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.
Highlights
The temporal and spatial organization of intrinsic brain activity is currently a subject of intense research
Functional magnetic resonance imaging studies have shown that spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signal are organized into distinct and reproducible resting-state networks, such as the sensorimotor, default-mode, or executive-control networks (Buckner et al, 2013; Fox and Raichle, 2007; Power et al, 2014)
Magnetic resonance imaging (MRI) data were acquired in an eyesopen state on a 3 T system (Magnetom Trio, Siemens, Erlangen, Germany). functional magnetic resonance imaging (fMRI) data were collected as the last session in a larger spinal fMRI experiment consisting of two sensory and two motor sessions using a recently developed slice-specific z-shim protocol (Finsterbusch et al, 2012)
Summary
The temporal and spatial organization of intrinsic brain activity is currently a subject of intense research. With the neurophysiological origin of these resting-state signals becoming more evident (Leopold and Maier, 2012; Schölvinck et al, 2013) and their clinical relevance more appreciated (Fox and Greicius, 2010; Zhang and Raichle, 2010), they are increasingly used to probe the integrity and properties of neural circuits in health and disease These organized resting-state fluctuations are not an exclusively cortical phenomenon, but have been observed in subcortical regions as low as the pons and medulla (Beissner et al, 2014; Bianciardi et al, 2016), raising the question whether they constitute a functional signature of the entire central nervous system and might be detectable in the spinal cord as well. The clinical significance of such resting-state connectivity was recently demonstrated in a non-human primate model of spinal cord injury, where a spatially-specific influence of lesions on spinal cord functional connectivity was observed (Chen et al, 2015)
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