Brain connectivity and cognitive processing speed in multiple sclerosis: A systematic review

Background: Processing speed (PS) decline is the most commonly observed cognitive deficit in people with multiple sclerosis (MS) resulting in a significant impact on quality of life. Despite its importance, knowledge of the underlying neural substrates is lacking. Objective: As MS is increasingly recognised as a disconnection syndrome, our aim was to carry out a systematic literature review to clarify the relationship between PS performance and MRI measures of structural and functional brain connectivity in people with MS. Search methods: A literature search was carried out on PubMed and Web of Science that included publications predating September 2017. Additional articles were added after inspection of the reference lists of all selected papers. Data extraction All selected papers were categorised in three sections according to the MRI measures investigated, independently or both. Quality assessment was carried out using a customised set of criteria. Results: Thirty-two articles met the inclusion criteria and were included in the review. Microstructural integrity of the anterior corpus callosum and functional connectivity of frontal areas were more consistently found to correlate with PS performance, though high variability of findings was observed across studies. Several methodological flaws emerged from the reviewed literature. Conclusions: Despite the observed trends, no definite conclusions can be drawn on the relationship between brain connectivity and PS decline in MS given the limitations of the current literature. Future investigations may benefit from theoretical and methodological advances to clarify how MS-related brain damage affects patients' cognition.