• Anand Tekriwal, Gidon Felsen, Steven G Ojemann, Aviva Abosch, and John A Thompson.
• Departments of Neurosurgery and Physiology and Biophysics, Neuroscience Graduate Program, Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA andy.tekriwal@cuanschutz.edu.
• J. Neurol. Neurosurg. Psychiatr. 2022 Apr 1; 93 (4): 386394386-394.

ObjectiveThe 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.MethodsWe 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.ResultsAs 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.ConclusionsOur 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.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

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