Developing Process-Specific Verbal Memory Interventions for Veterans With Tramatic Brain Injury (TBI)
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional

Summary: 
      Blast-related and blunt traumatic brain injury is a key priority area of Rehabilitation
      Research & Development (RR&D) and represents a critically important public health problem
      facing the Veteran population. Developing efficacious treatments for persistent memory
      deficits seen in this population is a key step in reducing the impact that such problems have
      in the everyday lives of Veterans. Memory problems after TBI in Veterans are quite
      heterogeneous, and efficacy will likely be maximized by developing and disseminating multiple
      alternative treatments individually matched to the Veteran's key deficits, and by research
      that seeks to understand the cognitive and neural basis of treatment-related change over
      time. The results of this approach may aid clinical decision making and assignment of
      patients to rehabilitative treatments most likely to improve memory capacity and functional
      outcome.
    

Detailed description: 
      Memory dysfunction can result from impairments along a continuum of information processing,
      from poor initial acquisition of information during learning to disturbed retrieval of stored
      memory when it is later needed to perform a task1. The heterogeneous nature of TBI-related
      memory impairment is well-known, and there is a critical need to better understand such
      disease heterogeneity in order to enhance diagnosis and therapeutic management2. Several
      subtypes of memory dysfunction after TBI have been identified3,4. First, some TBI survivors
      exhibit impaired memory acquisition/encoding (e.g., frontal system damage)5. Second, some
      exhibit impaired memory consolidation/storage impairment (e.g., prominent damage to temporal
      lobe systems6). Third, some show impairment in retrieval of information5,7. This
      heterogeneity results from the variable nature and severity of underlying brain trauma
      resulting from unpredictable mechanical forces2,8.

      It has been suggested that parsing this underlying variability should take precedence over
      generalities regarding the effect of TBI on memory when conceptualizing or treating memory
      disorders in this population8 Nevertheless, many rehabilitation programs utilize a "one size
      fits all" approach to memory training, based (typically) on training compensatory strategies,
      with no training specifically targeted to the identifiable component processes of memory that
      could be differentially impaired (encoding, consolidation/storage, and retrieval), and which
      might respond differentially to more specifically targeted treatment. This situation in
      clinical practice is due to the lack of evidence upon which to base informed decision-making
      in allocating specifically targeted memory re-training for individual survivors of TBI, based
      on clinical test results identifying which memory component processes are impaired (encoding,
      consolidation/storage, and retrieval). Because of this, there is little attempt to
      appropriately match patient impairment to targeted treatments.

      There are existing training protocols for training these three components of memory
      processing, as follows: encoding (memory strategy training9), consolidation (errorless
      learning10), and retrieval (retrieval practice11, but their efficacy has not been tested in
      TBI survivors with documented impairments in each component. That is, to the investigators'
      knowledge, there is no solid evidence for memory training in TBI survivors that supports the
      widely held belief that specifically matching the patient impairment to the treatment leads
      to better treatment outcomes. This proposal attempts to fill this gap in the investigators'
      knowledge. Prior to testing the efficacy of these three types of training in a large trial,
      it is important to make standard preparations, such as refining and testing training
      materials and ensuring fidelity of treatment methods across clinicians.

      Aim 1. Aim 1 is to refine and validate three separate, process-specific memory rehabilitation
      treatments that focus on improving information-processing at the encoding, consolidation, or
      retrieval stage for Veterans with chronic moderate/severe TBI.

      Objective 1.1. Generate treatment manuals for three process-specific memory treatments.

      Objective 1.2. Test and refine treatment fidelity so that each of the three interventions can
      be reliably delivered by different clinicians.

      Aim 2. Aim 2 is to provide a preliminary test of the response to the three memory
      interventions. At baseline, TBI survivors will be evaluated for memory function in each of
      these three memory component processes using established neuropsychometric methods. Their
      experimental treatment allocation will be to the treatment targeting their most impaired
      memory component. In addition, each subject will serve as his/her own control, by engaging in
      a treatment targeted to another memory component ('mismatched' group).

      Hypothesis A. Matched vs. mismatched group will show differential improvement in memory
      component function, with the former group benefitting to a significantly greater degree.
      (Primary measures: Memory component performance, encoding, consolidation, retrieval;
      secondary: cognitive function and quality of life).

      Aim 3. Aim 3 is to establish links between the behavioral taxonomy of the three memory
      components and differences in brain structure and function documented with diffusion tensor
      imaging and functional connectivity analysis. This is a key first step in establishing
      brain-based metrics of neuroplastic change after memory therapy in the investigators'
      research program.

      Objective 3.1. Identify specific and unique imaging signatures that distinguish patients with
      deficits in encoding, consolidation, and retrieval, respectively. Primary measures:
      structural measures of morphometry and white matter integrity (FA) and functional
      connectivity (cross correlation and total interdependence) in identified brain networks
      damaged in TBI.

      Clinical Implications. This research has the potential to devise a method to match specific
      subcomponents of memory impairment to specifically targeted memory interventions, thus
      maximizing recovery of memory and function. The results of this investigation will be used to
      refine the interventions, to evaluate cognitive and functional endpoints, and to power a
      larger clinical trial that will yield data enabling clinicians to match TBI patients to
      effective treatments based on their individual profile of memory dysfunction.
    

Intervention name(s): Memory Strategy Training; Errorless Learning; Retrieval Practice
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): This intervention involves intervention that teaches participants to use active encoding strategies to learn and remember new information. The intervention will be implemented using verbal and face-name paired associate learning.; This intervention enhances consolidation of correct target information by preventing false recall of incorrect information during the acquisition phase. Participants are encouraged to recall target information only if they are sure it is correct, thus eliminating errors. The intervention will be implemented using verbal and face-name paired associate learning.; This intervention enhances retrieval of correct target information by actively practicing retrieval in the presence of a cue. The intervention will be implemented using verbal and face-name paired associate learning.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: TBI; memory disorder; injury, brain, traumatic; rehabilitation