The lead article this week, Two gut microbiota significantly depleted after concussion; diagnostic and treatment possibilities, is in the Therapies & Diagnostic Tools Under Research category.

In this newsletter: Opportunities, Sports, Cannabis & Psychedelics, Pathophysiology, Self-Care, Therapies Currently Available, Therapies & Diagnostic Tools Under Research, Mental Health, and CTE & Neurodegeneration Issues.

We appreciate the Concussion Alliance Volunteers who created this edition:

Writers: Sravya Valiveti, Minhong Kim, Claire Holmes, Conor Gormally, & Malayka Gormally

Editors: Conor Gormally and Malayka Gormally

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Opportunities

Wednesday, June 1, 1 pm PST: a free online class, Building Self-Advocacy for Survivors and Families, presented by Certified Life Coach Anita Chin. Hosted by the Brain Injury Alliance of WA State. You don't have to be a WA State resident to attend. Register in advance.

Wednesday, June 1: season 2 of the podcast Sharing Experiences with Concussions/TBI is available for streaming.

Thursday, June 2, 12 pm EST: a free webinar, Post-Concussion Autonomic Dysfunction: Impact & Treatment Techniques, presented by "Ali Kraus, Neurologic Physical Therapist at the Fixel Institute, and Aliyah Snyder, Assistant Professor in the Department of Clinical and Health Psychology." Hosted by the University of Florida Brain Injury, Rehabilitation, and Neuroresliience Center. Register in advance.

Tuesday, June 7, 12 pm PST: free online class, Therapeutic Songwriting, presented by Megumi Azekawa, Neurologic Music Therapist, who will "engage with participants in drafting a song that reflects their thoughts and feelings around their journey with Traumatic Brain Injury." Hosted by the Brain Injury Alliance of WA State. You don't have to be a WA State resident to attend. Register in advance.

Be part of a study on brain health and head impacts from sport: The Head Impact and Trauma Surveillance Study (HITTS) is recruiting study participants who will take a fully online, annual survey. "Anyone age 40 or older who played soccer or tackle football at any level (youth, high school, college, or pro/elite) can enroll."

Sports

Concussion risk during targeting plays is greater than concussion risk during nontargeting plays in collegiate American football

A study focusing on American collegiate football, published in the Orthopaedic Journal of Sports Medicine, found that the concussion rate during plays in which a targeting penalty was called was significantly higher than the concussion rate for all other plays. Authors Douglas F. Aukerman et al. concluded that “the risk of concussion during targeting plays was 36.9 times greater than that for all other plays.”

The targeting rule was implemented in 2008 by the National Collegiate Athletic Association (NCAA) to penalize dangerous contact to the head or neck area during football matches. According to the NCAA Rule Book, a targeting penalty is called when a player “takes aim at an opponent for purposes of attacking with forcible contact that goes beyond making a legal tackle or legal block or playing the ball.” However, the targeting rule has been the subject of much controversy because of football officials’ seemingly inconsistent calls.

To investigate the reasonableness of the targeting rule, Aukerman et al. compared the rate of concussions during targeting versus nontargeting plays. After all, if targeting plays and nontargeting plays carry the same risk for concussions, continuing to implement a targeting rule would be illogical.

The researchers analyzed football data from the Pac-12 Conference, an NCAA Division I level athletic conference. Concussions during games were classified into two categories: occurring during a play where a targeting penalty was called or occurring during a nontargeting play. “Targeting plays were further categorized to either those in which the call was upheld or those overturned by the on-field official after replay review.”

The authors used data from 538 Pac-12 Conference games, consisting of 68,670 plays; 213 concussions occurred in these games, with 15 occurring during targeting plays and 198 occurring during other (nontargeting) plays. Concussion incidence was 106.4 per 1000 for targeting plays and 2.9 per 1000 for nontargeting plays. The researchers found that the overall concussion risk for both overturned and upheld targeting plays was 36.9 times greater than for all other (nontargeting) plays. Concussion risk for targeting plays upheld after replay review was 49.0 times greater than that for all other (nontargeting) plays. Ultimately, these results demonstrate that concussion risk during targeting plays is greater than concussion risk during nontargeting plays in American collegiate football, suggesting that the NCAA should continue to penalize targeting plays.

Cannabis & Psychedelics

Psilocybin with psychotherapy produced long-lasting reduction in major depression

In a study published in Journal of Psychopharmacology, authors Natalie Gukasyan et al. found that two doses of psilocybin, along with patient-directed psychotherapy, had significant and stable antidepressant effects immediately and throughout the study’s one-year follow-up period. The subject group consisted of 24 participants aged 21-75 with unipolar major depressive disorder (MDD); on average, participants were 39 years old, diagnosed with MDD 21 years ago, and two years into their current major depressive episode. At the 12-month follow-up, 75% of participants had shown a clinical response (score reduced by 50%), and 58% were in remission (score ≤ 7).

Participants received 6-8 hours of preparatory meetings with a pair of facilitators, at least one of whom had a “master’s or doctoral level of clinical training in mental health.” The researchers administered two doses of psilocybin in a comfortable setting approximately two weeks apart. The preparatory facilitators provided nondirective psychotherapy during the psilocybin sessions, allowing the participants to direct the flow of conversation. “Participants returned for follow-up at 1 day and 1 week following each drug administration session, and then at 1, 3, 6, and 12 months following the second session” to receive a 1-2 hour therapy follow-up and be evaluated for depression severity.

Gukasyan N, Davis AK, Barrett FS, et al. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. *J Psychopharmacol*. 2022;36(2):151-158. doi:10.1177/02698811211073759

The researchers evaluated participants’ depression severity and their perception of the psilocybin sessions as a mystical experience (using the Mystical Experience Questionnaire). They also used four single-item measures to evaluate the degree to which patients found their treatment “personally meaningful, spiritually significant, psychologically insightful, and psychologically challenging.” They also measured the participants’ perceptions of “overall well-being attributed to psilocybin,” evaluated on five subscales of “attitudes about life, attitudes about self, mood, relationships, and behavior.”

Depressive scores of 25+ are considered severe depression, 18-24 moderate depression, and 7 or below represent absence or remission of depression. Patient “scores for the overall treatment sample decreased from a mean of 22.8 at pretreatment baseline to 8.7 at 1 week, 8.9 at 4 weeks, 9.3 at 3 months, 7.0 at 6 months, and 7.7 at 12 months post-treatment.”

No patients reported adverse events at any point of the study or follow-up. “Patient ratings of personal meaning, spiritual significance, and MEQ30 scores after psilocybin sessions significantly correlated with a measure of overall well-being at most follow-up timepoints.” The authors argue that this study “significantly extends” previous studies’ findings of psilocybin’s antidepressant effects through 4 weeks, 6 weeks, and 6 months. Their results indicate the need for further research evaluating the stable antidepressant effects of psilocybin beyond one year.

BrainSPORT Podcast episode focuses on psychedelics

We recommend this entertaining and informative interview with a psychedelics expert. “UCLA psychiatrist and psychedelic expert, Dr. Walter Dunn and @Ahdelneuro discuss the history of psychedelic use, evidence substantiating the use of psychedelics as a treatment for diseases,” future research at UCLA, and potential pitfalls of underground psychedelic use. The interview is available on YouTube.

Pathophysiology

Reduced resting-state functional connectivity in concussion patients

Concussed adolescents had significantly reduced resting-state functional connectivity "between the dorsal attention network (DAN) and right inferior frontal gyrus (RIFG)" compared to non-concussed controls, according to a study published in the Journal of Clinical Medicine. Authors Stephen J. Suss et al. used resting-state functional magnetic resonance imaging (fMRI) to compare 38 adolescents who had sustained a concussion within ten days of imaging and 14 adolescent controls with no concussion history.

The authors clarify that "controls demonstrated a significant positive DAN-RIFG functional connectivity, whereas DAN-RIFG connectivity in concussed adolescents" was virtually zero. The authors explain that "The DAN is primarily involved in goal-directed attention" and demonstrates "sustained activation when individuals are engaged in focused attention." They surmise that "Considering that the RIFG plays an important role in shifting attention, disruptions in DAN-RIFG connectivity may potentially affect an individual's ability to orient and subsequently maintain focus of attention during tasks."

However, the study found that the fMRI findings were NOT associated with the concussed adolescents' scores on standard concussion assessments. Given this lack of association, the researchers "propose that the reduction in this connectivity may reflect a global non-specific brain response to concussion that occurs during the subacute phase of post-concussion recovery."

Within the concussed adolescent group, there was no difference in DAN-RIFG connectivity between those who had had a prior concussion and those who did not. Because of this, the authors "believe that after recovery, the DAN-RIFG connectivity likely returns to baseline." The researchers call for further studies on how DAN-RIFG might contribute "to the presence or absence of post-concussion symptoms and how this connectivity might be related to recovery trajectory."

Self-Care

Mindfulness: why it works, positive effects on problems common to concussion

An article by Harvard professor Arthur C Brooks for The Atlantic addresses mindfulness; although the article is not specific to concussion, meditation lessens many of the symptoms common to concussion. The Mayo Clinic defines mindfulness as “a type of meditation in which you focus on being intensely aware of what you’re sensing and feeling in the moment, without interpretation or judgment.” Brooks writes about the uncomfortableness and painfulness of mindfulness, but he emphasizes that these struggles are why mindfulness is effective. The practice is so effective that “it has been shown to lessen depression, lower anxiety, improve memory, and decrease back pain.”

Ignoring emotions and engaging in distracting behaviors can result in “mind-wandering” and only makes the situation or feelings worse. However, mindfulness should be used to acknowledge emotions and be aware of yourself, but becoming too self-concerned will also create issues. Brooks recommends interpreting mindfulness as “a sense of yourself as part of the wider world, and an observation of your emotions without judgment.” Ultimately, practicing mindfulness is a very healthy habit, and many people could benefit from it with the understanding that it is not always a pleasant experience as we traverse through life.

Therapies Currently Available

60-day average wait for concussion care, says Australian expert

In an interview with Gabrielle McCulloch published in stuff, Auckland University of Technology TBI Network Director Alice Thedom speaks about delayed care for New Zealanders with concussion and TBI. According to Theadom, concussion patients often face wait times averaging 60 days to see a concussion clinic for specialized care. Theadom has been working with New Zealand’s Accident Compensation Corporation (ACC) on a trial program to improve the referral process and reduce wait times. The ACC has also temporarily “enabled GPs [General practitioners] to directly refer patients to concussion clinics in 2022.”

This trial program will also include a “nationwide educational campaign to help GPs learn more about concussion care.” Theadom says that many GPs don’t know what concussion services are available, creating an onus on patients to seek and find help.

Therapies & Diagnostic Tools Under Research

Two gut microbiota significantly depleted after concussion; diagnostic and treatment possibilities

In the first study to assess potential changes in the gut microbiome after a concussion, researchers found that two specific bacteria were “significantly depleted” after a concussion – suggesting a new potential diagnostic tool. The study, published in Brain, Behavior, & Immunity – Health, indicates that gut microbiota could also be a tool indicating when an athlete is ready to return to play – and a potential target for treatments.

Sirena Soriano et al. studied “33 male Division I collegiate football players” over the course of the season, during which four players suffered a concussion. The study looked at gut microbiota effects of subconcussive hits on all 33 players (findings which this synopsis does not address) and changes to gut microbiota in the four players who received a concussion.

Bacteria levels for Eubacterium rectale and Aerostipes hadrus were lower in concussed players. Eubacterium rectale has been “correlated with peripheral inflammation in patients suffering from cognitive impairment.” The research team also took blood and saliva samples, finding that “The decrease in the anti-inflammatory microbe Eubacterium rectale was associated with the presence of blood biomarkers for inflammation.”

In an article for News Medical, the study authors suggest that a gut microbiota test might not only diagnose acute concussions but also “signal when it’s safe to return to action [play].” Study author Sonia Villapol, PhD, states that “Until your gut microbiome has returned to normal, you haven’t recovered.”

In addition, targeted gut microbiota interventions may be a future treatment for concussions. As a starting point, the authors reference a study in which severe TBI patients were treated with probiotic supplements, leading to shortened stays in the ICU.

Concerning microbiota interventions, the authors note that “These observed benefits are commonly attributed to probiotic-induced reductions in systemic and central inflammation. Similarly, thinking about a post-concussion clinical treatment, novel preventive and therapeutic strategies, including nutritional diets, microbiota manipulations with probiotics or prebiotics, or strengthening the enteric barrier could be applied to modulate the intestinal microbiota and ultimately improve both cognitive and functional TBI health outcomes.”

The study has several limitations; the small number of concussed individuals (4) and the all-male cohort of study participants.

Mental Health

Almost half of concussion patients develop mental illness disorder within 3 years

Researchers Heath, J. W. et al. examined the relationship between mild TBI and how it related to the development of mental illness disorders. The research, published in the American Journal of Physical Medicine and Rehabilitation, found that “within 3 years following a concussion, 48% of patients were later diagnosed with a mental illness”.

The authors investigated the proportion of concussion patients who developed mental health conditions within three years of a concussion. The researchers also wanted to assess the impact of demographic factors on the development of specific mental health conditions.

Researchers used a national database to query for patients, ages ranging from 18 to 45, with a recent concussion diagnosis but no prior mental illness diagnosis. They then followed up with these patients to evaluate if they had developed a mental health condition over the three years following their concussion. Only those patients who developed certain mental health conditions such as depression, anxiety, panic disorder, PTSD, bipolar disorder, and schizophrenia were considered for this study.

The authors note that the mechanisms underlying the relationship between TBI and a mental illness diagnosis are currently unclear and need to be further elucidated. They concluded that a higher proportion of patients who have suffered concussions are diagnosed with a mental illness within three years compared to the general population. Since patients with a concussion history are at higher risk of developing mental illness, they propose these patients would likely “benefit from screening for the development of a mental illness.”

CTE & Neurodegeneration Issues

White matter damage from repetitive head impacts and concussions; abnormalities persist at six months

A study published in the American Journal of Neuroradiology found similar white matter tract damage in the brains of both non-concussed collegiate football players and concussed players, implying that repetitive head impacts appear to cause white matter damage. While authors S. Chung et al. found that while white-matter abnormalities in the concussed players lessened over time, there may be only partial recovery.

At a 6-month follow-up scan, concussed players had persistent white matter abnormalities, particularly in the corpus callosum, “suggesting longer-term persistence of microstructural changes associated with sports-related concussion,” according to an article in Radiology Business.

The researchers “analyzed the cases of 78 college athletes in the Federal Interagency Traumatic Brain Injury Research registry” split into three groups; 24 football players who had sustained a concussion, 26 football players without a concussion, and 28 controls who were non-contact sports athletes. Using diffusion MRI, “Significantly increased” white matter abnormalities were “observed diffusely across the whole-brain” for the non-concussed and the concussed football players compared to the control group. The concussed players also showed increased abnormality in “some focal areas.”

The authors conclude that “This work reinforces previous work showing that the corpus callosum is specifically implicated in sports-related concussion and also suggests this to be true for repetitive head impacts.”