Hypoconnectivity and hyperfrontality in retired American football players

Adam Hampshire, Alex MacDonald, Adrian M Owen, Adam Hampshire, Alex MacDonald, Adrian M Owen

Abstract

Recent research has raised concerns about the long-term neurological consequences of repetitive concussive and sub-concussive injuries in professional players of American Football. Despite this interest, the neural and psychological status of retired players remains unknown. Here, we evaluated the performances and brain activation patterns of retired National Football League players (NFL alumni) relative to controls using an fMRI-optimised neuropsychological test of executive function. Behaviourally, the NFL alumni showed only modest performance deficits on the executive task. By contrast, they showed pronounced hyperactivation and hypoconnectivity of the dorsolateral frontal and frontopolar cortices. Critically, abnormal frontal-lobe function was correlated with the number of times that NFL alumni reported having been removed from play after head injury and was evident in individual players. These results support the hypothesis that NFL alumni have a heightened probability of developing executive dysfunction and suggest that fMRI provides the most sensitive biomarker of the underlying neural abnormality.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1. The Spatial Planning Task (SP).
Figure 1. The Spatial Planning Task (SP).
(1a) The SP task is a variant on the Tower of London paradigm, which is commonly used to assess executive function. Two arrays of coloured balls are presented in vertical tubes. In the planning condition, the participant must work out the minimum number of moves required to rearrange the balls in the top array so that they match those in the bottom array. Difficulty varies from 2 to 4 moves. There are also counting trials, in which different numbers of balls are placed in the two arrays and the participant must subtract the number of balls at the top from the number at the bottom. (1b) In the fMRI analysis, the counting condition is used as a visual and attentional control. Contrasting planning minus counting (voxel-wise FDR correction for the whole brain mass p < 0·05) localises a dorsal frontoparietal network including middle frontal gyrus, frontopolar cortex, and inferior parietal cortex. (1c) In the ROI analysis, there was significantly greater activation in the DLPFC in NFL alumni relative to controls, particularly at the more difficult planning levels (error bars report 90% confidence interval). (1d) There was a significant interaction between planning level and group within the FPC ROI (error bars report 90% confidence interval). (1e) In accordance with the ROI analysis, NFL alumni showed extensive clusters of hyperactivation within the DLPFC bilaterally (rendered at p < 0·01 with 500 voxel extent threshold. Peak coordinates significant with whole brain FDR voxel-wise correction – see table 1a). (1f) The interaction between Group and Planning Level showed extensive clusters of hyperactivation in NFL alumni relative to controls within the frontopolar cortices (rendered at p < 0·01 uncorrected with a 500 voxel extent threshold. Peak activation coordinates significant with whole brain FDR voxel-wise correction – see table 1b).
Figure 2. Non-parametric correlations and functional connectivity…
Figure 2. Non-parametric correlations and functional connectivity analysis.
(2a) When the ranked number of times NFL alumni had been sent off the field due to head injury (Ranked Times Off - RTO) was used to predict activation during the SP task in a non-parametric permutation analysis, extensive clusters of activation were evident in the right DLPFC extending into the FPC. A more focal cluster was also evident within the PC (image rendered at p < 0·01 uncorrected with FWE cluster correction within a mask that includes all regions that are active during task relative to rest – see table 1c). (2b) When beta weights for the physiological predictor function were contrasted across groups, NFL alumni showed generally lowered functional connectivity between the right DLPFC seed region and the left DLPFC, the right FPC and the PC bilaterally. Yellow regions show the t-test of beta weights for the physiological predictor collapsed across participants with FWE voxel-wise correction of p < 0·05 for the whole brain mass t and p values report cross-group analyses for the indicated connections.
Figure 3. Granger Causality analysis of affective…
Figure 3. Granger Causality analysis of affective connectivity.
NFL alumni had lowered mean GC within the dorsal frontoparietal network relative to controls. This abnormal affective connectivity was characterised by a significant reduction in GC from the PC to the DLPFC, from the FPC to the DLPFC, and from the PC to the FPC. Red lines represent links with significantly reduced GC in NFL alumni relative to controls. Inset graphs display GC for NFL alumni and control groups with error bars reporting the standard error of the mean.

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