The present invention relates to a method and system for managing pharmacological patient treatment based on measurements of the electrical activity of the brain.
The treatment of developmental, neurological, or psychiatric disorders may involve prescribing one or more medications. In selecting the medication and determining a dosage, a physician typically performs a symptomatological diagnosis that is normally compliant with a formal schedule of diagnostic criteria. In performing such a diagnosis, the physician will determine the symptoms, either by observing the patient for abnormal behavior or listening to the patient describe his symptoms. After evaluating the symptoms in light of clinical intuition and past experience, the physician may prescribe one or more medications.
Because of its subjective nature, this typical approach to prescribing medications can be inaccurate. If a diagnosis lacks an objective basis rooted in physio-neurological measurements, physicians' assessments may be far from the mark, causing the prescription of medications that are not beneficial or even harmful.
In an exemplary embodiment of the present invention, data corresponding to the electrical activity produced by the brain of a patient such as, for example, the data of a quantitative electroencephalogram (QEEG), is processed to determine which brain activity data for the patient deviates from corresponding brain activity data of a normative profile. The deviant brain activity data is used to determine a brain state vector (BSV) in a multidimensional brain electrical signal space. The orientation of the vector indicates the nature of the deviation from a normal state and may also be used to select the medicine that ought to be prescribed to the patient, while the length of the vector quantifies the degree of abnormality exhibited by the patient and may also indicate the dosage to be administered to the patient.
In the system 100 of
Alternatively, a subset of the number of electrodes prescribed by the 10/20 Electrode Placement System may be applied to the patient 1. Specifically, in one example, the electrodes may be applied only to the forehead such that each of the electrodes is only sensitive to activity in the frontal regions of the brain. Knowledge of the normative covariance matrix describing relationships between such a subset and the full 10/20 array may be used to augment the data recorded directly from the subset. The reduced number of electrodes is less cumbersome to the person applying the embodiment of the present invention and may be particularly useful for a portable version of the embodiment of
In the stationary implementation of the QGSM system 100, the electrodes 2 preferably use a standard electrolyte gel, or other application method, so that the impedance of each electrode-skin contact is below 5000 ohms. Alternatively, for some applications, a plurality of needle electrodes, a pre-gelled electrode appliance with adhesive or other means of fixation, or an electrode cap or net with preselected electrode positions may be used. The QGSM system 100 automatically checks the electrode-skin impedance of each electrode 2 at frequent intervals, (e.g., every minute), and displays a warning (e.g., a red LED light) if any such impedance increases above 5000 ohms.
Electrode leads connect each of the electrodes 2 to a respective EEG/EP amplifier 3 of a processing unit 1, with each amplifier 3 preferably including an input isolation switch (e.g., a photo-diode and LED coupler) to prevent current leakage to the patient 1. The amplifiers 3 are high-gain, low-noise amplifiers, preferably having, for example, a maximum peak-to-peak noise of 1 microvolt, a frequency range of 0.5-200 Hz, a fixed gain of 10,000 and a common mode rejection of 100 dB or more (4 amplifiers). The amplifiers 3 are analog amplifiers and may be connected to an analog-to-digital multiplexer 4 (“A/D multiplexer”). Alternatively, the amplifiers 3 may be digital 24-bit amplifiers, thus obviating the need for the A/D multiplexer 4. In the case where amplifiers 3 are analog, the A/D multiplexer 4 may sample the amplified analog brain waves at a rate of, for example, 5 KHz for each channel. The A/D multiplexer 4 is connected to a filtering arrangement 8 which is, in turn, connected to a central processing unit 25 including a dedicated digital signal processor (“DSP”) 7, such as, for example, model TMS320C44® (Texas Instruments). Alternatively, the DSP 7 may be a Pentium 4 Processor® (Intel) or a digital signal processor such as the TMS320C44® (Texas Instruments) along with a microprocessor.
Using techniques that would be understood by those skilled in the art, the system 100 collects analog EEG signals from the patient 1, digitizes the signals via the A/D multiplexer 4 and, under the control of a suitably programmed DSP 7 in CPU 25, performs on the digitized EEG signals a Fast Fourier Transform via FFT module 9 to extract from the EEG signals QEEG data representing the power spectra of the EEG signals at predetermined frequency intervals. The present invention is also consistent with QEEG data that has been derived from techniques other than FFT, such as a Wavelet Transform Analysis, Independent Component Analysis, etc. As shall be explained more fully below, the system 100 according to the present invention constructs from the QEEG information a brain state vector (“BSV”), which may be used to optimize pharmacological treatment of the patient 1.
Each dimension n of the BSV may, for instance, signify a single frequency band of interest while the value assigned to each dimension n signifies a deviation between the brain activity measured from the patient 1 (e.g., in the QEEG data) for the frequency band of interest and the normative brain activity for that frequency band obtained from normative database 10. The elements comprising the BSV may also represent symmetries or synchronies between spectral descriptors in selected regions or sets of regions. The system 100 may calculate such deviations for each of a plurality of frequency bands or sets of descriptors. For instance, the system 100 may determine whether deviations in QEEG data exist for any of the alpha (8-14 Hz), beta (14-30 Hz), gamma (26-100 Hz), delta (0.5-4 Hz), and theta (4-8 Hz) frequency bands in any electrode or the ratio of voltages or the phase relationship of oscillations at any frequencies within or between any pair of electrodes. Other frequency bands of interest may serve as the basis for the analysis performed by system 100. For example, the system 100 may perform the analysis on frequency intervals located within the very narrow band (VNB) power spectrum. As mentioned above, each dimension compressed into the BSV may correspond to one frequency band. If the frequency bands of interest are the alpha, beta, gamma, delta and theta bands, then the BSV will be compressed from four dimensions, representing the standard score or Z-value for each band. The present invention is not limited to constructing BSVs composed of dimensions associated with the alpha, beta, gamma, delta, and theta bands, but is instead capable of constructing BSVs having as many dimensions as there are frequency bands of interest, relations or interactions among sensors of brain activity in a particular application, or other descriptors (e.g., blood pressure, heart rate, EKG). If the user of the system 100 is interested in determining the deviation from the norm population in QEEG data in 12 frequency bands, then system 100 is capable of computing a brain state vector from data with twelve dimensions, one for each frequency band of interest.
In order to perform the analysis on selected frequency bands, processing unit 1 includes a filtering arrangement 8 that operates according to known high-pass, low-pass and band-pass filtering techniques in order to isolate QEEG data for specific frequency intervals of interest. For example, known filtering techniques may be employed such as those described in U.S. Pat. No. 4,705,049 to John and U.S. Pat. No. 6,556,861 to Prichep the entire disclosures of which are hereby incorporated by reference in their entireties.
The method of
CPU 25 obtains the QEEG value for all Z-scores in the set of descriptors which are above the selected threshold relative to a normative database 10 (step 302). The QEEG value derived from patient 1 used in this method can be a value that has just been calculated from a real-time EEG obtained while patient 1 is still joined to the system via the scalp electrodes 2, or it can be one that was previously calculated and recorded onto an electronic storage medium (e.g., flash memory, CD-ROM, etc.) and read out for the purpose of performing the analysis described herein (step 303). CPU 25 then determines whether a significant difference is present in the patient 1 relative to the normative database 10 (step 304). If there is a difference between the normative value and the present reading, the method proceeds to step 305 wherein the BSV may be conceptualized as a vector from the point of origin of the signal space and a tip at the multivariate distance from the origin, which would represent the mean values of the normative distribution of all the variables in the BSV.
If no difference is observed, the method may proceed to step 306, wherein the system 100 may determine if the method has reached the last dimension of interest. If the present N value is the last dimension of interest, the method may end. If the present dimension is not the last dimension of interest, the method may process to step 307 wherein a different N value, which corresponds to an EEG frequency band of interest, may be selected. In the exemplary embodiment shown, the system 100 scans for abnormalities in the EEG systematically based on the frequency band associated with each N value. Those skilled in the art will understand that the assignment of N values may be preset or may be defined by a user of the system 100 so as to limit or expand a scan set to a desired set of frequencies. After a new frequency band of interest has been assigned in step 307, the method returns to step 302 to scan this N value for abnormalities. After scanning of all frequency bands of interest has completed, the method may end and the resultant BSV computed.
As seen in
In order to determine the association between a BSV orientation and particular medicines, a population of normal persons across a wide range of ages (e.g., ranging from newborn to 90 years) exhibiting no signs symptomatic of brain disorder would be prescribed various psychotropic drugs. The brain activity of each subject would be monitored before and after the administration of the drug to determine a BSV resulting from the drug with a magnitude of the resulting BSV being correlated to the dosage administered. For instance, the orientation and magnitude of each of the BSVs produced in a population by a drug would be correlated to the age and dosage for each subject. This data may then be recorded into the medicine database 5. Different drugs may be tested on the control population and the respective BSVs may be recorded until a complete medicine database 5 is produced, containing a plurality of drugs and respective BSV orientation/magnitude data correlated again by age of the subjects (age regression may be used).
After determining the orientation of the BSV for patient 1 (step 501), the CPU 25 may use the orientation for the determined BSV to look up in the medicine database 5 the recommended pharmacological treatment for the patient 1. The medicine database 5 may be arranged as a look-up table, although any other data structure may be used that is capable of associating the determined orientation with a recommended treatment. Each BSV orientation may be associated with one or more drugs, drug regimens or class of drugs. In the case of a patient 1 exhibiting the BSV 600 shown in
The system shown in
As the drug is administered to the patient 1 by the system 100, the system 100 may also monitor the patient BSV in real time to determine whether or when it is being reduced in length in a direction toward the point of origin of the multidimensional brain electrical signal space. The response of the patient 1 to the drug may be nonlinear, which means that after a certain point, a further increase in dosage will not produce a proportionate improvement in the patient 1, and may in fact begin eroding the previous benefits achieved at lower dosages. This monitoring may be done, for instance, by repeating at predetermined intervals the method of constructing a BSV to observe whether, over time, the BSV for the patient 1 is shrinking toward the point of origin. If increased dosages of the administered drug cause the patient 1 to regress, a real-time monitoring of the patient's BSV will indicate either that the BSV is no longer moving back to the point of origin of the vector space, or that the BSV is actually increasing in magnitude. At this point, a switch in medication is warranted. The system 100 may select another drug within the class of drugs associated with the orientation of the patient BSV. On the other hand, there may be no other drugs in the medicine database 5 that may have, or may be close to having, an orientation that is the opposite of the patient BSV orientation. In this case, the system 100 may need to select a combination of drugs associated with different respective orientations. The system 100 may select drugs with respective BSV orientations so that, when their respective BSVs are added through typical vector summation techniques, the summation will produce a resultant vector with an orientation that is the opposite (or close to the opposite) of the patient BSV.
The exemplary system and method of the present invention may not be limited to use with the EEG and QEEG but may also be utilized to create BSVs for metabolic measures of different brain regions or for any other physiological measurements such as blood pressure, heart rate, electrocardiogram descriptors, cerebral blood flow measurements obtained from single photon emission computed tomography (“SPECT”), regional glucose metabolic measurements obtained from positron emission tomography (“PET”), etc.
An exemplary alternate embodiment of the present invention is described with respect to
An appropriate drug or combination of drugs may then be administered to the patient 1 (step 703). After the desired drug or combination of drugs has been administered to the patient 1, a follow-up MRS may be performed to determine the level of efficacy of the drug(s) (step 704). Specifically, the follow-up MRS may determine the neurotransmitter levels after the drug(s) has taken effect to determine, in conjunction with further QEEG analysis, if a change in a desired direction has taken place and what the magnitude of this change was. Data from the follow-up MRS of the patient 1 before and after administering the drug(s) may be recorded in a database similar to the medicine database 5. As increasing amounts of information is entered relating to different drugs and dosages, a master MRS database may be created that may serve as a reference for the system to properly diagnose an individual based on exhibited MRS activity (step 705). The master MRS database may include information regarding the effects of dosages of specific drugs on the MRS of selected ROIs when the maximum LORETA effects of each drug were found.
Furthermore, the exemplary method of
Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
This application claims priority to U.S. Provisional Application Ser. No. 61/014,068, entitled “QEEG-Guided Selection and Titration of Psychotropic Medications” filed on Dec. 18, 2007. The specification of the above-identified application is incorporated herewith by reference.
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/US08/86609 | 12/12/2008 | WO | 00 | 1/14/2011 |
Number | Date | Country | |
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61014618 | Dec 2007 | US |