Right-handedness is associated with myelination asymmetry of the motor tracts in the human spinal cord
Manuel Taso1,2,3,4, Oliver M. Girard1,3, Guillaume Duhamel1,3, Maxime Guye1,3, Jean-Philippe Ranjeva1,3,4, and Virginie Callot1,3,4

1CRMBM UMR 7339, Aix-Marseille Université, CNRS, Marseille, France, 2LBA UMR T 24, Aix-Marseille Université, IFSTTAR, Marseille, France, 3CEMEREM, AP-HM, Pôle d'imagerie médicale, Marseille, France, 4iLab-Spine international associate laboratory, Marseille/Montréal, France

### Synopsis

Handedness is known to influence brain structure. However, no evidences of such influence in the spinal cord (SC) exist. Hence, we propose to use multi-parametric MRI (DTI and inhomogeneous MT, both sensible to microstructural properties), combined with atlas-based analysis in specific fascicles, to assess the influence of handedness on the SC structure. Results demonstrated that right-handers presented higher ihMTR/MTR values in the right motor tracts, suggesting an asymmetric myelination while left-handers did not present differences between left and right regions. This is consistent with brain findings suggesting that right-handedness is associated with higher structural asymmetry in the central nervous system.

### Target audience

Neuroscientists and clinicians involved in spinal cord structure and function assessment using MRI

### Introduction

Handedness is known to influence brain structure, and more especially asymmetry of the brain microstructure. This has been previously assessed using morphological analyses (especially sulcal depth1) and diffusion MRI2,3,4, demonstrating structural asymmetry differences between left-handed and right-handed healthy subjects. The objectives of this work were to assess whether handedness-related asymmetry also exists within the spinal cord (SC) and whether it may influence tract organization and myelination of the lateral motor tracts. For that purpose, diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT)5,6, which were shown to be robust and sensitive to detect variations in SC microstructure7, have been used.

### Material and methods

MR scanning: 29 volunteers (mean age 31±9yo) were recruited. Handedness was assessed using the Edinburgh test 8 leading to a cohort of 10 left-handed (LH, Edinburgh < -50%) and 19 right-handed volunteers (RH, Edinburgh > 50%). MRI was performed at 3T using standard coils. Anatomical imaging consisted in an axial ECG-gated T2*-w sequence (0.5x0.5x5mm3, 7 slices, 1 slice/cervical level positioned mid-vertebrally and perpendicularly to the SC curve). Axial HASTE ihMT5,6 sequence was acquired at the C2 and C5 levels (resolution 0.9x0.9x10mm3, ECG-gating, TR=4s, 500 saturation pulses, offset 7 KHz, alternation between single and dual frequency saturation experiments). Retrospective data filtering9 was performed using ECG data prior to ihMTR (=ihMT/M0) and MTR (=1-MT/M0) calculation. Monopolar single-shot SE-EPI DTI was acquired at the same levels (0.9x0.9x10mm3, b=0 and 800 s/mm2, 30 directions, ECG-gating). FA, ADC, $\lambda_{//}$ and $\lambda_{\bot}$ and were estimated using vendor software.

Post-processing: an automated post-processing pipeline previously described was used7, providing an automated SC segmentation10 as well as a normalization of both mp-MRI and anatomical data in a reference space11, thereby allowing quantification of the DTI/ihMT metrics in specific WM fascicles and GM horns. In this study we looked more specifically at the lateral motor tracts (corticospinal/rubrospinal/reticulospinal tracts) derived from the WM pathways atlas12 included in the MNI-Poly-AMU template13 and at the left and right anterior GM horns7. Asymmetry (A) of the metrics, defined as the right-to-left ratio of the metric were also calculated. Statistical analyses (two-sample t-test, JMP9, SAS) were performed to compare not only LH and RH groups in the left and right regions, but also left and right tracts within RH or LH group, as well as asymmetry coefficients for both LH and RH groups.

### Results

No significant differences were observed when considering the diffusion metrics (FA, ADC, $\lambda_{\ //}$ and $\lambda_{\bot}$). When considering the MT and ihMT ratios and asymmetry coefficient, no significant difference could be observed between LH and RH volunteers when looking at the motor regions. However, significant differences were detected between left and right regions within the RH group (fig.2). More specifically, higher ihMTR (5.96±0.55 vs 5.58±0.64% for right and left tracts respectively, p<0.001 ; A = 1.07) (cf. fig. 1) and MTR (27.4±2.4 vs 25.4±3% respectively, p<0.0005, A=1.08) were observed in the right WM motor tracts as compared to the left ones. When performing the same comparison within the LH volunteers, no significant differences were detected for ihMTR (6.02±0.72 vs 5.85±0.69 for right and left motor tracts respectively, p=0.81 ; A=1.03) nor MTR (26.9±4.2 vs 26.4±3.6 % respectively, p=0.99; A=1.03). No significant differences were detected in the somato-sensory tracts, nor in the GM.

### Discussion/Conclusion

Through the observation of MT and ihMT metrics variations, this study highlighted significant structural differences in the SC when considering LH and RH. In particular, myelination differences in the lateral motor tracts seems to be right-hander specific as seen when comparing left and right regions in each group. This study is the first reporting an asymmetric behavior in the SC according to handedness, with a focus on motor tracts myelination. Although structural asymmetry has been demonstrated in the brain using either DTI2,3,4 or morphometry1, no report demonstrated different myelination in the pyramidal tract in the brain so far. A first interesting perspective would therefore be to use ihMT to study the normal brain myelination asymmetry and to see whether confirmation of the results presented here could arise in the brain. Reversely, extension of the present work to study handedness influence on the SC motor GM morphometry, as performed in the brain, is under investigation. These results may be of particular interest to study for example normal or pathological aspects of SC structure and function using MRI.

### Acknowledgements

No acknowledgement found.

### References

1 Amunts et al, NeuroImage, 1996. 4(3 Pt 1): p. 216-22; 2 Powell et al, Neuroscience, 2012. 207: p. 227-42; 3 Seizeur et al, Surg Radiol Anat, 2014. 36(2): p. 111-24; 4 Buchel et al, Cerebral Cortex, 2004. 14(9): p. 945-51; 5 Varma et al, MRM, 2015. 73(2): p. 614-22; 6 Girard et al, MRM, 2015. 73(6): p. 2111-21; 7 Taso et al, ISMRM 2015 p.681; 8 Oldfield, Neuropsychologia, 1971. 9(1): p. 97-113; 9 Girard et al., MRM, 2015 (in revision) ; 10 De Leener et al, NeuroImage, 2014. 98: p. 528-36; 11 Taso et al, NeuroImage, 2015. 117: p. 20-28; 12 Lévy et al, NeuroImage, 2015. 119(0): p. 262-271; 13 Fonov et al, NeuroImage, 2014. 102P2: p. 817-827

### Figures

Fig. 1 Distribution of ihMTR (fig 1a) and MTR (fig 1b) values for right-handed and left-handed volunteers in left motor and right motor ROIs

Fig. 2 (a) AMU40 T2*-w template with left (blue) and right (green) lateral motor regions (b) average ihMTR maps for RH exhibiting asymmetry in the lateral motor tracts

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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