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Alterations in Network Connectivity Within Special Forces Military Personnel: A Combined Resting-FMRI and DTI Study

Allen A Champagne¹, Nicole S Coverdale², Andrew Ross³, Christopher I Murray³, Isabelle Vallee⁴, and Douglas J Cook⁵
¹School of Medicine, Queen's University, Kingston, ON, Canada, ²Center for Neuroscience Studies, Queen's University, Kingston, ON, Canada, ³Performance Phenomics, Toronto, ON, Canada, ⁴National Defence Headquarters, Ottawa, ON, Canada, ⁵Department of Surgery, Queen’s University, Kingston, ON, Canada

Synopsis

Chronic exposure to head trauma in Special Forces personnel may provide a mechanism for changes in connectivity making-up the architectural organization of functional hubs. Here, resting-state MRI and diffusion tensor imaging are integrated to highlight interdependent differences in functional and structural connectivity of Canadian military Special Operations Forces personnel, when compared to civilian. Changes in white matter integrity of fibers directly connecting functional nodes were observed, which may explain, at least in part, changes in functional markers within networks. These findings suggest a potential structural compensatory relationship between axonal injury and neural recruitment following head trauma from high-exposure military duties.

Introduction

Military personnel who engage in duties that involve repetitive firing of large caliber weapons, or exposure to explosive devices, are exposed to a significant amount of head trauma.¹ Chronic exposure to mechanical loading forces that result from such trauma may induce changes in functional and structural connectivity that make-up networks within the brain.^2–5 Altogether, these findings emphasize the need to better our understanding of the effects of repeated sub-concussive injury on the relationship between structural and functional biomarkers as an avenue to improve the existing guidelines in place to balance exposure to head impacts in military personnel, while optimizing training conditions and performance during field duties.

In this study, we use a multimodal approach to characterize the chronic effects of exposure to repetitive head trauma in Canadian Special Operations Forces (CANSOF) personnel, compared to control civilians with no lifetime exposure to head trauma. We hypothesized that distance-based⁶ changes in functional connectivity strength (FCS) would be associated with changes in white-matter (WM) integrity within the CANSOF group, as an index for the compensatory mechanisms in place within the brain to maintain architectural organization of the functional hubs that make up large-scale networks.

Methods

Fifteen CANSOF members and an equal age-matched cohort of civilian (CTLs) were enrolled in this cross-sectional design. Imaging was performed on a Siemens 3.0 T Magnetom Tim-Trio system using a 32-channel receiver head coil. BOLD-based rs-fMRI datasets (36 slices; matrix, 68x68; TR, 2000 ms; TE, 30 ms; voxel size, 3.5 mm isotropic; flip angle, 90°; no slide gap; field of view, 240 mm; GRAPPA imaging (acceleration factor, 2))⁷ were combined with DTI (60 slices; matrix, 128 mm; TR, 7800 ms; TE, 95 ms; field of view, 256 mm; slice thickness, 2 mm; voxel size, 2 mm; 30 anterior-posterior phase-encoding directions; b-value = 1000 s/mm2; GRAPPA imaging (acceleration factor, 3))⁷ to reconstruct the functional and structural networks using independent component analyses (Figure 1) and probabilistic tractography (Figure 2 and 3).^8,9

Functional and structural connectivity markers were computed based on the distance between functional seeds, in order to assess for possible group-based differences in injury susceptibility of short- (< 75mm) and long- (> 75mm) range connections within the brain (Figure 1).⁶Short- and long-FCS maps were compared between the groups using a voxel-based Student t test in AFNI’s⁹ 3dMVM.¹⁰ Results were corrected for multiple comparisons and family-wise error using a parameter-specific cluster size determined with 3dFWHMx (with spatial AutoCorrelation) and 3dClustSim,¹¹ at a corrected P-value set to 0.05. Significant clusters were used to reconstruct the associated structural networks, as described above.

Reconstructed WM tracts were assessed for possible group differences in fractional anisotropy (FA) and mean diffusivity (MD) along the tracts using the same voxel-based statistical approach described above. All parameters showing significant cluster-based differences were extracted from each region of interest and used to perform post-hoc analyses to describe the direction of the group effect.

Results

Group comparison of functional connectivity strength revealed significant differences in short- (Figure 2) and long-range (Figure 3) cortical connections across the grey-matter, between the groups. Both hyper- and hypo-connectivity differences in functional markers were observed in the CANSOF members, compared to the CTLs (Figure 2 and 3). Significant alterations in white-matter integrity of neuronal fibers (increased mean diffusivity) directly connecting disrupted functional nodes were specific to long-range connections showing hyper-connectivity patterns only (Figure 4).

Discussion

In this study, rs-fMRI and DTI were integrated to provide insight into distance-based differences in functional and structural connectivity in CANSOF personnel, in comparison to civilians. Alterations in structural integrity of fibers directly connecting functional networks may suggest potential compensatory relationship between axonal injury and neural recruitment following repetitive head trauma from high-exposure military duties.

Findings from this study emphasize that multi-parametric imaging is essential for understanding the relationship between the functional and structural components that make up neurological networks and how those may be disrupted following exposure to repetitive head trauma. This study also provides an opening for further discussions about the need to combine neuroimaging, neurocognitive, biomechanical studies, along with training modification and guidelines, to ensure that training-based exposure to head trauma for military personal can be minimized, while maintaining high-level performance and operational readiness.

Acknowledgements

The authors of this study would like to thank Mr. Don Brien for his help with data collection, as well as members of the Canadian Special Operations Forces military personnel and staff for their collaboration in this study.

References

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Figures

Figure 1. Characterization of the independent spatial components and computation of distance-based functional network masks

Figure 2. Statistical results from the voxelwise analysis of short-range FCS ((a); CANSOF_FCS = 1.73 ± 0.47, CTL_FCS = 2.21 ±0.37; P = 0.0041) and data-driven reconstruction of associated white-matter network using probabilistic tractography (b). CTLs = controls, CANSOF= Canadian special operations forces command, FCS = functional connectivity strength, ROI = region of interest, WM = white matter

Figure 3. Statistical results from the voxelwise analysis of long-range FCS showing two clusters ((a); CANSOF_FCS = 0.85 ± 0.17, CTL_FCS = 1.22 ± 0.32; P < 0.0001) and ((c); CANSOF_FCS = 2.06 ± 0.45, CTL_FCS= 1.56 ± 0.28; P = 0.0010). The data-driven reconstruction of associated white-matter network for each clusters (a,b) and (c,d) are shown respectively. CTLs = controls, CANSOF= Canadian special operations forces command, FCS = functional connectivity strength, ROI = region of interest, WM = white matter

Figure 4. Statistical results from the voxelwise analysis of the white-matter network associated with the long-range functional connectivity cluster in Fig. 3c,d (CANSOF_MD = 10.00 ± 2.13, CTL_MD = 7.43 ± 0.67; P < 0.0001). CTLs = controls, CANSOF= Canadian special operations forces command

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)

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