This week, our lead article, Omega-3 fats associated with lower levels of neuroaxonal injury from a season of repetitive hits in American football players, is in the Self-Care category.

In this newsletter: Opportunities, Self-Care, Therapies Currently Available, Therapies & Diagnostic Tools Under Research, and CTE & Neurodegeneration.

We appreciate the Concussion Alliance volunteers and staff who created this edition:
Writers: Zoe Heart, Fadhil Hussain, Ella Webster, and Myla Hightower

Editors: Malayka Gormally and Zoe Heart

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Opportunities

Friday, March 7, 11 am PST: A free online class, Concussion 101: Fundamental Concussion Knowledge, presented by Ted Albrecht, PsyD, and hosted by Brain Northwest. Register in advance.

Tuesday, March 11, 6 pm EST: A free webinar, Prevention of Subsequent Concussions presented by Stephanie Cowle & Dr. Firas Al Rawi, hosted by the Canadian Concussion Centre. Register in advance.

Join a webinar presented by Concussion Alliance Co-Founders!

Tuesday, March 25, 6 pm EST: A free webinar, Concussion Alliance – Creating Accessible Patient-facing Resources, presented by Concussion Alliance Co-Founders Conor Gormally and Malayka Gormally, hosted by the Canadian Concussion Centre. Register in advance.

Call for study participants: military veterans who have had exposure to blasts, concussions, and/or a traumatic brain injury, including any injury to your head or neck that caused you to lose consciousness or feel dazed/confused/experience a gap in memory. Read our blog post for more information on the Late Effects of TBI (LETBI) study. If you are interested, please contact Julia Kirschenbaum at julia.kirschenbaum@mountsinai.org, call us at 212-241-5152, or sign up online.

Self-Care

Omega-3 fats associated with lower levels of neuroaxonal injury from a season of repetitive hits in American football players

A recent meta-analysis of three studies, published in Child Developments in Nutrition, investigated long-chain omega-3 polyunsaturated fatty acids (LC ω-3 PUFAs) as a possible protector against repetitive subconcussive head impacts in contact sport athletes. The team of reviewers that wrote the paper, led by Jeffery Heileson at Baylor University, deduced that there is early empirical evidence that LC omega-3 PUFAs have a small prophylactic effect in the brain, as two of the three studies found that, post-season, biomarkers of neuronal damage were found in lower levels in football players who ingested LC ω-3 PUFA supplements during the football season. The authors emphasized that although the evidence for omega-3 as a preventative measure against repetitive subconcussive head impacts is promising, more research is needed to determine the effect and appropriate supplementation of LC ω-3 PUFAs. However, Heileson et al. note that previous studies have found athletes to have insufficient levels of LC ω-3 PUFAs in their blood and recommend that athletes consume 2 grams per day of LC omega-3 PUFA, as "the current evidence suggests that athletes tend to consume <500 mg" per day, even while taking LC omega-3 PUFA supplements.

Omega-3 polyunsaturated fatty acids, which are naturally abundant in oily fish and seafood and are also found in some vegetarian and vegan sources, are known to strengthen various types of cells by incorporating themselves into the cell membranes in the form of phospholipids, which are in part made up of fatty acids. Omega-3s are known colloquially as "nutritional armor." Football players in three different studies ingested LC ω-3 PUFA supplements during their seasons. Researchers then measured the level of Neurofilament-light (Nf-L), a biomarker of neuroaxonal injury, in these players compared to players who had not received omega-3 supplements. In two out of the three studies, LC ω-3 PUFA supplementation during the football season was associated with a lower level of Nf-L's post-season, indicating a lower level of neuroaxonal damage.

The authors noted that the studies reviewed should be interpreted as a starting point for research on the relationship between omega-3 supplementation and neuroaxonal injury. One significant limitation of the studies is that the threshold for Nf-L levels "that would indicate clinically relevant neuronal damage" has yet to be decided, and no "clear guidelines" exist to denote normal ranges. Additionally, researchers pointed out that many athletes consume a diet with limited omega-3, and therefore, athletes may be differently affected by omega-3 supplementation depending on pre-existing omega-3 deficiencies. Heileson stated, "Despite the findings, we consider the evidence preliminary rather than conclusive, and therefore more hypothesis-driven and carefully designed research is warranted." That being said, the possible potential of omega-3 supplementation to increase neuron durability is exciting to those at risk for brain injury, as currently, preventative options against concussion and the effects of repetitive subconcussive impacts are rare.

March is Brain Injury Awareness Month!

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Therapies Currently Available

Hyperbaric oxygen: a promising treatment for persistent post-brain-injury symptoms

A study published in Nature found that hyperbaric oxygen therapy (HBO2) improved persistent symptoms in people with brain injuries, including those with mild traumatic brain injuries. Participants who received HBO2 therapy for 12 weeks showed greater reductions in symptoms on the Neurobehavioral Symptom Inventory (NSI) compared to those who received a sham treatment. They also experienced improvements in anxiety, sleep, and balance, among other outcomes. Unlike previous studies focused on military populations, this research by Lindell K. Weaver et al. included a more diverse participant group with a greater proportion of women, lower rates of PTSD, and a broader range of brain injury causes––including traumatic brain injury (TBI) of all severities, carbon monoxide poisoning, and hypoxia (oxygen deprivation).

The trial included 47 participants randomly assigned to receive either HBO2 therapy or a sham treatment. The HBO2 group underwent 40 sessions in a hyperbaric chamber over 12 weeks, breathing 99% oxygen at 1.5 times normal atmospheric pressure, while the sham group breathed room air at standard pressure. Researchers assessed participants at the start of the study, after 13 weeks, and at 6 months. After this follow-up, all participants were offered 40 additional HBO2 sessions, with long-term outcomes measured up to 36 months. The primary outcome was the NSI, but researchers collected a number of secondary outcomes, including the Rivermead Post-Concussion Questionnaire.

At 13 weeks, both groups showed some improvement, but the HBO2 group improved significantly more, with NSI scores dropping an average of 7 points more than the sham group. HBO2 participants saw benefits across all symptom categories—cognitive (thinking and memory), emotional (mood and anxiety), and physical (headaches, dizziness, balance). Only the HBO2 group maintained its improvements beyond 6 months. By 12 months, both groups showed better scores on the Rivermead Post-Concussion Questionnaire, but the HBO2 group had greater gains. The sham group’s benefits faded over time, suggesting some initial improvements may have been due to study participation effects, such as rest time in the chamber or the expectation of improvement. Further, the participants who received 40 HBO2 treatments and then did the additional 40 HBO2 sessions (a total of 80 HBO2 sessions), reported not only “greater improvement in total NSI score compared the sham group” but also greater improvement “compared to their own total NSI scores after only 40 HBO2 sessions.”

No serious adverse effects were reported, though the study excluded participants with certain medical conditions that could increase risks. According to the researchers, this study is one of the few to examine the long-term effects of HBO2 therapy for brain injuries, with follow-ups extending beyond a year. The findings suggest that HBO2 could be a promising option for people with persistent symptoms, improving “clinically meaningful outcomes.” Additionally, the results suggest that “80 HBO2 sessions may be superior to 40 sessions for treatment of long term brain injury outcomes.”

Therapies & Diagnostic Tools Under Research

New transcranial magnetic stimulation treatment protocols to reduce symptoms of depression in 5 days and ease chronic post-concussion symptoms

A UCLA Health press release discusses several of their studies and highlights the effective new uses of precision transcranial magnetic stimulation (TMS) in treating depression and chronic concussion symptoms. UCLA Health researchers have developed a new method of precision TMS delivery to relieve symptoms of depression in as few as 5 days. The researchers are developing a TMS protocol to treat chronic post-concussion symptoms supported by a grant from the Department of Defense.

TMS Traditionally, TMS treatment for depression involves daily sessions over six to nine weeks—an extended process that can be difficult for many patients to complete. To address this, UCLA Health has developed a new protocol called 5x5, where patients receive five treatments per day for five consecutive days. This accelerated method provides faster symptom relief while maintaining the therapy's high success rate. Each treatment is personalized using MRI scans to precisely target brain areas affected by depression precisely, with advanced robotics ensuring accuracy even if patients move slightly during the session.

Researchers have also discovered a link between pupil constriction and treatment outcomes. Pupil size reflects the autonomic nervous system's function, which is often disrupted in individuals with depression. By measuring how much a patient's pupils constrict in response to light before starting TMS, specialists can better predict who will respond most effectively to different stimulation protocols.

Currently, UCLA Health is applying TMS to help individuals suffering from persistent symptoms following a concussion. These symptoms, such as headaches, dizziness, and brain fog, may result from an oversensitive brain circuit (a circuit between the prefrontal cortex and amygdala) contributing to a phenomenon known as "fear avoidance." This "fear avoidance" causes patients to avoid engaging in activities that they suspect may induce symptoms, but the avoidance can create a sensitivity, leading to a feedback loop of lingering symptoms. According to Dr. Bickart at UCLA BrainSPORT, preliminary studies of chronic concussion patients used MRIs to "detect a blood flow pattern indicating a rigid connection between the prefrontal cortex and the amygdala." The amygdala is primarily responsible for emotion generation and regulation, and Dr. Bickart believes that the rigidness of the connection could be a maladaptation that makes it harder for patients to reduce fears and resolve symptoms.

By using MRI to create personalized plans of brain stimulation, researchers aim to target this maladapted, overly rigid connection between the prefrontal cortex and amygdala, with the treatment promoting "more flexibility and adaptability to help the brain address the triggering situations. The team's research will have control and intervention groups; for the intervention group, the treatment will consist of 10 appointments over the course of a month; during each appointment, patients will receive 1-2 minutes of TMS while listening to "self-recorded scripts about activities they fear will trigger symptoms and activities that are more neutral". The goal of this is to improve patients' coping abilities and reduce their fear of returning to normal activities. While there will be multiple treatment sessions and MRI assessment points, Dr. Bickert notes that "We expect that after a single day of treatment, their MRI will look better or show a decrease in prefrontal to amygdala connectivity."

While this field of research is still evolving, early results are promising, offering hope for more accessible and effective treatments for both depression and chronic concussion symptoms.

March is Brain Injury Awareness Month, and we're hosting a webinar for our community!

Join us on Wednesday, March 13th at 4 pm EST | 3 CST | 1 PST for a virtual "lunch and learn" with Concussion Alliance Co-Founders Conor Gormally and Malayka Gormally.

This webinar is free to our community and will include a crash course on the most up-to-date best practices for concussion recovery, a few of our personal highlights from recent Concussion Update Newsletters, and more about our story and journey from concussion patient and advocate to building a nonprofit.

We will also have a Q&A, so you'll have the opportunity to ask us any burning questions!

Here are the details:

March 13th at 4 pm EST | 3 CST | 1 PST

Google Calendar Link

We look forward to seeing you there!

CTE & Neurodegeneration Issues

Perceived CTE increases suicidality among retired professional American football players

A study published in JAMA Neurology found that former professional football players who believe they have chronic traumatic encephalopathy (CTE) are more than twice as likely to report suicidal thoughts (“suicidality”) compared to those who do not––even adjusting for other risk factors. CTE is a neurodegenerative condition associated with repeated head trauma, but because it can only be diagnosed postmortem, many former athletes are left uncertain about their condition. Rachel Grashow et al. used data from the Football Players Health Study at Harvard University to survey 1,980 retired American football players in their investigation of the psychological impact of perceived CTE. They found that a third of retired players (34.4%) perceived that they had CTE and that these former players had significantly more depression, chronic pain, cognitive problems, and suicidality. Significantly, 25.4% of those who believed they had CTE reported experiencing suicidality, compared to just 5.0% of those without perceived CTE. Even after accounting for depression, anxiety, and other established risk factors, perceived CTE remained a strong predictor of suicidality; former players who believed they had CTE were still more than twice as likely to report suicidal thoughts as those who did not.

The authors emphasize that fear and uncertainty surrounding CTE could be exacerbating mental health struggles in this population and “that some suicidality may stem from the assumption that a former player has an untreatable neurodegenerative disease.” The study authors stress the importance of diagnosing and addressing treatable medical and behavioral conditions that might be misattributed to CTE to improve overall health outcomes. A Harvard Medical School article about the study by Liana Wait noted that persistent fears about having CTE can negatively affect mental well-being and may deter individuals from seeking effective treatments for other conditions “that cause similar neurocognitive symptoms.” Study coauthor Ross Zafonte, MD, notes, “The symptoms that raise CTE concerns are real and CTE concerns are valid, but it’s critical to understand that having persistent fears about this condition can take a toll on mental health. When these concerns discourage former NFL players from receiving effective treatments for other or interrelated conditions related to physical and emotional health, it’s our responsibility to intervene.”

The study surveyed former professional American football players, collecting self-reported data on CTE-like symptoms, mental health history, and suicidality. While the presence of CTE can only be confirmed postmortem, these findings suggest that even the perception of having the condition can have profound mental health implications and possibly deter addressing treatable conditions. A noteworthy limitation of the study is its reliance on self-reported data, which could introduce bias if participants misinterpret or overestimate their symptoms. Additionally, it is unclear how many of the participants actually had CTE. Future research should aim to “determine the degree to which perceived CTE aligns with the true presence” of CTE as substantiated, ideally, by a future test that can diagnose CTE in the living. Future research may also lead to additional strategies for supporting former athletes xwho are struggling with mental health concerns. For example, “Certain modifiable lifestyle behaviors may be protective against suicidality and perceived CTE, as seen in the association of reduced risk with increased physical activity.