WO2002047547A1

WO2002047547A1 - A method of measuring the activity of a biological system

Info

Publication number: WO2002047547A1
Application number: PCT/AU2001/001620
Authority: WO
Inventors: Burkhard K. H. G. Franz
Original assignee: Franz Burkhard K H G
Priority date: 2000-12-15
Filing date: 2001-12-14
Publication date: 2002-06-20
Also published as: AUPR205400A0; AU2002220377A1

Abstract

The method and apparatus for measuring the activity of a biological system, particularly the vestibular organ, to a single stimulus by applying the stimulus to the biological system, detecting an electrical response of the system to the single stimulus and processing the electrical response to identify at least one repeated periodic signal. An alternative method and apparatus for measuring the activity of a biological system is described where, in the absence of any external stimulus to the biological system, the method includes detecting an electrical output produced by the system and processing the electrical output to identify a repeated periodic signal. Tinnitus may be detected by this method using an electrode in the tympanic recess.

Description

A METHOD OF MEASURING THE ACTIVITY OF A BIOLOGICAL SYSTEM

The present application is directed to a method of measuring the activity of a biological system and to a method of diagnosis. In one embodiment this application is directed to a method of diagnosing disorders of the vestibular organ, and of its parts the semicircular canal and the otolithiic organ. Another embodiment is directed to providing an objective measurement of tinnitus. However, these are only some of the applications of the present application, albeit preferred and it should be understood that in its broadest scope the invention is not limited to these applications.

There are numerous diseases and problems of the vestibular organ including allergies, sudden vestibular loss, vestibular neuritis, vestibular neuropathy, Meniere's disease, benign positional vertigo, tumours of the vestibular organ and autoimmune disorders of the vestibular organ.

Disorders that affect the functioning of the vestibular organ can be diagnosed by stimulating the vestibular organ, indirectly measuring the response and then analysing the measured response. Previous methods of such diagnosis have been to apply a thermal stimulus to a patient's inner ear by introducing hot or cold water into the opening of the ear canal and measuring eye movement in response to this stimulation. Another method has been to place electrodes on the head of the patient, place the patient in a rotatory chair and measure brain voltages following rotation. A disadvantage of both of these methods is that they are indirect measuring techniques and do not measure the specific activity of the vestibular organ. The former method measures the response of another sensory modality affected by the activity of the vestibular organ. The latter method can only provide an indication of the combined activity of both the left and right vestibular organs and therefore is not specific nor ideal for detecting those disorders which reside or affect one organ only. Also the latter method does not record early vestibular evoked potentials, but rather later cortical potentials which are not a result of the sensory organ alone. The electrical voltage of the response produced by an organ to a stimulus can be measured, however, the response of the organ is typically very small compared with other background electrical signals that may be present. One means employed to measure such small level signals in the presence of other signals is to apply multiple stimulations and record and average the response of each stimulation to obtain an accurate indication of the response.

Whereas the required averaging measurement period can be a fraction of a second, the overall response of an organ such as the vestibular organ can last several minutes and the recovery of the organ 5 to 10 minutes. So as to avoid interference from previous stimulations the interval between stimulations using this technique should be no less than 5-10 minutes. Accordingly, this approach does not provide a practical way of measuring the activity of an organ such as the vestibular organ and performing a diagnosis.

The inventor has discovered that a biological system produces a repeated, periodic electrical signal. Furthermore, a single stimulus will elicit this repeated periodic signal. This repeated, periodic signal can be measured using techniques such as averaging and the signal can provide an indication of the activity of the biological system and a direct diagnosis of a biological system can be performed.

With regard to the vestibular organ, this allows one to more directly measure early evoked potentials and their latencies, including early evoked brainstem or higher potentials, using one or more electrodes.

The inventor has also found that such measuring techniques can be employed to measure tinnitus and objectively demonstrate the presence of tinnitus.

Tinnitus is the perception of sound when no external sound is present.

This condition is colloquially referred to as "ringing in the ears". The detection of tinnitus is relatively difficult, with current procedures relying on having the patient relaying symptoms to the medical professional for subsequent diagnosis. This is a particular problem where the patient has not perceived all of the tinnitus effects or where the patient is unable to communicate the effects to the physician.

Tinnitus is a condition where there exists spontaneous activity of a biological system without any external stimulus. The inventor has discovered that the electrical signal that results from this spontaneous activity is also a repeated periodic signal. Identifying this repeated periodic signal can be used as a means of objectively measuring the tinnitus.

The inventor has recognised that the principles relied upon in the method of objectively measuring tinnitus, can be applied to other biological systems. For example, the method can be utilised to objectively measure pain or objectively measure hearing loss.

In one aspect the present invention is a method of measuring the activity of a biological system to a single stimulus, including:

- applying a single stimulus to the biological system;

- detecting an electrical response of the biological system to the single stimulus; and

- processing the electrical response to identify at least one repeated, periodic signal.

One method of processing the electrical response is averaging. This can be performed by making multiple recordings of the response at a predetermined period and an average of the multiple recordings is made to identify the repeated, periodic signal.

The predetermined period is that period which most closely approximates the period of the natural response of the biological system or is a harmonic of this period.

In a preferred embodiment, phase correction is performed during the recording of the electrical response so as to align the recording period. Alternatively, or in addition to this, the average of the multiple recordings is calculated using phase correction so as to align the measurement results upon such calculation.

The methods described above rely upon multiple recordings being made. An alternative approach to processing the electrical response is to take one continuous recording over an interval of time and split the recording up into periods corresponding to the natural period of the response of the biological system or a harmonic of this frequency and averaging these periods. A further step in this method may include analysing the electrical response that is obtained to determine the natural period. In this averaging method the period of recording is preferably up to 60 seconds.

The predetermined period or natural period of the response of the biological system can be determined in a variety of ways.

For example, the period of the response can be determined by applying a stimulus to the biological system, making multiple recordings of the electrical response of the biological system to this stimulus at a preselected period and then increasing and/or decreasing the preselected period until the repeated, periodic signal is clarified. The increased or decreased preselected period corresponds to the natural period of the biological system.

An alternative method for identifying the natural period of the response of the biological system includes applying a stimulus to the biological system, obtaining the frequency spectrum of the electrical response of the biological system to the stimulus, obtaining the frequency spectrum of a base-line signal recorded in the absence of stimulus, subtracting the base-line frequency from the response frequency spectrum and identifying peaks in the adjusted frequency spectrum, these peaks corresponding to the natural period or harmonics of the natural period. One or more of these peaks may be chosen as the preselected period for use in the previous trial and error method. In this way the peaks which correspond to the preferred period for recording, being the period corresponding to the clearest response of the biological system, can be identified.

A base-line frequency spectrum is that frequency spectrum of a recording of electrical activity in the absence of any stimulation of the biological system. This recording can be described as a recording of a background signal, which does not emanate from the biological system.

These methods of identifying the natural period of the response of a biological system to a stimulus are considered to be new, as they are based on the discovery that a biological system produces a repeated periodic signal in response to a single stimulus.

Other methods of processing that can be utilised are FFT techniques and wavelet analysis.

Where a technique using wavelets is utilised, wavelet analysis can be used to extract features from the non-stationary signal retrieved from the biological system. The inventor has found that the measured signal can be recorded and then transformed into coefficients using a wavelet transform. The coefficients can then be analysed and unwanted coefficients adjusted by zeroing. The remaining coefficients can then be used to reconstruct the signal with the aid of an inverse wavelet transform. The adjustment of coefficients before reconstruction of the signal allows suppression of any undesirable features within the signal. It should be noted that in the analysis of biological systems using wavelets, it is not necessarily the largest coefficients that should be zeroed. In fact, the inventor has found that in many cases, in analysis of a biological system, that it is the largest coefficients that represent unwanted noise within the signal.

The present invention is particularly useful for measuring the activity of the vestibular organ. The inventor has found that if an averaging technique is used, then the preferred predetermined period for recording the response of the vestibular organ to a single stimulus is either 1/23 or 1/46 seconds.

The inventor has further found that the response of the vestibular organ occurs in the first part of the predetermined period, which can be designated the prime response period. Thus, in an alternative embodiment measurements are taken for a portion of each period. In some cases only the first 10 milliseconds of each period are recorded and these portions of the response are averaged to identify the repeated periodic signal produced by the vestibular organ.

Other parts of the response relate to the response of higher centres of the vestibular pathway such as the brain stem, cerebellum and cortex. These parts may be recorded to obtain the signal of these other organs.

It is preferred that in this method of processing the response of the vestibular organ, the recordings continue over an interval of up to 10 seconds. It has been determined that if the recordings are carried out over a longer interval, the recordings can cancel each other out.

When the above methods are carried out in respect of the vestibular organ, the stimulus of the vestibular organ may be any type of stimulus or any combination of stimulus, such as kinetic or motion stimulus, drug induced stimulus, electrical stimulus or thermal stimulus which can include hot or cold water, other fluids or gaseous substance introduced into the patient's ear canal. It is theorised by the inventor that this stimulus may be functioning as a declining stimulus over time.

When the vestibular organ responds to a stimulus, the inventor has been able to identify distinct parts of the signal, including the summating potential of the sensory cells of the vestibular organ (designated SP) and the action potential of the vestibular nerve (designated AP) and the latency of the response. To the inventor's knowledge, this is the first time anyone has been able to identify and measure the SP of the vestibular organ in response to a stimulus. Accordingly, in another aspect the present invention is directed to a method of measuring the summating potential of the sensory cells of the vestibular organ to a single stimulus including:-applying a single stimulus to the vestibular organ;

- detecting an electrical response of the vestibular organ to the single stimulus;

- processing the electrical response to identify at least one repeated, periodic signal; and - measuring from the repeated, periodic signal the summating potential of the sensory cells of the vestibular organ.

In a preferred embodiment, the action potential of the vestibular nerve is also measured from the repeated, periodic signal and the ratio of the summating potential and action potential is calculated.

In another aspect the present invention is directed to a method of measuring the latency of response of a vestibular organ to a single stimulus including:

- applying a single stimulus to the vestibular organ;

- recording an electrical response of the biological system to the single stimulus;

- processing the electrical response to identify at least one repeated, periodic signal; and

- measuring from the repeated, periodic signal the latency of the response of the vestibular organ.

An electrocochleograph device can be used to carry out the recordings of the vestibular response. The device is intended to be used to measure the response of the cochlea to multiple stimuli and functions by making a series of rapid audible clicks, being cochlear stimulation, and making voltage recordings after each click. To adapt the machine to be used in the method for measuring the vestibular response described above, the stimulus generating function of the device is deactivated.

The methods described above can also be used to measure the activity of the otolithiic organ. The primary role of the otolithic organ is in sensing linear motion and gravity. The otolithiic organ broadly comprises two units: the utriculus and the sacculus.

The stimulus to the otolithic organ can be applied by tilting the person's head.

Where the method is applied in respect of the otolithic organ and the processing step is carried out by making recordings at a predetermined period, the predetermined period is preferably 1/23 seconds. When multiple recordings at this period are averaged, the inventor has been able to identify a single repeated signal from each of the utriculus and sacculus. Within these signals, the inventor has been able to identify a part corresponding to the nerve action potential and a part corresponding to the summating potential of the sensory cells

The inventor believes that this is the first time any one has been able to measure the summating potential of the sensory cells of the otolithic organ.

Accordingly in another embodiment the present invention is directed to a method of measuring the summating potential of the sensory cells of the otolithic organ to a single stimulus including:

- applying a single stimulus to the otolithic organ;

- detecting an electrical response of the otolithic organ to the single stimulus;

- measuring from the repeated, periodic signal the summating potential of the sensory cells of the otolithic organ. The summating potential of the sensory cells of the utriculus and sacculus can also be measured in this way.

Recording of the electrical response of the otolithiic organ is preferably made within ten seconds of applying the stimulus, otherwise the recording frequency and response frequency go out of phase.

Measurement of activity of a biological system provides a means of diagnosing disorders of the system. For example, the identified repeated period signal of the biological system in a patient can be compared to the repeated period signal that would be expected for the same biological system in a healthy person.

Accordingly, in another aspect the present invention is directed to a method of diagnosing disorders of a biological system including:

- applying a single stimulus to the biological system;

- detecting an electrical response of the biological system to the single stimulus; - processing the electrical response to identify at least one repeated, periodic signal; and

- analysing the signal to diagnose the biological system.

The processing step may be done in accordance with any of the methods described above.

The analysis can be carried out by comparing the identified signal to the signal of a healthy biological system.

In preferred embodiments this method can be used to diagnose disorders of the vestibular organ, more preferably such disorders including allergies, sudden vestibular loss, vestibular neuritis, vestibular neuropathy, Meniere's disease, benign positional vertigo, tumours of the vestibular organ and autoimmune disorders of the vestibular organ. The inventor has discovered that the SP/AP ratio as well as the latency of the response of a biological system provide an indicator of the integrity of this biological system. If this ratio exceeds the determined "normal" ratio by statistically significant amounts, a diagnosis can be made that the system is not functioning normally. Equally the latency of the response can be used for diagnostic purposes.

In another aspect the present invention is directed to a method of diagnosing a disorder of the vestibular organ including:

- applying a single stimulus to the vestibular organ;

- processing the electrical response to identify at least one repeated, periodic signal; - measuring from the repeated, periodic signal the summating potential of the sensory cells of the vestibular organ (SP) and the action potential of the vestibular nerve (AP);

- calculating the ratio of SP/AP; and

- comparing the measured SP/AP ratio with a predetermined SP/AP.

In another aspect the present invention is directed to a method of diagnosing disorders of a vestibular organ to a single stimulus including:

- applying a single stimulus to the vestibular organ;

- detecting an electrical response of the biological system to the single stimulus;

- processing the electrical response to identify at least one repeated, periodic signal;

- measuring from the repeated, periodic signal the latency of the response of the vestibular organ; and - comparing the measured latency of response with a predetermined latency of response.

The SP/AP ratio and latency of response of a normal biological system such as the vestibular organ can be determined by selecting a group of people each having a normally functioning vestibular organ, measuring the summating potential of the sensory cells of the vestibular organ and the action potential of the vestibular nerve and latency of response for each person using the method of measuring the activity of this organ as described above, calculating the ratio of SP/AP and their latencies for each person and calculating the average SP/AP ratio and average latency of response.

The SP/AP ratio and latency of response of a biological system such as the vestibular organ having a particular disease or affliction can be determined by selecting a group of people each suffering from the particular disease or affliction of the vestibular organ, measuring the summating potential of the sensory cells of the vestibular organ and the action potential of the vestibular nerve as well as the latency of response for each person using the method described above and calculating the average SP/AP ratio and average latency of response.

The SP/AP ratio and latency of response calculated using this method corresponds to the SP/AP ratio and latency of response of a vestibular organ suffering from the particular disease or affliction and can therefore be used to diagnose the disease or affliction in patients.

The inventor has determined the SP/AP ratio for a healthy vestibular organ is preferably in the range of 16 to 30% and is more preferably 23%, and if the measured SP/AP value for a patient exceeds these values, this is an indication that the vestibular system is not functioning normally. The inventor has also determined the latency of response for a healthy vestibular organ is preferably between 1.6 to 2.2 milliseconds and is more preferably 1.8 milliseconds and if the measured latency for a patient exceeds these values, this is an indication that the vestibular organ is not functioning normally. It has been further discovered that certain SP/AP ratios and certain latencies of response correlate with certain diseases and afflictions of the vestibular organ, including allergies, sudden vestibular loss, vestibular neuritis, vestibular neuropathy, Meniere's disease, benign positional vertigo, tumours of the vestibular organ and autoimmune disorders of the vestibular organ. An electrode can be used in the method of this invention to measure the activity of the biological system. The activity of the vestibular organ or otolithic organ can be measured using an electrode placed in the ear canal of the patient. To the inventor's knowledge, use of an electrode in this manner to measure the activity of these organs is new. Accordingly, in another aspect the present invention is directed to a method of measuring the activity of the vestibular organ or otolithic organ including:

- placing an electrode in the ear canal of a patient; - applying a single stimulus to the vestibular organ or otolithic organ;

- detecting with the electrode an electrical response of the vestibular organ or otolithic organ to the single stimulus; and

- processing the electrical response to identify at least the repeated, periodic signal.

The present inventor has also discovered a method of measuring the latency of the response of the vestibular organ which is thought to be new. Previously, the latency of the response was measured by placing an electrode directly onto the vestibular nerve during surgery. The present inventor has found that the latency of response can be measured by placing an electrode in the ear canal of a patient. Accordingly, in another aspect the present invention is to a method of measuring the latency of response of the vestibular organ to a stimulus including:

- placing an electrode in the ear canal of the patient; - stimulating the vestibular organ of a patient; and

- measuring the latency of the response.

In a preferred embodiment, the electrode is placed in the tympanic recess or alternatively in the external ear canal.

In another preferred embodiment, the biological system is the otolithiic organ and the method is utilised to diagnose disorders of this organ. By comparing the measured activity of the otolithiic organ in a patient with values expected in a healthy, functioning organ, diagnosis of disorders of the otolithiic organ can be made.

The inventor has found that when the stimulation applied to the otolithiic organ is an ipsilateral head tilt, the SP/AP ratio of the response of a normally functioning utriculus is 18.3 plus or minus 4.9%. When the stimulation that is applied is a contralateral head tilt, the SP/AP ratio of the response of a normally functioning utriculus is 32.3 plus or minus 13.7%. These two values can be combined to provide a co-efficient of 0.62 plus or minus 0.2 and this co-efficient is characteristic of a normally functioning utriculus. The inventor has found that a utriculus that is not functioning properly, typically shows a co-efficient above one.

The inventor has found that when the stimulation applied to the otolithiic organ is an forward head tilt, the SP/AP ratio of the response of a normally functioning sacculus is 18.5 plus minus 6.9% and when the stimulation is a backward head tilt, the SP/AP ratio of the response of a normally functioning sacculus is 33.6 plus or minus 11.8%. These two values can be combined to provide a co-efficient of 0.61 plus or minus 0.28 and this co-efficient is characteristic of a normally functioning sacculus. The inventor has found that a sacculus that is not functioning normally typically shows a co-efficient above one.

Thus, by measuring the activity of the utriculus and sacculus in a patient in response to ipsilateral and contralateral head tilt, calculating these ratios and co-efficients and comparing these ratios and co-efficients to those observed in the utriculus and sacculus of a healthy otolithiic organ, diagnosis of disorders of the utriculus and sacculus and of the otolithiic organ can be made.

A further application of the present invention is an objective test for hearing loss. In this method, the stimulus is an auditory stimulus, such as a pure tone. The hearing test is carried out by presenting a pure tone of a certain frequency and intensity to the patient; detecting the response of the cochlea and processing the response to identify a repeated, periodic signal. The test is repeated by progressively lowering the intensity of the stimulus until the repeated, periodic signal can no longer be detected. This point represents the patient's threshold of hearing at the frequency of the pure tone.

In this test, the electrical response can be detected by an electrode placed in the tympanic recess of the ear. Where the processing is carried out by an averaging technique and recordings are made at a predetermined period, the period can correspond to a harmonic of the frequency of the pure tone stimulus. Thus, if the stimulus has frequency of 1000 htz, a predetermined period of 1/15.63 sec can be chosen. If stimulus frequency is 3000 htz, predetermined periods of 1/11.72 sec or 1/23.44 sec may be chosen.

It is envisaged that this method will provide a far more accurate test for hearing loss than the previously practised subjective test where sounds are presented to a patient and the patient is asked to respond. The method is especially valuable where the patient is incapable of communicating with the person conducting the test.

The inventor has found that the method of measuring the activity of a biological system as described above can also be used where spontaneous activity of the biological system is present and therefore stimulation is not required. Where this spontaneous activity is a symptom of a disorder of the biological system, the method provides a means of objectively detecting this disorder.

Accordingly, in another aspect the present invention is directed to a method of detecting the activity of a biological system in the absence of any external stimulation including:

- detecting an electrical output produced by the biological system; and - processing the electrical output to identify a repeated, periodic signal produced by the biological system. As discussed above, the processing step can be carried out using a variety of techniques such as averaging, FFT or wavelet analysis.

The inventor has found that where the averaging technique is used to process the electrical output by recording at pre-determined intervals, it is preferable to record at a period corresponding to the natural frequency of the biological system or a harmonic of this frequency.

Tinnitus is an indicator of a fault in the auditory system. It is often termed the pain of the ear.

One application of this method is an objective means of detecting the presence of tinnitus. This is especially valuable where the patient is unable to communicate with the physician or where the patient cannot perceive all of the effects of the patient's own tinnitus condition. In some cases a patient may believe they experience tinnitus where in fact no tinnitus exists. The perception of sound may be a psychiatric disorder.

To objectively detect tinnitus using the method of this invention, the processing step can be carried out using the averaging technique. One approach is to average at different predetermined periods corresponding to frequencies from 7.8 htz up to 15.7 htz in 0.1 intervals until a record of a clear action potential or more preferably, a sine wave signal is identified. A sine wave signal will appear where the predetermined period corresponds to a harmonic of the tinnitus frequency. Thus the appearance of a clear action potential that does not change with repeated measurements or a sine wave signal is an indication that tinnitus is present. The inventor has calculated that the frequencies between 7.8 hts and 15.7 htz should correspond to harmonics of tinnitus frequencies.

Where the patient is able to communicate with the physician, the predetermined period to be used in the recordings can be determined by asking the patient to identify the frequency of the perceived tinnitus sound. Sub- harmonics of this identified frequency are then calculated and recordings are made at periods matching these sub-harmonic frequencies until a recording period is identified that produces the clearest repeated, periodic signal having a sine wave characteristic. The presence of tinnitus can therefore be verified.

Different parts of the repeated, periodic signal that is identified correspond to the nerve action potential and sensory cell potential. The signal also provides a measure of the tinnitus latency and an indication where in the cochlea the fault lies. Furthermore, the signal provides an accurate measurement of the actual tinnitus frequency. This frequency can be used in tinnitus suppression treatment as described in PCT application AU01/00332.

The tinnitus is measured using an electrode in the tympanic recess of the patient.

The method described above for detecting the activity of a biological system in the absence of any external stimulus can be used as a means of objectively detecting the presence of pain. Pain is associated with the firing of nerve fibres. The present method can be used to detect the electrical output of the nerve firing and process this output to identify a repeated, periodic signal. The presence of this signal is an objective indicator of the pain. Information regarding the type and intensity of pain can also be gleaned from the nature of the signal itself.

The apparatus used in the method of measuring the activity of a biological system and method of diagnosis as discussed above, includes:

- at least one electrode for detecting an electrical response or output of the biological system; and

- computing apparatus operatively connected to said at least one electrode, said computing apparatus having software enabling the computing apparatus to process the electrical response and identify within the response a repeating, periodic signal. The software may enable the analysis to be performed in a number of ways, including averaging, FFT or using a wavelet approach, or combinations thereof.

Where the apparatus is used in the detection of tinnitus and the software enables the processing to be performed by an averaging technique, a preferred feature of the software is that it enables the apparatus to make recordings at different predetermined intervals until a repeated periodic signal is identified. In other words it enables the apparatus to sweep through a range of predetermined periods.

Preferably the apparatus includes a pre-amplifier. It is also preferred that the computing apparatus enables the repeated, period signal that is identified to be displayed visually in a graphic form with the vertical axis showing voltage and horizontal axis showing time

In another aspect, the invention is directed to a system for measuring the activity of a biological system to a single stimulus, including:

(a) means for applying a single stimulus to the biological system; (b) means for detecting an electrical response of the biological system to the single stimulus; and

(c) means for processing the electrical response to identify at least one repeated periodic signal.

In a further aspect the present invention is directed to a system for detecting the activity of a biological system in the absence of any external stimulation, including:

(d) means for detecting an electrical output produced by the biological system; (e) means for detecting the electrical output;

(f) means for processing the electrical output to identify a repeated, periodic signal produced by the biological system. The invention will now be described in further detail by reference to the enclosed drawings illustrating example forms of the invention. It is to be understood that the particularity of the drawings does not supersede the generality of the preceding description of the invention. In the drawings:

Figure 1 is a graph of intensity versus frequency of the response of a vestibular organ to a signal and provides the frequency spectrum of the response.

Figure 2 is a graph showing the measurement of the response of a vestibular organ using the method of this invention

Figure 3 & 4 show some typical signal measuring timing diagrams as may be used to collect and process such signals and indicate the various periods used in the methods of the present invention.

Figure 5 is a diagram illustrating one embodiment of the apparatus used in the invention.

Figure 6 is a schematic diagram illustrating the interaction between components of the apparatus.

Figure 7 is a diagram illustrating interconnection between a number of components of an embodiment of the apparatus of invention.

Figure 1 illustrates a graph of intensity verses frequency. This graph provides a frequency response of a vestibular organ when the vestibular organ is subjected to an external stimulus. This figure is the result of subtracting the frequency response of a baseline signal from the frequency response of the recorded signal. A number of prominent peaks, independent of background signals, can be clearly seen. These peaks correspond to frequencies of 11.5, 23, 34.5, 46, 92, and 184 Hz. For the method shown here, the frequency of 23Hz was chosen this being one of the larger obvious peaks in the figure. One stimulus was applied to the vestibular organ with cold water initially at a temperature of 16 degrees Celsius. The response of the vestibular organ to this stimulus is shown in Figure 2. By utilising an electrode lying in the tympanic recess, a recording of the response was made at a predetermined period of 1/23 seconds. Each measurement lasted approximately 10 milliseconds, this time being determined as the prime response period, and recording continued over a time of 10 seconds. Three consecutive recording periods followed immediately with each recording period lasting for approximately 10 seconds until a distinction between response and other activity could no longer be observed. SP corresponds to the summating potential of the sensory cells of the vestibular organ, and AP corresponds to the action potential of the vestibular nerve. The SP/AP ratio and the latency of the response is an indicator of the integrity of this particular biological system.

The tail of the response curve represents potentials stemming from more central parts of the vestibular pathway and corresponds to early vestibular brainstem responses. These measurements allow an assessment of not only the sensory organ but also of parts of the ascending vestibular central pathway, brainstem, cerebellum and the cortex.

Figure 3 and Figure 4 show some typical signal measuring timing diagrams as may be used to collect and process such signals and indicate the various periods used in the methods.

Figure 5 illustrates an apparatus that can be used in the method of the present invention. These components allow the collection of signals from biological systems, such as the Vestibular organ. The signal electrode 5 is placed within the ear cavity of the patient 8. Another reference electrode 6 is also placed in contact with the patient. Both the signal electrode 5 and the reference electrode 6 are connected to a pre-amplifier. In one embodiment the pre-amplifier performs the function of isolating a high voltage device to protect the patient from high voltage shocks, it also allows for the amplification of low level signals originating in close proximity to the pre-amplifier and conversion of such signals to higher voltage and power signals suitable for transmission to a personal computer 1. Furthermore, the pre-amplifier allows for conversion of data channel signals to a standard analogue or digital form suitable for input to the data capture card.

The signal electrode 5 has it's tip placed in close proximity to the biological system to be measured. It acts as a conduit of electricity and is preferably shaped to avoid damage to sensitive tissue upon insertion, removal or operation of the electrode. The ground wire 9 acts to ground the pre- amplifier. This can also be attached to the patient 8. The control channel 2 is connected between the personal computer 1 and the pre-amplifier 4. Control channel 2 is a conductor or series of conductors suitable for the transmission of bi-directional or uni-directional control signals between the personal computer 1 and the pre-amplifier 4. The control signals travelling through can be either direct or encoded. The data channel 3 is also a conductor or series of conductors suitable for the transmission of unidirectional data signals from the pre-amplifier 4 to the personal computer 1. Signals travelling through can also be direct or encoded; they may also be in either analogue or digital form.

Figure 6 is a schematic diagram illustrating interaction between components of the apparatus where data from the patient 8 is processed. The data channel 3 is connected to a data capture card 7 inside a personal computer 1. The data channel 3 acts to detect the potential difference between the signal electrode 5 and the reference electrode 6. This difference is amplified by the pre-amplifier and transmitted to the data capture card 7.

The digital control channel 2 passes control signals between the personal computer 1 and the pre-amplifier. The data capture card 7 may be a suitable analogue or digital data capture card of suitable bandwidth, sensitivity or other parameters so as to be capable of capturing signals from the data channel 3 and control channel 2. The personal computer 1 has a CPU 10 that can perform processing and generate a display or printer 13 instructions under the control of the operating system 11 and the application software 12. Any suitable operating system can be used with the present invention including Solaris, Windows and Mac OS.

Another diagram showing the interconnection between components is shown in Figure 7.

The physical components previously described can be used to perform a diagnosis in the following manner. The electrodes are connected to the patient 8. They are also connected to the pre-amplifier 4 and grounded 9. The pre- amplifier 4 is connected to a personal computer 1 via a data capture card 7. The personal computer and application software are then used to capture normative data. A small amount of solution is injected into the electrode 5 tip to facilitate conduction with the biological system. The gain of the pre-amplifier and the other operating parameters can then be adjusted to bring the normative signal into the base range.

After stimulation of the biological system, by the injection of cold water through the electrode, data is collected for a period of time. This data may be tagged by input from the operator to mark times when the operator has seen, via the computer display, the type of signal indicative of a preferred measurement.

The application software 12 then analyses the collected data and uses signal processing means (such as averaging, Fast Fourier transforms (FFT), wavelets or combinations thereof) to determine the signal corresponding to the response of the biological system. The signal processing means is used to separate the response of the biological system from any noise to allow the characteristics of the system to be determined. An operator can display and/or print such output representing the characteristics of the biological system as it is measured.

A person who is suitably qualified may then determine the diagnosis of the patient based on the comparison of the measured response of the biological system and the measured response of a comparative results from a sample of patients without any deficiency or affliction. The data from the stimulation can then be stored on the personal computer for further analysis at a later date.

In one particular this application is directed to a method of diagnosing disorders of the vestibular organ and in particular, the otolithiic organ. In another particular application the invention is directed to a method of detecting the presence of tinnitus in a patient. It should however be understood that these are only two, albeit preferred, applications of the present invention and that it should be understood that in its broadest scope the invention is not limited to this application.

It should be appreciated that various modifications and variations may be made to the method and apparatus as described above without departing from the spirit and ambit of the invention.

Claims

1. A method of measuring the activity of a biological system to a single stimulus, including:

- applying a single stimulus to the biological system;

2. The method of claim 1 wherein the processing includes making multiple recordings of the electrical response at a predetermined period and averaging the multiple recordings to identify the repeated, periodic signal.

3. The method of claim 1 wherein the processing includes making one continuous recording of the electrical response over an interval of time and splitting the recording into periods corresponding to the natural period of the response of the biological system or a harmonic of this period and averaging these periods.

4. The method of any one of claims 1-3 wherein the biological system is the vestibular organ.

5. The method of claim 2 wherein the biological system is the vestibular organ and the pre-determined period for recording the response is either 1/23 or

1/46 seconds.

6. The method of claim 5 wherein each recording is confined to the first ten milliseconds of each pre-determined period and the multiple recordings are made over an interval of up to ten seconds.

7. Use of the method of any one of claims 1 to 7 to identify the summating potential of the sensory cells of the vestibular organ.

8. The method of claims 2 or 3 wherein the biological system is the otolithiic organ, the pre-determined period is 1/23 seconds and the single stimulus is applied by a head tilt.

9. The method of claims 2 or 3 wherein the biological system is the utriculus organ, the pre-determined period is 1/23 seconds and the single stimulus is applied by a head tilt.

10. The method of claims 2 or 3 wherein the biological system is the sacculus organ, the pre-determined period is 1/23 seconds and the single stimulus is applied by a head tilt.

11. A method of diagnosing disorders of a biological system including:

- applying a single stimulus to the biological system; - detecting an electrical response of the biological system to the single stimulus;

- analysing the signal to diagnose the biological system.

12. A method of diagnosing a disorder of the vestibular organ including:

- applying a single stimulus to the vestibular organ;

- measuring from the repeated, periodic signal the summating potential of the sensory cells of the vestibular organ (SP) and the action potential of the vestibular nerve (AP);

- calculating the ratio of SP/AP; and

- comparing the measured SP/AP ratio with a predetermined SP/AP.

13. A method of diagnosing disorders of a vestibular organ including: - applying a single stimulus to the vestibular organ;

- detecting an electrical response of the biological system to the single stimulus; - processing the electrical response to identify at least one repeated, periodic signal;

- measuring from the repeated, periodic signal the latency of the response of the vestibular organ; and

- comparing the measured latency of response with a predetermined latency of response.

14. The method of diagnosis of claim 12 wherein the predetermined SP/AP ratio is 30% and a disorder of the vestibular organ is diagnosed if the measured SP/AP ratio is greater than 30%.

15. The method of diagnosis of claim 11 wherein the biological system is a utriculus organ and the single stimulation is an ipserlateral head tilt or a contralateral head tilt.

16. The method of diagnosis of claim 11 wherein the biological system is a sacculus organ and the single stimulation is either a forward head tilt or a backward head tilt.

17. The method of any one of claims 4 to 6, 9, 10, 12 to 16 wherein an electrode is used to detect the electrical response, the method including placing the electrode in a tympanic recess.

18. A method of detecting the activity of a biological system in the absence of any external stimulation including:

- detecting an electrical output produced by the biological system; and

- processing the electrical out put to identify a repeated, periodic signal produced by the biological system.

19. A method of diagnosing a disorder of a biological system, including:

- detecting an electrical output produced in the biological system in the absence of any external stimulus;: - processing the electrical output to identify a repeated, periodic signal produced by the biological system; and

-analysing the repeated, periodic signal to diagnose a disorder of the biological system.

20. A method of determining the presence of tinnitus in a person including:

- placing an electrode in the tympanic recess of the person; -detecting an electrical output; and

- processing the electrical output to identify a repeated periodic signal, the repeated periodic signal indicating the presence of tinnitus.

21. An apparatus for use in the method of any one of claims 1-6, 8-20 including:

- computing apparatus operatively connected to said at least one electrode, said computing apparatus having software enabling the computing apparatus to process the electrical response and identify within the response a repeating, periodic signal.

22. A system for measuring the activity of a biological system to a single stimulus, including:

(a) means for applying a single stimulus to the biological system;

(b) means for detecting an electrical response of the biological system to the single stimulus; and

23. a system for detecting the activity of a biological system in the absence of any external stimulation, including:

(a) means for detecting an electrical output produced by the biological system; (b) means for detecting the electrical output;

(c) means for processing the electrical output to identify a repeated, periodic signal produced by the biological system.