Rehabilitation of Executive function in Paediatric Traumatic brain injury (REPeaT): protocol for a randomized controlled trial for treating working memory and decision-making

Paediatric Traumatic Brain Injury (TBI) is one of the leading causes of death and disability in children and adolescents worldwide. TBI is defined as “an alteration in brain function, or other evidence of brain pathology, caused by an external force to the head” [1]. Substantial literature on paediatric TBI has identified acute and long-term impairments in higher order cognitive processes often identified as impairments in executive function (EF) [2‐4].

Definitions of EF indicate that it encompasses the highest level of human functioning such as working memory (WM), decision-making (DM), aspects of attention, cognitive control, and inhibition [5, 6]. Neural substrates linked to WM and DM include the frontal lobes, prefrontal subregions, posterior cortex, and subcortical structures [7‐9] These brain regions mature from childhood into early adulthood with different trajectories across sex and are specifically vulnerable following TBI sustained in childhood [10‐12]. Findings from brain imaging studies also suggest that the integrity of these brain regions and the neural circulatory connecting them is crucial for WM [13, 14] and DM [6, 15‐17]. With regards to sex, previous research shows difference in performance on WM and DM tasks in girls and boys post childhood TBI [12, 18].

WM is a limited multi-component system that facilitates maintenance and manipulation of information in an active state for short period of times. It is involved in goal-directed cognitive functioning and in the acquisition of academic skills including mathematical computation, reading, and writing [19‐24]. Impairments in WM post TBI are common, often with implications in a multitude of cognitive processes and adaptability in daily life [25, 26].

DM is defined as the fundamental skill for identifying, processing, and selecting one course of action from multiple alternatives [27]. Thus, DM is a stepwise process as proposed by the process tracing models of DM [28]. Myriad disciplines have studied DM from different theoretical assumptions ranging from normative theories of subjective expected utility [29], to dual process theories of information processing [30, 31], and to somatic marker hypothesis [32], with less research on process tracing methods of information acquisition in DM [33]. One such method pertains to the use of information boards [34‐36]. More recently, an emerging field of decision neuroscience has led to an integrated study of DM by taking into account the neural substrates, cognitive processes, and the association between one’s decisions and social outcomes [4, 37‐39]. Findings from these studies suggest WM allows multiple units of information to be assimilated and compared in DM [4, 40]. Additionally, DM has also been associated with functional outcomes such as return to school. In TBI, recent studies have also indicated deficits in DM [41‐47]. While there are studies that contradict DM’s association with WM in children with or without brain injuries, findings in support of this association demonstrate a pleading case for more research in this area [48‐54].

It is clear that EF domains such as WM and DM provide a target for intervention, given they are frequently impaired post childhood TBI, and are associated with everyday function and social functioning. Previous studies estimate that one-third of children post TBI benefit from intervention approaches [55]. Recently, several computerized interventions or training programs have been successfully trialled for executive function rehabilitation in other clinical populations. Despite this, there is a paucity of research in the intervention area, with even less research pertaining to the effectiveness of interventions implemented following childhood TBI [56, 57]. Methodological limitations of existing research include reliance on case studies instead of RCT design; no preregistration of trials; lack of an active-control group, no blinding, small sample size, and limited use of clinically meaningful outcome measures [58].

The Cogmed Working Memory Training program (Cogmed), is a popular computerized cognitive intervention that is based on the multi-component theory of memory [59] and the theory of neuroplasticity [26]. Cogmed was first trialled in an RCT of 53 children with ADHD [60]. This trial aimed to investigate the impact of Cogmed in improving WM in this clinical population. Results immediately post-intervention and at 3 months follow-up suggested significant benefits in working memory, ADHD symptoms, and several other executive tasks thereby implying the benefits from the intervention were also transferrable. Since then Cogmed has been trialled in typical adults [61], pre-term children [62], children with ADHD, and school-aged children with low WM [63, 64]. However, evidence for benefits from Cogmed in children with TBI is scarce, where to date only seven published studies have investigated the efficiency of Cogmed post brain injury. Of these, six studies involved adults with acquired brain injuries [65‐70]. Additionally, limitations of these studies included small sample size, lack of an active-control group, and shorter length of follow-up. A single recent study involving children post-TBI [57] investigated the impact of Cogmed on various components of WM. Findings from this study provided preliminary evidence for the efficacy of Cogmed in improving WM, attention, and academic skills. However, findings are limited by a small sample size, lack of consideration of injury-related factors, and short length of follow-up post intervention. While research investigating the impact of Cogmed in brain injuries supports improvements in similar tasks as those in Cogmed training, other results are inconclusive. [71]. Hence, further research investigating the efficacy of Cogmed in improving performance in similar tasks as well as generalizability to other functional outcomes is required.

In summary, ours is the first study to use a novel task of DM to investigate the relationship between WM and DM, and to study the impact of Cogmed on WM, DM, and functional outcomes in paediatric TBI.

The overall aim of the proposed study is to evaluate the effectiveness of Cogmed post childhood TBI. RCT methodology with the inclusion of an active-control group and a larger sample size will be implemented to address previous limitations in this area. In addition to the primary executive function outcomes post intervention, this trial will investigate the generalized impact (far transfer) of Cogmed in improving everyday function including social functioning. The follow-up assessments will be completed at two time points, namely, immediately post-intervention, and at 6-months follow-up. This RCT will be a novel study to identify the relationship between WM, DM, functional outcomes and the impact of Cogmed in all these areas in children post TBI.

It is hypothesized that: (a) immediately post-intervention and at 6 months post-intervention compared to the active-control group the treatment group will report improvements in WM and DM; (b) improvements in WM will be associated with an increase in DM, academic achievement (mathematics), social skills, behavioural, and quality of life outcomes; and (c) age and sex will have an impact on WM and DM of children post- TBI (see Fig. 1).

Impairments in WM and DM commonly occur following childhood TBI. Currently there is minimal literature and a poor evidence base regarding intervention in this area. It is essential that effective treatment options are made available. The expected outcome of this proposed study is that the Cogmed program will be shown to be effective in improving WM and DM, and will also lead to generalised improvements in functional skills in children post-TBI. Our team will play a key role in translating Cogmed into standard clinical care, schools, and community settings. However, if findings are not significant, it will still be significant in knowing that Cogmed may not be an effective intervention for this population, suggesting it may need to be adapted for implementation in this clinical group.