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Associations between fronto-limbic white matter connections and internalizing symptoms in pediatric demyelinating
Liliana C Wu1, Sonya Bells2, Julie Tseng3
1Department of Psychology, University of Toronto, Toronto, Canada; Neurosciences and Mental Health Program, Research Institute, Hospital for Sick Children, Toronto, Canada.
Insights
Children with neuroinflammatory disorders show white matter changes linked to emotional symptoms. Higher relapse rates may surprisingly protect against white matter disruption in those with high internalizing symptoms.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Psychiatry
Background:
- Children with neuroinflammatory disorders like MS, NMOSD, and MOGAD experience high rates of anxiety and depression.
- These psychological symptoms may stem from disruptions in fronto-limbic white matter tracts crucial for emotional regulation.
Purpose of the Study:
- To investigate the relationship between white matter (WM) microstructure in fronto-limbic tracts and internalizing symptoms in children with neuroinflammatory disorders.
- To compare WM integrity and symptom levels across different neuroinflammatory conditions and healthy controls.
Main Methods:
- Diffusion tensor imaging (DTI) was used to assess white matter tract integrity in 33 children with neuroinflammatory disorders and 28 healthy controls.
- Key tracts analyzed included the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF), with the acoustic radiation serving as a control tract.
- Differences in WM microstructure and internalizing symptoms were examined between high and low symptom groups.
Main Results:
- High internalizing symptoms were reported by 40% of MS, 28% of MOGAD, and 25% of NMOSD participants.
- MOGAD patients showed reduced axonal water fraction, while both MS and MOGAD groups exhibited signs of demyelination and axonal damage.
- No direct link was found between high/low symptom groups and WM integrity, but higher relapse rates correlated with less WM disruption in highly symptomatic individuals.
Conclusions:
- Neuroinflammatory disorders in children are associated with alterations in fronto-limbic white matter and increased internalizing symptoms.
- Disease relapse may play a role in modulating white matter structure and psychological resilience.
- The study's cross-sectional design limits causal inference, and medical factors may influence findings.
Introduction:
Children with neuroinflammatory disorders, such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-associated disorder (MOGAD), have high rates of anxiety and depression. These symptoms may be linked to disruptions in fronto-limbic white matter (WM) tracts, including the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus (UF), which support emotional regulation.
Methods:
We studied 33 children with neuroinflammatory disorders and 28 healthy controls. Diffusion tensor imaging and white matter tract integrity maps were generated, focusing on WM tracts of interest (CB, IFOF, UF) and a control tract (acoustic radiation). We examined differences in WM microstructure and internalizing symptoms between high and low symptom groups.
Results:
Participants with MS (40%), MOGAD (28%), and NMOSD (25%) reported high levels of internalizing symptoms. MOGAD participants showed lower axonal water fraction compared to MS and controls. Both MS and MOGAD groups exhibited reduced intra-axonal diffusivity and increased extra-axonal diffusivity, indicating demyelination and axonal changes. No significant differences were found between high and low internalizing groups, but higher relapse rates were linked to less WM disruption in those with high internalizing symptoms.
Limitations:
The cross-sectional design limits causal interpretations, and medical covariates may affect WM structure.
Conclusion:
Neuroinflammatory disorders are linked to fronto-limbic WM changes and high internalizing symptoms. Relapse may influence WM structure and psychological resilience in this population.
