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. 2017 Feb 15;147:589-601.
doi: 10.1016/j.neuroimage.2016.12.072. Epub 2016 Dec 24.

Investigating Resting-State Functional Connectivity in the Cervical Spinal Cord at 3T

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Free PMC article

Investigating Resting-State Functional Connectivity in the Cervical Spinal Cord at 3T

Falk Eippert et al. Neuroimage. .
Free PMC article

Abstract

The study of spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord. Two ultra-high field functional magnetic resonance imaging (fMRI) studies in humans have provided evidence for reproducible resting-state connectivity between the dorsal horns as well as between the ventral horns, and a study in non-human primates has shown that these resting-state signals are impacted by spinal cord injury. As these studies were carried out at ultra-high field strengths using region-of-interest (ROI) based analyses, we investigated whether such resting-state signals could also be observed at the clinically more prevalent field strength of 3T. In a reanalysis of a sample of 20 healthy human participants who underwent a resting-state fMRI acquisition of the cervical spinal cord, we were able to observe significant dorsal horn connectivity as well as ventral horn connectivity, but no consistent effects for connectivity between dorsal and ventral horns, thus replicating the human 7T results. These effects were not only observable when averaging along the acquired length of the spinal cord, but also when we examined each of the acquired spinal segments separately, which showed similar patterns of connectivity. Finally, we investigated the robustness of these resting-state signals against variations in the analysis pipeline by varying the type of ROI creation, temporal filtering, nuisance regression and connectivity metric. We observed that - apart from the effects of band-pass filtering - ventral horn connectivity showed excellent robustness, whereas dorsal horn connectivity showed moderate robustness. Together, our results provide evidence that spinal cord resting-state connectivity is a robust and spatially consistent phenomenon that could be a valuable tool for investigating the effects of pathology, disease progression, and treatment response in neurological conditions with a spinal component, such as spinal cord injury.

Figures

Fig. 1.
Fig. 1
Group-averaged tSNR. On the left side, group-averaged voxel-wise maps of the tSNR in the different spinal segments are displayed (transversal slice at the middle of each segment). The background image is the T2-weighted MNI-Poly-AMU template, the red-to-yellow coded tSNR is displayed only in voxels belonging to the probabilistic grey matter masks, and the colour scale is identical for all images. On the right, group-averaged segmental tSNR estimates are displayed for each horn (averaged across all voxels within a horn for each participant, i.e. taking into account all slices belonging to a segment). Both the maps on the left and the averaged estimates on the right are based on tSNR after motion correction, physiological noise modelling, and high-pass filtering (but no smoothing). Error bars represent the standard error of the mean. Abbreviations: LD, left dorsal horn; LV left ventral horn; RD, right dorsal horn; RV, right ventral horn. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 2.
Fig. 2
Laterality difference in dorsal-ventral correlations. Both for the whole cord as well as for each segmental level, we calculated the laterality difference in dorsal-ventral horn correlation coefficients. The filled black dot represents the median, the edges of the boxes cover represent the 25th and 75th percentiles and whiskers encompass approximately 99% of the data; outliers are represented by non-filled circles. Abbreviations: W, within-hemicord dorsal-ventral correlations (positive difference reflects left-dorsal-with-left-ventral > right-dorsal-with-right-ventral); B between-hemicord dorsal ventral correlations (positive difference reflects right-ventral-with-left-dorsal > right-dorsal-with-left-ventral).
Fig. 3.
Fig. 3
Connectivity averaged along the cord. The transversal slice is taken from the T2-weighted MNI-Poly-AMU template at the middle of segment C6, with the four horn masks overlaid in white and coloured arrows indicating the four different types of horn-to-horn connectivity we investigated (dorsal-dorsal connectivity is depicted in red, ventral-ventral connectivity in green, within-hemicord dorsal-ventral connectivity in blue, and between-hemicord dorsal-ventral connectivity in yellow). The bar-plot displays the group averaged correlation (+/- the standard error of the mean) for each of the four horn-to-horn correlations and the circles indicate participant-specific correlations. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
Segment-specific connectivity. The image on the left is a midline sagittal slice through the T2-weighted MNI-Poly-AMU template, with the thresholded probabilistic segments overlaid as outlines. The four transversal slices in the middle are taken from the centre of each of the segments, with the four horn masks overlaid in white. The violin plots on the right demonstrate the correlation between the four horn masks within each segment as smoothed histograms of the distributions (the mean is indicated by the grey circle; color-coding as in Fig. 3). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5.
Fig. 5
Similarity in segmental connectivity patterns. The box-plots show how strongly the connectivity pattern (i.e. the four intra-segmental correlations) of each segment correlate with the connectivity pattern in every other segment, dependent on the distance between segments (one-segment distance: C6-C7, C7-C8, C8-T1; two-segment distance: C6-C8, C7-T1; three-segment distance: C6-T1). The filled black dot represents the group median, the edges of the boxes cover represent the 25th and 75th percentiles and whiskers encompass approximately 99% of the data.
Fig. 6.
Fig. 6
Robustness of connectivity. a) Depicted are the number of analyses (out of a total of 96) that show positive (white) or negative (black) connectivity. Only dorsal-dorsal and ventral-ventral connectivity is robust against variations in the analysis pipeline. Abbreviations: D, dorsal-dorsal; V, ventral-ventral; W, within-hemicord dorsal-ventral; B, between-hemicord dorsal-ventral. b) Depicted are the number of analyses (out of a total of 96) that show significant (light grey) or nonsignificant (dark grey) connectivity, this time limited to dorsal-dorsal and ventral-ventral connectivity. Abbreviations: D, dorsal-dorsal; V, ventral-ventral. c) The radial bar-plots depict which analysis choices contribute to significant/nonsignificant connectivity as observed in b). The innermost ring shows significance/nonsignificance and is a grouping factor for the next rings: ROI creation, temporal filtering, nuisance regression, and connectivity metric. Abbreviations: PROB, probabilistic masks; COG, centre of gravity masks; HP, high-pass temporal filtering; BP, band-pass temporal filtering; WM, white matter; CSF, cerebrospinal fluid; NS, non-spinal; FULL: full correlation; PARTIAL: partial correlation; REGPARTIAL, regularized partial correlation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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References

    1. Alstermark B., Kümmel H. Transneuronal transport of wheat germ agglutinin conjugated horseradish peroxidase into last order spinal interneurones projecting to acromio- and spinodeltoideus motoneurones in the cat. 1. Location of labelled interneurones and influence of synaptic activity on the transneuronal transport. Exp. Brain Res. 1990;80:83–95. - PubMed
    1. Andersson, J., Jenkinson, M., Smith, S., 2010. Non-linear registration, aka spatial normalisation. FMRIB technical report TR07JA2.
    1. Balchandani P., Naidich T.P. Ultra-high-field MR Neuroimaging. AJNR Am. J. Neuroradiol. 2015;36:1204–1215. - PMC - PubMed
    1. Bannatyne B.A., Edgley S.A., Hammar I., Jankowska E., Maxwell D.J. Differential projections of excitatory and inhibitory dorsal horn interneurons relaying information from group II muscle afferents in the cat spinal cord. J. Neurosci. 2006;26:2871–2880. - PMC - PubMed
    1. Baron E. Spinal cord and spinal nerves: gross anatomy. In: Standring S., editor. Gray's Anatomy: The Anatomical Basis of Clinical Practice. 2015. pp. 762–773.

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