Anatomical Etiology of AR Subtype of Parkinson’s Disease Linked to Altered Functional Connectivity

Vignesh Subramanian ’24

Figure 1: Parkinson’s disease (PD) patients are classified by their motor subtype during or immediately following diagnosis.

Parkinson’s disease (PD) is a neurodegenerative movement disorder causing progressive loss of motor control that afflicts over ten million people worldwide. The disease is characterized by a loss of dopaminergic neurons in the substantia nigra region of the brain, contributing to widespread network alterations that disrupt communication with the body’s muscles. PD patients are classified by their most prominent resulting clinical symptoms, typically distinguished between tremors and involuntary movement – the tremor-dominant (TD) motor subtype – or muscle rigidity, bradykinesia, and akinesia, encompassed by the akinetic/rigid (AR) motor subtype. AR symptoms are associated with more aggressive spread of PD pathology, being linked to both alterations of the basal-ganglia motor loops – which inhibit competing motor circuits that undermine cognitive command – and of motor planning in various frontoparietal networks. The neural correlates of the AR subtype – the minimal degree of brain activity required to induce these abnormalities – have not previously been studied over extended periods of time. To better understand the relationship between anatomical degeneration and severity of the AR subtype, Stony Brook researcher Dr. Hoi-Chung Leung and her team explored the rates of brain tissue death and shifts in signaling patterns associated with baseline symptoms. 

Researchers used UPDRS III ratings paired with behavioral assessments to determine the extent of motor impairment and progression of independent symptoms in 274 newly diagnosed PD patients over four years. A subset of 50 participants was then subjected to voxel-compression mapping procedures that imaged longitudinal gray matter loss in the basal ganglia and relevant cortices. Finally, a second subset of 87 participants underwent resting-state functional magnetic resonance imaging procedures scanning for functional connectivity – the concurrence of separate but related neurophysiological events central to the mechanisms of information processing.

Subsequent whole brain multiple regression analyses found that individuals with baseline AR symptoms demonstrated significant gray matter volume depletion in the paracentral and posterior superior parietal lobules, recognized for their roles in motor awareness and execution, while no such correlation existed in TD symptom individuals. The same analyses also determined that greater AR symptom severity was strongly associated with weaker functional connectivity between the motor cortex and pre-supplementary motor area. Overall, these findings suggest that PD patients with severe AR symptoms have distinct patterns of longitudinal anatomical decline, indicating that disruptions to functional connectivity may become predictable in future courses of treatment using connectomes, or maps of such neural connections, as progression markers for the disease.

Works Cited:

[1] H.C. Leung, et al., Akinetic rigid symptoms are associated with decline in a cortical motor network in Parkinson’s disease. Nature (NPJ) 6, 19 (2020). doi: 10.1038/s41531-020-00120-3

[2] Image retrieved from: https://www.niehs.nih.gov/health/topics/conditions/parkinson/index.cfm

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