Functional Connectivity in Multiple Sclerosis

Functional connectivity examines the temporal correlations in neural activity between distinct brain regions, often using resting-state functional MRI or electrophysiological techniques. In multiple sclerosis (MS), demyelinating lesions and neurodegeneration disrupt structural pathways and trigger widespread alterations in functional networks. Early stages may show compensatory increases in connectivity, whereas progressive disease often leads to reduced modularity and impaired hub function, particularly within the thalamus and default-mode network. Dynamic analyses have revealed that the temporal variability of network configurations—sometimes referred to as brain flexibility—can both reflect and predict clinical impairment. Integrating structural and functional connectome data through graph-theoretical approaches has advanced our understanding of the thresholds beyond which compensatory mechanisms fail, leading to a ‘network collapse’ that heralds accelerated cognitive and physical decline. Such insights are guiding the development of network-informed biomarkers and rehabilitation strategies.

Research from Nature Portfolio

A foundational study combined diffusion tractography and resting-state functional MRI in clinically isolated syndrome and MS patients. Graph analyses demonstrated that structural connectome alterations emerge as early as the first clinical event, while detectable functional changes arise later in established MS. Importantly, structural and functional disruptions co-localised within sensorimotor circuits and correlated with disability measures. This work provided the first direct evidence that early white matter disconnection precedes widespread functional reorganisation and validated an integrated connectome framework for probing disease progression.

Functional Connectivity in Multiple Sclerosis publication trend

The graph below shows the total number of articles in functional connectivity in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Resting-state functional connectivity: Statistical dependence in ongoing neural activity between regions when a subject is not performing a task.

Static functional connectivity: Time-averaged measure of synchrony between brain areas across an entire scan or recording session.

Dynamic functional connectivity (dFC): Time-varying changes in functional connectivity patterns, often quantified via sliding-window or state-based analyses.

Connectome: Comprehensive map of structural or functional connections in the brain, represented as a network of nodes and edges.

Network hub: Brain region with disproportionately high connectivity that plays a central role in information integration.

Network collapse: Tipping point at which progressive loss of connectivity causes breakdown of compensatory network function and rapid clinical deterioration.

References

1. Male and female are not the same: a multicenter study of static and dynamic functional connectivity in relapse-remitting multiple sclerosis in China. Frontiers in Immunology (2023).
2. Flexibility of brain dynamics is increased and predicts clinical impairment in relapsing–remitting but not in secondary progressive multiple sclerosis. Brain Communications (2024).
3. Functional Connectivity in Multiple Sclerosis: Recent Findings and Future Directions. Frontiers in Neurology (2018).
4. Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis. Scientific Reports (2016).
5. The network collapse in multiple sclerosis: An overview of novel concepts to address disease dynamics. NeuroImage Clinical (2022).