Spinal Cord Inflammation Seen to Change Brain Connectivity on fMRIs

Findings may have important applications for rehabilitation of NMOSD patients

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Inflammatory episodes in the spinal cord of people with neuromyelitis optica spectrum disorder (NMOSD) resulted in changes in functional connectivity in the brain, an imaging study shows.

Functional connectivity refers to the correlation between brain signals over time that reflects functional connections between two or more brain regions.

Reduced functional connectivity in a brain area called the basal ganglia network was associated with worse physical disability and, particularly, gait disturbances in patients diagnosed with NMOSD.

The researchers suggested that these findings may have important applications in monitoring and designing rehabilitative approaches.

The imaging study, “The role of basal ganglia network in neural plasticity in neuromyelitis optica spectrum disorder with myelitis,” was published in the journal Multiple Sclerosis and Related Disorders.

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Brain Inflammation May Complicate NMOSD Diagnosis

NMOSD is a progressive autoimmune disease marked by inflammation of the optic nerve (optic neuritis), which sends and receives signals from the eyes, and the spinal cord (myelitis), leading to symptoms such as vision problems, pain, and sleep difficulties.

The long-term impact of spinal cord injury on brain function has been demonstrated in many spinal cord disorders. Such injury can lead to altered brain activity and nerve degeneration.

Studies in NMOSD patients have also suggested alterations to brain structure and activity after myelitis. Still, this research mainly focused on certain brain regions without exploring functional connectivity changes across the whole brain.

Now, researchers based at the University of Electronic Science and Technology of China applied functional MRI (fMRI), which measures whole brain activity, to NMOSD patients with myelitis to find connections between clinical features and functional connectivity.

“The aim of this study was to characterize neural representation after spinal cord injury in NMOSD and provide a research basis for developing new neurorehabilitation strategies,” the researchers wrote.

The team compared fMRI images from 20 NMOSD patients to 19 age- and sex-matched healthy individuals. All patients had experienced at least one acute myelitis attack and were still within the chronic disease stage when enrolled. Optic neuritis attacks were reported in 11 patients (55%), and four (20%) had severe visual impairment.

Imaging analysis shows some brain abnormalities in NMOSD

fMRI analysis revealed brain regions with significantly different functional connectivities between the NMOSD and control groups. Patients exhibited significantly increased functional connectivity in the basal ganglia network, a group of nerve clusters in the brain’s center involved in motor control, pain regulation, and emotion.

Functional connectivity was also enhanced in part of the frontoparietal network, involved in problem-solving and working memory (memory required for day-to-day tasks). In contrast, decreased connectivity was observed in the sensorimotor network, responsible for sensing physical inputs, and the dorsal attention network, for the control of attention and working memory.

The team then compared image data with patients’ disabilities, as assessed by the expanded disability status scale (EDSS), with higher scores reflecting worse disability.

Higher EDSS scores significantly correlated with reduced functional connectivity strength in the amygdala, part of the basal ganglia network responsible for decision-making and emotional responses (including fear, anxiety, and aggression). This correlation was mainly driven by the EDSS subscores related to gait (walking). Further, gait subscores also correlated with connectivity in the default mode network, a network more active while resting than while performing attention-demanding tasks.

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According to the researchers, in the chronic stages of NMOSD, the basal ganglia network may be highly active in neural plasticity processes, the ability of nerve networks in the brain to change by growth and reorganization.

Correlations between the functional connectivity of other regions of interest and EDSS scores or subscores for gait function were not statistically significant.

Finally, functional connectivity between regions of interest and the whole brain was examined. Compared to controls, the patients presented significantly increased functional connectivity strengths between the caudate, part of the basal ganglia network, and several brain regions, including the cerebellum at the base of the brain, and different areas within the cerebral cortex, the brain’s outermost layer.

“Our study demonstrated wide resting-state functional connectivity alterations in patients with NMOSD after myelitis,” the researchers concluded. “Understanding neural plasticity phenomena and characteristics, especially in NMOSD patients after myelitis, may have important applications in monitoring and designing rehabilitative approaches.”