Altered functional connectivity underpins cognitive changes in chronic spinal cord injury

Individuals with spinal cord injury are subject to a higher risk of cognitive impairment, with executive functions being amongst the most affected ones. Even though the occurrence of cognitive impairment following spinal cord injury has been confirmed in several studies, the related alterations in the brain are not known yet. This prospective observational study aims to tackle this issue by investigating the neural correlates of executive functions in spinal cord injury. Twenty-six individuals with chronic spinal cord injury (mean age = 45.8 +/- 11.0 years, mean time since injury = 13.3 +/- 11.1 years) and 26 age- and sex-matched non-injured controls (mean age = 43.1 +/- 11.5 years) performed a phonemic verbal fluency task as a proxy for executive functions during functional magnetic resonance imaging. We compared task performance, as well as differences in brain activity and seed-based functional connectivity between groups using general linear models. Additionally, we correlated performance and functional connectivity using Pearson correlation. Performance on the verbal fluency task was significantly lower (15% less correct words) in individuals with spinal cord injury, compared to non-injured controls (P = 0.02). For the imaging analysis, two individuals with spinal cord injury were removed due to excessive motion and non-attentiveness during the imaging task, leading to a sample size of 24 for the spinal cord injury group. There was significantly lower activity in the right putamen in individuals with spinal cord injury compared to non-injured controls (P = 0.015 corrected with family-wise error). Functional connectivity between the left insula and the superior frontal gyrus was lower in spinal cord injury individuals compared to controls (P < 0.001 corrected with family-wise error). In spinal cord injury individuals, verbal fluency performance negatively correlated with functional connectivity between the right insula and the right postcentral gyrus (r = -0.82, P = 0.001 corrected with family-wise error), and between the left putamen and the bilateral precentral gyrus (r = -0.74, P = 0.002 corrected with family-wise error). Altered brain activity and functional connectivity were found in regions typically associated with executive functions in individuals with spinal cord injury. As the insula acts as a switch between brain networks, including the central executive network, to reallocate cognitive resources, its altered functional connectivity with prefrontal areas may be linked to deficits in executive functions in spinal cord injury. Interestingly, the functional connectivity of sensorimotor regions correlated with verbal fluency performance, suggesting an interference of the disrupted sensorimotor domain with cognitive functions.