The pervasiveness of traumatic brain injuries (TBIs) and the functional problems they entail are often tragic for injured individuals, their relations, and society as a whole. TBI is a major cause of death and disability, with as many as 1.7 million cases per year , and has a high incidence in adolescents and young adults . TBI incidents in the US commonly occur because of vehicle accidents, falls, and assaults . In the past decade, the incidence of TBI has risen sharply, to an estimated 19 percent in military populations, because of the wars in Iraq and Afghanistan [3, 4].
Traumatic brain injury (TBI) survivors, including those with mild injuries, may continue to experience significant difficulties in functioning relative to optimal levels at work, home, or in the community even years post-injury [5, 6]. Impairments are especially prominent in tasks and daily activities that draw upon higher-order cognitive processes mediated by the frontal lobes, an area of the brain that is exceptionally vulnerable to trauma. Rehabilitation efforts to remediate frontal lobe-related cognitive impairments are relatively rare, especially in chronic stages of recovery. Traditional cognitive training targets remediation of specific cognitive skills (e.g., memory) that do not necessarily draw upon frontal lobe-dominant integrative functions. Additionally, access to and availability of functionally relevant theoretical frameworks to guide brain training are often limited. Furthermore, TBI training studies rarely include imaging measures to characterize structural and functional brain changes.
To address prior shortcomings, researchers have begun developing cognitive rehabilitative therapies that target frontal lobe-mediated top-down modulatory processes. Top-down control processes are deliberate, effortful cognitive processes that both focus attention on task-relevant stimuli and screen out irrelevant distractions [7, 8]. At the level of the brain, top-down modulation involves governing the operations of enhancement and suppression of neural activity based on the relevance of the information to task goals. Increasingly, neuroimaging results highlight the role of the prefrontal cortex in top-down modulatory tasks . Accordingly, training frontal-mediated top-down processes in adults with TBI could be beneficial in restoring and improving higher-order cognitive functions.
In the current randomized control trial, we study the efficacy of a functionally relevant cognitive training program applied to individuals who are experiencing the effects of chronic TBI. The top-down training program labeled SMART (Strategic Memory Advanced Reasoning Training) adopts an integrative approach to train functionally relevant complex reasoning abilities (versus specific skills). This integrative approach focused on frontal lobe functions has shown promising results in a preliminary study . SMART is compared to an equally engaging education-based program labeled BHW (Brain Health Workshop). Both SMART and BHW are short-term, intensive (18 h of training over 8 weeks) group training programs that are comparable with regard to training time, amount of information, group discussions, and homework assignments. The overall goal of this trial is to examine how training integrative frontal lobe-mediated processes might improve functioning in brain injury survivors, including military service and civilian populations. We include a range of individuals with different injury types and functional abilities. We use a broad variety of assessment tools, including cognitive, neuroimaging, and functional measures, to compare the training groups.
Our overall goal is to improve the fidelity of TBI diagnoses and to achieve higher levels of functional recovery in soldiers and civilians who have suffered mild to moderate TBIs and are at the chronic stage of brain recovery. This study is also to determine the efficacy of an empirically and theoretically driven framework to enhance frontal lobe-mediated reasoning ability in individuals with TBI, given a relatively short training duration, on trained and untrained cognitive skills, on brain changes, and on measures of real-life function.
Toward these aims, this trial is enrolling both soldiers and civilians with a TBI (approximately 50 mild and 50 moderate chronic TBI patients). We use cognitive tests (assessing memory, reasoning, and comprehension abilities), functional MRI scans (performing tests of cognitive function while the subject is receiving an MRI scan), and white matter maps constructed using diffusion tensor imaging (DTI) scans. The MRI scans will be used to provide biomarkers of the contributions of different brain regions to performing cognitive tasks (e.g., memory, reasoning, etc.), as well as assessments of brain efficiency, functional brain connectivity, and brain morphology. We use these measurements to gain an understanding of each individual’s cognitive skills and neural measures prior to cognitive intervention. These measures also serve as indicators of the baseline function of each soldier or civilian, to be compared with after intervention, at which point they undergo post-training cognitive, MRI, and DTI assessments, enabling us to make outcome comparisons between the two different cognitive interventions. Finally, we conduct a follow-up assessment with neuropsychological and cognitive measures and neuroimaging 3 months after the interventions to assess how individuals maintain any functional changes that may occur because of the cognitive interventions.
We are targeting this intervention toward mild and moderate TBI participants, who have relatively high functioning skills. The demands of the training can be too high for some individuals falling into the more severe range, in the frequency, duration, and type of strategies and skills emphasized. We also aim to address the high level of need placed upon studies of milder TBI cases, particularly with military populations. This priority is also emphasized by the sponsoring agency, the US Department of Defense, advocating for more studies of mild TBI under the funding mechanism supporting this work.
Aim 1. Examine the short-term effects of SMART compared to BHW on cognition and real-life outcomes in soldiers and civilians with TBI.
Hypotheses related to Aim 1
Subjects who receive SMART show a greater increase from baseline on measures of attention, memory, and reasoning when compared to those who receive BHW.
Subjects who receive SMART show greater improvements in untrained cognitive measures that engage executive functions (e.g., measures of inhibition, non-verbal reasoning, task switching, working memory, and fluency) compared to those who receive BHW.
Subjects who receive SMART show greater improvement on rating scales of life skills functioning than those who receive BHW.
Aim 2. Examine changes in functional magnetic resonance imaging (fMRI) measures as a result of SMART versus BHW.
Hypotheses related to Aim 2
Subjects who receive SMART show greater modulation of ventral temporal regions previously shown to be a biomarker of attention toward relevant information relative to BHW participants.
Subjects who receive SMART will show greater activation of the frontal cortex relative to BHW participants following the intervention.
Aim 3. Determine whether the effects of SMART versus BHW training are maintained at a time point 3 months after cognitive intervention training.
Hypotheses related to Aim 3
The effects of SMART on abstract reasoning ability are maintained at 3 months after training, with no predicted change in the BHW group.
The effects of SMART on untrained executive function measures are maintained at 3 months after training, with no change in the BHW group.
The effects of SMART on daily life function measures are maintained at 3 months after training.