Plasticity of the Injured Human Spinal Cord: Insights Revealed by Spinal Cord Functional MRI

Abstract

IntroductionWhile numerous studies have documented evidence for plasticity of the human brain there is little evidence that the human spinal cord can change after injury. Here, we employ a novel spinal fMRI design where we stimulate normal and abnormal sensory dermatomes in persons with traumatic spinal cord injury and perform a connectivity analysis to understand how spinal networks process information.MethodsSpinal fMRI data was collected at 3 Tesla at two institutions from 38 individuals using the standard SEEP functional MR imaging techniques. Thermal stimulation was applied to four dermatomes in an interleaved timing pattern during each fMRI acquisition. SCI patients were stimulated in dermatomes both above (normal sensation) and below the level of their injury. Sub-group analysis was performed on healthy controls (n = 20), complete SCI (n = 3), incomplete SCI (n = 9) and SCI patients who recovered full function (n = 6).ResultsPatients with chronic incomplete SCI, when stimulated in a dermatome of normal sensation, showed an increased number of active voxels relative to controls (p = 0.025). There was an inverse relationship between the degree of sensory impairment and the number of active voxels in the region of the spinal cord corresponding to that dermatome of abnormal sensation (R2 = 0.93, p<0.001). Lastly, a connectivity analysis demonstrated a significantly increased number of intraspinal connections in incomplete SCI patients relative to controls suggesting altered processing of afferent sensory signals.ConclusionsIn this work we demonstrate the use of spinal fMRI to investigate changes in spinal processing of somatosensory information in the human spinal cord. We provide evidence for plasticity of the human spinal cord after traumatic injury based on an increase in the average number of active voxels in dermatomes of normal sensation in chronic SCI patients and an increased number of intraspinal connections in incomplete SCI patients relative to healthy controls.

Characterizing the Location of Spinal and Vertebral Levels in the Human Cervical Spinal Cord

“…12,18 The development of methods to manage the hostile imaging environment and to account for cardiorespiratory-related motion has allowed improved applications to detect structural (such as diffusion and magnetization transfer imaging) and functional anomalies that occur in relation to traumatic injury of the spinal cord. 1,2,19,20 Other disorders, such as multiple sclerosis, have also benefited from spinal cord imaging. 21 Degenerative spinal disease, such as cervical spondylosis, is an increasing health burden due to the aging population.…”

“…For example, diffusion tensor imaging and magnetization transfer can be used to follow the integrity of white matter tracts in specific regions of the human spinal cord 1 ; fMRI can be used to track the spinal response to a particular stimulus, reflecting the integrity of specific functional circuits. 2 Recently, the microstructure of the corticospinal motor pathway was mapped; imaging characteristics of this map correlated with clinical function. 3 The ultimate goal of early detection of subclinical recovery or deterioration should be to personalize treatment strategies in both the acute and chronic phases of injury.…”

“…For example, manually segmented templates have been created on the basis of specific anatomic information of the nerve rootlet position. 2 Perhaps most common is to infer neuroanatomic positions within the spinal cord by counting the adjacent vertebral bodies and stating that, for example, the C6 spinal cord segment is adjacent to the C5 vertebral body. 7 This latter approach coincides with widely accepted neuroanatomy textbooks, but the error associated with vertebral body measurements to predict the immediate caudal spinal cord segment has not been investigated.…”

Intrinsically organized resting state networks in the human spinal cord

“…Distinct spatial maps due to cardiac and respiratory noise sources have been revealed by single subject ICA (25)(26)(27), and a seed-based approach demonstrated correlations between ventral horns and between dorsal horns (28), but no group patterns of circumscribed motor or sensory networks have yet been found; also only a few investigations of task-based functional connectivity have been performed (29)(30)(31). One reason for the apparent lack…”

From Pneumomyelography to Cord Tractography: Historical Perspectives on Spinal imaging

“…In multiple sclerosis, magnetization transfer imaging [23], DTI fiber tractography [24], myelin water fraction estimation [25] and DTI metrics [26] have all been successfully correlated with clinical metrics. Spinal functional MRI has been applied both to multiple sclerosis [27] and chronic incomplete spinal cord injury [28]. The majority of quantitative spinal cord MRI studies are undertaken in ALS, MS and spinal cord injuries and very few dedicated imaging studies can be identified in hereditary spastic paraparesis and spinocerebellar ataxias [29].…”