Current understanding of neurostimulation for Parkinson's disease

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Abstract

Specific mechanisms underlying the therapeutic effects of neurostimulation in Parkinson's disease remain a topic of discussion and intense study. Understanding these mechanisms can serve as the foundation for developing and selecting more effective parameters to relieve the symptoms of Parkinson's disease, maximize the advantages, and reduce the adverse effects and need for surgical intervention. The article discusses existing models of motor control in the basal ganglia in healthy individuals and in PD from the point of view of neuromodulation (changes in the impulse flow model, oscillatory model), as well as the current understanding of the mechanisms of action of deep brain stimulation (DBS): the block depolarization hypothesis, neural interference hypothesis, synaptic depression hypothesis, synaptic modulation hypothesis, and the DBS astrocytes hypothesis. Factors such as DBS location and neurostimulation parameters, affecting the clinical outcome, are considered in detail. The neuroprotective effect of DBS is also touched on.

About the authors

Ekaterina V. Bril

Russian Medical Academy of Continuing Professional Education; Burnasyan Federal Medical Biophysical Center

Author for correspondence.
Email: e.brill@inbox.ru
ORCID iD: 0000-0002-6524-4490

Cand. Sci. (Med.), Associate Professor, Department of neurology, Head, Movement disorders department

Russian Federation, Moscow; 123098, Moscow, Marshala Novikova str., 23

Elena M. Belova

Semenov Institute of Chemical Physics of the Russian Academy of Sciences

Email: e.brill@inbox.ru
ORCID iD: 0000-0002-8179-5807

Cand. Sci. (Biol.), leading researcher

Russian Federation, Moscow

Aleksey S. Sedov

Semenov Institute of Chemical Physics of the Russian Academy of Sciences

Email: e.brill@inbox.ru
ORCID iD: 0000-0003-3885-2578

Cand. Sci. (Biol.), senior researcher

Russian Federation, Moscow

Anna A. Gamaleya

N.N. Burdenko National Medical Research Center of Neurosurgery

Email: agamaleya@mail.ru
ORCID iD: 0000-0002-6412-8148

neurologist

Russian Federation, Moscow

Anna A. Poddubskaya

N.N. Burdenko National Medical Research Center of Neurosurgery

Email: anna.poddubsk@gmail.com
ORCID iD: 0000-0002-5776-3442

neurologist

Russian Federation, Moscow

Natalia V. Fedorova

Russian Medical Academy of Continuing Professional Education

Email: Natalia.fedorova@list.ru
ORCID iD: 0000-0003-2168-2138

D. Sci. (Med.), Professor

Russian Federation, Moscow

Аleksey A. Tomskiy

N.N. Burdenko National Medical Research Center of Neurosurgery

Email: alexey_tomskiy@mail.ru
ORCID iD: 0000-0002-2120-0146

Cand. Sci. (Med.), senior researcher, Head, Department of functional neurosurgery

Russian Federation, Moscow

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2. Fig. 1. Diagram of the main projections inside the motor control system in healthy individuals (A) and in PD (B). С — initial diagram of the projections [4]; D — updated diagram of the projections inside the motor control system, showing a more complex organization and the presence of reciprocal connections, which can help to maintain the pathological oscillations inside the system (adapted from [8]). SNr — substantia nigra pars reticulate; SNc — substantia nigra pars compacta.

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3. Fig. 2. Diagrams of interactions inside the motor control systems for the changes in impulse flow model (A) and the oscillatory model (B). Arrow width reflects the strength of the signal transmission between structures.

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4. Fig. 3. Diagram of the main effects of DBS at the cellular and synaptic levels. Adapted from [51]. 1 — entrainment of axonal orthodromic action potentials (APs); 2 — antidromic APs collide with intrinsic orthodromic APs; 3 — excitation of afferent inhibitory and excitatory fibers projecting to target neurons; 4 — excitation of passing fibers projecting to the targets; 5 — neurotransmitter release; 6 — microenvironmental effects on non-neuronal cells; 7 — effects on bllod-brain barrier.

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5. Fig. 4. Example of a peristimulus spectrogram of recordings of local potentials in the STN of a patient with PD. А — spectrogram showing desynchronization of β-oscillations (13–17 Hz) and synchronization of γ-oscillations (60–70 Hz) when performing motor tests. x axis is time, y axis is frequency, Hz, amplitude of the power spectrum is shown in colour, %. B — rectified EMG signal of the patient's arm muscle (own data). x axis is time, y axis is amplitude, μV.

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6. Fig. 5. Time of symptom change during stimulation.

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Copyright (c) 2022 Bril E.V., Belova E.M., Sedov A.S., Gamaleya A.A., Poddubskaya A.A., Fedorova N.V., Tomskiy А.A.

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