# Patent

## Title
Methods and systems for automatically determining a neural response threshold current level

## Abstract

Methods of automatically determining a neural response threshold current level include identifying one or more neural response signals at one or more corresponding stimulation current levels, identifying one or more non-response signals at one or more corresponding stimulation current levels, and analyzing a trend between the neural response signals and the non-response signals. Systems for automatically determining a neural response threshold current level include one or more devices configured to identify one or more neural response signals at one or more corresponding stimulation current levels, identify one or more non-response signals at one or more corresponding stimulation current levels; and analyze a trend between the neural response signals and the non-response signals.

## Background
BACKGROUND
The sense of hearing in human beings involves the use of hair cells in the cochlea that convert or transduce acoustic signals into auditory nerve impulses. Hearing loss, which may be due to many different causes, is generally of two types: conductive and sensorineural. Conductive hearing loss occurs when the normal mechanical pathways for sound to reach the hair cells in the cochlea are impeded. These sound pathways may be impeded, for example, by damage to the auditory ossicles. Conductive hearing loss may often be helped by the use of conventional hearing aids that amplify sound so that acoustic signals reach the cochlea and the hair cells. Some types of conductive hearing loss may also be treated by surgical procedures.
Sensorineural hearing loss, on the other hand, is due to the absence or the destruction of the hair cells in the cochlea which are needed to transduce acoustic signals into auditory nerve impulses. Thus, people who suffer from sensorineural hearing loss are unable to derive any benefit from conventional hearing aid systems.
To overcome sensorineural hearing loss, numerous cochlear implant systems—or cochlear prosthesis—have been developed. These devices seek to bypass the hair cells in the cochlea by presenting electrical stimulation directly to the auditory nerve fibers. This leads to the perception of sound in the brain and at least partial restoration of hearing function. To facilitate direct stimulation of the auditory nerve fibers, an array of electrodes may be implanted in the cochlea. A sound processor processes an incoming sound and translates it into electrical stimulation pulses applied by these electrodes which directly stimulate the auditory nerve.
Many cochlear implant systems, as well as other types of neural stimulators, are configured to measure the effectiveness of an electrical stimulation current applied to neural tissue (e.g., the auditory nerve) by using a process known as neural response imaging (NRI). In NRI, the neural stimulator delivers an electrical stimulus to the neural tissue with a stimulating electrode and then records the resulting electrical activity of the neural tissue with a recording electrode. This resulting electrical activity is often referred to as an evoked neural response and occurs when the neural tissue depolarizes in response to the applied stimulus.
An evoked neural response may serve as a diagnostic measure to determine whether the neural stimulator is functioning correctly. NRI may also be used to determine optimal stimulation parameters for each electrode or electrode configuration. For example, NRI may be used to determine the lowest level of stimulation current that is required to evoke a neural response in a particular nerve. This information may then be used to optimize the stimulation parameters or settings of the cochlear implant system. NRI may also be used for a number of additional reasons.
In practice, however, the signal recorded by the recording electrode often includes undesirable signals that interfere with detection of the desired neural response. The terms “neural recording” and “neural recording signal” will be used herein and in the appended claims, unless otherwise specifically denoted, to refer to any signal recorded by the recording electrode. As will be explained in more detail below, a neural recording signal may include any combination of a neural response signal, noise, and/or stimulus artifact. Neural recording signals are sometimes referred to as evoked potential recordings.
As mentioned, a neural recording signal may include noise. Noise refers to any signal that is not correlated with the stimulus that is applied to the neural tissue by the neural stimulator. Noise is generally unpredictable.
Furthermore, a neural recording signal may also include stimulus artifact. Stimulus artifact includes signals, other than the neural response, that are correlated with the stimulus that is used to evoke the neural response. For example, the stimulus artifact may include the voltage potential of the stimulus pulse itself. Another source of stimulus artifact is cross-talk between the recording circuit and the stimulation circuit.
The presence of noise and stimulus artifact often makes it difficult to determine whether a neural recording includes a neural response. A number of conventional techniques exist for removing noise and stimulus artifact from a signal. However, these techniques are often ineffective when applied to a neural recording signal.
For example, filtering may be used to remove noise that has a different frequency than the frequency of a particular signal of interest. However, in neural stimulation systems, the frequency of the noise and the frequency of an evoked neural response signal are often similar. Thus, conventional filtering cannot always be used to remove noise from a neural recording.
Signal correlation may also be used to remove noise from a signal of interest. In signal correlation, a measured signal is correlated with a known reference signal to remove uncorrelated noise from the measured signal. However, evoked neural responses are often variable from patient to patient. Hence, a single reference signal cannot be used to correlate evoked neural responses from multiple patients. The signal correlation technique is therefore ineffective in many instances in removing noise from a neural recording.
Likewise, a number of conventional techniques exist for removing stimulus artifact from a neural recording. These techniques include alternating polarity, forward masking, third-phase compensation, and scaled template techniques. For example, in the alternating polarity technique, the neural response within the neural recording is estimated to be the average of the responses to a first stimulation pulse having a first polarity (e.g. cathodic) and a second stimulation pulse having the opposite polarity (e.g. anodic). The neural response stays the same polarity with the reverse in polarity of the stimulus. However, the stimulus artifact reverses polarity with the reverse in polarity of the stimulus. Consequently, the average response to the two polarities has a lower artifact component than either of the responses taken by themselves. While the alternating polarity technique is sometimes successful in reducing stimulus artifact in a neural recording, it does not eliminate it in all cases. Furthermore, the alternating polarity, as well as the other conventional techniques, often leaves large, residual stimulus artifacts in the neural recording.
As mentioned, it is often desirable to determine the minimum stimulation current level needed to evoke a neural response. This minimum stimulation current level is referred to as a “neural response threshold current level” or simply as a “neural response threshold.” The neural stimulator may then be configured to apply effective, comfortable, and optimal stimulus levels that conserve the power available to the stimulator. However, when a neural recording signal is marred by noise and artifact signals, it is often difficult to visually distinguish between a neural recording signal that includes a neural response signal and a neural recording signal that does not include a neural response signal. Thus, it is often difficult to determine the neural response threshold current level.
SUMMARY
Methods of automatically determining a neural response threshold current level include identifying one or more neural response signals at one or more corresponding stimulation current levels, identifying one or more non-response signals at one or more corresponding stimulation current levels, and analyzing a trend between the neural response signals and the non-response signals.
Systems for automatically determining a neural response threshold current level include one or more devices configured to identify one or more neural response signals at one or more corresponding stimulation current levels, identify one or more non-response signals at one or more corresponding stimulation current levels; and analyze a trend between the neural response signals and the non-response signals.



BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings illustrate various embodiments of the present invention and are a part of the specification. The illustrated embodiments are merely examples of the present invention and do not limit the scope of the invention.
FIG. 1 shows a lead having an electrode array with electrodes E1 through E8 according to principles described herein.
FIG. 2 illustrates an exemplary stimulus that may be delivered to neural tissue via a stimulating electrode according to principles described herein.
FIG. 3 shows an exemplary cochlear implant system that may be used as a neural stimulator according to principles described herein.
FIG. 4 is a functional block diagram of an exemplary speech processor and an implantable cochlear stimulator according to principles described herein.
FIGS. 5A and 5B show a spinal cord stimulator (SCS) system that may be used as a neural stimulator according to principles described herein.
FIG. 6A is a graph depicting an exemplary evoked neural response signal according to principles described herein.
FIG. 6B is a graph depicting an exemplary artifact signal according to principles described herein.
FIG. 6C is a graph depicting an exemplary neural recording signal according to principles described herein.
FIG. 7A is a graph depicting an exemplary noise signal according to principles described herein.
FIG. 7B is a graph depicting the effect of the noise signal of FIG. 7A on the evoked neural response signal of FIG. 6A according to principles described herein.
FIG. 7C is a graph depicting the effect of the noise signal of FIG. 7A on the artifact signal of FIG. 6B according to principles described herein.
FIG. 7D is a graph depicting the effect of the noise signal of FIG. 7A on the neural recording signal of FIG. 6C according to principles described herein.
FIG. 8 is a flow chart illustrating an exemplary method of automatically identifying a neural recording signal that includes a neural response signal according to principles described herein.
FIG. 9 is a flow chart illustrating an exemplary method of denoising a neural recording signal according to principles described herein.
FIG. 10 is a graph showing the percent of unaccounted variance in a matrix of evoked neural recording signals as a function of number of components according to principles described herein.
FIG. 11 is a graph illustrating the difference of standard deviations of the errors in the beginning versus in the end of the waveforms in the matrix of evoked neural recording signals as a function of the number of components included according to principles described herein.
FIG. 12 is a graph showing seven basis functions or components according to principles described herein.
FIG. 13 is a graph showing the amount by which noise is reduced for each point of the waveform representing the incoming neural recording signal according to principles described herein.
FIG. 14 is a graph illustrating the relative contribution of the noise and the artifact model to the overall uncertainty of the artifact model according to principles described herein.
FIGS. 15A and 15B are graphs illustrating net confidence intervals that are used to determine whether a neural recording signal includes a neural response signal according to principles described herein.
FIG. 16 is a graph that shows error rates of the automatic neural response identification method when compared to visual identification of neural response signals by expert medical practitioners for a number of different threshold values according to principles described herein.
FIG. 17 is a flow chart illustrating an exemplary method of automatically determining a neural response threshold current level according to principles described herein.
FIG. 18A shows a number of neural recording signals obtained at different current levels according to principles described herein.
FIG. 18B shows the measurement sequence of the neural recording signals of FIG. 18A according to principles described herein.
FIG. 19 is a graph illustrating an exemplary analysis of the neural responses and the non-responses that may be used to determine the neural response threshold current according to principles described herein.



Throughout the drawings, identical reference numbers designate similar, but not necessarily identical, elements.
DETAILED DESCRIPTION
Methods and systems for automatically determining a neural response threshold current level are described herein. A number of neural recording signals are obtained at different stimulation current levels. A minimum number of these neural recording signals are identified as including a neural response signal and a minimum number of these neural recording signals are identified as not including a neural response signal. The trend of the stimulation current levels corresponding to the identified signals are analyzed to determine the value of the neural response threshold current.
In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present systems and methods. It will be apparent, however, to one skilled in the art that the present systems and methods may be practiced without these specific details. Reference in the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearance of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.
FIG. 1 shows a lead (101) supporting an electrode array with electrodes E1 through E8. The lead (101) may be attached to a neural stimulator (not shown). The stimulator is configured to provide an electrical current via the electrode array to stimulate target tissue, e.g., neural tissue (102). The stimulation current output at each of the electrodes (E1-E8) maybe independently controlled by the stimulator. The lead (101) of FIG. 1 includes eight electrodes for illustrative purposes only. It will be recognized that the lead (101) may include any number of electrodes. Furthermore, the electrodes may be arranged in any of a number of configurations. For example, the electrodes may be arranged as an array having at least two or at least four collinear electrodes. In some embodiments, the electrodes are inductively coupled to the stimulator. The lead (101) may be thin (e.g., less than 3 millimeters in diameter) and flexible such that the lead (101) may be readily positioned near target neural tissue (102). Alternatively, the electrodes may be coupled directly to a leadless stimulator.
In some embodiments, each electrode (E1-E8) may be selectively configured to function as a stimulating electrode or a recording electrode as best serves a particular application. For example, E1 may be a used as a stimulating electrode and E2 may be used as a recording electrode. A stimulus, e.g., an electrical stimulation current, may then be applied to the neural tissue (102) via the stimulating electrode E1. The resulting electrical activity of the nerve (102) when the nerve (102) depolarizes in response to the applied stimulus is recorded with the recording electrode E2. As mentioned previously, this electrical activity is referred to as an evoked neural response or simply a neural response.
FIG. 2 illustrates an exemplary stimulus (120), e.g., an electrical stimulation current pulse, that may be delivered to neural tissue via a stimulating electrode. The stimulus (120) of FIG. 2 is biphasic. In other words, the stimulus (120) includes two parts—a negative first phase having an area A1 and a positive second phase having an area A2. It is usually the negative phase that causes neural tissue to depolarize (fire). The biphasic stimulus (120) shown in FIG. 2 has an amplitude of 1 milliamp (ma) and a pulse width of 20 microseconds (μsec) for illustrative purposes only. It will be recognized that any of the characteristics of the stimulus (120), including, but not limited to, the pulse shape, amplitude, pulse width, frequency, burst pattern (e.g., burst on time and burst off time), duty cycle or burst repeat interval, ramp on time, and ramp off time may vary as best serves a particular application.
The biphasic stimulus (120) shown in FIG. 2 is “charge balanced” because the negative area A1 is equal to the positive area A2. A charge-balanced biphasic pulse is often employed as the stimulus to minimize electrode corrosion and charge build-up which can harm surrounding tissue. However, it will be recognized that the biphasic stimulus (120) may alternatively be charge-imbalanced as best serves a particular application.
In some embodiments, when the amplitude and pulse width of the stimulus (120) of FIG. 2 reach a supra-threshold (i.e., a threshold stimulus large enough to depolarize a target nerve), the voltage gradient at some surface point on the nerve (102; FIG. 1) will be sufficiently negative as to cause the nerve (102; FIG. 1) to depolarize from its resting state and propagate an electrical signal along the length of the nerve (102). The voltage gradient of this electrical signal propagation can be captured with a recording electrode as the evoked neural response of the target nerve.
Before discussing the present methods and systems of automatically determining a neural response threshold current, it is helpful to understand the components of a number of exemplary neural stimulators in which the present methods and systems may be employed.
FIG. 3 shows an exemplary cochlear implant system (20) that may be used as a neural stimulator in accordance with the present methods and systems. Exemplary cochlear implant systems suitable for use as described herein include, but are not limited to, those disclosed in U.S. Pat. Nos. 6,219,580; 6,272,382; and 6,308,101, all of which are incorporated herein by reference in their respective entireties. The cochlear implant system (20) includes a speech processor portion (10) and a cochlear stimulation portion (12). The speech processor portion (10) may include a speech processor (SP) (16), a microphone (18), and/or additional circuitry as best serves a particular application. The cochlear stimulation portion (12) may include an implantable cochlear stimulator (ICS) (21), a number of electrodes (50) arranged in an electrode array (48), and/or additional circuitry as best serves a particular application. The components within the speech processor portion (10) and the cochlear stimulation portion (12) will be described in more detail below.
The microphone (18) of FIG. 3 is configured to sense acoustic signals and convert such sensed signals to corresponding electrical signals. The electrical signals are sent to the SP (16) over an electrical or other suitable link (24). Alternatively, the microphone (18) may be connected directly to, or integrated with, the SP (16). The SP (16) processes these converted acoustic signals in accordance with a selected speech processing strategy to generate appropriate control signals for controlling the ICS (21). These control signals may specify or define the polarity, magnitude, location (i.e., which electrode pair or electrode group receive the stimulation current), and timing (i.e., when the stimulation current is to be applied to a particular electrode pair) of the stimulation current that is generated by the ICS (21).
The electrode array (48) of FIG. 3 is adapted to be inserted within a duct of the cochlea. As shown in FIG. 3, the array (48) includes a multiplicity of electrodes (50), e.g., sixteen electrodes, spaced along its length. Each of the electrodes (50) is individually connected to the ICS (21). The electrode array (48) may be substantially as shown and described in U.S. Pat. Nos. 4,819,647 or 6,129,753, each of which is incorporated herein by reference in its respective entirety. Electronic circuitry within the ICS (21) is configured to apply stimulation current to selected pairs or groups of the individual electrodes (50) included within the electrode array (48) in accordance with a specified stimulation pattern defined by the SP (16).
The ICS (21) and the SP (16) may be electronically connected via a suitable data or communications link (14). In some embodiments, the SP (16) and the microphone (18) comprise an external portion of the cochlear implant system (20) and the ICS (21) and the electrode array (48) comprise an implantable portion of the system (20). In alternative embodiments, one or more portions of the SP (16) are included within the implantable portion of the cochlear implant system (20). The implantable portion of the cochlear implant system (20) is implanted within the patient's body. Thus, the data link (14) is a transcutaneous (through the skin) data link that allows power and control signals to be sent from the SP (16) to the ICS (21). In some embodiments, data and status signals may also be sent from the ICS (21) to the SP (16).
The external and implantable portions of the cochlear implant system (20) may each include one or more coils configured to transmit and receive power and/or control signals via the data link (14). For example, the external portion of the cochlear implant system (20) may include an external coil (not shown) and the implantable portion of the cochlear implant system (20) may include an implantable coil (not shown). The external coil and the implantable coil may be inductively coupled to each other, thereby allowing data to be transmitted between the external portion and the implantable portion. The data may include, for example, the magnitude and polarity of a sensed acoustic signal. The external coil may also transmit power from the external portion to the implantable portion of the cochlear implant system (20). It will be noted that, in some embodiments, both the SP (16) and the ICS (21) may be implanted within the patient, either in the same housing or in separate housings. If the SP (16) and the ICS (21) are in the same housing, the link (14) may be realized with a direct wire connection within such housing. If the SP (16) and the ICS (21) are in separate housings, the link (14) may be an inductive link, for example.
FIG. 4 is a functional block diagram of an exemplary SP (16) and ICS (21). The functions shown in FIG. 4 are merely representative of the many different functions that may be performed by the SP (16) and/or the ICS (21). A more complete description of the functional block diagram of the SP (16) and the ICS (21) is found in U.S. Pat. No. 6,219,580, which is incorporated herein by reference in its entirety.
As shown in FIG. 4, the microphone (18) senses acoustic information, such as speech and music, and converts the acoustic information into one or more electrical signals. These signals are then amplified in audio front-end (AFE) circuitry (22). The amplified audio signal is then converted to a digital signal by an analog-to-digital (A/D) converter (28). The resulting digital signal is then subjected to automatic gain control using a suitable automatic gain control (AGC) function (29).
After appropriate automatic gain control, the digital signal is then processed in one of a number of digital signal processing or analysis channels (44). For example, the SP (16) may include, but is not limited to, eight analysis channels (44). Each analysis channel (44) may respond to a different frequency content of the sensed acoustical signal. In other words, each analysis channel (44) includes a band-pass filter (BP1-BPFn) or other type of filter such that the digital signal is divided into n frequency channels. The lowest frequency filter may be a low-pass filter, and the highest frequency filter may be a high-pass filter.
As shown in FIG. 4, each analysis channel (44) may also include a detection stage (D1-Dn). Each detection stage (D1-Dn) may include an energy detection circuit (not shown), which may be realized, e.g., through a rectification circuit followed by an integrator circuit. As shown in FIG. 4, each of the detection stages (D1-Dn) may alternatively be bypassed depending on the particular signal processing strategy being used.
After energy detection, or bypassing of such, the signal from each of the n analysis channels (44) is forwarded to a mapping stage (41). The mapping stage (41) may be configured to map the signals in each of the analysis channels (44) to one or more of the m stimulus channels (46). The mapping stage (41) may be further configured to perform additional processing of the signal, such as signal compression. The signals output by each analysis channel (44) may then be serialized by a multiplexer (45) into one serial data channel. The multiplexed signal may then be further processed according to information included in a pulse table (42) connected to an arithmetic logic unit (ALU) (43). After the signal is appropriately processed, compressed, and mapped, the signal may be input into the ICS (21) to control the actual stimulus patterns that are applied to the patient via the electrode array (48; FIG. 3).
As mentioned, each of the n analysis channels (44) may be mapped to one or more stimulus channels (46). In other words, the information contained in the n analysis channels (44) controls the stimulus patterns that are applied to the patient by the ICS (21) and its associated electrode array (48; FIG. 3). Stimulus current may be applied to any number of stimulation sites within the patient's cochlea via the m stimulus channels (46). As used herein and in the appended claims, the term “stimulation site” will be used to refer to a target area or location at which the stimulus current is applied. For example, a stimulation site may refer to a particular location in the neural tissue of a cochlear implant patient. Through appropriate weighting and sharing of currents between the electrodes (50; FIG. 3), stimulus current may be applied to any stimulation site along the length of the electrode array (48; FIG. 3).
FIGS. 5A and 5B show a spinal cord stimulator (SCS) system (110) that may be used as a neural stimulator in accordance with the present methods and systems. The SCS (110) may be used to treat a number of different medical conditions such as, but not limited to, chronic pain.
As shown in FIG. 5A, the SCS (110) may include an implantable pulse generator (IPG) (112), a lead extension (114), and an electrode lead (116) having an electrode array (118) thereon. The electrode array (118) includes a plurality of electrodes (117). The electrodes (117) may be arranged, as shown in FIG. 5A, in an in-line array near the distal end of the lead (116). Other electrode array configurations may also be used. The lead extension (114) need not always be used with the SCS (110), but may be used depending on the physical distance between the IPG (112) and the stimulation site within the patient. The IPG (112) is configured to generate stimulation current pulses that are applied to a stimulation site via one or more of the electrodes (117). Exemplary spinal cord stimulators suitable for use as described herein include, but are not limited to, those disclosed in U.S. Pat. Nos. 5,501,703; 6,487,446; and 6,516,227, all of which are incorporated herein by reference in their respective entireties.
FIG. 5B shows that the electrode array (118) of the SCS (110) may be implanted in the epidural space (120) of a patient in close proximity to the spinal cord (119). Because of the lack of space near the lead exit point (115) where the electrode lead (116) exits the spinal column, the IPG (112) is generally implanted in the abdomen or above the buttocks. However, it will be recognized that the IPG (112) may be implanted in any suitable implantation site. The lead extension (114) facilitates implanting the IPG (112) at a location that is relatively distant from the lead exit point (115).
The cochlear implant system (20; FIG. 3) and the SCS (110; FIG. 5A) are merely illustrative of many types of neural stimulators that may be used to perform NRI. For example, the neural stimulator may additionally or alternatively include an implantable pulse generator (IPG) coupled to one or more leads having a number of electrodes, a deep brain stimulator, an implantable microstimulator, an external stimulator, or any other type of stimulator configured to perform NRI. Exemplary IPGs suitable for use as described herein include, but are not limited to, those disclosed in U.S. Pat. Nos. 6,381,496, 6,553,263; and 6,760,626. Exemplary deep brain stimulators suitable for use as described herein include, but are not limited to, those disclosed in U.S. Pat. Nos. 5,938,688; 6,016,449; and 6,539,263. Exemplary implantable microstimulators, such as the BION® microstimulator (Advanced Bionics® Corporation, Valencia, Calif.), suitable for use as described herein include, but are not limited to, those disclosed in U.S. Pat. Nos. 5,193,539; 5,193,540; 5,312,439; 6,185,452; 6,164,284; 6,208,894; and 6,051,017. All of these listed patents are incorporated herein by reference in their respective entireties.
As mentioned, it is often desirable to deliver a stimulus to neural tissue with a stimulating electrode and then record the resulting electrical activity of the neural tissue with a recording electrode. This resulting electrical activity is referred to as an evoked neural response or simply, a neural response, and occurs when the neural tissue depolarizes in response to the applied stimulus.
For example, in a normal ear, a single auditory nerve fiber or cell generates an action potential when the cell's membrane is depolarized to a threshold value, after which a spike occurs. Sodium ions entering the cell make the inside of the cell more positive, that is, depolarized. In some embodiments, an electrical stimulation current may be used to depolarize the nerve cell. This depolarization effect can be likened to taking a photograph by pressing the shutter button on a camera. Pressing on the button has no effect until it crosses a threshold pressure, and then “click”—the shutter opens and the film is exposed. In the same way, depolarizing a neuron has no effect until the depolarization reaches a threshold, and then, all at once, an action potential is generated.
The evoked neural response as recorded by the recording electrode includes a sum of action potentials of a number of nerve cells. FIG. 6A is a graph depicting an exemplary evoked neural response signal (160). As shown in FIG. 6A, the horizontal axis represents time in samples and the vertical axis represents the amplitude of the response in microvolts (μV). As shown in FIG. 6A, the evoked neural response signal (160) is typically characterized by a first negative peak (N1) followed by a first positive peak (P1). It will be recognized that evoked neural responses differ in timing and amplitude from patient to patient.
Unfortunately, the recording electrode may additionally or alternatively record noise and/or stimulus artifact. In general, a neural recording may include any combination of a neural response signal, noise, and/or stimulus artifact. In some instances, the neural recording obtained by the recording electrode only includes stimulus artifact and noise. For example, if the stimulus pulse is too low to trigger depolarization of the nerve (102), the nerve (102) will not produce a neural response and the recording electrode will only record the stimulus artifact and any noise that is present.
FIG. 6B is a graph depicting an exemplary artifact signal (161). The artifact signal. (161) is typically characterized as a sum of two decaying exponentials, one with a fast time constant and one with a slow time constant.
FIG. 6C is a graph depicting a neural recording signal (162) that includes both the evoked neural response signal (160) of FIG. 6A and the artifact signal (161) of FIG. 6B. As shown in FIG. 6C, the neural recording signal (162) is a sum of the evoked neural response signal (160; FIG. 6A) and the artifact signal (161; FIG. 6B).
As mentioned previously, the neural recording signal obtained by a recording electrode may also include noise. Noise refers to any signal that is not correlated with the stimulus pulse and is generally unpredictable. FIG. 7A is a graph depicting an exemplary noise signal (170) that may be recorded by the recording electrode. Because the noise signal (170) is unpredictable, the noise signal (170) may have any frequency or amplitude.
FIGS. 7B-7D are graphs depicting the effect (171) of the noise signal (170; FIG. 7A) on the evoked neural response signal (160) of FIG. 6A, the effect (172) of the noise signal (170; FIG. 7A) on the artifact signal (161) of FIG. 6B, and the effect (173) of the noise signal (170; FIG. 7A) on the neural recording signal (162) of FIG. 6C, respectively.
It is often desirable to determine whether a neural recording signal includes a neural response signal or whether the neural recording signal only includes noise and/or artifact signals. Currently, medical practitioners typically need to be trained to identify signals as containing valid neural responses from a visual display of the neural recording signal. For example, a typical neural response signal of the auditory nerve to a stimulus pulse includes a negative peak followed by a positive peak, such as the signal (160) shown in FIG. 6A. Waveforms that do not fall into this pattern are assumed to be recordings that contain only noise and/or stimulus artifact. However, because medical practitioners may have various degrees of training, the results of identifying signals containing valid neural responses may vary greatly from one practitioner to the next. In addition, some valid neural responses do not follow typical neural response patterns. Whether these responses will be correctly identified as valid neural responses depends on the judgment of the practitioner.
To overcome the inaccuracies of practitioner identification of valid neural responses and to improve NRI performance, the identification of a neural recording signal that includes a neural response signal may be automated. FIG. 8 is a flow chart illustrating an exemplary method of automatically identifying a neural recording signal that includes a neural response signal. The method described in connection with FIG. 8 is more fully described in a related application entitled “Methods and Systems for Automatically Identifying a Neural Recording Signal as Including a Neural Response Signal” to Litvak et al., client docket number AB-613U, which application was filed simultaneously with the present application on Jun. 1, 2005. The AB-613U application is incorporated herein by reference in its entirety.
The method described in connection with FIG. 8 may be used in connection with any type of neural stimulator. Furthermore, the steps shown in FIG. 8 and described below may be modified, reordered, removed, and/or added to as best serves a particular application. It will be recognized that a computer, digital signal processor (DSP), mathematical application, or any other suitable device, signal processor, software, firmware, or application may be used to implement one or more of the steps described in connection with FIG. 8.
As shown in FIG. 8, a neural recording signal is first obtained (step 210). As described above, the neural recording signal may be obtained by stimulating neural tissue with a stimulating electrode and then recording the electrical response of the neural tissue with a recording electrode. It will be recognized that the neural recording signal may be evoked in response to stimulus applied to any neural tissue by any neural stimulator. For example, the neural recording signal may capture a neural response evoked by a stimulus applied to the auditory nerve with a cochlear implant system.
Once the neural recording signal has been obtained (step 210), the neural recording signal is conditioned (step 211). In some embodiments, the neural recording signal is conditioned by removing the mean of the data within the neural recording, removing a trend from the data, and/or removing an overall DC voltage level from the data. The neural recording signal may additionally or alternatively be conditioned using any other suitable conditioning technique.
The noise that is present in the neural recording signal is then estimated (step 212). A number of different techniques may be used to estimate the nose in the neural recording signal. For example, the noise may be estimated by computing the standard deviation of the data near the tail of the neural recording signal. Alternatively, the noise may be directly estimated by analyzing variability between a number of different neural recording signals that are obtained.
The neural recording signal is then denoised (step 213). The neural recording signal may be denoised using any of a number of different techniques. For example, the neural recording signal may be denoised by applying principle component analysis, as is more fully described in a related application entitled “Methods and Systems for Denoising a Neural Recording Signal” to Litvak et al., client docket number AB-611U, which application was filed simultaneously with the present application on Jun. 1, 2005. The AB-611U application is incorporated herein by reference in its entirety.
An exemplary method of denoising a neural recording signal by applying principal component analysis will now be described in connection with the flow chart shown in FIG. 9. The term “denoising” will be used herein and in the appended claims, unless otherwise specifically denoted, to refer to decreasing or removing noise from a neural recording signal or any other signal as best serves a particular application. The method may be used in connection with any type of neural stimulator. The steps shown in FIG. 9 and described below may be modified, reordered, removed, and/or added to as best serves a particular application.
As shown in FIG. 9, a number of basis functions are first derived using principal component analysis to describe a set of previously collected neural recording signals (step 180). Principal component analysis is a statistical technique used to derive a number of functions that, when summed together, describe a given set of data. These functions are often referred to as basis functions or principal components, both of which terms will be used interchangeably herein and in the appended claims unless otherwise specifically denoted.
An example of deriving a number of basis functions that describe a set of neural recording signals corresponding to the auditory nerve will now be given. It will be recognized that the following example is merely illustrative and that the neural recording signal may be evoked in response to stimulus applied to any neural tissue by any neural stimulator.
A large number of neural recording signals were evoked and recorded by audiologists over a period of time. Each measured waveform was computed by averaging the response to a cathodic-anodic and anodic-cathodic stimulus pulse. A two-point averaging filter was then applied to the data. In addition, synchronized noise was measured by recording the response to stimulation with zero current. The synchronized noise was then subtracted from the response to the cathodic-anodic and anodic-cathodic stimulus pulse.
The evoked neural recording signals were then collected into a measurement matrix M=[m1 . . . m8000]. As used herein and in the appended claims, unless otherwise specifically denoted, bold capital letters will be used to refer to matrices and bold lower-case letters will be used to refer to vectors. Hence, M is a matrix containing 8,000 measured neural recording signals m1 through m8000. Although M contains 8,000 measured neural recording signals in the present example, it will be recognized that M may contain any number of measured neural recording signals as best serves a particular application.
Eigenvalue decomposition was then used to compute the principal components of M. MATLABTM or any other mathematical tool may be used to perform the eigenvalue decomposition. First, the covariance matrix CM=COV(M′) was computed. A vector of eigenvalues (λ) and a matrix of eigenvectors arranged in columns (Vfull) were then computed. The matrix Vfull contains the full components that account entirely for the measurement matrix M.
Because the covariance matrix CM is symmetric, the eigenvectors within the matrix Vfull are orthogonal. The eigenvectors within the matrix Vfull may be normalized to have a norm of one.
Although Vfull contains the full components that account entirely for the data contained in measurement matrix M, it can be shown that a lesser number of these components may sufficiently account for the data in M. FIG. 10 is a graph showing the percent of unaccounted variance in M as a function of the number of components. As shown in FIG. 10, the percent of unaccounted variance decreases as more components are included. However, as shown in FIG. 10, a small number of components (e.g., 5 to 10 components) may account for approximately 98 to 99 percent of the variance.
FIG. 11 is a graph illustrating the difference of standard deviations of the errors in the beginning versus in the end of the waveforms in M as a function of the number of components included. The error bars (e.g., 190) are approximately 99 percent confidence intervals around the mean estimate of the error. As shown in FIG. 11, the difference becomes zero for eight components. For higher numbers of components, some noise is captured in the measurements. Hence, the error in the beginning portion of the stimulus is less than the standard of deviation.
The results shown in FIGS. 10 and 11 may be used to determine an optimal number of basis functions or components for a given application. For example, seven components capture approximately 98.6 percent of the variance in the data and have a 2 μV mean difference. Thus, seven components are sufficient for many different applications. The examples given herein will use seven components or basis functions. However, it will be recognized that any number of basis functions may be chosen to represent the set of evoked neural recording signals in M.
FIG. 12 is a graph showing seven basis functions or components. As shown in FIG. 12, the top basis function (basis function number 7) looks like a neural response signal. The remaining basis functions account for differences in the evoked neural recording signals in M. For purposes of the present example, the seven basis functions or components will be represented by the component matrix V=[v1 . . . v7], where v1 through v7 are vectors representing the seven basis functions. As will be described in more detail below, the component matrix V may be used to denoise an incoming neural recording signal.
Returning to the flow chart of FIG. 9, once the component matrix V has been determined, the next step is to determine relative weights for the basis functions v1 through v7 corresponding to an incoming neural recording signal (step 181). In other words, the amount of each basis function v1 through v7 that is present in the incoming neural recording signal is determined. A computer, digital signal processor (DSP), or any other suitable device or application may be used to determine the relative weights for the basis functions. As will be described in more detail below, the incoming neural recording signal is denoised by multiplying the weights with the basis functions v1 through v7.
For example, assume that the incoming neural recording signal is represented by m. The relative weights for the basis functions v1 through v7 are determined by correlating the incoming neural recording signal m with the basis functions in the component vector V. Hence, the weights are equal to V′ m.
As shown in FIG. 9, the weights are then multiplied with the basis functions to denoise the incoming neural recording signal (step 182). Thus, the denoised neural recording signal, mdenoised, is equal to V V′ m. For ease of explanation, mdenoised=T m, where T is the denoising matrix equal to V V′. A computer, digital signal processor (DSP), or any other suitable device or application may be used to resynthesize the weights.
Mathematically, the denoising effect of multiplying the weights with the basis functions can be shown by the following equations. Suppose that the incoming neural recording signal is m=s+n, where s represents the evoked neural response signal and/or artifact signal and n represents the uncorrelated noise. Without loss of generality, it can be assumed that n has a zero mean. The denoised waveform is then mdenoised=T m=T s+T n=sdenoised+T n. Therefore, the uncorrelated noise in the denoised waveform is ndenoised=mdenoised−sdenoised=T n.
Conceptually, the denoising effect of multiplying the weights with the basis functions can be illustrated by the following example. Suppose that there is only one basis function and the incoming neural recording only contains noise. When this incoming noise is correlated with the basis function, the resulting weight value is low, indicating that the noise does not correlate with the basis function. When the low weight number is multiplied with the basis function, the resulting signal is characterized by a smaller magnitude than the incoming noise signal.
On the other hand, suppose that the incoming neural recording is noiseless. Therefore, when the incoming neural recording signal is correlated with the single basis function, the resulting weight number is high, indicating that the incoming neural recording signal correlates with the basis function. When the high weight number is multiplied with the basis function, the resulting signal is characterized by a magnitude that is relatively close to the magnitude of the incoming neural recording signal.
The noise can be described by the covariance matrix CDn=E[n n′]=T E[n n′]T′=T Cn T′. The diagonal of the matrix CDn is the variance at any point. Therefore, the square root of the diagonal is equal to the standard deviation at any given point. Assuming that the incoming noise is white, with unity variance, the decrease in the noise standard deviation is shown in FIG. 13. FIG. 13 shows, as a function of sample number, the amount by which noise is reduced for each point of the waveform representing the neural recording. The horizontal line (193) represents the noise level of the incoming neural recording before denoising. The line (192) represents the noise level of the incoming neural recording signal after denoising. The shaded area represents the range of time where most of the response energy is maximal. In this area, as shown in FIG. 13, an average reduction in noise of nearly 50 percent is achieved by the denoising technique described herein.
In some embodiments, greater noise reductions may be achieved by including fewer components. However, the cost of including fewer components may be loss of some energy in the denoised signal.
Returning to the flow chart of FIG. 8, after the neural recording signal has been denoised (step 213), confidence intervals corresponding to the neural recording signal may be determined (step 214). The confidence intervals take into account the uncertainty in the denoised neural response signal. The confidence intervals may be derived from any combination of a number of contributing factors including, but not limited to, estimates of noise levels, relative noise levels before and after multiplying the weights with the basis functions, and other factors.
As shown in FIG. 8, the method also includes fitting an artifact model to the obtained neural recording signal (step 216). The artifact model describes a typical or model stimulus artifact signal, and, as will be described in more detail below, may be used to determine whether a neural recording signal includes a neural response signal.
As used herein and in the appended claims, unless otherwise specifically denoted, the variable am(t) will be used to represent an artifact model. As mentioned, a stimulus artifact signal can be characterized as a sum of two decaying exponentials. Hence, the artifact model may be described by the following equation: am(t)=A1·e−α·t+B·e−β·t, where α and β are time constants. Since the time constant β is large compared to the time scale of interest, the second exponential in this equation can be estimated by a linear trend. Hence, am(t)=A1·e−α·t+A2·t+A3. All of the parameters in this model are linear, except for the coefficient α. As will be described in more detail below, the values of the parameters [α, A1, A2, A3] may be adjusted to fit the artifact model to a neural recording signal.
The variable m(t) will be used herein and in the appended claims, unless otherwise specifically denoted, to represent a neural recording signal. Hence, m(t)=a(t)+s(t)+n(t), where a(t) represents the stimulus artifact signal, s(t) represents the neural response signal, and n(t) represents the noise signal. To fit the artifact model am(t) to the neural recording signal m(t), the model parameters [α, A1, A2, A3] are determined for which the error between the artifact model and the data within the neural recording signal is minimized. Heuristic optimizations may be applied to limit the artifact model. For example, the parameter A1 may be required to have a positive value. A computer, digital signal processor (DSP), mathematical application, or any other suitable device or application may be used to fit the artifact model am(t) to the neural recording signal m(t).
Once the artifact model has been fitted to the neural recording signal (step 216), the fitted artifact model signal is denoised (step 217). The fitted artifact model is denoised to eliminate or reduce distortions or uncertainties in the model due to the noise that is present in the neural recording signal. The fitted artifact model signal may be denoised using principal component analysis, as described above, or by using any other suitable denoising technique.
After the fitted artifact model signal has been denoised (step 217), confidence intervals for the fitted artifact model signal are determined (step 218). These confidence intervals are determined by a number of uncertainties in the artifact parameters given the noise level in the neural recording signal. For example, there may be uncertainty in the stimulus, uncertainty in the model, and uncertainty in the noise. FIG. 14 is a graph illustrating the relative contribution of the noise (230) and the artifact model (231) to the overall uncertainty of the fitted artifact model signal. The results in FIG. 14 and/or additional or alternative factors may be used in determining the confidence intervals for the fitted artifact model signal.
Returning to FIG. 8, once the confidence intervals have been determined for the neural recording signal (step 214) and for the fitted artifact model signal (step 218), net or total confidence intervals are computed by summing the neural recording signal confidence intervals and fitted artifact model signal confidence intervals (step 219). FIGS. 15A and 15B show exemplary net confidence intervals (240). As will be described in more detail below, these net confidence intervals (240) are used to determine whether a neural recording signal includes a neural response signal.
Returning to FIG. 8, after the net confidence intervals have been computed (step 219), a strength-of-response (SOR) metric corresponding to the observed neural recording signal is computed (step 220). The SOR metric describes the distance of the fitted artifact model signal to the observed neural recording signal relative to the net confidence intervals (240). A neural recording signal may be identified as including a neural response signal if the SOR metric exceeds a pre-determined threshold.
The SOR metric may be any metric that describes the distance of the fitted artifact model signal to the observed neural recording signal relative to the net confidence intervals (240). A number of different SOR metrics may be used. One exemplary SOR metric is




  
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where c(t) is the net confidence interval size. This equation may be modified as best serves a particular application.

The size of the SOR metric is then evaluated (step 221) to determine whether the neural recording signal includes a neural response signal or whether the neural recording signal only includes noise and artifact signals. The SOR metric evaluation may be performed automatically with a computer, DSP, mathematical application, or any other suitable device or application. If the SOR metric exceeds a pre-determined SOR threshold value, the neural recording signal is identified as including a neural response signal (222). Conversely, if the SOR metric is below the pre-determined SOR threshold, the neural recording signal is identified as not including a neural response signal (step 224).
Additionally or alternatively, further neural recording signals may be obtained and averaged (step 223) if the SOR metric is too close to the SOR threshold to accurately identify as corresponding to a neural recording signal that includes a neural response signal or not. A new SOR metric may be computed and evaluated for these additional neural recording signals.
An example of determining whether a neural recording signal includes a neural response signal by evaluating the SOR metric will be described in connection with FIGS. 15A and 15B. FIG. 15A shows a first exemplary neural recording signal (242) and a corresponding denoised neural recording signal (241) that has been fitted by the artifact model. As shown in FIG. 15A, the denoised recording signal (241) is relatively close to the confidence interval (240) and may therefore be difficult to visually identify as including a neural response signal. However, suppose that the pre-determined SOR threshold is m=35. Using the SOR metric equation shown above, the SOR metric for the denoised recording signal (241) is equal to m=39.059, well above the SOR threshold value of 35. Therefore, the neural recording signal (242) may be identified as including a neural response signal.
FIG. 15B shows a second exemplary neural recording signal (244) and its corresponding denoised neural recording signal (243) that has been fitted by the artifact model. The SOR metric for this neural recording signal (244) is equal to m=20.2673, well below the SOR threshold value of 35. Therefore, the neural recording signal (244) may be identified as not including a neural response signal.
An optimal threshold value may be determined using a number of different techniques. In some embodiments, the optimal threshold value is determined by comparing the results of the automatic neural response identification method of FIG. 8 to the results of visual identification of the same neural response signals by expert medical practitioners. For example, FIG. 16 is a graph that shows error rates of the automatic neural response identification method when compared to visual identification of neural response signals by expert medical practitioners for a number of different threshold values. Curve (250) shows the percentage of “false positives” (i.e., the percentage of neural recording signals falsely identified as including a neural response signal) per threshold value, curve (251) shows the percentage of “false negatives” (i.e., the percentage of neural recording signals falsely identified as not including a neural response signal) per threshold value, and curve (252) shows the net error rate per threshold value. The optimal threshold value is determined by choosing the threshold value that corresponds to the minimum value of the net error rate curve (252). Hence, the optimal threshold value for the curves shown in FIG. 16 is approximately equal to 35.
As mentioned, it is often desirable to determine the minimum stimulation current level needed to evoke a neural response, i.e., the neural response threshold current level. However, noise and artifact signals contained in a neural recording signal often make it difficult to determine the neural response threshold current level.
Hence, an exemplary method of automatically determining a neural response threshold current level will now be described in connection with the flow chart of FIG. 17. The steps shown in FIG. 17 and described below may be modified, reordered, removed, and/or added to as best serves a particular application. Furthermore, it will be recognized that a computer, digital signal processor (DSP), mathematical application, or any other suitable device, signal processor, software, firmware, or application may be used to implement one or more of the steps described in connection with FIG. 17.
The exemplary method shown in FIG. 17 includes identifying a number of neural recording signals at different stimulation current levels that most likely include neural response signals and a number of neural recording signals at different stimulation current levels that most likely do not include neural response signals. The neural response threshold current level may then be determined by analyzing the amplitudes of the neural recording signals and their corresponding stimulation current levels.
As shown in FIG. 17, a neural recording signal is first obtained with Astep averages (step 300). In other words, the neural recording signal is the average of Astep neural recordings at a particular stimulation current level. The value of Astep may vary as best serves a particular application. An exemplary, but not exclusive, value for Astep is 32.
An SOR metric is then computed for the obtained neural recording signal (step 301). The SOR metric may be computed using the method already described in connection with FIG. 8.
The computed SOR metric is then compared against an SOR threshold value to determine whether the neural recording signal includes a neural response signal. As used herein and in the appended claims, unless otherwise specifically denoted, the variable SORcrit will be used to represent the SOR threshold value. As described previously, if the SOR metric is too close to the SOR threshold, the probability of falsely identifying the neural recording signal as including a neural response signal or not is greatly increased. Hence, in step 302, the SOR metric is compared against SORmin and SORmax, upper and lower uncertainty limits, respectively, that surround the SOR threshold value. The values for SORcrit, SORmin, and SORmax may vary as best serves a particular application. Exemplary values obtained using the equation




  
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as described above, may be SORcrit=32, SORmin=27, and SORmax=35.

If the SOR metric value falls within these uncertainty limits (Yes; step 302), the SOR metric is too close to the SOR threshold to accurately identify the neural recording signal as having captured an actual neural response. Averaging in additional neural recording signals may reduce the effect of the noise and artifact signals enough to make a more accurate identification of the averaged neural recording signal. Hence, the method next determines whether additional neural recording signals may be obtained at the same stimulation current level to include in the average (step 303). If additional neural recording signals may be obtained at the same stimulation current level (Yes; step 303), the method returns to step 300 wherein additional neural recording signals are obtained and averaged.
In some instances, however, additional neural recording signals may not be obtained for inclusion in the average being calculated (No; step 303). For example, a medical practitioner may determine that additional time at the present stimulation current level may be harmful to the patient. Alternatively, the practitioner may have only a limited time for making the measurement. Hence, a maximum number of averages, Amax at the present stimulation current level may be specified by the medical practitioner. The total number of signals recorded and averaged together at a specific current level may not exceed Amax. If it is determined that no additional signals may be obtained (No; step 303), the method proceeds to step 304, which will be described in more detail below.
Returning to step 302, if the SOR metric value does not fall within SORmin and SORmax (No; step 302), an accurate identification of the neural recording signal may be made. If the SOR metric is greater than SORcrit, the neural recording signal is identified as including a neural response signal and the total number of neural responses R that have been identified is incremented by one (step 304). However, if the SOR metric is less than SORcrit, the neural recording signal is identified as not including a neural response signal and the total number “non-responses” NR that have been identified is incremented by one (step 305). As used herein and in the appended claims, unless otherwise specifically denoted, the term “non-response” and “non-response signal” will be used interchangeably to refer to a neural recording signal that does not include a neural response signal.
If there has not yet been a neural response R identified (No; step 306), it is next determined whether the stimulation current level can be increased (step 309). If the stimulation current level can be increased (Yes; step 309), the stimulation current level is increased from the highest previously-tried current level (step 311). New neural recordings may then be obtained at this higher current level (step 300). This process may be repeated until a neural stimulus R is identified (Yes; step 306).
However, in some instances, the stimulation current level cannot be increased (No; step 309). For example, a medical practitioner may stipulate that the stimulation current level cannot go above a particular maximum level. In these instances, more neural recording signals may be obtained and averaged at the current stimulation current level if the maximum number of allowable signals at that stimulation current level has not been exceeded (Yes; step 310). As mentioned above, collecting and averaging additional signals may enable a more accurate identification of an actual neural response. If more signals for the average cannot be obtained at the maximum current level (No; step 310), the method may end without identifying any neural responses R. In such a case, an option may be presented to the medical practitioner to obtain more neural recording signals at a higher stimulation current level and/or with a different recording electrode.
As shown in FIG. 17, once a neural response R has been identified (step 306), the method determines whether a minimum number of non-responses NRmin has been obtained (step 307). NRmin may vary as best serves a particular application. For example, in some embodiments, NRmin is two. If the minimum number of non-responses NRmin has not been obtained (No; step 307), the stimulation current level (step 312) may be gradually decreased until the minimum number of non-responses NRmin are recorded (Yes; step 307). NRmin may vary as best serves a particular application. For example, in some embodiments, NRmin is two.
Next, the stimulation current level may be increased (step 311) until a minimum number of responses are measured (Yes; step 308). Rmin may vary as best serves a particular application. For example, in some embodiments, Rmin is four. The neural response threshold current level may more accurately be determined with higher values of Rmin.
It will be recognized that the order in which the neural responses R and the non-responses NR are obtained may vary as best serves a particular application. For example, the non-responses NR may be obtained first. The stimulation current may then be increased to obtain the neural responses R. In any case, the identification of a minimum number of responses and non-responses increases the accuracy and confidence in the identified neural response threshold.
In some instances, a stray measurement may be obtained. For example, a neural response R may be obtained at a stimulation current level that is in between stimulation current levels corresponding to two non-responses NR or vice versa. These stray measurements may be ignored or otherwise dealt with as best serves a particular application.
The method of obtaining a number of neural responses Rmin and non-responses NRmin will be illustrated in connection with FIGS. 18A and 18B. For illustrative purposes only, both Rmin and NRmin are equal to four. FIG. 18A shows a number of neural recording signals (320-328) obtained at different current levels. Confidence intervals (e.g., 330) corresponding to each neural recording signal (320-328) are also shown.
FIG. 18B shows the measurement sequence of the neural recording signals (320-328) of FIG. 18A. As shown in FIG. 18B, a first neural recording signal (320) is obtained at a stimulation current level of 350 μA. This neural recording signal (320) is identified as a non-response. The stimulation current level is then increased to 400 μA and a second neural recording signal (321) is obtained. This neural recording signal (321) is also identified as a non-response. This process is repeated until at least two non-responses (NRmin) are obtained. As shown in FIG. 18A, five non-responses (320-324) are obtained before a neural response (325) is identified. If the neural response (325) is obtained prior to obtaining the minimum number of non-responses NRmin, the current may be decreased to a level below 350 μA to obtain the desired number of non-responses.
As shown in FIG. 18A, the first neural response (325) is identified at a current level of 600 μA. The amplitude of the first neural response (325) detected is often relatively small and additional neural response signals may have to be obtained at this current level and averaged to determine whether a neural response is actually present. Hence, as shown in FIG. 18B, after reaching the maximum allowable stimulation current level of 750 μA, the stimulation current may be decreased to 600 μA where additional neural recording signals are taken and averaged until a neural response is detected.
FIG. 18A shows that neural responses are identified at current levels of 600, 650, 700, and 750 μA. Hence, the neural recording signals (325-328) have been identified as including neural response signals.
Once the minimum number of neural responses Rmin and minimum number of non-responses NRmin have been obtained, as illustrated in connection with FIGS. 18A and 18B, the neural response threshold current may be determined by analyzing the identified neural responses and non-responses (step 313; FIG. 17). FIG. 19 illustrates an exemplary analysis of the neural responses and the non-responses that may be used to determine the neural response threshold current. The peak-to-peak amplitudes of the neural recording signals (320-328; FIG. 18A) obtained at each stimulus current level in the example described in connection with FIGS. 18A and 18B are plotted in the graph of FIG. 19. The unfilled points in the graph correspond to the non-responses (320-324; FIG. 18A) and the filled points correspond to the neural responses (325-328; FIG. 18A).
As shown in FIG. 19, a closest-fit line (340) may be fit to a number of the points corresponding to the neural responses (325-328; FIG. 18A) and non-responses (320-324; FIG. 18A) to analyze a trend in the data represented by the points. This closest-fit line (340) is referred to as a growth curve or contour.
The region (341) of the growth curve (340) between the highest stimulation current (342) corresponding to a non-response and the lowest stimulation current (343) corresponding to a neural response may be analyzed to determine the neural response threshold current level. In some embodiments, the neural response threshold current level is equal to a value that falls within this region (341). The accuracy of the neural response threshold current level may be maximized by increasing the number of signals averaged to obtain the responses and non-responses, increasing the number of neural responses and non-responses obtained, and/or decreasing the incremental step value of the stimulation currents from 50 μA to a smaller value.
The method illustrated in FIG. 17 of automatically determining a neural response threshold may be performed by an application, processor-readable instructions, or the like that may be stored in a processor readable medium. The processor readable medium may be a hard drive, optical disc, or any other storage device medium.
The preceding description has been presented only to illustrate and describe embodiments of the invention. It is not intended to be exhaustive or to limit the invention to any precise form disclosed. Many modifications and variations are possible in light of the above teaching.

## Claims

1. A method of automatically determining a neural response threshold current level, said method comprising:
obtaining a plurality of neural recording signals at a plurality of different stimulation current levels;
fitting an artifact model to each of said neural recording signals to obtain a plurality of fitted artifact model signals;
denoising each of said neural recording signals and each of said fitted artifact model signals;
computing a strength-of-response metric for each of said neural recording signals, said computation being based on at least one of said denoised neural recording signals and at least one of said fitted artifact model signals;
comparing each of said strength-of-response metrics to a strength-of-response threshold to identify one or more neural response signals and one or more non-response signals contained within said neural recording signals; and
analyzing a trend between said neural response signals and said non-response signals to determine said neural response threshold current level.

2. The method of claim 1, wherein each of said neural response signals and said non-response signals corresponds to one of said stimulation current levels and wherein said neural response threshold current level is substantially equal to a current level located in between a highest current level out of said stimulation current levels corresponding to said non-response signals and a lowest current level out of said stimulation current levels corresponding to said neural response signals.

3. The method of claim 1, further comprising identifying at least four neural response signals contained within said neural recording signals.

4. The method of claim 1, further comprising identifying at least two non-response signals within said neural recording signals.

5. The method of claim 1, wherein a highest stimulation current level out of said stimulation current levels corresponding to said neural response signals is less than or substantially equal to a maximum allowable current level.

6. The method of claim 1, wherein said step of analyzing said trend between said neural response signals and said non-response signals comprises generating and analyzing a growth curve corresponding to amplitudes of said neural response signals and said non-response signals.

7. The method of claim 1, further comprising:
computing a net confidence interval for each of said neural recording signals, said computation based on said denoised neural recording signals and said denoised fitted artifact model signals; and
basing said computation of said strength-of-response metric on said net confidence intervals.

8. A system for automatically determining a neural response threshold current level, said system comprising:
a stimulator configured to obtain a plurality of neural recording signals at a plurality of different stimulation current levels; and
one or more devices communicatively coupled to said stimulator and configured to
fit an artifact model to each of said neural recording signals to obtain a plurality of fitted artifact model signals;
denoise each of said neural recording signals and each of said fitted artifact model signals;
compute a strength-of-response metric for each of said neural recording signals, said computation being based on at least one of said denoised neural recording signals and at least one of said fitted artifact model signals;
compare each of said strength-of-response metrics to a strength-of-response threshold to identify one or more neural response signals and one or more non-response signals contained within said neural recording signals; and
analyze a trend between said neural response signals and said non-response signals to determine said neural response threshold current level.

9. The system of claim 8, wherein each of said neural response signals and said non-response signals corresponds to one of said stimulation current levels and wherein said neural response threshold current level is substantially equal to a current level located in between a highest current level out of said stimulation current levels corresponding to said non-response signals and a lowest current level out of said stimulation current levels corresponding to said neural response signals.

10. The system of claim 8, wherein said one or more devices are further configured to identify at least four neural response signals contained within said neural recording signals.

11. The system of claim 8, wherein said one or more devices are further configured to identify at least two non-response signals within said neural recording signals.

12. The system of claim 8, wherein a highest stimulation current level out of said stimulation current levels corresponding to said neural response signals is less than or substantially equal to a maximum allowable current level.

13. The system of claim 8, wherein said one or more devices are further configured to generate and analyze a growth curve corresponding to amplitudes of said neural response signals and said non-response signals to determine said neural response threshold current.

14. The system of claim 8, wherein said one or more devices comprises at least one or more of a computer, digital signal processor, and software application.

15. The system of claim 8, wherein said one or more devices are further configured to:
compute a net confidence interval for each of said neural recording signals, said computation based on said denoised neural recording signals and said denoised fitted artifact model signals; and
base said computation of said strength-of-response metric on said net confidence intervals.

16. A system for automatically determining a neural response threshold current level, said system comprising:
means for obtaining a plurality of neural recording signals at a plurality of different stimulation current levels;
means for fitting an artifact model to each of said neural recording signals to obtain a plurality of fitted artifact model signals;
means for denoising each of said neural recording signals and each of said fitted artifact model signals;
means for computing a strength-of-response metric for each of said neural recording signals, said computation being based on at least one of said denoised neural recording signals and at least one of said fitted artifact model signals;
means for comparing each of said strength-of-response metrics to a strength-of-response threshold to identify one or more neural response signals and one or more non-response signals contained within said neural recording signals; and
means for analyzing a trend between said neural response signals and said non-response signals to determine said neural response threshold current level.

17. The system of claim 16, wherein each of said neural response signals and said non-response signals corresponds to one of said stimulation current levels and wherein said neural response threshold current level is substantially equal to a current level located in between a highest current level out of said stimulation current levels corresponding to said non-response signals and a lowest current level out of said stimulation current levels corresponding to said neural response signals.

18. The system of claim 16, wherein a highest stimulation current level out of said stimulation current levels corresponding to said neural response signals is less than or substantially equal to a maximum allowable current level.

19. The system of claim 16, wherein said means for analyzing said trend between said neural response signals and said non-response signals comprises means for generating and analyzing a growth curve corresponding to amplitudes of said neural response signals and said non-response signals.

20. The system of claim 16, further comprising:
means for computing a net confidence interval for each of said neural recording signals, said computation based on said denoised neural recording signals and said denoised fitted artifact model signals; and
means for basing said computation of said strength-of-response metric on said net confidence intervals.