Directional connectivity of motor circuits is abnormal in Duchenne Muscular Dystrophy


Translational Research

Poster Number: 332


Mathula Thangarajh, MD, PhD, Virginia Commonwealth University, Matthew Ridder, B.S., Virginia Commonwealth University, Frederick Moeller, MD, Virginia Commonwealth University, James Bjork, PhD, Virginia Commonwealth University, Liangsuo Ma, PhD, Virginia Commonwealth University

Background: There is marked alteration in resting-state functional connectivity in frontal and parietal cortical regions in Duchenne Muscular Dystrophy compared to typically-developing. The mechanistic underpinnings of abnormal brain circuits in DMD remains enigmatic. To address this knowledge gap, we use effective connectivity—a functional MRI-based (fMRI) analytical method modeled on neuronal state change—to study the dynamic control of motor circuits in DMD. Effective connectivity provides a quantitative measure of the influence of one brain region over another brain region. We selected the primary motor cortex (M1) as the node of interest to evaluate the dynamic interaction between M1 and other associative cortical regions (premotor cortex, supplementary motor area) and subcortical regions (putamen).
Objective: To test the hypothesis that the directionality and strength of effective connectivity of motor circuits is abnormal in DMD compared to typically-developing boys.
Results: Non-sedated resting-state fMRI was performed in 7 boys with DMD matched to age-matched typically-developing boys. Effective connectivity analysis of the primary motor cortex (as node of interest) and premotor cortex, supplementary motor area and putamen was performed using dynamic causal modeling. Overall, the effective connectivity from the right primary motor cortex was positive to the contralateral putamen (i.e.,) suggesting an increase in neuronal drive to putamen. Likewise, the right premotor cortex in DMD had positive effective connectivity to the ipsilateral putamen and contralateral M1, suggesting increase in neuronal drives to these target brain regions.
Conclusion: Our results support that the intrinsic organization of the motor circuits in distinct in DMD compared to typically-developing and suggest an imbalance in excitatory-inhibitory networks in DMD. This knowledge is informative of the dynamic interactions between brain regions in DMD which can in turn be harnessed for non-invasive electrophysiological intervention such as transcranial magnetic stimulation.