# Shape analysis of the amygdala, hippocampus and thalamus in former American football players

## TL;DR

This study finds that former American football players have structural brain changes in the hippocampus, amygdala, and thalamus, linked to early exposure and head impacts.

## Contribution

The study introduces surface-based shape metrics as potential in vivo markers for brain changes due to repetitive head impacts in athletes.

## Key findings

- Former football players showed bilateral surface area contractions in the hippocampus and amygdala compared to controls.
- Earlier age of first football exposure correlated with surface contractions in the thalamus and left hippocampus.
- Greater cumulative linear acceleration was linked to hippocampal surface contractions and reduced thalamic thickness.

## Abstract

Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

This study demonstrates that former American football players showed localized shape alterations in the hippocampal, amygdala and selective thalamic changes relative to controls. Earlier first exposure to football and higher cumulative head-impact accelerations were associated with greater changes. Findings suggest that surface-based shape metrics may provide sensitive in vivo markers of exposure to repetitive head impacts.

Graphical Abstract