Investigating resting-state functional connectivity in the cervical spinal cord at 3T

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.

Resting‐state functional connectivity in the rat cervical spinal cord at 9.4 T

“…From group analysis box plots of different studies, specific horn–horn functional connectivity patterns within segments appears to vary across different species. For example, the functional connectivity between ventral and dorsal horns has been observed in squirrel monkeys, whereas such connections are still speculative in humans . Similarly, in rats, ipsilateral dorsal–ventral connectivity was observed to have a weaker correlation strength, but remains statistically significant when compared with control regions.…”

“…We previously reported robust detection of rsfMRI connectivity in human subjects at ultrahigh field (7 T) using a hypothesis driven region‐of‐interest (ROI) analysis . Specifically, Barry et al found consistent functional connectivity in bilateral motor and sensory networks, while a more recent paper from Eippert et al confirmed these findings and provided further convincing evidence that spinal cord rsfMRI may be a robust technique for clinical applications . Using a similar ROI‐based approach, Liu et al reported that resting‐state networks in the upper cervical spinal cord show strong connectivity, and compared rsfMRI signals across different vertebral levels .…”

Robust spinal cord resting‐state fMRI using independent component analysis‐based nuisance regression noise reduction

“…Spinal cord Resting‐State functional magnetic resonance imaging (rsfMRI) is a promising technique that offers a new way to investigate intrinsic spinal cord function in health and disease . However, several technical challenges still hamper its clinical application.…”

Neuroimaging mechanisms in pain: from discovery to translation

“…31,103 What is exciting now is that we are discovering new biology-for example, the fact that the human spinal cord has intrinsically organised resting state networks. 5,33,35,63 Working at ultra high fields, such as 7 Tesla, S118 I. Tracey · 158 (2017) S115-S122 PAIN ® brings very significant signal-to-noise benefits but with new hurdles to overcome. 13 The quality of the structural pictures is sufficient to drive clinical application now and hopefully it will not take much longer before we can deliver robust and reproducible functional data from controls, experimental medicine models, and patients 141 that will contribute further towards our understanding of the role of the human spinal cord in acute and chronic pain.…”