Evaluation of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury: A Large-Scale Network Analysis Using Network-Based Statistic

Abstract

Large-scale network analysis characterizes the brain as a complex network of nodes and edges to evaluate functional connectivity patterns. The utility of graph-based techniques has been demonstrated in an increasing number of resting-state functional MRI (rs-fMRI) studies in the normal and diseased brain. However, to our knowledge, graph theory has not been used to study the reorganization pattern of resting-state brain networks in patients with traumatic complete spinal cord injury (SCI). In the present analysis, we applied a graph-theoretical approach to explore changes to global brain network architecture as a result of SCI. Fifteen subjects with chronic (> 2 years) complete (American Spinal Injury Association [ASIA] A) cervical SCI and 15 neurologically intact controls were scanned using rs-fMRI. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI) or nodes. The average time series was extracted at each node, and correlation analysis was performed between every pair of nodes. A functional connectivity matrix for each subject was then generated. Subsequently, the matrices were averaged across groups, and network changes were evaluated between groups using the network-based statistic (NBS) method. Our results showed decreased connectivity in a subnetwork of the whole brain in SCI compared with control subjects. Upon further examination, increased connectivity was observed in a subnetwork of the sensorimotor cortex and cerebellum network in SCI. In conclusion, our findings emphasize the applicability of NBS to study functional connectivity architecture in diseased brain states. Further, we show reorganization of large-scale resting-state brain networks in traumatic SCI, with potential prognostic and therapeutic implications.

A Systematic Review of Investigations into Functional Brain Connectivity Following Spinal Cord Injury

“…Since the patients involved all suffered from complete cervical injury these results are observed in the absence or a residual reciprocal sensorimotor communication. The authors also analyzed their recordings on 15 patients with complete cervical SCI with GA of the FC using network-based statistics over 58 ROIs in each hemisphere (Kaushal et al, 2017a ). They observed diminished RS connectivity strengths of a whole-brain sub-network in SCI patients compared to healthy controls.…”

Quantitative MRI of rostral spinal cord and brain regions is predictive of functional recovery in acute spinal cord injury

“…Crucially, less atrophy in the cerebellum was associated with better sensory outcomes and increases in R2* in the cerebellum was associated with lower extremity motor scores. The association between structural changes in the cerebellum with sensorimotor outcomes highlights the role of the cerebellum in recovery processes after SCI ( Grabher et al, 2015 ; Kaushal et al, 2016 ). The observed changes might serve to facilitate recruitment of neural substrates to compensate for neural deficits following SCI.…”

Cortical Reorganization of Sensorimotor Systems and the Role of Intracortical Circuits After Spinal Cord Injury

“…Activation of novel secondary motor areas immediately after injury could reflect their involvement in the development of new motor strategies. The resting-state functional connectivity between brain regions also seems to change after spinal cord injury in humans [85][86][87].…”