Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain

Abstract

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Keywords: MRI; SCI; biomarkers; neuroplasticity.

FIG. 1.

Regions of interest (ROIs). Thirty-six ROIs were selected as seeds (red) for five resting-state networks (RSNs): default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), and unified somatomotor network (SMN).

FIG. 2.

Spinal cord injury (SCI) disrupts functional connectivity within resting-state networks (RSNs). (A) Connectivity matrixes showing correlations within and between regions of interest (ROIs) clustered into five RSNs after SCI. Exemplar SCI subject (SCI, left) is compared with an average of 37 normal subjects (CONT, right). Intra-network correlations in SCI subjects are compared with those of controls for (B) default mode network (DMN), (C) dorsal attention network (DAN), (D) control network (CON), (E) salience network (SAL), and (F) somatomotor network (SMN). n = 10 SCI subjects and 37 controls (CONT). Data are shown as notched box plots where the red line indicated median, notch indicates 95% confidence interval of the median, box indicates interquartile range (IQR), whiskers indicate 1.5 times IQR, and crosses indicate outliers. Asterisk indicates different from CONT, p < 0.05, two sample t test.

FIG. 3.

Spinal cord injury (SCI) disrupts functional connectivity between resting-state networks (RSNs). Inter-network correlations in SCI subjects are compared with those in controls among the five RSNs: default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), and somatomotor network (SMN). n = 10 SCI subjects and 37 controls (CONT). Asterisk indicates different from CONT, p < 0.05, two sample t test.

FIG. 4.

Resting-state network (RSN) correlations after incomplete (I, n = 6) and complete (C, n = 4) spinal cord injuries (SCI) were compared with those in controls (CT, n = 37). Connectivity within and among the default mode network (DMN), dorsal attention network (DAN), control network (CON), salience network (SAL), and somatomotor network (SMN) RSNs were measured. Asterisk indicates different from CT, p < 0.05, two sample t test.

FIG. 5.

Exemplar functional connectivity after complete spinal cord injury (SCI). Average functional connectivity maps are shown for select exemplar seed regions in ASIA (ASIA) A complete SCI subjects (n = 4). Left prefrontal cortex seed region showed robust connectivity with the anterior cingulate cortex and frontal lobes (top). The left insula seed was correlated with the ipsilateral and contralateral insula (middle). The left primary motor cortex correlated with the bilateral somatomotor regions (bottom).

FIG. 6.

Functional brain reorganization over time after spinal cord injury (SCI). Average change in functional connectivity between 2 months post-injury and >6 months post-injury is shown as heat maps for exemplar seed regions (n = 3 subjects). Average change in connectivity was assessed by subtracting the average of the correlation maps at two time points. The left primary motor cortex showed a robust decline in functional connectivity with the primary somatosensory cortex over time after SCI (top). The default mode network (DMN) seed, left cerebellum (Cereb) showed increased functional connectivity over time with the supplementary motor cortex, primary motor cortex, and somatosensory cortex after SCI (middle). The left visual cortex showed decreased connectivity with the primary motor cortex, but increased connectivity with the posterior cingulate gyrus and the parietal operculum (bottom).