INTRODUCTION: Long-term consequences of heading associated repetitive head impacts (RHIs) in football (soccer) are an area of scientific debate with large clinical relevance. Functional magnetic resonance imaging (fMRI) based resting-state functional connectivity (FC) in intrinsic networks of semi-professional football players revealed increased FC within the default mode network (DMN) with large exposure to RHIs, but longitudinal fMRI investigations are still sparse. We therefore aimed to determine and evaluate potential FC changes in the DMN and the salience network (SN) in relation to heading in professional football players prospectively. METHODS: 14 active professional male football players (20.36 ± 3.34 yrs.) were included in this exploratory, longitudinal study and were scanned twice with a 3T Philips Ingenia MRI scanner between November 2017 and May 2019. Between the scans, all trainings and matches were videotaped and all performed headers were counted. Resting-state fMRI data was analyzed with the CONN functional connectivity toolbox (v.20.b) using default preprocessing and denoising steps. Smoothing was set to 6mm. T1 weighted structural MRI sequences were included for individual anatomical reconstruction of the fMRI data. A region of interest (ROI)-to-ROI approach was applied to compare the differences between the measurements while controlling for age, focusing on ROIs of the DMN and the SN. 12 ROIs with 66 connections were analyzed with non-parametric statistics (cluster-level p-FDR <0.05). Spearman correlations between total header number and significant FC changes were calculated. RESULTS: During the observation period of 10 to 18 months (median 17.2 months) 5822 headers in total (min.: 146, max.: 943, median: 340.5) were documented. FC increased significantly within the SN (p-FDR=0.023) specifically between the right supramarginal gyrus (SMG) and the anterior cingulate cortex (p-FDR=0.050) and between the right SMG and the left rostral prefrontal cortex (p-FDR=0.02). The numbers of total headers did not correlate with any changes in FC. CONCLUSION: This study showed explorative FC changes within the SN, a relevant intrinsic network, suggesting functional resting-state changes in football players. However, within DMN changes with increasing impact exposure were not found. Duration of the observation period or level-of-play might have contributed to these results. A missing association between heading and SN FC changes might indicate an adaptation to playing football in general rather than a specific heading effect. To test this hypothesis larger samples and a control group are needed. Future studies should also include male and female football players of various levels-of-play and player`s incidence rates as the observation period of this study varied.
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