Striatal Dopaminergic Dysfunction Constrains Motor Invigoration in Parkinson's Disease
Bradykinesia is a cardinal motor feature of Parkinson's disease and is characterised by a reduced ability to generate movements with normal speed and force. Although nigrostriatal dopamine loss is regarded as the primary cause, direct human evidence linking dopaminergic degeneration to striatal dysfunction and impaired motor output and vigour remains limited. To investigate this relationship, we…
Parkinson's disease is characterized by bradykinesia, a motor impairment marked by slower, less forceful movements. While the primary cause of this condition is believed to be the loss of dopamine-producing neurons in the nigrostriatal pathway, the exact relationship between dopaminergic degeneration and impaired motor output remains unclear.
To address this gap, researchers developed a grip-force task that measured movement vigour, defined as the capacity to rapidly generate force. This task was performed in a scanner by 53 individuals with Parkinson's disease, including 30 with levodopa-induced dyskinesia and 23 without, alongside 25 healthy control participants. In addition to the task, 35 Parkinson's patients underwent dopamine transporter imaging to examine connections between nigrostriatal dopamine function, striatal activity, and motor performance.
The findings revealed that Parkinson's patients exhibited significant reductions in initial movement vigour, coupled with diminished activation in both putamen regions during force generation. Lower striatal dopamine transporter binding was linked to both poorer movement vigour and weaker grip-related striatal activation during functional MRI, establishing a direct correlation between nigrostriatal degeneration, impaired striatal recruitment, and motor slowing.
Furthermore, functional MRI unveiled reduced reward-related activation in the nucleus accumbens. Notably, stronger reward-related activity in the ventral striatum was associated with greater movement vigour, indicating that motivational processes contribute independently to motor performance. Patients with levodopa-induced dyskinesia displayed more severe putamen dopaminergic depletion compared to those without dyskinesia, yet they did not experience additional impairment in movement vigour or striatal task responses.
These findings offer direct in vivo evidence that dorsal nigrostriatal dopaminergic degeneration constrains movement vigour in Parkinson's disease by reducing striatal recruitment during action generation. Moreover, impaired reward-related signalling in the ventral striatum emerges as an additional, partly independent mechanism influencing motor performance, shedding light on the distinct motor and motivational contributions to bradykinesia.
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