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Original research
Motor context modulates substantia nigra pars reticulata spike activity in patients with Parkinson’s disease
  1. Anand Tekriwal1,
  2. Gidon Felsen2,
  3. Steven G Ojemann3,
  4. Aviva Abosch4,
  5. John A Thompson5
  1. 1 Departments of Neurosurgery and Physiology and Biophysics, Neuroscience Graduate Program, Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  2. 2 Department of Physiology and Biophysics, Neuroscience Graduate Program, Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  3. 3 Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  4. 4 Department of Neurosurgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
  5. 5 Departments of Neurosurgery and Neurology, Neuroscience Graduate Program, Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  1. Correspondence to Anand Tekriwal, 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{at}cuanschutz.edu

Abstract

Objective 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.

Methods 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.

Results 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.

Conclusions 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.

  • motor physiology
  • movement disorders
  • neurophysiology
  • paradoxical kinesis
  • parkinson's disease

Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, upon reasonable request. The data are not publicly available due to protection of study participants’ privacy and any unforeseen insights into participant identify and wellness.

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Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author, upon reasonable request. The data are not publicly available due to protection of study participants’ privacy and any unforeseen insights into participant identify and wellness.

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Footnotes

  • Contributors AT, GF and JAT designed the experiment. AT, SO, AA and JAT carried out the data collection. AT performed electrophysiological and behavioural analyses. JAT conducted the post hoc imaging verification. AT created the text and figures, with significant input from the other authors, especially JAT. AT is the guarantor of this work.

  • Funding This research was supported by funds from the National Institutes of Health National Institute of Neurological Disorders and Stroke (R01NS079518 and P30NS048154), the Boettcher Foundation’s Webb-Waring Biomedical Research Awards program (2017) and the University of Colorado Center for NeuroScience (2014). Engineering support, provided by the Optogenetics and Neural Engineering Core at the University of Colorado Anschutz Medical Campus, was funded in part by the National Institute for Neurological Disorders and Stroke of the National Institutes of Health (award number P30NS048154).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.