After a public outcry over the danger of the sport, the UFC adopted new rules for the safety of the athletes in 2001. The Association of Boxing Commissions and Combative Sports created the Unified Rules of Mixed Martial Arts in 2001. Since then, the rules have been amended several times, most recently in 2019 ( https://www.abcboxing.com/wp-content/uploads/2020/02/unified-rules-mma-2019.pdf ). The Unified Rules of MMA state that a fight must consist of 5-minute rounds and a 1-minute rest between rounds with no more than five rounds total. All athletes are required to wear a mouthguard during the game, thus the referee will call ‘time’ if the mouthguard becomes dislodged and needs to be replaced. Originally, MMA only prohibited biting and eye- gouging; however, the Association of Boxing Commissions and Combative Sports added additional fouls to the Unified Rules of MMA, which are delineated in Table 2.

Despite the rules in place, one of the main objectives of a fight is to knock the opponent unconscious. This is demonstrated by the types of decisions that determine the outcome of a fight, as described in the Unified Rules of MMA. The scenarios in which an athlete wins a fight include the following: technical submission (when a submission results in unconsciousness), technical knockout (TKO) by referee stoppage (when an athlete is not intelligently defending themselves, e.g., physical exhaustion), TKO by medical stoppage (includes when an athlete loses control of bodily function), and knockout (KO; when the referee stops a game because an athlete cannot intelligently defend themselves because they are unconscious). These decisions encourage strikes to the head, which can result in repetitive, subconcussive, or concussive head impacts, and eventually cause chronic traumatic encephalopathy (CTE).

A brief overview of the postconcussion protocol can be found in Table 3, and the full concussion protocol can be found in the UFC Performance Institute’s 2021 volume of research ( https://ufc-pi.webflow.io/ ). Following a fight, MMA athletes with suspected concussions should be assessed by a medical professional (McCrory et al., 2017). Concussion evaluation should include a detailed concussion history, presence of clinical symptoms and physical signs, and neurocognitive testing such as the Sport Concussion Assessment Tool-5 (SCAT5) (McCrory et al., 2017). The UFC concussion protocol states that athletes should be managed by a healthcare provider to ensure proper completion of each progression stage, and if at any point in the protocol athletes experience symptoms, they must rest and be symptom-free for at least 24 hr before returning to the stage prior to when symptoms arose.

As described above, the postconcussion protocol is fairly comprehensive, sequential, and detailed; however, it is only the first official concussion protocol of the UFC, and there is room for improvement. During stage one, the protocol requires athletes to go to the hospital if they experience ‘red-flag’ symptoms, but the red-flag symptoms are not listed on the protocol itself. It is recommended that the red-flag symptoms are detailed, so athletes can accurately identify them.

Elucidating the underlying mechanisms of head impacts that occur during MMA fights may be helpful to diagnose concussions (Karton and Hoshizaki, 2018). Concussions are difficult to diagnose because diagnoses are subjective in nature and rely on information obtained regarding signs and symptom severity, concussion history, and neurocognitive and behavioral testing (Jackson and Starling, 2019; McCrory et al., 2017); however, researchers are exploring new ways to potentially diagnose concussions. The objective of this section is to evaluate current neurocognitive and behavioral assessments that assist in concussion diagnosis, as well as explore novel diagnostic techniques such as imaging and biomarker analysis.

Many studies have examined the incidence of head strikes and concussion relationships in MMA; however, the literature reports significantly varying rates of concussions (Table 4). One study found the prevalence of concussions in MMA to be as low as 1.8% of injuries (Rainey, 2009), while another found it to be as high as 62.3% of injuries (Curran-Sills and Abedin, 2018). The study by Rainey (2009) should be interpreted carefully because injuries were self-reported and only 20.1% of MMA athletes received medical attention, thus injury rates may be underestimated. Likewise, Curran-Sills and Abedin (2018) may overestimate the rate of concussions in MMA by counting all TKOs as concussions even though a TKO does not necessarily occur due to head trauma (e.g., physical exhaustion). It was also reported that 8.3% of injuries sustained by MMA athletes were concussions, but only 4.2% of athletes lost consciousness (Karpman et al., 2016); this reinforced the knowledge that not all concussions result in LOC, so a postfight medical examination is of the utmost importance.

Not surprisingly, when analyzing concussion rates based on the winner and loser of a match, it was observed that the loser of both boxing and MMA matches sustains more suspected concussions compared to the winner, and the loser sustains the first concussion 98% of the time (Bernick et al., 2021). Another study reported differing results with only 83% of MMA athletes sustaining head injuries eventually losing the match; however, this takes into consideration all types of head injuries, not just concussions (Fares et al., 2021). Similarly, Curran-Sills and Abedin (2018) observed that 86.1% of injured MMA athletes lost their match. Additionally, it was found that 17.4% of losers sustained a concussion compared to 1.5% of winners in MMA (Ross et al., 2021).

On average, MMA athletes with a head injury sustained 32 significant head impacts during a single match (Fares et al., 2021). It was reported that the average time to stop a match following a KO was 3.5±2.8 sec, and during this time, knocked out athletes sustained an additional average of 2.6±3.0 strikes to the head (Hutchison et al., 2014). It is just as concerning that athletes who lost by TKO sustained 18.5±8.8 strikes in the 30 sec before match stoppage, and 92.3% of those strikes were to the head (Hutchison et al., 2014). Additionally, physicians analyzing videos of MMA matches reported that 43% should have been stopped an average of 44.5 sec sooner than they were (Bernick et al., 2021). Letting a match go longer than necessary can lead to additional head impacts and concussive injuries, with a potential for brain damage (Bernick et al., 2021).

When considering sex, Fares et al. (2021) discovered that males in MMA suffer from concussions at a rate of 17 injuries per 100 athletic exposures (AEs), while women suffer from concussions at a rate of 11 injuries per 100 AEs. In another Fares et al. (2019) study, males and females in MMA sustained similar head injury rates of 28 and 29 injuries per 100 AEs, respectively. Note that these head injuries included fractures, lacerations, and choking, not just concussions. In the same Fares et al. (2019) study, it was found that 36% and 14% of matches ended with TKO/KO for males and females, respectively, while 33% of matches overall ended with TKO/KO.

Research on the long-term effects of RHIs on MMA athletes is sparse, with most of the existing research focusing on boxers. The objective of this section is to evaluate CTE and examine long-term effects of RHIs, including changes in brain volume, brain structure, and cognition.

CTE is described as a progressive tauopathy of the brain found in individuals who have suffered repetitive subconcussive and/or concussive head impacts (McKee et al., 2013). CTE was first discovered in boxers who were described as “punch drunk” (Martland, 1928). Since then, the neuropathology, signs and symptoms, risk factors, and diagnostic criteria of CTE have been explored, but are not well-defined (D’Ascanio et al., 2018; McKee et al., 2018; McKee et al., 2013). CTE is characterized by hyperphosphorylated tau (p-tau) accumulation within neurons and astroglia at the depths of the cortical sulci (D’Ascanio et al., 2018). There are four stages of CTE, each with their own neuropathology (tauopathy) and signs and symptoms (D’Ascanio et al., 2018; McKee et al., 2018; McKee et al., 2013).

Stage I CTE is characterized by focal epicenters of p-tau at the depths of the cortical sulci. Subjects with stage I CTE suffer from varying symptoms including headaches, issues with attention and concentration, short-term memory loss, aggression, depression, executive dysfunction, and explosivity. In stage II CTE, p-tau spreads to adjacent superficial cortical layers. In addition to the symptoms seen in stage I CTE, those with stage II CTE experience mood swings, symptoms of motor neuron disease, impulsivity, suicidality, and language difficulties. Stage III CTE is characterized by p-tau widespread throughout the cortices. Symptoms of stage III CTE, in addition to those previously listed, include memory loss, visuospatial difficulties, apathy, and cognitive impairment. Finally, stage IV CTE is distinguished by widespread p-tau in the cerebrum, diencephalon, basal ganglia, brainstem, and spinal cord, as well as neuronal loss. Symptoms of stage IV CTE are more severe and include extreme memory loss in the form of dementia, executive dysfunction, paranoia, gait difficulties, dysarthria, Parkinson disease, and suicidality (D’Ascanio et al., 2018; McKee et al., 2018; McKee et al., 2013).

Unfortunately, risk factors for CTE are not well known; however, there are potential factors that have been explored. The most likely risk factor for CTE is RHIs, but not all individuals who experience RHIs are affected by CTE (D’Ascanio et al., 2018). This suggests that additional risk factors must be present for an individual to develop CTE. Advanced age may also play a role in CTE development, as seen in the study by McKee et al. (2013), where those exposed to RHIs but negative for CTE were on average 32.6±22.4 years old, while those exposed to RHIs and positive for CTE were on average 59.5±20.4 years old. Additional risk factors may include genetics, medical history, lifestyle, and other head impact variables like age of first exposure (AFE) to head impacts, frequency of impacts, and severity of impacts. These risk factors all warrant further research to best determine those that are modifiable in order to decrease the risk of CTE in individuals.

In addition to CTE, RHIs have been shown to affect brain volume, brain structure, and cognition. Much of the research on the long-term effects of RHIs in MMA athletes has been conducted through the Professional Athletes Brain Health Study (PFBHS), an observational and longitudinal study of the brain health of active and retired MMA athletes and boxers (Bernick et al., 2013). MMA athletes did not have a significant difference in brain structure volumes compared to healthy controls in the PFBHS; however, boxers had significantly lower left and right thalamus, caudate, putamen, hippocampus, and amygdala volumes compared to MMA athletes (Bernick et al., 2015). When combined, both MMA athletes and boxers had an estimated 0.3% decrease in caudate volume per professional fight (Bernick et al., 2015). MMA athletes had an estimated 0.2% and 0.3% decrease in thalamus volume for both the left and right sides, respectively, per professional fight (Bernick et al., 2015). Seemingly in opposition to those findings, when looking at a larger cohort from the PFBHS, AFE did not correlate with changes in the volume of the thalamus or caudate (Bryant et al., 2020). However, the same study found that AFE for active and retired athletes correlated with smaller left hippocampal, right hippocampal, and posterior corpus callosum volumes (Bryant et al., 2020). Interestingly, active athletes had smaller left amygdala volume in correlation with AFE, while retired athletes had smaller right amygdala volume (Bryant et al., 2020). Lee et al. (2020) found that boxers and MMA athletes have smaller thalamus (−650 mm³ mean difference) and corpus callosum (−402 mm³ mean difference) volumes when compared to healthy controls.

Two additional alterations in the brain, cavum septum pellucidum and cavum vergae, have been seen in MMA athletes (Lee et al., 2017; Lee et al., 2020). Cavum septum pellucidum and cavum vergae are two types of anterior midline intracranial cysts, which can be congenital and benign or form due to head trauma (Tubbs et al., 2011). The PFBHS found that boxers and MMA athletes had a higher prevalence of cavum septum pellucidum and cavum vergae compared to healthy controls. The presence of cavum vergae was associated with smaller brain volumes in the supratentorium, thalamus, corpus callosum, caudate, putamen, hippocampus, and amygdala compared to athletes without cavum vergae (Lee et al., 2020).

Compared to healthy controls, boxers and MMA athletes scored lower on processing speed and psychomotor speed (Lee et al., 2020). Lower processing speed scores were associated with increased number of professional fights, increased fight exposure scores, earlier AFE, and smaller volumes of the thalamus, amygdala, and left hippocampus for both MMA athletes and boxers combined (Bernick et al., 2015; Bryant et al., 2020). Interestingly, sex was found to moderate the effects of number of professional fights on brain structure volumes and cognition, with male athletes having significantly smaller brain regions than female athletes when associated with number of professional fights (Bennett et al., 2020). Additionally, as number of professional fights increased, male athletes had lower verbal memory scores, while female athletes had better verbal memory scores (Bennett et al., 2020). In retired boxers, earlier AFE was correlated with higher BESS test scores, meaning that earlier AFE is correlated with worse balance (Bryant et al., 2020). When measuring neuropsychiatric symptoms, there was a correlation between earlier AFE and depression, impulsivity, attention issues, and motor impairments in retired boxers (Bryant et al., 2020).

The biomechanics of head impacts have been studied more extensively compared to the epidemiology and long-term effects of concussions within MMA. Through different mechanisms of head impacts, linear and rotational accelerations/decelerations contribute to head injuries (Karton and Hoshizaki, 2018). Within MMA specifically, head impact biomechanics are not as well known. However, strain and shear stress in the brain have been documented in MMA athletes, with variation between weight classes, as well as within specific regions of the brain (Khatib et al., 2021; Tiernan et al., 2021).

The study of head impact biomechanics has largely focused on contact sports such as American football, ice hockey, soccer, and boxing. Head impacts in sports are each unique and depend on a set of characteristics, including magnitude, frequency, interval, and duration of head impact(s) (Karton and Hoshizaki, 2018). When these characteristics were compared between light weight (LW) and heavy weight (HW) MMA athletes, it was found that the frequency and interval of head impacts were similar between the weight classes; however, the magnitude of maximum principal strain (MPS) differed between the weight classes with the LW athletes sustaining a greater frequency of very low and high magnitude MPS head impacts (Khatib et al., 2021). Interestingly, LW athletes sustained high magnitude MPS impacts from punches to the head, while HW athletes sustained high magnitude MPS impacts from elbows to the head, implying that fighting-style differs between weight classes (Khatib et al., 2021). As seen in the study by Khatib et al. (2021), the magnitude, frequency, interval, and duration of head impact(s) are influenced by the type of head impact observed in sports, which include but are not limited to, collisions between athletes, falls, projectile impacts, and punches (Karton and Hoshizaki, 2018).

Linear and rotational accelerations contribute to the resulting head injury through different mechanisms (Karton and Hoshizaki, 2018). High linear acceleration/deceleration results in pressure changes in the head, which leads to brain injury (Gurdjian et al., 1958). Ommaya and Gennarelli (1974) argued that rotational acceleration causes shear stress between the skull and brain, thus resulting in brain injury, including concussions. Similar results were found in MMA athletes where knockouts resulting in transient LOC were overwhelmingly due to rotation of the head (Fogarty et al., 2019). Tiernan et al. (2021) found that the best strain indicator for concussion is the corpus callosum where concussed MMA athletes had 87.9% higher strain values than uninjured athletes. Furthermore, it was discovered that shear stress measured in the corpus callosum is the best predictor for concussion. This was evidenced by a 111.4% higher shear stress in the corpus callosum among concussed MMA athletes compared to uninjured athletes (Tiernan et al., 2021).

While there have been efforts to better define mTBI and concussion, consensus is required on the definitions of these conditions such that they can be used consistently across the literature. Currently, mTBI and concussion are used interchangeably (Greenwald et al., 2012; McCrory et al., 2017), while the literature defines them differently depending on the focus of the research, making it difficult to truly know the prevalence of concussions across all sports and within MMA.

The rules of MMA encourage head strikes, particularly ones that will knock out an opponent and result in a concussion. The best way to reduce head trauma sustained by MMA athletes is to change the rules. One method is to discourage head strikes by deducting points any time the head is hit. However, rules are unlikely to change this drastically. To mitigate the effects of head strikes, MMA athletes should always wear a mouthguard and headgear, but there is conflicting evidence on whether protective gear can reduce concussion risk. The UFC took a step in the right direction by implementing its first concussion protocol in 2021; however, one of the biggest issues with the concussion protocol is that athletes return home following a fight, so it is up to the athlete and the coach to turn to a healthcare provider for guidance in following the return-to-play protocol. Enforcing the concussion protocol will not be easy, so the UFC must better educate athletes and coaches on the symptoms and dangers of concussion.

Diagnosis of CTE is another area that merits further research because CTE can only be diagnosed postmortem (D’Ascanio et al., 2018; Lin et al., 2018; Zetterberg and Blennow, 2018). Through a literature review on CTE, McKee et al. (2013) defined neuropathologic diagnosis of CTE as the presence of the following: “(a) perivascular foci of p-tau immunoreactive astrocytic tangles and neurofibrillary tangles; (b) irregular cortical distribution of p-tau immunoreactive neurofibrillary tangles and astrocytic tangles with a predilection for the depth of cerebral sulci; (c) clusters of subpial and periventricular astrocytic tangles in the cerebral cortex, diencephalon, basal ganglia and brainstem; and (d) neurofibrillary tangles in the cerebral cortex located preferentially in the superficial layers.” However, this diagnostic criterion can only be used when examining a brain postmortem. Clinical diagnosis is not currently possible, but researchers have proposed clinical diagnostic criteria that have not yet been accepted. There is a need for neuroimaging biomarkers or fluid biomarkers that can be used to diagnose CTE antemortem (Lin et al., 2018; Zetterberg and Blennow, 2018). Neuroimaging technology that may potentially be adapted in the future to diagnose CTE includes PET, MRS, MRI, DTI, and fMRI (Lin et al., 2018). Fluid biomarkers found in CSF, blood, saliva, urine, and tears still need to be explored, especially because p-tau is associated with other tauopathies, like Alzheimer disease, and may not be distinguishable from p-tau associated with CTE (Zetterberg and Blennow, 2018).

It is also important to accurately determine the prevalence of concussions in MMA because studies show conflicting results. To aid in this, concussions must be defined consistently across the literature. One study counted all TKOs as concussions (Curran-Sills and Abedin, 2018), but this is not necessarily true. Another study only counted KOs as concussions (Ngai et al., 2008), but not all concussions result in LOC. Finally, an additional study relied on self-reported injury, with only 20.1% of athletes receiving medical attention, likely underestimating the concussion rate (Rainey, 2009). All MMA athletes must be examined by a medical professional after a fight, and notes from the examination should be documented properly.

To aid in the diagnosis of concussions, the biomechanics of head impacts sustained by MMA athletes must be observed and analyzed. Few studies have reported on the head impact biomechanics of MMA athletes (Bartsch et al., 2012; Fogarty et al., 2019; Khatib et al., 2021; Tiernan et al., 2021), but knowing the mechanism of injury could provide additional information to assist in diagnosing concussions. Of the utmost importance is developing novel, reliable diagnostic measures that can objectively determine the presence or absence of a concussion. Imaging and fluid biomarkers show the most promise, and future studies should focus on finding novel biomarkers to be used moving forward. This also applies to the diagnosis of CTE, which is currently only possible postmortem. Focusing on the prevention of head injuries and mitigation of risk factors will hopefully decrease the prevalence of concussions and reduce the long-term effects of RHIs.