A recent functional magnetic resonance imaging (fMRI) study provides new insights into the neural circuits involved in lower limb function for individuals with Parkinson’s disease (PD) compared to healthy older adults. The researchers utilised a novel MRI-compatible ankle dorsiflexion device that produces minimal head motion and a force control paradigm sensitive to PD deficits.
Twenty-four PD participants and 21 healthy older adults completed the study. The groups were matched for age, sex, cognitive status, and tested side. The Montreal Cognitive Assessment Test (MOCA) was used to screen for cognitive impairment, while the motor section of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) was administered to assess disease severity in PD and rule out motor symptoms in control participants. The findings were published in NeuroImage: Clinical.
The results showed an extensive pattern of hypoactivity in PD participants during ankle dorsiflexion compared to controls, encompassing the primary nodes of the motor circuit: basal ganglia, cerebellum, and M1. The fMRI activity within the M1 foot area was markedly lower in those PD exhibiting more severe symptoms based on clinical examination.
While previous studies have investigated the functional activation profile for upper limb motor control in PD, research on lower limb control has been limited. The current study’s ankle dorsiflexion task revealed significant hypoactivation in PD participants within the primary nodes of the motor network: basal ganglia, M1, and cerebellum. Importantly, these results were found in the absence of significant head motion or group differences in head motion and performance on the force task.
The study’s findings contribute to the existing imaging literature in PD by showing that the cortico-basal ganglia and cortico-cerebellar motor circuits are impaired not only during upper limb movements but also during lower limb movements. These results suggest that the pathophysiology of lower limb symptoms in PD possibly extends beyond the nigrostriatal circuit to include the cerebellum and M1.
The study’s authors note that although the cerebellum’s role in PD is controversial, it is a structure with a significant influence on the motor output. Some studies have reported hyperactivation of the cerebellum and support the hypothesis that it plays a compensatory role in PD, while other studies, including this one, have found hypoactivation of the cerebellum in PD.
The correlation between the activity level of the M1 foot area and foot symptoms based on the MDS-UPDRS-III reinforces the theory that the pathophysiology of PD is not confined to the nigrostriatal dopaminergic pathway but propagates along the basal ganglia-thalamo-cortical neural network. The authors suggest that non-pharmacologic interventions involving the cerebellum itself or nodes of the cerebello-thalamo-cortical pathways such as the M1 foot area may be beneficial, particularly since the positive effect of acute levodopa has been shown to be limited to the putamen and thalamus in an fMRI study involving active ankle movements.