U.S. patent number RE34,015 [Application Number 07/083,848] was granted by the patent office on 1992-08-04 for brain electrical activity mapping.
This patent grant is currently assigned to The Children's Medical Center Corporation. Invention is credited to Frank H. Duffy.
United States Patent |
RE34,015 |
Duffy |
August 4, 1992 |
**Please see images for:
( Certificate of Correction ) ** |
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.
Inventors: |
Duffy; Frank H. (Boston,
MA) |
Assignee: |
The Children's Medical Center
Corporation (Boston, MA)
|
Family
ID: |
26769808 |
Appl.
No.: |
07/083,848 |
Filed: |
August 7, 1987 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
Reissue of: |
263939 |
May 15, 1981 |
04421122 |
Dec 20, 1983 |
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Current U.S.
Class: |
600/544 |
Current CPC
Class: |
A61B
5/377 (20210101) |
Current International
Class: |
G06F
17/00 (20060101); A61B 005/0484 () |
Field of
Search: |
;125/731-733,903 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
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Classif. of Br. Electrical Activity"; Annals of Neur., vol. 7, #5,
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Duffy et al, "Dyslexia: Regional Diff. in Brain Electrical Activity
by Topographic Mapping"; Annals of Neur., vol. 7, #5, May 1980, pp.
412-420. .
Duffy et al, "Significance Probability Mapping; An Aid in the
Topographic Analysis of Brain Electrical Activity"; EEG & Clin
& Neurophys., 1981, pp. 1-8. .
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309-320. .
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similar people" Science vol. 196, pp. 1393-1410 (1977). .
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Paternoster et al., "A Colour Display Unit for a 21-Channel EEG
Monitor," Sigraph '79 Conference on Computer Graphics and
Interactive Technology pp. 210-217 (1979). .
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Elsevier Publishing Co., Amsterdam, NL. .
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Marguerite Zientara (CW Staff) Multiple Personalities `Mapped` by
Computer, Computer World publication, Jan. 24, 1983, p.
14..
|
Primary Examiner: Kamm; William E.
Attorney, Agent or Firm: Hamilton, Brook, Smith &
Reynolds
Claims
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.sub.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.
Description
The invention described herein was made in the course of work under
a grant or award from the Department of Health and Human
Services.
BACKGROUND OF THE INVENTION
This invention relates to analysis of brain electrical activity and
diagnosis of brain disorders.
Traditional electro-encephalographic (EEG) techniques of analyzing
brain electrical activity to diagnose brain dysfunction require the
skilled neurophysiologist to observe and distinguish time and
frequency related characteristics of many channels of voltage
waveforms derived from an individual's brain and to determine,
largely from memory, differences between that individual's
waveforms and waveforms characteristic of a normalized population.
The process necessarily fails to take account of many subtle but
potentially useful pieces of information contained in the analyzed
data.
Signal averaged sensory evoked potential (EP) transient responses
have also been used as a source for brain electrical activity
analysis, but large amounts of useful information contained in such
transient .Iadd.response .Iaddend.waveforms have traditionally been
disregarded because of the difficulty of visualizing the
inter-relationship over time of many channels of such
information.
SUMMARY OF THE INVENTION
The invention features, in one aspect, apparatus for generating
topographic displays of information on electrical activity of the
brain produced at a plurality of transducers on the skull in the
form of EP responses to repeated sensory stimuli; the stimulus is
triggered by a pseudorandom timer at pseudorandom time intervals,
each interval including a pre-determined pre-stimulus time
sub-interval, a pre-determined post-stimulus time sub-interval, and
a pseudorandomly varying time sub-interval; the repeated EP
responses at each transducer are averaged by averaging means; a
processor generates one or more data matrices from the EP
responses, and a display means displays the matrices as topographic
maps. The pseudorandomly varying time sub-interval can include a
sub-interval that varies from 0 to a period longer than the
post-stimulus time sub-interval and/or a sub-interval that varies
from 0 to a period (which can be 100 milliseconds) longer than the
wavelength of the major prominent frequency (which can be 10 Hz) of
steady-state brain activity; the pseudorandom timer can include a
clock, a sequential counter, a comparator, and a memory for storing
a sequence of pseudorandom numbers which can be used for triggering
succeeding stimuli; means can be provided for the operator to
interrupt temporarily the triggering of stimuli; means can be
provided for triggering a repeated sequence of plural stimuli,
which can be of different types, particularly light stimuli and
sound stimuli; the stimulus can be repeated at least 100 times; the
stimuli can be any one of a single flash, a single click, a visual
pattern reversal, and a somatosensory stimulus, or can be an
auditory or visual event infrequently of a first type and more
frequently of a second type; and said first and second events can
be similar sounding spoken words.
In another aspect the invention features a method of extracting
clinically useful information on the electrical activity of a
patient's brain; applying electrical activity transducers to the
skull; administering a series of tests selected to put the brain in
a simple resting state and then in non-resting states of varying
activity level; processing the resulting measured electrical
activity into one or more display matrices of elements, each
representing electrical activity at a location on the skull; and
displaying the matrices as topographic maps. In preferred
embodiments, the processing of electrical activity can be done
while the brain state is unchanging and not subject to artifactual
interference; four specific tests can be used to put the brain in a
simple resting state; nine specific tests can be used to put the
brain in non-resting state of varying activity level; the total
time for each test can range from 20 seconds to 3 minutes; testing
of infants can be based on two resting state tests and two
non-resting state tests.
In another aspect, the invention also features producing matrices
from electrical responses measured at the transducers, each matrix
containing elements representing particular skull locations; a
statistical processor for generating a statistical comparison
matrix from two other matrices in which each element of the
comparison matrix represents a statistical difference between
corresponding points on the two other matrices; a displayer for
displaying the companion matrix as a topographic map; and a grid
sector analyser for determining the means of elements of the
comparison matrix lying within sectors of a grid. In preferred
embodiments, the grid sector sizes can be changed, the means
determined with respect to each grid, and histograms prepared of
the numbers of grid sectors having mean values falling within
selected mean value ranges; the grids can have from 2 to 4000
sectors; and grids of 16, 64 or 4000 sectors can be used.
In another aspect, the invention features using topographic maps of
brain electrical activity to determine brain regions with different
electrical activity for normal and abnormal groups; applying
transducers to a group of normal patients and a group of abnormal
patients; administering a series of tests to cause selected brain
electrical activity while storing responses measured by the
transducer; processing the responses into matrices for each brain
activity and each patient, each matrix having elements representing
brain electrical activity at different skull locations; generating
a statistical comparison matrix between the normal and abnormal
groups for each brain activity; displaying the comparison matrices
as topographic maps; and identifying map regions displaying
statistically significant differences between the normal and
abnormal population groups.
In another aspect, the invention features using topographic maps of
brain electrical activity to aid diagnosis of a selected brain
abnormality in a patient; applying skull transducers; administering
tests to cause selected brain electrical activity while storing
portions of the responses measured by the transducers; generating
matrices of brain electrical activity, each element of a matrix
representing a different skull location; generating a significance
probability map for each brain activity representing the
statistical difference between the patient and the normal
population; displaying the matrices as topographic maps; and
assessing selected regions of the maps to identify differences
between the patient and the normal population. In preferred
embodiments, the maps are assessed by generating quantitative
measures of the statistical differences between the patient and the
normal population, and comparing the measures against predetermined
values to provide diagnostic information on the likelihood that the
individual has a selected abnormality; specific tests to be
administered, specific matrix processing steps, specific regions to
be analyzed, and specific assessments to be made or identified with
respect to the analysis and diagnosis of dyslexia, emotional
dysfunction, schizophrenia, infant learning and emotional problems,
senile or presenile dementia, migraine headache, epilepsy, and
supratentorial lesions.
In another aspect, the invention features assessing the brain
region in which an epileptic spike originates; using a plurality of
skull transducers; causing an epileptic spike to occur and storing
the transducer responses; generating a time sequence of matrices
sufficiently large in number to capture the onset of the epileptic
spike; displaying the matrices as a time sequence of topographic
maps; slowing the frame rate during display to permit observation
of the onset of the spike; and assessing the brain region in which
the spike originates.
The use of such a pseudorandom timer reduces the effect of noise
caused by contingent negative variation and by prominent signal
frequencies in background EEG. The topographic display enables the
user to easily view the movement of EP electrical activity over
different parts of the brain. By interrupting the stimulus
triggering process, the operator can avoid accumulating data during
the occurrence of artifact. By selecting from among different
stimuli and parts of stimuli offered in a sequence, the operator
can observe the electrical activity in different parts of the brain
and at different levels of activity. By administering a variety of
tests to a patient, the operator can establish a variety of
different states in the brain, and in the left and right
hemispheres of the brain, to maximize the amount of available
information. Grid sector analysis enables identification of brain
activity features which are significant indicators of the
differences between a dysfunctional group and a normal group.
Topographic display of statistical differences between two
population groups enables effective identification of brain regions
in which the two groups differ. The diagnosis of specific
dysfunctions using regional measurements of statistical maps to
identify useful tests, processing steps, regions for analysis, and
criteria for assessment, provides a powerful clinical tool, which
has significant advantages over presently used techniques.
In preferred embodiments, the invention features interpolating to
form additional matrix elements between the transducer points; the
interpolation can be three-point interpolation, particularly
three-point linear interpolation to the values of the three closest
transducers; the number of transducers can be in the range of 10 to
200; and the number of picture elements is at least 5 times the
number of transducers. The expansion of a matrix of a small number
of points to a display matrix of a large number of points
significantly improves the smoothness, readability and utility of
the resulting topographic displays.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram of the brain electrical activity mapping
system.
FIG. 2 is a representation of the organization of samples of data
in the BEAM system.
FIG. 3 is a representation of the formation of a topographic
display from a frame of data in the brain electrical activity
mapping system.
FIG. 4 is a block diagram of the functions performed by the BEAM
system.
FIG. 5 is a block diagram of the define protocols operation.
FIG. 6 is a block diagram of the disk data sampling operation.
FIG. 7 is a data file format diagram of the raw data file.
FIG. 8 is a block diagram of the core averaging operation.
FIG. 9 is a graph of an average EP transient response waveform
after automatic baseline zeroing.
FIG. 10 is a block diagram of the raw data quality control
operation.
FIG. 11 is a block diagram of the raw data topographic display
operation.
FIG. 12 is a block diagram of the create interpolation file
operation.
FIG. 13 is a block diagram of the raw data reduction operation.
FIG. 14 is a data file format diagram of signal averaged EP
data.
FIG. 15 is a data file format diagram of FFT ensemble data.
FIG. 16 is a data file format diagram of individual FFT data.
FIG. 17 is a data file format diagram of an EP file.
FIG. 18 is a data file format diagram of an FFT file.
FIG. 19 is a block diagram of the reduced data quality control
operation.
FIG. 20 is a graph of an average EP transient response waveform
after automatic baseline zeroing and after manual baseline
readjustment.
FIG. 21 is a block diagram of the reduced data topographic
operation
FIG. 22 is a block diagram of the group file production
operation.
FIG. 23 is a block diagram of the group topographic display
operation.
FIG. 24 is a block diagram of the individual vs. group comparison
operation.
FIG. 25 is a block diagram of the group difference detection and
feature selection operation.
FIG. 26 is a data file format diagram of a saved frame file.
FIG. 27 is a block diagram of the BEAM to TICAS file transfer
operation.
FIG. 28 is a block diagram of the TICAS feature selection and
evaluation operation.
FIG. 29 is a block diagram of TICAS generate decision rules
operation.
FIG. 30 is a block diagram of TICAS test decision rules
operation.
FIG. 31 is a block diagram of pseudorandom stimulus controller.
FIG. 32 is a sample of topographic displays generated by a brain
electrical activity mapping system.
DESCRIPTION OF THE PREFERRED EMBODIMENT
We now turn to a description of the preferred embodiment.
System Organization and Software
FIG. 1 illustrates the components of a brain electrical activity
mapping .[.Brain electrical activity mapping.]. system. Twenty
electrodes 5 (e.g., Grass gold cup) are attached to subject's skull
4 in a conventional international 10-20 format. Twenty leads 6 from
electrodes 5 are connected through switch 7 to conventional
24-channel polygraph 10 (e.g., Grass 8- 24D), which contains
parallel variable grain differential amplifiers and strip chart
recorders. Calibration signal source 8, an A.C. generator, is also
connected through switch 7 to polygraph 10. Stimulus A 2 (e.g.,
Grass Model PS1 strobe light) and stimulus B 3 (e.g., click
generator) present stimuli to the subject under the control of
pseudorandom stimulus controller 9, which also provides
pre-stimulus and stimulus trial marker signals (5 volt spikes) of
opposite polarity to one of the input channels to 24-channel FM
analog tape recorder 11 (e.g., Honeywell 5600E). In other
embodiments, recorder 11 is eliminated and polygraph 10 is
connected directly to filter 12 for real-time loading of data. The
21 active outputs of recorder 11 are connected to the inputs of 21
parallel variable band pass filters 12 (e.g., Butterworth filters;
EEG Associates Mark 4.times.24) having variable gain controls. The
21 outputs of filters 12 are connected to 21 of the input terminal
of two 16-channel, 12-bit analog-to-digital converters 15, 16
(Digital Equipment Corporation AA-11K), which comprise part of
digital computer 13 (Digital Equipment Corporation PDP 11/60).
Analog-to-digital converters 15, 16 are attached to data bus 14
(Digital Equipment Corporation Unibus). Also attached to data bus
14 are 4-channel, 12-bit digital-to-analog converter 17 (Digital
Equipment Corporation AD-11K) whose three outputs control black and
white television monitor 18 (Digital Equipment Corporation VR 17)
for waveform displays; color display control 19 (Digital Equipment
Corporation VSV 01) whose three outputs control 12" color
television monitor 20 (CONRAC) for topographic displays; 8 serial
line controller 24 (Digital Equipment Corporation DZ 11) two
outputs of which control interactive keyboard and video character
display terminal 22 (Digital Equipment Corporation VT 100) and
printer 23 (Digital Equipment Corporation LA 120); 256K byte memory
24 containing operating system software 27 (Digital Equipment
Corporation RSX 11/M); BEAM software 28 (Agrippa Data Systems), and
analytic software 29 (TICAS; University of Arizona); floating point
processor 25 (Digital Equipment Corporation FPP-11); central
processing unit 26 (Digital Equipment Corporation PDP 11/60); and
disk controller 27 controlling at least one disk drive 28.
Software Description
In general, the brain electrical activity mapping system creates
color topographic displays reflecting brain electrical activity
using, as input, continuous electrical waveforms recorded from a
number of points on the skull. The color topographic displays
consist of discrete matrices of a large number of display points
(also called pixels), each of which has a color or intensity of
other visible characteristic which indicates a certain value or
values at the location of that point analogous to a point on the
skull. In order to generate discrete topographic display matrices
having many thousands of display points from continuous analog
waveforms at a limited, e.g. 20, number of points on the skull, the
brain electrical activity mapping system, as illustrated in FIG. 2,
converts the data to digital form and generates discrete sample
frames 40, each sample or frame initially comprising 20 recorded
values 41 from 20 channels of information. The system treats
related groups of samples 40 as segments 42. In the case of EP
data, for example, a segment would consist of a series of frames or
samples, each 4 milliseconds in length, the series together
representing one transient response sequence from the beginning of
a pre-stimulus period to the end of the post-stimulus transient
response. In the case of steady-state EEG data, a segment would
consist of 2 seconds of data divided into 256 samples. A spectral
analysis of the EEG data then produces 256 samples, each of which
reflects the energy level in a small, e.g. 1/2 Hz, energy band and
a segment consists of the entire series of 256 spectral samples.
For signal averaging purposes, the system considers a set of
segments together, e.g., 500 segments each representing a transient
response to a given stimulus. The 500 segments taken together are
known as an ensemble 43. Frames of data can be raw data or data
which has been processed or transformed by the system. In any case,
as illustrated in FIG. 3, when a frame 40 is to be displayed it is
expanded into a matrix 45 consisting of a large number of display
points 46 which are determined by an interpolation process from the
original frame data points 47. Each point of the matrix is then
converted to a visual display point 47 which forms part of the
final topographic display 48.
FIG. 4 illustrates the organization of the operations which
comprise brain electrical activity mapping software 28 and TICAS
analytic software 29. Raw and processed data is stored in disk
files 51. Operations 52-65 and 67-69 use data stored in files 51 to
perform data manipulation, data display and data storage functions.
Operations 54 and 55 also process data from the outputs of
converters 15, 16.
FIG. 5 illustrates the function of define protocols operation 53.
Protocol files 73 are generated and edited by program `SETPAR` 71
based on control information 70 provided by the operator through
terminal 22, the results of the operation being displayed (block
72) on terminal 22 to the operator. Each protocol file 73 contains
information which governs the manner in which other operations are
performed on a particular type of data file (e.g., one protocol
might apply to the processing of EP transient response data from
strobe light stimuli). The protocol information may include the
number and identity of input channels, the labeling of the output
channels to correspond to specific points on the final display, the
identity of the trial marker channel, the voltage level above which
to search for the trial markers, the rate in samples per second of
sampling of the data, the number of samples in a segment, the
number of segments .[.is.]. .Iadd.in .Iaddend.an ensemble, the
number of ensembles, the number of points in a baseline, the
microvolt level of the calibration signal (e.g., 100 microvolts at
10 Hz), a multiplication factor, the number (up to 20) and size
(width) of integration bands, the label of the protocol, the
percent of taper of samples in a segment of data for fast fourier
transform processing, the number of automatic smoothing passes, the
high and low values for automatic rejection of data during
accumulation, the stimulus interval and location in seconds, and
channel labels related to electrode positions on the skull.
FIG. 6 illustrates the function of disk data sampling operation 54.
Program `DATACOL` 75 loads raw data from the .[.outpput.].
.Iadd.output .Iaddend.of converters 15, 16 into raw data file 79,
which is divided into 19 buffers 80 which hold ensembles of data
related to particular brain states or stimuli. The operator
provides control information 76 designating the patient to whom the
data relates and the name of the applicable protocol file 73. Other
control information 76 governs the beginning, end, and pauses in
data sampling, and the performance of a calibration of signal
levels. Calibration data is initially stored in a buffer 80 of raw
data file 79. When the operator requests (block 76) a calibration,
and designates which buffer 80 contains the raw calibration data,
program `DATACOL` computes the root mean square value and the mean
of at least 30,000 points in each channel of calibration data and
divides the root mean square value by 0.707 to establish the
assumed peak value of the calibration signal. The peak value,
representing the level of the original calibration voltage, and the
mean value, representing the D.C. offset of the calibration voltage
value for each channel, are stored in calibration file 78.
The format of raw data as stored in raw data file 79 is illustrated
in FIG. 7. Each buffer 80 contains header block 81, having protocol
and other housekeeping information concerning the data stored in
the buffer; calibration block 82 containing for each channel of
data the calibration value in microvolts per bit and the number of
microvolts by which the calibration signal was offset from zero
both of which values were found in calibration file 78 at the time
raw data was loaded; bad segment block 83 identifying segments of
data which the operator will later decide to exclude from
subsequent operations; an unused segment 84; and a series of data
segments 85, which hold a series of data samples, each containing
values for all 20 channels. The data segments 85 are interleaved
with no gaps.
FIG. 8 illustrates the function of core averaging operation 55,
usually used for loading and signal averaging raw EP transient
responses. Data from converters 15, 16 is read by program `CORAVG`
86. User provided control information 88 designates the protocol,
obtained from protocol file 73, under which the operation is
performed, and determines start, end, and pauses of the operation.
Program `CORAVG` 86 samples data beginning at points labled by the
prerecorded trial markers and forms signal averaged EP transient
responses from a series of transient responses resulting from
repetition of a stimulus. The series of transient response data are
accumulated and held in EP file 87, which is a reduced data file as
described below. Calibration file 78 holds calibration information
accumulated from the data channels in the manner previously
described. Program `CORAVG` 86 automatically rejects as "bad data"
any segment which contains values outside of preset limits. Program
`CORAVG` 86 also automatically adjusts the zero baseline with
respect to each electrode's average EP transient response, by
subtracting the mean of the pre-stimulus period values for a
channel from each point in that channel's transient response
curve.
FIG. 9 illustrates a plot of an average EP transient response 90 of
microvoltage against time as it could be displayed on monitor 18
following core averaging operation 55. The stimulus was presented
at time 93, the transient response includes pre-stimulus period
between time 92 and time 93, and the plot shows calculated zero
baseline 91.
FIG. 10 illustrates the function of raw data quality control
operation 56, which enables the operator interactively to review
and eliminate bad segments of raw data before other operations are
performed. By means of control information 94 the operator can
select for review the contents of any buffer 80 in raw data file
79. The buffer data is displayed (block 105) segment by segment by
program `GLITCH` 95 on television monitor 18 to the operator as an
analog waveform. The operator can label any segment of bad data,
which causes the bad data segment to be identified on bad segment
block 83. Control information 94 can also include the insertion of
trial markers indicating a point on a waveform at which subsequent
operations should begin, and display to the operator the microvolt
value of individual points on a displayed curve.
FIG. 11 illustrates raw data topographic display operation 57,
which provides topographic time sequenced displays (cartoons) of
raw data frames. Program `RAWMOV` 96 expands the 20 channels of
each data frame into a matrix of 128.times.128 data points by
three-point linear interpolation. The operator provides control
information 102 designating the disk buffer 80 on raw data file 79
which contains the data to be displayed; the number of display
matrices to be produced; the parameters for interframe
interpolation; and the parameters and options (described below) for
scaling the data points among the available grey color tones of the
display. Program `RAWMOV` 96 calculates each interpolated data
point for the display matrix using three-point linear interpolation
from the three closest original channels and scales the data to the
available grey color tones of the display. The interpolation is
performed using preset coefficients stored in interpolation file 97
by an operation described below.
The display matrices produced by program `RAWMOV` 96 are stored in
sequence in disk movie file 98. Program `RAWDIS` will display
(block 101) the frames stored in disk movie file 98 on monitor 20.
Control information 100 permits the operator to designate the file
to be displayed, the frame rate, and the starting, stopping and
reversing of the display sequence. The displays include labels of
information taken from the protocol block, e.g., patient
identification.
FIG. 12 illustrates the functions of create interpolation file
operation 52. Program `POINTS` 110 creates points file 115
reflecting the X and Y coordinates of each point in the original
electrode layout with respect to the 128.times.128 grid and
associating with each point in the 128.times.128 display matrix the
identity of the three original electrode points with respect to
which it should be interpolated. Control information 120 provided
by the operator includes the X and Y coordinates of each channel
and the identity of the three interpolation points for each display
point. Program `OUTLINE` 111 identifies and stores in outline file
116 the X and Y coordinates of the points which outline the plan
view of the skull to be included in the display, based on control
information 121. Program `MAKCOF` 112 generates and stores in
coefficient file 117 the coefficients needed to perform the
three-point linear interpolation for each matrix display point
within the skull outline, using points file 115 and outline file
116 as input. Program `MAKOVR` 113 stores in overlay file 118 the
operator provided (block 123) coordinates of the overlay of the
skull, nose and ears outline for the display. Program `SETOVR` 114
generates interpolation file 119 from overlay file 118 and
coefficient file 117. Interpolation file 119 then contains the
information required to compute interpolated matrix data points and
the skull overlay for display.
FIG. 13 illustrates the function of the raw data reduction
operation 58. Three alternative programs can operate on data in
buffers 80 to produce reduced data files 125. Program `DSKFFT` 126
accepts segments of EEG data from raw data file 79, performs a fast
fourier transform analysis which produces a new segment of data
reflecting the spectral energy in each of a sequence of frequency
bands. Program `DSKFFT` 126 also generates, for each group of
segments, an ensemble consisting of the sums (used in a later step
to form the average values) and sums squared (used in a later step
to form the standard deviations) for each channel across all
segments in the group, values reflecting each of the sums as a
percentage of the total spectral energy in the segment, and values
reflecting the coefficient of variation (the standard deviation
divided by the mean) for each channel across an ensemble. FIG. 15
illustrates the format of the resulting ensemble of FFT data stored
in reduced data file 125. The sums data 130 is filed in sequence by
channel for the first frequency band 131, e.g., 0.5 Hz. Similar
sums data follows for the other frequency bands. After all sums
data is stored, the sums squared data 132, the normalized power
spectral density sums, and the coefficient of variation data are
stored in similar fashion. In addition to storing the sums and sums
squared data for all segments in the ensemble, program `DSKFTT` can
store spectral information for each segment analyzed. As
illustrated in FIG. 16, the data is stored as sine and cosine
coefficients for each channel for each frequency band, and as
normalized sine and cosine coefficients as a percentage of total
spectral energy. As illustrated in FIG. 18, the FFT data file 191
stored on reduced data file 125 also includes a header block 192 of
housekeeping information.
In FIG. 13, program `DSKAVG` 127 performs a function similar to
core averaging operation 55 in signal averaging EP transient
response waveforms, but uses as input raw data stored in raw data
file 79 and permits the operator to review each waveform and select
those to be used in the averaging process, rejecting others.
Program `MANAVG` 128 permits a similar operator-assisted signal
averaging process when the raw data does not contain preset
stimulus trial markers, requiring the operator to indicate the
point at which averaging is to begin for each waveform. FIG. 14
illustrates the format of signal averaged data produced by programs
`CORAVG` 86, `DSKAVG` 127 and `MANAVG` 128. The sums of each
channel for all trials for the first time frame 133, e.g., 0-4
milliseconds, are loaded in order, followed by similar information
with respect to all subsequent time frames for a given segment. As
illustrated in FIG. 17, such EP files 190 are preceded by header
block 193.
FIG. 19 illustrates the function of reduced data quality control
operation 59, which permits the operator interactively to review
and modify data in reduced data file 125. By providing control
information 204, the operator can select the file to be reviewed
and indicate whether it contains FFT spectral information or EP
time-sequenced information. For FFT information, program `FFTLUK`
201 displays (block 202) selected channels of spectral data as
frequency-voltage curves on monitor 18 and permits the operator to
low-pass filter the waveforms and display the value of particular
data points. For EP data, program `EPLUK` 203 displays (block 202)
selected channels as time-voltage curves and permits the operator
to reset the zero baseline, to filter high frequency noise from a
channel, and to display the value of any point on a curve. FIG. 20
illustrates the function of manual baseline relocation. Because
pre-stimulus period response 180 was not level, automatic baseline
176 set by program `CORAVG` 86 inaccurately reflects the true zero
level for transient response curve 175. The operator can relocate
the baseline to a new level 177 by moving cursor 179 to the desired
level, causing that voltage value to be subtracted from each point
of data along curves 180 and 175.
FIG. 21 illustrates the functions of reduced data topographic
display operation 60. For single frame display of FFT data, program
`FFTTVM` 206 reads data from reduced data file 125 as selected by
operator control information 214. The data is scaled in accordance
with instructions included in control information 214. The selected
frame is provided to program `TVM16` 213 which interpolates a
matrix of 128.times.128 points using the coefficients and other
information contained in interpolation file 97, and provides the
resulting matrix to color display 212. For single frame EP display,
program `EPTVM` 205 performs an analogous process to that of
program `FFTTVM` 206. Programs `EPTVM` 205 and `FFTTVM` 206 also
perform compilations of sequences of frames into one display
matrix, in accordance with predefined groupings set forth in
protocol blocks.
A sequence of FFT matrices or EP matrices can be displayed in rapid
time sequence as a cartoon by the use of program `FFTMOV` 208 and
program `EPMOV` 207, respectively, each of which processes
sequences of selected matrices of data from reduced data file 125,
using scaling control information 215; interpolates full
128.times.128 matrices for each frame; interpolates a selected
number of additional matrices between the original frames; and
stores the resulting matrices in movie file 211. Based on control
information 216 specifying data to be displayed, the frame rate of
display, start, stop, backward, forward and pause, program `FFTDIS`
210 and program `EPDIS` 209 provide cartooned matrices for viewing
on color display 212.
FIG. 22 illustrates group file production operation 61. Program
`GRPBLD` 221 creates and updates a composite group file 223 working
from selected individual reduced data files 125. Control
information 222 provided by the operator indicates the identity of
individual reduced data files to be included. The group files 223
consist of the sums and the sums squared for all homologous points
in the reduced data files 125 of all individuals in the group.
Normalized sums and coefficients of variation may also be produced
and stored. Hard copy 224 listing the individuals in each group and
the values of group file data are available based on control
information 222.
FIG. 23 illustrates the function of group topographic data display
operation 62 which is analogous to the operation of the single
frame display of reduced data file information, illustrated in FIG.
21, except that the data displayed is from group file 223 instead
of reduced data file 125.
FIG. 24 illustrates the function of individual versus group
comparison operation 63. Programs `EPTVM` 205 and `FFTTVM` 206 are
performed respectively on EP and FTT data. In each case, the
program generates a frame of points, each of which is the number of
standard deviations (z-statistics) by which an individual's point,
taken from individual file 226 differs from the average of the
group's corresponding points taken from group file 223. The
resulting frame is displayed (block 216) by program `TVM16` 213,
which interpolates additional data points to form a 128.times.128
matrix in the manner previously described.
FIG. 25 illustrates the function of group difference detection and
feature selection operation 64, which computes frames of
t-statistics reflecting the level of statistical difference between
two groups based on the means and standard deviations of homologous
data points for the two groups. Program `GRPCMP` 230 computes
t-statistics and degrees of freedom from the sums and sums squared
data contained in two different group files 223 designated in
control information 231 provided by the operator. The resulting
frames are stored in group comparison file 232. Based on file and
frame designations set forth by the operator in control information
235, program `GRPDIS` 234 transmits a selected t-statistic frame
for display by program `TVM16` 213 as previously described. Program
`TVM16` 213 also returns a fully expanded 128.times.128 matrix back
to program `GRPDIS` 234. Through control information 235, the
operator may store such a t-statistic matrix in saved frame file
233. FIG. 26 illustrates the format of saved frame file 233. Header
block 240 contains the number of saved frames, and for each frame
identifies the time frame length or frequency band and the protocol
under which the data was collected. Frames 241 contain
128.times.128 matrices of floating point t-statistics generated by
program `GRPDIS` 234.
FIG. 27 illustrates the functions of the brain electrical activity
mapping to TICAS file transfer operation 65, which converts
features of brain electrical activity mapping data to a form usable
with TICAS software 29. Program `FEADEF` 245 generates feature list
file 247 from feature definitions and names of saved frame files
234 provided by the operator in control information 246. Program
`FEAGET` 248 then generates TICAS format file 249 from reduced data
files 125, saved frame file 233, and feature list file 247,
identified by the operator in control information 250. The feature
definitions which may be selected and stored in TICAS format file
249 for subsequent TICAS analysis include nearly all combinations
of data found in all individual files, all combinations of
integrated bands of frames (e.g., alpha bands) in individual files
grouped according to preset protocol specifications, or
combinations of individual frame files weighted by the values in a
saved t-statistic frame.
FIG. 28 illustrates the functions of TICAS feature selection and
evaluation operation 67. In control information 266, 264 the
operator designates two groups 262, 263 from TICAS format file 249
whose features are to be analyzed, the type of data to be analyzed,
the number of input features to be analyzed, and the number of
output features to be produced. Program `UTEST` 261 performs a
standard two-sample Wilcox-Mann-Whitney U-test and provides a list
of U-test scores in rank order which are printed on printer 23 and
stored. Program `FMTST` 260 performs a final merit value (FMV) test
and provides and stores a list of values for features in order of
final merit values. Program `FMTST` 260 first determines
intermediate merit values as a combination of the standard receiver
operating characteristic (ROC) curve or d' value and the results of
an ambiguity function analysis. The final merit values for each
feature are then determined by correlation of the intermediate
merit value with all features ranked higher in intermediate value.
Program `MERGE` 267 selects from Group A features 268 and Group B
features 269, based on the FMV values and U values, those features
which are most useful, which are then stored in disk files 270 and
271.
FIG. 29 illustrates the functions of TICAS generate decision rules
operation 68. Program `SLPRT` 275 uses an operator controlled
(block 278) subset of selected Group A features 276 and selected
Group B features 277 to generate disk stored interim rules 279, by
a method controlled (block 278) by the operator. The computation
method may be a non-parametric d-selection technique, a parametric
classification technique, or a combination of the two. Program
`CLSFY` 284 uses operator selected (block 285) interim rules 279 to
classify operator selected subjects having operator selected
features, from selected group features files 280 or refined group
features files 281, 282, printing the results on printer 23,
thereby permitting the operator to evaluate the efficacy of each
selected interim rule 279. Program `DSC` 286 combines operator
chosen (289) features from selected Group A features 287 and
selected Group B features 288 into new features on the basis of the
weighting functions of a standard linear discriminate analysis,
subject to the operator's choice (group 289) of discriminant
function parameters. Discriminant function weights for the best
features are then loaded into a disk file 290. Program `LINCOM B`
293 uses the original selected Group A features 291 and selected
Group B features 292 and the discriminate function weights 290 to
create refined Group A features 294 and refined Group B features
295, which are linear or other operator selected (block 296)
combinations of the original features. Refined Group A features 294
and refined Group B features 295 can replace the original selected
features 276 and 277 as input to program `SLPRT` 275 to permit an
iterative process of decision rule generation.
FIG. 30 illustrates test decision rules operation 69. Program
`CLSFY` 284 uses final sets of decision rules, e.g., rules A 304
and rules B 305, to classify individuals in original Group A 300,
original Group B 301 and new unknown groups, e.g., Group C 302 and
Group D 303, to determine the efficacy of the final decision rules,
the results being provided on printer 23.
OPERATION
Data Gathering
Accumulation of raw EEG and EP data is accomplished by first
attaching 20 electrodes 5 to the scalp of an individual subject in
a conventional international 10-20 format. In other embodiments,
information from between 10 and 200 electrodes can be gathered and
analyzed. Before recording, and if desired during recording, the
operator observes the signal levels on the 20 channels of chart
recording of polygraph 10 and adjusts the gain on weak signals to
produce usable waveforms. A calibration signal of 100 microvolts
(10 Hz) from source 8 is recorded on all twenty channels on tape
recorder 11 at the beginning of each session and whenever any of
the gain levels on polygraph 10 is adjusted.
Data gathering typically begins with a careful administration of a
sequence of tests, each of which is intended to establish a
particular steady-state electrical condition in the subject's
brain. The sequence of tests usually includes instructions to relax
and remain still with eyes open, to relax and remain still with
eyes closed, to become drowsy, to breathe deeply for
hyperventilation, to listen to music and to listen to speech. Other
tests require the subject to (1) listen carefully to a story and
answer simple questions about its content when completed, (2)
remember a set of six abstract figures (often resembling an unknown
language alphabet) in black ink on index cards presented by the
examiner, (Kimura Figures-Instruction) (3) select the six
previously presented figures from a set of 38 figures, verbally
indicating yes or no (Kimura Figures-Test), (4) associate each of
four abstract figures on index cards with a particular artificial
name spoken by the examiner (Paired Associates-Instruction), (5)
name each of the four abstract figures when tested by the examiner
(Paired Associates-Test), (6) read silently three previously unread
paragraphs (e.g., example test from the Gray Oral Reading Test) so
as to answer questions subsequently (Reading Test-Instruction), (7)
identify whether 34 typed sentences presented by the examiner were
previously included in the three paragraphs (Reading Test-Test),
and (8) read text upside down: The tests are designed to permit
recording of brain electrical signals during simple resting brain
activity and during different levels of activation of the left
hemisphere, the right hemisphere and both hemispheres of the brain
together. This permits the demonstration of pathologies present at
rest and those present upon brain activation. The development of
specific tests and the choice of tests is determined by the user
based in part on the subject being tested and the information being
sought as described in greater detail below. Between twenty seconds
and three minutes of steady state brain electrical activity is
recorded on all 20 channels during each of the tests. Appropriate
records of the tape location of each test are kept. These tests
have been used with the brain electrical activity mapping system to
demonstrate group differences between normal subjects and those
with dyslexia or specific reading disability at the 10-12 year age
level and at the six-year age level; to differentiate demented
patients from normals and aged patients from younger patients in
clinical settings; to identify patients with an organic basis for
sociopathic behavior and other forms of mental illness; to
demonstrate epilepsy when the resting background EEG failed to show
any abnormalities; to demonstrate abnormalities in EEG and EP data
for schizophrenic subjects; and to determine when a brain tumor,
previously treated, is about to recur.
With young infants, the brain states tested include sleep, alert
and attending to visual and auditory stimuli, alert but not
attending to visual and auditory information, and drowsiness. Using
these states, it is possible to discriminate among children with
poor behavioral scores on a psychological test and those with high
psychological scores.
A series of sensory evoked potential (EP) transient responses are
then recorded from all electrodes while the subject is repeatedly
exposed to a selected stimulus, e.g., a strobe light or a click
generator or to a predetermined sequence of two alternate stimuli.
Because the EP transient response is weak compared to the
background steady-state brain electrical activity, the stimulus
must be presented many times (e.g., 500) to the subject for later
signal averaging. The total response period of interest is
typically 1024 milliseconds, comprising 512 milliseconds before
stimulus and 512 milliseconds after stimulus. The process is
repeated for different stimuli.
Stimuli presented to the subject can range from simple flash,
simple click, simple pattern reversal and simple somatosensory
stimulation to those requiring complex decisions. Requiring a
subject to discriminate between subtly different auditory stimuli
(e.g., the words "tight" and "tyke") is useful in diagnosing
dyslexia. This procedure is known as the Tight-Tyke evoked
potential phenomic discrimination test. Picking an infrequently
different stimulus from among other more frequent stimuli is useful
evaluating subjects who have functional brain disorder.
Auditory stimuli generate a set of fast and a set of slow transient
responses. The fast responses eminate from the brainstem and have a
typical duration of 20 milliseconds. Braimstem responses are
normally sampled for a total response period of 40 milliseconds
comprising 20 milliseconds before stimulus and 20 milliseconds
after stimulus. Filters 12 are adjusted to exclude frequencies
below 300 Hz and to include frequencies up to 8000 Hz.
When EP transient responses from such stimuli are averaged to
eliminate noise, two types of interference can occur. The first
type, known as contingent negative variation (CNV), relates to the
connection made by the brain between consecutive equally spaced
stimuli when the subject is told to count the stimuli. The D.C.
component of the resulting transient response shows a gentle dip
and a sharp rise immediately before each stimulus, attributable to
subject's anticipation of the next stimulus. The sharp rise
contaminates the evoked potential transient .[.reponse.].
.Iadd.response .Iaddend.and makes it difficult to establish a zero
baseline. By including as part of the interval between stimuli a
first pseudorandom time element which varies from 0 to a period
longer than the post-stimulus response and is also a multiple of
the wavelength of the interfering frequency described below, the
CNV effect is greatly reduced.
The second type of interference results from the existence of
background noise at certain characteristic frequencies, e.g., 10
Hz, which reflect prominent bands of steady-state brain wave
activity. The major interfering frequency of a given subject may be
determined by a spectral analysis of his background EEG signal. The
interference problem is especially significant in adults with
prominent alpha waves and children with prominent slow brain wave
activity. By including in the time interval between stimuli a
second pseudorandom time element whose period varies from zero to
the wavelength of the major interfering frequency, the background
noise can be substantially reduced in the averaging process.
The inclusion of a prestimulus period of recording for each
transient response permits an accurate baseline determination at a
later stage of signal processing in order to establish a true zero
level for the post-stimulus response and permits a determination of
the quality of the signal averaging process.
Pseudorandom stimulus controller 9 measures the interval between
stimuli as a combination of the post-stimulus response period, the
first pseudorandom period described above, the second pseudorandom
period described above, and the pre-stimulus response period.
As illustrated in FIG. 31, .[.pseurandom.]. .Iadd.pseudorandom
.Iaddend.stimulus controller 9 comprises a four-stage timer, each
stage of which in turn measures one of the four periods included in
the interval between stimuli. The first stage comparator 406
measures the pre-stimulus period P.sub.1 /f.sub.c1 where P.sub.1 is
a number preset by the operator in register 408 and f.sub.c1 is the
frequency set on variable frequency clock 404. When the first stage
timing is completed, the second stage times the post-stimulus
period as P.sub.2 /f.sub.c2 where P.sub.2 is a number preset in
register 414 and f.sub.c2 is the preset frequency on clock 410. At
the end of the first stage timing period, a stimulus trial marker
(5 volt spike) is recorded on the trial marker channel of tape
recorder 11 and stimulus 409 is triggered. The selected
post-stimulus period is long enough to permit a full decay of the
transient response being observed. At the end of the second stage
timing period, the third stage measures the first pseudorandom time
period P.sub.3 /f.sub.c3, where P.sub.3 is the next pseudorandom
number in programmable read only memory (PROM) 419 and f.sub.c3 is
the preset frequency of variable clock 415. PROM 419 has been
preloaded with a pseudorandom sequence of numbers. At the end of
the third stage timing, the fourth stage measures a second
pseudorandom period in an analogous manner based on a pseudorandom
sequence in PROM 424 and a preset frequency on clock 420. When the
fourth stage timing period is over, a pre-stimulus trial marker (5
volt spike) is recorded on the trial marker channel of recorder 11.
A new timing cycle is then completed and the process is reiterated
until the total number of transient responses recorded equals a
preset number in register 426 or the process is stopped by the
operator. The entire process is begun by pushing button 401, which
causes the recording of a pre-stimulus trial marker. Temporary
delay button 431 can be used to temporarily delay the continued
operation of the timer at the operator's discretion, as for example
when the subject is distracted in a manner which would render the
transient response useless.
A low order bit in PROM 424 or PROM 419 can be set to 0 or 1 by the
operator for each number loaded into PROM 24 or PROM 19 so that two
different stimuli (e.g., auditory and visual) can be triggered in a
preselected order or pattern, with one stimuli being presented more
frequently than the other.
The result of the recording session is an analog tape of raw EEG
and EP voltage data and calibration voltages on 20 channels with
trial markers on a twenty-first channel. The next step is to load
the data into computer 13.
As previously described, brain electrical activity mapping software
28 performs data collection, data manipulation, and data display
functions in accordance with central information provided by the
operator. The various operations can be performed in any sequence
and the operator can perform a series of functions iteratively. The
operator provides control information through the keyboard of
terminal 22 and receives information concerning the various
operations on printer 23, waveform monitor 18 and topographic color
monitor 20. The flexibility of operation heightens the system's
utility as a diagnostic and analytical tool.
Data Loading
Under operator control, EEG data for each brain state and related
calibration signals are loaded directly onto disk storage from
recorder 11 after passing through filters 12 set to pass frequency
components between 0.5 and 50 Hz or between 0.5 and 1000 Hz and
epileptic spike data. Gain controls on the filters are adjusted to
fully utilize the signal capacity of converters 15, 16. EEG data
can be sampled at rates as high as 20,000 samples per second.
Under operator control, EP data is passed through filters 12 set to
eliminate frequencies above a selected frequency of between 40 and
100 Hz, or below 300 Hz for brainstem data, and is signal averaged
in core memory using averaging operation 55, which automatically
rejects bad data and sets the zero baseline.
Typically EP data is sampled every 4 milliseconds, or every
microseconds for brainstem analysis, and 256 samples are taken, 128
pre-stimulus and 128 post-stimulus. If the operator determines that
the EP transient response data is very noisy, he may alternatively
record the data as raw data and use raw data reduction operation 58
to average only selected transient response trials. In cases where
the transient response data may not contain the necessary stimulus
trial markers, such as in recordings of rapid eye movement (REM)
sleep, the data can similarly be recorded as raw data and trial
markers can be added manually by the operator, using raw data
operation 58, before signal averaging is done.
Raw Data Quality Control and Display
To assure the maximum accuracy and utility of raw data, the
operator can, using raw data quality control operations 56, display
recorded waveforms, accept or reject each waveform for later
processing, have mathematical smoothing operations performed, reset
baselines or eliminate certain points of data.
The operator views the EP transient responses for the 20 channels
for the purpose of evaluating the utility of each curve and
specifying modifications which will improve their utility when
displayed. The operator may direct a further adjustment of the
baseline, which has already been set automatically, by having a
constant number added to or subtracted from the value in each
frame, or can determine to have the automatic baseline
determination redone using a smaller number of the later
pre-stimulus frames as the baseline. This procedure is particularly
useful when the early pre-stimulus frames are found to contain the
tail end of the transient response of the prior stimulus. By
reviewing the relative levels of V.sub.RMS (pre-stimulus) and
V.sub.RMS (post-stimulus) for a given channel, the operator can
determine whether the background noise level is unacceptably large
with respect to the transient response, necessitating another
recording session with the subject. The operator may also filter
any high frequency noise in the post-stimulus period by three-point
interpolation.
As part of the raw data quality control process, if a channel
contains spurious values (e.g., voltage spikes) in particular
frames, the operator can eliminate those values and substitute
values interpolated from the next prior and next later frames. If
the voltage levels on one channel are substantially higher than for
the other channels, the operator can flag that channel to indicate
that the channel should be excluded from the subsequent display
scaling procedure (described below). Based on the operator's
instructions, the automatic baseline determination may be redone
and the results are viewed again until the operator is satisfied
that the set of transient responses contain satisfactorily low
noise levels and are properly zeroed.
Raw data topographic display operation 57 enables the operator to
display a cartoon series of topographic maps of raw data, which has
been expanded by interpolation into a matrix of 128.times.128
points. The cartoon can be started or stopped and run forward or
reversed at will. When raw EEG data is to be cartooned, the
operator can sample the data at a high rate, e.g., 400 frames per
second, and then display the information at slower speed or in a
series of matrices, each of which is an average of a sequence of
frames. The averaging can be done on a running basis, so that the
first N frames are averaged and displayed, then the N frames
beginning with the second frame are averaged and displayed, and so
on.
EEG Data Reduction
Raw EEG data is converted to spectral data using the fast Fourier
transform process of raw data operation 58, as previously
described. The segments of raw EEG curves whose spectral data is
averaged are generally about 2 seconds in length each, which is
shorter than the average period between spurious artifact signals.
Typically from 15 to 90 segments are spectrally analyzed and the
spectra averaged. The spectra usually consist of 128 frequency
bands or 1/2 Hz in width covering the spectrum from 0 to 64 Hz. The
ends of each segment can be tappered in accordance with the
operator's discretion in connection with the Fourier transform
process.
Reduced Data Quality Control and Topographic Display
Working with reduced EP and EEG data, that is sequences of time
frames of transient response data and groups of spectral band data,
the operator can use reduced data quality control operation 59 to
view the waveforms, discard bad data reflecting movement artifact,
eye blink, or muscle activity and eliminate high frequency noise.
The reduced data can then be topographically displayed on a frame
by frame or cartooned basis using the recorded data topographic
display operation 60. In either case, the operator can form frames
which represent combinations of underlying frames. For example,
groups of 1/2 Hz bandwidth frames can be combined into larger
bandwidth frames corresponding with typical spectra of clinical
interest, e.g., alpha, beta, delta and theta. Bands of any desired
width can be formed. In addition to displaying raw spectral energy
information from EEG data, it is possible to display normalized
spectral energy in which the points on each display are normalized
to the overall spectral energy of each electrode or to the average
overall spectral energy at all electrodes. In the case of EP data,
it is similarly possible to display each point as a normalized
value to the value at one specific electrode, e.g., the vertex
electrode designated "C.sub.z ", or to a standardized value, or to
a selected value, or to the V.sub.RMS of the background activity at
each electrode, or to the V.sub.RMS of all electrodes. Similarly,
the 128 frames of an EP transient response can be grouped into
frames of greater time duration for display.
Group Data Analysis
By accumulating a number of stored data frames, it is possible for
the operator to assemble and display group data files using group
file production operation 61 and group topographic data display
operation 62.
Significance Probability Mapping (SPM)
Using stored data for various groups and individuals, the operator
can perform and display topographically t-statistic comparisons
between groups of frames and z-statistic comparisons between an
individual frame and a group of frames. Any other statistical group
comparison can also be used to form a display matrix to illustrate
group differences. This type of analysis, significance probability
mapping (SPM), enables the operator to identify significant brain
activity features related to various neurophysiological illnesses
and conditions.
Grid Sector Analysis
Frames produced by the SPM procedure may be further analyzed by a
Grid Sector Analysis (GSA). While the frames produced by the SPM
procedure reflect regional abnormalities, the GSA procedure
produces numerical measures of the degree of global or focal
deviations from normal, which can assist in automatic determination
of the existence of regional abnormalities in unknown subjects.
The first step in the GSA process conceptually requires the
division of a frame into a number of different grids, each divided
into sectors of a uniform size. Within each grid sector, the mean
of all values of the data points lying within the sector is
determined as the value of that sector. The process is repeated for
grids of different fineness. Preferably three grids, of 4000
sectors, 64 sectors, and 16 sectors respectively, are used.
Histograms of sector values are then prepared for each grid
reflecting sector t-statistic or z-statistic values on the
horizontal axis and numbers of sectors having that value on the
vertical axis for each grid. Various analyses of the histograms,
which differ for focal and global abnormalities, which indicate
whether an abnormality is focal, i.e., localized in one area, or
global, i.e., diffused over a large part of the brain. One such
analysis would simply be the observation that the peak number of
sectors for the coarser grids will be at lower z or t values in the
case of a global abnormality than in the case of a focal
abnormality.
In the case of focal abnormalities, there is a marked difference in
the histograms for the three grids, while in the case of global
abnormalities, there is little or no .[.diffeence.].
.Iadd.difference .Iaddend.for the three grids. A variety of
features can be developed from the histograms to serve as possible
diagnostic rules. The maximum z-value for each grid, the maximum
amount of asymmetry between homologous grid regions, the mean
asymmetry between homologous grid regions, and the difference
between the absolute values of the sum of all left hemisphere and
all right hemisphere values. Also, one can calculate the number of
regions above certain criterion levels for each histogram.
A group of spectral maps or a series of EP responses can be
analyzed as an ensemble by forming at each matrix point the mean of
the values of each map in the ensemble. The grid region on each
individual map showing the largest value is given a score of 4, the
next largest a score of 2, the third largest a score of 1, and the
rest a score of 0. The scores are then summed by region across all
maps in the ensemble, and the regions having the three largest
scores and their sum are stored as indications of focal features.
The same process is repeated for the three regions having the
greatest asymmetries in each image between corresponding grid
sectors. The resulting information can serve as features which can
be processed using TICAS to develop diagnostic rules to classify
unknown subjects between a group of normals and a group having a
particular dysfunction. The numerical descriptors generated by GSA,
when used for statistical analysis are approximately as successful
in the identification of patients with brain tumors as visual
inspection of EEG data by expert clinicians.
Coefficient of Variation Analysis
Given an ensemble of segments of data, the operator can determine
the mean and the standard deviation of each point across the
segments. By displaying the standard deviations as percentages of
mean at each point, the coefficient of variation (C/V) across the
skull can be observed topographically. The normal expect range of
C/V values is 40-60% and deviations from that range are immediately
evident from the displays. The C/V display is useful in
demonstrating head regions where there are wide variations in
activity, e.g., epileptogenic regions.
.[.Different.]. .Iadd.Difference .Iaddend.Maps
A display matrix can be formed to represent at each point, the
difference in value of corresponding points on two underlying
frames. This permits, for example, displays which suggest the
regions of the brain activated by patterned light, by comparing the
frames corresponding to plain light stimulation and to patterned
light stimulation.
Automatic Diagnostic Rules
Working from significant brain activity features and using
TICAS-related operations 65, 67, 68 and 69, the operator can
develop and test diagnostic rules for accurately classifying
unknown subjects between normal and abnormal groups.
Scaling
Several of the available BEAM system operations produce color
topographic displays. Video monitor displays typically involve
assigning to each point on the display a grey tone of color which
represents the value of the point. Sixteen tones of color represent
16 different graduated values. For example, red can be used for
positive values and blue can be used for negative values with the
grey tone of blue or red indicating the level of positive or
negative value. An absence of color represents zero. In order to
maximize the visual effectiveness of the display, it is desirable
to scale the values of the data points to the available color tone
levels in such a way that the useful variations in value are spread
among the maximum range of color tones. The scaling can be done
according to a variety of options. The data points can be scaled so
that the maximum absolute value of the data points over a set of
matrices will be equivalent to the maximum positive and negative
color tones and all other points will be scaled linearly to the
intermediate color tones. Scaline can be done from zero to the
maximum absolute value. The same scaling technique can be
accomplished with one or more channels excluded by the operator
from the scaling process so that unusually high value data points
will now skew the scaling process. Scaling can be done on a matrix
by matrix basis rather than across a group of matrices. Scaling can
be done to a maximum value chosen by the operator. In the scaling
process, any data value which is larger than the brightest
available grey color will be truncated and displayed as that
brightest color.
Three-Point Linear Interpolation
Since the data frames to be presented for display originally
contain a relatively small number of points, e.g., 20 points, and
the display is preferably of a continuous matrix of 128.times.128
points, expansion of the data by some form of interpolation is
required. The expansion is accomplished by three-point linear
interpolation, in which each display point is determined as a sum
of the valves of the three nearest data points on the original data
frame, each multiplied by a predetermined coefficient which
reflects the precise location of the display point. As an
alternative to the software previously described, the calculation
of the display point can be done on hardware having an extremely
short processing time, making possible "real-time" displays, that
is, each display matrix is calculated in a time shorter than the
display time for each display matrix. A detailed description of the
three-point interpolation technique is contained in U.S. patent
application Ser. No. 221,830 (.Iadd.Us. Pat. No.
4,417,591).Iaddend.(hereby incorporated by reference).
Display Features; Multidimensional Display
As illustrated in FIG. 32, the each topographic display comprises
an outline of the skull with an indication of its orientation with
respect to the ears and nose. All display points outside the
outline are suppressed. Within the skull outline are displayed the
grid of data points, each of which reflects a value or values for
that point on the skull. The number of dimensions of information
which may be represented by a given point varies with the display
method. Frequently only one dimension of information is presented
at any point in the form of a grey-tone of color on a predetermined
grey-tone scale. Alternatively additional dimension may be
reflected at a point as a unique combination of three colors. Three
dimensions can be represented by the quantity of each of the
original colors which is mixed into the combination and a fouth
dimension could be the lightness or darkness of the three. In this
manner, for example, spectral EEG data for four frequency bands of
brain activity could be displayed simultaneously. A detaled
description of this four-dimensional display is contained in U.S.
patent application Ser. No. 221,830.
Whenever displays are cartooned, the operator may select the frame
rate of display from stationary to ten frames per second minimum.
The cartoon can also be displayed legarithmically with time, so
that the later matrices are displayed in faster sequence then the
earlier ones, which visually compensates for the fact that more EP
response information is available just after the stimulus than
toward the end of the response period.
Examples of System Use
The brain electrical activity mapping system offers a powerful
brain diagnostic and research tool by permitting immediate video
display of information about steady-state brain waves, EP transient
responses, spectral analyses of EEG signals, and statistical
information based on these types of data, and the ability to
develop diagnostic rules from selected features of data. The
following examples illustrate the versatility and utility of the
system.
Suspected Epilepsy
Although the "spike and wave" as seen on routine EEG graphs is
virtually diagnostic of epilepsy, over 10% of all true epileptics
fail to demonstrate this abnormality. Use of special electrodes,
sleep studies, and activating drugs often fails to produce spikes
in true epileptics. This means that although an epileptic may have
brain cortex that is capable of demonstrating sufficient
irritability at times to produce a seizure, that at other times it
fails to be sufficiently irritative to produce a spike on the EEG
and thus eludes diagnosis. Topographic display is of great
assistance in such situations. Such suspected epileptic patients
should have eyes open (EO) and eyes closed (EC) topographic studies
performed. Irritative cortex presents itself as focal increases of
activity over all frequency bands, especially the high frequency
beta bands. The visual evoked EP response (VER) topographic study
should also be performed. Irritative cortex leads to focal
increases of both positive and negative waves. If the epilepsy is
associated with an atrophic lesion, a region of reduced EEG and EP
activity may be found in close association with the focal
irritability.
When spikes are found, displays of their topographic extent are
extremely useful in determining their point of origin. In this
case, raw EEG data is displayed in cartoon form thus delivering the
epileptic dipole.
Suspected Supratentorial Brain Lesion
Patients are often referred for EEG tests in order to rule in or
out a lesion of one or both cerebral hemispheres. This includes
tumor, stroke, abscess, atrophy, arterio-venous malformation,
congenital malformation, hemorrhage, regional encephalitis. These
subjects should be subjected to topographic studies in the eyes
open and eyes closed brain states, and for the VER and bilateral
somotosensory evoked response (BSER) EP situations. In general
these lesions may be recognized by the pattern .[.or.]. .Iadd.of
.Iaddend.hypo- or hyperactive cortex that become visible on the
brain electrical activity mapping images. For example, tumors show
decrease in activity early, excessive activities later, and reduced
activity at the vertex. Brain electrical activity mapping greatly
adds to the information obtained by radiographic scanning as it is
sensitive to the functional disturbances produced by these lesions
which usually extend beyond the anatomical limits of the
lesion.
To pinpoint abnormalities the technique of significance probability
mapping (SPM) should be used. Furthermore, quantification of a
lesion by grid sector analysis (GSA) is often useful.
.[.Beam.]. .Iadd.Brain .Iaddend.electrical activity mapping is most
useful when tests must be applied to a large population for
screening purposes or repeatedly to a single person. Such uses
would include screening for tumor and stroke, determining whether a
lesion is increasing or decreasing, and assessing the effects of
treatment on a lesion. .[.Beam.]. .Iadd.Brain .Iaddend.electrical
activity mapping is completely non-invasive, and not dangerous as
radiographic techniques would be in such circumstances. There is
also evidence that many lesions produce electrical (functional)
disturbances before they can be detected by radiographic means.
Suspected Learning Disabilities
Beam electrical activity mapping studies are most useful in the
elucidation of regional abnormalities of brain activity found in
dyslexia, hyperactivity, dyscalculia, and combinations of the
above. For example, dyslexia reveals abnormalities not just in the
classic left temporal lobe speech areas but in the medial frontal
lobe bilaterally. To demonstrate these abnormalities, one needs to
perform the full test battery which includes: right hemispheric
activiting tests (the Kimura Figures task and listening to music as
described elsewhere); left hemispheric activating (listening to
speech and reading Grey Oral passages as described elsewhere); and
bi-hemispherical tests (Paired Associates test and the Tight-Tyke
evoked potential phenomic discrimination test as described
elsewhere).
Automated classification tests to discriminate among these clinical
entities can be developed.
Emotional Dysfunction
Many forms of emotional disorder can be caused by the lesions
mentioned above. .[.Beam.]. .Iadd.Brain .Iaddend.electrical
activity mapping can be more useful in the recognition of covert
pathology in this patient population than radiographic techniques.
In addition, certain forms of psychopathology have recognizable
brain electrical activity mapping signatures. For example
sociopathic behavior is associated with lack of synchrony between
the frontal lobes; e.g., the VER may show different electrical
polarity between the right and left frontal lobes. Schizophrenia
shows markedly increased EEG slow activity overlying the frontal
regions. In this group of subjects, the eyes open and eyes closed
EEG and VER studies are most useful.
Infant Competence
Discrimination between babies at risk for future learning and
emotional problems is a frequent clinical request. Brain electrical
activity mapping has proven useful in accomplishing such
discrimination. In addition to studying the EEG and VER in stages 1
and 2 sleep, the EEG should be studied while the babies are brought
into the alert state and maintained there as discussed elsewhere.
Less competent babies, for example, show paradoxical increases in
frontal delta slowing as they are alerted.
Suspected Dementia
Senile and pre-senile dementia represent a major problem for
gerontologists and neurologists. Radiographic evidence of brain
abnormality may not be found until the clinical symptom complex is
well established. On the other hand, brain electrical activity
mapping studies demonstrate early abnormalities is a non-invasive
manner. The best battery of tests is similar to those described
above for suspected learning disabilities, but generally the
tight-tyke EP is replaced by another EP where the subject must
discriminate between frequently and infrequently heard tone pips of
differing frequency. A different EP between the response to the two
different tone pips is produced. The topographic display of the
difference EP shows a marked reduction in dementia and may be used
to follow the course of dementia and the response of dementia to
pharmacotherapies.
Headache
Headache may be caused by many factors. Brain electrical activity
mapping is very useful to screen out serious lesions of the types
described as supratentorial lesions above. The specific syndrome of
migraine headache has a frequently seen pattern on brain electrical
activity mapping of excessive 8-11 Hz occipital oscillations and
excessive occipital activity, it is best to use the EO and EC EEG
and VER for headache. Occasionally the BSEP is useful.
Comparison of Individual to Group
As described above, the brain electrical activity mapping system is
generally able to compare an individual statistically to a group
and display the result topographically. In a clinical setting, the
individual in question, who may have displayed a normal CT scan, is
compared to an age matched/sex matched group of normals, and
abnormalities are then displayed in color-mapped form, wherein
bright colors show high abnormality and dull colors show
insignificant abnormality. This technique provides an effective
diagnostic tool.
Comparisons of Groups; Automatic Diagnosis Rules
The result of a group comparison under the system is a topographic
display of statistical difference expressed as t-statistics, which
when coupled with the number of degrees of freedom available in the
calculation, produce a probability level of significant difference
between two groups at a particular brain state. For instance, a
group of normals could be compared to a group of schizophrenics by
the creation of t-statistic displays with respect to a variety of
brain states and stimuli. The user looks for displays which exhibit
high degrees of coherence and statistical difference. This is
normally shown on a screen in color. The larger statistical
differences appear as brighter colors. The degree to which the
differences are focused at particular points or diffused over the
skull is also apparent. Smoothness in the lines dividing areas of
different brightness suggests focused differences, while diffuse
differences are suggested by ragged edges betwen dim and bright
areas. It is possible for the researcher, upon selection of a
particular map that shows something interesting, to save the matrix
for later analysis. Such a saved matrix of t-statistics can be used
to non-linearly weight the underlying data frames to create
features which can be analyzed using TICAS. Once a set of saved
frames representing group difference information is accumulated, he
then converts all of the saved information, representing features
which tend to distinguish the two groups into a file format which
is suitable for analysis by TICAS, which is a multi-variate
classification systen, publicly available from the University of
Arizona, courtesy of Dr. Peter H. Bartell.
TICAS is designed to sift through all of the features saved in the
course of the inter-group analysis and pick those which prove to be
the most discerning mathematically to produce a set of features
which succinctly allows automatic diagnosis of a patient.
This procedure has been used to successfully discriminate between
normal subjects and those with dyslexia, to discriminate between
normal subjects and those with supertentorial brain tumor, and to
discriminate between subjects with exposure to organophosphate
compounds and nonexposed controls.
Dyslexia Analysis
An article, Dyslexia Regional Differences in Brain Electrical
Activity by Topographic Mapping, Duffy et al. (Annals of Neurology,
Vol. 7, No. 5, May, 1980), hereby incorporated by reference,
describes the use of the brain electrical activity mapping system
to identify the parts of the brain whose electrical activity
differs for individuals suffering from reading disability
(dyslexia) as compared with normal individuals, and to establish
objective standards for diagnosing dyslexia. The previously
described battery of brain state tests were administered to a
dyslexic group and a control group. Visual and auditory stimuli
were repeatedly presented to both groups and recorded with the
appropriate trial markers. The stimuli were offered in pseudorandom
fashion. Using the brain electrical activity mapping system,
topographic displays of the alpha (8 to 11.75 Hz) and theta (4 to
7.75 Hz) activity at each electrode for each tested brain state for
each subject were produced. Similar cartoons of 128 frames (4
milliseconds each) were prepared for each type of EP response for
each subject. The resulting brain state frames and EP response
frames for the dyslexic group and the control group were then
averaged to form mean frames of each group for each state and
stimulus. The two groups of mean images were then compared using
the t-statistic function. A further transformation produced a
matrix of percentile index values (PI) whose value is related
inversely to t-values. The PI values permit a graphic localization
of regions of maximum difference between the dyslexic group and the
control group. By topographically displaying the PI matrices for
alpha and theta for each brain state and for each EP stimulus, it
was possible to identify the brain regions which differed between
the dyslexics and the controls. As a final step, a new display
matrix was formed which summarized the differences reflected in all
of the PI matrices as indicated by the occurrence of a certain PI
level on at least one of the underlying PI matrices. The map of PI
differences having a value of at least 2 identified four brain
areas related to dyslexia: (1) bilateral medical frontal, (2) left
anteriolateral frontal, (3) left mid-temporal and (4) left
posterolateral quadrant. Classic concepts of dyslexia had not
suggested the involvement of all of these brain areas in dyslexics.
The study also indicated that alpha brain activity was involved in
dyslexia as well as the theta activity which has previously been
viewed as of primary importance.
In Dyslexia: Automated Diagnosis by Computerized Classification of
Brain Electrical Activity, Duffy et al. (Annals of Neurology, Vol.
7, No. 5, May, 1980) hereby incorporated by reference, specific
highly effective diagnostic rules for identifying dyslexics were
developed by a rule selection process applying TICAS software to
the brain wave data derived in the study described immediately
above. Working from displays of brain electrical activity, 183
features were identified for particular regions and brain states in
which the strongest differences between the dyslexic group and the
normal group occurred. Two of the 183 features were identified as
capable of classifying unknown subjects as dyslexic or normal with
a success of 80-90%.
Localization of Tumor
In Brain Electrical Activity Mapping (B.E.A.M.); A Method for
Extending the Clinical Utility of EEG and Evoked Potential Data,
Duffy, et al (Annals of Neurology, Vol. 5, No. 4, April, 1979),
hereby incorporated by reference, the use of brain electrical
activity mapping system topographic displays to identify the
location of a brain tumor was discussed. Spectral EEG data in the
four classic bands (delta, theta, alpha, and beta) was recorded for
various tested brain states. Average EP response data for strobe
light stimuli comprising 128 time frames of 4 milliseconds each was
also recorded. After three-point linear interpolation to expand the
matrix, displays of spectral EEG data, and cartooned EP data were
obtained. FIG. 5 of the article illustrates the spectral EEG
displays in the four classic bands of brain activity for a patient
with a known tumor, which had been located by CT scanning. The
assymetries in the spectral displays also identify the area of the
tumor, although the suggested lesion size was larger than indicated
by CT scanning. Analysis of 7 tumor patients, whose classic EEG's
were normal or non-localizing, showed that brain electrical
activity mapping studies were able to define the lesions almost as
effectively as CT scan.
Use of Significance Probability Mapping with B.E.A.M. to Compare
Groups and Compare Individuals to Groups
In Significant Probability Mapping: An Aid in the Topographic
Analysis of Brain Electrical Activity, Duffy et al., accepted for
publication (hereby incorporated by filing a copy thereof as an
Appendix) the authors describe the use of topographic displays of
statistical transformations of data. In one application, EP
response data was obtained from a group of subjects with brain
tumors and a second control group of subjects. The data was broken
into sequential frames of 4 milliseconds each. For the control
group, new matrices of mean and variance of each electrode over all
members of the group were prepared. A z-statistic matrix was formed
for each tumor subject to illustrate his deviation from the normal
population. Using the z-statistic display a clinical
neurophysiologist was able to identify 11 of 12 tumor subjects.
In a second application, discussed in the same article, EEG
steady-state signals were recorded for three different brain states
(resting but alert with no external stimulation, listening to a
tape recording of speech, and listening to a tape recording of
music) for individuals in a group of dyslexics and individuals in a
group of normal readers. Matrices of alpha band activity were
produced for each individual, and mean and variance matrices for
each state were prepared for each of the two groups. For each group
t-statistic matrices were formed to compare the resting and
listening to speech states and the resting and listening to music
states. By examining the t-statistic displays for the two groups it
was possible to infer the differences in speech-induced and
music-induced brain activity between the dyslexics and the normal
readers. Those determinations could not have been made from an
analysis of the underlying EEG alpha matrices.
Use of Grid Sector Analysis of B.E.A.M. SPM Data to Determine
Degree of Focal or Global Deviation From Normal
In an unpublished article, "Quantification of Focal Abnormalities
in BEAM Data by Grid Sector Analysis: Automated discrimination
Between Normal Subjects and Patients with Supratentorial Brain
Tumor", Duffy, et al., (hereby incorporated by filing a copy
thereof as an Appendix) describes uses of grid sector analysis as
part of the brain electrical activity mapping system for the
purpose of automated neutophysiological diagnosis of brain tumor.
In this application, EEG and visual EP data were recorded from a
group of patients with confirmed supratentarial brain tumor and
from a control group. SPM matrices were prepared comparing the
tumor subjects to a normal group and comparing the control group to
the tumor group. Four 96 millisecond time periods of EP data were
analyzed. Grid sector analyses on the data resulted in a set of
1096 combined global and focal features from the combined EEG and
EP data. By a process of features selection and rule development
and testing, two features were identified as most useful in
distinguishing the tumor subjects from the control subjects. When
classification rules developed on the initial group of 30 subjects
were applied to a new group of 10 subjects, containing 5 normals
and 5 subjects with brain tumor, all ten were correctly
classified.
Other Embodiments
Other embodiments of the invention are within the following claims.
For exaple, the input data may be obtained from any type of
transducer capable of measuring brain electrical activity, and
topographic displays can be prepared from the signals taken from
the skull, without interpolation of additional points to form a
display matrix.
Related Applications
This application is related to the following applications, each of
which is hereby incorporated by reference:
(1) Frank H. Duffy and Norman David Culver, Brain Electrical
Activity Mapping .[.(BEAM).]..Iadd., U.S. Pat. No. 4,408,616
.Iaddend.
(2) Norman David Culver, Brain Electrical Activity Mapping
.[.(BEAM).]..Iadd., U.S. Pat. No. 4,407,299 .Iaddend.
(3) Norman David Culver, Analysis of Brain Electrical
Activity.Iadd., U.S. Ser. No. 263,931 (abandoned) .Iaddend.
(4) Norman David Culver, Apparatus and Method for Topographic
Display of Multichannel EEG Data, .[.U.S. Ser. No. 221,830.].
.Iadd.U.S. Pat. No. 4,417,591
* * * * *