6.3 Remediation of Executive Functioning

Executive functions refer to higher-level cognitive functions that are primarily mediated by the frontal lobes. These functions include insight, awareness, judgment, planning, organization, problem solving, multi-tasking and working memory50. Executive deficits are particularly relevant following traumatic brain injury from both a pathophysiologic as well as a psychosocial perspective. The frontal lobes tend to be one of the brain areas most likely to be injured following trauma 51. Frequently bilateral frontal lobe injury occurs following TBI in contrast to typical unilateral insults following vascular injury. Not only direct contusion to the frontal and temporal lobes but also diffuse axonal injury sustained as a result of TBI affect executive functioning. TBI patients often present with cognitive and behavioural deficits in the presence of little physical impairment.

Cicerone et al. 1reviewed 14 studies dealing with executive functioning and problem-solving Only 3 of the identified studies were classified as a randomized controlled trial or non-randomized cohort study.

In an updated review, Cicerone et al. 2identified 9 additional studies. Some of these studies were not included in our review as they dealt with mild severity of injury.  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 primarily 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 52.

Within the typical medical and rehabilitation settings, executive function deficits themselves are difficult to identify and evaluate since there is a tendency to focus on other cognitive functions such as memory and attention.  The importance of evaluating effective interventions for treating executive dysfunction following brain injury is apparent since impairment can ultimately hinder successful community re-integration.

 

According to ABIKUS Recommendations3

Executive Functions

Use of metacognitive strategy training (e.g. goal/plan/do/review, goal management training) is recommended for people with executive dysfunction (ABIKUS A) (G41-p.22)

The following interventions are not recommended due to demonstrated lack of efficacy:

  • Sole reliance on repeated exposure and practice on computer based tasks with some involvement by a therapist
  • Specific structured attention programs using drill and practice

(ABIKUS A) (G42-p.22)


6.3.1 Group Interventions

What evidence is there supporting group interventions for executive dysfunction post ABI?
There is conflicting evidence supporting the use of group-based interventions to treat executive dysfunction post ABI.

Although executive function deficits are a common and important impairment post brain injury, there is little overall research directly addressing the impact of rehabilitation on executive function.  However, community integration is highly related to executive function and it is possible that programs and interventions aimed at improving community re-integration may in fact be focusing efforts on instrumental activities of daily living for which intact executive functions are required. 

In an RCT conducted byOwnsworth et al. 53, subjects were randomly assigned to a diary only (DO - n=10) group or a diary and self-instructional training (DSIT-n=10) group. The DO group participated in a 6 week “Bottom-Up” approach program that emphasized the development of functional skills using compensation based, on task,-specific learning.  The DSIT group participated in a 10 week “Top-Down” approach program that emphasized the capacity for self-regulation and self-awareness using “Self Instructional Training.”  The comparison group (n=31), individuals who had not sustained a TBI, completed the self-report memory questionnaires. Results indicate no significant differences on the performance self-ratings, satisfaction self-ratings, relatives’ performance ratings, and relatives’ satisfaction ratings (p>0.05) for the intervention group. The satisfaction self ratings between pre and post assessment, indicated an improvement after each intervention (individual p<0.001; group p<0.025; combined p<0.01).  At follow-up an improvement in self-rated satisfaction was noted for the group and combined interventions only (p<0.01). Results from the CPOM indicate that there were no significant differences when looking at the scores from the group intervention pre to post comparison (p<0.028). Significant improvement was noted when looking at the scores for the individual and combined interventions (p<0.01 and p<0.025 respectively).  Pre assessment and follow-up assessment for the relatives’ ratings of performance was significant for all three interventions (individual p<0.01; group p<0.01; combined p<0.025). Relatives’ ratings of satisfaction (pre and post) found a significant improvement for the individual (p<0.025) and combined (p<0.01) interventions but not for the group intervention (p<0.117).  A look at the psychosocial outcomes for each intervention group showed few significant differences.

Ownsworthet al.54studied the effect of group therapy aimed at improving self regulation skills as well as psychosocial functioning for brain injury survivors greater than 1 year post injury. Self regulation was evaluated using the self regulation skills interview which examines how brain injury survivors would handle self identified difficulties 54. Both self regulation abilities and psychosocial functioning improved following the treatment intervention and improved performance was maintained at 6 month follow up.

6.3.2 Goal Management Training

What is the evidence for goal management training of executive functioning deficits post ABI?

  1. There is Level 2 evidence, based on a single RCT, that goal management training is effective for improving paper and pencil everyday tasks and meal preparation skills for persons with an ABI.
  2. There is Level 4 evidence, based on a single group intervention, that a goal planning in the form of a leisure activities is effective for achieving identified goals following injury.

With cognitive rehabilitation, much of therapy is patient goal directed with both long and short term goals often identified 55. The ability to manage goals is often emphasized as a component of brain injury community reintegration programs and is integral in the completion of instrumental activities of daily living.

Levine et al. 56completed a 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 task heavily reliant on self-regulation.

Walker et al. 57conducted an alternative goal planning, cognitive rehabilitation program focusing on the development and achievement of goals following brain injury. This single group intervention involved three phases: (1) nine-months of planning and fund-raising for an outdoor adventure course; (2) a nine-day outdoor course; and (3) four-months following the course, the participants focused on goal achievement and problem-solving skills. More than 80% of the identified goals of participants were achieved. No significant pre- and post-treatment differences were noted on psychological measures: Depression, Anxiety Stress Scales (DASS), the General Well-Being Schedule (GWB), and the European Brain Injury Questionnaire (EBIQ). This program demonstrated a unique and challenging, community-based intervention for group goal management following brain injury.

6.3.3 Pharmacological Intervention

 

According to ABIKUS Recommendations 3

Medication for Executive Dysfunction

Bromocriptine in a dose of 2.5 mg is recommended for use in enhancing aspects of executive functioning (e.g. divided attention/central executive functions) in patients with severe TBI (ABIKUS B, adapted from GPT, I, p.1482)

6.3.3.1 Amantadine

What is the evidence for amantidine improving executive functioning post ABI?

There is Level 4 evidence that amantadine does help to improve executive functioning based on the conclusions of a single group intervention.

Amantadine is anon-competitive N-methyl-D-aspartate receptor antagonist and is currently used as an antiviral agent used as a prophylaxis for influenza A, for the treatment of neurological diseases such as Parkinson’s Disease and in the treatment of neuroleptic side-effects such as dystonia, akinthesia and neuroleptic malignant syndrome 47It is thought to work pre- and post-synaptically by increasing the amount of dopamine 5.

Kraus et al. 48demonstrated significant improvements in executive functioning following administration of amantadine over a 12-week treatment period.  It should be noted that there were no significant differences noted for measures of memory deficits or attention.

Kraus MF, Smith GS, Butters M, Donnell AJ, Dixon E, Yilong C, Marion D. 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 Injury, 2005; 19(7):471-479.

  • Participants in the current study (n=22) were administered 400 mg of amantadine per day for a period of 12 weeks
  • A series of neuropsychological tests were administered pre and post administration of the amantadine.
  • Post treatment executive function scores significantly improved (t(21)= -2.47, p=0.02).
  • Scores on the memory and attention domains showed no significant improvement.

 6.3.3.2 Bromocriptine

What is the evidence for bromocriptine in treating executive functioning post ABI?
  1. Based on a two RCTs there is conflicting evidence supporting the use of bromocriptine to enhance cognitive functioning.

Bromocriptine is adopaminergic agonist, which primarily affects D2 receptors 58. It has been suggested that dopamine is an important neurotransmitter for prefrontal or frontal lobe function 59

In a randomized placebo controlled cross over study conducted by Whyte et al. 58bromocritpine was administered to a group of individuals.  Administration of bromocriptine was begun at 1.25mg/BID and increased to 5mg/BID.  Individuals received the medication for 3 weeks before being titrated off the medication and placed on a placebo. Test results for all subjects indicate bromocriptine had little significant effect on their abilities to perform on a range of measures of attentional function. It was noted that several participants did experience moderate to severe drug effects and withdrew or were withdrawn from the study.

In an earlier study, McDowell et al. 59examined the effects of low dose bromocriptine in a double-blinded, placebo-controlled cross-over design trial. Testing revealed that a low dose of bromocriptine (2.5 mg/daily) improved functioning on tests of executive control including a dual task, trailmaking test, the Stroop test, the Wisconsin Card-Sorting Test and the controlled oral word association test (FAS test).  However, bromocriptine did not significantly influence working memory tasks.

Although the McDowell et al. 59study demonstrated benefits following administration of bromocriptine, there was only a single administration of bromocriptine or placebo and the dose was considerably lower than that given by Whyte et al. 58.  Spontaneous recovery may have been a factor leading to the improved abilities in individuals receiving a single dose (2.5mg daily) of the medication; however, study results did not answer this question.  Results from Whyte et al. 58noted that the placebo group demonstrated better (although not significant) trends in improvement on the various tasks administered.

Whyte J, Vaccaro M, Grieb-Neff P, Hart T, Polansky M, Coslett HB. The effects of bromocriptine on attention deficits after traumatic brain injury: a placebo-controlled pilot study.  Am J Phys Med Rehabil. 2008; 87:85-99.

  • 12 participants were randomized to either the bromocriptine/placebo group (n=6) or the placebo/bromocriptine group (n=6)
  • Participants received the bromocriptine or placebo for 4 weeks.
  • Bromocriptine was started at 1.25 mg twice daily for 2 days, the dose was then increased to 2.25 mg twice daily for 3 days, then increased to 5 mg twice daily for the next 3 weeks. Following the 4th week, participants on bromocriptine were given the placebo and those in the placebo group were started on bromocriptine.
  • Overall the administration of bromocriptine had little effect on the participants’ abilities to perform on a range of measures of attentional function.

McDowell S, Whyte J and  D’Esposito M. Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain, 1998; 121(6):1155-1164.

  • In the following double blind cross over RCT, 24 participants were given 2.5 mg of bromocriptine or placebo.
  • Participants were asked to complete the following cognitive tests: Stroop test, Spatial delayed-response task, Wisconsin Card Sorting Test (WCST), Verbal span task, Trailmaking test, and controlled oral word association test (FAS test).
  • Bromocriptine was found to improve function on tasks that engage executive processes (dual task, trailmaking test, Stroop Test, verbal fluency and WCST) but it did not improve working memory (spatial delayed response task or reading span).

6.3.4  Summary of Executive Function

The current studies support the notion that group cognitive interventions may be effective for improving executive functionThere is also some evidence that pharmacological intervention, amantadine, may be effective in improving executive function. Evidence supporting the use of bromocriptine is inconclusive.  Ultimately, further research is required to determine which methods are most effective for improving executive function.