Brain electrical activity mapping

Abstract

Apparatus for generating a topographic display of information on brain electrical activity based on responses of electrical-activity transducers placed on the skull. In different aspects, the brain is stimulated at pseudorandom intervals to produce EP responses; matrices corresponding to the electrical responses are processed to generate a statistical comparison matrix and the corresponding display map is grid sector analyzed; a series of tests is administered some of which put the brain in a simple resting state, others putting the brain in nonresting states of varying activity level; statistical comparison matrixes are generated representing the statistical difference between normal and abnormal groups at different skull locations with respect to different brain activities; significance probability maps are generated each representing the statistical difference between a patient and the normal population with respect to different brain activities; and an epileptic spike is caused, a sufficient number of data matrices is generated to capture onset of the spike, and the frame rate of display of the corresponding topographic maps is selectably changed for observing the onset.

What is claimed is: 
     
       1. Apparatus for generating a topographic display of information on the electrical activity of the brain, said apparatus comprising a plurality of electrical-activity transducers adapted for placement at spaced apart locations on the skull of a patient,   stimulus means for repeatedly generating a sensory stimulus for the brain to produce at said transducers repeated segments of data each associated with one EP response, said stimulus means including   pseudorandom timing means for triggering successive said stimuli at times spaced apart by pseudorandom time intervals, and for determining each said pseudorandom time interval as a combination of a subinterval of fixed length and a subinterval of pseudorandomly determined length, each said fixed length subinterval comprising a pre-stimulus subinterval of predetermined length and a post-stimulus subinterval of predetermined length,   averaging means connected to be responsive to said transducers for averaging said repeated segments to generate average segments for each transducer,   processing means connected to be responsive to said averaging means for processing said average segments to generate one or more matrices, each element said one or more matrices representing information on the electrical activity of the brain at one location on the skull,   display means connected to be responsive to said processing means for displaying said one or more matrices as topographic maps of the skull, each said matrix element forming a discrete point of said maps.   
     
     
       2. The apparatus of claim 1 wherein said pseudorandomly determined subinterval includes a subinterval that varies pseudorandomly from zero to a period longer than the post-stimulus response time, whereby interference due to .[.contigent.]. .Iadd.contingent .Iaddend.negative variation is reduced. 
     
     
       3. The apparatus of claim 1 wherein said pseudorandomly determined subinterval includes a subinterval that varies pseudorandomly from zero to a period longer than the wavelength of a prominent of frequency of steady-state brain activity, whereby interference due to such steady-state brain activity is reduced. 
     
     
       4. The apparatus of claim 3 wherein said prominent frequency is 10 Hz and said subinterval varies from zero to 100 milliseconds. 
     
     
       5. The apparatus of claim 1 wherein said pseudorandom timing means includes a clock for generating timing pulses,   a sequential counter connected to be responsive to said clock for counting said pulses,   a comparator connected to be responsive to said counter for comparing the contents of said counter to a stored number, and signalling the end of one said subinterval when said count equals said stored number,   a memory for storing a sequence of pseudorandom numbers, and   means for replacing said stored number with a different one of said pseudorandom numbers for each succeeding stimulus.   
     
     
       6. The apparatus of claim 1 further comprising means connected to influence said stimulus means, for temporarily delaying triggering of said stimuli in response to a signal from the operator of said apparatus. 
     
     
       7. The apparatus of claim 1 wherein said stimulus means comprises means for generating a repeated sequence of plural stimuli. 
     
     
       8. The apparatus of claim 7 wherein said plural stimuli are of different types. 
     
     
       9. The apparatus of claim 8 wherein said different types include light stimuli and sound stimuli. 
     
     
       10. The apparatus of claim 1 wherein said stimulus is repeated at least 100 times. 
     
     
       11. The apparatus of claim 1 wherein said stimuli are any one of the following: a single flash, a single click, a visual pattern reversal, and a somatosensory stimulus. 
     
     
       12. The apparatus of claim 7 wherein said stimulus consists of an auditory or visual event that is infrequently of a first type and more frequently of a second type. 
     
     
       13. The apparatus of claim 12 wherein said first and second events are spoken words that are similar in sound. 
     
     
       14. Apparatus for generating a topographic display of information on the electrical activity of the brain, said apparatus comprising a plurality of electrical-activity transducers adapted for placement at spaced apart locations on the skull of a patient,   processing means connected to be responsive to said transducers for processing electrical .[.response.]. .Iadd.responses .Iaddend.measured at said transducers to produce one or more matrices, each matrix containing a plurality of elements, said elements representing information on the electrical activity of the brain at particular skull locations,   statistical processing means connected to be responsive to said processing means for processing at least two said matrices to generate a statistical comparison matrix, said statistical comparison matrix having elements each of which is representative of a statistical difference between the corresponding elements in said two matrices,   display means connected to be responsive to said statistical processing means for displaying said statistical comparison matrix as a topographic map of the skull, said matrix elements forming discrete points of said map, and   grid sector analysis means connected to be responsive to said display means including means for assigning points of said map to sectors of a grid and means for determining the mean of said statistical comparison elements in each said sector.   
     
     
       15. The apparatus of claim 14 wherein said grid sector analysis means further comprises means connected to be responsive to said grid sector analysis means for changing the sector size in said grid and repeating the determination of the .[.means.]. .Iadd.mean .Iaddend.for the new sector size,   means for determining a histogram for each of the grid sector sizes, each said histogram constituting numbers of grid sectors having mean values falling within selected mean value ranges.   
     
     
       16. The apparatus of claim 15 wherein said means for changing the sector size includes means for forming grids with from 2 to 4000 sectors. 
     
     
       17. The apparatus of claim 16 wherein said means for changing the sector size includes means for forming grids with either 16, 64, or 4000 sectors. .[.18. A method of extracting clinically useful information on the electrical activity of a patient's brain, comprising the steps of: applying electrical-activity transducers at spaced apart locations on the skull of the patient,   administering a series of tests to the patient while processing responses measured by said transducers, one or more of said tests being selected to put the brain in a simple resting steady state and   a plurality of other tests being selected to put the brain in nonresting steady states corresponding respectively to different levels of activity, and   processing resulting responses measured during each said state to generate one or more matrices of display elements, each display element representing information on the electrical activity of the brain at one location on the skull, and   displaying said one or more display matrices in the form of topographic maps, with each display element forming a discrete point on the maps..]. .[.19. The method of claim 18 wherein said processing is done intermittently at times while the brain is in a single state and not while the brain is changing between states and not while there exists a condition in the patient's activity that would generate an artifact in the response..]. .[.20. The method of claim 18 wherein said tests for putting the brain in a simple resting steady state are selected from the following:   (1) patient relaxes and remains still with eyes closed,   (2) patient relaxes and remains still with eyes open,   (3) patient hyperventilates, and   
     
     
       (4) patient becomes drowsy..]. 21. .[.The method of claim 18.]. .Iadd.A method of extracting clinically useful information on the electrical activity of a patient's brain, comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient,   administering a series of tests to the patient while processing responses measured by said transducers, one or more of said tests being selected to put the brain in a simple resting steady state and   a plurality of other tests being selected to put the brain in non-resting steady states corresponding respectively to different levels of activity, and   processing resulting responses measured during each said state to generate one or more matrices of display elements, each display element representing information on the electrical activity of the brain at one location on the skull, and   displaying said one or more display matrices in the form of topographic maps, with each display element forming a discrete point on the maps, .Iaddend.wherein said plurality of tests for putting the brain in nonresting steady states of varying activity levels are selected from the following:   (1) patient listens carefully to a story and answers simple questions about its content when completed,   (2) patient listens to music,   (3) patient remembers a set of abstract figures presented by the examiner,   (4) patient selects the previously presented figures from a larger set of figures by verbally indicating yes or no,   (5) patient associates abstract figures with particular artificial names spoken by the examiner,   (6) patient names each of the abstract figures when tested by the examiner,   (7) patient reads silently three previously unread paragraphs in preparation to answer questions subsequently,   (8) patient identifies whether sentences presented by the examiner were previously included in the three paragraphs, and   
     
     
       (9) patient reads text upside down. .[.22.  The method of claim 18 wherein the total time of the responses for each test in said series is in the 
     
     
        range from 20 seconds to 3 minutes..]. 23. .[.The method of claim 18.]. .Iadd.A method of extracting clinically useful information on the electrical activity of a patient's brain, comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient,   administering a series of tests to the patient while processing responses measured by said transducers, one or more of said tests being selected to put the brain in a simple resting steady state and   a plurality of other tests being selected to put the brain in non-resting steady states corresponding respectively to different levels of activity, and   processing resulting responses measured during eash said state to generate one or more matrices of display elements, each display element representing information on the electrical activity of the brain at one location on the skull, and   displaying said one or more display matrices in the form of topographic maps, with each display element forming a discrete point on the maps, .Iaddend.wherein said patient is an infant and said tests for putting the brain in a simple resting steady state are selected from the following:   (1) infant is sleeping and   
     
     
       (2) infant is drowsy. 24. .[.The method of claim 18.]. .Iadd.A method of extracting clinically useful information on the electrical activity of a patient's brain, comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient,   administering a series of tests to the patient while processing responses measured by said transducers, one or more of said tests being selected to put the brain in a simple resting steady state and   a plurality of other tests being selected to put the brain in non-resting steady states corresponding respectively to different levels of activity, and   processing resulting responses measured during each said state to generate one or more matrices of display elements, each display element representing information on the electrical activity of the brain at one location of the skull, and   displaying said one or more display matrices in the form of topographic maps, with each display element forming a discrete point on the maps, .Iaddend.wherein said patient is an infant and said tests for putting said brain in said non-resting steady states are:   (1) infant is stimulated by face-to-face visual contact and   (2) infant is alert but not attending to visual and auditory information.   
     
     
          . A method of using topographic maps of brain electrical activity to determine brain regions with different electrical activity for normal and abnormal groups, comprising the steps of applying electrical-activity transducers at spaced apart locations on the skulls of a group of normal patients and a group of abnormal patients,   administering to the patients a series of tests that cause selected brain electrical activity while simultaneously storing portions of responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity and each patient, the one or more matrices having elements representing brain electrical activity at different skull locations,   processing the one or more matrices to generate a statistical comparison matrix for each selected brain activity, each statistical comparison matrix having elements representing the statistical difference between the normal and abnormal groups at different skull locations,   displaying each statistical comparison matrix as a topographic map of the skull, with each element defining a discrete point of the map, and   identifying map regions in which normal and abnormal population groups have statistically significant differences in brain electrical activity.   
     
     
        .[.     A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient, comprising the steps of applying electrical-activity transducers at spaced apart locations on the skull of the patient,   administering to the patient one or more tests that cause selected brain electrical activity while simultaneously storing portions of responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain electrical activity at different skull locations,   processing the one or more matrices to generate a significance probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said matrix elements forming discrete points of the said maps, and   assessing selected regions of said one or more maps to identify differences in those regions between the patient and the normal population..]. .[.27. The method of claim 26 wherein said assessing step comprises the steps of   processing the elements within said selected regions to generate one or more quantitative measures of the statistical difference between the patient and the normal population,   comparing said one or more measures against predetermined values to provide diagnostic information on the likelihood that the individual has said   
     
     
        selected abnormality..]. 28. .[.The method of claim 27.]. .Iadd.A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient, administering to the patient one or more tests that cause selected electrical activity while simultaneously storing portions of responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain activity at different skull locations,   processing the one or more matrices to generate a significant probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said one or more matrices having discrete points of the said maps, and assessing selected regions of said maps to identify differences in those regions between the patient and the normal population,   processing the elements within said selected regions to generate one or more quantitative measures of the statistical difference between the patient and the normal population,   comparing said one or more measures against predetermined values to provide diagnostic information on the likelihood that the individual has said selected abnormalities, .Iaddend.wherein said abnormality is a migraine headache, said tests include causing the patient to assume a resting eyes-open state and a resting eyes-closed state, and providing repeated visual stimuli to produce repeated EP responses, said processing includes producing spectral energy matrices for the 8-11 H z  frequency band from the background data taken during the resting states and producing a time-sequence of matrices from the EP responses, and wherein said assessing step includes assessing from said matrices the presence of   
     
     
        increased occipital activity. 29. The method of claim 28 wherein said tests further include providing repeated bilateral somatosensory stimuli 
     
     
        to generate repeated EP responses. 30. .[.The method of claim 26.]. .Iadd.A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient, comprising the steps of: applying electric activity transducers at spaced apart locations on the skull of the patient,   administering to the patient one or more tests the cause brain electrical activity while simultaneously storing portions of the responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain electrical activity at different skull locations,   processing the one or more matrices to generate a significance probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said one or more matrices having discrete points of the said maps and assessing selected regions of said maps to identify difference in those regions between the patient and the normal population, .Iaddend.wherein said abnormality is an emotional dysfunction, said regions include the frontal lobes, and said assessing steps includes assessing the lack of synchrony   
     
     
        between said frontal lobes. 31. The method of claim 30 wherein said tests include repeated visual stimuli to generate repeated EP responses, and said assessing includes assessing the difference in electrical polarity 
     
     
        between the right and left frontal lobes. 32. The method of claim 30 wherein said emotional dysfunction is schizophrenia and said tests include causing the patient to assume resting eyes-open and resting eyes-closed states and providing a repeated visual stimulus to generate repeated EP responses, said processing includes producing spectral-energy matrices from the background activity stored during the eyes-open and eyes-closed tests and producing a time-sequence of matrices from the EP responses, and said assessing includes assessing the presence of increased activity 
     
     
        overlying the frontal regions. 33. .[.The method of claim 26.]. .Iadd.A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient,   administering to the patient one or more tests that cause selected electrical activity while simultaneously storing portions of responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain activity at different skull locations,   processing the one or more matrices to generate a significant probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said one or more matrices having discrete points of the said maps, and assessing selected regions of said maps to identify differences in those regions between the patient and the normal population, .Iaddend.wherein said abnormality is learning and emotional problems in an infant, said tests include sleeping, providing repeated visual stimuli during sleep, causing the baby to become alert from a sleeping state, said processing includes producing spectral energy matrices from the background activity stored during the sleeping and the alert states and a time-sequence of matrices from the EP responses to the visual stimuli and wherein said assessing step includes assessing increased activity in the frontal regions of the delta spectral-energy matrices for data taken as the infant   
     
     
        is being alerted. 34. .[.The method of claim 26.]. .Iadd.A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient comprising the steps of: applying electrical activity transducers at spaced apart locations on the skull of the patient,   administering to the patient one or more tests that cause selected electrical activity while simultaneously storing portions of responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain activity at different skull locations,   processing the one or more matrices to generate a significant probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said one or more matrices having discrete points of the said maps, and assessing selected regions of said maps to identify differences in those regions between the patient and the normal population, .Iaddend.wherein said abnormality is senile or pre-senile dementia, said tests include requiring the patient to repeatedly discriminate between frequently and infrequently heard tone pips of differing frequency, said processing includes producing a time-sequence of matrices representing the difference   
     
     
        between the EP responses to the two different tone pips. .[.35.  The method of claim 26 wherein said abnormality is epilepsy, said tests include causing the patient to assume a resting state with eyes closed and causing the patient to assume a resting state with eyes open,   said processing includes determining the Fourier transforms of the stored responses and determining from the transforms, for each transducer, the spectral energy contained in selected frequency bands, and processing the output of said spectral processing means to generate, for each selected activity, a plurality of matrices, one of said matrices for each selected frequency band, the elements of said matrices representing the spectral energy within the respective frequency band at one location on the skull, and   said assessing step includes assessing from said maps whether, as compared to the normal population, there are focal increases of activity in the selected frequency bands..]. .[.36. The method of claim 26 wherein said abnormality is epilepsy and wherein   said tests include providing a repeated visual stimulus to the patient to generate repeated EP responses,   said processing includes averaging the repeated responses to produce an average response for each transducer, zeroing each average response using a baseline determined from the pre-stimulus portion of each average response, and processing the zeroed average responses to generate one or more matrices, each element of which represents information on the EP response at one location on the skull, and   said assessing step includes assessing from said maps whether, as compared to the normal population, there are focal increases of activity..]. .[.37. The method of claim 26 wherein said abnormality is a supratentorial lesion and wherein   said tests include causing the patient to assume a resting state with eyes closed and causing the patient to assume a resting state with eyes open,   said processing includes determining the Fourier transforms of the stored responses and determining from the transforms, for each transducer, the spectral energy contained in selected frequency bands, and processing the output of said spectral processing means to generate, for each selected activity, a plurality of matrices, one of said matrices for each selected frequency band, the elements of said matrices representing the spectral energy within the respective frequency band at one location on the skull, and   said assessing step includes assessing from said maps whether, as compared to the normal population, there exists a pattern of hypo- or hyperactive   
     
     
        cortex..]. 38. The method of claim 26 wherein said abnormality is a supratentorial lesion and wherein said tests include providing a repeated visual stimulus to the patient to generate repeated EP responses,   said processing includes averaging the repeated responses to produce an average response for each transducer, zeroing each average response using a baseline determined from the pre-stimulus portion of each average response, and processing the zeroed average responses to generate one or more matrices, each element of which represents information on the EP response at one location on the skull, and   said assessing step includes assessing from said maps whether, as compared to the normal population, there are focal increases of activity. .[.39. The method of claim 26 further comprising the step of selecting one or more features each corresponding to one or more predetermined regions of said maps and to one or more predetermined said tests, said features being indicative of said abnormality, and wherein said selected regions include   
     
     
        said predetermined regions..]. 40. .[.The method of claim 39.]. .Iadd.A method of using topographic maps of brain electrical activity to aid diagnosis of a selected brain abnormality in a patient, comprising the steps of: applying electric activity transducers at spaced apart locations on the skull of the patient,   administering to the patient one or more tests that cause brain electrical activity while simultaneously storing portions of the responses measured by the transducers,   processing the stored responses to generate one or more matrices for each selected brain activity, the one or more matrices having elements representing brain electrical activity at different skull locations,   processing the one or more matrices to generate a significant probability map for each selected brain activity, each statistical probability map having elements representing the statistical difference between the patient and the normal population,   displaying said one or more matrices as topographic maps of the skull, said one or more matrices having discrete points of the said maps, and assessing selected regions of said maps to identify differences in those regions between the patient and the normal population,   selecting one or more features each corresponding to one or more predetermined regions of said maps and to one or more predetermined said tests, said features being indicative of said abnormality, and wherein said selected regions include said predetermined regions, .Iaddend.wherein said abnormality is dyslexia, and   one said feature corresponds to a region in the right occipital portion of the skull and to a tight-tyke auditory evoked potential test, and another said feature corresponds to a region in the left rear quadrant of the top   
     
     
        of the skull, and to an auditory (click) evoked potential test. 41. A method for assessing the brain regions in which an epileptic spike originates, comprising the steps of: applying a plurality of electrical-activity transducers at spaced apart locations on the skull,   causing an epileptic spike to occur while storing responses of said transducers,   processing the responses of said transducers to generate a time sequence of matrices, each said matrix having elements representing the instantaneous amplitudes of said responses at various locations on the skull and there being a sufficient number of said matrices for a selected time period of actual brain activity for capturing onset of the epileptic spike,   displaying said matrices as a time sequence of topographic maps of the skull at a variable frame rate, said matrices having elements defining discrete points of said maps,   selectably slowing the frame rate at which said topographic maps are displayed so as to permit observation of onset of said spike, and   assessing from said display the brain region or regions in which an   
     
     
        epileptic spike originates. 42. A method for generating a topographic display of information on the electrical activity of the brain, said method comprising the steps of placing a plurality of electrical-activity transducers at spaced apart locations on the skull of a patient,   repeatedly generating a sensory stimulus for the brain to produce at said transducers repeated segments of data each associated with one EP response, said stimulus step including   triggering successive said stimuli at time spaced apart by pseudorandom time intervals, and determining each said pseudorandom time interval as a combination of a subinterval of fixed length and a subinterval of pseudorandomly determined length, each said fixed length subinterval comprising a pre-stimulus subinterval of predetermined length and a post-stimulus subinterval of predetermined length,   averaging said repeated segments to generate average segments for each transducer,   processing said average segments to generate one or more matrices, said one or more matrices having elements,   each of which represents information on the electrical activity of the brain at one location on the skull, and   displaying said matrices as topographic maps of the skull, said matrices   
     
     
        having elements forming discrete points of said maps. 43. A method for generating a topographic display of information on the electrical activity of the brain, said method comprising the steps of placing a plurality of electrical-activity transducers for placement at spaced apart locations on the skull of a patient,   processing electrical responses measured at said transducers to produce one or more matrices, each of said matrices containing a plurality of elements, said elements representing information on the electrical activity of the brain at particular skull locations,   statistically processing at least two said matrices to generate a statistical comparison matrix, said matrix having elements, each of which is representative of a statistical difference between the corresponding elements in said two matrices,   displaying said statistical comparison matrix as a topographic map of the skull, said matrix elements forming discrete points of said map,   assigning points of said map to sectors of a grid, and   determining the mean of said statistical comparison elements in each said   
     
     
        sector. .Iadd.44.  The apparatus of claim 1 wherein said display means further comprising a scaled color means connected to be responsive to said processing means for producing scaled coloring of said topographic maps of the skull, each said point of said maps having a discrete scaled color. .Iaddend. .Iadd.45. The apparatus of claim 14 wherein said display means further comprising a scaled color means connected to be responsive to said statistical processing means for producing scaled coloring of said topographic maps of the skull, each said point of said maps having a discrete scaled color. .Iaddend. .Iadd.46. The method of claim 25 further comprising the step of processing each matrix element to produce scaled coloring of said topographic maps of the skull, each said point of said 
     
     
        maps having a dicrete scaled color. .Iaddend. .Iadd.47.  The method of claim 41 further comprising the step of processing each matrix element to produce scaled coloring of said topographic maps of the skull, each said point of said maps having a discrete scaled color. .Iaddend. .Iadd.48. The method of claim 42 further comprising the step of processing each matrix element to produce scaled coloring of said topographic maps of the skull, each said point of said maps having a discrete scaled color. .Iadd.49. The method of claim 43 further comprising the step of processing each statistical comparison matrix element to produce scaled coloring of said topographic maps of the skull, each said point of said maps having a discrete scaled color. .Iaddend.