Task-based effective connectivity finds alterations in frontoparietal network in Duchenne muscular dystrophy

Mathula Thangarajh, Matthew Ridder, Hakinya Karra, Sanjana Javalkar, Edward Zuniga, Amy Harper, Nitai D Mukhopadhyay, Robert Cadrain, F Gerard Moeller, James M Bjork, Liangsuo Ma

Brain Commun 2025 Oct 28;7(5):fcaf356.

https://academic.oup.com/braincomms/article/7/5/fcaf356/8305067

 

Duchenne muscular dystrophy is best known for its effects on muscles, but it can also affect learning, attention, and memory. In this study, researchers used brain scans to explore how different parts of the brain work together during a memory task.

They found that communication between key brain regions involved in attention and working memory was different in boys with DMD compared with children without DMD. These findings improve our understanding of how DMD may affect the brain and could help guide future approaches to support cognitive and educational outcomes for people living with the condition.

Task-based effective connectivity finds alterations in frontoparietal network in Duchenne muscular dystrophy

Scientific Summary

Duchenne muscular dystrophy (DMD), an X-linked disorder caused by absence of dystrophin, is associated with significant executive dysfunction in addition to its neuromuscular phenotype. Working memory and inhibitory control are particularly affected and contribute to the characteristic poorer academic and neurobehavioural outcomes, yet their neural substrates remain insufficiently characterized.

This study examined task-dependent effective connectivity within the frontoparietal network during an fMRI n-back working memory paradigm, using dynamic causal modelling in 11 males with DMD and 9 neurotypical controls. Despite comparable standardized working memory performance between groups, DMD participants exhibited reduced task-related activation in frontoparietal–occipital regions and lower effective connectivity within the frontoparietal network.

Interestingly, increased right posterior parietal-to-dorsolateral prefrontal cortex connectivity was inversely correlated with working memory performance in DMD, suggesting inefficient or maladaptive network engagement. Behaviourally, DMD participants demonstrated slower response times, reaching significance only in an emotionally salient (fearful face) condition.

These findings indicate disrupted frontoparietal network dynamics and altered perceptual processing in DMD, implicating abnormal effective connectivity as a potential mechanism underlying executive dysfunction and a target for therapeutic intervention.

Take home messages

  • Reduced brain activation: DMD patients showed hypoactivation in frontoparietal–occipital regions during the working memory task.
  • Decreased effective connectivity: Frontoparietal network connectivity was lower in DMD (moderate Bayesian evidence).
  • Maladaptive connectivity pattern: Stronger right parietal → dorsolateral prefrontal connectivity was associated with worse working memory performance in DMD.
  • Slower processing speed: Reaction times were generally longer in DMD, though not statistically significant overall.