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The purpose of this study is to examine the combined effects of hypoxia and a short bout of subconcussive head impacts on neurocognitive and ocular-motor function and plasma expression of brain-derived blood biomarkers.
The purpose of the pilot study is to observe preliminary trends in neural response to subconcussive head impacts in hypoxic condition. This work will provide a critical un-tested knowledge regarding the combined effects of subconcussion and hypoxic condition (mimicking high altitude), which will be used in our upcoming grant proposal to the Department of Defense (DoD). Military personnel, particularly those who are deployed to Afghanistan, are constantly subjected to hypoxic condition, given that the majority of military land operations in Afghanistan occur at 2000-3000 meters (6500-10,000 feet). This level of altitude does not elicit major side effects, yet neural functions may experience some degree of perturbation (i.e., slowed reaction time, altered night vision). Concurrently, these military personnel, who operate at high altitudes, often incur subconcussive forces to the head. These subconcussive head impacts can be induced by exposure to, for example, flash-bang grenades, artillery fire, recoilless rifle, improvised explosive devices (IEDs), and head collision. The combined effects of these two stressors have the potential to attenuate one's readiness, operational efficiency, and overall brain function, but the combined effects have never been studied to date. As a result, one of four study topics that the Defense Centers of Excellence deems urgent is: Document the effects of altitude exposure on mild traumatic brain injury (mTBI) and blast-induced neurotrauma (BINT). To answer the question, we hypothesized that there will be an exponential worsening in neurocognitive function and in ocular-motor system functioning, and increased plasma expression of brain-derived biomarkers, after subconcussive head impacts under hypoxic conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normobaric Hypoxia | Experimental | Large weather balloons will be filled with a normobaric hypoxic inspirate (FiO2 = 0.15) produced by a nitrogen generator (CAT 12; Colorado Altitude Training, Boulder, CO) to simulate an altitude of 2600 m (8500 ft). Participants breathed this inspirate through a two-way non-rebreathing valve (2700; Hans Rudolph, Kansas City, KS) and an oronasal mask (7450 V2; Hans Rudolph, Kansas City, KS). Participants breathed this inspirate from 15 minutes before the pre-heading time point until the conclusion of the 0h post-heading time point. |
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| Normobaric Normoxia | Placebo Comparator | Large weather balloons will be filled with room air (FiO2 = 0.21). Participants breathed this normobaric normoxic inspirate through a two-way non-rebreathing valve (2700; Hans Rudolph, Kansas City, KS) and an oronasal mask (7450 V2; Hans Rudolph, Kansas City, KS). Participants breathed this inspirate from 15 minutes before the pre-heading time point until the conclusion of the 0h post-heading time point. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Soccer heading | Behavioral | A standardized and reliable soccer heading protocol will be used to induce subconcussive impacts for the experiment. A triaxial accelerometer (Triax Technologies, Norwalk, CT) embedded in a head-band pocket and positioned back of the head to monitor linear and rotational head accelerations. A JUGS soccer machine (JUGS Sports, Tualatin, OR) will be used to simulate a soccer throw-in with a standardized ball speed of 25 mph across all groups. The ball speed is similar to when soccer players make a long throw-in from the sideline to mid-field. Soccer players frequently perform this maneuver during practices and games. Participants will stand approximately 40ft away from the machine to perform the heading. Participants will perform a total of 10 headers at a rate of 1 header per minute and will be instructed to direct the ball back towards the JUGS machine. Previous uses of this soccer heading model have reported an average peak linear acceleration per header of 14.5 to 33.5 g. |
| Measure | Description | Time Frame |
|---|---|---|
| Acute change in neurocognitive function from pre-heading at 0 hour post-heading | Participants will complete a computerized neurocognitive assessment (Immediate Post-Concussion Assessment and Cognitive Testing). | Neurocognitive function will be assessed at pre- and 0 hour post-heading |
| Acute change in convergence function from pre-heading at 0 hour post-heading | Participants will undergo near-point of convergence (in centimeter) to evaluate how closely one can visualize a moving target without double vision occurs. | Conversion function will be assessed at pre- and 0 hour post-heading |
| Acute change in brain-derived blood biomarkers from pre-heading at 0 hour post-heading | Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Plasma will be aliquoted and stored at -80 degree celsius until analysis. Plasma samples will be assayed for neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and tau. | Blood samples will be collected at pre- and 0 hour post-heading |
| Measure | Description | Time Frame |
|---|---|---|
| Change in neurocognitive function at 24 hours post-heading follow-up | Upon their return to the laboratory, participants will again complete a computerized neurocognitive assessment (Immediate Post-Concussion Assessment and Cognitive Testing). | Neurocognitive function will also assessed at 24 hours post-heading |
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Inclusion Criteria:
Exclusion Criteria:
Conditional Exclusion Criteria
Based on participants' self report: those who meet any of the following criteria, he/she will be either excluded or rescheduled (if they still wish to participate in the study):
As a part of the neurocognitive assessment, participants self-select one of the gender options from a list.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University | Bloomington | Indiana | 47405 | United States |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| D000860 | Hypoxia |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Change in ocular-motor function at 24 hours post-heading follow-up |
Upon their return to the laboratory, participants will again undergo three ocular-motor assessments: 1) near-point of convergence; 2) King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing; and 3) the EYE-SYNC smooth pursuit task. |
| Ocular-motor function will also assessed at 24 hours post-heading |
| Change in brain-derived blood biomarkers at 24 hours post-heading follow-up | Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Plasma will be aliquoted and stored at -80 degree celsius until analysis. Plasma samples will be assayed for neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and tau. | A third blood sample will be collected at 24 hours post-heading |
| Acute change in saccadic eye movement function from pre-heading at 0 and 24 hour post-heading | Participants will undergo King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing | Saccadic eye movement function will be assessed at pre- , 0, and 24 hour post-heading |
| Acute change in smooth eye pursuit function from pre-heading at 0 and 24 hour post-heading | Participants will undergo the EYE-SYNC smooth pursuit task. | Smooth eye pursuit function will be assessed at pre- , 0, and 24 hour post-heading |
| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |