Altered Brain Connectivity in Posttraumatic Headache: Insights into Potential Biomarkers and Neuroplasticity (7/18/24 Internship Newsletter)
This week’s lead article, Altered Brain Connectivity in Posttraumatic Headache: Insights into Potential Biomarkers and Neuroplasticity, is in the Pathophysiology category.
Welcome to the first newsletter of our 2024 Summer Concussion Education & Advocacy Internship! This summer, we’ll be publishing newsletters every week to give our fantastic cohort of interns opportunities to practice their accessible science writing skills! You can learn more about the internship program here.
In this newsletter: Opportunities, Pathophysiology, Self Care, Veterans & Service Members, Statistics, and Youth.
We appreciate the Concussion Alliance interns who created this edition:
Writers: Sahil Bains, Zoe Marquis, Sam Gossard, Gabriel Marotti, and Adalia Shultz
Editors: Malayka Gormally and Conor Gormally
Do you find the Concussion Update helpful? If so, forward this to a friend and suggest they subscribe.
Opportunities
Action alert from the Brain Injury Association of America: the U.S. Congress may cut all of the CDC’s brain injury and concussion-specific programs, including HEADS UP and the National Concussion Surveillance System. Click here for an easy form to contact your representative.
The form will automatically send your message to your U.S. Representative. You can optionally customize your message by adding your representative’s name, which you can find here by inputting your zip code.
August 20, 4 pm EDT: A live webinar, Attention and Information Processing Speed Following Brain Injury – An Interdisciplinary Approach, presented by Tracy Graham, MSP, CCC-SLP, CBIS, Amanda Heys, OTR/L, and Tori Stramara, DPT, CBIS, and hosted by the Brain Injury Association of America. Free to patients, $50 for CE credit; register in advance.
Pathophysiology
Altered Brain Connectivity in Posttraumatic Headache: Insights into Potential Biomarkers and Neuroplasticity
Research published in the Journal of Headache and Pain reveals altered connectivity between certain brain regions in patients with posttraumatic headache (PTH) following mild traumatic brain injury (mTBI). Yishi Wang et al. reported that mTBI patients with PTH exhibit both increased and decreased connectivity between brain regions responsible for pain processing and sensorimotor tasks when compared to mTBI patients without headache. These connectivity alterations correlated with headache characteristics, suggesting brain connectivity alterations play a role in PTH pathophysiology. The study authors suggest these connectivity measures potentially serve as biomarkers for early PTH diagnosis and tracking disease progression. Moreover, they highlight the role of neuroplasticity, conveying that the brain’s ability to reorganize itself may offer hope for alternative therapeutic strategies.
The study assessed 94 mTBI patients using arterial spin labeling (ASL) perfusion MRI, a type of imaging that measures blood flow in the brain. Blood flow is a proxy for functional connectivity (FC) because regions with synchronized activity often have similar blood flow patterns. The authors found that changes in blood flow (and therefore FC) in the insular subregions of patients with PTH were associated with headache intensity and frequency. Patients with PTH exhibit both increases and decreases in connectivity of insular subregions, mainly pain processing and sensorimotor areas.
The authors highlight the potential for neuroplasticity after PTH, suggesting that the observed changes in FC might reflect the brain’s ability to reorganize itself, which may offer hope for alternative therapeutic strategies. Some limitations of the study include a small sample size and lack of a healthy control group. More studies are recommended to assess the correlation between differences in connectivity based on PTH development.
Concussion Alliance has covered studies regarding photobiomodulation and its effect on improving functional connectivity in individuals with persistent post-concussive symptoms. Here is our blog post about a case-series report published in the Journal of Alzheimer’s Disease Reports, which involves four former football players with CTE-like symptoms showing significant cognitive and mood improvements after treatment with transcranial photobiomodulation (tPBM), which is a specific light therapy. Here is our blog post about another related study published in Frontiers in Neurology, where a 23-year-old professional hockey player with persistent post-concussive symptoms conveyed structural and functional improvements in brain scans and neuropsychological tests after an 8-week home-use light therapy treatment using Vielight devices.
Self Care
Nutrients common in the Mediterranean diet may promote healthy brain aging; novel study of nutrients in blood plasma, cognitive tests, and brain imaging
A recent correlational study published in Nature: npj Aging identified 13 nutrients that “may promote healthy brain aging.” Rather than using the typical approach of dietary questionnaires, researchers Christopher Zwilling and colleagues identified nutrients in blood plasma and then correlated nutrition profiles with brain aging as measured by imaging and cognitive tests. The 13 nutrients the researchers found, including fatty acids, antioxidants, carotenoids, and vitamins, are commonly found in the Mediterranean diet in foods such as fish, nuts, oils, and leafy greens.
Based on the results of the cognitive tests and brain imaging measures, the researchers categorized 100 caucasian adults, aged 65 to 75, as having either “accelerated brain aging” or “delayed brain aging.” The researchers then took plasma samples for each participant and measured the concentrations of various nutrient biomarkers associated with good brain health.
The 13 key nutrients the researchers identified were found in higher concentrations for those in the delayed brain aging group than those in the accelerated brain aging group. These differences could not be explained by participant demographics, fitness levels, or bodily measures (weight, height, hip and waist circumference).
Research using randomized controlled trials is needed in order to determine whether these nutrients indeed lead to better brain health. Additionally, future research should work with non-white populations to make results more generalizable, and researchers should seek to better understand the mechanisms through which these nutrients impact the brain.
Veterans & Service Members
High cumulative blast exposure in military personnel is associated with worsening brain function and lower quality of life
In a multimodal study published in Proceedings of the National Academy of Sciences, Natalie Gilmore et al. found that higher cumulative blast exposure was associated with decreased brain function and lower quality of life. According to a New York Times article, the damage seen in these brains was not CTE but a new pathology that shows that astrocytes, a type of cell essential to brain function, “had grown into gargantuan, tangled masses that barely functioned.” Furthermore, decreased connectivity and increased cortical thickness were found in specific brain regions, emphasizing the need for further research into this pathology.
During two days of intensive assessments, 30 active-duty Special Operations Forces participated in neuroimaging, blood tests, cognitive tests, and surveys of self-reported brain health to assess psychological health, cognitive ability, and brain structural integrity. The authors also collected self-reported data on repeated blast exposure (RBE) and any TBI history, performing statistical analyses to correlate the tested measures with RBE.
Cumulative high blast exposure was associated with decreased connectivity in the executive control network (responsible for complex reasoning and decision-making) and abnormal thickness in some brain areas. The abnormal thickness of the rostral anterior cingulate cortex (rAAC) may hinder cognition and modulation of emotion. This area of the brain relies on astrocyte cells for immune protection, and these cells have formed into tangles in the study participants. The astrocyte tangles hinder the role that the rAAC region plays in cognitive, emotional, and executive networks, as well as default processing. Default processing consists of automatic cognitive behaviors such as social cognition, mind-wandering, and memory recall.
Further research will improve the understanding of the pathology related to RBE and should strive to further our understanding of its mechanisms. The authors recognize that a limitation in this study is that there was no control group; further studies should keep this in mind. Implementing regulatory measures and increasing awareness of the impacts of repeated blast exposure within the US military may help reduce poor mental health and suicide. To learn more about the recent attention to blast-related TBI research and policy, check out Concussion Alliance’s recent blog posts on this issue here, here, and here.
Statistics
Study finds 1 in 8 older Americans suffered TBI in a representative cohort
In a longitudinal study published in JAMA Network Open, researchers discovered that over 18 years, 13% of older Americans suffered a traumatic brain injury (TBI). Researchers Erica Kornblith et al. measured the incidence of TBI over an 18-year period (August 2000 to December 2018) in 9239 community-dwelling seniors who were enrolled in the Health and Retirement Study (HRS) and had linked Medicare data. Although existing literature suggests that males, non-whites, and people with lower socio-economic status may be more likely to be diagnosed with TBI, this study found an “increased rate of TBI was associated with healthy, wealthy, White female individuals.”
In a UCSF press release, journalist Suzanne Leigh notes the TBIs in this study typically occurred due to “falls from ground level.” Further, the activity levels of older adults who are at higher risk of sustaining a TBI may be higher than average, as subjects “who went on to be diagnosed with TBI were less likely when they enrolled in the study to have lung disease and to have trouble with the activities of daily living, like bathing, walking and getting out of bed.” This finding suggests that individuals in the study who sustained a TBI had the ability to carry out basic dynamic movements that some older adults may not be able to do. In the press release, lead author Kornblith notes, “It’s possible that our findings reflect that adults who are healthier, wealthier and more active are more able or likely to engage in activities that carry risk for TBI.” Leigh points out that while physical activity is neuroprotective and may “reduce or slow the development of dementia,” a TBI in an elderly person increases the likelihood of dementia, Parkinson’s, seizures, cardiovascular disease, anxiety, and depression.
The study authors collected Medicare data for two older adult cohorts who were coded for a TBI diagnosis: those who had gone to an emergency department (ED) and had received an MRI or CT scan and those who had gone to a “nonhospital setting,” presumably an outpatient clinic or provider. Further research must be conducted to identify groups that may not have the means to seek medical attention for TBI diagnosis and care. The researchers identify that “lower resourced” and marginalized communities tend to distrust medical care in part because of “the racial and ethnic microaggressions that commonly occur in the medical setting.” People from these communities may be less likely to seek medical care and, subsequently, not receive an official TBI diagnosis. The study authors also add that “older adults who experience falls, the largest segment of US citizens experiencing incident TBI, are also the least likely to seek care.” Hence, the nonreporting by these populations may have played a role in the outcomes of this study. Journalist Suzanne Leigh reinforces the need to identify populations who do not seek medical care for a TBI and how best to provide for them. While the current study’s findings are profound, further research must be conducted on populations that may not have been accounted for in this cohort.
Youth
Children sustaining concussions outside of sports see specialists later and have less access to appropriate care despite being more common than sport-related concussions
In a recent observational study published in The Journal of Pediatrics, researchers found that recreation-related concussions (RRC)––such as those from recess, gym class, and play––and non-sport or recreation-related concussions (non-SRRC)––from events like motor vehicle crashes, falls, and assault––are more common among patients 5 through 12 years old than sports-related concussions (SRC) from organized sports. Additionally, as stated in an article published by Physician’s Weekly, the study found that “patients with RRC and non-SRRC were first evaluated by specialists 4 and 6 days later than those with SRC.”
The study authors, Patricia Roby et al., identified the need to study RRC and non-SRRC separately from SRC due to differences such as less “supervision available at time of injury” and less direct access to established and informed concussion healthcare. According to the Physician’s Weekly article, the disparities in time between injury and first specialist visit for RRC and non-SRRC may also lead to “greater symptom burden and prolonged recovery.” Although most concussion research has focused on sports, SRC “represented less than one-third of concussions in [the] study sample.”
When compared to children with RRC and SRC, children with non-SRRC present to specialty care reporting a higher reported symptom burden, “more frequent visio-vestibular abnormalities, and more changes to sleep and daily habits.” The study authors note that this greater severity of symptoms is “associated with greater effects on academic performance” and suggests expanding the role of school nurses. These findings indicate not only a need for further research in concussions as it pertains to “children outside of [organized] sports,” but also that education of physicians who see RRC and non-SRRC patients would make quality care more accessible to all children “regardless of the mechanism of injury,” as supported by a press release published by the Children’s Hospital of Philadelphia.
Conducted retroactively, researchers at Children’s Hospital of Philadelphia (CHOP) utilized “electronic health records for patients seen for a concussion within the specialty care concussion program at…(CHOP)” for 1,141 patients between the ages of 5 and 12 who attended their first care visit within 28 days of the injury. The researchers then assigned patients to groups according to injury description: RRC, non-SRRC, and SRC. Patients were also categorized by date of injury as pre-, early-, and late-COVID, as the study was conducted between January 1, 2018, and September 12, 2022.
The large proportion of RRC and non-SRRC cases suggests the need for an increase of research specific to these situations to further assist patients. The study authors emphasized the importance of educating primary-care providers and emergency departments on current concussion protocols and, according to the Physician’s Weekly abstract, developing “tailored management and intervention strategies” that recognize the distinct needs of young RRC and non-SRRC patients.