Subthalamic nucleus shows opposite functional connectivity pattern in Huntington's and Parkinson's disease

Area of Science:

• Neuroscience
• Movement Disorders Research
• Neuroimaging

Background:

• Huntington's disease (HD) and Parkinson's disease (PD) are distinct basal ganglia disorders.
• The subthalamic nucleus (STN) is crucial for motor control but its in-vivo function in HD and PD is poorly understood.
• Previous studies often required invasive methods to assess STN function.

Purpose of the Study:

• To investigate and compare the resting-state functional connectivity (rsFC) of the subthalamic nucleus (STN) in early HD and PD.
• To determine if the STN exhibits opposite functional signatures in these two movement disorders.
• To correlate STN rsFC alterations with clinical symptom severity.

Main Methods:

• Utilized ultra-high-field 7T MRI for high-resolution whole-brain imaging.
• Included premanifest HD carriers and early-stage PD patients with unilateral symptoms.
• Performed group comparison interaction analyses against 24 healthy controls.

Main Results:

• Revealed differential and opposite effects of HD and PD on STN rsFC within the sensorimotor network compared to controls.
• Identified disease-specific STN connectivity alterations, including the deep brain stimulation 'sweet spot' in PD.
• Found associations between the direction and magnitude of STN rsFC deviation and motor/cognitive symptom severity in both diseases.

Conclusions:

• Demonstrated for the first time non-invasively a differential and clinically relevant impact of HD and PD pathophysiology on STN functional connectivity.
• Highlighted opposite functional alterations in the STN and sensorimotor cortex in HD versus PD.
• Provided novel insights into the shared and distinct neurobiological underpinnings of these movement disorders.