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Article Excerpt
Since its first description in 1980 (Cooper, Upton, & Amin, 1980), deep brain stimulation (DBS) has become a remarkably effective therapy for an expanding range of neurological and psychiatric disorders. It is standard accepted therapy for Parkinson's disease (PD) (Deep-Brain Stimulation for Parkinson's Disease Study Group 2001), essential tremor (Koller et al., 1997), dystonia (Kupsch et al., & Deep-Brain Stimulation for Dystonia Study, 2006), other hyperkinetic or involuntary movement disorders (Montgomery, 2004a), and cerebellar outflow tremor such as in multiple sclerosis (Montgomery, Baker, Kinkel, & Barnett, 1999). Clinical trials are underway for depression (Mayberg et al., 2005), obsessive compulsive disorder (Abelson et al., 2005), epilepsy (Hamani, Hodaie, & Lozano, 2005), and minimally conscious states (Yamamoto et al., 2005), among others.
DBS is even more impressive when one considers that it succeeds in patients who have failed to benefit from pharmacology (Deep-Brain Stimulation for Parkinson's Disease Study Group 2001; Schupbach et al., 2007) or dopamine cell replacement (Graff-Radford et al., 2006; Olanow et al., 2003). However, this should not be surprising. Neurotransmitters, which are the basis for most pharmacological treatments, are the messengers, not the message. In the nervous system, information is encoded electrically in the sequences of action potentials, which are electrical impulses generated by neurons, like the sequences of "zeros and ones" that make up the binary code of computer operations or the series of "dots and dashes" that make up Morse code.
When electrical impulses conducted down the axons reach the next neuron through a contact called a synapse, the electrical impulse is converted to a pulse of a chemical neurotransmitter that diffuses across the junction between neurons to bind on the surface of the next neuron. The release of chemical neurotransmitters in response to the action potential reaching the synaptic terminal is microscopic in amount and lasts fractions of a second. When the neurotransmitter binds to the surface of the next neuron in the sequence, it generates electrical changes known as postsynaptic potentials. An inhibitory neurotransmitter causes an inhibitory postsynaptic potential that results in the electrical state of the neuron becoming more negative and further away from the threshold needed to generate an action potential. An excitatory neurotransmitter causes an excitatory postsynaptic potential that results in the electrical state becoming less negative and closer to the threshold for generation of an action potential. If the net effect of combined inhibitory and excitatory influences is the electrical state being less negative than the threshold, an action potential is generated. Note that this is a stochastic process, meaning that the electrical state of the neuron only determines the probability of an action potential being generated. Thus, information is processed electrically as the various electrical impulses that converge onto a neuron are integrated.
The signs and symptoms of some neurological disorders are likely to result from malfunction of this electrical system, creating misinformation in the brain. While pharmacological therapies, of which dopamine cell replacement is a variation, are intended to mimic the effects of the neurotransmitters, in actuality they flood the brain for hours in contrast to the manner in which neurotransmitters are controlled by the electrical activity of neurons. Consequently, pharmacological therapies cannot replicate the precise information conveyed in the sequence of electrical impulses in neurons. By contrast, DBS may be affecting the information and/or misinformation directly. As I will discuss later, there is no better example of the importance of appropriate information processing than in speech and language.
Normally, the action potential is transmitted along the axon, away from the cell body of the neuron (i.e., orthodromic conduction). However, impulses may also be transmitted in the opposite direction (i.e., antidromic conduction). When the electrical stimulation affects the axon, the action potential can travel in both directions. Indeed, axons have the second to lowest threshold for electrical stimulation (the synaptic terminals having the lowest). Thus, antidromic activation of axons near the DBS electrode may be an important therapeutic mechanism (Montgomery, 2006).
The use of electrical stimulation of the brain, in its modern form, is revolutionary and is a radical departure from pharmacological or surgical ablative therapies. Clearly, DBS and its future variations will be an important alternative or adjunct to pharmacological and surgical ablative therapies. For those conditions without pharmacological or surgical alternatives, DBS may be the only hope. There is reason to believe that, one day, DBS and related therapies could be effective for a wide array of speech and language disorders. When that day arrives, physicians and surgeons will look to speech-language pathologists to help implement these therapies. It is not unreasonable to think that some day speech-language pathologists may be programming DBS systems for patients with speech and language disorders, just as audiologists program cochlear implants for patients with deafness.
CURRENT DBS SYSTEMS
DBS involves implanting permanent electrodes into various targets in the brain and providing electrical stimulation. Current DBS electrodes have four contacts, oriented in a row along a flexible shaft or lead. These contacts are 1.5 mm in length and 1.27 mm in diameter and are separated by either 1.5 or 0.5 mm (Figure 1). The DBS electrode lead exits the skull through a small burr hole approximately 14 mm in diameter. The electrode lead is connected to an extension wire that is tunneled under the skin to an impulse generator (IPG) that typically is placed under the skin over the chest. Current systems provide constant stimulation, though the rate (pulses per second [pps]), voltage, and pulse width can be varied. Also, various combinations of active electrodes can be used, including both electrodes on the lead and the metal case of the IPG, which can be used as an electrode. These settings are controlled using a hand-held device that sends radiotelemetry to the IPGs.
Precise placement of the DBS electrode lead is critical to success. There is no mandated method for placement of the devices, and the FDA only regulates the interstate commerce of the devices. Nearly every surgical center chooses the electrode placement site based on some combination of MRI and/or CT images, but some only use MRI or CT. In the opinion of most experts, however, this is insufficient for accurate placement of the DBS electrode lead. More refined localization of the target requires the additional use of microelectrode recordings of electrical impulses generated by individual neurons (Baker, Boulis, Rezai, & Montgomery, 2004). Neurons in different anatomical structures have characteristic discharge patterns. Microelectrodes detect these unique patterns and allow fine-grained localization so that the exact target can be identified prior to placement of the permanent DBS electrode lead.
DBS TARGETS
For patients with PD, the typical DBS targets are the sensorimotor regions of the subthalamic nucleus (STN) and globus pallidus internal segment (GPi). In the past, the ventrolateral nucleus of the thalamus (VL) was targeted primarily for tremor associated with PD. Most centers no longer target the VL, however. Although it is effective for tremor, it does...
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