Motor context modulates substantia nigra pars reticulata spike activity in patients with Parkinson's disease

The severity of motor symptoms in Parkinson's disease (PD) depends on environmental conditions. For example, the presence of external patterns such as a rhythmic tone can attenuate bradykinetic impairments. However, the neural mechanisms for this context-dependent attenuation (e.g., paradoxical kinesis) remain unknown. Here, we investigate whether context-dependent symptom attenuation is reflected in single-unit activity recorded in the operating room from the substantia nigra pars reticulata (SNr) of patients with PD undergoing deep brain stimulation surgery. The SNr is known to influence motor planning and execution in animal models, but its role in humans remains understudied.

We recorded SNr activity while subjects performed cued directional movements in response to auditory stimuli under interleaved 'patterned' and 'unpatterned' contexts. SNr localisation was independently confirmed with expert intraoperative assessment as well as post hoc imaging-based reconstructions.

As predicted, we found that motor performance was improved in the patterned context, reflected in increased reaction speed and accuracy compared with the unpatterned context. These behavioural differences were associated with enhanced responsiveness of SNr neurons-that is, larger changes in activity from baseline-in the patterned context. Unsupervised clustering analysis revealed two distinct subtypes of SNr neurons: one exhibited context-dependent enhanced responsiveness exclusively during movement preparation, whereas the other showed enhanced responsiveness during portions of the task associated with both motor and non-motor processes.

Our findings indicate the SNr participates in motor planning and execution, as well as warrants greater attention in the study of human sensorimotor integration and as a target for neuromodulatory therapies.