Summary: MRI scans of former American football players reveal subtle but consistent differences in the brain’s outer grooves (sulci) compared with scans from otherwise healthy men who never played contact or collision sports. The changes—most notably shallower grooves in a frontal region previously associated with chronic traumatic encephalopathy (CTE)—align with patterns seen in autopsy-confirmed CTE and may represent early structural biomarkers for the disease.
Although CTE can currently only be confirmed after death, these new findings point toward the possibility of detecting risk-related brain changes in living people. The study also identified a relationship between years of play and structural alterations in other sulci, suggesting a dose-response effect from repetitive head impacts. Further validation is required before clinical use, but the results advance efforts to develop in vivo biomarkers for CTE.
Key Facts
- Structural differences: Former football players showed significantly shallower left superior frontal sulci compared with matched controls.
- Exposure link: Longer playing careers were associated with widening of the left occipitotemporal sulcus, supporting a connection between cumulative head impacts and sulcal change.
- Biomarker potential: MRI-detected sulcal morphology could become part of a multi-feature risk assessment to identify individuals at higher risk of CTE while they are still alive.
Source: NYU Langone
New research shows discernible differences in sulcal morphology on MRI between former football players and men without exposure to contact or collision sports. Researchers suggest these patterns may signal early structural changes linked to chronic traumatic encephalopathy (CTE).
CTE is a progressive neurodegenerative disease associated with a history of repetitive head impacts. Pathologically, it is characterized by abnormal accumulations of phosphorylated tau protein, often concentrated at the depths of specific sulci such as the superior frontal sulcus. Until now, clinicians have relied on postmortem tissue to diagnose CTE; the new analyses aim to translate postmortem findings into detectable in vivo markers.
An international team led by NYU Langone Health examined single structural MRI scans from 169 former college and professional football players and compared them with scans from 54 carefully matched men of similar age, body habitus, and education who had no history of contact or collision sports or active military service. The study focused on sulcal depth and width in two regions commonly implicated in CTE pathology: the superior frontal sulcus and the occipitotemporal sulcus.
On average, former football players had shallower left superior frontal sulci than controls. In addition, greater exposure—measured by total years of play and age of first exposure—was associated with widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure correlated with reduced depth in the left superior frontal region, supporting the idea that repeated impacts may leave measurable structural signatures.
Sulci are small cortical grooves—typically no more than about 1.5 millimeters wide and up to 15 millimeters deep—yet they appear to concentrate pathological changes in CTE, making them a logical target for imaging-based biomarker research. Despite detectable sulcal differences, the study did not find corresponding group differences on standard neuropsychological memory or learning tests, self-reported head injury counts, or PET imaging with flortaucipir for tau uptake in this cohort.
Study investigators caution that these MRI findings are an important early step rather than a diagnostic breakthrough. Larger, longitudinal, and postmortem-validated studies are necessary to determine whether sulcal morphology can reliably predict CTE pathology in living people. If confirmed, measurements of sulcal depth and width could be combined with other imaging and fluid biomarkers to form a more comprehensive risk assessment and staging framework for CTE.
The volunteer cohort included former college players with at least six years of football experience and former professional players with at least 12 years. Positions represented were linemen, receivers, and running and defensive backs; quarterbacks were excluded because of lower typical exposure to head impacts. The authors plan to broaden their research to include athletes from additional contact and collision sports and to examine other brain regions susceptible to CTE-related changes.
Funding: This research was supported by grants from the National Institutes of Health (U01NS093334, R01NS100952, K00NS1134919, R21NS140565, L32MD016519) and the Alzheimer’s Association (grant 25AARG-NTF-1377286).
Lead and participating investigators include Hector Arciniega, PhD; Leonard Jung, MD; Anya Mirmajlesi, BS; Jared Stearns, BS; Carina Heller, PhD; Brian Im, MD; Shae Datta, MD; Laura Balcer, MD; and many collaborators across institutions including Harvard Medical School, Boston University, Arizona State University, the Mayo Clinic, the Cleveland Clinic Lou Ruvo Center for Brain Health, the University of Nevada Las Vegas, Universite du Quebec, and Ludwig-Maximilians-Universitat Munchen.
Key Questions Answered:
A: The study found shallower grooves in the left superior frontal region and widening in the left occipitotemporal sulcus in players, consistent with structural alteration from repeated head impacts.
A: They may represent the first observable structural differences on MRI that reflect postmortem CTE patterns, bringing researchers closer to identifying risk markers in living subjects.
A: Not yet. The authors emphasize that further replication, longitudinal follow-up, and postmortem validation are required before these measures could be used clinically.
About this CTE and neurology research news
Author: David March
Source: NYU Langone
Contact: David March – NYU Langone
Image: Image credited to Neuroscience News
Original Research: Open access. “Sulcal morphology in former American football players” by Hector Arciniega et al., published in Brain Communications.
Abstract
Sulcal morphology in former American football players
Repetitive head impacts are linked to structural brain changes and an increased risk for chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease currently diagnosable only after death. CTE is defined by abnormal accumulation of phosphorylated tau protein, frequently concentrated at the depths of the superior frontal sulcus. Because cortical atrophy associated with tau accumulation may produce shallower and wider sulci, sulcal morphology is a promising imaging marker for identifying individuals at risk.
This study measured sulcal depth and width using automated tools on structural MRI scans from 169 former male football players (mean age 57.2 years) and 54 age-matched, unexposed male controls (mean age 59.4 years). Researchers focused on superior frontal and occipitotemporal sulci in both hemispheres and examined associations with age, football exposure metrics (age of first exposure, total years played, cumulative head impact), clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for CTE pathology, neuropsychological performance, and tau PET imaging (flortaucipir).
Statistical models showed significantly shallower left superior frontal sulci in former football players versus controls. Earlier age of first exposure and longer careers were associated with widening of the left occipitotemporal sulcus, and higher cumulative head impact exposure correlated with reduced depth in the left superior frontal region. Sulcal morphology did not correlate with clinical diagnosis, certainty levels, neuropsychological test scores, or flortaucipir uptake in this cohort.
These results indicate that sulcal morphology may reflect cumulative exposure to repetitive head impacts, especially in brain regions vulnerable to CTE pathology. Future ante- and postmortem validation studies are needed to determine whether sulcal measurements can serve as reliable in vivo biomarkers of CTE risk.