Mild TBI Assessment & Rehabilitation

Combat-related mild traumatic brain injury (mTBI) and co-morbid conditions are prevalent in
returning Veterans with the reported rates ranging from 14- 22%. Chronic sequela of mTBI can
be highly debilitating due to deficits in the cognitive control processes, including
attention, executive functions, and memory. In prior studies, individuals with chronic
acquired brain injury who participated in a cognitive training program, Goal-Oriented
Attentional Self-Regulation (GOALS), which targets executive control functions of applied
mindfulness-based attention regulation and goal management, improved cognitive performance in
areas of: complex attention/executive function and memory, complex functional task
performance, and daily functioning. Furthermore, functional MRI (fMRI) results after training
indicated significantly enhanced modulation of neural processing. Preliminary data from
recently completed randomized-control GOALS study in 32 Veterans with chronic TBI also show
both short and longer term (up to 2 years) improvements in attention and executive function,
complex real-life tasks, and emotional regulation.

The primary objectives of this study are to investigate the potential short and longer term
effects of GOALS cognitive training program, and to use advanced MRI to investigate changes
in brain structure and function in the circuits that regulate attention, memory, executive
function and emotion in Veterans with chronic mTBI.

The investigators postulate that 1) GOALS training will improve neurocognitive function in
attention and executive function domains, complex functional task performance, and emotional
regulation in Veterans with chronic mTBI; 2) improved neurocognitive function will be
correlated with macrostructural, microstructural and functional changes in the corresponding
brain networks on high field (3T) and ultra-high field (7T) structural MR imaging, diffusion
tensor imaging (DTI) and resting state fMRI performed pre- and post-training; 3) Changes in
both behavioral function and imaging measures will be maintained at 6 months post-training
and be associated with improvements in activities and participation.

AIM 1: To determine the short and long term effects of GOALS training on neuro-cognitive
performance and neural plasticity of attention and executive control networks in mTBI.

AIM 2: To determine the short and long term effects of GOALS training on complex functional
task performance and daily functioning, and on plasticity in pathways related to memory
function, in mTBI.

AIM 3: To determine the short and long term effects of GOALS training on measures of
emotional regulation, and on plasticity of frontolimbic networks related to emotion
processing, in mTBI In a randomized, controlled interventional study design, 36 Veterans with
a history of chronic (> 6 month) mTBI and residual cognitive difficulties will be randomized
to participate in 5 weeks of cognitive training (GOALS) or a treatment as usual (TAU)
comparison. At baseline, week 5 (post GOALS), and at 6 months, participants will undergo a
multi-level assessment battery consisting of: 1) neuroimaging with high field (3T) and
ultra-high field (7T) structural MR imaging, diffusion tensor imaging (DTI) and resting state
fMRI; 2) neuropsychological assessment focusing on complex attention and executive function;
3) complex 'real life' functional task performance; and 4) self-report measures of daily
functioning and emotional regulation/heath.

When completed, this project will determine whether training core attentional self-regulatory
control functions via personally-relevant activities will be effective in improving quality
of life and daily functioning for Veterans with mTBI. The study design will provide a test of
potential benefits on real-life functioning, and also determine to what extent these benefits
are related to actual changes in hypothetically targeted cognitive/behavioral functions and
brain networks corresponding to these functions.

Inclusion Criteria:

- A history of mild TBI (as defined by DOD / VA; confirmed by medical records and in
person Ohio State University TBI Instrument)

- Chronic, stable phase of recovery (>6 months from last post-concussive event)

- Report of residual cognitive difficulties

- 1 moderate or severe cognitive symptom(s) on the Neurobehavioral Symptom
Inventory (NSI) that interfere(s) with daily function

- Able and willing to commit to participate in training and assessments

- On stable psychoactive medications (> 30 days)

Exclusion Criteria:

- A history of moderate or severe TBI

- Unstable medical, neurologic, or psychiatric condition, including severe cognitive
dysfunction, or other reasons for being unable or unwilling to participate in study
procedures

- (e.g., contraindications to MRI)

- Ongoing illicit drug or alcohol abuse (AUDIT>8)

- Psychosis

- Severe depression, anxiety or PTSD precluding participation in research activities

- Poor English comprehension

- Eligible participants may have other co-morbid stable neuropsychiatric disorders,
including depression and PTSD

- There will be no restriction in regard to gender, race and socioeconomic status