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Detection of Motor Changes in Huntington's Disease Using Dynamic Causal Modeling
Lora Minkova1, Elisa Scheller2, Jessica Peter2
1Department of Psychiatry and Psychotherapy, University Medical Center Freiburg Freiburg, Germany ; Freiburg Brain Imaging Center, University Medical Center Freiburg Freiburg, Germany ; Laboratory for Biological and Personality Psychology, Department of Psychology, University of Freiburg Freiburg, Germany.
Huntington's disease (HD) alters motor control neural circuits. Dynamic causal modeling (DCM) revealed changes in brain connectivity from pre-symptomatic stages to early HD, offering insights into disease progression.
Area of Science:
- Neuroscience
- Neurology
- Systems Neuroscience
Background:
- Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor deficits.
- Understanding the neural circuitry changes underlying motor control is crucial for HD research.
Purpose of the Study:
- To investigate alterations in neural circuitry associated with motor control in Huntington's disease progression using fMRI and DCM.
- To identify group differences in brain connectivity between healthy controls, pre-symptomatic HD gene carriers (preHD), and early HD patients.
Main Methods:
- Functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were employed.
- A finger-tapping task varying in speed and complexity was performed by 77 controls, 62 preHD, and 16 earlyHD participants.
- Hierarchical clustering was used to analyze DCM parameters and capture heterogeneity among HD gene carriers.
Main Results:
- DCM identified group differences in brain connectivity not detected by conventional fMRI.
- An inhibitory parietal-to-premotor connection in preHD became excitatory in earlyHD, correlating with putamen atrophy.
- A distinct modulation of caudal-to-pre-SMA connectivity was observed in earlyHD compared to controls and preHD.
Conclusions:
- Dynamic causal modeling is effective in detecting subtle group differences in neural circuitry related to HD progression.
- DCM analysis revealed significant changes in motor control network connectivity associated with Huntington's disease.
- The findings highlight the utility of DCM in understanding between-subject heterogeneity in neurodegenerative disorders.
