Abstract:
A multi-electrode probe is used to create an electrophysiological depth profile during stereotactic neurosurgery. A surgeon uses CT or MRI images to identify the general location of a target site in the brain and then inserts the multi-electrode probe into this area. Each electrode on the probe produces a signal that indicates the level of activity in a nearby neuron or cluster of neurons. A processor converts these signals into an electrophysiological depth profile indicating the level of activity detected by each of the electrodes. The surgeon identifies the precise location of the target site by watching the display to determine which electrode or group of electrodes detects the highest level of neuronal activity as the stimulus is provided.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 60/075,741, filed on Feb. 23, 1998. 
    
    
     TECHNOLOGICAL FIELD 
     This application relates to the use of electrode probes in stereotactic neurosurgery. 
     BACKGROUND 
     Certain neurosurgical procedures require the determination of the precise location of target tissue, and fine discrimination of the target from adjacent non-target tissue. For example, during a “pallidotomy,” a procedure often performed on patients with Parkinson&#39;s disease, the neurosurgeon must carefully introduce a lesioning device into a small area deep in the brain called the Globus pallidus internus (Gpi), while avoiding the adjacent Globus pallidus externus (Gpe). Computed tomography (CT) and magnetic resonance imaging (MRI) are typically used to guide the surgeon to the Gpi/Gpe region. More precise, localized targeting is often achieved by means of electrophysiological localization techniques. 
     Conventional electrophysiological localization techniques typically involve the insertion of a tungsten electrode into the brain to detect neural activity. Because different brain areas produce characteristic patterns of neural activity, the signals picked up by the electrode at different locations are used to finely distinguish between the different brain areas. The Gpe and Gpi, for example, produce different characteristic patterns of activity, as monitored on the tungsten electrode. This knowledge is used during a pallidotomy to determine the boundary between the two structures, which allows the subsequent introduction of a lesion into the Gpi while avoiding lesioning the Gpe. 
     Because the tungsten electrode detects activity at only one site in the brain at any given time, the surgeon moves the electrode sequentially to multiple sites, stopping at each site for some time to monitor the local neuronal activity. Typically the electrode is inserted into the brain at a few different surface locations, and several depth locations are monitored along each electrode insertion track. Characteristic patterns of neural activity are noted at several of these electrode locations. As this information builds up over the course of the surgery, the surgeon derives an anatomical and/or functional map of that part of the brain. 
     The success of electrophysiological localization depends largely on the skill of the surgeon, who must accurately position the electrode at several sites in the brain and then accurately interpret the measurements taken by the electrode. Even the slightest misguidance of the electrode or misinterpretation of the measurements can lead to brain damage. As the number of monitored sites increases, so does the time required, and therefore the risk of brain damage, the cost of surgery, and the risk to the patient&#39;s health. 
     SUMMARY 
     The inventors have developed a technique for using a multi-electrode probe to rapidly create an electrophysiological depth profile during stereotactic neurosurgery. The depth profile provides information about concurrent neuronal activity at a set of positions, or depths, along the probe insertion track. This information supplants the limited information that neurosurgeons currently receive by taking a set of individual measurements at multiple depth positions with a single-electrode probe, and then manually assembling the sequentially-obtained information into a composite depth profile. One measurement with the multi-electrode probe allows the derivation of a depth map that normally is possible only with many measurements using a single-electrode probe, thus saving surgical time and reducing the associated costs and risks. Simultaneous measurement at multiple locations, which is impossible with single-electrode probes, also provides information about correlations between different neural groups. This information is useful in improving the quality of data interpretation and surgical targeting. 
     In one aspect, the invention features a technique for using a multi-electrode probe to locate a target site in a brain during stereotactic neurosurgery. The surgeon first identifies an area of a brain that includes a target site to be treated. The surgeon then inserts a multi-electrode probe into this area of the brain. The probe includes multiple electrodes that concurrently produce output signals indicative of concurrent neuronal activity at multiple sites in the brain. The output signals are used to generate a user interface that provides an indication of the level of concurrent neuronal activity at each of the multiple sites. 
     In another aspect, the invention features a multi-electrode probe system for use in locating a target site in a brain during stereotactic neurosurgery. The system includes a multi-electrode probe inserted into an area of a brain that includes a target site to be treated. The probe includes multiple electrodes that produce output signals indicative of concurrent neuronal activity at multiple sites in the brain. The system also includes a processor that receives the output signals from the electrodes and derives the level of concurrent neuronal activity that occurs at each of the multiple sites. A user interface displays an indication of the level of concurrent neuronal activity at each of the multiple sites. 
     In some embodiments, the user interface provides a depth profile indicating the level of concurrent neuronal activity at various depths in the brain. Some versions of the user interface provide an indication of spike rate for individual neurons at the multiple sites. The user interface often includes a graphical display or a sound signal that provides a visual or audible indication, respectively, of the level of neuronal activity at each of the multiple sites. Other embodiments require the surgeon to provide a stimulus directed to neurons at the target site to increase the level of neuronal activity at the target site. 
    
    
     DESCRIPTION OF THE DRAWINGS 
     FIG. 1 shows a multi-electrode probe for use in stereotactic neurosurgery. 
     FIG. 2 shows a multi-electrode probe system for use in stereotactic neurosurgery. 
     FIG. 3 is an example of a visual display provided by the system of FIG. 2 during neurosurgery. 
     FIG. 4 is another example of a visual display provided by the system of FIG. 2 during neurosurgery. 
    
    
     DETAILED DESCRIPTION 
     FIG. 1 shows a multi-electrode probe  10  that is used in locating a target site in the brain during stereotactic neurosurgery. The probe  10  includes one or more relatively thin shafts  12 A- 12 B that penetrate the brain. Each shaft  12 A- 12 B includes an array of spaced electrodes  14 A-J that detect activity in the neurons of the brain. This activity generally appears in the form of current spikes in the neurons. These current spikes produce corresponding voltage spikes, or event potentials, in the matter surrounding the neurons. The electrodes  14 A-J detect these event potentials and produce continuous output voltages that vary in magnitude as the event potentials are detected. Because the probe  10  includes an array of electrodes  14 A-J, the probe  10  is able to detect concurrent activity at multiple sites in the brain. 
     A group of conductors  16  on the probe link the electrodes  14 A-J to an optional signal processing circuit  18 . This circuit  18  includes conventional signal processing electronics, such as amplifying, filtering, and digital signal processing (DSP) circuitry, that prepare the electrode signals for external processing. The probe  10  also includes a signal transmission element, such as a conductive cable  19  or an infrared (IR) transmitter, that delivers the signals to an external processor (described below). 
     The probe shafts  12 A,  12 B serve several functions, such as providing structural support for the electrodes and the signal conductors. The probe shafts  12 A,  12 B are manufactured from a combination of structural, conductive, and insulating materials, such as silicone, polyimide, glass, epoxy, tungsten, and gold. The electrodes  14 A-J are manufactured from any of a variety of materials that conduct electrically, including metals such as tungsten and gold, metal compounds such as iridium oxide, polymers such as polyimide and silicone, and semiconductors such as doped silicon. One technique for manufacturing the probe  10  is the silicon-based micromachining technique described in Kewley, et al., “Plasma-etched Neural Probes,” Sensors and Actuators A 58 (1997), pp. 28-35, the full disclosure of which is incorporated by reference. 
     In general, the probe  10  is manufactured with dimensions tailored to the specific part of the brain in which the probe  10  is to be used. For example, one probe design, for use in performing a pallidotomy on a typical human brain, includes a single shaft that is approximately 190-250 mm long and has a linear array of thirty-two electrodes separated from each other by approximately 40 μm near the tip of the shaft. 
     FIG. 2 shows a multi-electrode probe system  20  for use in performing neurosurgery. The system includes a conventional micromanipulator  21  that mounts on a stereotactic frame  25  bolted to the patient&#39;s head  23 . A typical micromanipulator  21  includes a stepper motor that accurately positions the probe in the patient&#39;s brain. The micromanipulator  21  moves the probe  10  in increments that often are as small as 1 μm. 
     The system  20  also includes an analog or digital processor  22  that receives the signals from the probe  10  via the conductive cable  19  and derives information useful to the neurosurgeon. The processor  22  records this information in an optional storage device  24  and provides this information to the neurosurgeon on an optional video display  26  or through another output device, as described below. The processor  22  also receives information from the micromanipulator  21  indicating the probe&#39;s position in the brain, or “brain depth,” with respect to a predetermined reference position. 
     In stereotactic neurosurgery, the surgeon typically needs to know the “spike rate” generated by individual neurons. A neuron&#39;s spike rate indicates the number of current spikes occurring in a brain cell during a given time period, usually measured in terms of spikes per second. Because an electrode often detects signals from multiple neurons, and because several electrodes often detect signals generated by a single neuron, the processor performs an optional spike sorting algorithm to determine which neurons generated which of the detected spikes. Examples of suitable spike sorting algorithms are described in the following documents, the entire disclosures of which are incorporated by reference: U.S. Provisional Application 60/099,184, filed on Sep. 4, 1998, by Andersen, Pezaris, and Sahani, and entitled “Probabilistic Algorithms for the Separation of Signals in Neural Microelectrode Recordings”; and Sahani, et al., “On the Separation of Signals from Neighboring Cells in Tetrode Recordings,” Advances in Neural Information Processing Systems 10 (1998). The processor  22  stores all of this information in the storage device  24  and, in some embodiments, indexes the stored information with the brain depth of the site from which the information was derived. 
     FIG. 3 is one example of the type of information that is presented on the video display  26 . The information in this example is derived from a probe  30  having a single shaft  32  with eight evenly-spaced electrodes  34 . The information is presented in the form of a color-coded graph  36  that provides information on three axes: a horizontal axis  38  representing time; a vertical axis  40  representing brain depth; and a color axis  42  representing signal voltage, or level of neuronal activity. At each position on the horizontal (time) axis  38 , the graph  36  includes a color-coded box  44  for each of the electrodes  34  on the probe  30 . The position of the box  44  along the vertical (depth) axis  40  indicates the depth of the corresponding electrode in the brain. The color of the box  44  indicates the magnitude of the voltage detected by the corresponding electrode. In this example, lighter colors indicate larger detected voltages. In some implementations, the display includes traces  46  showing the instantaneous values of the signals produced by the electrodes  14 A- 14 J. These traces are similar to the oscilloscope traces traditionally used by surgeons in performing stereotactic neurosurgery. 
     FIG. 4 is another example of the type of information that is presented on the video display  26 . In this example, the display  50  provides a histogram  51  indicating the spike rates of nine individual brain cells, as detected by a probe with eight electrodes. The display  50  includes a set of icons  52 A-H representing the eight electrodes. These icons  52 A-H are arranged spatially in a manner that represents the positions of the electrodes on the probe. The display  50  also includes a set of icons  54 A-I representing the nine brain cells. These icons  54 A-I are arranged in a manner that represents the approximate spatial orientation of the brain cells, as determined by the spike sorting algorithm in evaluating the strengths of the signals produced by the electrode array. The display  50  also displays an indication  56  of the brain depth at which the electrodes and the brain cells are located. When a conventional micromanipulator is used, these values indicate the distance between the corresponding portion of the probe and the reference point. 
     During surgery, the neurosurgeon uses conventional techniques, such as CT and MRI scans, to locate the general area in which target site lies. The surgeon then inserts an appropriately designed multi-electrode probe into the brain and positions the probe near the target area. Once in the brain, the electrodes produce signals that indicate the presence of activity in nearby neurons. For a pallidotomy procedure, the target site lies within the Globus pallidus internus. 
     Neurons in the Gpi typically fire at spike rates greater than 60 spikes per second, while neurons in the Gpe typically fire at rates between 30-60 spikes per second. The display identifies the boundary between the Gpi and the Gpe by showing where the spike rate changes significantly. For some types of neurosurgery, the surgeon stimulates a particular portion of the brain, e.g., by moving one of the patient&#39;s limbs, to intensify the differences in spike rate between two adjacent areas of the brain. 
     Other embodiments are within the scope of the following claims. For example, some systems present neuronal activity information to the surgeon in a non-visual manner, such as through audible signals that change in tone as the level of neuronal activity changes. In some cases, each of the electrodes is mapped to a unique sound, which allows the surgeon to distinguish changes in activity at one electrode from changes at other electrodes. These sound-based systems free the surgeon&#39;s eyes to focus on the probe itself and on other video-based equipment. Other embodiments use virtual reality equipment, such as 3D goggles and data gloves, to indicate the level of neuronal activity. Data gloves give non-visual information about neuronal activity by supplying sensory feedback to the fingers of the person wearing the gloves. Moreover, while the invention has been described in terms of neuronal spike analysis, other techniques for monitoring neuronal activity and other types of information are useful as well.