Patent Description:
Neuromodulation is used to treat a variety of disorders including chronic pain, Parkinson's disease, and migraine. A neuromodulation system applies an electrical pulse to tissue in order to generate a therapeutic effect. When used to relieve chronic pain, the electrical pulse is applied to the dorsal column (DC) of the spinal cord or dorsal root ganglion (DRG).

Such a system typically comprises an implanted electrical pulse generator and a power source, such as a battery, that may be rechargeable by transcutaneous inductive transfer. An electrode array is connected to the pulse generator and is positioned in the dorsal epidural space above the dorsal column. An electrical pulse applied to the dorsal column by an electrode causes the depolarisation of neurons and generation of propagating action potentials. The fibres being stimulated in this way inhibit the transmission of pain from that segment in the spinal cord to the brain.

While the clinical effect of spinal cord stimulation (SCS) is well established, the precise mechanisms involved are poorly understood. The DC is the target of the electrical stimulation as it contains the afferent A-beta fibres of interest. A-beta fibres mediate sensations of touch, vibration and pressure from the skin. The prevailing view is that SCS stimulates only a small number of A-beta fibres in the DC. The pain relief mechanisms of SCS are thought to include evoked antidromic activity of A-beta fibres having an inhibitory effect and evoked orthodromic activity of A-beta fibres playing a role in pain suppression. It is also thought that SCS recruits A-beta nerve fibres primarily in the DC with antidromic propagation of the evoked response from the DC into the dorsal horn thought to synapse to wide dynamic range neurons in an inhibitory manner.

Neuromodulation may also be used to stimulate efferent fibres, for example to induce motor functions. In general, the electrical stimulus generated in a neuromodulation system triggers a neural action potential which then has either an inhibitory or excitatory effect.

Effects can be inhibitory e.g. used to modulate an undesired process such as the transmission of pain, or stimulatory e.g. causing a desired effect such as the contraction of a muscle.

Spinal cord stimulators provide tissue stimulation using electrodes and circuits to deliver electrical energy to the nervous tissue. They can use charge balanced biphasic pulses or monophasic pulses with resistors and capacitors for charge recovery. Some stimulators use tri-phasic stimulation.

<FIG> illustrates a spinal cord stimulator using an example power path. A battery <NUM>, typically <NUM>-<NUM>. 2V provides power to a switch-mode power supply <NUM> that pumps the voltage to a supply called VddHV, at typically <NUM>-15V. A current mirror (P1, P2) <NUM> controlled by a reference current <NUM> creates a controlled current which then flows through switches <NUM>, <NUM>, <NUM>, <NUM> to tissue <NUM>. The switches <NUM>, <NUM>, <NUM>, <NUM> are arranged in an H-bridge allowing current to be driven using either polarity into the tissue. With the switches <NUM>, <NUM>, <NUM>, <NUM> in the position shown, charge flows from left to right. A shorting switch allows unbalanced charge to be recovered. Alternately this can be achieved by closing switch <NUM> and switch <NUM> together. Capacitors <NUM> and <NUM> block DC current from flowing in tissue <NUM>. By using two such capacitors, no DC current can flow even when one capacitor fails. The voltage across the tissue <NUM> can be as high as 14V, so VddHV values of <NUM>. 5V are common.

It takes power to drive current into tissue. This power is drawn from the battery <NUM> and drains it so that it must be recharged regularly. Recharging the battery is an inconvenience to the patient. It is desirable to build a stimulator that is as efficient as possible, while not changing stimulation strength as the patient changes posture.

With current drive, the battery is pumped up to VddHV which exceeds the maximum induced tissue voltage by at least <NUM>. 5V, which is used to bias the current driver transistors. This 'lost' voltage is marked as Vloss <NUM> and can be expressed as Vloss = VddHV - Vload and Ploss = Iload (VddHV-Vload). Power is dissipated in the implant when the current flows through the transistors of current source <NUM>.

The power lost can also be given by the following equation where VL is the lost voltage and I is the stimulation current.

Since a single value of VddHV is often chosen, when the patient has the stimulation strength turned low, the power lost in the drive transistors can exceed the power delivered to the patient. It is clearly desirable to reduce this lost power to maximize battery life and so improve patient convenience. In general, switched-mode power supplies obey conservation of power, with the current and voltage on input and output being related (ignoring the switcher efficiency term) by: <MAT>.

It is thus recognized that if VDDHV is pumped to 16V, for example, but the patient tissue only requires 4V, <NUM>% of energy drawn from the battery is wasted. If the rest of the implant were to be designed to use less power than this (as is desirable) then the time between battery recharges is potentially <NUM> times shorter than it need be.

<CIT> discloses an electrical stimulation device for a biological load for applications such as transcutaneous nerve stimulation, neuromuscular electrical stimulation, or electrical muscle stimulation. The device comprises a controller, a power generation circuit for output of power to electrodes and a feedback compensation circuit that has a sensor for sensing delivered current in the load and for providing feedback to the power delivery circuit.

<CIT> discloses devices, systems and methods for the treatment of chronic inflammatory disorders that include an implantable microstimulator and an external charger/controller wherein the controller is configured to operate using closed-loop feedback.

<CIT> discloses a method of treating a patient, comprising: sensing a biological parameter indicative of respiration; analyzing the biological parameter to identify a respiratory cycle; identifying an inspiratory phase of the respiratory cycle; and delivering stimulation to a hypoglossal nerve of the patient, wherein stimulation is delivered if a duration of the inspiratory phase of the respiratory cycle is greater than a predetermined portion of a duration of the entire respiratory cycle.

<CIT> discloses a system of non-linear feedback control for spinal cord stimulation. The system comprises a lead adapted to be implanted within an epidural space of a dorsal column of a patients spine, and a pulse generator (PG) electrically coupled to the lead. The PG is configured to deliver spinal cord stimulation (SCS) therapy.

<CIT> discloses an Implantable Pulse Generator (IPG) that is capable of sensing a degree to which recruited neurons in a patient's tissue are firing synchronously, and of modifying a stimulation program to promote desynchronicity and to reduce paresthesia.

Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each of the appended claims.

A device for applying a neural stimulus comprises:.

It is an advantage that the voltage converter controls the voltage applied to the electrode. In contrast to current control this direct voltage control is more energy efficient because losses across a typical current mirror is avoided. A further advantage is that the control based on the measured nervous response leads to automatic compensation of impedance variation due to in-growth or change in posture. As a result, the stimulation results in a desired neural response, which previously required current control with the associated low energy efficiency.

The voltage converter may comprise a processor programmed to calculate a voltage value based on the measured nervous response and to generate a control signal to the voltage converter indicative of the calculated voltage value.

The voltage converter circuit may be a linear voltage-to-voltage converter.

The voltage converter may be a switched-mode voltage to voltage converter.

The voltage converter may comprises a pulse generator configured to generate a pulse signal to control switching of the switched-mode voltage to voltage converter.

The pulse signal may be based on the measured nervous response of the tissue.

The pulse generator may be a digital processor.

The device may comprise an analog-to-digital converter to provide a digital signal indicative of the measured nervous response of the tissue to the digital processor.

The voltage converter may comprise a switch that is controlled by a control signal based on the measured nervous response of the tissue to thereby control the voltage applied to the electrode based on the measured nervous response of the tissue.

The control signal may define a duty cycle based on the nervous response of the tissue, such that the control signal controls the switch and the duty cycle defines the output voltage to thereby control the voltage applied to the electrode based on the measured nervous response of the tissue.

The control signal may be an analog voltage signal provided by a processor and the voltage signal controls the switching of the switch to thereby control the voltage applied to the electrode based on the measured nervous response of the tissue.

The voltage converter may comprise an oscillator with an oscillation frequency and the voltage signal controls the oscillation frequency to thereby control the voltage applied to the electrode based on the measured nervous response of the tissue.

In many cases current drive is preferred by patients as they find wide pulse widths more 'soothing'. Due to the reactive nature of the tissue electrode interface, when tissue is driven with a voltage source, the current has a large spike at the beginning, then tails off. <FIG> illustrates the resulting voltage and current waveforms for voltage stimulation. <FIG> on the other side, illustrates the voltage and current waveforms for current stimulation. The voltage stimulation is akin to a narrow stimulation pulse. In contrast, with current drive, a wide rectangular stimulation can be produced which is preferred.

This disclosure will focus on systems using biphasic stimulation, although methods described can be adapted to greater or lesser numbers of phases. It will also describe both voltage and current source systems.

<FIG> shows a general architecture <NUM> of a stimulator. An amplifier <NUM> amplifies a physiological signal that, for an evoked compound action potential (ECAP), will typically be 10uV to 100uV. Its amplitude is then detected using a variety of methods, though a correlator and <NUM>-lobe detector is preferred. <FIG> illustrates an example array of electrodes <NUM>, which are spaced apart by <NUM>. At a typical propagation velocity of the ECAP of <NUM>/s, the travel time between two adjacent electrodes is <NUM>. <FIG> also shows the ECAP waveform <NUM> at the same scale as the electrode array <NUM> to illustrate the wavelength against the size of the electrode. At the currently illustrated point in time, the ninth electrode <NUM> measures the P1 peak of the ECAP and the fifth electrode <NUM> measures the N1 peak. A differential amplifier <NUM> amplifies the difference between two electrodes which results in a filter for the ECAP signal. The distance between two electrodes that are connected to the differential amplifier <NUM> may be between <NUM> and <NUM>, which relates to between <NUM> and <NUM> electrodes for a <NUM> spacing between adjacent electrodes.

<FIG> illustrates a signal flow for processing the output signal from amplifier <NUM> in <FIG>, which is now input signal <NUM>. A first mixer <NUM> mixes a reference sine wave <NUM> with a window function <NUM> and a gain module <NUM> scales the result by a weighting factor. A second mixer <NUM> mixes the scaled result with the input signal <NUM>. A summation module <NUM> sums up the samples over the time window of the window function <NUM> similar to a continuous integral and provides an output signal <NUM>. As a result of the mixing, the summed output reflects the similarity between the input signal and the windowed sine function, which is also referred to as a template function. That is, when the P1 peak of the ECAP signal coincides with the maximum of the sine function, the output <NUM> has a maximum value. When the input signal <NUM> is misaligned or contains mainly noise, the output <NUM> is minimal. One example of this correlation process is a four-lobe correlation where the length of the window function <NUM> spans four extrema of the sine wave, that is, the length of the window function <NUM> is twice the period of reference sine wave <NUM>.

The described process is similar to a correlation function between two signals where one signal is time-shifted and integrated for each value of the correlation function. For this reason, the described process is also referred to as a correlation process and suppresses noise and artefacts such that the maximum of the correlation signal <NUM> can be used as a feedback value in the controls disclosed herein. The template can be time-aligned with the expected ECAP curve by calculating an expected time of arrival, which depends on the distance from the stimulating electrode assuming t=<NUM> from the start of the cathodic (negative) pulse, where the ECAP begins to propagate. For example, it takes <NUM> for the ECAP to travel to an electrode <NUM> from the stimulation site and PW is <NUM>, then the sample delay is: <NUM> - PW = <NUM>. Time of arrival can also be simply measured. Further details of ECAP measurement are provided in <CIT> and <CIT>.

Once the evoked response amplitude has been calculated, such as the value of the correlation, a comparator compares the amplitude of the detected evoked response with the desired response. A controller integrates the error signal at a rate that sets the loop time constant and a stimulator then generates a controlled stimulus pulse. Either the amplitude or the pulse width may be controlled.

<FIG> illustrates an example device <NUM> for applying a neural stimulus as described above. The device <NUM> comprises a battery <NUM> to supply electrical energy at a battery voltage <NUM> and an electrode <NUM> that applies the electrical energy to neural tissue (not shown). Device <NUM> further comprises a circuit <NUM> that measures the nervous response of the tissue, such as the ECAP described above. Further, there is a voltage converter <NUM> that receives the electrical energy from the battery and controls a voltage applied to the electrode based on the nervous response of the tissue measured by circuit <NUM>. As shown in <FIG> the ECAP may be measured by a sense electrode <NUM>, which may be located at a distance from the stimulation electrode <NUM> as described above with reference to <FIG>. This way the sense electrode <NUM> can capture the evoked neural response once it has travelled the distance between the output electrode <NUM> and the sense electrode <NUM>. To avoid error measurements, the ECAP detection is disabled during the stimulation itself and shortly thereafter. This reduces artefacts caused by the settling of the circuitry, such as operational amplifiers.

It is noted that when the stimulator <NUM> in <FIG> is compared to prior art stimulator <NUM> in <FIG>, the voltage converter <NUM> is connected directly to the output electrode <NUM> without the use of a current driving circuit, such as current mirror <NUM>. The power-saving stimulator design presented in <FIG> combines voltage drive and local feedback. The feedback compensates for the changes in stimulation current with tissue growth and posture. As the tissue is driven directly, the power that is dissipated by current mirror <NUM> (as shown in <FIG>) is saved, which means the battery <NUM> lasts longer without being re-charged. At the same time, the feedback <NUM> of the evoked response allows the control of the output voltage such that a desired response can be maintained, which would previously have been achieved by current mirror <NUM> without feedback.

In one example, the converter <NUM> comprises digital circuitry, such as a microprocessor, in contrast to analogue circuitry, such as operational amplifiers and current mirrors. In the digital case, the microprocessor calculates a voltage value that is to be applied to the electrode <NUM>. The voltage value may be in the form of an binary number, such as an <NUM> bit string. An digital to analogue converter can then convert the bit string into a voltage and delivered to electrode <NUM> through a driver circuit. The processor may have stored on memory a desired value of neural stimulation, which can be adjusted externally by the patient or the clinician. In that case, the processor receives the measured ECAP from circuit <NUM> and compares the received ECAP with the stored desired ECAP. If the received ECAP is less than the desired ECAP, the processor increases the voltage. On the other hand, if the received ECAP is greater than the desired ECAP, the processor decreases the voltage. The processor may also implement a proportional/integral/differential (PID) control mechanism which optimally responds to changes in the ECAP. The input (process variable) of the PID control is the measured ECAP while the error value is the difference of the input to the stored desired ECAP and the output is the electrode voltage or an output signal that directly controls the electrode voltage. This can be useful if the patient moves and the impedance of the electrodes changes or more generally the evoked response changes for a given electrode voltage. The PID control loop can be parameterised for different objectives, such as fast response or minimal overshoot to avoid patient discomfort. The general PID calculation is given by <MAT>.

In another example, the voltage converter <NUM> comprises a linear voltage-to-voltage converter also referred to as linear voltage regulator. In such a case, the processor provides an output signal to the linear voltage-to-voltage converter to control the linear voltage-to-voltage converter to adjust the voltage as indicated by the PID control method. <FIG> illustrates an example where processor <NUM> provides a control signal <NUM> to an operational amplifier <NUM> that drives the gate of an output transistor <NUM>. This means the output voltage of the processor <NUM> or DAC connected to the processor <NUM> constitutes the output value of the PID control. It is noted that the linearity of the regulator, such as the output transistor <NUM>, is not crucially important because the PID control automatically adjusts the voltage by relatively small variations and a slight non-linearity should not affect the operation of the overall control loop.

In yet another example, the voltage converter <NUM> in <FIG> comprises a switched-mode voltage to voltage converter. In this case, the processor controls the duty cycle of the switching, that is, the processor varies the ratio of on-to-off time. During the on-time an inductor is charged while during off-time the energy stored in the inductor is consumed by the electrodes. According to the principle of switched-mode voltage converters, a higher duty cycle increases the output voltage while a lower duty cycle reduces the output voltage. Consequently, the processor can control the output voltage by controlling the duty cycle.

<FIG> illustrates another example device <NUM> for applying a neural stimulus. Device <NUM> comprises a battery <NUM> to supply electrical energy at a battery voltage <NUM> and an electrode <NUM> to apply the electrical energy to neural tissue. A circuit <NUM> connected to a sense electrode <NUM> measures the nervous response of the tissue. In this case, the device performs current drive and therefore comprises a current mirror <NUM> to deliver a current to the electrode <NUM>. A reference current source <NUM> provides a constant reference current to current mirror <NUM>, which can be adjusted by the clinician or the patient to adjust the level of perceived effect of the stimulation. The reference current source <NUM> is also controlled by the neural response measured by circuit <NUM>. Current mirror <NUM> then mirrors the reference current from source <NUM> and delivers it to the output electrode <NUM>. As a result, the current delivered to the output electrode is based on the measured nervous response in the sense that a lower response leads to an increased reference current and a higher response leads to a lower reference current. Again, the circuit <NUM> may include a processor and the processor may perform PID control to generate the signal that controls the reference current source <NUM>.

Importantly, a voltage converter <NUM> receives the electrical energy from the battery and controls a voltage applied to the current mirror based on a voltage between the stimulating electrodes. This means the voltage applied to the current mirror can be reduced to reduce the voltage drop across the current mirror and thereby reduce the power dissipated in the current mirror. There is also an H-Bridge <NUM> to switch the output current to the output electrode <NUM>.

In the example of <FIG> device <NUM> comprises an operational amplifier <NUM> (i.e. differential amplifier) that provides the feedback signal to converter <NUM>. The inputs of amplifier <NUM> are connected to the output electrode <NUM> and the drain <NUM> of a first transistor <NUM> of sub-regulator <NUM>, which also comprises a second transistor <NUM>. Since the gates of the first transistor <NUM> and the second transistor <NUM> are connected, the gate source voltage is identical leading to approximately identical drain currents according to the principles of current mirrors. The difference between the gate voltage and the electrode voltage is then the gate drain voltage of the second transistor <NUM>. The aim should be to keep this voltage to a minimum to reduce the power dissipated in the second transistor <NUM>. Therefore, the output of amplifier <NUM> is connected as a control input to voltage converter <NUM> such that the voltage converter <NUM> reduces its output voltage when there is a large gate drain voltage across the second transistor. In other words, if a large voltage is created on stimulation electrode <NUM>, the gate-drain voltage across second transistor <NUM> will be low and converter <NUM> will keep or increase its output voltage. On the other hand, if a low voltage is created on stimulation electrode <NUM> (due to lower tissue impedance, for example) the gate drain voltage across second transistor <NUM> is larger, which causes converter <NUM> to decrease its output voltage thereby reducing losses across second transistor <NUM>.

The Vloss term is kept to one transistor turn-on voltage and power loss is reduced. The drain-source voltage of second transistor <NUM> is just sufficient for second transistor <NUM> to be saturated, where a simple mirror operates it with a drain voltage equal to the saturation voltage plus a threshold. For a typical CMOS process with threshold voltages of <NUM>. 5V, additional improvement can be obtained by biasing second transistor <NUM> closer to its saturation limit as shown in <FIG> where an additional transistor <NUM> is included between first transistor <NUM> and the reference current <NUM>.

In one example, converter <NUM> is a switched-mode voltage converter where the duty cycle of charging the internal inductance depends on the output signal of amplifier <NUM>.

<FIG> illustrates a further example device <NUM> for applying a neural stimulus. Device <NUM> comprises a battery <NUM> to supply electrical energy at a battery voltage <NUM>. Device <NUM> further comprises an electrode <NUM> to apply the electrical energy to neural tissue and a circuit <NUM> connected to a sense electrode <NUM> to measure the nervous response of the tissue. There is also a switched mode voltage to current converter <NUM> to receive the electrical energy from battery <NUM> and to control a current applied to the stimulating electrode <NUM>. Importantly, there is no current mirror in <FIG> because the switched mode converter <NUM> provides the current directly to output electrode <NUM>. Circuit <NUM> is connected to converter <NUM> to control switching of the switched mode voltage converter based on the measured nervous response of the tissue. In other words, this takes the feedback control <NUM> directly into the converter <NUM>, and avoids the use of a sub-regulator <NUM> in <FIG> and <FIG>. The solution described in <FIG> and the related subsequent Figures provide most of the benefits of voltage drive, while fitting within the framework of existing clinical systems. This means there is provided a way to build a current source for tissue stimulation that uses less power than previous implementations.

Current source stimulators typically provide current over a range from 50uA to <NUM>. 5mA and should be selectable. Device <NUM> provides a fixed pulse width that is stable from one stimulation cycle to the next. As a result, the ECAP appears at a predictable time and can be detected. The pulse width is usually adjusted by the clinician to a value that is preferable to a patient. The battery voltage changes as the battery is discharged and the tissue voltage changes during the stimulation pulse. The current mirror <NUM> in <FIG> addresses these issues but the problem of power loss remains.

<FIG> illustrates converter <NUM> in more detail, which comprises a charge pump to multiply the battery voltage <NUM> to the higher voltage used to stimulate the tissue. It is noted that the charge pump <NUM> is connected directly to tissue <NUM>. Importantly, converter <NUM> comprises an inductor <NUM> and a switch <NUM> that closes a circuit including only inductor <NUM> and battery <NUM>. As a result, a current will flow through inductor <NUM> and switch <NUM>. This current will be low due to the self-inductance of inductor <NUM> and then rise as the magnetic field builds up. According to the principles of inductors, when switch <NUM> is opened the current through inductor <NUM> remains constant, which means that the voltage can increase above the battery voltage if the connected resistance is high. This value of the voltage depends on the energy stored in inductor <NUM> and therefore on how long switch <NUM> was closed before it was opened. A capacitor <NUM> smooths the voltage to largely eliminate any spikes from switching and a diode <NUM> avoids reverse current from the capacitor <NUM> into the inductor <NUM>. A Zener diode <NUM> provides over voltage protection. This stops the output voltage from going too high and damaging components that have a stress limit e.g. when the load is accidentally disconnected. In this case this diode is connected to a small resistor RP <NUM>.

<FIG> illustrates the operation switch <NUM> in the context of neural stimulation. Switch <NUM> connects inductor <NUM> to battery <NUM> for time t<NUM>. Switch <NUM> then connects inductor <NUM> to tissue <NUM> and current flows for a time t<NUM>. Pulses are generated with a period t<NUM> and last for a period equal to the stimulus pulse width PW. The time t<NUM> controls how much energy is stored in the inductor. The problem of designing a useful current source consists of controlling these times in a useful manner. It is understood the time PW is simply the time the current source is enabled. The method to generate t<NUM>, t<NUM> and t<NUM> is described below.

Once connected to the load, the inductor will pump charge into the load until it has no more energy to do so, and then due to the presence of diode <NUM> the current will cease in a self-regulating manner. So the time t<NUM> is self-regulating.

To appreciate how to control t<NUM>, t<NUM> and t<NUM> in light of the requirements previously provided, it is useful to derive the equations of the switched mode charge pump of <FIG>.

Assuming the charge pump cycle begins with zero current in inductor <NUM>, its current is given by: <MAT> where the voltage source voltage is V, the time the inductor is connected is t and the inductance is L. The identical equation describes the time taken for the inductor to dump all its power into a load, ending with the current in the inductor being zero. Thus, this equation applies to <FIG> with the switch in either position.

The energy stored by the inductor is <MAT>.

Since energy is the product of power and time, and charge is the product of current and time: <MAT>.

Although the time t<NUM> can be controlled, the time t<NUM> then depends on V<NUM> and V<NUM> in order to obey conservation of energy.

The charge delivered each cycle is: <MAT>.

And the average current delivered is <MAT>.

Since t<NUM> is the reciprocal of f : <MAT>.

Since the charge delivered depends on t<NUM>, t<NUM>, t<NUM>, V<NUM> and V<NUM>, it is useful to provide a predictable average current and to eliminate these dependencies.

<FIG> illustrates a circuit component <NUM> that can be used to achieve this in the sense that circuit component <NUM> creates a time delay inversely proportional to a control voltage. This is called a "voltage controlled delay" (VCD) circuit and in this form it has two controls with the delay being proportional to the ratio of the two voltages. Circuit component <NUM> comprises a capacitor <NUM> that is discharged through a discharge transistor <NUM> when a trigger signal <NUM> connected to the base of discharge transistor <NUM> goes high. A current mirror <NUM> charges the capacitor <NUM> by mirroring a reference current <NUM> when the trigger signal <NUM> goes low. This reference current <NUM>, in turn, is controlled by the second voltage VI <NUM> amplified by amplifier <NUM> which is buffered by buffer transistor <NUM> including a negative feedback that ensures that the emitter voltage (i.e. the voltage across resistor <NUM>) is equal to VI <NUM>. As a result, reference current <NUM> is <MAT>.

In essence, if VI <NUM> is high, a high reference current flows throw resistor <NUM>, leading to a high current into capacitor <NUM> and a shorter time for charging capacitor <NUM>. Therefore, the delay for a rising edge is inversely related to VI. The delay for a falling edge is determined by dimensions of transistor <NUM>, which can be chosen such that the delay for the falling edge is relatively short. In other words the falling edge is substantially instantaneous with a negligible delay caused by discharge transistor <NUM>. Conversely, a lower second voltage VI <NUM> leads to a longer delay of the rising edge because the time to charge capacitor <NUM> is longer. On the other hand, a high voltage for Vp <NUM> leads to a longer delay since the voltage across capacitor <NUM> needs to rise further before the output goes high. More formally, the general current voltage relation for capacitor <NUM> is <MAT>, so <MAT>. Substituting the (constant) reference current yields <MAT>. Considering that the required voltage difference to cause the output to switch is dV = VP , the time from the trigger pulse going low to the response signal going high is <MAT>.

In this, VP is considered the proportional control voltage and VI is the inverse control voltage.

In order to use component <NUM> to generate the time t<NUM> the battery voltage is used as the inverse control VI <NUM> and the proportional control voltage is kept constant. The result is for some constant a : <MAT> with a = RCVP. The variation of energy in the inductor due to the varying battery voltage is hence eliminated.

To control the average current the situation is more complicated. It is desirable to increase the inductor energy to compensate for the decreased charge that is delivered as the load voltage increases. At the same time it is necessary to provide current control for the clinician, patient and the control loop. This control signal is digital.

<FIG> illustrates a digital controlled resistor circuit <NUM> comprising four resistors <NUM>, <NUM>, <NUM>, <NUM> and corresponding switches <NUM>, <NUM>, <NUM>, <NUM>. In this example, each resistor has a resistance that is double the resistance of the next smaller resistor similar to a binary number system. Each switch is controlled by one bit in a digital control signal M <NUM>. As a result, the overall resistance of the resistor circuit <NUM> is set by the digital signal M <NUM> such that each bit in M reduces the overall resistance by adding a parallel path. When resistor <NUM> in <FIG> is now replaced by controlled resistor circuit <NUM>, the reference current <NUM> increases with each active bit in M, which in turn decreases the charge time of capacitor <NUM> decreasing delay t<NUM> which leads to a shorter charge time of inductor <NUM> in <FIG> which finally leads to a decreased stimulation current.

Since the resistance is a multiplicative term in the expression above, the resulting circuit with controlled resistor circuit <NUM> replacing resistor <NUM> is referred to as "multiplying VCD" (MVCD) which multiplies the compensating term from the load voltage and the digital control. So, the MVCD has three inputs, Vi, Vp and M.

<FIG> illustrates a control circuit <NUM> which implements the feedback circuit <NUM> in <FIG>. The control circuit <NUM> comprises an MVCD <NUM> as shown in <FIG> but with the digitally controlled resistor circuit <NUM> from <FIG> in place of resistor <NUM>. Control circuit <NUM> further comprises a VCD <NUM> as shown in <FIG>. A feedback loop <NUM> including an inverter <NUM> causes an intermediate signal <NUM> to oscillate and the oscillation frequency depends on the delay created by MVCD <NUM> and generates the time t<NUM> where the pump output V<NUM> (voltage across switch <NUM> in <FIG>) is connected as the inverse control voltage VI. VCD <NUM> is used with V<NUM> (battery voltage) as its inverse control, we can write, for some constant b of the second VCD circuit: <MAT>.

At this point we have a current source that is controllable. The time between rising edges is controlled by.

It is desirable that a clinician can detect when a current source goes out of compliance. In this case, this occurs when the shunt voltage regulator <NUM> of <FIG> starts to conduct. A monitor on the resistor RP <NUM> achieves this.

In the case where the battery voltage varies from <NUM>. 2V to <NUM>. 25V (a typical range for a lithium-ion rechargeable cell) the value of t<NUM> varies over a range of <NUM>: <NUM>. This is a small range and so the design of the t<NUM> VCD is not problematic. This leaves room for additional control for the overall feedback and clinician control.

The VP inputs to the two VCDs are unused. They could be controlled by DACs to provide different current ranges. The range from 50uA to <NUM>. 5mA varies by <NUM>:<NUM>. The load can vary from 1V to 15V, so the total variation is greater than <NUM>:<NUM>. If the PW=<NUM>, then the required resolution is 26ns. This is technically difficult. The Vp inputs provide additional degrees of freedom to span this space.

A solution to this problem is to waste a bit of voltage in the load as shown in <FIG>. The cascode p-channel FET <NUM> limits the load voltage to the sum of the voltage VL plus the p-FET turn on voltage <NUM>. 6V, at small values of the load impedance or small currents. At higher impedances, the load voltage becomes larger and in the limit the FET drain-source voltage tends to zero and the FET becomes a small parasitic resistance in the current delivery chain. This modification will limit the battery life improvements for patients who have comparatively low tissue impedances, but there will still be considerable improvement compared to the alternative of dissipating power in the current source transistor.

Depending on the load, the voltage V<NUM> can vary between the maximum the circuitry can withstand and where the Zener diode turns on (at say <NUM>. 5V) to the sum of the p-FET source voltage when there is a zero ohm load plus the diode voltage. Since VL is under the control of the designer this can be arbitrarily chosen; a value of 5V would be suitable. In this instance the voltage V<NUM> would vary from <NUM>. 5V to 5V i.e. a range of <NUM>. Again, there is room to incorporate additional control.

<FIG> show examples of a digitally controlled resistance or conductance, respectively. Observing that <FIG> has two resistors (one in MVCD <NUM> and one in VCD <NUM>) and either can be a controlled resistance or a controlled conductance, and one appears in the numerator and one in the denominator of the current equation, then there are a lot of options. Now these can be placed in the R spot, or driven with a current source to provide the proportional and inverse inputs.

<FIG> illustrates a deterministic way of combining two amplitude controls in a pulse modulation system. It is also possible to use random values as per a delta-sigma DAC.

Inverting the equation
<MAT>
we get
<MAT>.

Substituting V<NUM> = <NUM>, t<NUM> = 500ns, I = <NUM>. 5mA, t<NUM> = <NUM>us, V<NUM> = <NUM>V gives L = 7uH.

This provides <NUM> per pulse (<NUM> to charge the inductor, <NUM> to dump it), so in a <NUM> stimulus pulse, we have about <NUM> bits of control. However, a feedback term and clinician term may need to be included.

<FIG> illustrates another example for a device <NUM> for applying a neural stimulus. In this example, device <NUM> comprises a battery <NUM> to supply electrical energy at a battery voltage and a fixed current source <NUM> powered by battery <NUM>. The fixed current source <NUM> is fixed in the sense that it is set at a relatively high current. For example, the current may be set at a maximum value and then modulate the pulse width. Or there may be coarse control of current by the clinician, setting it at approximately at the expected or estimated maximum required for that patient. While this current source can be implemented with a current mirror, it is noted that keeping the current fixed at a relatively high current or maximum current, reduces the voltage drop across the current mirror and therefore reduces the power dissipated in the current mirror.

Device <NUM> further comprises a pulse generator <NUM> that is connected to an electrode selector <NUM> controlled by an electrode selection signal <NUM> (set by the clinician). The electrode selector <NUM> selects from multiple electrodes a stimulation electrode <NUM> to apply the electrical energy to neural tissue <NUM>, return electrode <NUM>, measurement (sense) electrode <NUM> and reference electrode <NUM>.

Device <NUM> further comprises a differential amplifier <NUM> that amplifies the signal captured by sense electrode <NUM> and provides that to a correlator <NUM> to calculate an ECAP amplitude <NUM> as described above with reference to <FIG>. In the example of <FIG>, the ECAP amplitude is again the input to a feedback control circuit <NUM>, which calculates a pulse width <NUM> provided to the pulse generator <NUM>. In this sense, the feedback control circuit <NUM> increases the pulse width to provide more stimulation energy when the ECAP amplitude is below a desired value and decreases the pulse width when the ECAP amplitude is above a desired value. For example, a switched-mode converter with a current or voltage output may be configured to provide a fixed amplitude output, with the pulse width being varied to provide the stimulus variation needed for a closed loop stimulation system.

<FIG> illustrates the manner in which a stimulus <NUM> produces an ECAP <NUM>, which is then aligned with a template <NUM> to provide amplitude measurement in the manner described in <CIT> and with reference to <FIG>, which is included in its entirety herein by reference.

As nerve cells are mostly triggered throughout the duration of the cathodic phase of the stimulus pulse, when feedback control circuit <NUM> changes the pulse width <NUM> provided to the pulse generator <NUM>, the time between the start of the stimulus and the arrival of response at the recording electrodes varies. The time of arrival of the ECAP <NUM> can be measured as the time to the arrival of the first peak of the ECAP, the P1 peak, although other features may also be used. In order for the detector/correlator <NUM> to work properly, the detector template is aligned to be synchronous with the ECAP a during the detection process.

One example of aligning the template <NUM> involves a lookup table <NUM> which indicates the optimum delay between the stimulus and the detection process for that particular pulse width. This optimum delay is then fed to a variable delay circuit <NUM>, which might be a variable-length shift register, to trigger the correlator, which determines the ECAP amplitude as per <CIT> and shown in <FIG> above.

As a result, the device <NUM> generates stimulation current pulses and adjust the pulse length of the current pulses based on the measured nervous response of the tissue to reduce the dissipated power, while at the same time aligning the template to the ECAP signal to accurately measure the ECAP amplitude that is used for the feedback control that ultimately controls the width of the stimulation pulses.

In one example, the pulse width is controlled digitally by a microprocessor. As a result, the pulse width has a limited number of different values, such as <NUM> different values for an <NUM>-bit pulse width signal. In that case, the lookup table may have <NUM> different delay values, which is one delay value for each pulse width value. The delay values may be in the form of counter values for an internal processor counter to reach the counter value before the template signal is generated. In other examples, the pulse width is continuous, such as a float number or an analogue signal and the look-up table stores <NUM> values. The variable delay <NUM> module may then interpolate between the closest values in the lookup table <NUM> to determine the optimum delay. The look-up table <NUM> may be replaced by a functional approximation of the relationship between the pulse width and the template delay, such as a linear function with two parameters or a polynomial with further parameters.

It is noted that the variable pulse width control described with reference to <FIG> may be combined with the switched-mode current source of <FIG> potentially including the circuits from <FIG>, <FIG>. In that case and referring back to <FIG>, the resulting circuit would control t<NUM> and t<NUM> as well as the pulse width PW to adjust the stimulation level. However, in other examples, the circuit maintains t<NUM> and t<NUM> constant and only adjusts PW.

<FIG> illustrates a further example where the feedback control is implemented directly in the converter, and avoids the use of a sub-regulator. In particular, <FIG> illustrates an implantable stimulation device <NUM> comprising a battery <NUM>, a switched-mode power supply (SMPS) converter <NUM>, an H-bridge drive <NUM> and an output electrode <NUM> to supply an electrical stimulus to nervous tissue. There is also a sense electrode <NUM> to capture an evoked response and a feedback circuit <NUM>. Importantly, the feedback circuit <NUM> is now connected directly to the converter <NUM>.

When the converter is a voltage-to-current converter, the operation is as discussed above. If the converter is voltage-to-voltage, then this an introduction to subsequent sections of this document.

The stimulator described below provide most of the benefits of voltage drive, while fitting within the framework of existing clinical systems and may be preferred amongst the variants mentioned in this disclosure.

<FIG> illustrates a further example stimulation device <NUM> comprising a battery <NUM>, a voltage-to-voltage SMPS converter <NUM> connected to a sub-regulator <NUM> (similar to the current mirror in the previous figures) and a smoothing capacitor <NUM>. The sub-regulator <NUM> mirrors a control current <NUM> to an H-bridge drive <NUM> which, in turn, delivers the current to a stimulation electrode output <NUM>. A sample and hold circuit <NUM> samples the stimulation voltage and a sense electrode <NUM> senses the evoked response, which is amplified by an amplifier <NUM>. The signals from amplifier <NUM> and sample and hold circuit <NUM> are selectively switched by a switch <NUM> onto an analog-to-digital converter <NUM> that converts the selected signal to a digital input of a digital controller <NUM>. The controller <NUM> can then use the sampled stimulation output voltage and the sensed evoked response to calculate a control current of current source <NUM> and a control voltage for converter <NUM>. Both are provided by respective digital-to-analog converters <NUM>, <NUM>. It is noted that the DACs <NUM>, <NUM> and ADC <NUM> may be integrated into the digital controller <NUM>.

This design moves the SMPS control loop into digital controller <NUM>. The peak stimulus voltage is obtained by sample circuit <NUM> sampling the stimulus electrode at the end of the stimulus. This can be held in the sample-hold circuit <NUM>, and converted to a digital value in the ADC <NUM>. This ADC <NUM> can be the same one used for digitizing the physiological feedback. Since the digital controller <NUM> will also be used to operate the physiologic control loop, it will have available the stimulus amplitude used for the next stimulus, and, via the digital control of the SMPS <NUM>, can prepare the power supply for the next stimulus i.e. use feed-forward in the loop. The sample rate is typically <NUM> for many neuro-modulation applications, so the SMPS <NUM> has more than <NUM> to respond to the updated control voltage, making it a simpler design than that of <FIG> and <FIG> which respond during the stimulus.

The digital controller <NUM> can be a programmable microcontroller or a dedicated state-machine.

<FIG> illustrates a voltage-drive version of <FIG>. Again, there is a battery <NUM>, a voltage-to-voltage converter <NUM>, an H-bridge <NUM> connected to a stimulation electrode <NUM>. There is also a sense electrode <NUM> connected to an amplifier <NUM> and a switch <NUM> that selectively connects the voltage from the converter <NUM> or from amplifier <NUM> to an ADC <NUM> connected to controller <NUM>. The controller calculates the control voltage for converter <NUM>, which is provided through DAC <NUM> on an analog control voltage signal <NUM>. While the components shown in <FIG> are similar to those in <FIG>, in <FIG> there is no sub-regulator <NUM> as in <FIG>. Instead, the converter <NUM> delivers the voltage directly to the stimulus output <NUM> (via H-bridge <NUM>). "Directly" in this context means without further voltage or current control since the H-bridge <NUM> is only a connection circuit with no regulating function. In other words, the switches in H-bridge drive <NUM> remain unchanged (on or off) during stimulation, while the switches in converter <NUM> change many times to control the voltage.

It is noted that most available converters that can be used as SMPS <NUM> have a feedback input to feedback the voltage at their output. This feedback input is now used in <FIG> to provide the control voltage signal <NUM> to converter <NUM>. The main difference to the common use case of closed-loop wired voltage feedback is that the feedback signal <NUM> is now generated by digital controller <NUM>. This way, controller <NUM> can control the converter <NUM> by adjusting the voltage on control signal <NUM>. In one example, digital controller <NUM> sets the control signal <NUM> to a voltage level that is the desired voltage. However, there may be a difference, such as an offset between the desired output voltage and the control voltage <NUM> if the converter <NUM> includes a scale factor or offset due to varying battery voltage, for example.

With this implementation, controller <NUM> can monitor the output voltage of the power supply to detect any over-voltage or to detect that despite the maximum voltage has been applied there is little increase in the physiological response. Further, controller <NUM> receives the feedback signal from amplifier <NUM> and can compare it to a desired value. Controller <NUM> can then perform a control algorithm, such as PID, to reduce the difference between the measure and the desired evoked response by varying the output signal provided to DAC <NUM>. This may result in improved dynamic characteristics of converter <NUM>, such as settling time and ringing, compared to direct voltage feedback through analog comparison with a reference voltage. It also reduces the need for analog components with are often a source of fluctuation and other implementation difficulties. It is noted that DAC <NUM> may also be integrated into converter <NUM> in the sense that converter <NUM> is configured to accept a digital signal and to control the output voltage accordingly.

In one example, converter <NUM> is a ringing choke converter comprising primary and secondary windings of a transformer and a base winding on the primary side. A transistor is connected to the base winding so that a self-oscillation occurs in the primary side and at each oscillation the transistor switches. This oscillation results in an induced current in the secondary side, which can be smoothed by a transistor into a DC signal. Importantly, the switching frequency depends on the input voltage and the state of the load. Now, the digital controller <NUM> controls that input voltage via voltage signal <NUM> and therefore, controls the switching frequency in converter <NUM>. In turn, this controls the output voltage of converter <NUM> and finally the stimulation intensity on electrode <NUM>. As described herein, the controller <NUM> adjusts the voltage on control signal <NUM> based on the physiological input.

<FIG> illustrates a further implementation of an implantable stimulation device <NUM> where, compared to <FIG>, the DAC <NUM> is omitted and the controller <NUM> directly provides the timed pulses for the switching in switched-mode power supply converter <NUM> through a pulse width modulation output <NUM>. In particular, controller <NUM> generates arbitrary waveforms. It is noted that many microcontrollers already provide the functionality of a pulse width modulation (PWM) control output. Therefore, processor <NUM> may be a general purpose microcontroller or other processor circuit, such as an FPGA or ASIC.

The duty cycle (ratio between ON and OFF), as defined by the PWM signal, defines the voltage of the output signal. This means that a change in the conductance of the neural tissue is automatically compensated in the sense that a lower conductance leads to a higher voltage to achieve the same evoked response.

More particularly, there may be two control loops. A first control loop controls the output voltage while a second control loop controls the evoked neural response. In one example, the first control loop is repeatedly executed during the application of a stimulation pulse. A desired output voltage is stored in digital controller <NUM> and during the stimulation, the controller <NUM> compares the present voltage (provided through switch <NUM>) to the desired voltage. If there is a difference, controller <NUM> adjusts the duty cycle, such that the duty cycle is increased if the output voltage is less than the desired voltage and vice versa. The second control loop is executed once per stimulation phase, where the desired output voltage is adjusted based on a comparison between a desired evoked response and the measured evoked response. For example, controller <NUM> increases the desired output voltage if the measured evoked response is below the desired evoked response and vice versa. Then, the desired voltage is used in the first control loop during the next stimulation phase. Known topologies for buck-boost converters include SEPIC and Cúk topologies.

Fig. <NUM> illustrates a method <NUM> for neural stimulation. The method comprising repeatedly performing the following steps in the sense that the following steps are repeated to provide continuous stimulation by multiple stimulation pulses. So in one example, method <NUM> is performed once for each stimulation pulse.

The method <NUM> commences by generating <NUM> a stimulation voltage signal at a stimulation voltage, such as by switching a switched-mode power supply. Next, the stimulation voltage signal is applied <NUM> to neural tissue. A measurement circuit then measures <NUM> a nervous response of the tissue. Finally, the stimulation voltage is adjusted <NUM> based on the measured nervous response.

Claim 1:
A device (<NUM>) for applying a neural stimulus comprising:
a battery (<NUM>) to supply electrical energy at a battery voltage (<NUM>);
an electrode (<NUM>) to apply the electrical energy to neural tissue;
a circuit (<NUM>) to measure a nervous response of the neural tissue; and
a voltage converter (<NUM>) to receive the electrical energy from the battery (<NUM>) and to control a voltage applied to the electrode (<NUM>) based on the measured nervous response of the tissue.