Subthalamic nucleus neuronal firing rate increases with Parkinson's disease progression

The neuronal basis of hyperkinetic movement disorders has long been unclear. We now test the hypothesis that changes in the firing pattern of neurons in the globus pallidus internus (GPi) are related to dyskinesias induced by low doses of apomorphine in patients with advanced Parkinson's disease (PD). During pallidotomy for advanced PD, the activity of single neurons was studied both before and after administration of apomorphine at doses just adequate to induce dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these spike trains demonstrated an initial fall in firing from baseline. In nine neurons, the onset of on was simultaneous with that of dyskinesias. In these spike trains, the initial fall in firing rate preceded and was larger than the fall at the onset of on with dyskinesias. Among the three neurons in which the onset of on occurred before that of dyskinesias, the firing rate did not change at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias during on with dyskinesias often fluctuated between transient periods with dyskinesias and those without. Average firing rates were not different between these two types of transient periods. Transient periods with dyskinesias were characterized by interspike interval (ISI) independence, stationary spike trains, and higher variability of ISIs. A small but significant group of neurons demonstrated recurring ISI patterns during transient periods of on with dyskinesias. These results suggest that mild dyskinesias resulting from low doses of apomorphine are related to both low GPi neuronal firing rates and altered firing patterns.

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Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease

Clinical Parkinsonism & Related Disorders ◽

10.1016/j.prdoa.2019.100032 ◽

2020 ◽

Vol 3 ◽

pp. 100032 ◽

Cited By ~ 1

Author(s):

Heet Kaku ◽

Musa Ozturk ◽

Ashwin Viswanathan ◽

Joohi Shahed ◽

Sameer A. Sheth ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Subthalamic Nucleus ◽

Unsupervised Clustering ◽

Neuronal Firing ◽

Firing Patterns ◽

Spatially Varying

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Multistable properties of human subthalamic nucleus neurons in Parkinson’s disease

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1912128116 ◽

2019 ◽

Vol 116 (48) ◽

pp. 24326-24333 ◽

Cited By ~ 1

Author(s):

Jeremy W. Chopek ◽

Hans Hultborn ◽

Robert M. Brownstone

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Subthalamic Nucleus ◽

Neural Circuits ◽

Silent Period ◽

Neuronal Firing ◽

Awake Surgery ◽

Finite State ◽

Subthalamic Neurons ◽

Firing Properties

To understand the function and dysfunction of neural circuits, it is necessary to understand the properties of the neurons participating in the behavior, the connectivity between these neurons, and the neuromodulatory status of the circuits at the time they are producing the behavior. Such knowledge of human neural circuits is difficult, at best, to obtain. Here, we study firing properties of human subthalamic neurons, using microelectrode recordings and microstimulation during awake surgery for Parkinson’s disease. We demonstrate that low-amplitude, brief trains of microstimulation can lead to persistent changes in neuronal firing behavior including switching between firing rates, entering silent periods, or firing several bursts then entering a silent period. We suggest that these multistable states reflect properties of finite state machines and could have implications for the function of circuits involving the subthalamic nucleus. Furthermore, understanding these states could lead to therapeutic strategies aimed at regulating the transitions between states.

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