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

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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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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High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson’s disease

Neuroscience ◽

10.1016/s0306-4522(02)00538-9 ◽

2002 ◽

Vol 115 (4) ◽

pp. 1109-1117 ◽

Cited By ~ 97

Author(s):

C Magariños-Ascone ◽

J.H Pazo ◽

O Macadar ◽

W Buño

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Subthalamic Nucleus ◽

High Frequency ◽

Cellular Mechanism ◽

High Frequency Stimulation ◽

Frequency Stimulation ◽

Subthalamic Neurons ◽

Stimulation Of

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Increased Gamma Oscillatory Activity in the Subthalamic Nucleus During Tremor in Parkinson's Disease Patients

Journal of Neurophysiology ◽

10.1152/jn.90837.2008 ◽

2009 ◽

Vol 101 (2) ◽

pp. 789-802 ◽

Cited By ~ 76

Author(s):

M. Weinberger ◽

W. D. Hutchison ◽

A. M. Lozano ◽

M. Hodaie ◽

J. O. Dostrovsky

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Subthalamic Nucleus ◽

Field Potential ◽

Gamma Oscillations ◽

Neuronal Firing ◽

Oscillatory Activity ◽

Frequency Range ◽

Resting Tremor ◽

Gamma Frequency

Rest tremor is one of the main symptoms in Parkinson's disease (PD), although in contrast to rigidity and akinesia, the severity of the tremor does not correlate well with the degree of dopamine deficiency or the progression of the disease. Studies suggest that akinesia in PD patients is related to abnormal increased beta (15–30 Hz) and decreased gamma (35–80 Hz) synchronous oscillatory activity in the basal ganglia. Here we investigated the dynamics of oscillatory activity in the subthalamic nucleus (STN) during tremor. We used two adjacent microelectrodes to simultaneously record neuronal firing and local field potential (LFP) activity in nine PD patients who exhibited resting tremor during functional neurosurgery. We found that neurons exhibiting oscillatory activity at tremor frequency are located in the dorsal region of STN, where neurons with beta oscillatory activity are observed, and that their activity is coherent with LFP oscillations in the beta frequency range. Interestingly, in 85% of the 58 sites examined, the LFP exhibited increased oscillatory activity in the low gamma frequency range (35–55 Hz) during periods with stronger tremor. Furthermore, in 17 of 26 cases where two LFPs were recorded simultaneously, their coherence in the gamma range increased with increased tremor. When averaged across subjects, the ratio of the beta to gamma coherence was significantly lower in periods with stronger tremor compared with periods of no or weak tremor. These results suggest that resting tremor in PD is associated with an altered balance between beta and gamma oscillations in the motor circuits of STN.

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