Abstract:
A system and method for application of pseudospontaneous neural stimulation is provided that can generate stochastic independent activity across an excited nerve or neural population without an additional disadvantageous sensations. High rate pulse trains, for example, can produce random spike patterns in auditory nerve fibers that are statistically similar to those produced by spontaneous activity in the normal ear. This activity is called “pseudospontaneous activity”. Varying rates of pseudospontaneous activity can be created by varying the intensity of a fixed amplitude, high rate pulse train stimulus, e.g., 5000 pps. The pseudospontaneous activity can further desynchronize the nerve fiber population as a treatment for tinnitus but if indiscriminately applied can generate potentially uncomfortable biological and somatosensory sensations over intervals of time. A method for generating pseudospontaneous activity in an auditory nerve according to the present invention can include generating an electrical signal, and modifying the electrical signal to a sustained effective level while the electrical signal remains substantially physiologically imperceptible to the patient. The applied electrical signal can generate pseudospontaneous activity in the auditory nerve to suppress tinnitus.

Description:
This application is a continuation-in-part application of U.S. patent application Ser. No. 09/023,278 filed on Feb. 13, 1998, entitled “Pseudospontaneous Neural Stimulation System and Method,” now U.S. Pat. No. 6,078,838 which is hereby incorporated by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates generally to an apparatus and method for providing stochastic independent neural stimulation, and in particular, a neural stimulation system and method for initiating pseudospontaneous activity in the auditory nerve, which can be used to treat tinnitus. 
     2. Background of the Related Art 
     Fundamental differences currently exist between electrical stimulation and acoustic stimulation of the auditory nerve. Electrical stimulation of the auditory nerve, for example, via a cochlear implant, generally results in more cross-fiber synchrony, less within fiber jitter, and less dynamic range, as compared with acoustic stimulation which occurs in individuals having normal hearing. 
     FIG. 1 shows the magnitude of a related art pattern of electrically-evoked compound action potentials (EAPs) from an auditory nerve of a human subject with an electrical stimulus of 1 kHz (1016 pulses/s). The EAP magnitudes are normalized to the magnitude of the first EAP in the record. FIG. 1 shows the typical alternating pattern previously described in the art. This pattern arises because of the refractory period of the nerve and can degrade the neural representation of the stimulus envelope. With a first stimulus  102  a large response occurs, likely because of synchronous activation of a large number of fibers. These fibers are subsequently refractory driving a second pulse  104 , and accordingly a small response is generated. By the time of a third pulse  106 , an increased pool of fibers becomes available (non-refractory) and the corresponding response increases. The alternating synchronized response pattern can be caused by a lack or decrease of spontaneous activity in the auditory nerve and can continue indefinitely. 
     Loss of spontaneous activity in the auditory nerve is one proposed mechanism for tinnitus. Proposed biological mechanisms for the loss of spontaneous activity in the auditory nerve include loss of hair cells in the cochlea. In addition, the loss of hair cells over time is a proposed mechanism for the loss of auditory neurons likely caused by related activities at synapses connecting the hair cells to the auditory neurons in the cochlea. 
     Tinnitus is a disorder where a patient experiences a sound sensation within the head (“a ringing in the ears”) in the absence of an external stimulus. This uncontrollable ringing can be extremely uncomfortable and often results in severe disability. Restoration of spontaneous activity may potentially improve tinnitus suppression. Tinnitus is a very common disorder affecting an estimated 15% of the U.S. population according to the National Institutes for Health, 1989 National Strategic Plan. Hence, approximately 9 million Americans have clinically significant tinnitus with 2 million of those being severely disabled by the disorder. 
     Methods and apparatus that generate stochastically independent or “pseudospontaneous” neural activity in the auditory nerve have been modeled and tested with discernable improvements in auditory capabilities including reductions in tinnitis. See U.S. patent application Ser. No. 09/023,279 filed on Feb. 13, 1998, entitled “Speech Processing System and Method Using Pseudospontaneous Stimulation,” which is hereby incorporated by reference. However, biological and somatosensory responses to gradual or rapid reversals of the loss of spontaneous activity in the auditory nerve, for example, were heretofore unknown. Preferably, pseudospontaneous neural activity would be introduced without perception to a patient. For example, in an auditory nerve the desired treatments of tinnitus associated with sensorineural hearing loss would suppress the tinnitus without producing any additional sensations and auditory percepts. 
     SUMMARY OF THE INVENTION 
     An object of the present invention is to provide an apparatus and method of neural stimulation that substantially reduces or obviates at least one of the problems caused by disadvantages of the related art. 
     Another object of the present invention is to provide an apparatus and method that imperceptibly generates stochastically independent or “pseudospontaneous” neural activity. 
     Yet another object of the present invention is to provide an apparatus and method that imperceptibly generates statistically independent or “pseudospontaneous” activity in an auditory nerve to suppress tinnitus. 
     Still yet another object of the present invention is to provide an inner ear or middle ear auditory prosthesis that suppresses tinnitus without producing additional sensations. 
     A further object of the present invention is to provide an apparatus and method that determines and imperceptibly achieves electrical stimulation to increase stochastic independence of a plurality of nerve fibers. 
     A still further object of the present invention is to provide an apparatus and method that delivers an undetected high frequency signal to generate desired activity in a nerve. 
     A still further object of the present invention is to provide an apparatus and method that increases hearing capabilities by providing a prescribed signal to auditory neurons. 
     To achieve at least the above objects in a whole or in parts, there is provided a method and apparatus according to the present invention for generating pseudospontaneous activity in a nerve that includes generating an electrical signal, modifying the electrical signal to a sustained effective level while the electrical signal remains substantially physiologically imperceptible to the patient, and applying the electrical signal to the auditory nerve to generate pseudospontaneous activity in the auditory nerve. 
     To further achieve at least the above objects in a whole or in parts, there is provided a neural prosthetic apparatus for treatment of a patient with tinnitus, including a pseudospontaneous signal generator that generates an electrical signal, an adaptor coupled to the generator that modifies the electrical signal to a sustained effective level while the electrical signal remains substantially physiologically imperceptible to the patient, an arrangement of at least one electrical contact adapted to be affixed nearby the cochlea of the patient, a stimulation device coupled to the adaptor that applies the electrical signal to the at least one electrical contact, the electrical signal capable of generating pseudospontaneous activity in the auditory nerve, and wherein the neural prosthetic apparatus effectively alleviates the tinnitus of the patient. 
     To further achieve at least the above objects in a whole or in parts, there is provided a neural prosthetic apparatus for treatment of a patient with tinnitus, including an adaptor circuit coupled to the stimulation device that modifies one or more electrical signals that include transitions between first and second amplitudes occurring at a frequency greater than approximately 2 kHz to a sustained effective level while the electrical signal remains substantially physiologically imperceptible to the patient, an arrangement of at least one electrical contact adapted to be affixed within the cochlea of the patient, and electrical coupling means for electrically coupling the at least one electrical contact to the stimulation device, and wherein the neural prosthetic apparatus effectively alleviates the tinnitus of the patient. 
     To further achieve at least the above objects in a whole or in parts, there is provided a method of making a neural prosthetic apparatus, including generating a pseudospontaneous electrical signal, determining the parameters for ramping the pseudospontaneous electrical signal from a first voltage level to a second voltage level, wherein the pseudospontaneous electrical signal applied to an auditory nerve of a patient at the second voltage level effectively generates pseudospontaneous activity in the auditory nerve, and wherein the parameters maintain the pseudospontaneous electrical signal at an approximate level below which pain is perceived by the patient. 
     To further achieve at least the above objects in a whole or in parts, there is provided a method for applying a high frequency signal to a nerve, including identifying a voltage level of high frequency signal that is sufficient to cause desired activity in the nerve, wherein the high frequency signal applied at said voltage level further is perceived as pain, modifying the high frequency signal to be the sufficient voltage level while the electrical signal remains substantially physiologically imperceptible to the patient, and applying the electrical signal to the auditory nerve to generate pseudospontaneous activity in the auditory nerve. 
     Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention. The objects and advantages of the invention may be realized and attained as particularly pointed out in the appended claims. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will be described in detail with reference to the following drawings in which like reference numerals refer to like elements wherein: 
     FIG. 1 is a diagram showing related art EAP N1P1 magnitudes in a human subject subjected to a low rate stimulus; 
     FIG. 2 is a diagram showing a section view of the human ear as seen from the front showing the relative positions of the hearing elements including the external ear, auditory cortex, cochlea and cochlear nucleus; 
     FIG. 3 is a diagram showing an exemplary embodiment of a driving signal that generates statistically independent activity in a nerve; 
     FIGS. 4A and 4B are diagrams showing histograms of modeled responses of the human auditory nerve to a high rate pulse train; 
     FIG. 5A is a diagram showing two exemplary unit waveforms; 
     FIG. 5B is a diagram showing an interval histogram; 
     FIGS. 5C-5D are diagrams showing exemplary recurrence time data; 
     FIG. 6 is a diagram of a flowchart showing a preferred embodiment of a method of generating desired activity in a nerve of a patient; 
     FIG. 7 is a diagram of a flowchart showing a preferred embodiment of a controlled application process to suppress tinnitus in an auditory nerve; 
     FIG. 8 is a diagram showing an exemplary driving signal voltage application pattern; 
     FIG. 9 is a diagram of a flowchart showing another preferred embodiment of a controlled application process to suppress tinnitus in an auditory nerve; 
     FIG. 10 is a diagram showing another exemplary driving signal voltage application pattern; 
     FIG. 11 is a diagram of a flowchart showing another preferred embodiment of a controlled application process to suppress tinnitus in an auditory nerve; 
     FIG. 12 is a diagram showing a preferred embodiment of an apparatus that provides a substantially imperceptible driving signal to the auditory nerve according to the present invention; and 
     FIG. 13 is a diagram showing an exemplary adaptor circuit of the apparatus of FIG.  12 . 
    
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
     The auditory system is composed of many structural components, some of which are connected extensively by bundles of nerve fibers. The auditory system enables humans to extract usable information from sounds in the environment. By transducing acoustic signals into electrical signals, which are processed in the brain, humans can discriminate among a wide range of sounds with great precision. 
     FIG. 2 shows a side cross-sectional view of a human ear  5 , which includes the outer ear  5 A, middle ear  5 B and inner ear  5 C. The outer ear  5 A includes pinna  7  having folds of skin and cartilage and outer ear canal  9 , which leads from the pinna  7  at its proximal end to the eardrum  11  at its distal end. The eardrum  11  includes a membrane extending across the distal end of the outer ear canal  9 . The middle ear  5 B is located between the eardrum  11  and the inner ear  5 C and includes three small connected bones (ossicles), namely the hammer  12 , the anvil  14 , and the stirrup  16 . The hammer  12  is connected to the inner portion of the eardrum  11 , the stirrup  16  is attached to oval window  20 , and the anvil  14  is located between and attached to each of the hammer  12  and the stirrup  16 . A round or oval window  20  leads to the inner ear  5 C. The inner ear  5 C includes the labyrinth  27  and the cochlea  29 , each of which is a fluid-filled chamber. The labyrinth  27 , which is involved in balance, includes the semicircular canals  28 . Vestibular nerve  31  attaches to the labyrinth  27 . Cochlea  29  extends from the inner side of the round window  20  in a generally spiral configuration, and plays a key role in hearing by transducing vibrations transmitted from middle ear  5 B into electrical signals for transmission along auditory nerve  33  to the hearing centers of the brain. The cochlea  29  is tonotopically organized, meaning different parts of the cochlea  29  respond optimally to different tones; one end of the cochlea  29  responds best to high frequency tones, while the other end responds best to low frequency tones. The cochlea  29  converts the tones to electrical signals that are then received by a cochlea nucleus (not shown), which is an auditory structure located in the brain. 
     In normal hearing, sound waves collected by the pinna  7  are funneled down the outer ear canal  9  and vibrate the eardrum  11 . The vibration is passed to the ossicles (hammer  12 , anvil  14 , and stirrup  16 ). Vibrations pass through the round window  20  via the stirrup  16  causing the fluid within the cochlea  29  to vibrate. The cochlea  29  is equipped internally with a plurality of hair cells (not shown). Neurotransmitters released by the hair cells stimulate the auditory nerve  33  thereby initiating signal transmission along the auditory nerve  33 . In normal hearing, the inner hair cell-spiral ganglion is inherently “noisy” in the absence of sound because of the random release of neurotransmitters from hair cells. Accordingly, in normal hearing, spontaneous activity in the auditory nerve occurs in the absence of sound. 
     Sound produces a slowly progressive response within and across fiber synchronization as sound intensity is increased. The absence of spontaneous activity in the auditory nerve can lead to tinnitus as well as other hearing-related problems. 
     Preferred embodiments of the present invention emphasize delivery of stochastic independence across an excited neural population without introducing any additional audible or sensory percepts. An exemplary high rate pulse train driving signal  302  according to the first embodiment is shown in FIG.  3 . However, broadband additive noise (e.g., because of rapid signal amplitude transitions), sinusoidal waves, and periodic signals can evoke pseudospontaneous activity similar to the high rate pulse train. 
     A population of 300 modelled auditory nerve fibers (ANF) has been simulated on a Cray C90 (vector processor) and IBM SP-2 (parallel processors) system. The ANF model used a stochastic representation of each node of Ranvier and a deterministic representation of the internode. Recordings were simulated at the 13th node of Ranvier, which approximately corresponds to the location of the porus of the internal auditory canal assuming the peripheral process has degenerated. Post-stimulus time (PST) histograms and interval histograms were constructed using 10 ms binning of the peak of the action potential. As is well-known in the art, a magnitude of the EAPs is measured by the absolute difference in a negative peak (N 1 ) after pulse onsets and a positive peak (P 2 ) after pulse onsets. 
     Stimuli presented to the ANF model were a high rate pulse train of 50 μs monophasic pulses presented at 5 kHz for 18 ms from a point source monopolar electrode located 500 μm perpendicularly from the peripheral terminals of the axon population. All acoustic nerve fibers were simulated as being in the same geometric location. Thus, each simulation can be considered to represent either 300 fibers undergoing one stimulus presentation or a single fiber undergoing 300 stimulus presentations. In addition, a first stimulus of the pulse train was of sufficient magnitude to evoke a highly synchronous spike in all 300 axons; all subsequent pulses are of an equal, smaller intensity. The first stimulus substantially increased computational efficiency by rendering all fibers refractory with the first pulse of the pulse train. 
     Two fibers were simulated for eight seconds using the parameters described above. Spike times were determined with one μs precision and assembled into 0.5 ms bins. Conditional mean histograms, hazard functions and forward recurrence time histograms were calculated (using 0.5 ms bins because of the small number of spikes (1000) simulated) as known to one of ordinary skill in the art. For example, see  Analysis of Discharges Recorded Simultaneously From Pairs of Auditory Nerve Fibers,  D. H. Johnson and N. Y. S. Kiang, Journal of Biophysics, 16, 1976, pages 719-734, (hereafter Johnson and Kiang), hereby incorporated by reference. See also  “Pseudospontaneous Activity: Stochastic Independence of Auditory Nerve Fibers with Electrical Stimulation ,” J. T. Rubinstein, et al., pages 1-18, 1998, hereby incorporated by reference. 
     FIG. 4A shows a post-stimulus time (PST) histogram  402  of discharge times from the ANF model with a stimulus amplitude of 325 μA. A highly synchronous response  404  to a first, higher amplitude pulse was followed by a “dead time”  406 . Then, an increased probability of firing  408  was followed by a fairly uniform firing probability  410 . The y-axis of the PST histogram has been scaled to demonstrate temporal details following the highly synchronous response to the first pulse. There was a small degree of synchronization with the stimulus as measured by a vector strength of 0.26. 
     FIG. 4B shows an interval histogram of the same spike train. As shown in FIG. 4B, a dead time  412  was followed by a rapid increase in probability  414  and then an exponential decay  416 . The interval histogram is consistent with a Poisson process following a dead time, a renewal process, and greatly resembles interval histograms of spontaneous activity in the intact auditory nerve. These simulation results correspond to a spontaneous rate of 116 spikes/second measured during the uniform response period of 7 to 17 ms. 
     Normal spontaneous activity is independent across neurons. A rigorous evaluation of fiber independence is a recurrence-time test. (See, for example, Johnson and Kiang.) By using a bin size of 0.5 ms, useful recurrence-time histograms were assembled from two 2-second spike trains of the ANF model simulation. FIG. 5A shows a 50 ms sample of spike activity from two “units” (i.e., two simulated neurons). FIG. 5B shows an ISI histogram from an eight second run of “unit” b. FIG. 5C shows a forward recurrence-time histogram of “unit” b to “unit” a, and a theoretical recurrence-time from “unit” b assuming that “units” a and b are independent. The theoretical forward recurrence-time curve is flat during the refractory period. Theoretical limits are shown at ρ&lt;0.0124 (2.5 standard deviations). FIG. 5D shows residuals calculated by subtracting the curves in FIG.  5 C. 
     Driving a population of simulated auditory nerve fibers with high rate pulses according to an exemplary pseudospontaneous driving signal produces independent spike trains in each simulated fiber after about 20 ms. This pseudospontaneous activity is consistent with a renewal process and yields statistical data comparable to true spontaneous activity within computational limitations. Thus, the ANF model demonstrated pseudospontaneous activity caused by high rate pulse train stimulation. Further, any signal that results in pseudospontaneous activity that meets the same tests of independence as true spontaneous activity can be used as the driving signal. 
     According to the preferred embodiments of the present invention, the artificial induction of a random pattern of activation in the auditory nerve of a tinnitus patient or a hard-of-hearing patient mimics the spontaneous neural activation of the auditory nerve, which routinely occurs in an individual with normal hearing and lacking tinnitus. The artificially induced random pattern of activation of the auditory nerve is hereafter called “pseudospontaneous”. In the case of an individual having a damaged cochlea, such induced pseudospontaneous stimulation activation of the auditory nerve may be achieved, for example, by the delivery of a high rate pulse train directly to the auditory nerve via a cochlea implant. Alternatively, in the case of a patient with a functional cochlea, pseudospontaneous stimulation of the auditory nerve may be induced directly by stimulation via an appropriate middle ear implantable device. Applicants have determined that high frequency signals of sufficient intensity to induce pseudospontaneous activity, desynchronizing the auditory nerve, and or alleviate the symptoms of tinnitus are substantially physiologically undetectable in a steady state condition of the patient. In dramatic and unanticipated contrast, the identical signals are physiologically and somatosensory detectable as uncomfortable pain, unpleasant noise and/or auditory percepts in a transient period. Such extreme opposite reactions do not appear to be explained using only a physical or only a psychological basis. However, preferred embodiments of a system and method for application of pseudospontaneous neural stimulation can control the transient period to provide a pseudospontaneous neural stimulation without producing an audible percept using inner ear and middle ear neural prosthetic devices, for example, to suppress tinnitus in the auditory nerve. 
     Preliminary studies by the Applicants showed remarkable but temporary auditory and sensory perceptual effects of a high frequency neural stimulation in human subjects. In one patient, a profoundly deaf individual with a cochlear implant, it was demonstrated that the loudness of a suprathreshold 5 kHz biphasic pulse train adapted substantially during continuous presentation. After about 2 or 3 minutes, depending on the stimulus conditions, the initially suprathreshold stimuli became inaudible. In a second patient with mild high frequency hearing loss and severe tinnitus, temporary placement of a promontory electrode stimulated by a 5 kHz biphasic pulse train repeatedly caused substantial but incomplete suppression of the subject&#39;s tinnitus with electrical stimulation. In the second patient, even after the stimulus was adapted to and became inaudible, the stimulus remained effective in reducing the tinnitus loudness. 
     A first preferred method for generating desired activity in a nerve according to the present invention will now be described. As shown in FIG. 6, the process starts in step S 600 . From step S 600 , control continues to step S 610 . In step S 610 , a pseudospontaneous driving signal (PDS) is generated. For example, a driving signal according to the first preferred embodiment can be generated or selected via a selection unit. An exemplary stimulus paradigm for a high-rate pulse train stimulation excepting the amplitude, frequency or interpulse period, which can be adjusted, is shown in FIG.  3 . The high rate pulses  302  have a constant amplitude, pulse width and frequency of approximately 5 kHz as shown in FIG.  3 . From step S 610 , control continues to step S 620 . 
     In step S 620 , an electrical contact is preferably coupled between a nerve such as the auditory nerve in the ear of a patient and the PDS. The electrical contact can be, for example, an electrode array having a plurality of contacts with a prescribed arrangement such as a tonotopic arrangement. Alternatively, a single electrode can be provided to the middle ear region and preferably at or near the round window as well as to the cochlea using a middle ear implant electrically coupled to the auditory nerve and cochlea in the inner ear or the like. From step S 620 , control continues to step S 630 . 
     In step S 630 , the application of the PDS is controlled or tuned to generate a desired activity in the nerve of a patient, for example, suppressing tinnitus in the auditory nerve. The control or tuning preferably accomplishes the application of the PDS to the nerve without generating additional sensations. For example, the tuning applies the PDS to the nerve without generating pain, or generating tolerable levels of pain (i.e., patient specific subjective amounts of pain) over a long term or a short term. From step S 630 , control continues to step S 640  where the process is completed. 
     The controlled application of step S 630 , for example, can include a linear ramping from an initial imperceptible voltage level of the PDS at time zero to a desired voltage level that produces the intended activity in the nerve at time sufficiently after the time zero. The controlled application step according to the first preferred embodiment can optionally include a feed-back test loop to modify or merely select one of a plurality of selectable pseudospontaneous driving signals based on a subset of parameters specifically designed, determined and tested for an individual patient. For example, an exemplary controlled application in step S 630  of a PDS according to the first preferred embodiment can suppress or reduce tinnitus without producing any additional sensation such as pain or audible noises to the patient. 
     The PDS signal at a prescribed level has also generated pain when applied to a sensory nerve. In particular, an exemplary PDS signal applied at 1-2 milliamps to the tongue generated mild pain for approximately 2 seconds. However, when the PDS signal was ramped manually to 1-2 milliamps over a range of seconds such as 5 seconds, application of the 1-2 milliamp PDS signal was not detected (i.e., pain free). However, the rate of firing of the nerves of the tongue may preclude psuedospontaneous activity. 
     FIG. 7 shows a first preferred embodiment of the controlled application process of step S 630  to suppress tinnitus in an auditory nerve. In step S 700 , the process begins. From step S 700 , control continues to step S 710  where an appropriate baseline measurement of the auditory nerve of the patient is performed. Since the desired activity according to the first preferred embodiment of the controlled application step shown in FIG. 7 is to suppress tinnitus in the auditory nerve, two exemplary types of tinnitus patients will be described. One tinnitus patient type has severe-profound hearing loss treated by cochlear implantation and electrical stimulation will be via a cochlear implant. The second tinnitus patient type has mild-moderate high-frequency sensorineural hearing loss and electrical stimulation will be via an acutely placed transtympanic round window electrode or promontory electrode. Accordingly, in step S 710 , assessment procedures including at least one of a level of hearing ability and a level of tinnitus will be determined for each patient regardless of type of tinnitus. However, the two types preferably undergo different baseline or pre-stimulation assessments. 
     Preferably, all mild-moderate subjects are baselined by a medical evaluation, standard audiometry, and measures of spontaneous and click-evoked otoacoustic emissions. All subjects regardless of tinnitus type should complete the Tinnitus Handicap Questionnaire or the like. The Tinnitus Handicap Questionnaire is reliable and its psychometric properties have been previously evaluated using tinnitus sufferers as is known to one of ordinary skill in the art. These measures will allow comparison of tinnitus severity across all subjects independent of subsequent loudness measures. All subjects preferably complete a loudness scaling assessment by reporting the loudness of their tinnitus using a previously evaluated scaling technique on a 100 point scale: 0 corresponding to “no tinnitus” and 100 corresponding to the “loudest tinnitus imaginable”. During subsequent electrical stimulation, loudness scaling for tinnitus as well as any electrically-induced percepts will be repeated in all subjects at all current or stimulation levels. 
     In addition to the questionnaire and the loudness scaling measures, the round window stimulation (mild-moderate) subjects preferably undergo extensive pre-stimulation psychophysical testing as part of baseline assessment. Loudness and dominant pitch of tinnitus will be assessed by comparison with tones presented to the contralateral ear. The amount of broadband noise required to mask the tinnitus in each ear could also be determined. In unilateral tinnitus, similar broadband noise levels required for masking across ears is suggestive of a central etiology. In bilateral tinnitus, the ability of a unilateral masker to suppress tinnitus bilaterally also suggests a central process. Psychophysical tuning curves for masking with tones and narrow-band noise can be performed both for the tinnitus and for tones of matching loudness and pitch. A “critical bandwidth” measurement for noise masking will preferably also be attempted. These latter two measures can be used to determine if the subject&#39;s tinnitus behaves consistently with a peripheral source. Correlations of such localization tests with an electrical suppression can also be evaluated based on assessment and treatment of a sufficient sample. Upon completion of a baseline assessment process in step S 710 , control continues to step S 720 . 
     In step S 720 , application of the PDS signal at an initial voltage V I  is provided to the auditory nerve of the patient. For example, as shown in FIG. 8, the initial voltage V I  can be a level sufficiently small to insure pseudospontaneous activity is not generated in the auditory nerve. Alternatively, the initial voltage V I  could be such that extremely localized pseudospontaneous activity is generated in the nerve. However, the initial voltage V I  is preferably a level that generates pseudospontaneous activity in the auditory nerve but does not generate a detectable auditory percept for the patient. Likely, the initial voltage V I  will be below a prescribed or desired voltage level V D  shown in FIG.  8 . The desired voltage level V D  of the PDS is one that reduces and preferably substantially suppresses tinnitus in the patient. Accordingly, the desired voltage level V D  may vary by patient or may be within a tolerance range suitable for substantially all patients. In addition, the desired voltage level V D  of the PDS could be one that suppresses a ratio or percentage of the detectable tinnitus, such as 50%. 
     As shown in FIG. 8, the initial voltage V I  is applied to the patient at time t equal zero (0) and the desired voltage level V D  is reached at a later exemplary time T 1  using a PDS voltage application pattern  802 . An envelope or boundary  804  passes through voltage level V N  at time zero and represents a voltage level of the PDS that is insufficient to suppress tinnitus but sufficient to generate an audible percept to the patient. Accordingly, any point above the envelope  804  shown in FIG. 8 will generate an audible percept for the patient and any point below the envelope  804  will not generate an audible percept to the patient. As described above, the Applicants initially determined that an application of the PDS at the desired voltage level V D  generated an uncomfortable audible noise relative to the first type of tinnitus patients for an approximate period of 60 seconds or more. At similar applied levels, Applicants determined for the second type of tinnitus patients that inaudible or slightly audible noise resulted. However, the audible noise is likely related to the desired voltage V D  or current level. Thus, the PDS voltage application pattern  802  according to the first preferred embodiment of the controlled application step to suppress tinnitus can be any process that moves the patient from the initial voltage V I  at time zero to the desired voltage V D  at the later time T 1  while remaining below the envelope  804 . Accordingly, the time T 1  preferably extends beyond an initial transient state an could equal, for example 90 seconds or more. The desired voltage level V D  may change for the patient over time. However, an optimal or preferred V D  (e.g., a lowest) may be selected from among voltages that effectively suppress tinnitus. Exemplary applications of the PDS voltage application pattern  802  can include a linear pattern, non-linear patterns including exponential patterns, continuous or intermittent positively sloped increments including discrete stepped voltage levels or the like. In addition, the PDS voltage application pattern  802  varies intensity of the voltage over time. However, the present invention is not intended to be so limited. For example, the PDS pattern could be a power variation over time or a current variation over time to transition the patient from an initial application level to a desired level sufficient to suppress tinnitus without generating additional sensations. From step S 720 , control continues to step S 730 . 
     In step S 730 , it is determined whether the applied PDS generates an audible percept. Preferably, in step S 730  the patient is asked whether the audible percept can be heard. For example, the patient can be asked: a) can you hear any unusual sounds coming from the stimulation; and b) what is the quality and quantity of any sounds or tinnitus you hear during stimulation? If the determination in step S 730  is negative, control continues to step S 740 . In step S 740 , it is determined whether the PDS is at the desired voltage level V D . Alternatively, step S 740  could be accomplished by asking the patient if the tinnitus is suppressed. For example, the patient can be asked: a) can you still hear your tinnitus? and b) what is the quality and quantity of any sounds or tinnitus you hear during stimulation? Such an alterative can be used even in cases where the desired voltage level V D  is not known ahead of time. Further, the determination in step S 740  could be whether the tinnitus is sufficiently suppressed to a prescribed level such as 50% or to a prescribed loudness magnitude. 
     During round window stimulation in step S 740 , loudness matching to a tone presented to the contralateral ear are preferably assessed for both tinnitus and any electrically-induced percepts at all stimulus levels to complement the scaling measures during the assessment period of step S 710 . In addition, sound-field pure-tone thresholds measured with contralateral masking can assess any possible threshold shift induced by the stimulus. Threshold measures will be repeated with and without electrical stimulation to control for the small conductive hearing loss produced by the myringotomy and electrode placement. Post-stimulus suppression and recovery effects are also preferably measured and classified in a manner similar to post-acoustic masking recovery. 
     In step S 740 , additional measurements of the PDS can preferably include current monitoring at the electrode. For subjects undergoing round window stimulation, a current generated by the applied voltage level of the PDS can be monitored, for example, in two ways. First, a battery-powered oscilloscope could constantly monitor the current flowing through the transtympanic electrode. In the first type tinnitus suppression using an inner ear implant, the processor of a cochlear implant for example can be calibrated with both in vitro resistive and realistic in vivo loads so that an approximate mapping from the clinical units used by the programming software to the current applied is generated. Such a mapping for the cochlear implant is obtained under the same PDS conditions that are used with promontory stimulation. Thus, prior to applying the PDS voltage level, an approximate current can be applied in the initial low setting is 50-75 microamperes. If the determination in step S 740  is negative, the process continues to step S 750 . 
     In step S 750 , the voltage level of the PDS is increased and the current delivered during the stimulation is preferably constantly monitored and measured. Preferably, the voltage level of the PDS is increased according to a prescribed pattern. The same preset stimulus can be used across subjects along with monitoring a degree of tinnitus suppression and duration of any recovery effect. Accordingly, alternative patterns can be determined, evaluated and compared. From step S 750 , control returns to step S 730 . 
     If the determination in step S 730  is affirmative, control continues to step S 760 . In step S 760 , another pattern for applying the PDS is selected and control returns to step S 720 . Alternatively, in step S 760  a user defined stimulus with or without monitoring could be selected and used. If the determination in step S 740  is affirmative, the process continues to step S 770 . Then, in step S 770  control returns to step S 640 . The first preferred embodiment of the controlled application step S 630  shown in FIG. 7 could further include a feed back loop such that a plurality of successful patterns are evaluated and quantitatively and qualitatively compared. 
     FIG. 9 shows a second preferred embodiment of the controlled application process of step S 630  to suppress tinnitus in an auditory nerve. In step S 900 , the process begins. From step S 900 , control continues to step S 910  where an appropriate baseline measurement of the hearing and tinnitus levels of the auditory nerve of the patient is performed. The process in step S 910  can be similar to the process in step S 710 . From step S 910 , control continues to step S 920 . 
     In step S 920 , application of the PDS signal at an initial voltage V I  is provided to the auditory nerve of the patient. For example, as shown in FIG. 10, the initial voltage V I  can be any level that preferably does not generate a detectable level of pain for the patient. Likely, the initial voltage V I  will be below a prescribed or desired voltage level V D  shown in FIG.  10 . The desired voltage level V D  of the PDS is preferably a lowest level voltage that reduces or substantially suppresses tinnitus in the patient. 
     As shown in FIG. 10, the initial voltage V I  is applied to the patient at time t equal zero (0) and the desired voltage level V D  is reached at a later exemplary time T 2  using a PDS voltage application pattern  1002 . An envelope or boundary  1004  passes through voltage level V P  at time zero and represents a voltage level of the PDS that is insufficient to suppress tinnitus but sufficient to generate pain detected by the patient. Accordingly, any point above the envelope  1004  shown in FIG. 10 will generate detectable or perceptible pain for the patient and any point below the envelope  1004  will not generate pain. As described above, the Applicants determined that an initial application of the PDS at the voltage level V D  generated an uncomfortable to severe level of pain for an approximate period of seconds for the second type of tinnitus patients. However, the pain is likely related to the desired voltage level V D  or a desired current level. Thus, the PDS voltage application pattern  1002  according to the second preferred embodiment of the controlled application step to suppress tinnitus can be any process that moves the patient from the initial voltage V I  at time zero to the desired voltage V D  at the later time T 2  while remaining below the envelope  1004 . Accordingly, the time T 2  preferably to extends beyond an initial transient state and could equal, for example 2 seconds or more. Exemplary applications of the PDS voltage application pattern  1002  can include a linear pattern, non-linear patterns including exponential patterns, continuous or intermittent positively sloped increments including discrete stepped voltage levels or the like. From step S 920 , control continues to step S 930 . 
     In step S 930 , it is determined whether the applied PDS generates detectable pain. Preferably, in step S 930  the patient is asked whether the pain is present and to describe the pain. For example, the patient can be asked: a) can you describe the pain level resulting from the stimulation; and b) what is the quality and quantity of any pain felt or tinnitus heard during stimulation? If the determination in step S 930  is negative, control continues to step S 940 . Steps S 940  through step S 970  are similar to steps S 740  through step S 770  of the first preferred embodiment of the controlled application to suppress tinnitus in an auditory nerve. Accordingly, a detailed description is omitted. It should be noted that the tinnitus suppression of step S 940  likely happens after a delay of 60 to 90 seconds or more after reaching the desired voltage V D . 
     FIG. 11 shows a third preferred embodiment of the controlled application process of step S 630  to suppress tinnitus in an auditory nerve. As shown in FIG. 11, step S 1100  through step S 1160  are similar to step S 700  through step S 760 , and step S 900  through step S 960  of the first and second preferred embodiments of the controlled application to suppress tinnitus in an auditory nerve, respectively. Accordingly, a detailed description is omitted. However, in step S 1130 , detectable noise and/or pain can be concurrently or sequentially evaluated for all tinnitus patients. If the determination in step S 1140  is affirmative, control continues to step S 1170 . 
     In step S 1170 , it is determined whether all possible patterns of a plurality of pattern such as a PDS voltage application or power application pattern have been evaluated. If the determination in step S 1170  is negative, control returns back to step S 1160  where another pattern is selected. If the determination in step S 1170  is affirmative, control continues to step S 1180 . In step S 1180 , the successful patterns as described above are compared and a preferred pattern is quantitatively or qualitatively determined and then selected. Further, a final desired voltage V D  can be determined. In other words, the desired voltage V D  may vary by patient and accordingly a preferred final desired voltage V D  can be quantitatively or qualitatively selected. From step S 1180 , control continues to to step S 1190 . Then, in step S 1190  control returns to step S 640 . 
     A second preferred embodiment of an apparatus to generate and substantially imperceptibly apply a pseudospontaneous driving signal to an auditory nerve according to the present invention will now be described. As shown in FIG. 12, the second preferred embodiment includes an inner ear stimulation system  1200  that directly electrically stimulates the auditory nerve (not shown). The inner ear stimulation system  1200  can include two components: (1) a wearable or external system, and (2) an implantable system. An external system  1202  includes a signal generator  1210 . The signal generator  1210  can include a battery, or an additional equivalent power source  1214 , and further includes electronic circuitry, typically including a controller  1205  that controls the signal generator  1210  to produce prescribed electrical signals. 
     The signal generator  1210  produces a driving signal or conditioner  1216  to generate pseudospontaneous activity in the auditory nerve. For example, the signal generator can produce a pseudospontaneous driving signal (PDS) in accordance with the first preferred embodiment. The signal generator  1210  can be any device or circuit that produces a waveform that generates pseudospontaneous activity. That is the signal generator  1210  can be any device that selects the PDS. For example, an application program operating on a special purpose computer or microcomputer combined with an A/D converter, and LC resinating circuit, firmware or the like can be used, depending on the exact form of the pseudospontaneous driving signal. Further, the inner ear stimulation system  1200  can preferably suppress, effectively alleviate or eliminate tinnitus in a patient without generating additional sensory percepts. The signal generator  1210  can vary parameters such as the frequency, amplitude, pulse width of the driving signal  1216 . The external system  1202  can be coupled to a head piece  1212 . For example, the head piece can be an ear piece worn like a hearing aid or surgically implanted under the skin behind the ear. Alternatively, the external system  1202  can be a separate unit. 
     As shown in FIG. 12, the controller  1205  is preferably implemented on a microprocessor. However, the controller  1205  can also be implemented on a special purpose computer, microcontroller and peripheral integrated circuit elements, an ASIC or other integrated circuit, a hardwired electronic or logic circuit such as a discrete element circuit, a programmable logic device such as a PLD, PLA, FGPA or PAL, or the like. The controller  1205  includes an adaptor circuit  1207 . However, the adaptor circuit  1207  can be a separate unit from the controller  1205  in the external system  1202 , outside the external system  1202  or as part of the implantable system  1220 . In general, any device on which a finite state machine capable of controlling a signal generator and implementing the flowchart shown in FIGS. 6-7,  9  and  11  can be used to implement the controller  1205 . 
     As shown in FIG. 12, the implantable system  1220  of the inner ear stimulation system  1200  can include a stimulator unit  1222  directly coupled to the auditory nerve. For example, the stimulator unit  1222  can include an electrode array  1224  or the like for implantation into the cochlea of a patient. The electrode array  1224  can be a single electrode or multiple electrodes that stimulate several different sites at arranged sites along the cochlea to evoke nerve activity normally originating from the respective sites. Preferably, the single electrode is adapted to be affixed as close to the round window to allow stimulation of the auditory nerve and cochlea according to the PDS voltage application pattern The stimulation unit  1222  is preferably electrically coupled to the auditory nerve. The stimulation unit  1222  can be located in the inner ear, middle ear, ear drum or any location that effectively couples the stimulation unit  1222  to the auditory nerve directly or indirectly, and produces pseudospontaneous activity in the auditory nerve caused by the stimulation unit  1222 . In addition, the implantable system  1220  can be directly or indirectly coupled to the external system  1202 . 
     If indirectly coupled to the external system  1202 , the stimulator  1222  can include a receiver  1226 . The receiver  1226  can receive information and power from corresponding elements in the external system  1202  through a tuned receiving coil (not shown) attached to the receiver  1226 . The power, and data as to which electrode to stimulate, and with what intensity, can be transmitted across the skin using an inductive link from the external signal generator  1210 . For example, the receiver  1226  can then provide electrical stimulating pulses to the electrode array  1224 . Alternatively, the stimulation unit  1222  can be directly coupled to the external system  1202  via a conductive medium or the like. 
     The patient&#39;s response to electrical stimulation by the driving signal  1216  can be subsequently monitored or tested. The results of these tests could be used to modify the driving signal  1216  or to select from a plurality of driving signals using a selection unit  1218 . 
     In particular, according to the second preferred embodiment of an apparatus to generate and substantially imperceptibly apply a pseudospontaneous driving signal to an auditory nerve, the adaptor circuit  1207  is provided to transition through an initial transient state upon application of the PDS. The adaptor circuit  1207  can control, for example, according to the PDS voltage application pattern  1002  shown in FIG. 10, application of the desired voltage level V D  to suppress tinnitus. An exemplary circuit for the adaptor circuit  1207  is shown in FIG.  13 . As shown, the adaptor circuit  1207  is coupled to the driving signal  1216  used for the electrical stimulation. As shown in FIG. 13, the adaptor circuit  1207  includes series coupled switch  1302  and resistance unit  1304 . The resistance unit  1304  is preferably a variable resistance unit that is selectively coupled to the driving signal  1216 . As the resistance of the variable resistance unit  1304  is varied while coupled to the driving signal  1216 , a controlled increased current will be diverted from the stimulation unit  1222 . The adapter circuit  1207  may also include a user controllable adjuster unit or mechanism (not shown) to enable the user to control the adjustment or select a pattern. A built-in safety mechanism would be included in the adapter circuit  1207  to ensure the patient cannot cause injury. Thus, any one of a plurality of driving signals  1216  including a linear pattern, non-linear patterns like exponential patterns, continuous or intermittent positively sloped increments including discrete stepped voltage levels or the like can be provided using the adaptor circuit to the stimulation unit  1222 . 
     When the stimulation unit  1222  includes the electrode array  1224 , the stimulator unit  1222  can operate in multiple modes such as, the “multipolar” or “common ground” stimulation, and “bipolar” stimulation modes. However, the present invention is not intended to be limited to this. For example, a multipolar or distributed ground system could be used where not all other electrodes act as a distributed ground, and any electrode could be selected at any time to be a current source, current sink, or to be inactive during either stimulation phase with suitable modification of the receiver-stimulator. Thus, there is great flexibility in choice of stimulation strategy to provide the driving signal  1216  to the auditory nerve. However, the specific method used to apply the driving signal must result in the pseudospontaneous activity being generated. In addition, the present invention is not intended to be limited to a specific design of the electrode array  1224 , and a number of alternative electrode designs as have been described in the prior art could be used. 
     The preferred embodiments according to the present invention are described above primarily with respect to a controlled voltage. However, a current source or current controlled stimulation is preferable for generating nerve responses. Movement of the electrode or the type of surrounding tissue can effect impedance and accordingly effect an applied voltage and for example, reproducible results. 
     As described above, the preferred embodiments of a system and method for application of pseudospontaneous neural stimulation according to the present invention have various advantages. The preferred embodiments generate stochastically independent or pseudospontaneous neural activity, for example, in an auditory nerve to suppress tinnitus. Further, based on likely physiological recognition of the pathogenesis of tinnitus at the periphery, psychoacoustical studies of tinnitus patients and biophysical studies of cochlear implantation, the preferred embodiments of a method and apparatus for application of pseudospontaneous neural stimulation selects specific patterns of electrical to suppress tinnitus without producing an auditory percept. Accordingly, a stimulus that evokes pseudospontaneous activity and is not be perceptible over the long term when the rate is physiologic is also not perceptible over the short term or initially. Thus, an inner ear or middle ear auditory prosthesis can be provided that substantially imperceptibly suppresses tinnitus. In addition, the preferred embodiments provide an apparatus and method that delivers a prescribed signal such as a high rate pulse train to imperceptibly generate neural pseudospontaneous activity and may be used in conjunction with a suitable auditory prosthesis to increase hearing capability by providing a prescribed signal to auditory neurons. 
     The foregoing embodiments are merely exemplary and are not to be construed as limiting the present invention. The present teaching can be readily applied to other types of apparatuses. The description of the present invention is intended to be illustrative, and not to limit the scope of the claims. Many alternatives, modifications, and variations will be apparent to those skilled in the art.