SURGICAL TREATMENT OF PARKINSON'S DISEASE

INTRODUCTION
The full potential of intraoperative neurophysiology is realized during the performance of so-called functional neurosurgical procedures. During these interventions therapeutic lesions or stimulating electrodes are stereotactically placed within deep brain structures to treat movement disorders such as Parkinson’s disease (PD), essential tremor (ET), dystonia, affective disorders, and chronic neuropathic pain.
The deep location of these structures precludes direct surgical approaches. Instead, surgeons rely on a combination of image-guided stereotactic techniques and intraoperative neurophysiology to place the therapeutic lesions or stimulating electrodes with acceptable accuracy and safety. Unlike tumors, which are relatively large and easily identified on CT or MRI, functional neurosurgical targets typically are small and poorly visualized with current imaging modalities. Moreover, because these are physiologic as much as anatomic targets, image-based targeting may incompletely identify the desired location. Consequently, intraoperative recording and stimulation techniques have been developed to aid target localization. These techniques complement anatomical targeting by providing real-time electrophysiological data concerning probe position and the surgical target. The surgeon and physiologist use these data to “fine-tune” their anatomic targeting before completing the therapeutic intervention. Thus employed, intraoperative neurophysiology does not simply monitor surgical activity; it guides it.

Surgical History of Movement Disorders
Sir Victor Horsely is reported to have performed the first neurosurgical procedure for a movement disorder when, in the late 1800s, he resected part of the precentral gyrus in a patient with athetoid movements. The surgery halted the abnormal movements but caused dyspraxia and paralysis of the limb.
The first successful basal ganglia surgery is credited to Meyers, who reported improvement in a patient with postencephalitic parkinsonism in 1939. Prior to this landmark report, surgery within the basal ganglia was avoided because it was believed that human consciousness resided in these structures. Despite the high mortality rates (10–12%) that plagued these “open” procedures (i.e., via craniotomy), Meyers demonstrated the potential benefits of basal ganglia surgery and opened the door for the application of less invasive stereotactic approaches to these deep brain structures. He also provided the first accounts of human basal ganglia physiology, describing the frequency, phase, and amplitude of neuronal signals from the striatum, pallidum, corpus callosum, internal capsule, subcallosal bundle, and dorsal thalamus in patients with and without movement disorders. Meyers quickly realized the potential value of the accumulated data, which he ultimately employed to help localize specific deep brain structures during movement disorder surgery.
Robert Clarke designed the first stereotactic frame in 1908. His frame employed skull landmarks to target deep brain structures in small animals, a technique that could not be translated to clinical use because of the more varied and complex shape of the human skull and brain. Consequently, it was not until 1947, after the introduction of ventriculography, that Spiegel and Wycis performed the first human stereotactic surgeries, for psychiatric illness and Huntington’s chorea. In following years a number of human stereotactic atlases were published, and standard meridia (e.g., the intercommissural line) from which stereotactic coordinates could be determined were established.
Effective targets for stereotactically guided neuroablation were discovered empirically. For example, Cooper stumbled upon the beneficial effects of globus pallidus lesioning by accidentally ligating the anterior choroidal artery of a PD patient while performing a pedunculotomy. He later adopted stereotactic approaches to pallidal lesioning, reporting favorable results and reduced surgical mortality rates (∼3%) as compared to open procedures. Laitinen described how Leksell further improved the results of pallidotomy by placing the lesion more posteriorly and ventrally within the internal
segment of the globus pallidus (GPi), that portion of the nucleus that we now know is responsible for sensorimotor processing. In 1963, Spiegel et al. described campotomy, in which the fibers of the pallidofugal, rubrothalamic, corticofugal, and hypothalamofugal pathways are interrupted within the H fields of Forel. They reported promising results in 25 patients with tremor and 25 with rigidity. In the end, however, thalamotomy emerged as the most commonly performed movement disorder procedure in the pre-levodopa era because of the consistent tremor control it provided. Though most surgery for PD ceased after the introduction of levodopa in 1967, small numbers of thalamotomies were performed for medically refractory tremor during the next 25 years, until the reintroduction of Leksell’s pallidotomy by Laitinen et al. in 1992.

Neurophysiology and Movement Disorder Surgery
Most early electrophysiologic studies of the human thalamus and basal ganglia were performed with macroelectrode techniques that yielded relatively crude, EEG-like responses. Electrodes and recording techniques were refined over subsequent decades, culminating in the development of single-cell microelectrode recording. Of note is the work of Albe-Fessard, who refined microelectrode techniques for experimental purposes and paved the way for their intraoperative use. It was her belief that micro-electrode recording (MER) would “provide a powerful tool in improving stereotactic localization and that it would furthermore reduce the risk due to anatomical variability”. In recent years, Madame Albe-Fessard’s vision has been realized as MER has gained in popularity and ready-to-use recording systems have become commercially available.
The history of electrical brain stimulation begins with Fritsch and Hitzig, who in 1870 elicited limb movement in dogs by stimulating the frontal cortex, and then defined the limits of the motor area electrophysiologically. Intraoperative cortical stimulation studies by Penfield and colleagues from the late 1920s through the late 1940s contributed seminal information concerning the somatotopic organization of the cerebral cortex by defining the motor and sensory “homunculi.” In 1950, Spiegel et al. described the use of stimulation during surgery at the H fields of Forel to both “test the position of the electrode and to avoid proximity to the corticospinal pathways ventrally, the sensory thalamic-relay nuclei dorsally, and the third nucleus posteriorly”.
Other neurophysiological techniques, such as impedance monitoring and evoked potential recordings also have been employed as localization tools; however, these techniques serve predominantly as adjuncts to recording and stimulation.
Perhaps the most significant advance in functional neurosurgery in the last decade has been the introduction of chronic electrical stimulation (termed “deep brain stimulation” or DBS) as a therapeutic alternative to neuroablation.
Deep brain stimulation provides three potential advantages when compared to neuroablation:
1. DBS is reversible. If stimulation induces an unwanted side-effect, one simply turns the stimulator off or adjusts parameters. Thus the risk of permanent adverse neurological events is reduced.
2. Stimulation parameters may be customized to each patient, potentially enhancing therapeutic efficacy.
3. Access to the surgical target is maintained via the implanted electrode and programmable pulse generator. Therefore, therapy may be modified over time through simple stimulation adjustments, potentially increasing the longevity of response.

Thus far, two studies that compared thalamic DBS to thalamotomy for the treatment of tremor have been published. Both studies found DBS to be the superior treatment modality in large part because of the ability to adjust stimulation parameters in the event of symptom recurrence.
Presently, movement disorder surgery is focused on three structures: the ventrolateral (VL) nucleus of the thalamus, the globus pallidus pars internus (GPi), and the subthalamic nucleus (STN) (Fig.1).
Each of these structures can be targeted for ablation in procedures that are, respectively, termed thalamotomy, pallidotomy, and subthalamotomy. Alternatively, each can be targeted for chronic electrical stimulation. The choice of target is based largely on clinical diagnosis and the symptoms to be treated.

THEORETICAL BASIS FOR SURGERY IN THE BASAL GANGLIA
Our current understanding of the functional organization of the basal ganglia and PD pathophysiology is based predominantly on data derived from the study of primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism. Microelectrode techniques also have contributed greatly to this body of knowledge. Though incomplete, the current model of basal ganglia function is partly responsible for the rebirth of movement disorder surgery, providing a scientific basis for selecting those deep brain structures that are currently targeted for therapeutic interventions.
The model is depicted in Fig.2. The basal ganglia are composed of two principal input structures (the corpus striatum and the STN), two output structures (GPi and substantia nigra pars reticulata [SNr]), and two intrinsic nuclei (external segment of the globus pallidus [GPe] and substantia nigra pars compacta [SNc]). Five parallel basal ganglia-thalamo-cortical circuits (motor, oculomotor, two prefrontal, and limbic) have been described. While surgical interventions target the motor circuit, it is likely that lesioning and stimulation also impact other circuits as well.

The corpus striatum, which is composed of the caudate and putamen, is the largest nuclear complex of the basal ganglia. The striatum receives excitatory (glutamatergic) input from several areas of the cerebral cortex as well as inhibitory input from the dopaminergic cells of the SNc. Cortical and nigral inputs are received via the “spiny” neurons. One subset of these cells projects directly to the GPi, forming the “direct pathway,” while another subset projects to the GPe, the first relay station of a complementary “indirect pathway,” that passes through the STN before terminating at GPi. The antagonistic actions of the direct and indirect pathways regulate the neuronal activity of GPi, which, in turn, provides inhibitory input to the pedunculopontine nucleus (PPN) and the VL nucleus of the thalamus. The VL nucleus projects back to the primary and supplementary motor areas, completing the cortico-ganglio-thalamo-cortical loop. The direct pathway inhibits GPi, resulting in a net disinhibition of the motor thalamus and facilitation of the thalamo-cortical projections. The indirect pathway, via its serial connections, provides excitatory input to the GPi, inhibiting the thalamo-cortical motor pathway.
In PD, loss of dopaminergic input to the striatum leads to a functional reduction of direct pathway activity and a facilitation of the indirect pathway. These changes result in a net increase in GPi excitation and a concomitant hyperinhibition of the motor thalamus. The excessive inhibitory outflow from GPi reduces the thalamic output to supplementary motor areas that are critical to the normal execution of movement.
This model accounts well for the negative symptoms of PD (i.e., rigidity and bradykinesia) and supports both GPi and STN as rational targets for surgically treating PD. The model is incomplete, however, because it does not fully account for hyperkinetic features of PD such as tremor and levodopa-induced dyskinesias, physiological phenomena that are poorly understood.
Tremor activity is consistently detected in the VL nucleus of patients with PD or ET, and the VL nucleus continues to be the primary surgical target for treating medically refractory tremor. However, it is unclear if the motor thalamus is the primary generator of tremor activity or merely participates in the transmission of tremor-generating signals. Moreover, the evidence that both pallidotomy and STN DBS also control parkinsonian tremor suggests that intervention at many points within the tremor-generating loop may suppress this symptom.
Levodopa-induced dyskinesias (LIDs) are involuntary movements of the limbs or trunk that are temporally associated with levodopa administration. These movements are typically choreiform or dystonic in nature and are easily distinguished from the tremor of PD. Pharmacodynamic factors related to chronic exogenous dopaminergic stimulation probably play a fundamental role in levodopa-induced dyskinesia. According to the model, pallidotomy should worsen LID by reducing pallidal inhibition of the VL nucleus, a hypothesis that is supported by the experimental observation that STN lesions, which reduce the excitatory output from STN to GPi, cause dyskinesias in primates that are indistinguishable from LID. On the contrary, LID is the most responsive symptom to pallidotomy, a consistently observed phenomenon. It has been hypothesized that sensitization of dopamine receptors by exogenously administered levodopa may cause aberrant neuronal firing patterns with consequent disruption of the normal flow of information to the thalamus and the cortical motor areas. It follows that pallidotomy may improve LID by disrupting this aberrant flow.

MOVEMENT DISORDER SURGERY:
GENERAL OVERVIEW
There is no one best method for performing movement disorder surgery. Rather, stereotactic surgeons modify general approaches to target localization to suit their personal preferences and to take advantage of their institution’s strengths. Currently accepted technique involves frame-based anatomical localization supported by intraoperative physiological confirmation of proper targeting.
  Anatomical Targeting Techniques
In the pre-levodopa era, positive contrast and air ventriculography were employed to localize the foramen of Monro and the anterior and posterior commissures. The stereotactic coordinates of therapeutic targets were then determined based on their relationship to these structures as described in various stereotactic atlases. Targeting accuracy was therefore limited by the inaccuracies of these atlases, which were typically generated from just one or a few specimens whose true dimensions were distorted by formalin fixation and by anatomical distortions created by the intraventricular injection of air or contrast. Today, CT- and MRI-based techniques, which demonstrate the brain parenchyma noninvasively, have supplanted ventriculography as the primary means of anatomically localizing stereotactic targets. Nevertheless, ventriculography is still employed by many stereotactic surgeons and therefore remains an important technique.
The introduction of CT revolutionized the diagnosis and treatment of neurologic diseases and encouraged changes in stereotactic frame design, expanding the uses of frame-based stereotaxis to include tumor biopsy and resection. Soon after the introduction of MRI, Leksell et al. demonstrated its applicability to stereotactic systems. MRI provides superior resolution as compared to CT, as well as multiplanar images with minimal frame-related artifact. Nonreformatted MRI beautifully demonstrates the commissures, the thalamus, and most basal ganglia structures. These features permit direct stereotactic localization of the surgical target in some instances; however, indirect targeting, based on accurate localization of the commissures, may still yield the most reliable target coordinates.
The most significant drawback to targeting with MRI is the potential for image distortion introduced by nonlinearities within the magnetic field. Distortions can be generated by a number of factors, including the presence of ferromagnetic objects within the field, imperfections in the scanner’s magnets, and, most commonly, patient movement. Walton et al. demonstrated that targeting errors are greater in the periphery than in the center of the magnetic field and stereotactic space. MRI distortion may also be related to the pulse sequence(s) employed. For example, it has been suggested that fast spin-echo inversion recovery sequences resist imaging distortions secondary to magnetic susceptibility better than other image acquisition methods.
In contrast to MRI, CT maintains linear accuracy, thereby reducing image-induced targeting errors. However, metallic artifact can impede visualization of the commissures, CT tissue resolution is inferior to MRI, and axial images alone are provided. Commercially available targeting software packages can fuse CT and MRI images, but to our knowledge there are no studies to suggest that such image fusion techniques improve targeting accuracy.
Physiological Targeting: Recording Techniques
The four most commonly employed techniques for physiologic localization during movement disorder surgery are: (1) impedance measurements; (2) macroelectrode recordings and stimulation; (3) semimicroelectrode recording (and/or stimulation); and (4) microelectrode recording (with or without stimulation). Evoked potentials have also been employed at times, but at present these are primarily used as an adjunct to stimulation during thalamic interventions.
Impedance Techniques
Changes in electrical impedance can accurately demarcate the boundaries of neural structures and may therefore be used to define the borders of a surgical target. Impedance measurements can be performed with monopolar electrodes that are referenced to the scalp or with concentric bipolar electrodes employing the outer ring as the reference. Employing a test frequency of 1 KHz, impedances of 400 Ω or greater are recorded in the deep grey matter while white matter can be greater or less depending upon orientation. The major advantages of this technique are the ease with which it is performed and the fact that the same electrode can be used during both the localization and the lesioning phases of an ablative procedure. The major disadvantage is the relative crudeness of the physiological information provided. Moreover, impedance measures may not adequately distinguish borders between adjacent nuclei and work best when there are clear grey matter–white matter boundaries to be defined. Therefore, impedance recordings primarily are used for the localization of large white matter bundles and nuclear groups. We perform impedance measurements during ablative procedures only after the final target is selected via microelectrode recording, and simply to ensure that the lesioning electrode has not strayed from its desired trajectory and is located within grey matter.
Macroelectrode Recording
Macroelectrode (ME) recording, defined as any low-impedance (1–100 kΩ) recording that generates either multiunit potentials or neural background noise, provides somewhat more detailed physiologic information as compared to impedance measurements. The electrode tip may be as small as 50 μm and may be configured in a bipolar concentric fashion with an intertip distance of 200–300 μm, or as a single active tip referenced to the cortical surface via the insertion cannula or to the scalp via a surface electrode. The main advantage of ME recording is the ease and speed with which data are collected as compared to microelectrode techniques. The obvious disadvantage is that EEG-like field potentials lack the discrimination necessary to characterize single-unit firing features within the surgical target (Fig.3). Consequently, physiologic detail regarding the surgical target is lacking.

Semi-Microelectrode Technique
Electrodes that have small tip diameters (<50 μm) and impedances of 100–500 kΩ are referred to as semi-microelectrodes. These electrodes provide more detailed information than do macroelectrodes, but they still do not yield single-unit recordings. Semi-microelectrodes detect the responses of a few cells (∼10−100) (Fig.4) localized to a small area around the recording tip (∼10− 100 μm). These so-called field potentials are more refined than the EEG-like recordings provided by macroelectrodes but lack the detail provided by microelectrode techniques.

 

Microelectrode Techniques
Microelectrodes provide the most detailed picture of the neural elements encountered during movement disorder surgery. Microelectrode tips have diameters of 1–40 μm and impedances of ∼1 MΩ. By recording individual neuronal activity (Fig.5), microelectrodes provide real-time information concerning the physiological characteristics of the recorded neuron and thereby the nucleus within which the cell is located.
The major drawback to microelectrode recordings is the time and expertise required to perform the technique well. The sophisticated electronics equipment is expensive and must be maintained expertly. Thus the investment in machinery and personnel can be prohibitive to some centers. It is sometimes difficult to acquire a useful signal because of electrical noise in the operating room, and even in the best circumstances, recording tracts may take 20–40 min to complete. Finally, interpreting single-cell recordings is a skill that is mastered only with experience and patience. Once mastered, microelectrode recording can be performed efficiently and yields invaluable data concerning electrode position. For example, Alterman et al. demonstrated that in 12% of 132 consecutive pallidotomies, final lesion placement, as guided by microelectrode recording, was more than 4 mm removed from the site that was originally selected by the surgeon based on stereotactic MRI. This distance is considered significant, since it is equivalent to the diameter of the typical pallidotomy lesion.

OPERATING ROOM ENVIRONMENT AND BASIC EQUIPMENT
OPERATING ROOM
Electrical Noise (recording only)
It is difficult to record low-amplitude neural signals reliably in the electrically harsh operating room environment, which can affect even more robust, easily recorded signals, such as the EKG. Anesthesia equipment, electric cautery, lighting, radios, telemetry equipment, and countless other electronic devices can all negatively impact recording quality. While the surgical team can control the use of these devices within their own operating room, external electrical influences, such as ongoing construction, poor wiring, and the use of large pieces of equipment in adjacent operating rooms, may also erode recordings. In order to control for these external influences fully, movement disorder surgery procedures ideally should be performed in an electrically shielded operating room. Of course, few facilities possess such an expensive facility, so we make the following recommendations:
1. Minimize any stray electrical switching noises. Typically, this type of noise derives from two sources: lighting fixtures that are equipped with dimmers and poorly shielded computer equipment. A properly grounded recording head stage can be operated with minimal switching
interference when the dimmers are set either all the way on or all the way off. Fluorescent lighting may also interfere with the recording equipment, but such 60-Hz signals are attenuated easily with a notch filter. Computer monitors should be fitted with static screen covers that can be grounded. If the monitor is part of the recording system, it can be grounded to the common system ground. Otherwise, it should be grounded to the operating room grounding system.
2. Employ battery-powered anesthesia and monitoring equipment. Alternatively, position anesthesia equipment in such a way as to reduce electrical interference. Turn down audible indicators. One can reduce cross-talk by keeping monitoring and neural recording cables on opposite sides of the patient. Newer anesthesia systems are equipped with cathode ray tube (CRT), liquid crystal display (LCD), and/or plasma displays, the electromagnetic (EM) leakage from which can be bothersome. If the interference from such monitors becomes overpowering, a simple aluminum foil shield can be placed between the monitor and the recording stage and connected to the system ground.
3. Turn off and unplug all electrical equipment that is not in use during recording. Electric cautery, electrically controlled operating tables, and patient warmers generate very powerful electromagnetic radiation. Fortunately, these devices are not necessary during recording and can be unplugged.
4. Employ isolated power supplies for the recording equipment. Electrical equipment used in adjacent operating rooms may interfere with recording due to poor operating room wiring schemes. Employing isolated power supplies and grounded EM shields can minimize this interference.
Proper planning will help minimize most sources of noise, but noise will occur despite the most prudent planning. It is important that both the surgeon and the neurophysiologist are prepared for these occasional frustrations. The patient should also be informed of the possibility of delays during the surgery should electrical noise be encountered. Taking the aforementioned preventive steps minimizes the risk of encountering noise and provides a framework from which one can troubleshoot noise problems when they occur.
Electrical Noise (internal system influences)
Sources of electrical noise from within the recording system include: (1) the microelectrode transducer, which detects the neural activity; (2) the preamplifier, which is located close to the recording structure; (3) the amplifier; (4) signal conditioners; (5) the visual display; and (6) auditory processors (Fig.6).

However, electrical noise primarily enters the system proximal to the first stage of the preamplifier. The amplitude of the recorded signals is small (range: 100 μV to 100 mV) so that failure of any real-time component can severely compromise the integrity
of the signal and, in turn, the accuracy of the mapping. Poorly designed equipment is the most common cause of intrasystem noise; poor system maintenance is second. Connectors must be cleaned or replaced regularly to combat oxidation, particularly in high-humidity environments. Cables must also be inspected regularly and replaced when worn.
RECORDING ELECTRODES
Lenz has previously described the construction of recording microelectrodes, and Geddes provides a useful description of electrode properties. Microelectrode tips may be composed of a number of materials, including stainless steel and tungsten, but the authors prefer the platinum-iridium etched tip, which is glass coated. The tip diameter ranges from 1 to 40 μm and is beveled to a maximum diameter of 350–400 μm. The tip is coated with a thin layer of glass to make the maximum diameter between 400 and 450 μm. The electrode tip is connected to a stainless steel wire (diameter: 500 μm) and a glass soldered bead. Alternatively, Epoxylite is used to seal the junction. An outer insulating sheath is placed over the stainless steel wire, making the total shaft diameter 600–700 μm. An electrode (including the tip) is typically around 300 mm in length. The last 15–20 mm of insulation is removed in order to connect the electrode to the amplifier. The electrodes exhibit a low-frequency roll-off below 1000 Hz (Fig.7).

 

	FIGURE.7 The gain versus frequency of the recording system. The recording system acts as a high-pass filter. Below 1000 Hz there is a reduction in the system’s gain. This reduction is acceptable because most of the spike energy is contained in the higher frequencies of the spike.

The resulting reduction in transmitted power (frequency range: 100–2000 Hz) can be as much as 17.9 dB [161]. Even though cellular firing rates range from 5 to 500 Hz, it is the high-frequency components that are most important for auditory discrimination. The microelectrodes exhibit adequate response characteristics in these higher frequencies.
Semi-microelectrodes are usually made of either stainless steel or tungsten with tip diameters of less than 50 μm; however, tip impedance and geometry impact recording discrimination (i.e., field potentials vs. single unit recordings) more than tip diameter. Semi-microelectrodes are technically easier to produce than microelectrodes because they can be made from existing fine wire, while microelectrode tips must be electrolytically etched.
AMPLIFICATION
The preamplifier is the first active component of the recording system. Either referential or differential amplification techniques are employed to measure voltage variations at both the active and referential inputs. Referential amplifiers reference the active input to a second input that is either located far from the active input and/or has a larger surface area than the active input. The variations measured by the active input are independent of the relatively inactive reference input, permitting discrimination of the true signal. In reality, large amplitude signals in the reference electrode may conceal smaller voltage variations at the active electrode, masking signal. This possibility should be kept in mind if extensive noise is observed on the recording display. Another disadvantage of referential recording is the possibility of amplifying noise that is mistakenly interpreted as signal. Differential amplification is superior in this regard.
Differential amplifiers use two active inputs and electrically subtract signals that are common to both. The transmission cables of both inputs run to the amplifier side by side. The amplifier receives two of the same input signal, but one is 180° out of phase from the other (i.e., one is positive while the other is negative). The two active signals are then subtracted. Noise that is externally induced on the transmission cable is subtracted out since the same noise is theoretically induced in both the transmission and reference cables. Differences in the signals are also accentuated (SA1 + N − (−SA1 + N) = 2 SA1). The commonmode- rejection-ratio (CMRR) defines the ability of a differential amplifier to exclude common input noise. The larger this number, the greater is the reduction of the induced cable noise.
Shils J.L. et al. employ a differential amplifier for intraoperative single-unit recording. The ground and the active input are interconnected on a large ground plane to minimize voltage variations, which are typically close to zero. The ground plane includes the head stage, the cerebral cortex, and the base of the isolated amplifier. Isolation is important for safety. These amplifiers must have a very high input impedance (∼200 MΩ) to enhance signal transfer from the high-impedance electrode (∼1 MΩ). Considering the electrode and amplifier as a voltage
divider, the voltage at the amplifier is determined by the equation:

As the amplifier input impedance approaches the electrode impedance, signal transfer decreases. The amplifier output impedance is 10 Ω. The amplifier consists of two sections: the preamplifier and a built-in impedance test circuit. The preamplifier attaches to the head stage and serves not only as the first stage of the amplification section but also as a switchbox that is used to switch between recording, stimulation, and impedance testing modes. Since the preamplifier is isolated from the main amplifier by an optical connection, the preamplifier is powered from two 9-V batteries that are located in the main amplifier. Amplification control is possible via the main amplifier. The gain of the entire amplification system varies from 100 to 10,000 times with a CMRR of 80 dB at 1000 Hz. The noise floor level of the system is 5 μV when the inputs are shorted. The maximum input to the amplifier is ±15 V, while the maximum linear output is 20 Vp-p. The amplifier has built-in high- and low-pass variable single-pole filters (range: 1–500 Hz and 1–10 kHz, respectively). The second component of the amplifier is a built-in impedance test circuit. This circuit passes a 30-nA (max.) current through the electrode to ground and has a range of 10 kΩ to 5 MΩ. Standard settings are as follows: gain: approximately 4000 times; high pass filter: 100 Hz; low pass filter: 10 kHz.
STIMULATION
A number of stimulation techniques may also be performed during movement disorder surgery. Stimulation may be delivered via macro- or microelectrodes and may be used either to assess proximity to structures one wishes to avoid (e.g., internal capsule, optic tract) or to assess the potential clinical effects of chronic stimulation. Many microelectrode recording systems allow the surgical team to switch between recording and stimulation modes. This permits direct comparison of recording and stimulation data; however, stimulation leads to a more rapid degradation of the microelectrode, so a new electrode may be required for each recording tract. Moreover, the volume of tissue that can be affected with microelectrode stimulation is so small that gross clinical changes are rarely observed with this technique. It is therefore preferable to stimulate with macroelectrodes, employing either the Radionics (Burlington, MA) stimulator and lesion generator prior to performing a neuroablation, or the DBS lead itself when performing a DBS procedure. Single- and dual-channel “screener boxes” (Fig.8) are commercially available for this purpose (Models 3625 [single lead] and 3628 [dual lead]; Medtronics Inc., Minneapolis, MN).

During stimulation, a train of impulses is passed through the region of interest and the clinical effects are noted. The stimulus can be delivered in either a mono- or biphasic fashion. A monophasic stimulus varies from the reference by the signal amplitude and then returns to the reference. The rate of change can be edge, ramp, or sinusoidal in nature. A biphasic stimulus varies from the reference in both the positive and negative directions. Typically, the amplitude of the change is the same in both directions, but this is not always the case. The Medtronics, Inc. implantable neural stimulators generate a biphasic pulse with a positive component that is less intense than the negative component.
Stimulation may also be mono- or bipolar in nature. Monopolar stimulation is generated at the active tip and is referenced to some distant point. With bipolar stimulation, the active and reference electrodes are in close proximity so that current flows within a tightly defined space. The concentric ring electrode is a commonly employed bipolar stimulation configuration where the inner tip is the active electrode and the outer ring is the reference electrode. Chronically implanted DBS leads are equipped with four contacts arranged in series, allowing for either mono- or bipolar stimulation employing any one or combination of contacts. In order to deliver a monopolar stimulus, the active contact(s) is (are) referenced to the pulse generator case. Bipolar stimuli are conducted between any combination of contacts. Table.1 demonstrates some of the important specifications for stimulators.

 

TABLE.1 Stimulator Specifications
Feature	First type	Second type
Output Polarity	Bi-Phasic – Deviations in both the positive and negative directions from the reference point	Mono-Phasic – Single deviation from the reference point
Constant Measure	Constant Current – The current of the device is set by the user, and the stimulator adjusts the voltage to compensate for impedance deviations	Constant Voltage – The voltage of the device is set by the user, and the stimulator adjusts the current to compensate for the impedance deviations.
Pulse Width	The width of each pulse
Frequency	The number of pulses per second
Train Length	The time that the stimulator presents a set of pulses
Amplitude	The strength of the stimulus
Wave Shape	The type of waveform. Most stimulators used for these procedures generate square pulses.

  TECHNIQUE FOR MOVEMENT DISORDER SURGERY
GENERAL STEREOTACTIC TECHNIQUE
The stereotactic headframe is applied on the morning of surgery with local anesthetic (Fig.9). Care is taken to center the head within the frame and to
align the base ring of the frame with the orbitomeatal line, which approximates the orientation of the AC-PC line. In this way, axial images obtained perpendicular to the axis of the frame will run parallel to the AC-PC plane. The patient is transferred to radiology, where a stereotactic MRI is performed.

Axial fast spin-echo inversion recovery MRI is employed to localize the commissures and determine their stereotactic coordinates. We then derive the coordinates of the midcommissural point (MCP) by averaging the coordinates of the commissures and calculate the coordinates of our surgical target based on its relationship to the commissures and/or the MCP. The calculations employed for the most commonly targeted sites are given in Table.2.

The patient is returned to the operating room (Fig.10 shows the room layout that we employ at our center) and is positioned supine on the operating table, which is configured as a reclining chair for the patient’s comfort. The target coordinates are set on the frame, bringing the presumptive target to the center of the operating arc. The operation is performed through a 14-mm burr hole that is positioned approximately 1 cm anterior to the coronal suture and 2–3 cm lateral of the midline. The dura mater is opened and microelectrode recording is begun.

The microdrive adapter and the X-Y adjustment stage are mounted onto the operating arc. The microelectrode is back-loaded into the microdrive and zeroed to the guide tube. The electrode is withdrawn into the cannula (∼5 mm) for safe insertion. An insertion cannula is advanced through the frontal lobe to a point that is 20 mm anterosuperior to the presumptive target. The guide tube containing the recording electrode is inserted into the insertion cannula and the microdrive apparatus is mounted to the X-Y adjustment stage. At this point the guide tube, to the end of which the electrode tip position is zeroed, is flush with the end of the insertion cannula. Thus recording begins 20 mm anterosuperior to the presumptive target.
The electrode is driven 3.0 mm into the brain and the impedance of the electrode–tissue system is measured. In our experience, impedances of 700 KΩ to 1.2 MΩ provide the best single-unit recordings. Even with conditioning of the electrode and stimulation testing, these starting impedances allow for sufficient current passage without degradation of the recording electrode surface. If there is a large impedance drop following electrode conditioning, the electrode is deemed unacceptable and is replaced. We correct any noise problems at this time and then proceed to data acquisition.
At the conclusion of each recording trajectory, the collected data are mapped onto scaled sagittal sections derived from the Schaltenbrand-Wahren stereotactic atlas, and a determination is made as to tract location and orientation employing a “best fit” model (see data organization section). When the data suggest that our targeting is correct, we proceed either to test stimulation and ablation or DBS lead insertion.

GPi Procedures
Posteroventral pallidotomy and GPi deep brain stimulation are reported to improve tremor, rigidity, and LID in patients with medically refractory, moderately advanced PD. Though the published experience is limited, preliminary results suggest that GPi stimulation yields results that are similar to pallidotomy, with the added benefit that bilateral stimulation can be performed more safely than bilateral pallidotomy.
Profound improvements have also been reported in patients with DYT1- associated primary dystonia in whom GPi stimulation was performed. The authors have performed seven of these procedures, noting dramatic improvements in tone, posture, and overall motor function. Of course, further study is required before the full benefit of this surgery in primary and secondary dystonias is known.
Successful pallidal interventions require targeting of the sensorimotor region of GPi, which lies posterior and ventral in the nucleus. When recording in this region, three key nuclear structures must be recognized: the striatum, the GPe, and the GPi (Fig.11) (see also color plate). Our typical trajectory passes at a 60–70° angle above the horizontal of the AC-PC line, and at a medial-lateral angle of 90° (i.e., true vertical). By employing this purely parasagittal trajectory, we can more readily fit the operative recording data to the parasagittal sections provided in human stereotactic atlases. The first cells encountered during recording are in the corpus striatum (caudate and putamen; colored blue in Fig.11). They exhibit characteristic low-amplitude action potentials, which sound like corn popping (Fig.12A). Cellular activity in this area is extremely scanty, and the background is quiet. The electrode may also traverse some quiet regions that represent small fingerlike projections of the internal capsule into the striatum.

Either the detection of a border cell or an increase in background activity marks entry into the GPe, the next structure to be encountered. Border cells
(Fig.12B) exhibit very low frequencies (between 2 and 20 Hz) that are highly periodic and high-amplitude spikes with moderate to wide firing times. Though rare in this region, border cells greatly facilitate localization of the boundaries within the globus pallidus. Two major cell types are found within the GPe: pausers (Fig.12C) and bursters (Fig.12D). Pauser cells fire arrhythmically at a frequency of 30–80 Hz. They exhibit moderate to high amplitude discharges, a shorter time period, and lower amplitude than the border cells. They are distinguishable by their staccato-type, asynchronous
pauses. An extremely small number of pauser cells (<5%) may demonstrate somatotopically organized kinesthetic responses.
As their name implies, burster cells are distinguished by short bursts of high-frequency discharges, achieving rates as high as 500 Hz. Amplitudes vary but are usually less than the amplitudes of the pauser cells. It is important to differentiate bursters from what we refer to as X-cells (Fig.12E). X-cells exhibit high-frequency discharges (near 500 Hz) with a time-related (<30 s) decrease in amplitude, representing death of the cell.
We may encounter anywhere from 4 to 8 mm of GPe during one recording tract. Border cells are again encountered at the inferior border of GPe and are more plentiful in this region. A quiet laminar area (Fig.11) is encountered upon exit from the GPe, marked by a steep dropoff in background activity.
Border cells are again encountered upon entry into the GPi, and again, two classes of neurons predominate within the nucleus: tremor-related cells and
high-frequency cells. Tremor cells (Fig.12F) fire rhythmically in direct relation to the patient’s tremor. Single-unit recordings show a frequency modulation pattern, while semi-microelectrode recordings show a frequency and amplitude modulation pattern. The firing rate of these cells is between 80 and 200 Hz.
High-frequency cells (Fig.12G) are characterized by firing rates that are similar to the tremor cells (80–100 Hz), but are much more stable, exhibiting consistent amplitude and frequency. Many of these cells respond to active or passive range of motion of a specific joint or extremity. Guridi et al. have physiologically defined a somatotopic organization of the kinesthetic cells in the GPi, with the face and arm region located ventrolaterally and the leg dorsomedially. Taha et al. found a slightly different arrangement, with the leg sandwiched centrally between the arm in both the rostral and caudal areas. Vitek et al. have found the leg to be medial and dorsal with respect to the arm, and the face more ventral. The GPi is subdivided into external and internal segments, labeled GPie (external GPi) and GPii (internal GPi), respectively. Both regions exhibit similar cellular recording patterns, but GPie may exhibit less cellularity than GPii. Total GPi recordings normally span from 5 to 12 mm. A steep dropoff in background activity denotes exit from the
GPi inferiorly.
Three important white matter structures border the GPi and may be encountered during recording. The ansa lenticularis (AL), which emerges from the base of the GPi, carries motor-related efferents from the GPi to the ventrolateral thalamus, merging with its sister pathway, the lenticular fasciculus at the H field of Forel. The AL is an electrically quiet region, although rare cells of relatively low amplitudes and firing frequencies can be recorded. It has been proposed that lesioning within the AL generates the best results from posteroventral pallidotomy.
The optic tract (OT) lies directly inferior to the AL (Fig.11), accounting for the high rate of visual field complications reported in the early modern pallidotomy literature. With quality recordings, it is possible to hear the microelectrode tip enter the OT, the sound of which is reminiscent of a waterfall. Upon hearing this background change, one may confirm entry into the optic tract by turning off the ambient lights and shining a flashlight in the patient’s eyes. This will increase the recorded signal if the electrode is within the OT. Finally, one may encounter the internal capsule. Background recordings within the capsule are similar to those of the OT. Movement of the mouth or contralateral hemibody will generate a swooshing sound that is
correlated to the movement. Obviously, one wishes to avoid the posterior capsule when making a lesion or placing a DBS lead, since a hemiparesis or hemiplegia may result.
Macroelectrode stimulation is performed prior to lesioning to ensure that the electrode is a safe distance from the internal capsule and the OT. We conduct test stimulation with the Radionics 1.1-mm by 3-mm exposed-tip stimulating and lesioning electrode, employing a stimulation frequency of 60 Hz and a pulse width of 0.2 ms at 0–10 V. Stimulation of contralateral muscular contractions at less than 2.5 V suggests that the lesioning electrode is too close to the internal capsule and should be adjusted laterally. Induction of phosphenes at less than 2.0 V suggests that the electrode is too close to the OT and should be withdrawn slightly. Test stimulation should be performed at 2- to 3-mm intervals beginning 6–8 mm above the base of GPi as defined by MER. Decreasing voltage trends in the induction of muscular contractions and/or phosphenes should be monitored. If stimulation is begun inferiorly, one risks creating a tract through which current may leak, resulting in persistently low thresholds for the stimulation of phosphenes that will cause the lesioning probe to be withdrawn too far. A suboptimal lesion may result. Employing this technique, one of the authors (RLA) has performed more than 110 pallidotomies without inducing visual field abnormalities or hemiparesis.
If stimulation indicates that the targeted region is a safe distance from the internal capsule and OT, the therapeutic lesion is placed. Ablation begins at the base of the GPi and progresses upward in 2-mm increments, creating a cylindrical lesion that encompasses the span of GPi as defined by MER. A test lesion is initially performed at 40°C for 40 s, after which the patient’s visual fields and basic motor function are checked. If there are no adverse visual field or motor changes, a permanent lesion is performed at 80°C for 60 s. Ideally, lesions should not encroach upon the GPe, because the working model of basal ganglia physiology suggests that GPe lesioning may worsen parkinsonism.
Excellent pallidotomy results also have been reported without the use of microelectrode recording and with the performance of ablations of varying size ranges. To date, no correlation between lesion size and surgical outcome has been made.

VIM Procedures
Therapeutic neuroablation or chronic high-frequency electrical stimulation
within the ventral intermediate nucleus of the thalamus (VIM; Fig.13) suppresses parkinsonian and essential tremor without adversely affecting voluntary motor activity to a significant degree (thalamotomy may be associated with some loss of fine dexterity). Thalamic interventions are extremely gratifying to perform because of the immediacy of the results and the well-defined physiology of the motor and sensory thalamic nuclei.
When targeting VIM, our standard angles of approach are 60–70° relative to the AC-PC line, and 5–10° lateral of the true vertical. Pure parasagittal trajectories cannot be employed as they are in globus pallidus procedures due to the medial location of the target and a desire to avoid the ipsilateral lateral ventricle.

Transit through the ventricle may increase the risk of hemorrhage and typically leads to more rapid loss of cerebral spinal fluid (CSF) with resulting brain shift and loss of targeting accuracy. Recording begins in the dorsal thalamus, where cells characterized by low amplitudes and sparse firing patterns are encountered. Bursts of activity and small-amplitude single spikes (Fig.14A) are typical findings in this region. Upon exiting the dorsal thalamus, the electrode enters the VL nucleus, which is composed of nucleus ventralis oralis anterior (VOA), ventralis oralis posterior (VOP), and VIM. The dorsal third of the VL nucleus is sparsely populated such that cellular recordings in this area are similar to those of the dorsal thalamus. As the electrode passes ventrally within the VL complex, cellular density increases and cells with firing rates of 40–50 Hz (Fig.14B) are encountered. Kinesthetic cells with discrete somatotopic representation are routinely encountered. This organization permits an assessment of the mediolateral position of the electrode. The homunculus of the ventrocaudal (Vc) and VIM nuclei are virtually identical: representation of the contralateral face and mouth lies 9–11 mm lateral of midline, the arm is represented lateral to this at 13–15 mm lateral of midline, and the leg is more lateral still, adjacent to the internal capsule. Thus, if one encounters a cell that responds to passive movement of the ankle, one knows that one has targeted too laterally to treat an upper-extremity tremor and should adjust the mediolateral position accordingly.
In addition to kinesthetic neurons, one will routinely encounter “tremor” cells (Fig.14C) within the VIM of tremor patients. These cells exhibit a rhythmic firing pattern that can be synchronized to EMG recordings of the patient’s tremor. Lenz et al. demonstrated that these cells are concentrated within VIM, 2–4 mm above the AC-PC plane, a site that is empirically known to yield consistent tremor control.
The recording electrode may exit VIM inferiorly, passing into the zona incerta (ZI) with a resulting decrease in background signal, or it will enter Vc, the primary sensory relay nucleus of the thalamus. Entry into Vc is marked by a change in the background signal. Cells in this region are densely packed, exhibit high amplitudes, and respond to sensory phenomena (e.g., light touch) with a discreet somatotopic organization, which mirrors that of VIM and may also be used to assess target laterality (Fig.14D). A typical cell, which responds to lightly brushing the patient’s finger, is featured in Fig.14E. Note the increase in firing rate as a light bristle paintbrush is dabbed against the finger. The bars represent the times that the brush is being dabbed against the finger. If Vc is encountered early in the recording trajectory, the electrode may be targeted posteriorly and should be adjusted anteriorly. The nucleus ventrocaudalis parvocellularis (VCpc) rests inferiorly to Vc. Recordings within this nucleus are similar to those of Vc; however, stimulation in this location may yield painful or temperature-related sensations. Single-unit recordings in this area will respond to both painful and temperature-related stimuli applied within the cell’s receptive field.
Stimulation within the thalamus for the purposes of localizing therapeutic lesions may be performed with constant-voltage or constant-current devices, and with micro- or macroelectrodes. When stimulating with constant current, we employ 60 μs and 1 ms pulse widths at a frequency of 180 Hz. Regardless of technique, the reference is a cautery ground pad that is placed on the back of the thigh ipsilateral to the side of the stimulation. We consider a motor stimulation threshold of 1 mA or 3 V safe for placing a thalamotomy
lesion.
When performing VIM DBS, we use the lead itself to perform test stimulation. In such cases bipolar stimulation is performed so that a reference pad is
unnecessary. In our experience, a properly positioned DBS lead results in tremor arrest at <3 V (pulse width: 60 μs; frequency: 180 Hz). Transient paresthesias are common with a properly positioned electrode; however, persistent paresthesias, which are induced at low voltages, indicate that the electrode is positioned posteriorly, near or within Vc. Failure to suppress tremor or induce paresthesias, even at 5 V, suggests that the electrode is positioned anteriorly within VOA. Muscular contractions (typically of the contralateral face and/or hand) suggest that the lead is positioned too laterally and stimulation is affecting the internal capsule. Microelectrode stimulation may not suppress tremor at sites where macroelectrode stimulation is effective.

STN Procedures
Bilateral STN DBS appears to be the most effective treatment for PD since levodopa, which was introduced more than a generation ago. Subthalamic DBS improves all of the cardinal features of PD, dampens the severity of “on–off” fluctuations, alleviates freezing spells, and dramatically reduces medication requirements.
The STN is approached at an angle of 70° relative to the AC-PC line and 10–15° lateral of the true vertical. Microelectrode recording begins in the anterior thalamus and passes sequentially through the ZI, Forel’s field H2, the STN, and the substantia nigra pars reticulata (SNr) (Fig.15).
In the thalamus, one encounters cells that fire with low amplitude and frequency. Two patterns of activity may be identified: (1) bursts of activity(Fig. 16A) and; (2) irregular, low-frequency (1–30 Hz) activity (Fig.16B). The density of cellular activity varies in this region. For example, it is observed that VOA is more cellular than the reticular thalamus. The border between the thalamus and ZI (Fig.16C) may be very distinct, but not in all cases. Developmentally, the ZI is a continuation of the reticular nucleus of the thalamus, and the transition from one to the other may not be clear. The ZI can be differentiated electrophysiologically from the thalamus in two ways. First, cellular activity is more muffled or “muddy” in the ZI. By this we mean that the cellular firing rates slow and become a little more asynchronous, and the amplitudes decrease in intensity. These changes are subtle and can be missed by inexperienced observers. The second indication of transition from thalamus to ZI is a change in the background recordings.

Whereas the background of the thalamus proper is somewhat active, the ZI background is much quieter. Typically, the recording electrode will exit the thalamus 6–10 mm anterosuperior to our presumptive target and will pass through 2.5–4.0 mm of ZI before entering H2. If more than 4 mm of relative
“quiet” is encountered, a trajectory that is anterior or posterior to the STN should be suspected.
A decrease in background activity demarcates entry into Forel’s field H2, which lies immediately superior to the STN, 10–12 mm lateral of midline. Sparse cellular activity is detected over a span of 1–2 mm. Background activity increases as the recording electrode enters STN. Additionally, dense cellular activity is now encountered. Two patterns of cellular activity are observed within STN: (1) tremor activity (Fig. 16.16D, CD-STN sound 4) similar to that encountered in VIM or GPi; and (2) single-cell activity (Fig.16E) with frequencies that vary from ∼25 Hz to 45 Hz. Cells in the dorsal segments of the STN exhibit slower firing rates than those of the ventral STN. Kinesthetic related activity is often observed, but a clear somatotopy is not evident. Upon exiting the STN, the microelectrode may pass through a thin quiet zone or will pass directly into the SNr. Entry into the SNr is demarcated by significant increases both in background neural activity and in cellular firing rates (Fig.16F), which are usually greater than 60 Hz. Up to 7 mm of SNr may be encountered, depending on the anteroposterior position of the trajectory.
 

Required 4–6 mm of STN, preferably with evidence of kinesthetic activity, for implantation of the DBS lead. This large a span allows for two of the four electrode contacts to be placed within the nucleus, leaving the other two above the nucleus in the ZI and H2. Additionally, this large a span of STN recording ensures that the electrodes are implanted solidly within the nucleus and not near a border.
The primary goal of test stimulation at the STN is to check for stimulation-induced adverse events (AEs) because, aside from tremor arrest and some modest reductions in rigidity, positive STN stimulation effects may not be observed for hours or days. Test stimulation is performed in bipolar configuration with the implanted DBS lead and Medtronic’s single lead screener (model 3625, Medtronic, Minneapolis, MN). Parameters are: 60 μs, 180 Hz, 0–4 V. We do not stimulate higher than 4.0 V for fear of inducing hemiballism. Moreover, we have yet to employ amplitudes greater than 4 V to achieve clinical benefit at this target. Transient paresthesias are frequently encountered with the onset of stimulation. Persistent paresthesias indicate stimulation of the medial lemniscal pathway, which lies posterolateral to the nucleus. Stimulation-induced contractions of the contralateral hemibody and/or face indicate anterolateral misplacement of the lead. Finally, abnormal eye movements may be encountered if the lead is positioned too medially or deep to the nucleus. The first test stimulation is performed using contacts 0−, 1+ up to a voltage of 4.0 V. If no significant adverse effects are encountered with this focal test, we proceed to test stimulation employing all four contacts (i.e., 0−, 1−, 2+, 3+ up to a voltage of 4.0 V). This test covers the full contact space of the electrodes and focuses on identifying stimulation-induced adverse events in the ventral aspect of the stimulation
field. This is the area where most AEs have occurred in our experience. The final stimulation is performed using contacts 0+, 1+, 2−, 3− up to a voltage of 4.0 V. This examines the dorsal aspect of the stimulation field.

Data Organization
The data from each microrecording tract are plotted on scaled graph paper (1.0 cm: 1.0 mm). The borders of each encountered structure are marked, and the span of each region is represented by a different color for easy differentiation. In order to accurately account for our angle of approach, a line that is parallel to the intercommissural line is also drawn. The plotted tract is then traced onto a transparent plastic sheet. The transparency is placed on scaled maps (10:1) derived from the Schaltenbrand-Wahren human stereotactic atlas in order to determine to which map the trajectory best fits. The accuracy of the fit is dependent upon the number of trajectories, the number of structures encountered along each trajectory, and finally upon how well the patient’s anatomy fits the atlas, which is derived from a single human specimen. It can be difficult to find one place to which a single tract fits best, especially when performing pallidal or thalamic interventions. When mapping the STN, the many structures encountered along a single trajectory make fitting it to the atlas a little more straightforward. If there is any question about the proper fit of the data, we perform another recording tract. Knowing the spatial relationship between each tract, we can better fit all of the data to the atlas with each subsequent trajectory.

CONCLUSION
The fine details of these procedures vary from center to center, but the neurophysiological techniques used by each center can be divided into the following categories: (1) microrecording; (2) semi-microrecording; (3) stimulation; and (4) evoked response testing. In the over 1,500 trajectories performed by Shils J. L. et al., they feel that the information gathered with microrecording is of great benefit when performing these surgeries. Microrecording has been shown to be as safe as other stereotactic procedures when done properly. With these surgeries they tried to modify the physiology of a target structure; therefore, microrecording gives specific physiologic data to help determine the optimal placement. In most cases (43–88%, depending on the study), this physiological target corresponds to the anatomic target, but in the 12–67% of cases that is not the case. At present there is no way of knowing which of these patients will fall into either category before the surgery.
The neurophysiologic techniques used in the operating room require trained and skilled personnel, not only to acquire but also to interpret the data. If everything goes perfectly, the data are relatively easy to interpret, but when the signals are not textbook cases, this interpretation needs to be done by very experienced personnel. Up until the mid-1990s, centers had to put their own microelectrode recording systems together and build their own microelectrodes, since there were no commercially available systems. At the present time there now exist about 10 companies (internationally) that produce microrecording systems, and the first FDA-approved microelectrodes were placed on the market in 2000. The key points to get the best signals at are the microelectrode, preamplifier, and amplifier. The main feature of reliable microelectrode systems for neurophysiological targeting of deep brain structure is the quality of the recorded signal. This is more important than any of the fashionable features that many manufactures offer. No software-based interpretation scheme is going to replace the skilled human interpreter when the recordings are difficult.
As already stated, the operating room is very harsh electrically. The more we learn about the areas of interest, the faster and smoother each of these procedures will go.