prose Memory (MAS-PM) and “hidden belonging task” of the Rivermead Behavioural Memory Test (RBMT). A follow-up study further recognized the lack of improvement in the treatment group compared to controls in terms of memory capacity, however they did note that working memory capacity and long-term memory retainment were positively correlated with each other.
Further, similar results were found in an RCT by Novakovic-Agopian et al. (2011), where a goals training group showed significant improvement on attention and execute function assessments compared to the educational group. Despite switching interventions at the 5 week mark to the educational intervention, the goal training group continued to improve significantly.
In another RCT, 45 individuals were randomly assigned into one of 4 treatment groups (Shum et al., 2011). The treatment groups consisted of 4 different intervention programs: self-awareness plus compensatory prospective memory training; self-awareness training plus active control; active control plus compensatory prospective memory training and active control only. Pre intervention scores on the CAMPROMPT did not reveal any significant differences between any of the groups. Those assigned to the compensatory prospective memory training groups showed greater changes in strategies used to improve memory. Compensatory prospective memory training included use of a diary or organizational devices, and group members were encouraged to use written reminders, appointments and note taking. Although at total of 45 participants started the study, only 36 completed it.
In an RCT conducted by Vas et al. (2011), 28 individuals who had sustained a TBI and were at least 2 years post injury, were assigned to one of two groups: the strategic memory and reasoning training group or the Brain Health Workshop group. Each groups received 15 hours of training over an eight week period. Those in the strategic memory and reasoning training group were given information about brain injuries, were asked to read pieces of literature on brain injury and were given homework assignments to be completed for the next meeting. The strategic memory and reasoning training sessions were built around three strategies: strategic attention, integration (combining important facts to form higher order abstracted meaning) and innovation (derive multiple abstract interpretations). Those in the brain health workshop group participated in information sessions. Sessions for the brain health workshop groups included an introduction to brain anatomy, functions of the brain, neuroplasticity, and the effects of lifestyle on the brain (diets, exercises and cognitive changes following a TBI). Study results indicate that those assigned to the strategic memory and reasoning training group showed significant improvement on gist reasoning and measures of executive function.
Further lending support for attention training post TBI, one RCT showed that attention and information processing outcomes could be improved with dual-task training (Couillet et al., 2010; Sacco et al., 2016). Specifically, the group found that dual-task training significantly improved attentional behaviour and reaction time compared to a non-specific cognitive program.
An RCT conducted by Dou et al. (2006), found there were no significant differences in memory and cognitive improvements between participants receiving computer-administered or therapist-administered memory training, though both groups showed significant improvements compared to the control group that received no training
Thickpenny and Barker-Collo (2007) randomly assigned 14 individuals to either the treatment or control groups. Those in the treatment group participated in a memory rehabilitation program. The memory groups consisted of eight learning modules each 60 minutes long. They ran twice a week for 4 weeks. Memory improvement and difficulties were evaluated. Overall a reduction in memory impairment was noted at the end of the 4 weeks of intervention and again at the one month follow-up time period.
Further support for emotional oriented intervention can be found in an earlier study by Rath et al. (2003). The group completed an RCT comparing two cognitive rehabilitation therapies: conventional (cognitive remediation and psychosocial components) versus an innovative rehabilitation approach focusing on emotional self regulation and clear thinking. Outcomes were measured across multiple domains of cognition including attention, memory, reasoning, psychosocial functioning, and problem solving measures. Significant changes comparing baseline to post intervention outcomes were seen for each group, however, the improvements were different for the interventions. No between-group comparisons were made.
With respect to attention process training, it was shown that individuals receiving attention remediation significantly improved in memory and attention measurements compared to controls- whoTBI education alone (Sohlberg er al., 2000).
). Similarly, two trials did not find significant differences between groups for attentional, functional, and/or cognitive skills assessed (Lindelov et al., 2016; Novack et al., 1996). Novack et al. (1996) compared focused hierarchical attentional learning with an unstructured non-sequential, non-hierarchical intervention, while Lindelov et al. (2016) compared N-back training with visual search training. Overall there is weak evidence in support of training programs as an effective rehabilitation intervention for attention.
Recently, BrainHQ, a commercially available online computerized cognitive exercise program, did not significantly improve attention outcomes over time or compared to no intervention (O’Neil-Pirozzi & Hsu, 2016)
Gabbatore et al. (2015) implemented a cognitive group rehabilitation program for patients post TBI, and discovered that compared to before the intervention, patient’s recall (IDR), attention (WCST), and communication skills (ABaCo) all significantly improved.
Hellgren et al. (2015), found that a memory training program was successful in improving attentional scores on the Paced-Auditory Serial Attention Test, as well as further enhancing memory in general which is discussed later on in the chapter.
The Parrot Software is another computer-based cognitive retraining program, and was investigated by a pre-post study assessing the efficacy of using eight modules focussed on attention and memory (Li et al., 2015; Li et al., 2013). While significant post-treatment improvements in attention and memory on the Cognistat assessment were found in a pilot study (Li et al., 2013), a subsequent study did not find significant improvements on the attention and memory subscales of the Montreal Cognitive Assessment (MoCA) or a medication-box sorting task despite significantly improved overall MoCA scores (Li et al., 2015).
In a recent prospective cohort study, Johansson and Tornmalm (2012) looked at the benefits of a working memory program on 18 individuals who had sustained either a TBI or had had a stroke resulting in moderate to severe cognitive deficits. The working memory training program used the Cogmed QM (computerized training software) coaching, education and peer support to help improve the daily functioning of participants. Results show the Cogmed QM program helped to improve working memory and these benefits were seen at the 6th month follow up.
. Only one study (Serino et al., 2007) described the specific task which was successful in improving attention. This cognitive task involved mental addition in combination with two other standardized tasks and was an effective strategy for improving attention.
Boman et al. (2004) in a study of 10 individuals with mild or moderate TBI, after completing 1 hour of an individual cognitive training 3 times a week for 3 weeks, significant improvement was noted on the attention processing training test in sustained attention (p<0.05), selective attention (p<0.05), and alternating attention (p<0.01) pre to post training and at 3 month follow-up. Scores on the Rivermead Behavioural Memory Test were also seen to have significantly increased at the 3 month follow-up compared to pre test scores (p<0.05). Changes on the Claeson-Dahl Memory test did not increase pre to post to 3 month follow-up.
Quemada et al. (2003) examined memory rehabilitation following severe TBI in 12 individuals (no controls). The program ran for 6 months (50 minute sessions 5 days a week for 5 months and then 3 days a week for one month) and followed a specified format utilizing behavioural compensation techniques, mnemonic strategies, and environmental adaptations, external and internal aides. Results indicated little improvement in standard measures of memory functioning, although patients and family members report meaningful functional gains (self-report and observed behaviour in everyday functioning).
The findings of the previous experiment agree with the findings of the study by Laatsch et al. (1999), where cognitive rehabilitation therapy was found to increase productivity and everyday functioning. This older study also had the benefit of reporting SPECT imaging results, which revealed increases in cerebral blood flow during the intervention.
Parente et al. (1999) also studied retraining of working memory post traumatic brain injury. Although working memory would at first glance appear to be a primarily memory related brain function, the authors describe the concept of working memory as involving three main elements. These elements are the articulatory loop which hold verbal information, the visuospatial sketchpad which stores and interprets visual information and the executive system which organizes, prioritizes and allocates information processing resources. In this pilot study, 10 subjects were assigned to the intervention group who completed tasks to enhance working memory functioning between testing sessions. The testing sessions were only one hour apart. A control group matched for age, gender and injury type completed the same testing without training. The results showed a significant improvement for the letter number sequencing task for the intervention group, however there was no difference between groups on digit span task performance.
Finally, Chen et al. (1997) studied the effect of computer assisted cognitive rehabilitation versus traditional therapy methods. While measures of attention significantly improved in both groups after treatment, no significant differences were observed between groups (Chen et al., 1997). Cumulatively, by observing studies from across a period of nearly 20 years, the literature reveals little support for the use of computer software programs for the improvement of executive function post TBI.
Conclusions
There is level 1b evidence that the Short Memory Technique may not be more effective than standard memory therapy at improving memory in individuals post ABI.
There is level 2 evidence that participation in a goals training program, followed by an educational program, may be more effective for improving memory in individuals post ABI compared to receiving the treatment conditions in reverse order.
There is level 1b evidence that compensatory memory strategies, self-awareness training, and participation in memory group sessions may be effective for improving memory in individuals post ABI compared to no treatment.
There is level 2 evidence that Strategic Memory and Reasoning Training (SMART) may improve learning and working memory compared to no memory training in individuals post ABI.
There is level 2 evidence that dual-task training may be effective for improving memory in individuals post ABI when presented before the control condition, compared to the reverse.
There is level 2 evidence that both computer-administered and therapist-administered memory training may be more effective than no treatment for improving memory in ABI participants. However, no treatment appears to be better than the other.
There is level 2 evidence that both cognitive remediation and emotional self-regulation may be effective at improving different elements of memory in individuals post ABI.
There is level 1b evidence that attention processing training compared to supportive listening may improve memory in individuals post ABI.
There is level 2 evidence that BrainHQ is not an effective program for improving memory and learning compared to no intervention in individuals post ABI.
There is level 4 evidence that using mental representations and role-playing may not be effective at improving memory in individuals post ABI.
There is level 4 evidence that Cogmed training software may improve working memory performance and occupational performance in individuals post ABI.
There is conflicting (level 4) evidence regarding whether or not Parrot software is effective at improving memory and learning in individuals post ABI.
There is level 4 evidence that mental addition tasks may improve working memory in individuals post ABI.
There is level 4 evidence that the Wilson’s Structured Behavioral Memory Program is not effective for improving memory post ABI.
6.3.1.4 Cranial Electrotherapy Stimulation
Key Points
Discussion
Conclusions
6.3.2 Pharmacological Interventions
6.3.2.1 Donepezil
Key Points
Discussion
The most recent study, a pre-post by Khateb et al. (2005), found only modest improvement on the various neuropsychological tests used to measure executive function, attention, and learning and memory. Of note results from the learning phase of the Rey Auditory Verbal Memory Test (RAVMT) showed significant improvement (p<0.050). The Donepezil intervention also demonstrated improvement in executive function, as the results from the Stroop-colour naming test showed significant improvements (p<0.030). On the test for Attentional Performance a significant change was noted on the divided attention (errors) subsection of the test. Overall, donepezil was found to be effective in improving learning, memory, divided attention, and executive function. However, possible benefits of donepezil administration must be balanced against the observed side effects in 27% of the population. Further randomized control trials are required to better explore the efficacy of donepezil post TBI.
Conclusions
There is level 4 evidence that donepezil may be effective in improving short-term, long-term, verbal, and visual memory post ABI.
6.3.2.10 Acetylcholinesterase Inhibitors
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.2 Methylphenidate
Key Points
Response to methylphenidate likely varies depending on genotype at the catechol-O-methyltransferase (COMT) gene.
Evidence Table(s)
Discussion
In the first of two studies by Willmott, they and Ponsford (2009) found that administering methylphenidate (0.3 mg/kg, 2x/d, 6 wk) during inpatient rehabilitation significantly improved the patient’s speed of information processing and attention post TBI. In the more recent RCT (Willmott et al. 2013), the authors hypothesized that an individuals’ response to methylphenidate depends on their genotype. More specifically, that individuals possessing the methionine (Met) allele at the catechol-O-methyltransferase (COMT) gene would confer greater response to methylphenidate compared to those with the valine (Val) allele. While both Met/Met and Val/Val carriers performed more poorly in various attentional tasks compared to healthy controls, Met/Met carriers did show greater improvements in strategic control in attention than Val/Val carriers. As well, the authors were able to identify one significant drug and genetic interaction between Met/Met carriers and performance on the Symbol Digit Modalities Test (SDMT). These findings suggest Met/Met carriers may in fact be more responsive to methylphenidate than individuals with the Val genotype. However, further studies are needed to draw firm conclusions.
Conclusions
6.3.2.3 Sertraline
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.4 Amantadine
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.5 Pramiracetam
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.6 Physostigmine
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.7 Bromocriptine
Key Points
Evidence Table(s)
Discussion
Conclusions
There is level 4 evidence that bromocriptine may improve memory in patients post TBI.
6.3.2.8 Cerebrolysin
Key Points
Evidence Table(s)
Discussion
Conclusions
6.3.2.9 Growth Hormone (GH) Replacement Therapy
Key Points
The administration of recombinant human Growth Hormone (rhGH) might be superior at improving intelligence and cognition in patients with a growth hormone deficiency, versus those who do not, post TBI. Molecular markers of growth however may not be different post treatment between groups.
Evidence Table(s)
Discussion
Conclusions
There is level 2 evidence that growth hormone (GH) therapy is similar to placebo at improving quality of life, instrumental activities of daily living (iADL), attention, memory, and visuospatial ability in patients post TBI.
6.4 Remediation of Executive and General Cognitive Functioning
Cicerone et al. (2000) reviewed 14 studies dealing with executive functioning and problem-solving (Table 6.13). Only 3 of the identified studies were classified as a randomized controlled trial or non-randomized cohort study.
In the more current reviews by Cicerone et al. (2005; 2011) 9 and 18 additional studies were identified. Some of these studies were not included in our review as they did not meet our inclusion criteria. Based on the results of the studies in their review, Cicerone et al. (2000) recommended, “training of formal problem-solving strategies and their application to everyday situations and functional activities”.
Executive function deficits are particularly relevant to brain injury survivors who tend to be younger (average age less than 40) and who often desire to re-integrate back into pre-injury life roles. Patients with executive function deficits may have the capacity to be independent for basic activities of daily living where actions tend to be more ingrained and one-dimensional. However, instrumental activities of daily living such as banking, scheduling and household activities require intact executive functions due to the increased cognitive complexity and variability of the tasks. Of particular importance are the advanced tasks such as return to driving and competitive employment which are of increased relevance to the younger age demographic associated with TBI (Miller et al., 2003).
6.4.1 Non-Pharmacological Interventions
6.4.1.1 Remediation of Executive Functioning
6.4.1.1.1 Individual Interventions
Key Points
Attention improvement interventions may be superior to non-specific cognitive or education programs at improving memory and attention in patients post TBI.
A comprehensive cognitive treatment strategy is likely superior to a computerized training package at improving task initiation and completion in patients post TBI; this intervention may also improve cerebral blood flow.
It is unclear whether virtual-reality training is superior to conventional training at improving cognitive and executive function outcomes post TBI. Conflicting evidence exists, and further studies are required.
Computer or smartphone software programs (BrainHQ, Parrot Software, ProSolv app) may not be superior to common interventions at improving memory, attention, and problem-solving skills in patients post TBI.
Goal management training may superior to motor skills training at improving every day skills (meal preparation), but not intelligence or neuropsychological outcomes in patients post TBI.
Discussion
With respect to attention process training, it was shown that individuals receiving attention remediation significantly improved in memory and attention measurements compared to controls- whoTBI education alone (Sohlberg er al., 2000). Further lending support for attention training post TBI, one RCT showed that attention and information processing outcomes could be improved with dual-task training (Couillet et al., 2010; Sacco et al., 2016). Specifically, the group found that dual-task training significantly improved attentional behaviour and reaction time compared to a non-specific cognitive program.
In a recent RCT, Spikman et al. (2010) randomly divided a group of individuals who had sustained a TBI to either a multifaceted strategy training group or a control group. Those in the treatment group were taught a comprehensive cognitive strategy which allowed them to tackle the issues and problems of daily living, compared to the control group which received a computerized training package that was aimed at improving general cognitive functioning. Overall results indicate both groups improved on many aspects of executive functioning; however, those in the treatment group showed greater improvement in their ability to set and accomplish realistic goals and to plan, initiate real life tasks (Spikman et al., 2010). The findings of the previous experiment agree with the findings of the study by Laatsch et al. (1999), where cognitive rehabilitation therapy was found to increase productivity and everyday functioning. This older study also had the benefit of reporting SPECT imaging results, which revealed increases in cerebral blood flow during the intervention.
With the development of technology, the use of virtual-reality training and computer programs have gained traction as an intriguing tool used for improving executive function in patients post TBI. In terms of cognitive functioning, two RCTs found varying results executive functioning outcomes after training in a virtual environment (Jacoby et al., 2013; Man et al., 2013). One RCT focusing on vocational problem-solving skills (Man et al., 2013) identified significant improvements in both VR intervention and conventional psychoeducation control groups, but no differences between groups for cognitive or vocational outcomes except on WCST % errors and % conceptual level response (Man et al., 2013). On the other hand, Jacoby et al (2013) found that patients receiving virtual reality training improved more on multi-tasking measures and executive function when compared to the control group— who received general cognitive re-training treatment. The most recent study by Dadah et al. (2017), a pre-post investigation, investigated virtual reality interventions in a mixed ABI population. The researchers found that repetition of the Stroop test in different virtual reality environments showed limited improvement in performance on those specific tests (Dahdah et al., 2017). As a result of the mixed results reported on the efficacy of virtual reality training post ABI, it is difficult to make a conclusive decision on what aspects of executive functioning virtual reality benefits, and to what degree.
As previously mentioned, computer software programs have also been investigated for their efficacy in improving executive dysfunctions post TBI. Recently, BrainHQ, a commercially available online computerized cognitive exercise program, did not significantly improve attention outcomes over time or compared to no intervention (O’Neil-Pirozzi & Hsu, 2016).
The Parrot Software is another computer-based cognitive retraining program, and was investigated by a pre-post study assessing the efficacy of using eight modules focussed on attention and memory (Li et al., 2015; Li et al., 2013). While significant post-treatment improvements in attention and memory on the Cognistat assessment were found in a pilot study (Li et al., 2013), a subsequent study did not find significant improvements on the attention and memory subscales of the Montreal Cognitive Assessment (MoCA) or a medication-box sorting task despite significantly improved overall MoCA scores (Li et al., 2015). This lack of improvement compared to a control group was also seen by Powell et al. (2017) when the ProSolv smartphone application was used to improved pressure management and problem—solving skills. Finally, Chen et al. (1997) studied the effect of computer assisted cognitive rehabilitation versus traditional therapy methods. While measures of attention significantly improved in both groups after treatment, no significant differences were observed between groups (Chen et al., 1997). Cumulatively, by observing studies from across a period of nearly 20 years, the literature reveals little support for the use of computer software programs for the improvement of executive function post TBI.
Levine et al. (2000) completed an RCT comparing a group of patients taking goal management training strategies to a control group who were exposed to only motor skills training. The treatment group improved on paper and pencil everyday tasks as well as meal preparation-which the authors used as an example of a task heavily reliant on self-regulation- in comparison to the motor treatment group. It is important to note however that the motor group performed superiorly on timed neuropsychological tests, and no differences were found between treatments in terms of intelligence.
Conclusions
There is level 1b evidence that an attention remediation intervention is superior to TBI education alone and improving executive function in patients post TBI.
There is level 2 evidence that dual-task training may improve general cognitive functioning compared to a non-specific cognitive program in patients post TBI.
There is level 1b evidence that a comprehensive cognitive treatment strategy may be superior to a computerized training package at improving task initiating and goal achievement post TBI.
There is level 4 evidence that cognitive rehabilitation may increase productivity in everyday functioning, and cerebral blood flow during treatment in patients post TBI.
There is conflicting (level 1b and level 2) evidence as to whether virtual-reality training is or is not superior to conventional cognitive training at improving cognitive and executive function outcomes post TBI.
There is level 2 evidence that computer or smartphone software programs, such as BrainHQ, Parrot Software, ProSolv app, may not be superior to no intervention at improving problem-solving skills and general functioning in patients post TBI.
There is level 2 evidence that goal management training may be superior to motor skills training at improving everyday skills like meal preparation, but not neuropsychological tests or intelligence in patients post TBI.
6.4.1.1.2 Group-based Interventions
Key Points
Emotional regulation interventions delivered in a group setting may improve executive function in patients post TBI; however, it is unclear if it is superior at doing so compared to conventional cognitive remediation.
It is unclear whether cognitive interventions (such as the Metacognitive Strategy Instruction program) improves language ability, and executive/ cognitive function in patients post TBI.
Evidence Table(s)
Discussion
Emotional regulation was also examined as a potential intervention for the remediation of attention and executive dysfunction post ABI (Cantor et al., 2014). While this treatment was not seen to be effective in the recovery of attention, significant improvements on executive function were noted (EF, FeSBe, PSI). Further support for emotional oriented intervention can be found in an earlier study by Rath et al. (2003). The group completed an RCT comparing two cognitive rehabilitation therapies: conventional (cognitive remediation and psychosocial components) versus an innovative rehabilitation approach focusing on emotional self regulation and clear thinking. Outcomes were measured across multiple domains of cognition including attention, memory, reasoning, psychosocial functioning, and problem solving measures. Significant changes comparing baseline to post intervention outcomes were seen for each group, however, the improvements were different for the interventions. No between-group comparisons were made.
A pre-post study by Copley et al. (2015) investigated the effects of a Metacognitive Strategy Instruction (MSI) intervention on verbal and cognitive outcomes post ABI. The program was delivered individually, in a group-setting, and at home. Despite the multi-step process, no improvements were seen in cognitive or verbal abilities from baseline after the intervention. Gabbatore et al. (2015) implemented a cognitive group rehabilitation program for patients post TBI, and discovered that compared to before the intervention, patient’s recall (IDR), attention (WCST), and communication skills (ABaCo) all significantly improved.
Parente and Stapleton (1999) in a descriptive study compared brain injury survivors who completed a cognitive skills group to comparable controls. The cognitive skills group interventions included education regarding “thinking skills” such as problem solving, concentration/ attention, decision making, remembering names and faces, study skills, functional mnemonics, prosthetic memory devices, social cognition, organizational skills and goal setting. Other important aspects of the cognitive skills group included computer training, prosthetic aid training, interviewing skills training and focus on a model of clients teaching clients. There was no statistical analysis completed, however, the return to work rate for 13 of 33 participants assigned to the cognitive skills group training was 76% as compared to 58% for the control group. Competitive employment for the intervention group was maintained at 6-month follow up.
Conclusions
There is level 2 evidence that emotional regulation group interventions are effective at improving executive function in patients post TBI.
There is conflicting (level 4) evidence that group cognitive interventions (ie. Metacognitive Strategy Instruction) improves executive function in patients post TBI.
6.4.1.2 Remediation of General Cognitive Functioning
Key Points
Low intensity outpatient cognitive rehabilitation might improve goal attainment and cognitive function in patients post ABI.
Gordon et al. (2006) conducted an extensive review of the TBI rehabilitation literature and identified 13 studies dealing with rehabilitative treatments of cognitive deficits. Studies included in this review had a multitude of inclusion criteria. The studies identified were of limited methodological quality, but suggested that compensatory strategy training improved attention deficits and mild memory impairments (Gordon et al., 2006). Several researchers have noted that training-based therapies that target executive control, such as “attention, problem solving, and the use of metacognitive strategies” (Novakovic-Agopian et al., 2011) may improve functioning in those who sustain an ABI (Cicerone, 2002; Kennedy et al., 2008; Sohlberg et al., 2003b). Studies included in this section have examined the effects of cognitive rehabilitation strategies.
Evidence Table(s)
Discussion
Neistadt (1992) divided 45 patients into one of two groups: a remedial group who received individual training with parquetry block assembly, and an adaptive group who received functional skills training over a six-week period. Outcomes for the effect of treatment for constructional test performance revealed that the remedial group improved significantly more than the adaptive group on the Parquetry Block test. However, there were no significant differences on the WAIS-R Block Design subtest after treatment. Training-specific learning appears to be an effective approach to rehabilitation as demonstrated by the treatment effect.
In a more recent cohort study, Rasquin and colleagues (2010) investigated the effectiveness of a low intensity outpatient cognitive rehab program on those (n=27) who had sustained an ABI. All participants were in the chronic phase of recovery and all were asked to invite a care giver to attend sessions with them (n=25). Sessions ran for 2.5 hours each week for a total of 15 weeks. All were assessed prior to the session beginning, immediately afterward and again 6 months later. Participants worked on developing strategies to assist them with their attention, memory and problem solving difficulties. Social skills training sessions were also held. Changes were noted immediately after the cognitive rehab program ended and this improvement in goal attainment, and cognitive impairment was maintained at the 6th month follow-up.
Conclusions
There is level 4 evidence that a low intensity outpatient cognitive rehabilitation program may improve goal attainment and cognitive impairment in patients post ABI.
6.4.2 Pharmacological Interventions
6.4.2.1 Donepezil
Key Points
Evidence Table(s)
Discussion
Conclusions
6.4.2.2 Methylphenidate
Key Points
Evidence Table(s)
Discussion
Conclusions
6.4.2.3 Sertraline
Key Points
Evidence Table(s)
Discussion
Conclusions
6.4.2.4 Amantadine
Key Points
Evidence Table(s)
Discussion
Conclusions
6.4.2.5 Pramiracetam
Key Points
Evidence Table(s)
Discussion
Conclusions
There is level 4 evidence that bromocriptine may improve motivational deficits in patients post TBI.
6.4.2.6 Growth Hormone (GH) Replacement Therapy
Key Points
The administration of recombinant human Growth Hormone (rhGH) might be superior at improving intelligence and cognition in patients with a growth hormone deficiency, versus those who do not, post TBI. Molecular markers of growth however may not be different post treatment between groups.
Discussion
Conclusions
There is level 2 evidence that growth hormone (GH) therapy is similar to placebo at improving quality of life, instrumental activities of daily living (iADL), attention, memory, and visuospatial ability in patients post TBI.
There is level 2 evidence that recombinant human Growth Hormone (rhGH) administration improves intelligence and other cognitive subtests in TBI patients with growth hormone deficiency compared to TBI patients without; however, insulin-like growth factor-1 (IGF-1) levels may be the same between groups.
6.4.2.7 Acetylcholinesterase Inhibitors
Key Points
Evidence Table(s)
Discussion
Conclusions
6.5 Conclusions
Comparing the efficacy of various remediation efforts is also complicated by cross-study variability in treatment duration (e.g. from 30 minutes once a day for 5 days to 5 hours, every day for 6 weeks). Severity of injury and time since injury may also fluctuate from study to study. Over the past several years, Cicerone et al. (2000; 2005; 2011) reviewed a series of studies investigating the effectiveness of attentional retraining interventions during rehabilitation following traumatic brain injury and stroke.
Not all patients respond equally to all intervention strategies and no study in the current review indicated whether severity of memory impairment (or memory profile) interacts with a particular external memory aid. Technology has increased the availability of external aids, although some seem more feasible to use than others (e.g., cell phones or hand-held recorders). Unfortunately, the studies reviewed did not specify the length of time subjects required to master compensatory strategies or the nature of the long-term effects. Generally if these electronic appliances are used before the injury, they will are more likely to be used post injury. It was nuclear from the studies if any of the participants had had some knowledge of these appliances.
Most studies examined only tasks of word list recall and paired-associate learning suggesting that the mnemonic strategies reviewed may not generalize to other types of information (particularly real-world or functional information outside the laboratory). Errorless learning appears to be one procedure that can be used to enhance learning conditions. One study highlighted the difference between severity of impairment and ability to benefit from internal strategies.
Frequency of intervention has an impact on learning and retention, although the exact parameters of this are unclear at the present time. The optimal duration of a program is also open for speculation. No studies reviewed examined the number of sessions required for memory groups to be effective and only one study evaluated a difference in effectiveness between mild and severely impaired individuals after sessions. Pharmacologic intervention does not appear to be effective in improving learning and memory deficits.
Summary
There is level 3 evidence that attention processing training may improve attention compared to visual search training in ABI populations.
There is level 2 evidence that dual task training may be effective in improving attention task performance in ABI populations compared to non-specific training.
There is level 2 evidence that neither general nor name brand computer-based rehabilitation intervention may improve attention outcomes compared to usual care in ABI populations.
There is level 4 evidence that attention performance can be improved in ABI populations through repetition of tasks, either through computer-based or virtual reality environments.
There is level 2 evidence that adaptive training is no more effective than non-adaptive training in remediating attention in ABI populations.
There is level 1b evidence that emotional regulation therapy is not effective in treating attentional disorders compared to waitlist controls in ABI populations.
There is level 2 evidence that mindfulness training compared to no intervention may improve an individual’s ability to correctly reject inappropriate stimuli post ABI.
There is level 2 evidence to suggest goal management training, when compared to education, may be effective at improving attention in post-ABI individuals.
There is level 2 evidence that goal management training is more effective in remediating task completion times than motor skill training, however is not more effective in treating attention deficits, in post-ABI individuals.
There is conflicting (level 2) evidence that attentional control or processing training may not significantly improve attention in post-ABI individuals compared to control training.
There is level 4 evidence that summation tasks may be effective at improving attention in individuals post ABI.
There is level 4 evidence that a working memory training program may remediate attention in post-ABI individuals.
There is level 4 evidence that cognitive rehabilitation therapy may not be effective for improving attention post-ABI.
There is level 2 evidence that transcranial direct current stimulation compared to sham stimulation may improve divided attention in individuals post ABI.
There is level 1b evidence that donepezil may improve attention compared to placebo post ABI.
There is conflicting level 1b evidence regarding the effectiveness of methylphenidate following brain injury for the improvement of attention and concentration in individuals post ABI.
There is level 1a evidence that methylphenidate improves reaction time of working memory compared to placebo in individuals post ABI.
There is level 1b evidence that bromocriptine compared to placebo does not improve performance on attention tasks in patients post TBI.
There is level 2 evidence that bromocriptine improves attention, compared to placebo post ABI.
There is level 4 evidence that cerebrolysin may improve attention scores post ABI.
There is level 1b evidence that Rivastigmine compared to placebo may not be effective for improving concentration or attention in individuals post
There is level 4 evidence that the NeuroPage system may increase a patient’s ability and efficiency to complete tasks post TBI.
There is level 4 evidence that voice organizer programs are effective at improving recall of goals, and are found to be effective by patients post TBI.
There is level 2 evidence that personal digital assistants (PDAs) are superior to a paper-based schedule book at improving task completion rates post TBI.
There is level 1b evidence that the use of a personal digital assistant (PDA) in combination with conventional occupational therapy is superior to occupational therapy alone at improving memory in patients post TBI.
There is level 1b evidence that use of a personal digital assistant (PDA) after receiving systematic instructions is superior to PDA trial and error learning at improving the number and speed of correct tasks post TBI.
There is level 4 evidence that conventional or touch-screen personal digital assistant (PDA) use are similar at improving memory post TBI.
There is level 1b evidence that reminder text messages sent to patients through their smartphones, whether alone or in combination with goal management training, may improve goal completion post TBI.
There is level 2 evidence that a television assisted prompting (TAP) system is superior to traditional methods of memory prompting (paper planners, cell phones, computers) at improving the amount of completed tasks post TBI.
There is level 1b evidence that the audio-verbal interactive micro-prompting system, Guide, can reduce the amount of support-staff prompts needed for the patient to complete a task post TBI.
There is level 4 evidence that a computerized tracking system that sends reminders to patients when they are moving in the wrong direction reduces the amount of support-staff prompts needed for patients to complete a task post TBI.
There is conflicting (level 2) evidence regarding whether or not the use of a calendar, compared to diary training, is effective for improving memory post ABI.
There is level 2 evidence that the presence of a calendar may not improve orientation post ABI.
There is level 2 evidence that diary training in combination with self-instructional traning may be more effective than diary training alone at improving memory and task completion post ABI.
There is level 4 evidence that virtual reality (VR) training may improve learning performance post ABI, although the effect may not be different from non-VR training.
There is level 2 evidence that virtual reality training alone may be promising for improving memory outcomes, and has a positive impact on visual and verbal learning when in combination with exercise.
There is level 1b evidence that hypnosis compared to no treatment may not be effective at improving memory in individuals post ABI.
There is level 1b evidence that the Short Memory Technique may not be more effective than standard memory therapy at improving memory in individuals post ABI.
There is level 2 evidence that participation in a goals training program, followed by an educational program, may be more effective for improving memory in individuals post ABI compared to receiving the treatment conditions in reverse order.
There is level 1b evidence that compensatory memory strategies, self-awareness training, and participation in memory group sessions may be effective for improving memory in individuals post ABI compared to no treatment.
There is level 2 evidence that Strategic Memory and Reasoning Training (SMART) may improve learning and working memory compared to no memory training in individuals post ABI.
There is level 2 evidence that dual-task training may be effective for improving memory in individuals post ABI when presented before the control condition, compared to the reverse.
There is level 2 evidence that both computer-administered and therapist-administered memory training may be more effective than no treatment for improving memory in ABI participants. However, no treatment appears to be better than the other.
There is level 2 evidence that both cognitive remediation and emotional self-regulation may be effective at improving different elements of memory in individuals post ABI.
There is level 1b evidence that attention processing training compared to supportive listening may improve memory in individuals post ABI.
There is level 2 evidence that BrainHQ is not an effective program for improving memory and learning compared to no intervention in individuals post ABI.
There is level 4 evidence that using mental representations and role-playing may not be effective at improving memory in individuals post ABI.
There is level 4 evidence that Cogmed training software may improve working memory performance and occupational performance in individuals post ABI.
There is conflicting (level 4) evidence regarding whether or not Parrot software is effective at improving memory and learning in individuals post ABI.
There is level 4 evidence that mental addition tasks may improve working memory in individuals post ABI.
There is level 1b evidence that cranial electrotherapy stimulation may not improve memory and recall compared to sham stimulation post TBI.
There is level 1b evidence that donepezil improves short-term memory compared to X post ABI.
There is level 4 evidence that donepezil may be effective in improving short-term, long-term, verbal, and visual memory post ABI.
There is conflicting (level 1b) evidence regarding the effectiveness of the administration of methylphenidate compared to X following brain injury for the improvement of memory in patients post TBI.
There is level 1b evidence that sertraline may not improve memory compared to placebo in individuals who have sustained a moderate to severe TBI.
There is level 2 evidence that amantadine may not improve learning and memory deficits in patients post TBI.
There is level 2 evidence that pramiracetam may improve males’ memory compared to placebo post TBI.
There is level 1b evidence that oral physostigmine may improve long-term memory compared to placebo in men with TBI.
There is level 2 evidence that low-dose bromocriptine may improve cognitive function, but not working memory in patients post TBI.
There is level 4 evidence that bromocriptine may improve memory in patients post TBI.
There is level 4 evidence that cerebrolysin may improve memory function post ABI.
There is level 1b evidence that recombinant human Growth Hormone (rhGH) is similar to placebo at improving processing speed (6 mo), memory, executive function and learning in patients post TBI.
There is level 2 evidence that growth hormone (GH) therapy is similar to placebo at improving quality of life, instrumental activities of daily living (iADL), attention, memory, and visuospatial ability in patients post TBI.
There is level 1b evidence that rivastigmine may be effective in improving memory in ABI populations.
There is level 1b evidence that targeted hypnosis may transiently improve cognitive function in patients post TBI or stroke.
There is level 1b evidence that an attention remediation intervention is superior to TBI education alone and improving executive function in patients post TBI.
There is level 2 evidence that dual-task training may improve general cognitive functioning compared to a non-specific cognitive program in patients post TBI.
There is level 1b evidence that a comprehensive cognitive treatment strategy may be superior to a computerized training package at improving task initiating and goal achievement post TBI.
There is level 4 evidence that cognitive rehabilitation may increase productivity in everyday functioning, and cerebral blood flow during treatment in patients post TBI.
There is conflicting (level 1b and level 2) evidence as to whether virtual-reality training is or is not superior to conventional cognitive training at improving cognitive and executive function outcomes post TBI.
There is level 2 evidence that computer or smartphone software programs, such as BrainHQ, Parrot Software, ProSolv app, may not be superior to no intervention at improving problem-solving skills and general functioning in patients post TBI.
There is level 2 evidence that goal management training may be superior to motor skills training at improving everyday skills like meal preparation, but not neuropsychological tests or intelligence in patients post TBI.
There is conflicting evidence (level 1b and level 2) as to whether goal orientated group interventions are more than or equally as successful as educational interventions at improving cognitive and executive function in patients post ABI.
There is level 2 evidence that emotional regulation group interventions are effective at improving executive function in patients post TBI.
There is conflicting (level 4) evidence that group cognitive interventions (ie. Metacognitive Strategy Instruction) improves executive function in patients post TBI.
There is level 1b evidence that a remedial occupational therapy intervention may be superior compared to an adaptive occupational therapy intervention at improving general cognitive functioning in patients post TBI.
There is level 4 evidence that a low intensity outpatient cognitive rehabilitation program may improve goal attainment and cognitive impairment in patients post ABI.
There is level 4 evidence that donepezil is effective in improving learning, memory, divided attention, and executive function in patients post TBI.
There is conflicting (level 1a) evidence regarding the effectiveness of the administration of methylphenidate following TBI for the improvement of general functioning.
There is level 1b evidence that sertraline does not improve cognitive functioning in individuals who have sustained a moderate to severe TBI.
There is level 2 evidence that Amantadine does not help to improve general functioning deficits in patients post TBI compared to placebo.
There is level 2 evidence that low-dose bromocriptine may improve cognitive function in patients post TBI.
There is level 4 evidence that bromocriptine may improve motivational deficits in patients post TBI.
There is level 1b evidence that recombinant human Growth Hormone (rhGH) is similar to placebo at improving processing speed (6 mo), executive function and learning in patients post TBI.
There is level 2 evidence that growth hormone (GH) therapy is similar to placebo at improving quality of life, instrumental activities of daily living (iADL), attention, memory, and visuospatial ability in patients post TBI.
There is level 2 evidence that recombinant human Growth Hormone (rhGH) administration improves intelligence and other cognitive subtests in TBI patients with growth hormone deficiency compared to TBI patients without; however, insulin-like growth factor-1 (IGF-1) levels may be the same between groups.
There is conflicting (level 1b and level 4) evidence that rivastigmine is effective in improving memory in ABI populations.
There is conflicting (level 1b and level 4) evidence that rivastigmine may not be effective in improving memory in ABI populations.
References
Arciniegas, D. B. (2003). The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury. Curr Psychiatry Rep, 5(5), 391-399.
Azouvi, P., Couillet, J., Leclercq, M., Martin, Y., Asloun, S., & Rousseaux, M. (2004). Divided attention and mental effort after severe traumatic brain injury. Neuropsychologia, 42(9), 1260-1268.
Banos, J. H., Novack, T. A., Brunner, R., Renfroe, S., Lin, H. Y., & Meythaler, J. (2010). Impact of early administration of sertraline on cognitive and behavioral recovery in the first year after moderate to severe traumatic brain injury. J Head Trauma Rehabil, 25(5), 357-361.
Berg, I. J., Koning-Haanstra, M., & Deelman, B. G. (1991). Long-term effects of memory rehabilitation: A controlled study. Neuropsychological Rehabilitation, 1(2), 97-111.
Bergquist, T., Gehl, C., Mandrekar, J., Lepore, S., Hanna, S., Osten, A., & Beaulieu, W. (2009). The effect of internet-based cognitive rehabilitation in persons with memory impairments after severe traumatic brain injury. Brain Inj, 23(10), 790-799.
Bogdanova, Y., Yee, M. K., Ho, V. T., & Cicerone, K. D. (2016). Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review. Journal of Head Trauma Rehabilitation, 31(6), 419-433.
Boman, I. L., Lindstedt, M., Hemmingsson, H., & Bartfai, A. (2004). Cognitive training in home environment. Brain Inj, 18(10), 985-995.
Bondanelli, M., Ambrosio, M. R., Cavazzini, L., Bertocchi, A., Zatelli, M. C., Carli, A., Valle, D., Basaglia, N., & Uberti, E. C. (2007). Anterior pituitary function may predict functional and cognitive outcome in patients with traumatic brain injury undergoing rehabilitation. J Neurotrauma, 24(11), 1687-1697.
Bourgeois, M. S., Lenius, K., Turkstra, L., & Camp, C. (2007). The effects of cognitive teletherapy on reported everyday memory behaviours of persons with chronic traumatic brain injury. Brain Inj, 21(12), 1245-1257.
Burke, D. T., Leeb, S. B., Hinman, R. T., Lupton, E. C., Burke, J., Schneider, J. C., Ahangar, B., Simpson, K., & Kanoalani Mayer, E. A. (2001). Using talking lights to assist brain-injured patients with daily inpatient therapeutic schedule. J Head Trauma Rehabil, 16(3), 284-291.
Cacabelos, R. (2007). Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat, 3(3), 303-333.
Cantor, J., Ashman, T., Dams-O’Connor, K., Dijkers, M. P., Gordon, W., Spielman, L., Tsaousides, T., Allen, H., Nguyen, M., & Oswald, J. (2014). Evaluation of the short-term executive plus intervention for executive dysfunction after traumatic brain injury: a randomized controlled trial with minimization. Arch Phys Med Rehabil, 95(1), 1-9.e3.
Cappa, S. F., Benke, T., Clarke, S., Rossi, B., Stemmer, B., & van Heugten, C. M. (2005). EFNS guidelines on cognitive rehabilitation: report of an EFNS task force. Eur J Neurol, 12(9), 665-680.
Cardenas, D. D., McLean, A., Jr., Farrell-Roberts, L., Baker, L., Brooke, M., & Haselkorn, J. (1994). Oral physostigmine and impaired memory in adults with brain injury. Brain Inj, 8(7), 579-587.
Chen, A., Bushmeneva, K., Zagorski, B., Colantonio, A., Parsons, D., & Wodchis, W. P. (2012). Direct cost associated with acquired brain injury in Ontario. BMC Neurol, 12, 76.
Chen, A. J., Novakovic-Agopian, T., Nycum, T. J., Song, S., Turner, G. R., Hills, N. K., Rome, S., Abrams, G. M., & D’Esposito, M. (2011). Training of goal-directed attention regulation enhances control over neural processing for individuals with brain injury. Brain, 134(Pt 5), 1541-1554.
Chen, S. H., Thomas, J. D., Glueckauf, R. L., & Bracy, O. L. (1997). The effectiveness of computer-assisted cognitive rehabilitation for persons with traumatic brain injury. Brain Inj, 11(3), 197-209.
Chiaravalloti, N. D., Sandry, J., Moore, N. B., & DeLuca, J. (2016). An RCT to Treat Learning Impairment in Traumatic Brain Injury: The TBI-MEM Trial. Neurorehabil Neural Repair, 30(6), 539-550.
Cicerone, K. D. (2002). Remediation of “working attention” in mild traumatic brain injury. Brain Inj, 16(3), 185-195.
Cicerone, K. D., Dahlberg, C., Kalmar, K., Langenbahn, D. M., Malec, J. F., Bergquist, T. F., Felicetti, T., Giacino, J. T., Harley, J. P., Harrington, D. E., Herzog, J., Kneipp, S., Laatsch, L., & Morse, P. A. (2000). Evidence-based cognitive rehabilitation: recommendations for clinical practice. Arch Phys Med Rehabil, 81(12), 1596-1615.
Cicerone, K. D., Dahlberg, C., Malec, J. F., Langenbahn, D. M., Felicetti, T., Kneipp, S., Ellmo, W., Kalmar, K., Giacino, J. T., Harley, J. P., Laatsch, L., Morse, P. A., & Catanese, J. (2005). Evidence-based cognitive rehabilitation: updated review of the literature from 1998 through 2002. Arch Phys Med Rehabil, 86(8), 1681-1692.
Cicerone, K. D., Langenbahn, D. M., Braden, C., Malec, J. F., Kalmar, K., Fraas, M., Felicetti, T., Laatsch, L., Harley, J. P., Bergquist, T., Azulay, J., Cantor, J., & Ashman, T. (2011). Evidence-based cognitive rehabilitation: updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil, 92(4), 519-530.
Constantinidou, F., & Neils, J. (1995). Stimulus modality and verbal learning after moderate to severe closed head injury. The Journal of Head Trauma Rehabilitation, 10(4), 90-100.
Copley, A., Smith, K., Savill, K., & Finch, E. (2015). Does metacognitive strategy instruction improve impaired receptive cognitive-communication skills following acquired brain injury? Brain Inj, 29(11), 1309-1316.
Couillet, J., Soury, S., Lebornec, G., Asloun, S., Joseph, P. A., Mazaux, J. M., & Azouvi, P. (2010). Rehabilitation of divided attention after severe traumatic brain injury: a randomised trial. Neuropsychol Rehabil, 20(3), 321-339.
Dahdah, M. N., Bennett, M., Prajapati, P., Parsons, T. D., Sullivan, E., & Driver, S. (2017). Application of virtual environments in a multi-disciplinary day neurorehabilitation program to improve executive functioning using the Stroop task. NeuroRehabilitation, 41(4), 721-734.
Dirette, D. K., Hinojosa, J., & Carnevale, G. J. (1999). Comparison of remedial and compensatory interventions for adults with acquired brain injuries. J Head Trauma Rehabil, 14(6), 595-601.
Dockree, P. M., Bellgrove, M. A., O’Keeffe, F. M., Moloney, P., Aimola, L., Carton, S., & Robertson, I. H. (2006). Sustained attention in traumatic brain injury (TBI) and healthy controls: enhanced sensitivity with dual-task load. Exp Brain Res, 168(1-2), 218-229.
Dou, Z. L., Man, D. W., Ou, H. N., Zheng, J. L., & Tam, S. F. (2006). Computerized errorless learning-based memory rehabilitation for Chinese patients with brain injury: a preliminary quasi-experimental clinical design study. Brain Inj, 20(3), 219-225.
Dowds, M. M., Lee, P. H., Sheer, J. B., O’Neil-Pirozzi, T. M., Xenopoulos-Oddsson, A., Goldstein, R., Zainea, K. L., & Glenn, M. B. (2011). Electronic reminding technology following traumatic brain injury: effects on timely task completion. J Head Trauma Rehabil, 26(5), 339-347.
Dundon, N. M., Dockree, S. P., Buckley, V., Merriman, N., Carton, M., Clarke, S., Roche, R. A., Lalor, E. C., Robertson, I. H., & Dockree, P. M. (2015). Impaired auditory selective attention ameliorated by cognitive training with graded exposure to noise in patients with traumatic brain injury. Neuropsychologia, 75, 74-87.
Dvorkin, A. Y., Ramaiya, M., Larson, E. B., Zollman, F. S., Hsu, N., Pacini, S., Shah, A., & Patton, J. L. (2013). A “virtually minimal” visuo-haptic training of attention in severe traumatic brain injury. J Neuroeng Rehabil, 10, 92.
Dymowski, A. R., Owens, J. A., Ponsford, J. L., & Willmott, C. (2015). Speed of processing and strategic control of attention after traumatic brain injury. J Clin Exp Neuropsychol, 37(10), 1024-1035.
Evald, L. (2015). Prospective memory rehabilitation using smartphones in patients with TBI: What do participants report? Neuropsychol Rehabil, 25(2), 283-297.
Ewert, J., Levin, H. S., Watson, M. G., & Kalisky, Z. (1989). Procedural memory during posttraumatic amnesia in survivors of severe closed head injury. Implications for rehabilitation. Arch Neurol, 46(8), 911-916.
Fasotti, L., Kovacs, F., Eling, P. A. T. M., & Brouwer, W. H. (2000). Time Pressure Management as a Compensatory Strategy Training after Closed Head Injury. Neuropsychological Rehabilitation, 10(1), 47-65.
Fish, J., Evans, J. J., Nimmo, M., Martin, E., Kersel, D., Bateman, A., Wilson, B. A., & Manly, T. (2007). Rehabilitation of executive dysfunction following brain injury: “content-free” cueing improves everyday prospective memory performance. Neuropsychologia, 45(6), 1318-1330.
Foley, J. A., Cantagallo, A., Della Sala, S., & Logie, R. H. (2010). Dual task performance and post traumatic brain injury. Brain Inj, 24(6), 851-858.
Gabbatore, I., Sacco, K., Angeleri, R., Zettin, M., Bara, B. G., & Bosco, F. M. (2015). Cognitive Pragmatic Treatment: A Rehabilitative Program for Traumatic Brain Injury Individuals. J Head Trauma Rehabil, 30(5), E14-28.
Gentry, T., Wallace, J., Kvarfordt, C., & Lynch, K. B. (2008). Personal digital assistants as cognitive aids for individuals with severe traumatic brain injury: a community-based trial. Brain Inj, 22(1), 19-24.
Gerber, L. H., Narber, C. G., Vishnoi, N., Johnson, S. L., Chan, L., & Duric, Z. (2014). The feasibility of using haptic devices to engage people with chronic traumatic brain injury in virtual 3D functional tasks. J Neuroeng Rehabil, 11, 117.
Glenn, M. B. (1998). Methylphenidate for cognitive and behavioral dysfunction after traumatic brain injury. J Head Trauma Rehabil, 13(5), 87-90.
Glisky, E. L., & Delaney, S. M. (1996). Implicit Memory and New Semantic Learning in Posttraumatic Amnesia. The Journal of Head Trauma Rehabilitation, 11(2), 31-42.
Godfrey, J. (2009). Safety of therapeutic methylphenidate in adults: a systematic review of the evidence. J Psychopharmacol, 23(2), 194-205.
Goldstein, G., Beers, S. R., Longmore, S., & McCue, M. (1996). Efficacy of memory training: A technological extension and replication. The Clinical Neuropsychologist, 10(1), 66-72.
Gordon, W. A., Zafonte, R., Cicerone, K., Cantor, J., Brown, M., Lombard, L., Goldsmith, R., & Chandna, T. (2006). Traumatic brain injury rehabilitation: state of the science. Am J Phys Med Rehabil, 85(4), 343-382.
Gracey, F., Fish, J. E., Greenfield, E., Bateman, A., Malley, D., Hardy, G., Ingham, J., Evans, J. J., & Manly, T. (2017). A Randomized Controlled Trial of Assisted Intention Monitoring for the Rehabilitation of Executive Impairments Following Acquired Brain Injury. Neurorehabil Neural Repair, 31(4), 323-333.
Grealy, M. A., Johnson, D. A., & Rushton, S. K. (1999). Improving cognitive function after brain injury: the use of exercise and virtual reality. Arch Phys Med Rehabil, 80(6), 661-667.
Greenwald, B. D., Burnett, D. M., & Miller, M. A. (2003). Congenital and acquired brain injury. 1. Brain injury: epidemiology and pathophysiology. Arch Phys Med Rehabil, 84(3 Suppl 1), S3-7.
Hart, T., Hawkey, K., & Whyte, J. (2002). Use of a portable voice organizer to remember therapy goals in traumatic brain injury rehabilitation: a within-subjects trial. J Head Trauma Rehabil, 17(6), 556-570.
Hasegawa, J., & Hoshiyama, M. (2009). Attention deficits of patients with chronic-stage traumatic brain injury: a behavioral study involving a dual visuo-spatial task. J Clin Exp Neuropsychol, 31(3), 292-301.
High, W. M., Jr., Briones-Galang, M., Clark, J. A., Gilkison, C., Mossberg, K. A., Zgaljardic, D. J., Masel, B. E., & Urban, R. J. (2010). Effect of growth hormone replacement therapy on cognition after traumatic brain injury. J Neurotrauma, 27(9), 1565-1575.
Hillary, F. G., Schultheis, M. T., Challis, B. H., Millis, S. R., Carnevale, G. J., Galshi, T., & DeLuca, J. (2003). Spacing of repetitions improves learning and memory after moderate and severe TBI. J Clin Exp Neuropsychol, 25(1), 49-58.
Jacoby, M., Averbuch, S., Sacher, Y., Katz, N., Weiss, P. L., & Kizony, R. (2013). Effectiveness of executive functions training within a virtual supermarket for adults with traumatic brain injury: a pilot study. IEEE Trans Neural Syst Rehabil Eng, 21(2), 182-190.
JAMA. (1999). Rehabilitation of persons with traumatic brain injury Paper presented at the NIH Consensus Development Panel on Rehabilitation of Persons With Traumatic Brain Injury.
Johansson, B., & Tornmalm, M. (2012). Working memory training for patients with acquired brain injury: effects in daily life. Scand J Occup Ther, 19(2), 176-183.
Kelly, D. F., McArthur, D. L., Levin, H., Swimmer, S., Dusick, J. R., Cohan, P., Wang, C., & Swerdloff, R. (2006). Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma, 23(6), 928-942.
Kennedy, M. R., Coelho, C., Turkstra, L., Ylvisaker, M., Moore Sohlberg, M., Yorkston, K., Chiou, H. H., & Kan, P. F. (2008). Intervention for executive functions after traumatic brain injury: a systematic review, meta-analysis and clinical recommendations. Neuropsychol Rehabil, 18(3), 257-299.
Khateb, A., Ammann, J., Annoni, J. M., & Diserens, K. (2005). Cognition-enhancing effects of donepezil in traumatic brain injury. Eur Neurol, 54(1), 39-45.
Kim, H. J., Burke, D. T., Dowds, M. M., Jr., Boone, K. A., & Park, G. J. (2000). Electronic memory aids for outpatient brain injury: follow-up findings. Brain Inj, 14(2), 187-196.
Kim, J., Whyte, J., Patel, S., Europa, E., Wang, J., Coslett, H. B., & Detre, J. A. (2012). Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study. Psychopharmacology (Berl), 222(1), 47-57.
Kim, Y. H., Ko, M. H., Na, S. Y., Park, S. H., & Kim, K. W. (2006). Effects of single-dose methylphenidate on cognitive performance in patients with traumatic brain injury: a double-blind placebo-controlled study. Clin Rehabil, 20(1), 24-30.
Kline, A. E., Massucci, J. L., Marion, D. W., & Dixon, C. E. (2002). Attenuation of working memory and spatial acquisition deficits after a delayed and chronic bromocriptine treatment regimen in rats subjected to traumatic brain injury by controlled cortical impact. J Neurotrauma, 19(4), 415-425.
Kraus, M. F., Smith, G. S., Butters, M., Donnell, A. J., Dixon, E., Yilong, C., & Marion, D. (2005). Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj, 19(7), 471-479.
Laatsch, L., Pavel, D., Jobe, T., Lin, Q., & Quintana, J. C. (1999). Incorporation of SPECT imaging in a longitudinal cognitive rehabilitation therapy programme. Brain Inj, 13(8), 555-570.
Lannin, N., Carr, B., Allaous, J., Mackenzie, B., Falcon, A., & Tate, R. (2014). A randomized controlled trial of the effectiveness of handheld computers for improving everyday memory functioning in patients with memory impairments after acquired brain injury. Clin Rehabil, 28(5), 470-481.
Lemoncello, R., Sohlberg, M. M., Fickas, S., & Prideaux, J. (2011). A randomised controlled crossover trial evaluating Television Assisted Prompting (TAP) for adults with acquired brain injury. Neuropsychol Rehabil, 21(6), 825-846.
Levine, B., Robertson, I. H., Clare, L., Carter, G., Hong, J., Wilson, B. A., Duncan, J., & Stuss, D. T. (2000). Rehabilitation of executive functioning: an experimental-clinical validation of goal management training. J Int Neuropsychol Soc, 6(3), 299-312.
Lezak, M. D. (2004). Neuropsychological assessment. New York: Oxford university press.
Li, K., Alonso, J., Chadha, N., & Pulido, J. (2015). Does Generalization Occur Following Computer-Based Cognitive Retraining?-An Exploratory Study. Occup Ther Health Care, 29(3), 283-296.
Li, K., Robertson, J., Ramos, J., & Gella, S. (2013). Computer-based cognitive retraining for adults with chronic acquired brain injury: a pilot study. Occup Ther Health Care, 27(4), 333-344.
Lindelov, J. K., Dall, J. O., Kristensen, C. D., Aagesen, M. H., Olsen, S. A., Snuggerud, T. R., & Sikorska, A. (2016). Training and transfer effects of N-back training for brain-injured and healthy subjects. Neuropsychol Rehabil, 26(5-6), 895-909.
Man, D. W., Poon, W. S., & Lam, C. (2013). The effectiveness of artificial intelligent 3-D virtual reality vocational problem-solving training in enhancing employment opportunities for people with traumatic brain injury. Brain Inj, 27(9), 1016-1025.
Manasse, N. J., Hux, K., & Snell, J. (2005). Teaching face-name associations to survivors of traumatic brain injury: a sequential treatment approach. Brain Inj, 19(8), 633-641.
Masanic, C. A., Bayley, M. T., VanReekum, R., & Simard, M. (2001). Open-label study of donepezil in traumatic brain injury. Arch Phys Med Rehabil, 82(7), 896-901.
McDonald, A., Haslam, C., Yates, P., Gurr, B., Leeder, G., & Sayers, A. (2011). Google Calendar: a new memory aid to compensate for prospective memory deficits following acquired brain injury. Neuropsychol Rehabil, 21(6), 784-807.
McDowell, S., Whyte, J., & D’Esposito, M. (1998). Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain, 121 ( Pt 6), 1155-1164.
McHugh, L., & Wood, R. (2013). Stimulus over-selectivity in temporal brain injury: mindfulness as a potential intervention. Brain Inj, 27(13-14), 1595-1599.
McLean, A., Jr., Cardenas, D. D., Burgess, D., & Gamzu, E. (1991). Placebo-controlled study of pramiracetam in young males with memory and cognitive problems resulting from head injury and anoxia. Brain Inj, 5(4), 375-380.
McLean, A., Jr., Stanton, K. M., Cardenas, D. D., & Bergerud, D. B. (1987). Memory training combined with the use of oral physostigmine. Brain Inj, 1(2), 145-159.
McMillan, T., Robertson, I. H., Brock, D., & Chorlton, L. (2002). Brief mindfulness training for attentional problems after traumatic brain injury: A randomised control treatment trial. Neuropsychological Rehabilitation, 12(2), 117-125.
Michals, M. L., Crismon, M. L., Misko, J. S., & Childs, A. (1993). A double-blind, sham-controlled evaluation of cranial electrotherapy stimulation in posttraumatic memory impairment. The Journal of Head Trauma Rehabilitation, 8(4), 77-86.
Milders, M., Deelman, B., & Berg, I. (1998). Rehabilitation of memory for people’s names. Memory, 6(1), 21-36.
Milders, M. V., Berg, I. J., & Deelman, B. G. (1995). Four-year follow-up of a controlled memory training study in closed head injured patients. Neuropsychological Rehabilitation, 5(3), 223-238.
Miller, M. A., Burnett, D. M., & McElligott, J. M. (2003). Congenital and acquired brain injury. 3. Rehabilitation interventions: cognitive, behavioral, and community reentry. Arch Phys Med Rehabil, 84(3 Suppl 1), S12-17.
Moreau, O. K., Cortet-Rudelli, C., Yollin, E., Merlen, E., Daveluy, W., & Rousseaux, M. (2013). Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma, 30(11), 998-1006.
Morey, C. E., Cilo, M., Berry, J., & Cusick, C. (2003). The effect of Aricept in persons with persistent memory disorder following traumatic brain injury: a pilot study. Brain Inj, 17(9), 809-815.
Moseley, A. M., Herbert, R. D., Sherrington, C., & Maher, C. G. (2002). Evidence for physiotherapy practice: a survey of the Physiotherapy Evidence Database (PEDro). Aust J Physiother, 48(1), 43-49.
Napolitano, E., Elovic, E. P., & Qureshi, A. I. (2005). Pharmacological stimulant treatment of neurocognitive and functional deficits after traumatic and non-traumatic brain injury. Med Sci Monit, 11(6), Ra212-220.
Neistadt, M. E. (1992). Occupational therapy treatments for constructional deficits. Am J Occup Ther, 46(2), 141-148.
Novack, T. A., Caldwell, S. G., Duke, L. W., Bergquist, T. F., & Gage, R. J. (1996). Focused versus Unstructured Intervention for Attention Deficits after Traumatic Brain Injury. The Journal of Head Trauma Rehabilitation, 11(3), 52-60.
Novakovic-Agopian, T., Chen, A. J., Rome, S., Abrams, G., Castelli, H., Rossi, A., McKim, R., Hills, N., & D’Esposito, M. (2011). Rehabilitation of executive functioning with training in attention regulation applied to individually defined goals: a pilot study bridging theory, assessment, and treatment. J Head Trauma Rehabil, 26(5), 325-338.
O’Neil-Pirozzi, T. M., & Hsu, H. (2016). Feasibility and benefits of computerized cognitive exercise to adults with chronic moderate-to-severe cognitive impairments following an acquired brain injury: A pilot study. Brain Inj, 30(13-14), 1617-1625.
O’Neil-Pirozzi, T. M., Strangman, G. E., Goldstein, R., Katz, D. I., Savage, C. R., Kelkar, K., Supelana, C., Burke, D., Rauch, S. L., & Glenn, M. B. (2010). A controlled treatment study of internal memory strategies (I-MEMS) following traumatic brain injury. J Head Trauma Rehabil, 25(1), 43-51.
O’Neill, B., Best, C., O’Neill, L., Ramos, S. D. S., & Gillespie, A. (2017). Efficacy of a Micro-Prompting Technology in Reducing Support Needed by People With Severe Acquired Brain Injury in Activities of Daily Living: A Randomized Control Trial. J Head Trauma Rehabil.
Ownsworth, T. L., & McFarland, K. (1999). Memory remediation in long-term acquired brain injury: two approaches in diary training. Brain Inj, 13(8), 605-626.
Parente, R., Kolakowsky-Hayner, S., Krug, K., & Wilk, C. (1999). Retraining working memory after traumatic brain injury. NeuroRehabilitation, 13(3), 157-163.
Parente, R., & Stapleton, M. (1999). Development of a Cognitive strategies group for vocational training after traumatic brain injury. NeuroRehabilitation, 13(1), 13-20.
Park, N. W. (1999). Evaluation of the Attention Process Training Programme. Neuropsychological Rehabilitation, 9(2), 135-154.
Pavlovskaya, M., Hochstein, S., Keren, O., Mordvinov, E., & Groswasser, Z. (2007). Methylphenidate effect on hemispheric attentional imbalance in patients with traumatic brain injury: a psychophysical study. Brain Inj, 21(5), 489-497.
Plenger, P. M., Dixon, C. E., Castillo, R. M., Frankowski, R. F., Yablon, S. A., & Levin, H. S. (1996). Subacute methylphenidate treatment for moderate to moderately severe traumatic brain injury: a preliminary double-blind placebo-controlled study. Arch Phys Med Rehabil, 77(6), 536-540.
Potvin, M. J., Rouleau, I., Senechal, G., & Giguere, J. F. (2011). Prospective memory rehabilitation based on visual imagery techniques. Neuropsychol Rehabil, 21(6), 899-924.
Powell, J. H., al-Adawi, S., Morgan, J., & Greenwood, R. J. (1996). Motivational deficits after brain injury: effects of bromocriptine in 11 patients. J Neurol Neurosurg Psychiatry, 60(4), 416-421.
Powell, L. E., Glang, A., Ettel, D., Todis, B., Sohlberg, M. M., & Albin, R. (2012). Systematic instruction for individuals with acquired brain injury: results of a randomised controlled trial. Neuropsychol Rehabil, 22(1), 85-112.
Quemada, J. I., Munoz Cespedes, J. M., Ezkerra, J., Ballesteros, J., Ibarra, N., & Urruticoechea, I. (2003). Outcome of memory rehabilitation in traumatic brain injury assessed by neuropsychological tests and questionnaires. J Head Trauma Rehabil, 18(6), 532-540.
Rabinowitz, A. R., & Levin, H. S. (2014). Cognitive sequelae of traumatic brain injury. Psychiatr Clin North Am, 37(1), 1-11.
Rasquin, S. M., Bouwens, S. F., Dijcks, B., Winkens, I., Bakx, W. G., & van Heugten, C. M. (2010). Effectiveness of a low intensity outpatient cognitive rehabilitation programme for patients in the chronic phase after acquired brain injury. Neuropsychol Rehabil, 20(5), 760-777.
Rath, J. F., Simon, D., Langenbahn, D. M., Sherr, R. L., & Diller, L. (2003). Group treatment of problem-solving deficits in outpatients with traumatic brain injury: A randomised outcome study. Neuropsychological Rehabilitation, 13(4), 461-488.
Reimunde, P., Quintana, A., Castanon, B., Casteleiro, N., Vilarnovo, Z., Otero, A., Devesa, A., Otero-Cepeda, X. L., & Devesa, J. (2011). Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj, 25(1), 65-73.
Repantis, D., Schlattmann, P., Laisney, O., & Heuser, I. (2010). Modafinil and methylphenidate for neuroenhancement in healthy individuals: A systematic review. Pharmacol Res, 62(3), 187-206.
Sacco, K., Galetto, V., Dimitri, D., Geda, E., Perotti, F., Zettin, M., & Geminiani, G. C. (2016). Concomitant Use of Transcranial Direct Current Stimulation and Computer-Assisted Training for the Rehabilitation of Attention in Traumatic Brain Injured Patients: Behavioral and Neuroimaging Results. Front Behav Neurosci, 10, 57.
Sandry, J., Chiou, K. S., DeLuca, J., & Chiaravalloti, N. D. (2016). Individual Differences in Working Memory Capacity Predicts Responsiveness to Memory Rehabilitation After Traumatic Brain Injury. Arch Phys Med Rehabil, 97(6), 1026-1029.e1021.
Schefft, B. K., Dulay, M. F., & Fargo, J. D. (2008). The use of a self-generation memory encoding strategy to improve verbal memory and learning in patients with traumatic brain injury. Appl Neuropsychol, 15(1), 61-68.
Schneider, W. N., Drew-Cates, J., Wong, T. M., & Dombovy, M. L. (1999). Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Brain Inj, 13(11), 863-872.
Schneiderman, A. I., Braver, E. R., & Kang, H. K. (2008). Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent postconcussive symptoms and posttraumatic stress disorder. Am J Epidemiol, 167(12), 1446-1452.
Schretlen, D. J., & Shapiro, A. M. (2003). A quantitative review of the effects of traumatic brain injury on cognitive functioning. Int Rev Psychiatry, 15(4), 341-349.
Serino, A., Ciaramelli, E., Santantonio, A. D., Malagu, S., Servadei, F., & Ladavas, E. (2007). A pilot study for rehabilitation of central executive deficits after traumatic brain injury. Brain Inj, 21(1), 11-19.
Shin, H., & Kim, K. (2015). Virtual reality for cognitive rehabilitation after brain injury: a systematic review. J Phys Ther Sci, 27(9), 2999-3002.
Shum, D., Fleming, J., Gill, H., Gullo, M. J., & Strong, J. (2011). A randomized controlled trial of prospective memory rehabilitation in adults with traumatic brain injury. Journal of Rehabilitation Medicine, 43(3), 216-223.
Siddiqui, S. V., Chatterjee, U., Kumar, D., Siddiqui, A., & Goyal, N. (2008). Neuropsychology of prefrontal cortex. Indian journal of psychiatry, 50(3), 202.
Silver, J. M., Koumaras, B., Chen, M., Mirski, D., Potkin, S. G., Reyes, P., Warden, D., Harvey, P. D., Arciniegas, D., Katz, D. I., & Gunay, I. (2006). Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology, 67(5), 748-755.
Silver, J. M., Koumaras, B., Meng, X., Potkin, S. G., Reyes, P. F., Harvey, P. D., Katz, D. I., Gunay, I., & Arciniegas, D. B. (2009). Long-term effects of rivastigmine capsules in patients with traumatic brain injury. Brain Inj, 23(2), 123-132.
Sisto, S. A., Forrest, G. F., & Glendinning, D. (2002). Virtual reality applications for motor rehabilitation after stroke. Top Stroke Rehabil, 8(4), 11-23.
Sohlberg, M. M., Avery, J., Kennedy, M., Ylvisaker, M., Coelho, C., Turkstra, L., & Yorkston, K. (2003b). Practice guidelines for direct attention training. Journal of Medical Speech-Language Pathology, 11(3), xix-xxxix.
Sohlberg, M. M., McLaughlin, K. A., Pavese, A., Heidrich, A., & Posner, M. I. (2000). Evaluation of attention process training and brain injury education in persons with acquired brain injury. J Clin Exp Neuropsychol, 22(5), 656-676.
Sorita, E., N’Kaoua, B., Larrue, F., Criquillon, J., Simion, A., Sauzeon, H., Joseph, P. A., & Mazaux, J. M. (2013). Do patients with traumatic brain injury learn a route in the same way in real and virtual environments? Disabil Rehabil, 35(16), 1371-1379.
Speech, T. J., Rao, S. M., Osmon, D. C., & Sperry, L. T. (1993). A double-blind controlled study of methylphenidate treatment in closed head injury. Brain Inj, 7(4), 333-338.
Spikman, J. M., Boelen, D. H., Lamberts, K. F., Brouwer, W. H., & Fasotti, L. (2010). Effects of a multifaceted treatment program for executive dysfunction after acquired brain injury on indications of executive functioning in daily life. J Int Neuropsychol Soc, 16(1), 118-129.
Stuss, D. T., Stethem, L. L., Hugenholtz, H., Picton, T., Pivik, J., & Richard, M. T. (1989). Reaction time after head injury: fatigue, divided and focused attention, and consistency of performance. J Neurol Neurosurg Psychiatry, 52(6), 742-748.
Sumowski, J. F., Wood, H. G., Chiaravalloti, N., Wylie, G. R., Lengenfelder, J., & DeLuca, J. (2010). Retrieval practice: a simple strategy for improving memory after traumatic brain injury. J Int Neuropsychol Soc, 16(6), 1147-1150.
Tailby, R., & Haslam, C. (2003). An investigation of errorless learning in memory-impaired patients: improving the technique and clarifying theory. Neuropsychologia, 41(9), 1230-1240.
Takeda, A., Loveman, E., Clegg, A., Kirby, J., Picot, J., Payne, E., & Green, C. (2006). A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer’s disease. Int J Geriatr Psychiatry, 21(1), 17-28.
Thickpenny-Davis, K. L., & Barker-Collo, S. L. (2007). Evaluation of a structured group format memory rehabilitation program for adults following brain injury. J Head Trauma Rehabil, 22(5), 303-313.
Thoene, A. I., & Glisky, E. L. (1995). Learning of name-face associations in memory impaired patients: a comparison of different training procedures. J Int Neuropsychol Soc, 1(1), 29-38.
Tornas, S., Lovstad, M., Solbakk, A. K., Evans, J., Endestad, T., Hol, P. K., Schanke, A. K., & Stubberud, J. (2016). Rehabilitation of Executive Functions in Patients with Chronic Acquired Brain Injury with Goal Management Training, External Cuing, and Emotional Regulation: A Randomized Controlled Trial. J Int Neuropsychol Soc, 22(4), 436-452.
Twum, M., & Parente, R. (1994). Role of imagery and verbal labeling in the performance of paired associates tasks by persons with closed head injury. J Clin Exp Neuropsychol, 16(4), 630-639.
van den Broek, M. D., Downes, J., Johnson, Z., Dayus, B., & Hilton, N. (2000). Evaluation of an electronic memory aid in the neuropsychological rehabilitation of prospective memory deficits. Brain Inj, 14(5), 455-462.
Vas, A. K., Chapman, S. B., Cook, L. G., Elliott, A. C., & Keebler, M. (2011). Higher-order reasoning training years after traumatic brain injury in adults. J Head Trauma Rehabil, 26(3), 224-239.
Walker, W., Seel, R., Gibellato, M., Lew, H., Cornis-Pop, M., Jena, T., & Silver, T. (2004). The effects of Donepezil on traumatic brain injury acute rehabilitation outcomes. Brain Inj, 18(8), 739-750.
Watanabe, T. K., Black, K. L., Zafonte, R. D., Millis, S. R., & Mann, N. R. (1998). Do calendars enhance posttraumatic temporal orientation?: a pilot study. Brain Inj, 12(1), 81-85.
Whyte, J., Hart, T., Vaccaro, M., Grieb-Neff, P., Risser, A., Polansky, M., & Coslett, H. B. (2004). Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil, 83(6), 401-420.
Whyte, J., Vaccaro, M., Grieb-Neff, P., Hart, T., Polansky, M., & Coslett, H. B. (2008). The effects of bromocriptine on attention deficits after traumatic brain injury: a placebo-controlled pilot study. Am J Phys Med Rehabil, 87(2), 85-99.
Willmott, C., & Ponsford, J. (2009). Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry, 80(5), 552-557.
Wilson, B. A., Emslie, H., Quirk, K., Evans, J., & Watson, P. (2005). A randomized control trial to evaluate a paging system for people with traumatic brain injury. Brain Inj, 19(11), 891-894.
Wilson, B. A., Emslie, H. C., Quirk, K., & Evans, J. J. (2001). Reducing everyday memory and planning problems by means of a paging system: a randomised control crossover study. J Neurol Neurosurg Psychiatry, 70(4), 477-482.
Wilson, B. A., Evans, J. J., Emslie, H., & Malinek, V. (1997). Evaluation of NeuroPage: a new memory aid. J Neurol Neurosurg Psychiatry, 63(1), 113-115.
Wright, P., Rogers, N., Hall, C., Wilson, B., Evans, J., & Emslie, H. (2001a). Enhancing an appointment diary on a pocket computer for use by people after brain injury. Int J Rehabil Res, 24(4), 299-308.
Wright, P., Rogers, N., Hall, C., Wilson, B., Evans, J., Emslie, H., & Bartram, C. (2001b). Comparison of pocket-computer memory aids for people with brain injury. Brain Inj, 15(9), 787-800.
Yip, B. C., & Man, D. W. (2013). Virtual reality-based prospective memory training program for people with acquired brain injury. NeuroRehabilitation, 32(1), 103-115.
Zhang, L., Plotkin, R. C., Wang, G., Sandel, M. E., & Lee, S. (2004). Cholinergic augmentation with donepezil enhances recovery in short-term memory and sustained attention after traumatic brain injury. Arch Phys Med Rehabil, 85(7), 1050-1055.
Zickefoose, S., Hux, K., Brown, J., & Wulf, K. (2013). Let the games begin: a preliminary study using attention process training-3 and Lumosity brain games to remediate attention deficits following traumatic brain injury. Brain Inj, 27(6), 707-716.
Zlotowitz, S., Fallow, K., Illingworth, V., Liu, C., Greenwood, R., & Papps, B. (2010). Teaching action sequences after brain injury: a comparison of modelling and moulding techniques. Clin Rehabil, 24(7), 632-638.