RHI Interval Effects on Brain Health

The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically NF-L (neurofilament light).

The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically GFAP (glial fibrillary acidic protein; nanograms per milliliter).

The primary outcome analyses will be comparing group differences (group x time interactions) in blood biomarkers, specifically phosphorylated tau (picogram per milliliter).

Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be macula CSF thickness (an indicator of the gain or loss of neurons or glia in the inner nuclear, ganglion cell and nerve fiber layer). Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus.

Retinal neural structure will be imaged in one or both eyes using high-definition spectral domain OCT, which will be acquired using a Zeiss Cirrus OCT scanner. The primary OCT variables examined will be cup-to-disc ratio (an indicator of neurodegeneration at the optic disc).

Retinal vascular structure will be acquired using the OCT angiography (OCT/A) capability of the Cirrus. The primary OCT/A variable examined will be foveal avascular zone (FAZ) area reflecting the size of the central portion of the macula which contains no blood vessels, and which increases in size with loss of capillaries in the surrounding region).

An Investigational version of the BrainScope FDA-cleared qEEG acquisition device will be used in this study. The investigational nature of the device is simply based on the code which does not produce a diagnostic result for the blinded researcher. Thus, the manufacturer's full device indications/labeling document will be the same as the FDA-cleared version. An eyes-closed resting EEG will be recorded. An FDA cleared multivariate EEG marker of concussion, the Concussion Index (CI) will be used as input for this study modeling. The CI includes measures of power (absolute and relative), mean frequency, connectivity (asymmetry, coherence, phase lag, phase synchrony), complexity (fractal dimension and scale-free activity), and information theory (entropy), across and within frequency bands. Other features of interest will be included in the EEG data set. We will use all variables in a single model to analyze which variable, to what extent, contributed to group differences.

NPC will also be assessed on the BrainScope qEEG device. The automatic NPC measurement is administered in the same manner as the manual NPC test and takes less than a minute to perform. The participant focuses on the target at arm's length and slowly brings it toward the tip of their nose. The participant is instructed to stop moving the target when they see two distinct images or when the examiner observes an outward deviation of one eye. Blurring of the image is ignored. The distance between the target and the tip of the participant's nose is recorded in centimeters (cm), digitally and accurately computed by the BrainScope automated ocular function measurement (AOFM) feature.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Initial pupil diameter (maximum) is one of our outcomes.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Ending diameter (minimum) is another outcome.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Latency (time of onset of constriction following light stimulus) is one of our outcomes.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Constriction velocity (average) is one of our outcomes.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Maximum constriction velocity (average) is one of our outcomes.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. Dilation velocity (average) velocity (average) is one of our outcomes.

Pupillary Size Measurement and reactivity will be measured in one or both eyes using the NeurOptics PLR-4000 pupillometer device. The eye cup of the hand-held optical scanner system is placed over the participant's eye at a right angle to their axis of vision while the user uses a touchscreen to center the participant's pupil. Once centered, the user initiates the protocol by push-button, and light pulses of 121 uW intensity and 0.80 s duration are used to stimulate pupil reflex and dilation over approximately 6 seconds. T75 (time to reach 75% of original pupil baseline after peak constriction) is one of our outcomes.

CRT will also be assessed on the BrainScope qEEG device. CRT task includes a rule-based response instruction where the participant presses the right key for one set of numbers and the left key for the other set. Participants are instructed to respond quickly and accurately.