Dual Channel Implantation Neurostimulation Techniques

1. Field of the Invention

This invention relates to means of stimulating electrically excitable tissue, and more particularly relates to means for adjusting the locus at which action potentials are induced in such tissue.

2. Description of the Related Art

Two major practical problems reduce the efficacy of epidural spinal cord stimulation (SCS) for pain control. One is the difficulty of directing the stimulation-induced paresthesia to the desired body part and the other is the problem of disagreeable sensations or motor responses to the stimulation, which reduce the comfortable amplitude range of the stimulation. It is generally agreed that in SCS, for chronic pain, paresthesia should cover the whole pain region. With present stimulation methods and equipment, only highly skilled and experienced practitioners are able to position a stimulation lead in such a way that the desired overlap is reached and desired results are obtained over time with minimal side effects. It requires much time and effort to focus the stimulation on the desired body region during surgery and, with single channel approaches, it is difficult to redirect it afterwards, even though some readjustments can be made by selecting a different contact combination, pulse rate, pulse width or voltage.

Redirecting paresthesia after surgery is highly desirable. Even if paresthesia covers the pain area perfectly during surgery, the required paresthesia pattern often changes later due to lead migration, or histological changes (such as the growth of connective tissue around the stimulation electrode) or disease progression. The problem of lead placement has been addressed by U.S. Pat. No. 5,121,754 by the use of a lead with a deformable distal shape. These problems are not only found with SCS, but also with peripheral nerve stimulation (PNS), depth brain stimulation (DBS), cortical stimulation and also muscle or cardiac stimulation.

A system capable of some adjustment of spinal cord excitation is described in PCT International Publication No. WO 95/19804. However, that system requires three electrodes, optimally spaced, which is a serious handicap during the surgical procedure required in order to place these electrodes in the body. Three electrodes may require the use of a paddle arrangement which is surgically difficult to manipulate adjacent the spinal cord. In addition, that system has only limited adjustment capability, dependent on the distance from the electrodes to the spinal cord.

The present invention can be used to advantage for altering the locus in electrically excitable tissue at which action potentials are induced. According to a preferred embodiment, first and second electrodes are implanted adjacent the tissue to be stimulated. A first electrical signal is applied to the first electrode and a second electrical signal is applied to the second electrode. The frequency difference between the first and second signals is adjusted and the amplitudes of the first and second signals are adjusted such that the combined potentials induced in the locus by the first and second signals create action potentials in the locus, and the locus is altered.

By using the foregoing techniques, the degree of surgical precision required for the implanting of the electrodes is reduced, because the locus at which the nerve fibers are stimulated can be adjusted by merely changing the frequency difference and amplitudes of the signals applied to the electrodes after the surgical procedure is completed.

According to another embodiment of the invention, the signals may be either sinusoidal or pulsed.

These and other advantages and features of the invention will become apparent upon reading the following detailed description and referring to the accompanying drawings in which like numbers refer to like parts throughout and in which:

FIG. 1 is a diagrammatic view of a patient in which a preferred form of apparatus for spinal cord stimulation (SCS) made in accordance with the invention has been implanted;

FIG. 2 is a cross-sectional view of an exemplary spinal column showing a typical position at which electrodes made in accordance with the preferred practice of the invention have been implanted in the epidural space;

FIG. 3 is a cross-sectional view like FIG. 2 showing locus of potential changes induced in the spinal cord from a signal applied to a first one of two electrodes;

FIG. 4 is a view like FIG. 3 showing the locus of potential changes induced in the spinal cord from the application of a signal to the second of the electrodes;

FIG. 5 is a view like FIG. 4 showing the combined loci in the spinal cord at which potentials are induced from signals applied to the first and second electrodes;

FIG. 6 is a view like FIG. 5 showing the alteration of the loci due to increase in the amplitude of the signal applied to the first electrode and a decrease in amplitude of the signal applied to the second electrode;

FIG. 7 is a view like FIG. 6 showing the alteration of the loci due to an increase in amplitude of the signal applied to the second electrode and a decrease in amplitude of the signal applied to the first electrode; and

FIG. 8 is a timing diagram showing signals applied to the first and second electrodes illustrated in FIG. 2 in relationship to the potentials induced in tissue adjacent the electrodes.

FIG. 9 depicts an idealistic representation of the dual channel ITREL ("DCI") version of the implantable pulse generator utilized in one of the preferred embodiments of the present invention.

FIG. 10 shows the monolithic embodiment of switches N1 and N2 of FIG. 9 along with the additional circuitry required to actuate or toggle each switch into the closed or open position.

FIGS. 11A-D is a schematic of the electrode switch utilized in each stimulating ("S"), recharging ("R"), and stimulating or recharging ("S or R") switch depicted in FIG. 9.

FIG. 12 is a schematic of the circuit used to identify the most negative reference that is utilized as the AMP.sub.-- OUT voltage level of FIG. 9.

FIGS. 13 and 14A-E illustrate the top level representation--along with the relevant control signals driving the electrode switches--of the output circuit depicted in FIG. 9.

FIGS. 15A-15I, 16A-B, 17, 18, 19, 20, 21A-D, and 22A-C illustrate an alternative output circuit configuration for the implantable pulse generator. This alternative output circuit is called "transverse tripolar stimulation."

Referring to FIG. 8, a single electrical signal or pulse, such as P1, can cause depolarization near a cathode in electrically excitable tissue which includes neural tissue and muscle tissue. Neural tissue includes peripheral nerves, the spinal cord surface, deep spinal cord tissue, deep brain tissue, and brain surface tissue. Muscle tissue includes skeletal (red) muscle, smooth (white) muscle, and cardiac muscle. A locus includes a set of points in three-dimensional space and refers to a volume of cells or parts of cells. Due to the electrical characteristics of both the three-dimensional volume conductor and the membrane properties, the potentials outside and inside a neuron respond to the depolarization, usually with exponential-type increases and then attenuation over time. The time constant for an isolated neuron membrane typically is 5-15 milliseconds (Nerve, Muscle and Synapse by Bernard Katz, circa 1972). For myelinated axons or muscle cells, it may be considerably shorter.

As shown in FIG. 8, the local depolarization from a single pulse P1 results in a transmembrane potential PT1 between times T1 and T3. The peak of potential PT1 is below the transmembrane potential threshold TPT. As a result, the pulse fails to produce an action potential in that cell.

Action potential is an all-or-none, nonlinear phenomenon, caused by opening of sodium gates, inrush of sodium of ions, and a delayed opening of potassium gates and a restoration of the membrane potential. In general, a certain amount of charge must be passed at the electrodes (amplitude ›Volts!/ resistance ›Ohms!.times.pulse width ›time!) in order to cause enough depolarization for an action potential to begin. There is a reciprocal relationship between amplitude and pulse width: the product must reach a certain value before the threshold is reached. This relationship does not reach the Volts=0 axis. There is a certain minimum voltage needed, called rheobase, before an action potential can happen.

Basic neurophysiological principles, called "electrotonus", show that in any volume of electrically excitable tissue in which two or more pulses, each of which alone is insufficient to bring the cells to threshold, arrive closely together in time, at least part of their effect is additive, i.e., the memory of the first pulse is still present when the second pulse arrives. If the sum of the potentials (distorted by resistive and capacitive properties of the surroundings and the cell membranes) can get some cells depolarized to threshold, then an action potential will start in those cells.

Still referring to FIG. 8, the inducement of an action potential in a cell is illustrated by a transmembrane depolarizing potential PT3 reaching the transmembrane potential threshold TPT at time T4.

FIG. 1 is a schematic view of a patient 10 having an implant of a neurological stimulation system employing a preferred form of the present invention to stimulate spinal cord 12 of the patient. The preferred system employs an implantable pulse generator 14 to produce a number of independent stimulation pulses which are sent to spinal cord 12 by insulated leads 16 and 18 coupled to the spinal cord by electrodes 16A and 18A (FIG. 2). Electrodes 16A and 18A also can be attached to separate conductors included within a single lead.

In the preferred embodiment, implantable pulse generator 14 is either a modified ITREL II or a dual channel ITREL ("DCI"). Both models of these implantable pulse generators are commercially available from Medtronic, Inc. and are capable of delivering multiple signals to the one or more electrodes on different channels. The implantable pulse generator 14 can provide multiple signals at different adjustable frequencies, pulse widths, amplitudes, and repetition rates. However, in the DCI implantable pulse generator 14, the repetition rates on the different channels are synchronized. The detailed configuration of the output circuitry utilized in the DCI implantable pulse generator 14 is shown in FIGS. 9-14.

The idealistic representation of the DCI version of the implantable pulse generator 14 is depicted in FIG. 9. In this version of the implantable pulse generator 14, the pulse widths are digitally controlled by a timer. The implantable pulse generator 14 must be able to generate different amplitudes while preventing unwanted cross-conduction from occurring between different electrode switches during stimulation. In this version of the implantable pulse generator 14, only one of the channels of electrode switches are stimulated at any given time by the implantable pulse generator 14.

The programmed amplitude of the signal output of each channel of the DCI implantable pulse generator 14 is stored across two different capacitors, C2 and C3. These capacitors C2 and C3 are commonly referenced to the same node AMP.sub.-- OUT. Therefore, AMP1 and AMP2 represent the two amplitudes (voltages) that are stored across capacitors C2 and C3. The 183 ohm resistor and switch 52 is used to discharge all or a portion of the charge on capacitors C2 and C3, thereby reducing the stored amplitude(s). Similarly, the switching regulator 50 is used to increase the charge, and thus amplitude, on capacitors C2 and C3.

Thus, in order to use the electrodes (TPE) on channel 1 ("CH1") or channel 2 ("CH2") to stimulate the biological load or tissue "RL", switches N1 or N2 must first be respectively opened or closed. After switch N1 or N2 is closed, the tissue "RL" is stimulated when the stimulating switches (designated "S") or the stimulating/recharging switches (designated "S or R") are closed. After the stimulation pulse is complete, the system then waits a finite period of time before producing a recharging pulse. In the preferred embodiment, the finite period of time is 244 .mu.sec.; however, a delay of 100 to 500 .mu.sec. could be used. After the finite period of time elapses, the recharging switches (designated "R") or the "S or R" switches are closed in order to reverse the current through the tissue "RL", or in other words to recharge the tissue. The reason for the finite period of time delay is to prevent the physiological cancellation of the stimulation effect. The detailed circuit configuration of the "S", "R", and "S or R" monolithic switches can be seen in FIG. 11.

Other than capacitors C2 and C3, the capacitors 54 depicted in FIG. 9 are used to maintain charge balance. Similarly, capacitors can be installed between the following terminal pairs in order to maintain charge balance: CPB1.sub.-- 1--CPB1.sub.-- 2 and CPB2.sub.-- 1--CPB2.sub.-- 2.

As previously mentioned, FIGS. 15-22 illustrate an alternative output circuit configuration for the implantable pulse generator 14 called "transverse tripolar stimulation." This circuit configuration allows both channels to be utilized in order to simultaneously provide different amplitudes, frequencies, repetition rates, and pulse widths to three electrodes (one reference electrode and two electrodes at different amplitudes).

In the preferred embodiment of the present invention, the system employs a programmer 20 which is coupled via a conductor 22 to a radio frequency antenna 24. This system permits attending medical personnel to select the various signal output options--such as amplitude, pulse width, frequency, and repetition rate--after implant using radio frequency communications. While the preferred system employs fully implanted elements, systems employing partially implanted generators and radio-frequency coupling may also be used in the practice of the present invention (e.g., similar to products sold by Medtronic, Inc. under the trademarks X-trel and Mattrix).

FIG. 2 is a cross-sectional view of spine 12 showing implantation of the distal end of insulated leads 16 and 18 which terminate in electrodes 16A and 18A within epidural space 26. The electrodes may be conventional percutaneous electrodes, such as PISCES.RTM. model 3487A sold by Medtronic, Inc. Also shown is the subdural space 28 filled with cerebrospinal fluid (cfs), bony vertebral body 30, vertebral arch 31, and dura mater 32. The spine also includes gray matter 34 and dorsal horns 36 and 37 and white matter, for example, dorsal columns 46 and dorsal lateral columns 47.

Referring to FIG. 8, signal P1 is applied to electrode 18A (FIG. 2) and signal P2 is applied to electrode 16A (FIG. 2). Although signals P1 and P2 are shown as pulses, they also may comprises sinusoidal signals. Pulses P1 and P2 are generated at different frequencies. When the electric fields resulting from P1 and P2 pass through the same point in space at different frequencies, there is a difference frequency electric field set up corresponding to the difference between the frequencies of the two signals. For example, if P1 is generated at 150 Hz and P2 is generated at 50 Hz, the resulting difference frequency will be 100 Hz which is in the physiologic range.

Amplitude A1 of P1 is adjustable independently from amplitude A2 of P2. For the case in which amplitudes A1 and A2 are equal, the amplitude of the resulting difference frequency electric field is twice the amplitude of the individual electric fields.

Referring to FIG. 3, line L1 represents the edge of a three-dimensional locus L1A in which pulse P1 applied to electrode 18A induces a potential PT1 between times T1 and T3 that is less than the transmembrane potential threshold TPT for cells of interest in that locus.

Referring to FIG. 4, line L2 represents the edge of another three-dimensional locus L2A in which the application of pulse P2 (FIG. 8) to electrode 16A induces a depolarizing potential less than the transmembrane potential threshold TPT for cells of interest in that locus.

FIG. 5 illustrates a locus L3A representing the intersection of loci L1A and L2A in which the combined potentials induced in locus L3A from the difference frequency electric field produced by pulses P1 and P2 creates an action potential in cells of interest in locus L3A as illustrated by potential PT3 in FIG. 8. The potential induced in locus L1A outside locus L3A is illustrated by potential PT1 (FIG. 8). Since PT1 is lower than the transmembrane potential threshold TPT, there is no action potential created in locus L1A outside L3A. The potential created in locus in L2A outside L3A is illustrated by potential PT2 (FIG. 8). Since potential PT2 is less than the transmembrane potential threshold TPT, there is no action potential created in locus L2A outside locus L3A.

Referring to FIG. 6, line L4 represents the edge of another three-dimensional locus L4A resulting from the application of a pulse P1 to electrode 18A having an amplitude greater than amplitude A1 (FIG. 8), and line L5 represents the edge of another three-dimensional locus L5A resulting from the application of a pulse P2 to electrode 16A having an amplitude less than amplitude A2. The intersection of loci L4A and L5A represents a locus L6A resulting from the difference frequency electric field produced by pulses P1 and P2 in which action potentials are induced. Locus L6A is moved mostly to the right relative to locus L3A shown in FIG. 5. Action potentials are not induced outside locus L6A.

Referring to FIG. 7, line L8 represents the edge of another three-dimensional locus L8A resulting from the application of a pulse P2 to electrode 16A having an amplitude greater than amplitude A2 (FIG. 8), and line L7 represents the edge of another three-dimensional locus L7A resulting from the application of a pulse P1 to electrode 18A having an amplitude less than amplitude A1. The intersection of loci L7A and L8A represents a locus L9A resulting from the difference frequency electric field produced by pulses P1 and P2 in which action potentials are induced. It will be noted that the locus L9A is moved to the left compared with locus L3A shown in FIG. 5. Action potentials are not induced outside locus L9A.

The ability to move the locus in which action potentials are induced is an important feature. In many therapies, it is important to prevent action potentials being induced in gray matter 34 or dorsal horns 36 and 37, dorsal roots 38 and 40, dorsal lateral columns 47 or peripheral nerves 42 and 44 in order to minimize the possibility of causing pain, motor effects, or uncomfortable paresthesia. In the described techniques, the locus in which action potentials are induced (e.g., L3A, L6A or L9A) can be manipulated to a desired area of the dorsal columns 46 without inducing action potentials in dorsal horns 36 and 37, gray matter 34 or dorsal lateral columns 47. Moreover, the ability to move the locus in which action potentials are induced drastically reduces the accuracy necessary for surgically implanting electrodes 16A and 18A, and may eliminate the need for surgical lead revisions.

The foregoing techniques also may be applied to all electrically excitable tissue. Those skilled in the art will recognize that the preferred embodiments may be altered and amended without departing from the true spirit and scope of the appended claims.