Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans

Abstract

The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning <20 mm along the superior-inferior axis. In a subset of participants (n = 10), the cervical spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity.

Altered Cervical Spinal Cord Resting‐State Activity in Fibromyalgia

“…The mean ventral‐ventral (V‐V), dorsal‐dorsal (D‐D), ventral‐dorsal within (V‐D within) hemicord, and ventral‐dorsal between (V‐D between) hemicord functional connectivity was analyzed. Bilateral motor (V‐V functional connectivity) and sensory (D‐D functional connectivity) functional spinal cord networks have been observed and reproduced across studies in healthy individuals . In alignment with these previous observations, we observed significant V‐V connectivity (r > 0) for both the patients (mean ± SEM r = 0.078 ± 0.018, P < 0.001) and controls (r = 0.104 ± 0.033, P = 0.008), as well as significant D‐D connectivity for both the patients (r = 0.065 ± 0.014, P < 0.001) and controls (r = 0.087 ± 0.030, P = 0.013).…”

“…Neither V‐D within hemicord connectivity ( P = 0.149) nor V‐D between hemicord connectivity ( P = 0.409) differed between the groups. Using graph metrics, the functional spinal cord network demonstrated small world properties at the lower link densities for patients and controls as previously reported . Mean ± SEM small worldness at the 10% link density was 2.354 ± 0.365 and 2.240 ± 0.302 for the patients and controls, respectively.…”

“…44), and recently these metrics have been extended to the spinal cord (37). We recently demonstrated that unilateral thermal stimulation to the forearm disrupted the bilateral sensory network (D-D functional connectivity), while increasing global efficiency and decreasing modularity of the cervical spinal cord functional network in healthy controls (24). As sensory pro-cessing is thought to be altered in fibromyalgia, we expected to observe differences in the patterns of functional connectivity in patients compared to healthy controls.…”

“…Preprocessing of the functional cervical spinal cord images was performed as previously described using a combination of in‐house customized scripts, the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain software library (FSL), and the Spinal Cord Toolbox, version 3.0 (see Supplementary Methods).…”

“…More recently, this line of research has expanded to study the functional organization of intrinsic spinal cord networks. Growing evidence supports the presence of bilateral motor (left and right ventral horn functional connectivity) and bilateral sensory (left and right dorsal horn functional connectivity) rs-fMRI spinal cord networks (32)(33)(34), and the functional organization within these networks is altered in nonhuman primates after spinal cord injury and in humans during unilateral thermal stimulation (24,35). As aberrant sensory processing within the spinal cord is thought to partially underlie fibromyalgia, we also investigated the functional organization of spinal cord networks in the present study.…”