What is the mechanism of action for deep brain stimulation (DBS) to treat Parkinson disease (PD)?

Updated: Dec 09, 2020
  • Author: Konstantin V Slavin, MD; Chief Editor: Brian H Kopell, MD  more...
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Answer

Answer

Currently, the underlying mechanism of action of DBS for treatment of movement disorders is not clear, although different theories have been proposed.

DBS may function through local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, neuroprotection, and neurogenesis. [14]  DBS acts through not only inhibition but also excitation of basal ganglia circuits. DBS may inhibit the neuronal networks in the target. On the other hand, it may also activate the efferent axons. It may suppress pathological rhythms and involve neuronal networks with widespread connections, resulting in beneficial effects. [15] High-frequency stimulation may create a global hyperpolarization of the cell membrane, resulting in a loss of excitability. Alternatively, stimulation may "jam" signal flow out of an abnormally functioning structure. Antidromic and orthodromic depolarization currents may modulate neuronal activity at sites distant from the stimulation target. Finally, stimulation-induced disruption of pathologic network activity may explain the effects of DBS on disorders of abnormal movement. [16] It has also been reported that DBS creates an informational lesion in the circuit [17] and may control neuronal network activity by involving neurochemistry modulation, such as upregulation of dopamine and gamma-aminovutyric acid (GABA) through glia, which is induced by stimulation. [18]


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