Elsevier

The Lancet Neurology

Volume 1, Issue 4, August 2002, Pages 225-231
The Lancet Neurology

Review
Deep brain stimulation for Parkinson's disease: disrupting the disruption

https://doi.org/10.1016/S1474-4422(02)00101-1Get rights and content

Summary

Many people are disabled by Parkinson's disease (PD) despite the drug treatments that are currently available. For these patients, neurosurgery has the potential to help restore their function. The most effective neurosurgical procedures to date use electrical stimulation—deep brain stimulation (DBS)—of small targets in the brain by use of a pacemaker-like device to deliver constant stimulation. Although these operations can produce striking results, the mechanism by which delivery of electrical stimulation to targets deep in the brain can restore function in the motor system is not clear. This type of surgery probably works by interfering with and shutting down abnormal brain activity in areas where the current is delivered, such as the thalamus, globus pallidus, or the subthalamic nucleus. With this abnormal neuronal activity neutralised, motor areas of the brain can resume their function and normal movements are reinstated. Current research is aimed at elucidating how DBS works and using this information to develop better treatments for patients with PD and other neurological disorders.

Section snippets

How does DBS work?

High-frequency stimulation via electrode contacts in deep brain nuclei appears to have the same effect as a lesion—stimulation blocks neuronal transmission in the stimulated nucleus. Yet, in theory at least, stimulation according to the variables commonly used in human beings would be expected to activate myelinated axons rather than blocking them. Stimulation of the spinal cord, for example, is intended to do just that.7

So what happens when electrical stimulation is delivered through electrode

Stimulatory effects of DBS

In some instances, DBS seems to facilitate rather than inhibit neural systems. Single stimuli delivered to the STN evoke potentials that can be recorded at the scalp.17 The elements involved have a short chronaxie, so again they are likely to be large axons. With paired stimuli or trains, the evoked potentials are increased rather than decreased. This characteristic suggests that the activated neural elements have a short refractory period, and that the increased potentials are postsynaptic. In

Inhibitory effects of DBS

Several studies have examined neuronal activity during stimulation or in the period after the end of stimulation. In rat brain slice preparations, high-frequency electrical stimulation produces extended inactivation of voltage-gated sodium and calcium channels in STN neurons.21 Studies in hippocampal slices have shown that high-frequency stimulation leads to a depolarisation block, possibly related to an extracellular increase in potassium.22 Now there are also some data from studies in human

Downstream effects

Some experiments have also examined the effects of stimulation on downstream neurons, one or more synapses away from the point of stimulation.

What happens to cortical networks after DBS?

Stimulation of deep brain structures produces profound effects in remote brain areas. The downstream effects of DBS on cortical activity have been studied with functional imaging (PET and functional MRI [fMRI]), electroencephalography (EEG), and transcranial magnetic stimulation (TMS). These are complementary methods: functional imaging studies have high spatial resolution, whereas EEG methods have high temporal resolution, and measure neuronal activity rather than the more indirect measure of

Conclusion

Surprisingly little is known about the actions of DBS in patients. The stimulus variables used in DBS in patients are likely to activate large axons. The activation of large axons at high frequency could inhibit a nucleus by the presynaptic release of inhibitory transmitters, or could cause a neural network to dysfunction either by inducing decay at downstream synapses or by disrupting or stabilising the pattern of neuronal firing in the target area. DBS may not work in the same way at each

Search strategy selection and criteria

References from this review were identified from general reading and personal discussions with investigators in the field of DBS. Only papers published in English were reviewed.

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