WO1995002360A1

WO1995002360A1 - Measuring bioimpedance values and treating mental disorders

Info

Publication number: WO1995002360A1
Application number: PCT/US1994/008005
Authority: WO
Inventors: Yaacov Naisberg; Hilla Gruner
Original assignee: Sarid - Medical Instrumentation Ltd.; Friedman, Mark
Priority date: 1993-07-14
Filing date: 1994-07-13
Publication date: 1995-01-26
Also published as: IL106338A0; AU7399394A

Abstract

Bioimpedance measurement apparatus (100) and method for measuring bioimpedance values including at least two electrodes and a pulse generator (108) for providing electrical pulses between an electrode pair of at least two electrodes (116). The apparatus (100) also includes voltage determining apparatus (122) for determining the voltage across the electrode pair (116), current determining apparatus (126) for determining the current traversing between the electrode pair (116) and a calculating device (102) for calculating the bioimpedance value between the electrode pair (116). The apparatus (100) can also be used for treating mental disorders.

Description

MEASURING BIOIMPEDANCE VALUES AND TREATING MENTAL DISORDERS

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to apparatus and method for non- invasive, high frequency measurement of bioimpedance values in general and in particular to measurement of bioimpedance values within the central nervous system (CNS). Furthermore, the invention relates to apparatus and method for non-seizurable treatment of patients having aberrated electrical activity within their CNSs as reflected by abnormal bioimpedances and often manifested as mental disorders.

Information transfer within the central nervous system involves the transfer of electrical signals along neurons. This transfer takes place, in part, by means of ion flow through ion channels in the neurons and by synaptic neurotransmitters. It has recently been suggested that blockage of ion channels within neurons can significantly affect regional and/or total electric environments, and especially the extracellular liquid volume, as reflected by deviations in bioimpedance values within the central nervous system. Eventually such blockages can lead to ionic concentrations leading to pathological by-passes in electrical signaling and medical conditions such as mental disorders.

Various apparatus and methods have been suggested for measuring normal and abnormal electrical activity in the brain, for monitoring brain functioning and for treatment of mental disorders such as schizophrenia, depression, and the like.

One common technique is the electroencephalogram, commonly abbreviated as EEG, which measures the internal electrical activity of the brain (so-called "brain waves") by means of electrodes affixed to the scalp of the patient. EEG technology is designed to measure low frequency signals up to several hundred Hz that are produced in the process of postsynaptic activity. The EEG is useful in that it provides a non-invasive method of measuring inherent brain electrical activity and permits the comparison of that activity under the affects of different stimuli. However, the EEG suffers from the disadvantage that it can only measure superficial brain signals. Therefore, the use of EEG for diagnosing mental disturbances is limited to mental disorders, for example, some epilepsies, which display abnormal electrical activity in locations close to the scalp. There are a number of recent patents dealing with brain functioning.

U.S. Patent No. 4,630,615 describes an invasive method for measuring the impedance of brain including a neural stimulating system using a cathode implanted in the epidural space of the spine.

U.S. Patent No. 4,815,474 describes a method for mapping of brain electrical activity by combining an EEG and Evoked Potential temporal trajectory analysis. However, this method is not capable of analyzing activity in deep brain structures.

U.S. Patent No. 4,977,896 describes apparatus for measuring electromagnetic activity of the brain as received from an array of sensors sensitive to magnetic fields and/or electrical fields.

GB 2,160,323 and "Clinical and Physiological Application of EIT",

D.S. Holder, UCL Press, London, 1993 describe a tomographic method called Electrical Impedance Tomography (EIT) or Applied Potential

Tomography for imaging slices of an organ under study in an attempt to locate internal structures. In EIT, an electrical potential is applied across one pair of electrodes causing an electrical current to flow through the body while another pair of electrodes is used to measure the potential induced by the electrical field generated by the first pair of electrodes. The actual potential is compared to a theoretical expected potential calculated on the assumption that the body consists of one uniform medium. The resulting potential ratio enables the location, size and shape of a discontinuity within the organ. Attempts to image the brain have been found to be unsatisfactory due to consideration attenuation of signals and the fact that the resistivity of bone is far higher than that of the brain. Convulsive therapies, especially Electric Convulsive Treatment

(ECT) have been used in medicine for many decades to treat certain mental disturbances. The method typically uses 70 - 130 V pulses having pulse widths of 0.1 to 0.5 seconds. This method is widely applied for patients who suffer from drug-resistant Major Affective Disorder, particularly those who manifest suicidal behavior. The advantage of this method is a rapid clinical improvement, but there are two essential disadvantages: reversible short-memory decline and the public stigma associated with this procedure.

There is therefore a need for a bioimpedance measurement apparatus and method for measuring bioimpedance values for the detection of microstmcture extracellular fluid and ionic aberration including deviated electrical activity in a portion of the central nervous system. These phenomena manifest themselves as psychiatric symptoms and mental disorders in the central nervous system. Thus, by knowing some specific symptoms, such as hallucinations, various mental disturbances can correlated with particular neuronal electropathology. Accordingly, there is also the need for apparatus and method for treatment of mental disorders characterized by abnormal bioimpedance values by applying well controlled electrical pulses between one or more electrode pairs to discharge the aforementioned blockages to maintain the health of the patient.

SUMMARY OF THE INVENTION

The present invention is for an apparatus and method for non- invasive, high frequency measurement of bioimpedance values in general and in particular in the central nervous system including the brain for monitoring and analyzing abnormal bioimpedances. Furthermore, the present invention is for an apparatus and method for non-seizurable treatment of patients having aberrated electrical activity within their CNSs as reflected by abnormal bioimpedances and often manifested as mental disorders. There is thus provided in accordance with a first aspect of the present invention, bioimpedance measurement apparatus comprising: (a) at least two electrodes; (b) a pulse generator for providing at least one electrical pulse between an electrode pair of the at least two electrodes; (c) voltage determining means for determining the voltage across the electrode pair; (d) current determining means for determining the current traversing between the electrode pair; and (e) calculating means for calculating the bioimpedance value between the electrode pair.

According to further features of the present invention, the apparatus includes a pulse generator for providing electrical pulses of substantially uniform current amplitude. In this case, the voltage determining means includes an RMS detector for measuring the voltage induced across the electrode pair while the current determining means includes either an RMS detector for measuring the actual current traversing the electrode pair or a computer for providing the pre-determined value of the current traversing the electrode pair.

According to still further features of the present invention, the apparatus includes a pulse generator for providing electrical pulses of substantially uniform voltage. In this case, the current determining means includes an RMS detector for measuring the current traversing between the electrode pair while the voltage determining means includes either an RMS detector for measuring the actual voltage induced across the electrode pair or a computer for providing the pre-determined value of the voltage across the electrode pair.

According to still yet further features, the apparatus further includes selection means for selecting an electrode pair from the at least two electrodes and regulation means for regulating at least one of the parameters from the following group of parameters: current amplitude of the pulses, voltage amplitude of the pulses, pulse width, pulse frequency, cycle time between consecutive pulses and settling time between the onset of a pulse and the onset of a measurement.

According to still yet further features, the apparatus further includes scalp electrode apparatus including the at least two electrodes wherein the scalp electrode apparatus preferably includes at least one mobile electrode.

According to still yet further features, the apparatus further includes means for providing at least one from the following group: a Mean Bioimpedance Value per Electrode Pair chart, a Mean Bioimpedance Value per Electrode chart, a Mean Bioimpedance Value per Electrode Group chart and a Bioimpedance Value Encephalograph chart.

Still further, the apparatus preferably includes a phase detector for measuring the phase shift between the voltage across the electrode pair and the current between the electrode pair, EEG apparatus such that both superficial electrical activity and bioimpedance of the brain of a patient can be measured, and correlation apparatus for correlating between a bioimpedance and a mental disorder. There is also provided according to a second aspect of the present invention, a method for measuring bioimpedance values comprising the steps of: (a) applying at least two electrodes; (b) administering an electrical pulse between an electrode pair of the at least two electrodes; (c) determining the voltage across the electrode pair; (d) determining the current traversing the electrode pair; and (e) calculating the bioimpedance value between the electrode pair.

According to further features of the present invention, the method further includes the step of selecting at least one electrode pair from the at least two electrodes. This step can be extended such that substantially all possible electrode pairs of the at least two electrodes can be selected. According to still further features of the present invention, the method further includes the step of providing at least one of the following: a Mean Bioimpedance Value per Electrode Pair chart, a Mean Bioimpedance Value per Electrode chart, a Mean Bioimpedance Value within an Electrode Group chart and a Bioimpedance Value Encephalograph chart.

According to still yet further features of the present invention, the method preferably includes the steps of diagnosing a mental disorder, treating a mental disorder and evaluating the treatment of the mental disorder.

There is also provided according to a third aspect of the present invention, apparatus for treating a mental disorder, the apparatus comprising: (a) at least two electrodes; and (b) a pulse generator for providing at least one electrical pulse between an electrode pair of the at least two electrodes.

There is also provided according to a fourth aspect of the present invention, a method for treating a mental disorder, the method comprising the steps of: (a) applying at least two electrodes; and (b) administering at least one electrical pulse between an electrode pair of the at least two electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be further understood and appreciated from the following detailed description taken in conjunction with the drawings in which: FIG. 1 is a block diagram of the preferred embodiment of bioimpedance measurement apparatus constructed and operative in accordance with the teachings of the present invention; FIGS. 2a and 2b are schematic illustrations of possible configurations of scalp electrode apparatus of the bioimpedance measurement apparatus of Figure 1 ;

FIG. 2c is a schematic illustration of a mobile electrode of the scalp electrode apparatus of Figures 2a and 2b;

FIG. 3 is a flow chart illustrating the method for measuring bioimpedance values using the bioimpedance measurement apparatus of Figure 1;

FIG. 4 shows plots of the Mean Bioimpedance Value per Electrode Pair chart for four groups of subjects as measured during a clinical trial according to the method of the present invention;

FIG. 5 shows plots of the Mean Bioimpedance Value per Electrode chart for four groups of subjects as measured during the same clinical trial according to the method of the present invention; FIG. 6 shows plots of the Mean Bioimpedance Values Within

Electrode Groups charts for four groups of subjects as measured during the same clinical trial according to the method of the present invention;

FIG. 7 shows plots of Bioimpedance Encephalograph charts for six electrode pairs; and FIG. 8 is a block diagram of the preferred embodiment of an apparatus for treatment of patients with mental disorders constructed and operative according to the teachings of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a non-invasive, high frequency bioimpedance measurement apparatus and method for measuring bioimpedance values. The invention is particularly applicable to bioimpedance measurement of the central nervous system in general and the deep cortical layers of the brain in particular. These bioimpedance values enable investigation of neuronal activity leading to both diagnosis and treatment of various mental disturbances caused by aberrated electrical activity.

The principles and operation of the apparatus and method for measuring bioimpedance values and the apparatus and method for treatment of patients with mental disorders of the present invention may be better understood with reference to the drawings and the accompanying description.

With reference now to Figure 1, the block diagram shows the preferred embodiment of the bioimpedance measurement apparatus, generally designated 100, constmcted and operative according to the teachings of the present invention. For the purpose of exposition only, bioimpedance measurement apparatus 100 is described for measuring bioimpedance values of the central nervous system in general and the brain in particular. Hence, bioimpedance measurement apparatus 100 is hereinafter referred to as Brain Bioimpedance Analyzer (BBA). However, it should be appreciated that the apparatus of the present invention can be equally used for measuring bioimpedance values in other parts of the human body and other animals.

Brain Bioimpedance Analyzer (BBA) 100 can be used as a diagnostic system through the detection of abnormal bioimpedance values related to mental disorders. After detection, any deviation from accepted bioimpedance values can be interpreted as focal points of electrical conduction "blockages" and therefore constitute the basis for the diagnosis of a mental disorder which can be quantitatively classified and treated. Broadly speaking, according to the teachings of the present invention, the bioimpedance values are determined through measurement of voltages across electrode pairs induced by electrical pulses of known current amplitude and frequency. Alternatively, the bioimpedance values can be determined through measurement of current between electrode pairs induced by electrical pulses of known voltage and frequency. However, the preferred implementation of bioimpedance measurement apparatus 100 includes a pulse generator for providing electrical pulses of substantially uniform current amplitude such that the current amplitude of the pulses administered to a patient can be stringently controlled according to safety regulations.

It is a particular feature of the present invention that the bioimpedance measurement is a direct measurement in the sense that the same electrode pair used for the administration of the. electrical pulse of known current amplitude are also the electrode pair used for measurement of the voltage induced thereacross. An advantage rendered by this direct measurement technique is that far shorter pulse widths can be employed than previously suggested in the art. Furthermore, the pulses are typically so short and of such low energy that they do not affect the electrical activity of the brain which would cause incorrect bioimpedance measurements.

Brain Bioimpedance Analyzer 100 includes a computer 102 for controlling the bioimpedance measurement procedure and for calculating the bioimpedance data of the central nervous system. Computer 102 includes memory apparatus for the storage of measurement programs and patient data, a keyboard, and an SVGA color monitor. Computer 102 interfaces with a microcontroller 104 via an RS 232 interface 106 for loading values of parameters to microcontroller 104. The parameters include, but are not limited to, the current amplitude of the pulse, the pulse width, the pulse frequency, the cycle time between consecutive pulses, and the settling time from the onset of a pulse to the onset of a voltage measurement. Furthermore, computer 102 loads the sequence of the electrode pairs between which the bioimpedance measurements are to be taken.

A pulse generator 108, in the form of a current source powered by an isolated power supply 110, is controlled by microcontroller 104 via a current controller 112 and a frequency controller 114 for providing selectively variable, high frequency, low energy electrical pulses to electrodes 116 applied to the scalp of the patient. Current controller 112 controls the current amplitude of the pulses provided by pulse generator 5 108 while frequency controller 114 controls the frequency of the pulses provided by pulse generator 108.

Typically twenty four electrodes 116 are applied to the scalp of a patient such that a substantially complete bioimpedance topography of the patient can be prepared to enable a diagnosis of mental disorders. 0 However, it should be noted that any number of electrodes can be employed particularly when treating a known mental disorder which requires pulses to be administered between pre-determined locations of electrodes.

Twenty four electrodes 116 render 276 electrode pairs from (1,2), 5 (1,3)....(23,22) and (23,24) and therefore a multiplexer 118, under the control of a decoder 120, is provided for switching between electrodes 116 such that only a single electrode pair is operative at any one time. Decoder 120 receives its input from microcontroller 104 such that pulses are administered via electrode pairs selected according to a pre-determined 0 sequence.

Computer 102 preferably receives five pieces of information: the measured value of the voltage induced across an electrode pair, the actual value of the current amplitude of the electrical pulse administered to the patient, the bioimpedance between an electrode pair, the actual frequency 5 of the electrical pulse administered to the patient and the phase shift between the voltage across an electrode pair and the current through the electrode pair. It should be noted that the actual values of the current amplitude and the frequency of the pulses administered to the patient are obtained for feedback purposes to ensure that components of BBA 100 are 0 operating within acceptable tolerance limits. In other words, the bioimpedance value between an electrode pair can be calculated from the measured value of the voltage across the electrode pair and the pre¬ determined value of the current amplitude as provided to microcontroller 104 by computer 102. An RMS detector 122 is connected to multiplexer 118 for measuring the voltage induced across an operative electrode pair 116. RMS detector 122 provides the value of the measured voltage to computer 102 after amplification by a variable gain amplifier 124 also under the control of microcontroller 104. In a similar fashion, an RMS detector 126 is connected to multiplexer 118 for measuring the actual current amplitude of the electrical pulses administered to the patient. An analog divider 128 connected to RMS detector 122 and RMS detector 126 calculates the bioimpedance value between the selected operative electrode pair. A Frequency-to- Voltage Converter 130 calculates the voltage equivalent of the frequency of the actual electrical pulse provided across the selected electrode pair. And lastly, a Phase Detector 131 connected to the lines between multiplexer 118 and RMS detectors 122 and 126 is provided to measure the phase shift between the voltage across and the current through the selected operative electrode pair. Preferably, the values from RMS detector 122, RMS detector 126, analog divider 128 and Frequency-to-

Voltage Converter 130 are stored temporarily in buffer amplifiers 132-138, respectively, and are converted into digital signals by an ADC module 140.

In the instance that BBA 100 administers pulses of known voltage, pulse generator 108 is a voltage source and bioimpedance values are calculated by measuring the current traversing between an electrode pair while the voltage can be determined either by measuring the actual voltage across the electrode pair used for administering the pulses or using the pre¬ determined value of the voltage to be applied across the electrode pair. In addition, BBA 100 includes an isolated 220 V 50 Hz transformer 142 for isolating the system from the mains according to safety regulations and a Test Module 144 for testing the operation of the system. Test Module 144 operates by disconnecting electrodes 116 from the system and passing the electrical pulses from pulse generator 108 through a resistor of known value. Still further, BBA 100 includes EEG apparatus 146 for measurement of the inherent electrical activity of the brain and a switch 148 for connecting electrodes 116 either to current source 108 or EEG apparatus 146. The advantage rendered by including EEG apparatus 146 with BBA 100 is that it extends the analysis of the brain of a patient such that both superficial electrical activity and deep cortical electrical activity can be measured and monitored. It should be noted that one of the differences between BBA 100 and EEG apparatus 146 is that BBA 100 employs high frequency pulses for actively measuring the brain ionic activity while EEG apparatus 146 passively monitors the inherent low frequency electrical activity.

With reference to Figures 2a and 2b, the schematic illustrations show top views of two possible configurations of scalp electrode apparatus, generally designated 150 and 152, respectively, used with BBA 100. The use of scalp electrode apparatus 150 or 152 enables rapid deployment of the electrodes in their correct locations. It is of particular importance that there is high repeatability in the deployment of electrodes such that treatment of a mental disorder can be effected. However, electrodes can also be applied individually.

As shown, in both configurations, electrodes 116 are deployed in substantially uniform patterns such that the bioimpedance topography of the brain of the patient can be screened effectively. With particular reference to Figure 2b, scalp electrode apparatus 152 includes twenty four electrodes 116 configured in a 6 row by 4 column matrix. As shown electrodes 1 through to 6 are denoted CLM 4, electrodes 7 through to 12 are denoted CLM 3, electrodes 13 through to 18 are denoted CLM 2 and electrodes 19 through to 24 are denoted CLM 1.

Electrodes 116 can be of any kind suitable for application to the scalp while enabling the passage of current at the required current amplitude range and frequency range of the electrical pulses administered by BBA 100 and the measurement of voltage between any electrode pair. Electrodes 116 can be reusable or disposable and are preferably small, thereby enabling a more accurate application to the scalp. Furthermore, one or more "mobile electrodes" 154 (Figure 2c) can be employed such that they can be moved a small amount in one or more directions from its original location, thereby enabling a number of measurements to be taken from substantially the same location and also the accurate positioning of the electrodes. In the embodiment in Figure 2c, mobile electrode 154 includes a bar 156 extending along the y-axis with respect to the scalp of a patient, a screw-tightened device 158 for displacement along bar 156 and a slidable screw-tightened device 160 horizontally displaceable with respect to bar 156. Overall, a mobile electrode 154 can be spatially displaced in all directions within in a specified are with respect to the scalp of the patient. With reference now to Figure 3, the flow chart illustrates the use of bioimpedance measurement apparatus 100 for measuring bioimpedance values in the central nervous system of a patient and in particular the brain of the patient. BBA 100 is set up for a measurement session by inputting the patient's identification and selecting a measurement procedure from a library of pre-determined measurement procedures. Alternatively, a measurement procedure can be adapted by a physician on site according to his discretion. Measurement procedures can be classified or selected according to the age of the patient, the mental disorder under investigation, and the like. A measurement procedure includes both the values of parameters defining the electrical pulses to be provided by pulse generator 108 and the sequence of electrode pairs through which the electrical pulses are to be administered to the patient. The parameters defining the pulses include current amplitude, pulse width and pulse frequency. The preferred approximate ranges of these parameters are as follows:

- Pulse Current Amplitude: 0.1 mA to 5 mA

- Pulse Frequency: 5 kHz to 100 kHz

- Pulse Width: 10 to 30 msec It should be noted that administering pulses within these ranges enables measurement of bioimpedance values within the central nervous system without modifying the electrical environment as a result of the pulses. It should be appreciated that whatever the parameters of the pulses selected, the electrical pathway between an electrode pair is a three dimensional pathway in the sense that the electrical energy of the pulses passes concurrently along the scalp, the upper cortical areas and the deeper cortical areas. The actual value of the bioimpedance depends on the three dimensional electrical pathway taken by a pulse as a function of the prevailing electrical environment within the central nervous system of a patient. Typically higher frequencies are used for measuring bioimpedances between electrode pairs along electrical pathways through deeper cortical layers because impedance decreases inversely with respect to frequency.

Other parameters typically defined in a measurement procedure include the cycle time between consecutive pulses and the settling time between the onset of a pulse and the onset of a voltage measurement. The preferred approximate ranges of these parameters are as follows:

- Cycle Time between consecutive pulses: 100 to 999 msec

- Settling Time between the onset of a pulse and the onset of a voltage measurement: 5 to 50 msec Hence, for a particular measurement procedure, computer 102 sets pulse generator 108 to administer pulses at a pre-determined current amplitude, say, 0.5 mA, at a predetermined pulse width, say, 15 msecs and at a pre-determined high frequency, say, 50 kHz. In view of the disparate nature of patients, mental disorders, and the like, the current amplitude of the pulses and/or the pulse widths and/or the pulse frequencies may have to be varied during the procedure to ensure optimal diagnostic data.

After BBA 100 has been set-up, voltage measurements are taken for one or more electrode pairs up to the maximum, in this case, of 276 electrode pairs according to the sequence of the measurement procedure selected or as adapted on site. Depending on the cycle time, it typically takes in the order of a few minutes to complete 276 electrode pair measurements. Preferably five measurements of induced voltage across an electrode pair and actual current traversing therethrough are taken during a single pulse width such that their average values can be calculated to reduce artifacts. As shown in the flow diagram, the measurements are executed in a cyclic fashion such that after the last electrode pair has been selected, the procedure is repeated until a pre-determined time period has been completed. BBA 100 preferably provides the physician with several diagnostic tools for detection of any prevailing irregularities in electrical environments as evidenced by abnormal bioimpedance measurements. First, the physician can monitor the bioimpedance measurements for each electrode pair. Second, the physician can monitor the mean bioimpedance measurements for each electrode. Third, the physician can monitor bioimpedance encylographs of selected electrode pairs. Exemplary plots of the above can be displayed on the SVGA monitor or can be outputted on hardcopy. Furthermore, the classification and the diagnostic ability of BBA 100 can be enhanced by analyzing the phase shift between the voltage across and the current through an electrode pair. Alternatively, the bioimpedance measurements can be used to generate a spatial bioimpedance topographic map through reconstructions algorithms similar to those available for other non-invasive imaging techniques. Still again, the plots of bioimpedance measurements of patients can be compared using comparison algorithms to standard plots for providing information to the physician regarding any prevailing discrepancies.

With reference now to Figures 4, 5 and 6, the results of a clinical trial carried out on a sample of 71 patients are shown. The sample included four groups of patients in which: the first group of 17 patients, denoted NOR, were normal; the second group of 21 patients, denoted MED, were medicated schizophrenics showing no symptoms; the third group of 16 patients, denoted CHR, were medicated chronic schizophrenics still showing symptoms; and last group of 19 patients, denoted EPI, were medicated epileptics showing no symptoms.

The procedures were standardized, being the same in each case and during each recording session. The patients were alert and seated in the clinic room with their faces towards the computers with eyes open. The measurements were. carried out during the morning hours. The procedures were carried out twice in one session with an interval of between 5 and 7 minutes between each measurement. In a similar manner, the procedure was repeated after two weeks. The electrodes were placed on the patients' skull 10 minutes before the measurement in order to ensure that the electrodes were tightly affixed to the scalp. Each measurement was carried out for about 5 minutes. The measurements were done automatically by the BBA apparatus, so that the recording started with electrode pairs from electrode number 1 to 2, 1 to 3, and so on, arriving at 23 to 24 such that a total of 276 bioimpedance measurements were recorded for each patient. The parameters used in the trial were as follows:

- Current Amplitude: 0.5 mA

- Pulse frequency: 80 kHz

- Pulse width: 30 msec - Settling time: 5 msec

Figure 4 shows plots of Mean Bioimpedance Value per Electrode Pair charts for the four groups. It can be readily noticed that the patients in the CHR group exhibit high variability and higher bioimpedance values in comparison to the other three groups. These features indicate that this CHR group of patients was under severe psychiatric distress presumably with a lot of dispersed bypasses due to ionic blockage in the brain and closure of functioning electric pathways.

Figure 5 shows plots of Mean Bioimpedance Value per Electrode charts for the four groups where the mean impedance per electrode is defined as the mean of the twenty three bioimpedance values between a single electrode, say electrode 1, and the other electrodes, in this case, electrodes 2 through to 24. It can be readily seen that the average bioimpedance value per electrode is significantly higher in the CHR patients while the mean bioimpedance value per electrode of the MED patients is less than the average. These results tend to reinforce the suggested theory that suitable medication releases blockages, or in other word, opens up complementary collateral neuronal junctions, thereby decreasing the bioimpedance values even below normal values.

Figure 6 shows plots of Mean Bioimpedance Values within Electrode Group charts where in this case a group is defined as each column of the four columns of scalp electrode apparatus 152 of Figure 2b for each group. It can be readily seen that the plots of the CHR group, the EPI group and the MED group are asymmetrical while the plot of the NOR group is substantially symmetrical. This asymmetry provides a further diagnosis tool for a physician to classify different mental disorders. In the flow chart of a measurement procedure described hereinabove, it has been suggested that the bioimpedance measurements for one or more electrode pairs are taken at a fixed point in time. Another method for providing information regarding a mental disorder can be derived by measuring bioimpedance values over a period of time to produce a Bioimpedance Value Encephalograph chart.

In this method, the bioimpedance values between one or more electrode pairs is measured on a continuous basis to provide an EEG-like bioimpedance encephalograph chart for showing specific patterns of conductivity that may be consequential to certain mental and neurological disorders. As shown in Figure 7, for example, six bioimpedance value encephalograph charts can be displayed, in this case, for electrode pairs (1,2), (1,3), (1,4), (1,5), (1,6) and (1,7). One benefit provided by bioimpedance encephalography is in the testing of a patient to external stimuli such as a flashing light, noises and the like. These external stimuli, which are applied during the bioimpedance measurements, will affect the bioimpedance value encephalograph charts providing a further diagnostic tool.

With reference now to Figure 8, the block diagram shows the preferred embodiment of apparatus, generally designated 162, constmcted and operative according to the invention, for treatment of mental disorders which manifest themselves as abnormal bioimpedances as measured by BBA 100. Apparatus 162 is substantially similar to BBA 100 (Figure 1) and therefore similar components are likewise numbered. The main difference between apparatus 162 and BBA 100 is that apparatus 162 does not require the components for determining bioimpedances as will now become apparent.

Broadly speaking, the method for treating a specific mental disorder involves the administration of one or more highly regulated electrical pulses between one or more electrode pairs to provide relief to the patient. Regulation of pulses includes regulation of the current amplitude, the pulse width, the pulse frequency, the cycle time between consecutive pulses and the sequence of electrical pairs. Preferably, treatment procedures are stored in libraries such that a physician can readily recall the appropriate treatment for a specific mental disorder. Typically, the limits of the parameters of the pulses for treatment of mental disorders differ from the limits for measurement of bioimpedance values. The preferred limits of the parameters for treating abnormal bioimpedances are within the following approximate ranges: - Current Amplitude: 0.5 mA to 10 mA

- Pulse Frequency: 5 kHz to 100 kHz

- Pulse Width: 10 msec to 999 msec

- Cycle Time: 100 msec to 999 msec

As mentioned earlier, it has been suggested that blockages cause undesirable ionic concentrations resulting in electrical by-passes which manifest themselves as psychiatric symptoms and mental disorders. Hence, the motivation behind the suggested method of treating mental disorders that the pulses discharge the undesirable ionic concentrations, thereby restoring normal bioimpedance along the particular three dimensional electrical pathway between the electrode pair as defined by the parameters of the pulse. Hence, it should be appreciated that the pulses used for treatment are typically of greater energy than used for measurement because they are designed to modify the prevailing electric environment within the central nervous system while the pulses used for measurement are designed not to modify the electric environment.

Using BBA 100, treatment of a patient typically follows the following routine: First, measurement of bioimpedance values across electrodes pairs using electrical pulses having with a wide range of current amplitudes, pulse widths and pulse frequencies. Second, detection of any abnormal bioimpedances through analysis of the charts provided by BBA 100 or comparison of results to standardized data. Third, treatment through administration of one or more highly regulated electrical pulses using the same electrode pair between which an abnormal impedance was detected or another electrode pair as necessary. And finally, evaluating the treatment by measuring the bioimpedance again between the electrode pairs where the abnormal impedance value was detected. Hence, the advantage of BBA 100 is that BBA 100 can be employed for both diagnostic data and treatment by changing the parameters of the pulses administered to the patient. Alternatively, for a known mental disorder or a patient with a familiar medical history, the one or more electrode pairs between which there are abnormal bioimpedance values can be known in advance, such that the apparatus 162 can be employed without the need for measuring impedances.

While the invention has been described with respect to a limited number of embodiments, it will be appreciated that many variations, modifications and other applications of the invention may be made.

Claims

WHAT IS CLAIMED IS:

1. Bioimpedance measurement apparatus comprising:

(a) at least two electrodes;

(b) a pulse generator for providing at least one electrical pulse between an electrode pair of said at least two electrodes;

(c) voltage determining means for determining the voltage across said electrode pair;

(d) current determining means for determining the current traversing between said electrode pair; and

(e) calculating means for calculating the bioimpedance value between said electrode pair.

2. Apparatus as in claim 1, wherein said pulse generator provides electrical pulses of substantially uniform current amplitude.

3. Apparatus as in claim 2, wherein said voltage determining means includes an RMS detector for measuring the voltage induced across said electrode pair.

4. Apparatus as in claim 2, wherein said current determining means includes an RMS detector for measuring the actual current traversing said electrode pair.

5. Apparatus as in claim 2, wherein said current determining means includes a computer for providing the pre-determined value of the current traversing said electrode pair.

6. Apparatus as in claim 1, wherein said pulse generator provides electrical pulses of substantially uniform voltage.

7. Apparatus as in claim 6, wherein said current determining means includes an RMS detector for measuring the current traversing between said electrode pair.

8. Apparatus as in claim 6, wherein said voltage determining means includes an RMS detector for measuring the actual voltage induced across said electrode pair.

9. Apparatus as in claim 6, wherein said voltage determining means includes a computer for providing the pre-determined value of the voltage across said electrode pair.

10. Apparatus as in claim 1, further comprising selection means for selecting an electrode pair from said at least two electrodes.

11. Apparatus as in claim 1 , further comprising regulation means for regulating at least one of the parameters from the following group of parameters: current amplitude of the pulses, voltage amplitude of the pulses, pulse width, pulse frequency, cycle time between consecutive pulses and settling time between the onset of a pulse and the onset of a measurement.

12. Apparatus as in claim 1, further comprising scalp electrode apparatus including said at least two electrodes.

13. Apparatus as in claim 12, wherein said scalp electrode apparatus includes at least one mobile electrode.

14. Apparatus as in claim 1, further comprising means for providing at least one of the following group: a Mean Bioimpedance Value per Electrode Pair chart, a Mean Bioimpedance Value per Electrode chart, a Mean Bioimpedance Value per Electrode Group chart and a Bioimpedance Value Encephalograph chart.

15. Apparatus as in claim 1, further comprising a phase detector for measuring the phase shift between the voltage across said electrode pair and the current between said electrode pair.

16. Apparatus as in claim 1, further comprising EEG apparatus such that both superficial electrical activity and bioimpedance of the brain of a patient can be measured.

17. Apparatus as in claim 1, further comprising correlation apparatus for correlating between a bioimpedance and a mental disorder.

18. A method for measuring bioimpedance values comprising the steps of:

(a) applying at least two electrodes;

(b) administering an electrical pulse between an electrode pair of the at least two electrodes;

(c) determining the voltage across the electrode pair;

(d) determining the current traversing the electrode pair; and

(e) calculating the bioimpedance value between the electrode pair.

19. The method as in claim 18, further comprising the step of selecting at least one electrode pair from the at least two electrodes.

20. The method as in claim 19, wherein said step of selecting selects substantially all possible electrode pairs of the at least two electrodes.

21. The method as in claim 19, further comprising the step of providing at least one of the following group: a Mean Bioimpedance Value per Electrode Pair chart, a Mean Bioimpedance Value per Electrode chart, a Mean Bioimpedance Value within an Electrode Group chart and a Bioimpedance Value Encephalograph chart.

22. The method as in claim 19, further comprising the step of diagnosing a mental disorder.

23. The method as in claim 22, further comprising the step of treating a mental disorder.

24. The method as in claim 23, further comprising the step of evaluation of the treatment of the mental disorder.

25. Apparatus for treating a mental disorder, said apparatus comprising: a) at least two electrodes; and b) a pulse generator for providing at least one electrical pulse between an electrode pair of said at least two electrodes.

26. A method for treating a mental disorder, the method comprising the steps of: a) applying at least two electrodes; and b) administering at least one electrical pulse between an electrode pair of the at least two electrodes.