High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for Sensory Deficits in Complex Traumatic Brain Injury

Experimental Design and Methods Participants: 120 subjects will be recruited for this study,
40 healthy controls subjects for an imaging-only group, and 80 mTBI subjects for the
stimulation arm who have suffered injury at least 3 months prior to study enrollment, but not
more than 15 years prior to enrollment. All participants will be 18-59 years of age.

Recruitment: Human participants (ages 18-59) will be invited to come to the University of New
Mexico (UNM) to ask questions prior to providing consent. They will be provided with consent
forms that describe the study procedures and potential risks.

Once informed consent is obtained and the appropriate forms signed, the participant will be
assigned a unique research subject identifier (URSI) number, and from that point forward all
research data will only be labeled with the URSI number. The key linking identifiers of
participants to the URSI will be maintained on a separate database that will be stored behind
locked doors, in a locked filing cabinet in a secure area. All participants may then undergo
demographic data collection, neuropsychological assessments sensory evaluation, at UNM. They
may also undergo MEG and MRI at the Mind Research Network (MRN), located in the same
building.

Demographic Data: As part of the initial assessment, basic demographic data regarding the
subject may be noted down, including age, gender, socioeconomic status, educational
attainment, handedness, use of common stimulants such as caffeine, and brain injury severity.
They may also be asked if they are willing to allow their medical record to be accessed, for
the purposes of confirming details about any traumatic brain injury (TBI) as well as
obtaining results of neuroimaging studies done at the time of injury or afterward. This will
include medical, surgical, neurological and psychiatric history, results of lab tests, brain
scans, electroencephalography tests, medication lists, information from doctor's visits and
hospital visits.

Neuropsychological testing procedures: All neuropsychological testing will be administered in
the Center for Brain Recovery and Repair Core by trained study personnel under direct
supervision of core directors. The following domains and tests will be administered:
Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research
(Examiner); Digit Span; Delis-Kaplan Executive Function Systems (DKEFS) Trail-making Test
Conditions 2 and 4; Hopkins Verbal Learning Test (HVLT); Frontal Systems Behavior Scale
(FrSBe); Test of Memory Malingering (TOMM); Wechsler Test of Adult Reading (WTAR); Digit
Symbol Coding; Handedness; Socioeconomic Status (SES); Patient's Global Impression of Change
(PGIC); Glasgow Outcome Scale-Extended (GOSE).

Sensory Assessment: Hearing, balance, and vision will be assessed using Common Data Element
(CDE) instruments, including the Hearing Handicap Assessment, the Test for Visual Discomfort,
the modified Balance Error Scoring System. Oculomotor control will be assessed using virtual
reality goggles (Oculus) with implanted eye trackers (iScan).

Magnetoencephalography: Magnetoencephalography (MEG) may be done after neuropsychological
testing. The participant will sit in the MEG scanner to record brain magnetic fields. MEG
setup takes between 10 and 30 minutes, and subsequent recording takes one hour. During MEG
assessments participants will complete numerous tasks. Each task is designed to parse
different cognitive mechanisms that contribute to sensory performance. In perceptual tasks,
participants will discriminate tone pitches amongst novel distracting tones (Auditory
Orienting Task; AOT). For eye movement tasks, participants are asked look either towards or
away from a visual stimulus (Pro- and Anti-saccades).

Magnetic resonance imaging (MRI): MRI scan(s) will be obtained for integration with MEG, as
needed for analyses. Total scan time, including participant setup and removal, is expected to
take 1 hour. Participants may lie down on a table and be placed into a long donut-shaped
magnet. During the scan, participants will be asked to rest quietly or to fixate on a dot on
a screen in front of them, or to perform a memory task. No contrast will be used. Any female
over 18 who thinks she may be pregnant will complete a urine pregnancy screen before the MRI
scan.

Following initial testing, the participants in the stimulation arm of the study will receive
10 consecutive weekday sessions of high-definition transcranial direct current stimulation at
New Mexico Veterans Affairs Health Care System (NMVAHCS). 2 milliamperes active or sham
anodal current will be delivered to the left dorsolateral prefrontal cortex for 30 minutes.
During this time, participants will perform vision therapy tasks through a virtual reality
headset, or a computer-based working memory task. Skin sensations will be assessed every 10
minutes.

Post stimulation testing: the next available weekday following completion of the study
protocol at the NMVAHCS, subjects will return to UNM to repeat the demographic,
neuropsychological, sensory, and imaging assessments.

Long term followup: At 1 month, 3 months and 6 months after stimulation, subjects will be
contacted via telephone and administered the Beck Depression Inventory (BDI-II),
Posttraumatic Stress Disorder Checklist-Military (PCL-M), the Neurobehavioral Symptom
Inventory (NSI), and Patient Global Impression of Change (PGIC) quality of life assessment
tools utilized before and immediately after, after stimulation.

Inclusion Criteria:

1. are US Veteran or Active Duty Military personnel aged 18-59,

2. have suffered a mild TBI (alteration in neurological functioning < 24 hours, loss of
consciousness (LOC) less than 30 minutes, Glasgow coma scale (GCS) score (if
available) of between 13 and 15 acutely, and less than 24 hours of post-traumatic
amnesia (PTA));

3. were injured between 3 months and 15 years ago;

4. have post-traumatic sensory symptoms as evidenced by endorsing at least 2 out of 12
sensory symptoms on the Neurobehavioral Symptom Inventory (NSI), a measure of
post-traumatic symptoms from the NIH Common Data Elements (CDE) to a severity of "3"
or higher,

5. are fluent in English,

6. have been on stable doses of any psychotropic medications for the past 2 months.

7. The imaging-only group will have the same inclusion and exclusion criteria except they
will not have had a head injury.

Exclusion Criteria:

1. any history of moderate or severe TBI;

2. a prior history of other neurological disease or any history of seizures beyond
immediate post-traumatic seizure, to as to reduce risk of exacerbation of epilepsy or
other neurological symptoms;

3. history of psychosis, so as to reduce risk of psychiatric decompensation;

4. history of current or recent (within two years) substance/alcohol dependence, to
reduce confounding effects on cognition and plasticity;

5. any discontinuity in skull electrical conductivity (i.e., unhealed burr holes in
scalp) or artificially constructed (metal or plastic) craniotomy cover, to reduce risk
of unimpeded electrical current;

6. presence of any implanted electrical device (e.g. pacemaker), to reduce risk of device
malfunction;

7. recent medical hospitalization (within three weeks), to reduce risk of medical
decompensation during the study;

8. any condition that would prevent the subject from completing the protocol; 9)
appointment of a legal representative, as assessed via direct inquiry of the subject
and a designated trusted other, to avoid coercion of a vulnerable population;

10) any significant blindness, to screen out peripheral sensory damage; 11) any significant
deafness beyond mild hearing loss, to screen out peripheral sensory damage; 12) any ongoing
litigation related to TBI, to prevent interference with legal proceedings; 13) any
contraindication to MRI; 14) membership in an identified vulnerable population, including
minors, pregnant women, and prisoners, so as to prevent coercion.