Neuroimaging and Neurovision Rehabilitation of Oculomotor Dysfunction in Mild Traumatic Brain Injury

The primary objectives are: 1) To localize changes following mild traumatic brain injury
(mTBI) in subjects with vision dysfunction using functional magnetic resonance imaging (fMRI)
and diffusion tensor imaging (DTI). 2) To demonstrate the effectiveness of neuro vision
rehabilitation (NVR) on vision dysfunction initiated within nine months following mTBI by
normalizing objective visual measurements as well as changes on fMRI and DTI.

Mild (TBI) comprises 80% of the 3.65 million brain injuries in the United States and costs an
estimated 17 billion dollars annually. Mild TBI is a challenging diagnosis and can be as
disabling as a severe TBI when chronic symptoms develop. In the past several years,
researchers have found that a somewhat silent majority of mTBI patients who develop lasting
symptoms have concurrent vision dysfunction. This cohort of patients with post-traumatic
visual difficulty, regardless of mechanism of injury, seem to demonstrate more significant
and lasting disability and poorer overall outcome than other TBI cohorts, yet these
correlations have not been adequately studied. The studies that have been performed have
found that visual dysfunctions may not spontaneously improve and become chronic in absence of
direct diagnosis and treatment. Time after injury has been shown in studies to have no
influence on incidence or frequency of visual difficulties but once identified, these
pervasive visual dysfunctions significantly improve in response to interventions such as
prescription glasses and NVR.

For the past 16 months, the Center for Magnetic Resonance Research (CMRR) at the University
of Minnesota (U of M) and the TBI Center at the Hennepin County Medical Center (HCMC) have
closely collaborated in a pilot study. The goal of this study was to identify the location in
the brain of post traumatic visual changes in acute mTBI subjects (< 9 months from injury
date, ages 18-55) using resting state and task fMRI and DTI. Mild TBI subjects who had vision
dysfunction (vision group) were compared to mTBI subjects who did not have any vision
difficulties (controls). Task fMRI imaging demonstrated significant decreased brain activity
in the vision dysfunction subjects as compared to the controls in certain key vision areas.
Diffusion tensor imaging showed significant changes in certain areas of the corpus callosum.

This trial is designed as a longitudinal clinical study. Fifteen mTBI patients with vision
dysfunction (vision group) fitting the inclusion/exclusion criteria and 15 patients with mTBI
but with no findings on the visual screen (control group) within 9 months of their injury
will be included in the study. No subject will be excluded on the basis of sex/gender, race
or ethnicity. These mTBI subjects will initially be identified by physicians in the HCMC TBI
Clinic. If agreeable, consent will be obtained at both HCMC as well as prior to their
baseline MRI scans at CMRR. The subjects will then undergo objective testing by a specialized
eye doctor at HCMC to confirm if they do or do not have vision dysfunction related to the
mTBI. At CMRR, within 2 weeks of the visual testing, the whole brain will be imaged using
resting state and task fMRI and DTI using a 3T MRI machine. The subjects will then receive
neurovision rehabilitation for approximately 3 months at HCMC if they are in the vision
group. This treatment is standard care for this population. Both groups will then undergo
repeat objective vision testing by the specialized eye doctor at 3 and 6 months to confirm
that vision dysfunction has resolved. Resting state and task fMRI and DTI will be done at the
same time to compare functional and structural connectivity changes between the 2 groups.

Mild TBI is a significant cause of disability especially when symptoms become chronic. In
HCMC's clinical experience, this chronicity is often linked to vision difficulties. Vision
dysfunction will continue until properly identified and treated, especially with neuro vision
rehabilitation. The goals of this research study are to better understand cerebral structural
and metabolic changes associated with as well as the effectiveness of neuro vision
rehabilitation on post traumatic vision dysfunction by utilizing resting state and task fMRI
and DTI. A positive outcome will have a significant impact on the diagnosis and care of the
considerable numbers of mTBI patients suffering from vision dysfunction, especially because
neurovision rehabilitation will be more utilized by the medical community. In turn, the
overall functional outcomes after mTBI will improve, greatly relieving the suffering and
disability for these patients.

Inclusion Criteria:

- Mild TBI (GCS score > 13), Post Traumatic Amnesia < 24 hours, no brain CT findings

- Diagnosed with vision dysfunction by developmental optometrist

- Age equal to or > 16 years- 55 years.

- Injury between 1 - 9 months

- Informed consent obtained

Exclusion Criteria:

- Any type of bio-implant activated by mechanical, electronic, or magnetic means

- Any type of ferromagnetic bio-implant that could potentially be displaced

- Pregnant females

- Significant anxiety and/or claustrophobia

- Subjects who cannot adhere to the experimental protocol

- Brain tumor or stroke or severe traumatic brain injury or history of severe mental
retardation

- Any chemotherapy, immunomodulatory agents, or radiation treatment affecting the brain

- Two or more seizures, or been given a diagnosis of epilepsy

- Known ocular problems including orbital fractures, monocular vision, strabismus, -
Lasik surgery for monofixation, cataracts with visual acuity > 20/40

- History of intractable migraines

- History of major psychiatric disorder

- Taking medications which interfere with visual process

- Taking illicit drugs such as marijuana, cocaine, heroin, etc

- Age < 16 and > 55 years

- GCS score < 13

- Current TBI or still symptomatic from prior mTBI > 9 months

- Any vision rehabilitation

- Near point convergence > 70 cm or sustained diplopia

- Cranial nerve II, III, IV, or VI palsy

- Any findings on clinical brain CT or MRI

- Any subject with a professional or academic link to the PI