Publications & Posters

Exposure to Repetitive Head Impacts Is Associated With Corpus Callosum Microstructure and Plasma Total Tau in Former Professional American Football Players

Journal of Magnetic Resonance Imaging | June 16, 2021

Kochsiek J, O’Donnell LJ, Zhang F, Bonke EM, Sollmann N, Tripodis Y, Wiegand TLT, Kaufmann D, Umminger L, Di Biase MA, Kaufmann E, Schultz V, Alosco ML, Martin BM, Lin AP, Coleman MJ, Rathi Y, Pasternak O, Bouix S, Stern RA, Shenton ME and Koerte IK

J Magn Reson Imaging. 2021




Exposure to repetitive head impacts (RHI) is associated with an increased risk of later-life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown.


To investigate whether RHI exposure is associated with later-life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning.

Study Type

Retrospective cohort study.


Seventy-five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms.

Field Strength/Sequence

Diffusion-weighted echo-planar MRI at 3 T.


Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self-report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free-water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1-7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT-A) and Part B (TMT-B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF-A).

Statistical Tests

Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures.


RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Higher trace, AD, and RD of CC1 were associated with better performance (P < 0.05) in TMT-A (trace, r = 0.33; AD, r = 0.31; and RD, r = 0.28) and TMT-B (trace, r = 0.31; RD, r = 0.34). Higher FA and AD of CC2 were associated with better performance (P < 0.05) in TMT-A (FA, r = 0.36; AD, r = 0.28), TMT-B (FA, r = 0.36; AD, r = 0.27), COWAT (FA, r = 0.36; AD, r = 0.32), and BRI (AD, r = 0.29).

Data Conclusion

These results suggest an association among RHI exposure, CC microstructure, plasma total tau, and clinical functioning in former professional American football players.