Test and Evaluation of Non-Invasive Neuro-Assessment Devices (NINAD: Neurokinetics, Inc, iPAS

Traumatic brain injury is not only a significant medical and operational issue for the
military but is a significant public health issue in the United States. The CDC reports that
1.4 million Americans sustain traumatic brain injuries each year. Of these 50,000 die,
235,000 are hospitalized and 1.1 million are treated and released from the emergency
department. Among children fourteen years old and younger, there are an estimated 2685 TBI
deaths per year, 37,000 hospitalizations and 435,000 emergency room visits.

Additionally, the Centers for Disease Control (CDC) also notes that TBI is significantly
under-reported.

Traumatic brain injury is under detected. Neuropsychological evaluations are often
nondisclosing The DoD has invested considerable funds in the development of devices for use
in acute and chronic assessment of TBI. Unfortunately none of these devices have been tested
systematically to establish reliability of the equipment, reliability of the signals
obtained, or reliability of the measures derived from the signals obtained.

The NeuroKinetics i-PAS system is a mobile assessment device with an integrated display for
eye tracking with the following properties: a head mounted display, a sampling rate of 100
frames per second, eye tracking in the horizontal, vertical and torsional axes, and pupil
area measurement with a spatial resolution less than 0.1 o. The testing protocol includes:
optokinetic tracking, smooth pursuit horizontal, smooth pursuit vertical, saccade random
horizontal, saccade random vertical, saccade predictive horizontal, antisaccade (horizontal),
self-paced saccade, saccade and reaction times, visual reaction time, auditory reaction time,
gaze horizontal, light reflex, subjective visual (vertical) and subjective vertical
horizontal. Several quantitative measures are computed from the data acquired in each test,
and these measures are then employed in a multivariate diagnostic assessment.

It is important to distinguish between a device, a signal and a measure. As used here, the
term device refers to a hardware technology used to obtain a signal. In the case of
neurodiagnostic devices, the signal is usually a measurement of voltage as a function of
time. Examples of signals pertinent to the present discussion include the electrocardiogram
(providing an assessment of autonomic nervous system status), the electroencephalogram,
evoked potentials, event related potentials, balance records and eye movement trajectories. A
clear distinction must be drawn between a signal, typically a voltage record, and a measure
which is a number that is computed from the voltage signal. Reliability and validity must be
investigated separately for each measure For example, a dozen measures may be calculated from
the same EEG voltage signal. The reliability and validity of each measure must be evaluated.

The objectives of this initial study are limited. The investigators address the question: are
the measures obtained from the NeuroKinetics iPAS eye tracking system longitudinally stable
in a clinically stable healthy participant? These measures are described in a subsequent
section.

A single channel ECG will be acquired and measures of heart rate variability will be
calculated from this signal. Measures of heart rate variability provide an indirect surrogate
measure of complex multifactorial states that can have an impact on psychophysiological
variables. Alterations of heart rate variability (HRV) are associated with pain, attention
and cognitive function and fatigue, all of which can affect neurophysiological measures. High
intra-individual variability in a test-retest study is a warning sign that between recording
changes in the state of the participant rather than reliability failures in the eye tracking
measure may be playing a role in low reliability.

Following consent, eligibility will be established based on head injury history, the score on
the Symptom Checklist 90 (in the Supporting Documents file), the Short Form 36 (in the
Supporting Documents file), and the Defense Veterans Brain Injury Center (DVBIC) Three
Question Screening Tool.

The standard iPAS eye tracking evaluation as described below will be administered and the ECG
will be recorded simultaneously during this process.

A second recording will be obtained within two to six days of the first recording.

A third recording will be obtained at approximately four weeks following the first recording.

This study will establish normal values of neuroassessment measures obtained from healthy
controls and will be used to establish the statistical separation between healthy populations
and clinical populations presenting neuropsychiatric disorders including TBI-positive
patients.

Inclusion Criteria:

- Male and female participants

- Between 18 and 55 years old

- In good general health. Good general health is operationalized for the purpose of this
study by scores within one standard deviation of the mean in all eight sections of the
short form 36.

- A normalized Global Severity Scale of less than or equal to 65 on the Symptom
Checklist 90-R and subscale scores less than the cut scores indicating significant
pathology.

Exclusion Criteria:

- Traumatic brain injury positive as determined by the DVBIC 3 Question Screening Tool.

- Any history of seizures or Central Nervous System (CNS) tumors

- A normalized Global Severity Scale of more than 65 on the Symptom Checklist 90-R or
any subscale score indicating significant pathology.

- Scores greater than one standard deviation from the mean on all eight sections of the
Short Form 36.