Osteopathic Manipulative Treatment RCT and Computational Modeling for Head Injuries in Mixed Martial Artists

Investigating the benefits of osteopathic manipulative medicine (OMM) on head injury has the potential to advance the knowledge and application of osteopathy. Traumatic brain injury (TBI) including concussion, or mild traumatic brain injury (mTBI), is an injury resulting from a force directed towards the head that precedes and contributes to new onset symptoms and/or impairments in cognitive neuropsychology without discrete lesions detectable by traditional imaging. Its annual financial burden in the United States (USA) is $1.4-3.8 million, and there are limited treatments. Current practice guidelines (CPG) recommend rest with gradual return-to-play. Mixed martial artists (MMA) often sustain head injuries during fights or sparring matches, and they experience changes in cognitive neuropsychological testing. Faster recovery from symptoms and in visual memory and reaction time were found after OMM in a randomized controlled trial (RCT) in college athletes with acute uncomplicated concussions utilizing the same OMM methods in this proposal for use in MMA. This OMM sequence was previously outlined by the P.I. in 2016. The OMM treatment sequence addresses structural restrictions throughout the whole body, including improving glymphatic and venous circulation of the brain to allow for self-regulation, self-healing, and health maintenance. The purpose of this study is to test if OMM significantly improves symptoms and cognitive recovery after head injury during mixed martial arts (MMA) fights compared to a sham control group. Hypothesis: Participants with concussion during an MMA fight have significantly better recovery in neuropsychological tests and symptoms after receiving three OMM treatments compared to those receiving three Sham-Light touch control sessions over 1-week.

Aim 1: Determine if there is significant improvement in head injury-related impairments on ImPACT and Inquisit Web measures in individuals after three OMM sessions compared to three Sham-Light touch Aim 2: Determine if Pre-fight to Post-fight changes in cranial strain patterns are significantly correlated with ImPACT or Inquisit Web changes in individuals with head injuries during a recorded fight.

Aim 3: Test for significant associations between cranial strain patterns, forces causing injury, neuropsychologicalmeasures, and brain region impacted upon coup-contrecoup of the brain. Eligible, consented participants of any gender will be recruited for Part-1 of this study, which is an observation study of head injury dynamics and epidemiology; it doesn't include an intervention. Participants with concussion symptoms due to head injury during MMA fights within the preceding three (3) days will continue to Part-2-Interventions and be randomized into OMM or Sham-Light-touch control groups. Pre- to Post-Injury changes on ImPACT, Inquisit Web, and cranial strain patterns will be tested for significant correlations with the brain area impacted upon contrecoup according to the computational model. Post-Injury changes and Post-interventions tests will be compared utilizing a generalized linear model (GLM) by NYITCOM biostatistician.

Main study outcome measures:

1. The detailed physical examination for performing OMM is referred to as the osteopathic structural exam (OSE) for somatic dysfunctions, and OMM involves non-invasive manual treatments of the somatic dysfunctions to improve physiologic function. The OSE can reveal potential cranial somatic dysfunctions after concussion. Examining the cranium for somatic dysfunctions involves assessing sphenobasilar synchondrosis (SBS) biomechanics. The physiologic SBS somatic dysfunctions, sidebending rotation (SBR) or torsion patterns, are common and can happen organically. Sidebending of SBS somatic dysfunctions occurs around two vertical axes with rotation around an anteroposterior axis. Torsion occurs around an anteroposterior axis as well.

Conversely, nonphysiologic SBS somatic dysfunctions include vertical or lateral shears and/or compression patterns, which are less common. Lateral shears occur around two vertical axes, whereas vertical shears occur around two transverse axes. Research suggests that nonphysiologic somatic dysfunctions typically result from physical trauma and rarely resolve on their own. 2. Computational CSF dynamics 3. ImPACT : The computerized ImPACT measures visual memory (Visual), verbal memory (Verbal), visual-motor processing speed (PS), reaction time (RT), impulse control (IC), and patient-rating of symptom severity (SS). It's a well-established, validated tool widely utilized for measuring cognitive function following concussion injury. The ImPACT had 81.9% sensitivity and 89.4% specificity in detecting concussion-related new onset impairments (NOI) when administered during the pre-participation sports physical to establish Baseline, and, again, after sustaining a concussion (Post-Injury), compared to normalized, validated age-gender-matched demographic data. The demographic data section of ImPACT includes relevant sport, medical, and concussion history information.

The Inquisit Web (Millisecond Software LLC, Seattle, WA, USA) is another computer-based platform that allows for the administration of neuropsychological tests specifically for acute changes in information processing speed, inhibition, and visual and verbal learning memory tasks with a delayed memory recall. 4. Oxytocin ELISA

Inclusion criteria:

Part 1-head injury dynamics:

* (1) individuals participating in MMA fights or sparring matches, * (2) 18 to 50 years of age, * (3) able to complete online cognitive neuropsychology tests.

Part-2-Intervention:

\- (1) having a witnessed closed head injury during a fight exclusion criteria.

Part 1-head injury dynamics:

* (1) having a current or previous spinal cord injury, * (2) head injury within past six months, * (3) being unable to complete the assessment, * (4) been diagnosed with underlying neurodegenerative condition, * (5) pre-existing hypopituitary function, * (6) Pregnancy.

Part-2-Intervention:

* (1) has absolute contraindications to OMM (e.g. skull fracture, cervical spine fracture, signs of intracranial bleeding or increased intracranial pressure, cervical dissection, space occupying lesion in the cranium, or stroke), * (2) suffered a witnessed loss of consciousness (LOC) for greater than 2 minutes, seizures, intractable vomiting or paralysis at the time of the head injury.

Participants won't be referred to their private doctors for additional pituitary hormone testing unless there are clinical signs. The optional referral for growth hormone and other pituitary testing by glucagon stimulation Test at Quest labs will be contraindicated if there is risk of and/or a history of (1) cardiovascular (heart) disease, (2) disease of the blood vessel in your brain, or (3) seizures.

The investigators measuring cognitive neuropsychology and computational modeling will be blinded to grouping, and the investigators performing the OSE will be blinded to each others' diagnoses as well as the other outcome measures. If there are any concerns for health identified on cognitive neuropsychology testing, Dr. Amber Sousa, Ph.D is a clinical neuropsychologist who can direct participants for appropriate care.

Eligible, consented participants of any gender will be recruited for Part-1 of this study, which is an observation study of head injury dynamics and epidemiology; it doesn't include an intervention. Participants with concussion symptoms due to head injury during MMA fights within the preceding three (3) days will continue to Part-2-Interventions and be randomized into OMM or Sham-Light-touch control groups. Pre- to Post-Injury changes on ImPACT, Inquisit Web, and cranial strain patterns will be tested for significant correlations with the brain area impacted upon contrecoup according to the computational model. Post-Injury changes and Post-interventions tests will be compared utilizing a generalized linear model (GLM) by NYITCOM biostatistician.

Computerized cognitive neuropsychological tests:

The ImPACT is a widely used test that will be administered to athletes 12 years of age or older before sports to establish a baseline of cognitive function, and administered again with the suspicion of a brain injury to evaluate differences in cognitive function. ImPACT has been shown to be an effective adjunctive test for evaluation of concussion as part of a comprehensive medical diagnosis involving other testing methods. The positive predictive value (PPV-probability that a concussion is present when the test is positive) is 89.4% and the negative predictive value (NPV-probability that a concussion is not present when the test is negative) is 81.9% (Schatz 2006). ImPACT is a 25-minute online test to be administered through a secure web portal by a licensed healthcare provider. ImPACT will be administered via a link on a computer in a quiet office room according to the ImPACT guidelines, through the P.I.'s login. A new profile will be created for each participant by their study-participant#.

Participants will take a 4 hour break after ImPACT to minimize computer-use stress both pre- and post-fight for more consistent data. If a participant's IC index is elevated on the baseline testing, the participant will be asked to retest, and test-retest reliability computation will be done.

Lower reliability estimates (lower ICCs) were observed in a study utilizing the more stringent validity criteria of IC composites greater than 20 (Resch et al., 2013). The main aim of the IC index is Response Inhibition or Delay (Schatz 2006), however, the IC has been reported to be high at baseline due to a several factors. These include 'sandbagging' (purposing getting lower baseline score to avoid seeming like having a concussion Post-injury), Left-Right confusion, trouble with sleep, and oculomotor disorders (IC\>20) (Brett et al 2016, Schatz 2006, Mancini 2022). Re-testing for reliability has been found useful in previous research publications.

Then, participants will complete cognitive testing via the Inquisit Web (Millisecond Software LLC, Seattle, WA, USA) platform. This platform is a computer-based platform that allows for the administration of neuropsychological tests specifically for acute changes in information processing speed, inhibition, and word learning tasks with a delayed-recall. Measures from the platform that will be included are the Paced Auditory Serial Addition Test (PASAT) (8 min.), Continuous Performance test (20 min.), and Rey Visual Design Learning Test (15 min.). Participants will take a 5 min. break between tests. The PASAT is a measure of information processing speed in which participants listen to a string of digits and mentally sum the last two. The Continuous Performance Test is a test of sustained and selective attention. The Verbal Selective Reminding test is a 12- list word learning task with a delay recall condition. The Rey Visual Design Learning Test assesses visual memory. The total testing time is expected to be 69 minutes with break-time.

Inquisit Millisecond Measures Paced Auditory Serial Addition Test (PASAT) - 8 min. script implements a computerized version of the Paced Auditory Serial Addition Test (PASAT), a measure of information processing rate. Participants hear a sequence of single digit numbers (1-9) presented at a constant speed and are asked to mentally sum the last 2 digits (NOT a running total). Participants then select the current sum from a circle of numbers 1-18 (= nonverbal response) The implemented procedure is based on Gronwall, D. 1977.

Continuous Performance Test- 20 min. is for sustained and selective attention. Participants get presented a sequence of letters (one-by-one). Task1: press the Spacebar whenever the letter is an X Task2: press the Spacebar whenever the letter is an X that follows an A. Rosvold, et al. 1956. Rey Visual Design Learning Test- 15 min. (RVDLT) is an assessment too

• ImPACT and Inquisit Web cognitive neuropsychology tests [Срок оценки: 1 year]