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

Area of Science:

• Neuroscience
• Genetics
• Cognitive Science

Background:

• Duchenne muscular dystrophy (DMD), a genetic disorder, causes skeletal, cardiac, and executive function issues.
• Executive function deficits, particularly in working memory and inhibitory control, are prevalent in DMD and linked to poor quality of life.
• The neural basis of working memory challenges in DMD is poorly understood, despite the frontoparietal network's critical role.

Purpose of the Study:

• To investigate the neural substrates of working memory challenges in Duchenne muscular dystrophy.
• To analyze effective connectivity within the frontoparietal network during a working memory task in individuals with DMD.
• To explore the relationship between neural connectivity and working memory performance in DMD.

Main Methods:

• Used functional MRI with dynamic causal modeling to assess effective connectivity in the frontoparietal network.
• Compared 11 males with DMD to 9 neurotypical males performing an n-back working memory task.
• Administered out-of-scanner neurocognitive assessments to evaluate working memory performance.

Main Results:

• Individuals with DMD exhibited task-based hypoactivation in frontoparietal-occipital regions.
• Lower frontoparietal effective connectivity was observed in the DMD group compared to neurotypicals.
• Negative correlation found between right posterior parietal to dorsolateral prefrontal cortex connectivity and out-of-scanner working memory performance in DMD.
• Slower reaction times in DMD for certain working memory conditions, including fearful facial stimuli.

Conclusions:

• Atypical task-based effective connectivity within the frontoparietal network is implicated in Duchenne muscular dystrophy.
• Impaired perceptual processing may also contribute to cognitive challenges in DMD.
• Understanding these dynamic neural network signatures can guide interventions for executive function deficits in DMD.