US20140236042A1 - Method and apparatus for measurement of neural response - Google Patents

Method and apparatus for measurement of neural response Download PDF

Info

Publication number
US20140236042A1
US20140236042A1 US14/117,145 US201214117145A US2014236042A1 US 20140236042 A1 US20140236042 A1 US 20140236042A1 US 201214117145 A US201214117145 A US 201214117145A US 2014236042 A1 US2014236042 A1 US 2014236042A1
Authority
US
United States
Prior art keywords
conduction velocity
neural
neural response
stimulus
response
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/117,145
Inventor
John Louis Parker
Dean Michael Karantonis
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nicta IPR Pty Ltd
Saluda Medical Pty Ltd
Original Assignee
Saluda Medical Pty Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AU2011901817A external-priority patent/AU2011901817A0/en
Application filed by Saluda Medical Pty Ltd filed Critical Saluda Medical Pty Ltd
Assigned to SALUDA MEDICAL PTY LTD reassignment SALUDA MEDICAL PTY LTD ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KARANTONIS, DEAN MICHAEL, PARKER, John Louis
Publication of US20140236042A1 publication Critical patent/US20140236042A1/en
Assigned to SALUDA MEDICAL PTY LTD. reassignment SALUDA MEDICAL PTY LTD. CONFIRMATION OF ASSIGNMENT Assignors: NICTA IPR PTY LTD
Assigned to NICTA IPR PTY LTD reassignment NICTA IPR PTY LTD CONFIRMATION OF ASSIGNMENT Assignors: NATIONAL ICT AUSTRALIA LTD
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A61B5/04001
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/40Detecting, measuring or recording for evaluating the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/40Detecting, measuring or recording for evaluating the nervous system
    • A61B5/4029Detecting, measuring or recording for evaluating the nervous system for evaluating the peripheral nervous systems
    • A61B5/4041Evaluating nerves condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/0404Electrodes for external use
    • A61N1/0408Use-related aspects
    • A61N1/0456Specially adapted for transcutaneous electrical nerve stimulation [TENS]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0551Spinal or peripheral nerve electrodes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36071Pain
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128Control systems
    • A61N1/36135Control systems using physiological parameters

Definitions

  • the present invention relates to measurement of a neural response to a stimulus, and in particular relates to measurement of a compound action potential by using one or more electrodes implanted proximal to the neural pathway.
  • CAP compound action potential
  • 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.
  • the electrical pulse is applied to the dorsal column (DC) of the spinal cord.
  • DC dorsal column
  • 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.
  • stimuli are applied substantially continuously, for example at 100 Hz.
  • the DC is the target of the electrical stimulation, as it contains the afferent A ⁇ fibres of interest.
  • a ⁇ fibres mediate sensations of touch, vibration and pressure from the skin.
  • the prevailing view is that SCS stimulates only a small number of A ⁇ fibres in the DC.
  • the pain relief mechanisms of SCS are thought to include evoked antidromic activity of A ⁇ fibres having an inhibitory effect, and evoked orthodromic activity of A ⁇ fibres playing a role in pain suppression. It is also thought that SCS recruits A ⁇ 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.
  • the electrical stimulus generated in a neuromodulation system triggers a neural action potential which then has either an inhibitory or excitatory effect.
  • Inhibitory effects can be used to modulate an undesired process such as the transmission of pain, or to cause a desired effect such as the contraction of a muscle.
  • the action potentials generated among a large number of fibres sum to form a compound action potential (CAP).
  • the CAP is the sum of responses from a large number of single fibre action potentials.
  • the CAP recorded is the result of a large number of different fibres depolarising.
  • the propagation velocity is determined largely by the fibre diameter and for large myelinated fibres as found in the dorsal root entry zone (DREZ) and nearby dorsal column the velocity can be over 60 ms ⁇ 1 .
  • the CAP generated from the firing of a group of similar fibres is measured as a positive peak potential P 1 , then a negative peak N 1 , followed by a second positive peak P 2 . This is caused by the region of activation passing the recording electrode as the action potentials propagate along the individual fibres.
  • CAP recordings are sometimes made during surgical procedures on the spinal cord, to provide an indication of any potential neurological damage being caused by the procedure.
  • a site below (caudally of) the area being operated on is stimulated and recordings are made above (rostrally of) the site.
  • a diminishing response, or a change in response indicates a change in the neurological condition of the spinal cord and may indicate lasting damage.
  • monitoring is often performed during scoliosis surgery (straightening a curvature of the spine) to ensure that the decompression doesn't damage the spinal cord.
  • Somatosensory potentials are also used for spinal cord monitoring during surgery.
  • the monitoring techniques employed in surgery are “long range” techniques, in that the stimulation site and the recording site are a large distance apart, and are thus less sensitive at least due to attenuation.
  • Neural damage, degeneration or change can affect neural behaviour in a number of ways, such as by changing the number of fibres recruited by a given stimulus, the type of fibres recruited, and/or propagation characteristics of the action potential along a fibre once activated. Techniques which merely monitor the presence/absence, or the strength, of a detected neural signal may thus overlook important changes in other characteristics of the neural response.
  • the present invention provides a method for estimating conduction velocity of a neural response, the method comprising:
  • the present invention provides a device for estimating conduction velocity of a neural response, the device comprising:
  • the device may be configured for permanent implantation and ongoing operation while implanted. Alternatively the device may be configured for intra-operative use only.
  • Some embodiments of the invention may further provide for estimating from the conduction velocity of the neural response, or from changes in the conduction velocity of the neural response as detected from one measurement to a next measurement, an approximate proportion of fibre classes recruited to produce the neural response. For example, in such embodiments, a high conduction velocity may be taken as being indicative of recruitment of large fibres such as A ⁇ fibres. Similarly, an increased conduction velocity from one measurement to a next measurement may be taken as being indicative of increased recruitment of large fibres such as A ⁇ fibres. Such embodiments may be particularly useful in feedback control of an applied stimulus in order to preferentially recruit A ⁇ fibres to achieve beneficial therapeutic effects while minimizing recruitment of smaller fiber classes to avoid adverse side effects.
  • a measure of conduction velocity may be obtained both caudally of the stimulus site and rostrally of the stimulus site.
  • the measurements may be used as input to a feedback controller designed to effect differential control of fibre classes recruited in an evoked ascending volley as compared to fibre classes recruited in an evoked descending volley.
  • a measure of conduction velocity may reveal changes in stimulus efficacy, as for example may arise as a result of implant migration away from the ideal location, postural changes of the patient or changes in tissue properties over time.
  • the measurement(s) of conduction velocity may be used for feedback control of an applied stimulus in order to adjust device operation for such changes.
  • the present invention provides a method for diagnosing a disease which affects neural conduction velocity, the method comprising:
  • the disease may be diabetes mellitus.
  • Diabetes mellitus reversibly slows the neural conduction velocity in patients having insufficient metabolic control, so that detection of reductions in neural conduction velocity may assist in diagnosing the onset, state or progression of diabetes mellitus, and may for example trigger revision of a treatment schedule.
  • the disease may be central sensitization.
  • Central sensitization tends to reduce the neural conduction velocity, so that detection of reductions in neural conduction velocity may assist in diagnosing the onset, state or progression of central sensitization.
  • a conduction velocity map of the spinal cord may be obtained by progressively applying stimuli using each of a plurality of electrodes of an implanted electrode array, and using spaced apart measurement electrodes to obtain a measure of the conduction velocity resulting from each stimulus site. Mapping conduction velocity against location then will give an indication of the location(s) at which central sensitization has occurred. Such a map may then be used to optimize the location of therapeutic stimuli, either through a manual fitting of the device or through an automated feedback procedure carried out by an implanted control unit.
  • the present invention provides a method for characterizing incremental recruitment effected by a larger intensity neural stimulus compared to a smaller intensity neural stimulus, the method comprising:
  • subtracting the CAP responses from two different stimuli will yield the response from the additional fibres recruited by the additional current increment.
  • This method thus provides a way to look at subsets of the fibres recruited, and look at their properties, which can then be used for a feedback or control signal, or for a diagnostic purpose as described elsewhere herein.
  • the recruitment effected by the first and second stimuli may differ by a margin which is a fraction of a range of interest, and the method may further comprise repeatedly obtaining the difference measurement for varying values of stimulus parameters throughout the range of interest, to thus gain a finer resolution determination of the incremental recruitment obtained at multiple points throughout the range of interest.
  • the range of interest may be a therapeutic range, for example between a recruitment threshold and a maximum comfort threshold.
  • Some preferred embodiments of the invention may perform the method of the fourth aspect on each of two sense electrodes which are spaced apart along the neural pathway, in order to estimate the conduction velocity of the first and/or second neural response in accordance with the method of the first aspect of the invention.
  • Such embodiments, combing the first and fourth aspects of the invention may be particularly beneficial in allowing determination of both the conduction velocity and the contribution of the incrementally recruited fibres.
  • the present invention provides a computer program product comprising computer program code means to make a computer execute a procedure for estimating conduction velocity of a neural response, the computer program product comprising computer program code means for carrying out the method of the first aspect or fourth aspect.
  • the neural response may be a spinal cord response, or other human nerve response, or a neural response of a non-human subject.
  • the conduction velocity may be determined from the delay between measurements obtained from two electrodes, or from more than two electrodes.
  • FIG. 1 illustrates compound action potentials measured from a sheep spinal cord using spaced apart measurement electrodes, both in the ascending/rostral direction ( FIG. 1 a ) and descending/caudal direction ( FIG. 1 b );
  • FIG. 2 is a schematic diagram illustrating the relationships between the measured evoked response and the fibre properties, in which FIG. 2 a illustrates the compound action potential measured on two spaced apart electrodes, FIG. 2 b illustrates variation of peak amplitude (P 2 -N 1 ) with applied stimulus current, FIG. 2 c illustrates the relation between fibre diameter and conduction velocity, FIG. 2 d illustrates the inverse relationship between the threshold current and fibre diameter, and FIG. 2 e is a plot of inter-electrode delay L 1 vs. stimulus current level;
  • FIG. 3 further illustrates the relation between fibre diameter and conduction velocity
  • FIG. 4 illustrates an implantable device suitable for implementing the present invention.
  • FIG. 1 illustrates measured compound action potentials in the sheep spinal cord, both in the ascending/rostral direction ( FIG. 1 a ) and descending/caudal direction ( FIG. 1 b ).
  • the fibres responsible for inhibition of pain in therapeutic SCS are the A ⁇ fibres in the dorsal horn. Stimulation of these fibres produces an orthodromic (ascending) volley of discharges, and also an antidromic descending volley.
  • CAP compound action potential
  • FIG. 1 a a single ascending compound action potential (CAP) is measured as it passes 4 measurement electrodes (E 13 through E 16 ) which are spaced apart along the neural pathway, increasingly distant from the stimulus.
  • a single descending CAP is measured as it passes 4 measurement electrodes (E 5 through E 8 ) which are spaced apart along the neural pathway, increasingly distant from the stimulus.
  • FIG. 2 a illustrates the compound action potential measured on two electrodes which are spaced apart alongside a neural pathway and separated from each other by some known distance, this distance typically being defined by the physical layout of the electrode array and therefore accurately known.
  • the difference in peak position, L 1 is due to the propagation delay of the discharge (CAP). L 1 is thus a measure of the time it takes for the action potential to travel the known distance between the electrodes.
  • L 1 may be measured from any suitable feature or group of features in the CAP measurements, such as the time between the respective P 1 peaks, the time between the N 1 peaks, the time between the P 2 peaks, the time between the P 1 -to-N 1 zero crossing, or the like.
  • the peak amplitude (P 2 -N 1 ) varies with the applied current in the stimulus pulse, as illustrated in FIG. 2 b for each of the two electrodes used to obtain the measurements for FIG. 2 a .
  • the amplitude of the response is zero until a critical threshold value (T 1 ) is reached.
  • the threshold is related to the fibre diameter, with smaller fibres being more difficult to recruit and requiring more current to recruit, as illustrated in FIG. 2 d (in which a negative stimulus current is in use).
  • the amplitude-stimulus curves for the two electrodes have the same threshold T 1 , but differing amplitudes above T 1 due to attenuation of the neural response between the two electrodes.
  • the fibre diameter is also related to the conduction velocity as shown in FIG. 2 c , and FIG. 3 .
  • the present invention recognises that low stimulus currents can only recruit large fibres, which have high conduction velocities, so that plotting L 1 against the stimulus current level as shown in FIG. 2 e , gives an indication of the spread of fibre diameters which are being recruited.
  • FIG. 2 e it can be seen that with a low stimulus current which is only just above the threshold T 1 , L 1 is small and thus indicates that high conduction velocity fibres are primarily being recruited. As the stimulus current increases, L 1 increases, indicating that smaller fibres having slower conduction velocity are increasingly recruited.
  • FIG. 3 illustrates conduction velocity of a nerve fibre as a function of nerve diameter.
  • the conduction velocity of a fibre is related to the diameter of the fibre. Larger myelinated fibres conduct faster, thought to be because the nodes of Ranvier are further apart.
  • the data collected by measuring the evoked response in the sheep spine allows the determination of the conduction velocity from the N 1 peak position in the travelling wave.
  • a conduction velocity at 60 ms ⁇ 1 corresponds to a fibre diameter of 10 ⁇ m.
  • the present invention recognises that in the superficial dorsal horn, only a small proportion of fibres (perhaps 0.5%) are greater than 10.7 ⁇ m in diameter, and that the beneficial therapeutic effect of spinal cord stimulation (SCS) is thought to be generated primarily by fibres of this diameter. Moreover, adverse side effects of SCS can arise if recruitment of non-A ⁇ fibre types occurs, so that selectivity of recruitment of fibre type is advantageous in maximising beneficial effects while minimising adverse side effects. That is, the efficacy of spinal cord stimulation for the relief of chronic pain is related to the A ⁇ fibre recruitment, which the present invention recognises can be measured by considering the conduction velocity of the evoked response.
  • SCS spinal cord stimulation
  • the compound action potential measurements can thus be used to adjust the stimulation parameters and improve efficiency in a number of ways, including: 1) Maximising recruitment of specific fibre classes by adjustment of stimulus parameters, 2) Differential control of the ascending/descending volleys and associated blocking of these volleys, 3) Automatic variation of stimulation parameters to adjust for changes in use or environment, and 4) Detection of pathology within the underlying stimulated tissue.
  • Measurement of parameters such as those shown in FIG. 2 can be used for a number of further beneficial purposes as described below.
  • the measurements themselves or parameters extracted from measurements represent properties of the neuronal populations. For instance the peak to peak amplitude measured between the largest negative peak N 1 and largest positive peak P 2 is proportional to the level of recruitment of the nerve fibres.
  • the evoked CAP measurements may be made at very short distances from the stimulation site(s). Such embodiments may be effected by use of the neural response measurement techniques set out in the Australian provisional patent application No. 2011901817 in the name of National ICT Australia Ltd entitled “Method and apparatus for measurement of neural response” from which the present application claims priority.
  • the present invention recognises that using a suitable measurement technique to obtain a CAP measurement from very close to the stimulation site offers additional benefits to past “long range” approaches, and may have utility as described below during surgery to monitor local areas of the spine.
  • the neural response measurement may be conducted in accordance with any suitable CAP measurement technique, for example the techniques set out in Daly (US 2007/0225767), the content of which is incorporated herein by reference. Additionally or alternatively, the neural response measurement may be conducted in accordance with the techniques set out in Nygard (U.S. Pat. No. 5,785,651), the content of which is incorporated herein by reference. Additionally or alternatively, the neural response measurement may be conducted in accordance with the techniques set out in King (U.S. Pat. No. 5,913,882), the content of which is incorporated herein by reference.
  • Local compound action potentials recorded with an electrode array placed in the epidural space in the spinal cord display a fast response occurring within 1.5 ms, from large diameter fibres ( ⁇ 10 ⁇ m). This response can be recorded on electrodes adjacent to the stimulating site.
  • a number of basic fibre properties can be determined from the measurement of the compound action potentials.
  • the evoked response provides a measure of the properties of the nerve being depolarised.
  • the conduction velocity, fibre diameter and distribution of fibre diameters of the nerve can be determined by measurement of the evoked response.
  • the method of the present invention may further be used to monitor the effect of a delivered compound, where the compound affects the neural conduction velocity.
  • the administration of compounds (drugs or other chemical therapeutics) to effect a change in the nervous system is common for treatment of a wide number of diseases and disorders.
  • Anaesthetics of various types are administered to the spinal cord for the relief of pain. Perhaps the most common form is administration of anesthetics in the epidural space for pain relief during child birth.
  • Treatment efficacy may be determined intra-operatively, for example by using a catheter comprising a tube for administration of a drug into the epidural space, and an electrode array. Electrical stimulation can be delivered directly to the spinal cord and the effect of the administered drug can be directly measured in real time.
  • Alternative embodiments may be suitable for full implantation within the body of a subject and in such embodiments the evoked potential monitoring of the present invention could be used for ongoing administration of an active compound to produce a therapeutic benefit over time.
  • the implanted system could be integrated with an implantable pump to control the administration of the compound.
  • any factor which may affect the properties of the compound action potential could be subject to monitoring by the evoked response system described. For instance the conduction velocity of nerves is slowed reversibly in patients with diabetic mellitus where there is insufficient metabolic control.
  • the properties of the stimulated neural population may indicate an underlying pathology or the development of an underlying pathology.
  • the detection of the pathology may be used as a control signal for the regulation of the release of a drug.
  • One such pathology is the development of neuropathic pain via central sensitisation, and accordingly some embodiments of the invention may provide for identification of the onset, progression, or state of central sensitization, using an in-situ device in accordance with the present invention.
  • Central sensitisation is a well-accepted theory for development of chronic neuropathic pain. It relies on the nociceptive neurons in the dorsal horn becoming hyper-sensitised due to tissue damage or inflammation. Central sensitisation provides an explanation for allodynia (which is pain produced from what in normal circumstances would be non-noxious stimuli) due to expansion of the receptive fields.
  • Allodynia which is pain produced from what in normal circumstances would be non-noxious stimuli
  • the properties of the dorsal horn neurons have been studied in animal models of central sensitisation. There is however no direct evidence of central sensitisation from measurements of dorsal horn properties in humans. In animal models the properties of all the fibres change (as recorded by patch clamp experiments).
  • the method of the present invention provides a method for determining the properties of the neurons which are being stimulated and during normal spinal cord stimulation the target neurons are the A ⁇ fibres.
  • the properties of these fibres have been reported in both normal and central sensitised model and distinct differences have been noted. Distinct changes in conduction velocity of A ⁇ fibres in the centrally sensitised state have been reported. The shift in conduction velocity was of the order of 25% which is clearly detectable via CAP measurements in humans.
  • the procedure involves determining the conduction velocity in a portion of the spinal cord where it is apparently normal, and comparing that measure with conduction velocities measured over areas which correspond (according to dermatomes maps) where the central sensitisation should appear.
  • the conduction velocity distribution could be obtained over the entire electrode array by measuring the conduction velocity (both orthodromically and antidromically) from stimulation on each bipolar pair in turn.
  • conduction velocity both orthodromically and antidromically
  • other properties of the responding fibres could be used as markers of pathological change.
  • a spinal cord map obtained in such a way might also be used to provide an accurate indication of stimulation sites for trial in the stimulation procedure.
  • a significant number of patients undergoing back surgery will later develop chronic pain conditions.
  • the device has the capability to monitor the response of the spinal cord to electrical stimulation and detect the onset of central sensitisation.
  • the device equipped with ERT recording can be used to detect the onset of the neuropathic pain condition.
  • the device would start to stimulate and provide the inhibitory input which would prevent the further progression of the neuropathic condition.
  • a further improvement would be to include the functionality of the SCS within a spinal orthopaedic implant so that no additional implant structures are required.
  • Device 400 comprises an implanted control unit 410 , which controls application of neural stimuli, and controls a measurement process for obtaining a measurement of a neural response evoked by the stimuli.
  • Device 400 further comprises an electrode array 420 consisting of a three by eight array of electrodes 422 which may be selectively used as either the stimulus electrode or sense electrode, or both.

Abstract

A method for estimating conduction velocity of a neural response. Measurements of the neural response are obtained from at least two electrodes which are at distinct locations along a neural pathway. A delay between the time of arrival of the neural response at each respective electrode is determined from the measurements. From the delay, and from knowledge of electrode spacing, a conduction velocity of the neural response is estimated.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application claims the benefit of Australian Provisional Patent Application No. 2011901822 filed 13 May 2011, Australian Provisional Patent Application No. 2011901817 filed 13 May 2011 and Australian Provisional Patent Application No. 2011901824 filed 13 May 2011, each of which are incorporated herein by reference.
  • TECHNICAL FIELD
  • The present invention relates to measurement of a neural response to a stimulus, and in particular relates to measurement of a compound action potential by using one or more electrodes implanted proximal to the neural pathway.
  • BACKGROUND OF THE INVENTION
  • There are a range of situations in which it is desirable to measure a compound action potential (CAP). For example, 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. 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. To sustain the pain relief effects, stimuli are applied substantially continuously, for example at 100 Hz.
  • 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 Aβ fibres of interest. Aβ fibres mediate sensations of touch, vibration and pressure from the skin. The prevailing view is that SCS stimulates only a small number of Aβ fibres in the DC. The pain relief mechanisms of SCS are thought to include evoked antidromic activity of Aβ fibres having an inhibitory effect, and evoked orthodromic activity of Aβ fibres playing a role in pain suppression. It is also thought that SCS recruits Aβ 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. Inhibitory effects can be used to modulate an undesired process such as the transmission of pain, or to cause a desired effect such as the contraction of a muscle.
  • The action potentials generated among a large number of fibres sum to form a compound action potential (CAP). The CAP is the sum of responses from a large number of single fibre action potentials. The CAP recorded is the result of a large number of different fibres depolarising. The propagation velocity is determined largely by the fibre diameter and for large myelinated fibres as found in the dorsal root entry zone (DREZ) and nearby dorsal column the velocity can be over 60 ms−1. The CAP generated from the firing of a group of similar fibres is measured as a positive peak potential P1, then a negative peak N1, followed by a second positive peak P2. This is caused by the region of activation passing the recording electrode as the action potentials propagate along the individual fibres.
  • To better understand the effects of neuromodulation and/or other neural stimuli, it is desirable to record a CAP resulting from the stimulus. However, this can be a difficult task as an observed CAP signal will typically have a maximum amplitude in the range of microvolts, whereas a stimulus applied to evoke the CAP is typically several volts. To resolve a 10 μV spinal cord potential (SCP) with 1 μV resolution in the presence of an input 5V stimulus, for example, requires an amplifier with a dynamic range of 134 dB, which is impractical in implant systems.
  • CAP recordings are sometimes made during surgical procedures on the spinal cord, to provide an indication of any potential neurological damage being caused by the procedure. Typically, a site below (caudally of) the area being operated on is stimulated and recordings are made above (rostrally of) the site. A diminishing response, or a change in response, indicates a change in the neurological condition of the spinal cord and may indicate lasting damage. For example such monitoring is often performed during scoliosis surgery (straightening a curvature of the spine) to ensure that the decompression doesn't damage the spinal cord. Somatosensory potentials are also used for spinal cord monitoring during surgery. These are recorded on the scalp of the patient and are evoked from stimulation of a peripheral nerve, usually one of the tibial nerve, median nerve or ulnar nerve. Somatosensory potentials can also be measured in response to stimulation of the spinal cord. The monitoring techniques employed in surgery are “long range” techniques, in that the stimulation site and the recording site are a large distance apart, and are thus less sensitive at least due to attenuation.
  • Neural damage, degeneration or change can affect neural behaviour in a number of ways, such as by changing the number of fibres recruited by a given stimulus, the type of fibres recruited, and/or propagation characteristics of the action potential along a fibre once activated. Techniques which merely monitor the presence/absence, or the strength, of a detected neural signal may thus overlook important changes in other characteristics of the neural response.
  • Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It 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 invention as it existed before the priority date of each claim of this application.
  • Throughout this specification the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.
  • SUMMARY OF THE INVENTION
  • According to a first aspect the present invention provides a method for estimating conduction velocity of a neural response, the method comprising:
      • obtaining measurements of the neural response from at least two electrodes which are at distinct locations along a neural pathway;
      • determining a delay between the time of arrival of the neural response at each respective electrode; and
      • estimating from the delay, and from knowledge of electrode spacing, a conduction velocity of the neural response.
  • According to a second aspect the present invention provides a device for estimating conduction velocity of a neural response, the device comprising:
      • at least two electrodes which are configured to be positioned at distinct locations along a neural pathway; and
      • a control unit configured to obtain measurements of the neural response from each electrode, the control unit further configured to determine a delay between the time of arrival of the neural response at each respective electrode, and the control unit further configured to estimate from the delay, and from knowledge of electrode spacing, a conduction velocity of the neural response.
  • The device may be configured for permanent implantation and ongoing operation while implanted. Alternatively the device may be configured for intra-operative use only.
  • Some embodiments of the invention may further provide for estimating from the conduction velocity of the neural response, or from changes in the conduction velocity of the neural response as detected from one measurement to a next measurement, an approximate proportion of fibre classes recruited to produce the neural response. For example, in such embodiments, a high conduction velocity may be taken as being indicative of recruitment of large fibres such as Aβ fibres. Similarly, an increased conduction velocity from one measurement to a next measurement may be taken as being indicative of increased recruitment of large fibres such as Aβ fibres. Such embodiments may be particularly useful in feedback control of an applied stimulus in order to preferentially recruit Aβ fibres to achieve beneficial therapeutic effects while minimizing recruitment of smaller fiber classes to avoid adverse side effects.
  • In some embodiments of the invention, a measure of conduction velocity may be obtained both caudally of the stimulus site and rostrally of the stimulus site. In such embodiments, the measurements may be used as input to a feedback controller designed to effect differential control of fibre classes recruited in an evoked ascending volley as compared to fibre classes recruited in an evoked descending volley.
  • In some embodiments of the invention, a measure of conduction velocity may reveal changes in stimulus efficacy, as for example may arise as a result of implant migration away from the ideal location, postural changes of the patient or changes in tissue properties over time. In such embodiments, the measurement(s) of conduction velocity may be used for feedback control of an applied stimulus in order to adjust device operation for such changes.
  • According to a third aspect, the present invention provides a method for diagnosing a disease which affects neural conduction velocity, the method comprising:
      • repeatedly measuring a neural conduction velocity over time, using the method of the first aspect; and
      • determining from said measurements whether any changes in neural conduction velocity have occurred which are indicative of the disease.
  • In some embodiments of the third aspect of the invention, the disease may be diabetes mellitus. Diabetes mellitus reversibly slows the neural conduction velocity in patients having insufficient metabolic control, so that detection of reductions in neural conduction velocity may assist in diagnosing the onset, state or progression of diabetes mellitus, and may for example trigger revision of a treatment schedule.
  • In some embodiments of the third aspect of the invention, the disease may be central sensitization. Central sensitization tends to reduce the neural conduction velocity, so that detection of reductions in neural conduction velocity may assist in diagnosing the onset, state or progression of central sensitization. In such embodiments, a conduction velocity map of the spinal cord may be obtained by progressively applying stimuli using each of a plurality of electrodes of an implanted electrode array, and using spaced apart measurement electrodes to obtain a measure of the conduction velocity resulting from each stimulus site. Mapping conduction velocity against location then will give an indication of the location(s) at which central sensitization has occurred. Such a map may then be used to optimize the location of therapeutic stimuli, either through a manual fitting of the device or through an automated feedback procedure carried out by an implanted control unit.
  • According to a fourth aspect the present invention provides a method for characterizing incremental recruitment effected by a larger intensity neural stimulus compared to a smaller intensity neural stimulus, the method comprising:
      • obtaining a first measurement of a first neural response evoked by a first neural stimulus;
      • obtaining a second measurement of a second neural response evoked by a second neural stimulus, the second neural stimulus having different stimulus parameters and a different neural recruitment effect as compared to the first stimulus;
      • subtracting the first measurement and second measurement to yield a difference measurement; and
      • assessing the difference measurement to determine the nature of the differential recruitment effected by the first stimulus as compared to the second stimulus.
  • In accordance with the fourth aspect, subtracting the CAP responses from two different stimuli will yield the response from the additional fibres recruited by the additional current increment. This method thus provides a way to look at subsets of the fibres recruited, and look at their properties, which can then be used for a feedback or control signal, or for a diagnostic purpose as described elsewhere herein.
  • In some embodiments of the fourth aspect the recruitment effected by the first and second stimuli may differ by a margin which is a fraction of a range of interest, and the method may further comprise repeatedly obtaining the difference measurement for varying values of stimulus parameters throughout the range of interest, to thus gain a finer resolution determination of the incremental recruitment obtained at multiple points throughout the range of interest. The range of interest may be a therapeutic range, for example between a recruitment threshold and a maximum comfort threshold.
  • Some preferred embodiments of the invention may perform the method of the fourth aspect on each of two sense electrodes which are spaced apart along the neural pathway, in order to estimate the conduction velocity of the first and/or second neural response in accordance with the method of the first aspect of the invention. Such embodiments, combing the first and fourth aspects of the invention, may be particularly beneficial in allowing determination of both the conduction velocity and the contribution of the incrementally recruited fibres.
  • According to another aspect the present invention provides a computer program product comprising computer program code means to make a computer execute a procedure for estimating conduction velocity of a neural response, the computer program product comprising computer program code means for carrying out the method of the first aspect or fourth aspect.
  • The neural response may be a spinal cord response, or other human nerve response, or a neural response of a non-human subject.
  • The conduction velocity may be determined from the delay between measurements obtained from two electrodes, or from more than two electrodes.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • An example of the invention will now be described with reference to the accompanying drawings, in which:
  • FIG. 1 illustrates compound action potentials measured from a sheep spinal cord using spaced apart measurement electrodes, both in the ascending/rostral direction (FIG. 1 a) and descending/caudal direction (FIG. 1 b);
  • FIG. 2 is a schematic diagram illustrating the relationships between the measured evoked response and the fibre properties, in which FIG. 2 a illustrates the compound action potential measured on two spaced apart electrodes, FIG. 2 b illustrates variation of peak amplitude (P2-N1) with applied stimulus current, FIG. 2 c illustrates the relation between fibre diameter and conduction velocity, FIG. 2 d illustrates the inverse relationship between the threshold current and fibre diameter, and FIG. 2 e is a plot of inter-electrode delay L1 vs. stimulus current level;
  • FIG. 3 further illustrates the relation between fibre diameter and conduction velocity; and
  • FIG. 4 illustrates an implantable device suitable for implementing the present invention.
  • DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • FIG. 1 illustrates measured compound action potentials in the sheep spinal cord, both in the ascending/rostral direction (FIG. 1 a) and descending/caudal direction (FIG. 1 b). According to current theory the fibres responsible for inhibition of pain in therapeutic SCS are the Aβ fibres in the dorsal horn. Stimulation of these fibres produces an orthodromic (ascending) volley of discharges, and also an antidromic descending volley. In FIG. 1 a, a single ascending compound action potential (CAP) is measured as it passes 4 measurement electrodes (E13 through E16) which are spaced apart along the neural pathway, increasingly distant from the stimulus. In FIG. 1 b, a single descending CAP is measured as it passes 4 measurement electrodes (E5 through E8) which are spaced apart along the neural pathway, increasingly distant from the stimulus.
  • As can be seen in FIG. 1, in both the orthodromic and antidromic directions, the further away the measurement electrode is from the stimulus site, the greater is the delay of the CAP waveform measured by that electrode and the smaller is the peak amplitude of the measured CAP.
  • The present invention recognises that a great deal can be understood about the nature and properties of the fibres being recruited by electrical stimulation, by obtaining at least two measurements of a single CAP, from two spaced apart measurement electrodes along the neural pathway. FIG. 2 a illustrates the compound action potential measured on two electrodes which are spaced apart alongside a neural pathway and separated from each other by some known distance, this distance typically being defined by the physical layout of the electrode array and therefore accurately known. The difference in peak position, L1, is due to the propagation delay of the discharge (CAP). L1 is thus a measure of the time it takes for the action potential to travel the known distance between the electrodes. L1 may be measured from any suitable feature or group of features in the CAP measurements, such as the time between the respective P1 peaks, the time between the N1 peaks, the time between the P2 peaks, the time between the P1-to-N1 zero crossing, or the like.
  • The peak amplitude (P2-N1) varies with the applied current in the stimulus pulse, as illustrated in FIG. 2 b for each of the two electrodes used to obtain the measurements for FIG. 2 a. The amplitude of the response is zero until a critical threshold value (T1) is reached. The threshold is related to the fibre diameter, with smaller fibres being more difficult to recruit and requiring more current to recruit, as illustrated in FIG. 2 d (in which a negative stimulus current is in use). In FIG. 2 b the amplitude-stimulus curves for the two electrodes have the same threshold T1, but differing amplitudes above T1 due to attenuation of the neural response between the two electrodes. The fibre diameter is also related to the conduction velocity as shown in FIG. 2 c, and FIG. 3. The present invention recognises that low stimulus currents can only recruit large fibres, which have high conduction velocities, so that plotting L1 against the stimulus current level as shown in FIG. 2 e, gives an indication of the spread of fibre diameters which are being recruited. In particular, in FIG. 2 e, it can be seen that with a low stimulus current which is only just above the threshold T1, L1 is small and thus indicates that high conduction velocity fibres are primarily being recruited. As the stimulus current increases, L1 increases, indicating that smaller fibres having slower conduction velocity are increasingly recruited.
  • FIG. 3 illustrates conduction velocity of a nerve fibre as a function of nerve diameter. The conduction velocity of a fibre is related to the diameter of the fibre. Larger myelinated fibres conduct faster, thought to be because the nodes of Ranvier are further apart.
  • The data collected by measuring the evoked response in the sheep spine (FIG. 1) allows the determination of the conduction velocity from the N1 peak position in the travelling wave. A conduction velocity at 60 ms−1 corresponds to a fibre diameter of 10 μm.
  • The present invention recognises that in the superficial dorsal horn, only a small proportion of fibres (perhaps 0.5%) are greater than 10.7 μm in diameter, and that the beneficial therapeutic effect of spinal cord stimulation (SCS) is thought to be generated primarily by fibres of this diameter. Moreover, adverse side effects of SCS can arise if recruitment of non-Aβ fibre types occurs, so that selectivity of recruitment of fibre type is advantageous in maximising beneficial effects while minimising adverse side effects. That is, the efficacy of spinal cord stimulation for the relief of chronic pain is related to the Aβ fibre recruitment, which the present invention recognises can be measured by considering the conduction velocity of the evoked response.
  • The compound action potential measurements can thus be used to adjust the stimulation parameters and improve efficiency in a number of ways, including: 1) Maximising recruitment of specific fibre classes by adjustment of stimulus parameters, 2) Differential control of the ascending/descending volleys and associated blocking of these volleys, 3) Automatic variation of stimulation parameters to adjust for changes in use or environment, and 4) Detection of pathology within the underlying stimulated tissue.
  • Measurement of parameters such as those shown in FIG. 2, and knowledge of their relationships, can be used for a number of further beneficial purposes as described below. The measurements themselves or parameters extracted from measurements represent properties of the neuronal populations. For instance the peak to peak amplitude measured between the largest negative peak N1 and largest positive peak P2 is proportional to the level of recruitment of the nerve fibres.
  • In some embodiments of the invention the evoked CAP measurements may be made at very short distances from the stimulation site(s). Such embodiments may be effected by use of the neural response measurement techniques set out in the Australian provisional patent application No. 2011901817 in the name of National ICT Australia Ltd entitled “Method and apparatus for measurement of neural response” from which the present application claims priority. The present invention recognises that using a suitable measurement technique to obtain a CAP measurement from very close to the stimulation site offers additional benefits to past “long range” approaches, and may have utility as described below during surgery to monitor local areas of the spine.
  • Additionally or alternatively, the neural response measurement may be conducted in accordance with any suitable CAP measurement technique, for example the techniques set out in Daly (US 2007/0225767), the content of which is incorporated herein by reference. Additionally or alternatively, the neural response measurement may be conducted in accordance with the techniques set out in Nygard (U.S. Pat. No. 5,785,651), the content of which is incorporated herein by reference. Additionally or alternatively, the neural response measurement may be conducted in accordance with the techniques set out in King (U.S. Pat. No. 5,913,882), the content of which is incorporated herein by reference.
  • Local compound action potentials recorded with an electrode array placed in the epidural space in the spinal cord display a fast response occurring within 1.5 ms, from large diameter fibres (˜10 μm). This response can be recorded on electrodes adjacent to the stimulating site. A number of basic fibre properties can be determined from the measurement of the compound action potentials. There are a number of neurological conditions and non-neurological conditions which can affect the parameters determined by the conduction velocity measurements and so the measurement techniques of the present invention can serve as a useful diagnostic indicator. The evoked response provides a measure of the properties of the nerve being depolarised. The conduction velocity, fibre diameter and distribution of fibre diameters of the nerve can be determined by measurement of the evoked response.
  • The method of the present invention may further be used to monitor the effect of a delivered compound, where the compound affects the neural conduction velocity. The administration of compounds (drugs or other chemical therapeutics) to effect a change in the nervous system is common for treatment of a wide number of diseases and disorders. Anaesthetics of various types are administered to the spinal cord for the relief of pain. Perhaps the most common form is administration of anesthetics in the epidural space for pain relief during child birth. Treatment efficacy may be determined intra-operatively, for example by using a catheter comprising a tube for administration of a drug into the epidural space, and an electrode array. Electrical stimulation can be delivered directly to the spinal cord and the effect of the administered drug can be directly measured in real time.
  • Alternative embodiments may be suitable for full implantation within the body of a subject and in such embodiments the evoked potential monitoring of the present invention could be used for ongoing administration of an active compound to produce a therapeutic benefit over time. In such embodiments the implanted system could be integrated with an implantable pump to control the administration of the compound.
  • Any factor which may affect the properties of the compound action potential could be subject to monitoring by the evoked response system described. For instance the conduction velocity of nerves is slowed reversibly in patients with diabetic mellitus where there is insufficient metabolic control.
  • The properties of the stimulated neural population may indicate an underlying pathology or the development of an underlying pathology. The detection of the pathology may be used as a control signal for the regulation of the release of a drug. One such pathology is the development of neuropathic pain via central sensitisation, and accordingly some embodiments of the invention may provide for identification of the onset, progression, or state of central sensitization, using an in-situ device in accordance with the present invention.
  • Central sensitisation is a well-accepted theory for development of chronic neuropathic pain. It relies on the nociceptive neurons in the dorsal horn becoming hyper-sensitised due to tissue damage or inflammation. Central sensitisation provides an explanation for allodynia (which is pain produced from what in normal circumstances would be non-noxious stimuli) due to expansion of the receptive fields. The properties of the dorsal horn neurons have been studied in animal models of central sensitisation. There is however no direct evidence of central sensitisation from measurements of dorsal horn properties in humans. In animal models the properties of all the fibres change (as recorded by patch clamp experiments). Reductions in the conduction velocity have been observed in fibres of the segments of the dorsal horn which display characteristic properties of the central sensitised state. One study recorded the electrical activity (in the form of individual neuronal spikes) in the dorsal horns of rats elicited from mechanical stimulation. Activity recorded in a control group was compared to the activity recorded in rats with induced central sensitisation. This sensitised state was induced using the spared nerve injury model of neuropathic pain. The spontaneous activity resulting from a stimulus was different in the central sensitised state. There was an increase in higher frequency components and an increase in the after discharge rate. Central sensitisation is the result of the increase in synaptic efficiency and the reduction of inhibition of the pathways within the spinal cord for the transmission of painful stimuli. This leads to an amplification of pain and results in the experience of pain from other inputs such as the low threshold mechanical sensory inputs which would not normally produce pain inputs.
  • The method of the present invention provides a method for determining the properties of the neurons which are being stimulated and during normal spinal cord stimulation the target neurons are the Aβ fibres. The properties of these fibres have been reported in both normal and central sensitised model and distinct differences have been noted. Distinct changes in conduction velocity of Aβ fibres in the centrally sensitised state have been reported. The shift in conduction velocity was of the order of 25% which is clearly detectable via CAP measurements in humans.
  • The procedure involves determining the conduction velocity in a portion of the spinal cord where it is apparently normal, and comparing that measure with conduction velocities measured over areas which correspond (according to dermatomes maps) where the central sensitisation should appear. The conduction velocity distribution could be obtained over the entire electrode array by measuring the conduction velocity (both orthodromically and antidromically) from stimulation on each bipolar pair in turn. In addition to conduction velocity other properties of the responding fibres could be used as markers of pathological change.
  • A spinal cord map obtained in such a way might also be used to provide an accurate indication of stimulation sites for trial in the stimulation procedure. A significant number of patients undergoing back surgery will later develop chronic pain conditions. The potential exists, particularly with back surgery, to place a spinal cord stimulator at the time of the original surgery. The device has the capability to monitor the response of the spinal cord to electrical stimulation and detect the onset of central sensitisation. In effect the device equipped with ERT recording can be used to detect the onset of the neuropathic pain condition. Through appropriate algorithms the device would start to stimulate and provide the inhibitory input which would prevent the further progression of the neuropathic condition. A further improvement would be to include the functionality of the SCS within a spinal orthopaedic implant so that no additional implant structures are required. FIG. 4 illustrates an implantable device 400 which may exploit the present invention. Device 400 comprises an implanted control unit 410, which controls application of neural stimuli, and controls a measurement process for obtaining a measurement of a neural response evoked by the stimuli. Device 400 further comprises an electrode array 420 consisting of a three by eight array of electrodes 422 which may be selectively used as either the stimulus electrode or sense electrode, or both.
  • It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims (13)

1. A method for estimating conduction velocity of a neural response, the method comprising:
obtaining measurements of the neural response from at least two electrodes which are at distinct locations along a neural pathway;
determining a delay between the time of arrival of the neural response at each respective electrode; and
estimating from the delay, and from knowledge of electrode spacing, a conduction velocity of the neural response.
2. The method of claim 1 further comprising estimating, from the conduction velocity of the neural response, a proportion of fibre classes recruited to produce the neural response.
3. The method of claim 1 further comprising estimating, from changes in the conduction velocity of the neural response as detected from one measurement to a next measurement, a proportion of fibre classes recruited to produce the neural response.
4. The method of claim 2 further comprising using the estimated proportion of fibre classes recruited as an input to feedback control of an applied stimulus, in order to control the stimulus so as to preferentially recruit one or more desired fibre classes.
5. The method of claim 1, wherein the measurements of the neural response are obtained from locations both caudally of the stimulus site and rostrally of the stimulus site.
6. The method of claim 5 wherein a caudal conduction velocity and a rostral conduction velocity are each estimated from the measurements, and wherein the estimates are used as input to feedback control of the applied stimulus in order to effect differential control of fibre classes recruited in an evoked ascending volley as compared to fibre classes recruited in an evoked descending volley.
7. The method of claim 1 wherein the estimate of conduction velocity is used for feedback control of an applied stimulus in order to maintain stimulus efficacy during postural changes.
8. The method of claim 1 wherein the measurements of the neural response are obtained from at least three electrodes for each estimate of conduction velocity.
9. A device for estimating conduction velocity of a neural response, the device comprising:
at least two electrodes which are configured to be positioned at distinct locations along a neural pathway; and
a control unit configured to obtain measurements of the neural response from each electrode, the control unit further configured to determine a delay between the time of arrival of the neural response at each respective electrode, and the control unit further configured to estimate from the delay, and from knowledge of electrode spacing, a conduction velocity of the neural response.
10. The device of claim 9, wherein the device is configured for permanent implantation.
11. A method of claim 1 further comprising repeatedly measuring a neural conduction velocity over time and determining from said measurements whether changes in neural conduction velocity have occurred for diagnosing at least one disease which affects neural conduction velocity.
12. The method of claim 11 wherein the disease is diabetes mellitus, and wherein detection of a reduction in neural conduction velocity is used to trigger revision of a treatment schedule.
13. The method of claim 11 wherein the disease is central sensitization, the method further comprising obtaining a conduction velocity map of the spinal cord by progressively applying stimuli using each of a plurality of electrodes of an implanted electrode array, using spaced apart measurement electrodes to obtain a measure of the conduction velocity resulting from each stimulus site, and then mapping conduction velocity against location to indicate the location(s) at which central sensitization has occurred.
US14/117,145 2011-05-13 2012-05-11 Method and apparatus for measurement of neural response Abandoned US20140236042A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
AU2011901817A AU2011901817A0 (en) 2011-05-13 Method and apparatus for measurement of neural response - A
AU2011901824A AU2011901824A0 (en) 2011-05-13 Method and apparatus for measurement of neural response - G
AU2011901822A AU2011901822A0 (en) 2011-05-13 Method and apparatus for measurement of neural response - C
PCT/AU2012/000512 WO2012155184A1 (en) 2011-05-13 2012-05-11 Method and apparatus for measurement of neural response - c

Publications (1)

Publication Number Publication Date
US20140236042A1 true US20140236042A1 (en) 2014-08-21

Family

ID=47176029

Family Applications (2)

Application Number Title Priority Date Filing Date
US14/117,145 Abandoned US20140236042A1 (en) 2011-05-13 2012-05-11 Method and apparatus for measurement of neural response
US14/117,153 Active 2032-07-10 US10588524B2 (en) 2011-05-13 2012-05-11 Method and apparatus for measurement of neural response

Family Applications After (1)

Application Number Title Priority Date Filing Date
US14/117,153 Active 2032-07-10 US10588524B2 (en) 2011-05-13 2012-05-11 Method and apparatus for measurement of neural response

Country Status (2)

Country Link
US (2) US20140236042A1 (en)
WO (2) WO2012155190A1 (en)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9155892B2 (en) 2011-05-13 2015-10-13 Saluda Medical Pty Limited Method and apparatus for application of a neural stimulus
US9381356B2 (en) 2011-05-13 2016-07-05 Saluda Medical Pty Ltd. Method and apparatus for controlling a neural stimulus
US9386934B2 (en) 2011-05-13 2016-07-12 Saluda Medical Pty Ltd. Method and apparatus for measurement of neural response
WO2016161484A3 (en) * 2015-04-09 2016-12-22 Saluda Medical Pty Ltd Electrode to nerve distance estimation
US9872990B2 (en) 2011-05-13 2018-01-23 Saluda Medical Pty Limited Method and apparatus for application of a neural stimulus
US9974455B2 (en) 2011-05-13 2018-05-22 Saluda Medical Pty Ltd. Method and apparatus for estimating neural recruitment
US10206596B2 (en) 2012-11-06 2019-02-19 Saluda Medical Pty Ltd Method and system for controlling electrical conditions of tissue
US10368762B2 (en) 2014-05-05 2019-08-06 Saluda Medical Pty Ltd. Neural measurement
US10406368B2 (en) 2016-04-19 2019-09-10 Boston Scientific Neuromodulation Corporation Pulse generator system for promoting desynchronized firing of recruited neural populations
US10426409B2 (en) 2013-11-22 2019-10-01 Saluda Medical Pty Ltd Method and device for detecting a neural response in a neural measurement
US10500399B2 (en) 2014-12-11 2019-12-10 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
US10568559B2 (en) 2011-05-13 2020-02-25 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US10588524B2 (en) 2011-05-13 2020-03-17 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US10588698B2 (en) 2014-12-11 2020-03-17 Saluda Medical Pty Ltd Implantable electrode positioning
US10632307B2 (en) 2014-07-25 2020-04-28 Saluda Medical Pty Ltd Neural stimulation dosing
US10849525B2 (en) 2015-05-31 2020-12-01 Saluda Medical Pty Ltd Monitoring brain neural activity
US10918872B2 (en) 2015-01-19 2021-02-16 Saluda Medical Pty Ltd Method and device for neural implant communication
US10926092B2 (en) 2018-01-08 2021-02-23 Boston Scientific Neuromodulation Corporation Automatic adjustment of sub-perception therapy in an implantable stimulator using detected compound action potentials
US10940316B2 (en) 2010-06-18 2021-03-09 Cardiac Pacemakers, Inc. Methods and apparatus for adjusting neurostimulation intensity using evoked responses
US10974042B2 (en) 2018-03-26 2021-04-13 Boston Scientific Neuromodulation Corporation System and methods for heart rate and electrocardiogram extraction from a spinal cord stimulation system
US11006857B2 (en) 2015-06-01 2021-05-18 Closed Loop Medical Pty Ltd Motor fibre neuromodulation
US11006846B2 (en) 2014-11-17 2021-05-18 Saluda Medical Pty Ltd Method and device for detecting a neural response in neural measurements
US11040202B2 (en) 2018-03-30 2021-06-22 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device
US11110270B2 (en) 2015-05-31 2021-09-07 Closed Loop Medical Pty Ltd Brain neurostimulator electrode fitting
US11129987B2 (en) 2017-10-04 2021-09-28 Boston Scientific Neuromodulation Corporation Adjustment of stimulation in a stimulator using detected evoked compound action potentials
US11129989B2 (en) 2018-06-21 2021-09-28 Medtronic, Inc. ECAP based control of electrical stimulation therapy
US11129991B2 (en) 2018-06-21 2021-09-28 Medtronic, Inc. ECAP based control of electrical stimulation therapy
US11172864B2 (en) 2013-11-15 2021-11-16 Closed Loop Medical Pty Ltd Monitoring brain neural potentials
US11179091B2 (en) 2016-06-24 2021-11-23 Saluda Medical Pty Ltd Neural stimulation for reduced artefact
US11191966B2 (en) 2016-04-05 2021-12-07 Saluda Medical Pty Ltd Feedback control of neuromodulation
US11241580B2 (en) 2018-06-01 2022-02-08 Boston Scientific Neuromodulation Corporation Artifact reduction in a sensed neural response
US20220054843A1 (en) * 2013-02-22 2022-02-24 Boston Scientific Neuromodulation Corporation Neurostimulation system and method for automatically adjusting stimulation and reducing energy requirements using evoked action potential
US11259733B2 (en) 2019-03-29 2022-03-01 Boston Scientific Neuromodulation Corporation Neural sensing in an implantable stimulator device during the provision of active stimulation
US11504526B2 (en) 2019-05-30 2022-11-22 Boston Scientific Neuromodulation Corporation Methods and systems for discrete measurement of electrical characteristics
US11547855B2 (en) 2019-10-25 2023-01-10 Medtronic, Inc. ECAP sensing for high frequency neurostimulation
US11612751B2 (en) 2017-08-11 2023-03-28 Boston Scientific Neuromodulation Corporation Stimulation configuration variation to control evoked temporal patterns
US11623095B2 (en) 2019-06-20 2023-04-11 Boston Scientific Neuromodulation Corporation Methods and systems for interleaving waveforms for electrical stimulation and measurement
US11633138B2 (en) 2019-03-29 2023-04-25 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device in the presence of stimulation artifacts
US11707626B2 (en) 2020-09-02 2023-07-25 Medtronic, Inc. Analyzing ECAP signals
US11857793B2 (en) 2020-06-10 2024-01-02 Medtronic, Inc. Managing storage of sensed information
US11896828B2 (en) 2020-10-30 2024-02-13 Medtronic, Inc. Implantable lead location using ECAP
US11931579B2 (en) 2023-02-20 2024-03-19 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015143509A1 (en) 2014-03-28 2015-10-01 Saluda Medical Pty Ltd Assessing neural state from action potentials
EP3180072B1 (en) 2014-08-15 2018-11-28 Axonics Modulation Technologies Inc. Electromyographic lead positioning and stimulation titration in a nerve stimulation system for treatment of overactive bladder
EP3180073B1 (en) 2014-08-15 2020-03-11 Axonics Modulation Technologies, Inc. System for neurostimulation electrode configurations based on neural localization
WO2016025915A1 (en) 2014-08-15 2016-02-18 Axonics Modulation Technologies, Inc. Integrated electromyographic clinician programmer for use with an implantable neurostimulator
US10589089B2 (en) 2017-10-25 2020-03-17 Epineuron Technologies Inc. Systems and methods for delivering neuroregenerative therapy
AU2018354250A1 (en) 2017-10-25 2020-06-11 Epineuron Technologies Inc. Systems and methods for delivering neuroregenerative therapy
JP2022505633A (en) * 2018-10-23 2022-01-14 サルーダ・メディカル・ピーティーワイ・リミテッド Minimize artifacts in neurostimulation therapy
WO2020087123A1 (en) * 2018-10-30 2020-05-07 Saluda Medical Pty Ltd Automated neural conduction velocity estimation
US11439829B2 (en) 2019-05-24 2022-09-13 Axonics, Inc. Clinician programmer methods and systems for maintaining target operating temperatures
WO2020242900A1 (en) 2019-05-24 2020-12-03 Axonics Modulation Technologies, Inc. Trainer device for a neurostimulator programmer and associated methods of use with a neurostimulation system
EP3986535A1 (en) * 2019-06-19 2022-04-27 Galvani Bioelectronics Limited System and method for monitoring response to neuromodulation
US11364381B2 (en) 2019-10-01 2022-06-21 Epineuron Technologies Inc. Methods for delivering neuroregenerative therapy and reducing post-operative and chronic pain
AU2021209435A1 (en) * 2020-01-23 2022-08-25 Saluda Medical Pty Ltd Neuromodulation of primary and/or postsynaptic neurons
EP4153055A1 (en) * 2020-05-18 2023-03-29 Saluda Medical Pty Ltd Neural recording with stimulus crosstalk compensation

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3817254A (en) * 1972-05-08 1974-06-18 Medtronic Inc Transcutaneous stimulator and stimulation method
US5215100A (en) * 1991-04-29 1993-06-01 Occupational Preventive Diagnostic, Inc. Nerve condition monitoring system and electrode supporting structure
US20030045909A1 (en) * 2001-08-31 2003-03-06 Biocontrol Medical Ltd. Selective nerve fiber stimulation for treating heart conditions
US20040254494A1 (en) * 2003-06-11 2004-12-16 Spokoyny Eleonora S. Method and appartaus for use in nerve conduction studies
US20050010265A1 (en) * 2003-04-02 2005-01-13 Neurostream Technologies Inc. Fully implantable nerve signal sensing and stimulation device and method for treating foot drop and other neurological disorders
US20050065427A1 (en) * 2003-09-12 2005-03-24 Magill Peter James Methods of neural centre location and electrode placement in the central nervous system
US20060020291A1 (en) * 2004-03-09 2006-01-26 Gozani Shai N Apparatus and method for performing nerve conduction studies with multiple neuromuscular electrodes
US7450992B1 (en) * 2005-08-18 2008-11-11 Advanced Neuromodulation Systems, Inc. Method for controlling or regulating therapeutic nerve stimulation using electrical feedback
US20080300655A1 (en) * 2007-05-31 2008-12-04 Pacesetter, Inc. Techniques to monitor and trend nerve damage and recovery
US20110021943A1 (en) * 2008-01-16 2011-01-27 Cambridge Enterprise Limited Neural interface

Family Cites Families (247)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3736434A (en) 1971-06-07 1973-05-29 Westinghouse Air Brake Co Fail-safe electronic comparator circuit
US3898472A (en) 1973-10-23 1975-08-05 Fairchild Camera Instr Co Occupancy detector apparatus for automotive safety system
US4158196A (en) * 1977-04-11 1979-06-12 Crawford George E Jr Man-machine interface system
FR2419720A1 (en) 1978-03-14 1979-10-12 Cardiofrance Co IMPLANTABLE HEART STIMULATOR WITH THERAPEUTIC AND DIAGNOSTIC FUNCTIONS
US4474186A (en) 1979-07-17 1984-10-02 Georgetown University Computerized electro-oculographic (CEOG) system with feedback control of stimuli
US4807643A (en) 1982-08-16 1989-02-28 University Of Iowa Research Foundation Digital electroneurometer
US4628934A (en) 1984-08-07 1986-12-16 Cordis Corporation Method and means of electrode selection for pacemaker with multielectrode leads
CA1279101C (en) 1985-10-10 1991-01-15 Christopher Van Den Honert Multichannel electrical stimulator with improved channel isolation
US4817628A (en) * 1985-10-18 1989-04-04 David L. Zealear System and method for evaluating neurological function controlling muscular movements
DE3831809A1 (en) 1988-09-19 1990-03-22 Funke Hermann DEVICE DETERMINED AT LEAST PARTLY IN THE LIVING BODY
US5143081A (en) 1990-07-27 1992-09-01 New York University Randomized double pulse stimulus and paired event analysis
US5172690A (en) 1990-10-26 1992-12-22 Telectronics Pacing Systems, Inc. Automatic stimulus artifact reduction for accurate analysis of the heart's stimulated response
US5156154A (en) 1991-03-08 1992-10-20 Telectronics Pacing Systems, Inc. Monitoring the hemodynamic state of a patient from measurements of myocardial contractility using doppler ultrasound techniques
US5184615A (en) 1991-03-08 1993-02-09 Telectronics Pacing Systems, Inc. Apparatus and method for detecting abnormal cardiac rhythms using evoked potential measurements in an arrhythmia control system
US5188106A (en) 1991-03-08 1993-02-23 Telectronics Pacing Systems, Inc. Method and apparatus for chronically monitoring the hemodynamic state of a patient using doppler ultrasound
US5139020A (en) 1991-03-08 1992-08-18 Telectronics Pacing Systems, Inc. Method and apparatus for controlling the hemodynamic state of a patient based on systolic time interval measurements detecting using doppler ultrasound techniques
DE69119242T3 (en) 1991-07-15 2000-07-20 Medtronic Inc MEDICAL STIMULATION DEVICE WITH AN OPERATIONAL AMPLIFIER OUTPUT CIRCUIT
US5324311A (en) 1992-09-04 1994-06-28 Siemens Pacesetter, Inc. Coaxial bipolar connector assembly for implantable medical device
US5497781A (en) * 1992-10-30 1996-03-12 Chen; Yunquan Recording biological signals using Hilbert transforms
CA2152049C (en) 1992-12-22 2004-03-23 Tony Mikeal Nygard Telemetry system and apparatus
GB9302335D0 (en) 1993-02-05 1993-03-24 Macdonald Alexander J R Electrotherapeutic apparatus
US5417719A (en) 1993-08-25 1995-05-23 Medtronic, Inc. Method of using a spinal cord stimulation lead
US5431693A (en) 1993-12-10 1995-07-11 Intermedics, Inc. Method of verifying capture of the heart by a pacemaker
US5476486A (en) 1994-03-04 1995-12-19 Telectronics Pacing Systems, Inc. Automatic atrial pacing pulse threshold determination utilizing an external programmer and a V-sense electrode
US5458623A (en) 1994-03-04 1995-10-17 Telectronics Pacing Systems, Inc. Automatic atrial pacing threshold determination utilizing an external programmer and a surface electrogram
JP2596372B2 (en) 1994-04-21 1997-04-02 日本電気株式会社 Evoked potential measurement device
AUPM883794A0 (en) 1994-10-17 1994-11-10 University Of Melbourne, The Multiple pulse stimulation
US5785651A (en) 1995-06-07 1998-07-28 Keravision, Inc. Distance measuring confocal microscope
US6463328B1 (en) 1996-02-02 2002-10-08 Michael Sasha John Adaptive brain stimulation method and system
US6066163A (en) 1996-02-02 2000-05-23 John; Michael Sasha Adaptive brain stimulation method and system
US5702429A (en) 1996-04-04 1997-12-30 Medtronic, Inc. Neural stimulation techniques with feedback
EP0892654B1 (en) 1996-04-04 2003-06-11 Medtronic, Inc. Apparatus for living tissue stimulation and recording techniques
FR2796562B1 (en) 1996-04-04 2005-06-24 Medtronic Inc TECHNIQUES FOR STIMULATING LIVING TISSUE AND RECORDING WITH LOCAL CONTROL OF ACTIVE SITES
US6493576B1 (en) 1996-06-17 2002-12-10 Erich Jaeger Gmbh Method and apparatus for measuring stimulus-evoked potentials of the brain
US6157861A (en) 1996-06-20 2000-12-05 Advanced Bionics Corporation Self-adjusting cochlear implant system and method for fitting same
US6246912B1 (en) 1996-06-27 2001-06-12 Sherwood Services Ag Modulated high frequency tissue modification
US5792212A (en) 1997-03-07 1998-08-11 Medtronic, Inc. Nerve evoked potential measurement system using chaotic sequences for noise rejection
US5873898A (en) 1997-04-29 1999-02-23 Medtronic, Inc. Microprocessor capture detection circuit and method
US7628761B2 (en) * 1997-07-01 2009-12-08 Neurometrix, Inc. Apparatus and method for performing nerve conduction studies with localization of evoked responses
US5999848A (en) 1997-09-12 1999-12-07 Alfred E. Mann Foundation Daisy chainable sensors and stimulators for implantation in living tissue
US6522932B1 (en) 1998-02-10 2003-02-18 Advanced Bionics Corporation Implantable, expandable, multicontact electrodes and tools for use therewith
CA2223668C (en) 1998-02-23 2000-07-11 James Stanley Podger The strengthened quad antenna structure
US6421566B1 (en) 1998-04-30 2002-07-16 Medtronic, Inc. Selective dorsal column stimulation in SCS, using conditioning pulses
US6027456A (en) 1998-07-10 2000-02-22 Advanced Neuromodulation Systems, Inc. Apparatus and method for positioning spinal cord stimulation leads
US7277758B2 (en) 1998-08-05 2007-10-02 Neurovista Corporation Methods and systems for predicting future symptomatology in a patient suffering from a neurological or psychiatric disorder
US7231254B2 (en) 1998-08-05 2007-06-12 Bioneuronics Corporation Closed-loop feedback-driven neuromodulation
US6212431B1 (en) 1998-09-08 2001-04-03 Advanced Bionics Corporation Power transfer circuit for implanted devices
US20060217782A1 (en) 1998-10-26 2006-09-28 Boveja Birinder R Method and system for cortical stimulation to provide adjunct (ADD-ON) therapy for stroke, tinnitus and other medical disorders using implantable and external components
US6253109B1 (en) 1998-11-05 2001-06-26 Medtronic Inc. System for optimized brain stimulation
US6114164A (en) 1998-12-07 2000-09-05 The Regents Of The University Of Michigan System and method for emulating an in vivo environment of a muscle tissue specimen
US6898582B2 (en) 1998-12-30 2005-05-24 Algodyne, Ltd. Method and apparatus for extracting low SNR transient signals from noise
EP2291005B1 (en) 1999-07-21 2016-09-07 MED-EL Elektromedizinische Geräte GmbH Multichannel cochlea implant having neural telemetry reaction
US6381496B1 (en) 1999-10-01 2002-04-30 Advanced Bionics Corporation Parameter context switching for an implanted device
US6473649B1 (en) 1999-12-22 2002-10-29 Cardiac Pacemakers, Inc. Rate management during automatic capture verification
US20020055688A1 (en) 2000-05-18 2002-05-09 Jefferson Jacob Katims Nervous tissue stimulation device and method
AU2001268473A1 (en) 2000-06-20 2002-01-02 Advanced Bionics Corporation Apparatus for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US7305268B2 (en) 2000-07-13 2007-12-04 Northstar Neurscience, Inc. Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US7831305B2 (en) 2001-10-15 2010-11-09 Advanced Neuromodulation Systems, Inc. Neural stimulation system and method responsive to collateral neural activity
WO2002038031A2 (en) 2000-10-30 2002-05-16 Neuropace, Inc. System and method for determining stimulation parameters for the treatment of epileptic seizures
US7089059B1 (en) 2000-11-03 2006-08-08 Pless Benjamin D Predicting susceptibility to neurological dysfunction based on measured neural electrophysiology
US6594524B2 (en) 2000-12-12 2003-07-15 The Trustees Of The University Of Pennsylvania Adaptive method and apparatus for forecasting and controlling neurological disturbances under a multi-level control
US6600954B2 (en) 2001-01-25 2003-07-29 Biocontrol Medical Bcm Ltd. Method and apparatus for selective control of nerve fibers
US8060208B2 (en) 2001-02-20 2011-11-15 Case Western Reserve University Action potential conduction prevention
WO2002082982A1 (en) 2001-04-18 2002-10-24 Cochlear Limited Method and apparatus for measurement of evoked neural response
US6658293B2 (en) 2001-04-27 2003-12-02 Medtronic, Inc. Method and system for atrial capture detection based on far-field R-wave sensing
CN1287729C (en) * 2001-05-29 2006-12-06 生殖健康技术公司 System for detection and analysis of material uterine, material and fetal cardiac and fetal brain activity
US6936012B2 (en) 2001-06-18 2005-08-30 Neurometrix, Inc. Method and apparatus for identifying constituent signal components from a plurality of evoked physiological composite signals
US8571653B2 (en) 2001-08-31 2013-10-29 Bio Control Medical (B.C.M.) Ltd. Nerve stimulation techniques
US7778711B2 (en) 2001-08-31 2010-08-17 Bio Control Medical (B.C.M.) Ltd. Reduction of heart rate variability by parasympathetic stimulation
IL145700A0 (en) 2001-09-30 2002-06-30 Younis Imad Electrode system for neural applications
DE10151020A1 (en) 2001-10-16 2003-04-30 Infineon Technologies Ag Circuit arrangement, sensor array and biosensor array
US7493157B2 (en) 2001-10-24 2009-02-17 Gozani Shai N Devices and methods for the non-invasive detection of spontaneous myoelectrical activity
US7286876B2 (en) 2001-10-26 2007-10-23 Cardiac Pacemakers, Inc. Template-based capture verification for multi-site pacing
US7286878B2 (en) 2001-11-09 2007-10-23 Medtronic, Inc. Multiplexed electrode array extension
US6993384B2 (en) 2001-12-04 2006-01-31 Advanced Bionics Corporation Apparatus and method for determining the relative position and orientation of neurostimulation leads
US7881805B2 (en) 2002-02-04 2011-02-01 Boston Scientific Neuromodulation Corporation Method for optimizing search for spinal cord stimulation parameter settings
US7317948B1 (en) 2002-02-12 2008-01-08 Boston Scientific Scimed, Inc. Neural stimulation system providing auto adjustment of stimulus output as a function of sensed impedance
US6931281B2 (en) * 2002-04-12 2005-08-16 Pacesetter, Inc. Method and apparatus for monitoring myocardial conduction velocity for diagnostics of therapy optimization
AU2003231354A1 (en) 2002-06-05 2003-12-22 Nervetrack Ltd. Method and apparatus for measuring nerve signals in nerve fibers
US7203548B2 (en) 2002-06-20 2007-04-10 Advanced Bionics Corporation Cavernous nerve stimulation via unidirectional propagation of action potentials
WO2004007018A1 (en) 2002-07-17 2004-01-22 Remidi (Uk) Limited Apparatus for the application of electrical pulses to the human body
AU2002951218A0 (en) 2002-09-04 2002-09-19 Cochlear Limited Method and apparatus for measurement of evoked neural response
US7328068B2 (en) 2003-03-31 2008-02-05 Medtronic, Inc. Method, system and device for treating disorders of the pelvic floor by means of electrical stimulation of the pudendal and associated nerves, and the optional delivery of drugs in association therewith
US7415307B2 (en) * 2002-10-31 2008-08-19 Medtronic, Inc. Ischemia detection based on cardiac conduction time
US20040122482A1 (en) 2002-12-20 2004-06-24 James Tung Nerve proximity method and device
US7171261B1 (en) 2002-12-20 2007-01-30 Advanced Bionics Corporation Forward masking method for estimating neural response
DE10318071A1 (en) 2003-04-17 2004-11-25 Forschungszentrum Jülich GmbH Device for desynchronizing neuronal brain activity
US7930037B2 (en) 2003-09-30 2011-04-19 Medtronic, Inc. Field steerable electrical stimulation paddle, lead system, and medical device incorporating the same
US8489196B2 (en) 2003-10-03 2013-07-16 Medtronic, Inc. System, apparatus and method for interacting with a targeted tissue of a patient
US7236834B2 (en) 2003-12-19 2007-06-26 Medtronic, Inc. Electrical lead body including an in-line hermetic electronic package and implantable medical device using the same
US7412287B2 (en) 2003-12-22 2008-08-12 Cardiac Pacemakers, Inc. Automatic sensing vector selection for morphology-based capture verification
US7295881B2 (en) 2003-12-29 2007-11-13 Biocontrol Medical Ltd. Nerve-branch-specific action-potential activation, inhibition, and monitoring
US20050203600A1 (en) 2004-03-12 2005-09-15 Scimed Life Systems, Inc. Collapsible/expandable tubular electrode leads
GB0409806D0 (en) 2004-04-30 2004-06-09 Univ Brunel Nerve blocking method and system
US8224459B1 (en) 2004-04-30 2012-07-17 Boston Scientific Neuromodulation Corporation Insertion tool for paddle-style electrode
US7369900B2 (en) 2004-05-08 2008-05-06 Bojan Zdravkovic Neural bridge devices and methods for restoring and modulating neural activity
US8078284B2 (en) 2004-05-25 2011-12-13 Second Sight Medical Products, Inc. Retinal prosthesis with a new configuration
US7993906B2 (en) 2004-05-28 2011-08-09 The Board Of Trustees Of The Leland Stanford Junior University Closed-loop electrical stimulation system for cell cultures
US7618098B2 (en) * 2004-08-12 2009-11-17 Frear Joseph K Cutting tool retention apparatuses
US7613520B2 (en) 2004-10-21 2009-11-03 Advanced Neuromodulation Systems, Inc. Spinal cord stimulation to treat auditory dysfunction
US8332047B2 (en) 2004-11-18 2012-12-11 Cardiac Pacemakers, Inc. System and method for closed-loop neural stimulation
US10537741B2 (en) 2004-12-03 2020-01-21 Boston Scientific Neuromodulation Corporation System and method for choosing electrodes in an implanted stimulator device
US8103352B2 (en) 2004-12-03 2012-01-24 Second Sight Medical Products, Inc. Mimicking neural coding in retinal ganglion cells with short pulse electrical stimulation
US20110307030A1 (en) 2005-03-24 2011-12-15 Michael Sasha John Methods for Evaluating and Selecting Electrode Sites of a Brain Network to Treat Brain Disorders
WO2006091636A2 (en) 2005-02-23 2006-08-31 Digital Intelligence, L.L.C. Signal decomposition and reconstruction
US20070185409A1 (en) 2005-04-20 2007-08-09 Jianping Wu Method and system for determining an operable stimulus intensity for nerve conduction testing
US20060264752A1 (en) 2005-04-27 2006-11-23 The Regents Of The University Of California Electroporation controlled with real time imaging
US7818052B2 (en) 2005-06-01 2010-10-19 Advanced Bionics, Llc Methods and systems for automatically identifying whether a neural recording signal includes a neural response signal
US8639329B2 (en) 2005-08-30 2014-01-28 Georgia Tech Research Corporation Circuits and methods for artifact elimination
US20070073354A1 (en) 2005-09-26 2007-03-29 Knudson Mark B Neural blocking therapy
US9168383B2 (en) 2005-10-14 2015-10-27 Pacesetter, Inc. Leadless cardiac pacemaker with conducted communication
US7957796B2 (en) 2005-10-28 2011-06-07 Cyberonics, Inc. Using physiological sensor data with an implantable medical device
US7853322B2 (en) 2005-12-02 2010-12-14 Medtronic, Inc. Closed-loop therapy adjustment
US20070287931A1 (en) 2006-02-14 2007-12-13 Dilorenzo Daniel J Methods and systems for administering an appropriate pharmacological treatment to a patient for managing epilepsy and other neurological disorders
US8190251B2 (en) 2006-03-24 2012-05-29 Medtronic, Inc. Method and apparatus for the treatment of movement disorders
US7835804B2 (en) 2006-04-18 2010-11-16 Advanced Bionics, Llc Removing artifact in evoked compound action potential recordings in neural stimulators
DE102006018851A1 (en) 2006-04-22 2007-10-25 Biotronik Crm Patent Ag Active medical device implant with at least two diagnostic and / or therapeutic functions
US7792584B2 (en) 2006-04-25 2010-09-07 Medtronic, Inc. System and method for characterization of atrial wall using digital signal processing
US8099172B2 (en) 2006-04-28 2012-01-17 Advanced Neuromodulation Systems, Inc. Spinal cord stimulation paddle lead and method of making the same
US9084901B2 (en) 2006-04-28 2015-07-21 Medtronic, Inc. Cranial implant
US7515968B2 (en) 2006-04-28 2009-04-07 Medtronic, Inc. Assembly method for spinal cord stimulation lead
US20080051647A1 (en) 2006-05-11 2008-02-28 Changwang Wu Non-invasive acquisition of large nerve action potentials (NAPs) with closely spaced surface electrodes and reduced stimulus artifacts
US20070282217A1 (en) 2006-06-01 2007-12-06 Mcginnis William J Methods & systems for intraoperatively monitoring nerve & muscle frequency latency and amplitude
WO2008004204A1 (en) 2006-07-06 2008-01-10 University Of Limerick An electrical stimulation device for nerves or muscles
US8532741B2 (en) 2006-09-08 2013-09-10 Medtronic, Inc. Method and apparatus to optimize electrode placement for neurological stimulation
US9162051B2 (en) 2006-09-21 2015-10-20 Neuropace, Inc. Treatment of language, behavior and social disorders
US8588927B2 (en) 2006-10-06 2013-11-19 Neurostream Technologies General Partnership Implantable pulse generator
US7881803B2 (en) 2006-10-18 2011-02-01 Boston Scientific Neuromodulation Corporation Multi-electrode implantable stimulator device with a single current path decoupling capacitor
US8280514B2 (en) 2006-10-31 2012-10-02 Advanced Neuromodulation Systems, Inc. Identifying areas of the brain by examining the neuronal signals
US8691037B2 (en) * 2006-12-14 2014-04-08 The Boeing Company Method for minimizing fiber distortion during fabrication of one-piece composite barrel section
US8160719B2 (en) 2006-12-19 2012-04-17 Greatbatch Ltd. Braided electrical lead
US8057390B2 (en) 2007-01-26 2011-11-15 The Regents Of The University Of Michigan High-resolution mapping of bio-electric fields
US8224453B2 (en) 2007-03-15 2012-07-17 Advanced Neuromodulation Systems, Inc. Spinal cord stimulation to treat pain
US8406877B2 (en) 2007-03-19 2013-03-26 Cardiac Pacemakers, Inc. Selective nerve stimulation with optionally closed-loop capabilities
US9042978B2 (en) 2007-05-11 2015-05-26 Neurometrix, Inc. Method and apparatus for quantitative nerve localization
US7742810B2 (en) 2007-05-23 2010-06-22 Boston Scientific Neuromodulation Corporation Short duration pre-pulsing to reduce stimulation-evoked side-effects
KR100897528B1 (en) 2007-06-22 2009-05-15 주식회사 사이버메드 Method of determining the position of a deep brain stimulation electrode
US8649858B2 (en) 2007-06-25 2014-02-11 Boston Scientific Neuromodulation Corporation Architectures for an implantable medical device system
US20090008269A1 (en) * 2007-07-06 2009-01-08 Christopher William Heiss Electrocoagulation reactor and water treatment system and method
US8880180B2 (en) 2007-07-13 2014-11-04 Cochlear Limited Assessing neural survival
US8063770B2 (en) 2007-08-01 2011-11-22 Peter Costantino System and method for facial nerve monitoring
WO2009026625A1 (en) 2007-08-29 2009-03-05 Cochlear Limited Method and device for intracochlea impedance measurement
WO2009042172A2 (en) * 2007-09-26 2009-04-02 Medtronic, Inc. Frequency selective monitoring of physiological signals
CA2702326C (en) 2007-10-10 2018-09-18 Neurotech S.A. Neurostimulator and method for regulating the same
DE102007051847B4 (en) 2007-10-30 2014-07-17 Forschungszentrum Jülich GmbH Device for stimulating neurons with a pathologically synchronous and oscillatory neuronal activity
US8494645B2 (en) 2007-11-14 2013-07-23 Med-El Elektromedizinische Geraete Gmbh Cochlear implant stimulation artifacts
US20090157155A1 (en) 2007-12-18 2009-06-18 Advanced Bionics Corporation Graphical display of environmental measurements for implantable therapies
WO2009119236A1 (en) * 2008-03-26 2009-10-01 テルモ株式会社 Treatment apparatus
GR1006568B (en) * 2008-04-22 2009-10-13 Αλεξανδρος Μπερης Method and system for recording of, and aiding in, the regeneration of a peripheral nerve.
US9492655B2 (en) 2008-04-25 2016-11-15 Boston Scientific Neuromodulation Corporation Stimulation system with percutaneously deliverable paddle lead and methods of making and using
US20090287277A1 (en) 2008-05-19 2009-11-19 Otologics, Llc Implantable neurostimulation electrode interface
WO2009146427A1 (en) 2008-05-29 2009-12-03 Neurometrix, Inc. Method and apparatus for quantitative nerve localization
US20090306491A1 (en) 2008-05-30 2009-12-10 Marcus Haggers Implantable neural prosthetic device and methods of use
US8200340B2 (en) 2008-07-11 2012-06-12 Medtronic, Inc. Guided programming for posture-state responsive therapy
US8437861B2 (en) 2008-07-11 2013-05-07 Medtronic, Inc. Posture state redefinition based on posture data and therapy adjustments
WO2010013170A1 (en) 2008-07-29 2010-02-04 Koninklijke Philips Electronics N.V. System and method for communicating information between implantable devices
US7941713B2 (en) 2008-08-27 2011-05-10 Taiwan Semiconductor Manufacturing Company, Ltd. Programmable self-test for random access memories
US20100069835A1 (en) 2008-09-17 2010-03-18 National Ict Australia Limited Knitted catheter
WO2010032132A1 (en) * 2008-09-17 2010-03-25 Med-El Elektromedizinische Geraete Gmbh Stimulus artifact removal for neuronal recordings
US8428733B2 (en) 2008-10-16 2013-04-23 Medtronic, Inc. Stimulation electrode selection
JP2012507112A (en) 2008-10-27 2012-03-22 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ Method for driving a gas discharge lamp
US9987493B2 (en) 2008-10-28 2018-06-05 Medtronic, Inc. Medical devices and methods for delivery of current-based electrical stimulation therapy
US8560060B2 (en) 2008-10-31 2013-10-15 Medtronic, Inc. Isolation of sensing and stimulation circuitry
WO2010051382A1 (en) 2008-10-31 2010-05-06 Medtronic, Inc. Mood circuit monitoring to control therapy delivery
US8301263B2 (en) 2008-10-31 2012-10-30 Medtronic, Inc. Therapy module crosstalk mitigation
US8255057B2 (en) 2009-01-29 2012-08-28 Nevro Corporation Systems and methods for producing asynchronous neural responses to treat pain and/or other patient conditions
EP2346567A4 (en) 2008-11-13 2012-04-25 Proteus Biomedical Inc Multiplexed multi-electrode neurostimulation devices
US8504160B2 (en) 2008-11-14 2013-08-06 Boston Scientific Neuromodulation Corporation System and method for modulating action potential propagation during spinal cord stimulation
US9463321B2 (en) 2008-11-14 2016-10-11 Boston Scientific Neuromodulation Corporation System and method for adjusting automatic pulse parameters to selectively activate nerve fibers
AU2009322898B2 (en) 2008-12-05 2015-03-12 Spr Therapeutics, Inc. Systems and methods to place one or more leads in tissue to electrically stimulate nerves of passage to treat pain
US9084551B2 (en) 2008-12-08 2015-07-21 Medtronic Xomed, Inc. Method and system for monitoring a nerve
US20100179626A1 (en) 2009-01-09 2010-07-15 Medtronic, Inc. System and method for implanting a paddle lead
US20100222858A1 (en) 2009-02-27 2010-09-02 Meloy T Stuart Method and system for neurally augmenting sexual function during sexual activity
JP5582619B2 (en) 2009-03-13 2014-09-03 バクサノ,インク. Flexible nerve position determination device
US8504154B2 (en) 2009-03-30 2013-08-06 Medtronic, Inc. Physiological signal amplifier with voltage protection and fast signal recovery
WO2010117381A1 (en) 2009-04-08 2010-10-14 National Ict Australia Limited (Nicta) Stitched components of an active implantable medical device
EP2416841B1 (en) 2009-04-08 2015-09-23 Saluda Medical Pty Limited Electronics package for an active implantable medical device
WO2010117383A1 (en) 2009-04-08 2010-10-14 National Ict Australia Limited (Nicta) Bonded hermetic feed through for an active implantable medical device
ES2624748T3 (en) 2009-04-22 2017-07-17 Nevro Corporation Selective high frequency modulation of the spinal cord for pain inhibition with reduced side effects, and associated systems and methods
US8744588B2 (en) 2009-05-07 2014-06-03 Hani Midani Method and system for connecting an impaired nervous system to a muscle or a group of muscles based on template matching and intelligent end points
WO2010138915A1 (en) 2009-05-29 2010-12-02 University Of Washington Vestibular implant
US20100331926A1 (en) 2009-06-24 2010-12-30 Boston Scientific Neuromodulation Corporation Reversing recruitment order by anode intensification
WO2011011327A1 (en) 2009-07-20 2011-01-27 National Ict Australia Limited Neuro-stimulation
US20110028859A1 (en) 2009-07-31 2011-02-03 Neuropace, Inc. Methods, Systems and Devices for Monitoring a Target in a Neural System and Facilitating or Controlling a Cell Therapy
US20110093042A1 (en) 2009-10-21 2011-04-21 Medtronic, Inc. Stimulation with utilization of case electrode
US11045221B2 (en) 2009-10-30 2021-06-29 Medtronic, Inc. Steerable percutaneous paddle stimulation lead
WO2011066477A1 (en) 2009-11-26 2011-06-03 National Ict Australia Limited (Nicta) Methods for forming feedthroughs for hermetically sealed housings using powder injection molding
US8886323B2 (en) 2010-02-05 2014-11-11 Medtronic, Inc. Electrical brain stimulation in gamma band
US9888864B2 (en) 2010-03-12 2018-02-13 Inspire Medical Systems, Inc. Method and system for identifying a location for nerve stimulation
CN102905757B (en) 2010-03-22 2016-02-17 纽约城市大学研究基金会 Electric charge strengthens stimulation system
US9814885B2 (en) 2010-04-27 2017-11-14 Medtronic, Inc. Stimulation electrode selection
US8406868B2 (en) 2010-04-29 2013-03-26 Medtronic, Inc. Therapy using perturbation and effect of physiological systems
JP5464072B2 (en) 2010-06-16 2014-04-09 ソニー株式会社 Muscle activity diagnosis apparatus and method, and program
US9089267B2 (en) 2010-06-18 2015-07-28 Cardiac Pacemakers, Inc. Methods and apparatus for adjusting neurostimulation intensity using evoked responses
CN103096850B (en) 2010-07-29 2016-08-03 Med-El电气医疗器械有限公司 Measure by implanting the electricity induction brain stem response of prosthese
JP2013536044A (en) 2010-08-23 2013-09-19 ラファエル デベロップメント コーポレイション リミテッド Defibrillation pulse delivery and respiratory cycle synchronization
US20130289683A1 (en) 2010-08-31 2013-10-31 Saluda Medical Pty. Ltd. Distributed implant systems
EP2443995A3 (en) 2010-10-21 2013-02-27 Syncrophi Systems Ltd. An ECG apparatus with lead-off detection
US9420960B2 (en) 2010-10-21 2016-08-23 Medtronic, Inc. Stereo data representation of biomedical signals along a lead
WO2012056882A1 (en) 2010-10-27 2012-05-03 株式会社村田製作所 Detection circuit
KR101241943B1 (en) 2011-03-29 2013-03-11 한국과학기술연구원 Artificial Nerve Networking System and Method for Functional Recovery of Damaged Nerve
US10448889B2 (en) 2011-04-29 2019-10-22 Medtronic, Inc. Determining nerve location relative to electrodes
US9789307B2 (en) 2011-04-29 2017-10-17 Medtronic, Inc. Dual prophylactic and abortive electrical stimulation
US9872990B2 (en) 2011-05-13 2018-01-23 Saluda Medical Pty Limited Method and apparatus for application of a neural stimulus
US10568559B2 (en) 2011-05-13 2020-02-25 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
CA2835448C (en) 2011-05-13 2020-08-18 Saluda Medical Pty Limited Method and apparatus for controlling a neural stimulus - e
US20140236042A1 (en) 2011-05-13 2014-08-21 Saluda Medical Pty. Ltd. Method and apparatus for measurement of neural response
WO2012155189A1 (en) 2011-05-13 2012-11-22 National Ict Australia Ltd Method and apparatus for estimating neural recruitment - f
EP2707095B1 (en) 2011-05-13 2018-09-26 Saluda Medical Pty Limited Apparatus for application of a neural stimulus
JP6096759B2 (en) 2011-05-13 2017-03-15 サルーダ・メディカル・ピーティーワイ・リミテッド Method and apparatus for measurement of neural response
US20130172774A1 (en) 2011-07-01 2013-07-04 Neuropace, Inc. Systems and Methods for Assessing the Effectiveness of a Therapy Including a Drug Regimen Using an Implantable Medical Device
US9888861B2 (en) 2011-08-25 2018-02-13 Medtronic, Inc. Method and apparatus for detecting a biomarker in the presence of electrical stimulation
US8483836B2 (en) 2011-09-07 2013-07-09 Greatbatch Ltd. Automated search to identify a location for electrical stimulation to treat a patient
EP2771062B1 (en) 2011-10-24 2017-02-01 Purdue Research Foundation Apparatus for closed-loop control of nerve activation
US20140288577A1 (en) 2011-11-24 2014-09-25 Saluda Medical Pty Limited Electrode Assembly for an Active Implantable Medical Device
WO2013116161A1 (en) 2012-01-30 2013-08-08 The Regents Of The University Of California System and methods for closed-loop cochlear implant
FR2988996B1 (en) 2012-04-06 2015-01-23 Uromems METHOD AND DEVICE FOR CONTROLLING AN IMPLANTABLE DEVICE
EP2841152A1 (en) 2012-04-27 2015-03-04 Boston Scientific Neuromodulation Corporation Timing channel circuitry for creating pulses in an implantable stimulator device
WO2013188871A1 (en) 2012-06-15 2013-12-19 Case Western Reserve University Implantable cuff and method for functional electrical stimulation and monitoring
TWI498101B (en) 2012-08-30 2015-09-01 Univ Nat Chiao Tung Method of analyzing nerve fiber distribution and measuring standardized induced compound motion electric potential
DE102012218057A1 (en) 2012-10-02 2014-04-03 Forschungszentrum Jülich GmbH DEVICE AND METHOD FOR INVESTIGATING A NARROW INTERACTION BETWEEN DIFFERENT BRAIN SIZES
EP2908905B1 (en) 2012-11-06 2020-09-23 Saluda Medical Pty Limited System for controlling electrical conditions of tissue
AU2013344311B2 (en) 2012-11-06 2017-11-30 Saluda Medical Pty Ltd Method and system for controlling electrical conditions of tissue
US9533148B2 (en) 2013-02-22 2017-01-03 Boston Scientific Neuromodulation Corporation Neurostimulation system and method for automatically adjusting stimulation and reducing energy requirements using evoked action potential
US20140276925A1 (en) 2013-03-12 2014-09-18 Spinal Modulation, Inc. Methods and systems for use in guiding implantation of a neuromodulation lead
US10105091B2 (en) 2013-03-12 2018-10-23 The Cleveland Clinic Foundation Methods of using nerve evoked potentials to monitor a surgical procedure
US9446235B2 (en) 2013-03-14 2016-09-20 Medtronic, Inc. Low frequency electrical stimulation therapy for pelvic floor disorders
US9610444B2 (en) 2013-03-15 2017-04-04 Pacesetter, Inc. Erythropoeitin production by electrical stimulation
US11083402B2 (en) 2013-06-04 2021-08-10 Medtronic, Inc. Patient state determination based on one or more spectral characteristics of a bioelectrical brain signal
CN105848575B (en) 2013-11-15 2019-11-19 萨鲁达医疗有限公司 Monitor cerebral nerve current potential
AU2014353891B2 (en) 2013-11-22 2020-02-06 Saluda Medical Pty Ltd Method and device for detecting a neural response in a neural measurement
US10016606B2 (en) 2014-01-17 2018-07-10 Medtronic, Inc. Movement disorder symptom control
WO2015143509A1 (en) 2014-03-28 2015-10-01 Saluda Medical Pty Ltd Assessing neural state from action potentials
JP6674385B2 (en) 2014-05-05 2020-04-01 サルーダ・メディカル・ピーティーワイ・リミテッド Improve neurometry
US9302112B2 (en) 2014-06-13 2016-04-05 Pacesetter, Inc. Method and system for non-linear feedback control of spinal cord stimulation
AU2015292272B2 (en) 2014-07-25 2020-11-12 Saluda Medical Pty Ltd Neural stimulation dosing
EP3215216A4 (en) 2014-11-17 2018-08-22 Saluda Medical Pty Ltd Method and device for detecting a neural response in neural measurements
US20160166164A1 (en) 2014-12-11 2016-06-16 Saluda Medical Pty Limited Method and Apparatus for Detecting Neural Injury
WO2016090436A1 (en) 2014-12-11 2016-06-16 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
WO2016090420A1 (en) 2014-12-11 2016-06-16 Saluda Medical Pty Ltd Implantable electrode positioning
EP3229893B1 (en) 2015-01-19 2020-06-17 Saluda Medical Pty Ltd Method and device for neural implant communication
EP3280487B1 (en) 2015-04-09 2021-09-15 Saluda Medical Pty Limited Electrode to nerve distance estimation
CA2983333C (en) 2015-05-31 2023-09-19 Saluda Medical Pty Ltd Brain neurostimulator electrode fitting
EP3302258A4 (en) 2015-05-31 2018-11-21 Saluda Medical Pty Limited Monitoring brain neural activity
EP3261533A4 (en) 2015-06-01 2018-10-31 Saluda Medical Pty Ltd Motor fibre neuromodulation
DK3439732T3 (en) 2016-04-05 2021-09-06 Saluda Medical Pty Ltd IMPROVED FEEDBACK CONTROL OF NEUROMODULATION
WO2017219096A1 (en) 2016-06-24 2017-12-28 Saluda Medical Pty Ltd Neural stimulation for reduced artefact

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3817254A (en) * 1972-05-08 1974-06-18 Medtronic Inc Transcutaneous stimulator and stimulation method
US5215100A (en) * 1991-04-29 1993-06-01 Occupational Preventive Diagnostic, Inc. Nerve condition monitoring system and electrode supporting structure
US20030045909A1 (en) * 2001-08-31 2003-03-06 Biocontrol Medical Ltd. Selective nerve fiber stimulation for treating heart conditions
US20050010265A1 (en) * 2003-04-02 2005-01-13 Neurostream Technologies Inc. Fully implantable nerve signal sensing and stimulation device and method for treating foot drop and other neurological disorders
US20040254494A1 (en) * 2003-06-11 2004-12-16 Spokoyny Eleonora S. Method and appartaus for use in nerve conduction studies
US20050065427A1 (en) * 2003-09-12 2005-03-24 Magill Peter James Methods of neural centre location and electrode placement in the central nervous system
US20060020291A1 (en) * 2004-03-09 2006-01-26 Gozani Shai N Apparatus and method for performing nerve conduction studies with multiple neuromuscular electrodes
US7450992B1 (en) * 2005-08-18 2008-11-11 Advanced Neuromodulation Systems, Inc. Method for controlling or regulating therapeutic nerve stimulation using electrical feedback
US20080300655A1 (en) * 2007-05-31 2008-12-04 Pacesetter, Inc. Techniques to monitor and trend nerve damage and recovery
US20110021943A1 (en) * 2008-01-16 2011-01-27 Cambridge Enterprise Limited Neural interface

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Orstavik et al. "Pathological C-fibres in patients with a chronic painful condition" Brain (2003), 126, 567-578 *

Cited By (74)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10940316B2 (en) 2010-06-18 2021-03-09 Cardiac Pacemakers, Inc. Methods and apparatus for adjusting neurostimulation intensity using evoked responses
US11577083B2 (en) 2010-06-18 2023-02-14 Cardiac Pacemakers, Inc. Methods and apparatus for adjusting neurostimulation intensity using evoked responses
US11464979B2 (en) 2011-05-13 2022-10-11 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US11491334B2 (en) 2011-05-13 2022-11-08 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US10588524B2 (en) 2011-05-13 2020-03-17 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US9974455B2 (en) 2011-05-13 2018-05-22 Saluda Medical Pty Ltd. Method and apparatus for estimating neural recruitment
US10568559B2 (en) 2011-05-13 2020-02-25 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US10278600B2 (en) 2011-05-13 2019-05-07 Saluda Medical Pty Ltd. Method and apparatus for measurement of neural response
US9381356B2 (en) 2011-05-13 2016-07-05 Saluda Medical Pty Ltd. Method and apparatus for controlling a neural stimulus
US11324427B2 (en) 2011-05-13 2022-05-10 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US11439828B2 (en) 2011-05-13 2022-09-13 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US9386934B2 (en) 2011-05-13 2016-07-12 Saluda Medical Pty Ltd. Method and apparatus for measurement of neural response
US11554265B2 (en) 2011-05-13 2023-01-17 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US9872990B2 (en) 2011-05-13 2018-01-23 Saluda Medical Pty Limited Method and apparatus for application of a neural stimulus
US11426587B2 (en) 2011-05-13 2022-08-30 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US9155892B2 (en) 2011-05-13 2015-10-13 Saluda Medical Pty Limited Method and apparatus for application of a neural stimulus
US11445958B2 (en) 2011-05-13 2022-09-20 Saluda Medical Pty Ltd Method and apparatus for estimating neural recruitment
US11420064B2 (en) 2011-05-13 2022-08-23 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US11413460B2 (en) 2011-05-13 2022-08-16 Saluda Medical Pty Ltd Method and apparatus for application of a neural stimulus
US11045129B2 (en) 2011-05-13 2021-06-29 Saluda Medical Pty Ltd. Method and apparatus for estimating neural recruitment
US11819332B2 (en) 2011-05-13 2023-11-21 Saluda Medical Pty Ltd Method and apparatus for measurement of neural response
US11389098B2 (en) 2012-11-06 2022-07-19 Saluda Medical Pty Ltd Method and system for controlling electrical conditions of tissue
US10206596B2 (en) 2012-11-06 2019-02-19 Saluda Medical Pty Ltd Method and system for controlling electrical conditions of tissue
US20220054843A1 (en) * 2013-02-22 2022-02-24 Boston Scientific Neuromodulation Corporation Neurostimulation system and method for automatically adjusting stimulation and reducing energy requirements using evoked action potential
US11172864B2 (en) 2013-11-15 2021-11-16 Closed Loop Medical Pty Ltd Monitoring brain neural potentials
US11337658B2 (en) 2013-11-22 2022-05-24 Saluda Medical Pty Ltd Method and device for detecting a neural response in a neural measurement
US11890113B2 (en) 2013-11-22 2024-02-06 Saluda Medical Pty Ltd Method and device for detecting a neural response in a neural measurement
US10426409B2 (en) 2013-11-22 2019-10-01 Saluda Medical Pty Ltd Method and device for detecting a neural response in a neural measurement
US11457849B2 (en) 2014-05-05 2022-10-04 Saluda Medical Pty Ltd Neural measurement
US10368762B2 (en) 2014-05-05 2019-08-06 Saluda Medical Pty Ltd. Neural measurement
US10632307B2 (en) 2014-07-25 2020-04-28 Saluda Medical Pty Ltd Neural stimulation dosing
US11167129B2 (en) 2014-07-25 2021-11-09 Saluda Medical Pty Ltd Neural stimulation dosing
US11006846B2 (en) 2014-11-17 2021-05-18 Saluda Medical Pty Ltd Method and device for detecting a neural response in neural measurements
US11464980B2 (en) 2014-12-11 2022-10-11 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
US11344729B1 (en) 2014-12-11 2022-05-31 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
US11219766B2 (en) 2014-12-11 2022-01-11 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
US10588698B2 (en) 2014-12-11 2020-03-17 Saluda Medical Pty Ltd Implantable electrode positioning
US10500399B2 (en) 2014-12-11 2019-12-10 Saluda Medical Pty Ltd Method and device for feedback control of neural stimulation
US10918872B2 (en) 2015-01-19 2021-02-16 Saluda Medical Pty Ltd Method and device for neural implant communication
AU2016245335B2 (en) * 2015-04-09 2020-11-19 Saluda Medical Pty Ltd Electrode to nerve distance estimation
US10894158B2 (en) 2015-04-09 2021-01-19 Saluda Medical Pty Ltd Electrode to nerve distance estimation
WO2016161484A3 (en) * 2015-04-09 2016-12-22 Saluda Medical Pty Ltd Electrode to nerve distance estimation
US11110270B2 (en) 2015-05-31 2021-09-07 Closed Loop Medical Pty Ltd Brain neurostimulator electrode fitting
US10849525B2 (en) 2015-05-31 2020-12-01 Saluda Medical Pty Ltd Monitoring brain neural activity
US11006857B2 (en) 2015-06-01 2021-05-18 Closed Loop Medical Pty Ltd Motor fibre neuromodulation
US11191966B2 (en) 2016-04-05 2021-12-07 Saluda Medical Pty Ltd Feedback control of neuromodulation
US10406368B2 (en) 2016-04-19 2019-09-10 Boston Scientific Neuromodulation Corporation Pulse generator system for promoting desynchronized firing of recruited neural populations
US11623097B2 (en) 2016-04-19 2023-04-11 Boston Scientific Neuromodulation Corporation Pulse generator system for promoting desynchronized firing of recruited neural populations
US10960211B2 (en) 2016-04-19 2021-03-30 Boston Scientific Neuromodulation Corporation Pulse generator system for promoting desynchronized firing of recruited neural populations
US11826156B2 (en) 2016-06-24 2023-11-28 Saluda Medical Pty Ltd Neural stimulation for reduced artefact
US11179091B2 (en) 2016-06-24 2021-11-23 Saluda Medical Pty Ltd Neural stimulation for reduced artefact
US11612751B2 (en) 2017-08-11 2023-03-28 Boston Scientific Neuromodulation Corporation Stimulation configuration variation to control evoked temporal patterns
US11129987B2 (en) 2017-10-04 2021-09-28 Boston Scientific Neuromodulation Corporation Adjustment of stimulation in a stimulator using detected evoked compound action potentials
US10926092B2 (en) 2018-01-08 2021-02-23 Boston Scientific Neuromodulation Corporation Automatic adjustment of sub-perception therapy in an implantable stimulator using detected compound action potentials
US11786737B2 (en) 2018-01-08 2023-10-17 Boston Scientific Neuromodulation Corporation Automatic adjustment of sub-perception therapy in an implantable stimulator using detected compound action potentials
US10974042B2 (en) 2018-03-26 2021-04-13 Boston Scientific Neuromodulation Corporation System and methods for heart rate and electrocardiogram extraction from a spinal cord stimulation system
US11571566B2 (en) 2018-03-26 2023-02-07 Boston Scientific Neuromodulation Corporation System and methods for heart rate and electrocardiogram extraction from a spinal cord stimulation system
US11850418B2 (en) 2018-03-26 2023-12-26 Boston Scientific Neuromodulation Corporation System and methods for heart rate and electrocardiogram extraction from a spinal cord stimulation system
US11040202B2 (en) 2018-03-30 2021-06-22 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device
US11607549B2 (en) 2018-03-30 2023-03-21 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device
US11241580B2 (en) 2018-06-01 2022-02-08 Boston Scientific Neuromodulation Corporation Artifact reduction in a sensed neural response
US11129989B2 (en) 2018-06-21 2021-09-28 Medtronic, Inc. ECAP based control of electrical stimulation therapy
US11129991B2 (en) 2018-06-21 2021-09-28 Medtronic, Inc. ECAP based control of electrical stimulation therapy
US11633138B2 (en) 2019-03-29 2023-04-25 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device in the presence of stimulation artifacts
US11259733B2 (en) 2019-03-29 2022-03-01 Boston Scientific Neuromodulation Corporation Neural sensing in an implantable stimulator device during the provision of active stimulation
US11793438B2 (en) 2019-03-29 2023-10-24 Boston Scientific Neuromodulation Corporation Neural sensing in an implantable stimulator device during the provision of active stimulation
US11504526B2 (en) 2019-05-30 2022-11-22 Boston Scientific Neuromodulation Corporation Methods and systems for discrete measurement of electrical characteristics
US11623095B2 (en) 2019-06-20 2023-04-11 Boston Scientific Neuromodulation Corporation Methods and systems for interleaving waveforms for electrical stimulation and measurement
US11547855B2 (en) 2019-10-25 2023-01-10 Medtronic, Inc. ECAP sensing for high frequency neurostimulation
US11857793B2 (en) 2020-06-10 2024-01-02 Medtronic, Inc. Managing storage of sensed information
US11707626B2 (en) 2020-09-02 2023-07-25 Medtronic, Inc. Analyzing ECAP signals
US11931582B2 (en) 2020-10-08 2024-03-19 Medtronic, Inc. Managing transient overstimulation based on ECAPs
US11896828B2 (en) 2020-10-30 2024-02-13 Medtronic, Inc. Implantable lead location using ECAP
US11931579B2 (en) 2023-02-20 2024-03-19 Boston Scientific Neuromodulation Corporation Circuitry to assist with neural sensing in an implantable stimulator device

Also Published As

Publication number Publication date
WO2012155184A1 (en) 2012-11-22
WO2012155190A1 (en) 2012-11-22
US10588524B2 (en) 2020-03-17
US20140194772A1 (en) 2014-07-10

Similar Documents

Publication Publication Date Title
US20140236042A1 (en) Method and apparatus for measurement of neural response
US20210315502A1 (en) Method and Apparatus for Estimating Neural Recruitment
US20210162214A1 (en) Electrode to Nerve Distance Estimation
US11439828B2 (en) Method and apparatus for application of a neural stimulus
US11819332B2 (en) Method and apparatus for measurement of neural response
US20230158305A1 (en) Monitoring and regulating physiological states and functions via sensory neural inputs to the spinal cord
US20200289815A1 (en) Method and System For Physiological Target Localization From Macroelectrode Recordings and Monitoring Spinal Cord Function
US10849525B2 (en) Monitoring brain neural activity
CN106999088B (en) System and method for monitoring muscle rehabilitation
AU2022202211A1 (en) Method and apparatus for application of a neural stimulus
US20160166164A1 (en) Method and Apparatus for Detecting Neural Injury
Ward et al. A flexible platform for biofeedback-driven control and personalization of electrical nerve stimulation therapy
EP4079368B1 (en) Sensory information compliant spinal cord stimulation system for the rehabilitation of motor functions
Yazdan-Shahmorad Electrical Stimulation of Rat Primary Motor Cortex for Neurorehabilitation and Neuroprosthetic Applications.

Legal Events

Date Code Title Description
AS Assignment

Owner name: SALUDA MEDICAL PTY LTD, AUSTRALIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PARKER, JOHN LOUIS;KARANTONIS, DEAN MICHAEL;REEL/FRAME:031606/0430

Effective date: 20131111

AS Assignment

Owner name: SALUDA MEDICAL PTY LTD., AUSTRALIA

Free format text: CONFIRMATION OF ASSIGNMENT;ASSIGNOR:NICTA IPR PTY LTD;REEL/FRAME:038893/0001

Effective date: 20130117

Owner name: NICTA IPR PTY LTD, AUSTRALIA

Free format text: CONFIRMATION OF ASSIGNMENT;ASSIGNOR:NATIONAL ICT AUSTRALIA LTD;REEL/FRAME:038895/0299

Effective date: 20130117

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION