U.S. patent application number 11/845564 was filed with the patent office on 2008-04-24 for subjective significance evaluation tool, brain activity based.
This patent application is currently assigned to Technion Research & Development Foundation, Ltd. Invention is credited to Einat OFEK, Hillel PRATT.
Application Number | 20080097235 11/845564 |
Document ID | / |
Family ID | 39318876 |
Filed Date | 2008-04-24 |
United States Patent
Application |
20080097235 |
Kind Code |
A1 |
OFEK; Einat ; et
al. |
April 24, 2008 |
SUBJECTIVE SIGNIFICANCE EVALUATION TOOL, BRAIN ACTIVITY BASED
Abstract
A method and system for determining the subjective state of mind
of a human subject presented with a test audible or visual
stimulus. An electroencephalogram (EEG) recording unit is connected
to the human subject, recording the subject's EEG when presented
with one or more test stimuli. The recorded EEG signal is then
transformed to a 3-D map in order to visualize the brain areas that
were active when presenting the test stimuli. The given 3-D map of
the test stimuli is then compared with reference 3-D maps of
neutral and subjectively significant stimuli.
Inventors: |
OFEK; Einat; (Yokneam,
IL) ; PRATT; Hillel; (Nofit, IL) |
Correspondence
Address: |
BROWDY AND NEIMARK, P.L.L.C.;624 NINTH STREET, NW
SUITE 300
WASHINGTON
DC
20001-5303
US
|
Assignee: |
Technion Research & Development
Foundation, Ltd
Hafia
IL
|
Family ID: |
39318876 |
Appl. No.: |
11/845564 |
Filed: |
August 27, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60839909 |
Aug 25, 2006 |
|
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Current U.S.
Class: |
600/544 |
Current CPC
Class: |
A61B 5/377 20210101 |
Class at
Publication: |
600/544 |
International
Class: |
A61B 5/0476 20060101
A61B005/0476 |
Claims
1. A method for determining the subjective state of mind of a human
subject: presented with a test stimulus comprising the steps of:
(i) connecting an electroencephalogram (EEG) recording unit to the
human subject; (ii) presenting human subject with one or more test
stimuli; (iii) recording the human subject's EEG; (iv) performing a
3-D reconstruction of the recorded EEG signal in order to visualize
the brain areas that were active when presenting said one or more
test stimuli; and (v) comparing human subject's reactions to test
stimuli to reference data in order to determine if said one or more
test stimuli are subjectively significant or not.
2. A method according to claim 1, wherein said reference data
comprises 3-D reconstructions of EEG signals of subjectively
significant stimuli and/or 3-D reconstructions of EEG signals of
neutral stimuli.
3. A method according to claim 2, wherein said 3-D reconstructions
of EEG signals of neutral stimuli is obtained from reactions to
neutral stimuli and/or from predetermined mapping of certain brain
area known to be activated during different mind states.
4. A method according to claim 2, wherein said 3-D reconstructions
of EEG signals of neutral stimuli are obtained using the following
steps: (i) connecting an electroencephalogram (EEG) recording unit
to the human subject; (ii) preparing a list of significant and
neutral reference stimuli; (iii) providing reference stimuli to the
subject and recording his ERP; (iv) using a computer unit to
receive the recorded EEG and perform 3-D reconstruction of the EEG
signal; and (v) performing analysis of subject mental reaction to
reference stimuli.
5. A method according to claim 1, wherein said test stimuli are
provided via earphones, a computer screen and/or television
monitor.
6. A method according to claim 1, further including the step of
recording the human subject's Peripheral Arterial Tonometry
(PAT).
7. A method according to claim 1, for use in one or more of the
following applications: a psychological evaluation tool; a tool for
identification of subjectively significant response in comatose
patients; a tool for identification of a specific response in
demented patients; a tool for evaluation of psychological response
in psychiatric patients; a tool for evaluation of psychological
response in autistic children; a tool for evaluation of
subjectively significant response in locked in syndrome patients;
or a lie detector.
8. A method according to claim 1, wherein neural sources are
detected.
9. A method according to claim 1, wherein comparing human subject's
reactions to test stimuli to reference data reveals specific brain
responses.
10. A system for determining the subjective state of mind of a
human subject presented with a test stimulus comprising: (i) an
electroencephalogram (EEG) recording unit connected to the human
subject; (ii) means for providing stimuli to the human subject;
(iii) a computer unit adapted for receiving the recorded EEG signal
and performing a 3-D reconstruction of the recorded EEG signal in
order to visualize the brain areas that were active when presenting
said test stimuli; and (iv) means for comparing human subject's
reactions to test stimuli to reference data.
11. A system according to claim 10, wherein said reference data
comprises 3-D reconstructions of EEG signals of subjectively
significant stimuli and/or 3-D reconstructions of EEG signals of
neutral stimuli.
12. A system according to claim 11, wherein said 3-D
reconstructions of EEG signals of neutral stimuli is obtained from
reactions to neutral stimuli and/or from predetermined mapping of
certain brain area known to be activated during different mind
states.
13. A system according to claim 11, wherein said 3-D
reconstructions of EEG signals of neutral stimuli comprises: (i) an
electroencephalogram (EEG) recording unit connected to the human
subject; (ii) a list of significant and neutral reference stimuli;
(iii) means for providing reference stimuli to the subject and
recording his ERP; (iv) a computer unit adapted to receive the
recorded EEG and perform 3-D reconstruction of the EEG signal; and
(v) means for performing analysis of subject mental reaction to
reference stimuli.
14. A system according to claim 10, wherein said test stimuli are
provided via earphones, a computer screen and/or television
monitor.
15. A system according to claim 10, further comprising means for
recording the human subject's Peripheral Arterial Tonometry
(PAT).
16. A system according to claim 10, for use in one or more of the
following applications: a psychological evaluation tool; a tool for
identification of subjectively significant response in comatose
patients; a tool for identification of a specific response in
demented patients; a tool for evaluation of psychological response
in psychiatric patients; a tool for evaluation of psychological
response in autistic children; a tool for evaluation of
subjectively significant response in locked in syndrome patients;
or a lie detector.
17. A system according to claim 10, wherein neural sources are
detected.
18. A system according to claim 10, wherein comparing human
subject's reactions to test stimuli to reference data reveals
specific brain responses.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a method and system for
determining the subjective state of mind of a human subject and in
particular to assessment of neurophysiologic manifestations of
subjective significance.
BACKGROUND OF THE INVENTION
[0002] The neural substrates of emotional response have
traditionally been studied using universal sets of emotionally
loaded stimuli, regardless of their subjective significance to the
individual subject. Assessment of the unique brain response to
subjectively significant stimuli has not been studied before.
[0003] Deception is probably the best-studied mind states of all;
most of the present lie-detection testing techniques use polygraph
devices to examine the peripheral autonomic response to relevant
versus irrelevant questions. Present day polygraph devices can
combine measurements of electro-dermal skin conductance, blood
pressure, respiration and peripheral vasomotor activity, minute
changes in vocal response and face temperature. The increase in
autonomic response is interpreted as an attempt to deceive by the
investigated subject. This basic principle behind polygraph machine
hasn't changed since its invention over 80 years ago.
[0004] Lately, a newer method for lie detection which is based on
examining the amplitude of the P300 component of event-related
brain potentials was proposed (Farwell, L. A. & Smith, S. S. J.
Forensic Sci. 46, 135-143, 2001). When a human subject is exposed
to something that already is stored in memory, the brain emits an
electrical response called a P300 wave. The P300 is a non-specific
brain response, elicited in response to innovation, subject's own
name, surprise and task related stimuli. This phenomenon occurs
approximately 300 milliseconds after a meaningful stimulus. The
investigators extrapolate from an Electro-Encephalo-Graphy (EEG)
recording clues to differentiate between relevant and irrelevant
stimuli.
[0005] Another important known technique for mind state detection
is the functional magnetic resonance imaging (fMRI). Images of the
brain can be taken during activity at rest and during a specific
behavior, thus demonstrating the function of a particular area of
the subject's brain as well as its structure. An extensive research
is performed to detect the part of the brain active during a lie.
There are a number of reports in the literature about success in
detecting deception (Langleben, D. D. et al. NeuroImage 15,
727-732, 2002), (Kozel F. A. et al. Behav Neurosci. 2004 August;
118(4):852-6), (Ganis G et al. Cereb Cortex. 2003 August;
13(8):830-6), a number of brain regions were found to participate
in the deceptive response. This is an important discovery, since
even though a subject might control his autonomic responses, the
very thought of deception will be detected. A few studies were also
done concerning the subjective emotional experience of subjects.
However, fMRI require a large and expensive and non-mobile
instrumentation, and cannot get results within milliseconds
resolution.
SUMMARY OF THE INVENTION
[0006] It is an object of the present invention to define brain
activity to subjectively significant stimuli.
[0007] Another object of the present invention is to characterize
the time course of activity in the brain areas involved when
exposed to subjectively significant stimuli.
[0008] It is yet another object of the present invention to decide
if a given stimulus is subjectively significant or not to a human
subject.
[0009] The present invention thus relates to a method for
determining the subjective state of mind of a human subject
presented with a test stimulus and to a system for implementing
said method. The method comprises the following steps: [0010] (i)
connecting an electroencephalogram (EEG) recording unit to the
human subject; [0011] (ii) presenting human subject with one or
more test stimuli; [0012] (iii) recording the human subject's EEG;
[0013] (iv) performing a 3-D reconstruction of the recorded EEG
signal in order to visualize the brain areas that were active when
presenting the test stimuli; and [0014] (v) comparing human
subject's reactions to test stimuli to reference data in order to
determine if said one or more test stimuli are subjectively
significant or not.
[0015] The invention aims to determine if a given stimulus is
subjectively meaningful to an individual or if it is neutral to
that individual.
[0016] Preferably, several repetitions of the stimuli are used, so
that event related potentials (ERP) are recorded to enhance the
signal to noise ratio. The test stimuli are compared with reference
data that can be obtained from two sources: reactions to reference
stimuli and/or predetermined mapping of certain brain area known to
be activated during different mind states.
[0017] In addition, the EEG signal is also recorded shortly before
the stimulus is given in order to identify how the brain is active
before being exposed to the stimulus.
[0018] Measuring the reference stimuli is done in a similar way to
measuring the reactions to test stimuli. The human subject is
presented with two sets of stimuli: a first set that comprises
neutral, that is non-subjectively significant stimuli for that
individual; and a second set that comprises subjectively
significant stimuli for that individual. Measuring the reference
stimuli is obtained using the following steps: (i) connecting an
electroencephalogram (EEG) recording unit to the human subject;
(ii) preparing a list of significant and non significant reference
stimuli; (iii) providing reference stimuli to the subject and
recording his ERP; (iv) using a computer unit to receive the
recorded EEG and perform 3-D reconstruction of the EEG signal; and
(v) performing analysis of subject mental reaction to reference
stimuli.
[0019] The test stimuli 3-D reconstruction is compared to the 3-D
reconstruction of neutral and subjectively significant stimuli in
order to assess if the test stimuli are subjectively significant or
not.
[0020] The test stimuli, as well as the reference stimuli, can be
provided through common audio-visual means such as earphones, a
computer screen, a television monitor etc. The stimulus is
controlled by a computer unit so that the time of delivering the
stimulus is controlled with great precision. The EEG measures the
responses in different brain areas mostly between 200 milliseconds
(ms) and 950 ms after a stimulus is delivered.
[0021] Optionally, Peripheral arterial tonometry (PAT) recordings
can be used to check peripheral autonomic response. PAT can be used
instead of EEG readings, though the results are less precise.
[0022] One or more human subjects are presented with a set of
subjective significant stimuli and a set on neutral stimuli. The
EEG signals recorded are transformed to 3D maps of different brain
parts active at a given time point after the stimulus is received.
The end result is two set of maps of activities of different brain
parts at a given time point after the stimulus is received. One set
of maps corresponds to a neutral stimulus and the other set of maps
corresponds to a subjectively significant stimulus. Then if we wish
to determine if a new stimulus is subjectively significant or not
to a given individual, we can measure the brain activity after
receiving the stimulus and compare the reconstructed brain maps
with the previous two sets of maps for neutral or subjectively
significant stimuli. Comparing the new map to the two reference
maps (neutral and subjectively significant stimuli) will allow us
to determine if the new stimulus is subjectively significant or not
according to the resemblance of the new brains maps with either the
brain maps for neutral stimuli or the brain maps for subjectively
significant stimuli.
[0023] The invention may be used in a variety of applications
including but not limited to: a psychological evaluation tool, a
tool for identification of subjectively significant response in
comatose patients, a tool for identification of a specific response
in demented patients, a tool for evaluation of psychological
response in psychiatric patients and autistic children, a tool for
evaluation of subjectively significant response in locked in
syndrome patients, and as a lie detector.
[0024] Subjective significance evaluation tool, brain activity
based, may also serve as a tool for evaluating residual specific
brain activity in patients with no motor response, as in comatose
patients, locked in syndrome, or demented patients. It may also
serve the evaluation of specific response in clinically depressed
patients, or autistic children. In many psychiatric disorders, the
therapy is difficult to achieve since the patient is not
cooperative, and in many cases is not even aware of the
subconscious conflicts and drives which cause his/hers illness.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 shows event related potentials (ERP) to subjectively
significant and neutral names, grand average across 16 subjects,
from 11 electrodes: Fp1, Fp2, F3, Fz, F4, C3, Cz, C4, P3, Pz, P4.
Main ERP components are marked: P1, N2, N400, P600. Note the
enhanced components N2, N400 and P600 to subjectively significant
stimuli.
[0026] FIG. 2 illustrates the time course of statistically
significant activation in the vicinity of 13 areas in each
hemisphere to subjectively significant and neutral names, indicated
by time frames marked in black. Note that responses to subjectively
significant stimuli are: (1) overall enhanced compared to neutral
names, more so in the left-compared to the right hemisphere; (2)
particularly enhanced in the vicinities of the middle and superior
frontal gyri, Broca's area, Wernicke's area, insula, precentral
gyrus, precuneus and posterior cingulate gyrus in the left
hemisphere; (3) prominent in the later time frames in the vicinity
of the middle, superior, and medial frontal gyri, as well as in the
vicinity of the anterior, central and posterior cingulate gyri.
[0027] FIG. 3 illustrates the time course and level of significant
activation in the vicinity of specific brain areas in response to
subjectively significant vs. neutral stimuli. Level of activation
in the vicinity of each area was computed as the percentage of
voxels in the area that were significantly active at a given time
frame, multiplied by their average t value. The sections in the
middle column of the figure show activation in the vicinity of a
given area in response to subjectively significant stimuli, at the
time of its peak activation, marked by an arrow on the graph. The
respective time courses of activation in the vicinity of each area,
from 200 to 800 ms after stimulus onset, in response to
subjectively significant and to neutral stimuli, are also shown.
Note: (1) Enhanced activation in response to subjectively
significant stimuli; (2) differential pattern of activation in the
vicinity of concurrently active areas in response to subjectively
significant compared to neutral names; (3) prominence of the
response in left hemisphere; (4) earlier onset of activation in the
vicinity of the left middle frontal gyrus in response to
subjectively significant stimuli.
[0028] FIG. 4 shows the main cortical sources contributing to the
difference in ERP components-results of a statistical comparison
between subjectively significant and neutral names during several
time periods. For each component, the vicinity of the area found to
be most involved in the response is shown. On the right, the
corresponding time period from which the sources were estimated is
marked on the ERP waveform.
DETAILED DESCRIPTION OF THE INVENTION
[0029] In the following detailed description of various
embodiments, reference is made to the accompanying drawings that
form a part thereof, and in which are shown by way of illustration
specific embodiments in which the invention may be practiced. It is
understood that other embodiments may be utilized and structural
changes may be made without departing from the scope of the present
invention.
[0030] Human behavior is affected by the subjective significance of
events. The present invention aims to define brain activity to
subjectively significant stimuli, and characterize the time course
of activity in the brain areas involved. Previous studies on the
neural basis of emotions were typically fMRI or PET studies
(Crosson et al., 2002; Elliott et al., 2000, 2002; George et al.,
1995; Gundel et al., 2003; Maddock et al., 2003) whose temporal
resolution is in the order of seconds, whereas neural activity
related to emotional processing and behavior is in the sub-second
range. The present invention records Event-Related Potentials
(ERPs) from the scalp and uses current density source estimation
(Low-Resolution Electromagnetic Tomographic Analysis--LORETA;
Pascual-Marqui et al., 1994; Pascual-Marqui, 1999; Pascual-Marqui R
D, Michel C M, Lehmann D. Low resolution electromagnetic
tomography: a new method for localizing electrical activity in the
brain. International Journal of Psychophysiology 1994, 18:49-65) to
trace brain activity with temporal resolution of milliseconds and
spatial resolution in the order of millimeters.
[0031] The neurophysiological basis of emotional response to
stimuli has, for the most part, been studied assuming the same
affective valence for each stimulus across all subjects (Bremner et
al., 2001; Dietrich et al., 2001; Elliott et al., 2002; Hamann and
Mao, 2002). Previous studies have demonstrated the involvement of a
neural network consisting of the prefrontal cortex, both temporal
lobes and cingulate gyrus, in addition to other subcortical areas
(amygdala, hippocampus), in the emotional response to stimuli
(Crosson et al., 2002; Devinsky et al., 1995; Elliott et al., 2000;
Elliott et al., 2002; Esslen et al., 2004; George et al., 1995;
Imaizumi et al., 1997; Maddock and Buonocore, 1997; Maddock et al.,
2003). Contradictory results were reported by studies that used
such uniform sets of stimuli, regarding the involvement of certain
areas (e.g. anterior cingulate gyrus, see Blair et al., 1999, and
Esslen et al., 2004) and also regarding hemispheric lateralization
of the emotional response to stimuli (Jones and Fox, 1992; Davidson
and Irwin, 1999; Esslen et al., 2004).
[0032] The invention uses subjective significance to the individual
subject, rather than universal (objective) affective valence which
is assumed to be the same across all subjects. In general,
subjectively significant stimuli are more prone to evoke behavior
than other stimuli. When the same set of stimuli, assumed to be
universally affective, is used for all subjects, individual stimuli
may have different affective valence for different subjects. Thus,
comparing brain activity to such stimuli across subjects, for whom
the same stimulus may carry a different subjective significance,
does not allow isolating the net effect of affective valence.
[0033] For example, most verbal stimuli have more than one meaning
and may have several connotations; which complicates the
determination of their subjective affective valence. In contrast,
the subjective significance of first names is mostly acquired from
people familiar to the subject that carry the name. Therefore,
first names may be suitable for studying the neurophysiological
correlates of emotional significance. Furthermore, the very same
first name may have an emotional value to some subjects and be
neutral to others, providing a better control for the net effect of
subjective emotional significance of the very same stimulus, than
comparing different words. Several studies have demonstrated the
neural response to the subject's own name compared to neutral names
(Berlad and Pratt, 1995; Perrin et al., 1999; Kampe et al., 2003).
A comparison of the neural response to any subjectively significant
names with that to neutral names has not been reported. Moreover,
previous studies describing the neural response to the subject's
own name did not trace the exact time course and order of
activation of the brain areas involved.
[0034] The present invention identifies the specific neural
response to subjectively significant stimuli and traces neural
correlates of subjective emotional response. The general brain
response evoked by all subjectively significant stimuli, with both
negative and positive valence is captured. Moreover, because some
subjectively significant stimuli may have a mixed negative and
positive connotation (e.g. the subject's mother, depending on the
context and personal experience), brain responses to subjectively
significant stimuli are more readily defined than to stimuli
classified as `positive` or `negative`.
[0035] Results of experiments conducted show a consistent and
uniform pattern of brain response to subjectively significant
stimuli across all subjects of the same group. In each of the
subjects the response to subjectively significant stimuli included
neural activity in earlier time frames and in additional brain
areas compared to the response to neutral stimuli. Activation up to
200 ms from stimulus onset was apparently not uniform enough across
subjects to be statistically significant. During this early time
period, several brain areas may have been differentially involved
but did not attain significance in our analysis because of
different time courses of activation to different stimuli in
different subjects. The general features that were statistically
significant across all subjects show that brain response specific
to subjectively significant stimuli is characterized by 3 features:
(1) generalized enhancement of cortical activity; (2) a specific
localized response involving several distinct and concurrently
active brain areas at different times; (3) late (>700 ms)
activity unique to subjectively significant stimuli, after the
activity to neutral stimuli has subsided. The generalized
enhancement of activation (see statistical results and FIGS. 2 and
3) may be part of an arousal response mediated by the amygdala and
other parts of the limbic system (Critchley, 2003; Jones, 2003;
Shekhar et al., 2003). Significant amygdalar activation was not
found in our study, most probably because of its deep location
within the brain and the fact that its neurons are not spatially
aligned.
[0036] According to one embodiment of the present invention, any
audio and/or visual stimulus can be tested if it is subjectively
significant to an individual, by creating 3-D reference maps of
neutral and subjectively significant stimuli delivered to other
individuals from the same group. Defining the group of similar
individuals depends on the context of what is needed to be tested.
If the stimulus tested is a word in a given language, as in the
experiment described below, than all the individuals need to be
speakers of the same language. If the stimulus to be tested is a
visual stimulus of a technical object, the group of reference
individuals needs to be familiar with the technical object in order
to test if it is subjectively significant. Other factors may also
be determined in order to create a homogenous reference group, for
example, age, health, right-handed or left handed people, sex,
education etc.
[0037] According to another embodiment of the present invention,
reference stimuli can be measured in a group of reference
individuals that is not homogeneous.
[0038] When measuring reference stimuli, subjectively significant
stimuli can be determined by various non-exclusive methods, for
example, a questionnaire, an interview or prior knowledge about the
individual or subject.
[0039] The present invention can be used in a variety of
applications, for example:
[0040] 1. Truth Detection:
[0041] The present invention can serve as an important tool for
legal investigations, including screening of court witnesses for
intention to lie or a tool to probe the mental response of the
prosecuted individual to crime evidences. Another use of the
invention is in job screening and in other fields the polygraph
device is currently used. Another application is in crime
investigation whereas one can present suspects with a number of
probes that are unique details of a crime that only the culprit
could know. A guilty subject is expected to have memory of these
probes and therefore treat them differently than the innocent
person.
[0042] 2. Brain Computer Interface (BCI):
[0043] Current methods for using mental information to activate
computers or robots are based on plain EEG signals or on invasive
devices. Although individuals can learn to control and change at
will certain aspects of the EEG signal, the current rate of
information transfer with plain EEG recording is very low. In one
embodiment, the present invention enables to perform online 3D
reconstruction of the signal to capture the full potential of the
data encoded in the EEG.
[0044] 3. Improvement of Psychotherapeutical Treatment.
[0045] The psychiatric staff meets many problems diagnosing and
treating these subjects, since the behavior response is not a good
indication concerning the success/failure of the therapy. The
present invention can serve in psychological and psychiatric
investigation, in order to find what is really important to the
patient, or what is the source of the problem, in order to build a
therapeutic plan and find out what should be the focus of the
therapy. A mental response reader which is able to reveal specific
response to therapeutic inquiries can greatly assist in the
treatment of a range of mental conditions such as autistic,
psychotic and depressed patients and patients with post traumatic
stress disorder (PTSD). In addition, especially in PTSD patients
the present invention enables identifying stimuli which are related
to the trauma, which will be efficient to expose the patient to, or
to avoid.
[0046] 4. In `locked in` and comatose patients, in whom the level
of cortical activity can be probed and specific brain activity to
significant stimuli will be assessed (the technique of the
invention also allows for quick testing whether the comatose
patient is able to hear or to see).
[0047] 5. Revealing information (and subjective significance of
objects) in patients who are unable to talk--in autism, locked in
syndrome, comatose patients, severely disabled patients or patients
in a catatonic condition; and in patients who are unwilling to talk
(a lie detector).
Experiment Conducted
1. Methods
1.1 Subjects
[0048] Sixteen right handed, native Hebrew speaking, healthy normal
volunteers (7 males and 9 females; mean age: 22.7, SDZ2.8 years)
with no hearing complaints nor evidence of neurological disorders
participated in this study. Since subjects' first names were used
as auditory stimuli in the experiment, subjects were chosen so that
their first names were 2 syllable common Hebrew names, which began
with a sonorant. Subjects were paid for their participation.
Experimental procedures were approved by the Institutional Review
Board for experiments involving human subjects (Helsinki
Committee).
1.2 Experimental Procedure
[0049] Potentials were recorded from tin electrodes placed
according to the 10-20 system in an electrode cap (Electro-Cap
International Inc., Eaton, Ohio, USA). Activity was recorded
(Ceegraph IV Biologic Systems Corp. IL, USA) from 19 locations:
Fp1, Fp2, F7, F3, Fz, F4, F8, T3, C3, Cz, C4, T4, T5, P3, Pz, P4,
T6, O1, O2. Three additional tin electrodes, external to the cap,
were attached to the right and the left mastoids (A1 and A2), and a
third below the left eye, referenced to Fz, to monitor eye
movements (EOG). In total, EEG was recorded from a 21-electrode
array, in addition to an EOG channel. A ground electrode was placed
on the left forearm. All EEG electrodes were referenced to an
electrode midline on the chin, far from the brain, from facial and
lingual muscles and in the midline, thus avoiding asymmetry
distortions. Impedance at each electrode was maintained below 5
k.OMEGA..
[0050] Subjects listened to names presented binaurally by earphones
and performed an identification task, pressing a button in response
to each of 3 target names ending with a pre-assigned consonant,
from a repertoire of 29 names. Subjects performed the task
reclining in an adjustable armchair in an acoustically isolated
chamber. Subjects were instructed to avoid eye movements and
blinking as much as possible, and to keep their gaze on a fixed
point in front of them during task performance.
1.3 Stimuli
[0051] All stimuli were two syllable (700 ms duration) common
Hebrew first names, beginning with a sonorant so that all stimuli
had similar acoustic onset properties. In each experiment, 29 names
were randomly repeated. The stimuli were identical for each group
of 4 subjects, and included the subjects' own names, and 5 names of
important persons in each subject's life (a present or former
spouse, close family members, close friends, and a hated person).
Any given name in the list was thus subjectively significant to at
least one member of the group and was neutral to others. The
stimuli also included 3 target names that ended with the same
consonant. Target names were neutral to all subjects. Data about
names of important persons in the subject's life were collected
during a short interview 1-2 months before the experiment. Final
assessment of the subjective significance and affective valence of
each of the names in the list was conducted by an interview after
the experiment.
[0052] Stimuli were recorded from a native Hebrew speaker and saved
as digitized sound files. Stimuli were presented binaurally with an
inter-stimulus interval (between the onset of a name and onset of
the following name) of 2.2 s.
1.4 Experimental Paradigm
[0053] Subjects were instructed to press a button when they heard a
name that ends with a certain consonant (target name). Subjects
received 10 blocks, each consisting of 7 randomly distributed
repetitions of each of the 29 names in the list. The list of names
included in the experiment was identical for each group of 4
subjects. Short breaks were taken after each block.
1.5 Interview
[0054] Subjective affective significance of each name was assessed
after the experiment in an interview, based on a structured
questionnaire which was validated both statistically and by using
an autonomic activity measure (peripheral arterial tonometry). The
subject was asked about each name separately. The questionnaire
included 46 dichotomous and rating questions for each person
bearing each name. A subjective significance score was computed
accordingly for each name, for each subject. Names with scores
higher than a standard deviation above the subject's own score
averaged across all names were considered subjectively significant
to that subject, and names with scores lower than a standard
deviation below the subject's own averaged score were considered
neutral.
[0055] For each subject, names were ranked according to their
individual affective significance. Thus, a given name could be
significant to one subject and neutral to another, and the net
effect of subjective significance on brain activity could be
isolated.
1.6 ERP Recording and Measurement
[0056] Potentials from the EEG (X100,000) and EOG (X20,000)
channels were amplified, filtered (0.1-100 Hz, 6 dB/octave slopes),
digitized with a 12 bit A/D converter at a rate of 256 samples/s,
and stored for subsequent off-line analysis.
[0057] Continuous records were segmented beginning 300 ms
pre-stimulus until 2700 ms after stimulus onset (3 s total analysis
time), and averaged after eye-movement correction based on
eye-channel/EEG correlations (Attias et al., 1993).
[0058] Potentials were averaged separately for each non-target
first name, for each subject. Potentials to target names were not
included in the analysis. Thus, all the stimuli whose responses
were analyzed, neutral and subjectively significant, were
non-targets in this task. Two separate averages were derived for
each subject: (1) for the 3 most subjectively significant names;
(2) for the 3 least subjectively significant (`most neutral`)
names, according to the interview results (see above). In this
report, ERPs to all subjectively significant names were averaged
together, irrespective of positive or negative valence. The effects
of valence will be reported in a separate report. The averaged ERPs
were low-pass filtered with a cutoff at 20 Hz.
1.7 Current Density Estimations and Statistical Analysis
[0059] Neural sources of scalp-recorded potentials were estimated
using the LORETA procedures for estimating source current density
distribution in a 3D Talairach space of the brain's gray matter.
The LORETA procedure computes current density under the assumption
that for each voxel the current density should be as close as
possible to the average current density of the neighboring voxels
(`smoothness assumption`). LORETA has been shown to have a 7 mm
spatial resolution, and found superior to other localization
methods in localizing deep (subcortical) sources (Pascual-Marqui et
al., 1994; Pascual-Marqui, 1999; Pascual-Marqui et al., 2002).
[0060] LORETA current density estimations were performed on each
subject's ERP waveforms, separately for subjectively significant
and for neutral names. In order to negate non-specific effects
related to readiness and motor preparation, a baseline level and
distribution of activity was defined as the average for each voxel
over the 100 ms preceding stimulus onset. Only activity
significantly different than this baseline activity was analyzed.
Significance of activity was determined by nonparametric (SnPM)
paired comparisons of time frame by time frame current density in
each voxel with baseline, in the 800 ms following name onset. The
SnPM method estimates the probability distribution by using a
randomization procedure; it corrects for multiple comparisons, and
has the highest possible statistical power (Nichols and Holmes,
2002). Specifically, in our study we used the `pseudo-t` statistic
which reduced noise in the data by averaging over adjacent voxels
(Nichols and Holmes, 2002). Comparisons were conducted separately
for subjectively significant and for neutral names, compared to
baseline. An additional comparison (SnPM) was conducted for the
responses to subjectively significant compared to neutral names.
Level of activation in each area was computed as the percentage of
voxels in the vicinity of a specific area that were significantly
active at a given time frame, multiplied by their average t value.
Analysis of Variance procedures were conducted in order to assess
the effects of subjective significance (significant vs. neutral),
laterality (left vs. right hemisphere) and their interaction on
brain activity. Probabilities below 0.05, after Geisser-Greenhaus
and Bonferroni corrections (when appropriate), were considered
significant.
2. Results
[0061] FIG. 1 presents the potentials recorded from 11 of the 21
channels, in response to subjectively significant and to neutral
names. Overall, subjectively significant stimuli were associated
with enhanced activity relative to neutral stimuli. Table 1
summarizes activity in the vicinity of areas found to be
significantly active above baseline (P<0.05) in response to
subjectively significant and to neutral names during different time
periods after stimulus onset. The main areas specifically involved
in response to subjectively significant stimuli were in the
vicinities of Wernicke's area and Wernicke's homologous area in the
right hemisphere, of Broca's area, of left middle, medial and
superior frontal gyri (at different times), of the right auditory
cortex, of the left hippocampus and of the left precuneus.
TABLE-US-00001 TABLE 1 Areas involved in the response to
subjectively significant and neutral stimuli Areas involved in
response to both Areas involved only in response to neutral and
subjectively significant subjectively significant stimuli stimuli
Left Right Left Right Latency (ms) hemisphere hemisphere hemisphere
hemisphere 200-350 Central cingulate Mid. temporal G. Wernicke's G.
Sup. temporal G. homologuearea Insula 350-500 Ant. cingulate G.
Ant. cingulate G. Sup. frontal G. Orbital G. Central cingulate
Central cingulate G. Mid. frontal G. Mid. temporal G. Inf. frontal
G. Supramarginal G. Inf. Frontal G. Med. frontal G. G. Inf.
temporal Med. frontal G. Rectal G. Postcentral G. G. Rectal G. Sup.
temporal G. Wernicke's Subcallosal G. Insula homologue Inf.
parietal Precentral G. area lobule Parahippocampal G. Wernicke's
area Subcallosal G. Broca's area Uncus Insula Sup. temporal G.
Precentral G. Ant. cingulate G. 500-600 Ant. cingulate G. Ant.
cingulate G. Wernicke's area Mid. temporal Central cingulate
Central cingulate G. Broca's area G. G. Inf. frontal G. Sup.
temporal Med. frontal G. Med. frontal G. G. Mid. frontal G. Sup.
frontal G. Sup. frontal G. Rectal G. Rectal G. Subcallosal G.
Subcallosal G. Uncus Parahippocampal Parahippocampal G. G.
Hippocampus Insula Sup. temporal G. Uncus Precentral G. 600-700
Ant. cingulate G. Ant. cingulate G Wernicke's area Insula Central
cingulate Central cingulate G. Broca's area Precuneus G.. Inf.
frontal G. Mid. frontal G. Med. frontal G. Med. frontal G.
Precentral G. Inf. Frontal G. Mid. frontal G. Sup. temporal G. Sup.
Frontal G. Sup. frontal G. Inf. temporal G. Insula Rectal G. Inf.
parietal lobule Sup. paritetal lobule Precuneus Postcentral G.
Hippocampus 700-800 Ant. cingulate G. Ant. cingulate G. Broca's
area Sup. frontal G. Central cingulate Central cingulate G. Mid.
frontal G. Mid. frontal G. G. Inf. frontal G. Inf. frontal G. Sup.
frontal G. Med. frontal G. Precentral G. Med. frontal G. Rectal G.
Sup. temporal G. Rectal G. Orbital G. Insula Precuneus
Abbreviations used: G, gyrus; Ant., anterior; Mid, middle; Sup,
superior; Inf, inferior; Med, medial.
[0062] FIG. 2 presents bar graphs of the timing of activation in
the vicinity of the main areas involved in the left and right
hemispheres, demonstrating the more prevalent activation of left
hemisphere structures in response to subjectively significant
stimuli. Note the concurrent activation of the brain areas
involved. FIG. 3 shows the level of brain activity in the vicinity
of several areas in response to subjectively significant-compared
to neutral stimuli. The graphs also show the comparable activation
of homologous regions in both hemispheres. The areas detailed in
the figures were the most significantly activated brain regions in
the time period between 200 and 800 ms after stimulus onset. An
overall enhanced brain activity was found in response to
subjectively significant compared to neutral stimuli
[F(2,52)=12.39; P<0.005]. Enhanced activation was found in
response to both subjectively significant and neutral stimuli in
the left hemisphere compared to the right hemisphere
[F(2,52)=12.55; P<0.005]. A significant interaction between
subjective significance and laterality was found [F(2,52)=9.45;
P<0.01], with the subjective significance effect significantly
more prominent in the left hemisphere. FIG. 4 summarizes activity
in the vicinity of the main areas found to be specifically involved
in the response to subjectively significant stimuli, when their
activity was statistically compared to that of neutral stimuli,
during peaks of activation in the ERP waveforms.
3. The Questionnaire
[0063] The questionnaire used in the experiment (see Appendix)
intended to measure subjective significance to the subject of first
names. Subjective significance (or subjective affective valence) of
first names to the participant was defined as subjective
significance of people in the participants' life that bear that
name. Verbal stimuli in general have multiple dimensions (e.g.,
meaning, grammatical function, affective valence). In contrast,
first names have only one major semantic dimension (subjective
valence). The subjective meaning of a first name is mostly acquired
from familiar people in the participants' life that bear this name.
The questionnaire was developed in order to assess subjective
significance of people in the participant's life.
[0064] The questionnaire was planned to target 3 dimensions of
subjective significance: (1) General emotional significance; (2),
Negative impact; and (3) recency of contact (closeness, past and
present). Specific items were included to assess each of these
factors. Questionnaire items were formulated to assess the
following affective aspects: closeness, anger, liking, dislike,
frustration, love, hatred. Additional items were included to assess
duration and frequency of relationship. In addition, items targeted
past traumatic experiences.
[0065] Although the questionnaire was originally developed to
assess subjective significance of stimuli in the context of an
event related brain potentials study, it can also serve other
psychological and social studies of relationship and personality,
beyond the realm of brain research. This questionnaire may also
serve clinical practice, in mapping complicated relationships in
the participant's life, assessing supporting relationships and
characterizing relationships related to traumatic events in the
participant's life.
[0066] The questionnaire, in its final form, included 46 yes\no and
rating questions (see Appendix) on each name. The original
questionnaire included 70 questions, and was reduced after the
factor analysis. Each participant was questioned about all names in
a list of 30 two syllable, common Hebrew names. Initially, the
questionnaire included 70 items that were directed at 3 factors:
(1) general emotional significance; (2) negative impact; and (3)
recency of contact. Items were first formulated so that every
factor that might affect the relationship between 2 people would be
included and probed, with some redundant items asking about the
same issues in different manners.
[0067] Emotional content questionnaires were addressed as well.
Later, after a factor analysis, the detailed questionnaire was
reduced to include only the most relevant and discriminating items.
In rating answers, a positive answer indicated an emotionally
loaded name, and the numerical value reflected magnitude.
[0068] Validation of the affective valence score was performed
using a plethysmographic measure for sympathetic activation.
Sympathetic activation is known to be affected by emotional
response. The plethismographic measurement was conducted on the
same day as the interview, using a peripheral arterial tone (PAT)
device. The PAT device [Itamar Medical; Caesarea, Israel] is a
portable device based on the PAT signal. Finger pulse wave was
measured by a plethysmographic technique (Bar, A.; Pillar, G.;
Dvir, I.; Sheffy, J.; Schnall, R. P.; Lavie, P. Evaluation of a
portable device based on peripheral arterial tone for unattended
home sleep studies. Chest. 2003, 123(3):695-703; Dvir, I.; Adler,
Y.; Freimark, D.; Lavie, P. Evidence for fractal correlation
properties in variations of peripheral arterial tone during REM
sleep. Am. J. Physiol. Heart. Circul. Physiol. 2002,
283(1):H434-9). The PAT signal was recorded while the participants
were reclining in a comfortable armchair in an acoustically
isolated chamber, listening to names (all 30 names in the list)
presented by earphones. The participants were instructed to listen
to the names and think about persons they knew bearing those names,
without pressing any button. The interval between names was 20
seconds, to accommodate the slow time course and the known latency
of the autonomic response (several seconds). Mean peak amplitude
(MPA) was computed for 5 intervals of 3 seconds after each
stimulus, using a baseline of 3 seconds before each stimulus onset,
in order to track the minimal amplitude of PAT following the
stimulus. The interval with the minimal MPA after the stimulus was
chosen. PAT response was determined as the % of PAT signal change:
[(minimum MPA after the stimulus--MPA at baseline)/MPA at
baseline].times.100. Those computations were conducted for the 3
most subjectively significant and 3 least subjectively significant
names for each participant. ANOVA was performed to assess the
effect of affective valence on the PAT response.
[0069] Informed consent was obtained. The questionnaire was filled
in an oral interview. Each participant was asked the entire
questionnaire about each person he knew bearing a name from the
list of 30 common Hebrew names. For each name, the following
procedure was repeated: Participant was asked to recall all the
persons he knew, in the present and in the past, who bear that
specific name. Then, participants were asked to specify their
relationship with each person mentioned for that name (fellow
student, a childhood friend, a family member, the bus driver,
etc.). Participants were subsequently asked to shortly answer 70
questions about that person. Specific questions were included if
the participant was, or was not in contact with that person at the
time of interview. The questions were either dichotomic yes/no
questions, or rating questions (rating between 1 and 5). In the
rating questions, `1` meant "not at all", and `5` indicated
"applies very much". Answers were marked by the interviewer. Items
were scored so that higher scores mean higher subjective
significance.
[0070] Rating values were transformed to dichotomous values by
computing the average response for each participant on a given item
across all questionnaires (across different persons' names)
completed by that participant. Responses above that average were
assigned a positive value, and those under-negative. In all, 455
questionnaires were completed and processed. Thus, most subjects
rated more than one person for each name--in total 30-40
questionnaires were filled by each subject.
[0071] Factor analysis was conducted and internal consistency (for
each factor) was measured. Internal consistency was assessed within
each factor, between all the questions in this factor. Redundant,
ambiguous, or low item-to-total correlation items were removed from
the questionnaire and subsequently 46 of the original 70 items were
included in the final Varimax rotation factor analysis.
[0072] Following the initial analysis, 46 of the original 70 items
were found useful and were included in the questionnaire. The final
items are presented in the Appendix.
[0073] Factor analysis demonstrated that a 3-factor solution best
explained the variance in the responses to the questionnaire (98%).
Factor 1 ("subjective significance"; 26 items) explained 54% of
variance with loadings ranging from 0.76 to 0.43. Factor 2
("negative connection"; 12 items) contributed an additional 25% of
the explained variance with loadings ranging from 0.72 to 0.41, and
factor 3 ("recency of contact"; 8 items) contributed 19% of the
additional variance, with loadings ranging from 0.76 to 0.44. Table
1 lists the factor loadings for each item and Table 2 details the
questions that were associated with each factor. When data were
randomly halved, and factor analysis conducted separately for the
two halves, the factor structure results were repeated.
[0074] All factors demonstrated good reliability (see Table 3).
Factor 1 had a Cronbach's alpha of 0.94, while factor 2 was
associated with an alpha of 0.88 and factor 3--0.82.
[0075] Validity of the subjective significance questionnaire was
tested using an autonomic activation measure--the PAT signal.
Correlation between the subjective significance score and the
autonomic response measure was significant (p<0.05).
[0076] Enhanced autonomic response (reduced peak amplitude) was
found after subjectively significant stimuli compared to neutral
stimuli [F(2,8)=10.12, p<0.05]. Thus, subjective significance
correlated well with high % change of the PAT signal.
APPENDIX
[0077] Following are the final 46 items of the questionnaire and
their original numberings:
Factor 1:
[0078] Yes\No questions
1. Would you prefer to see that person more frequently than you do
at the present?
2. Do you see each other on your initiative more than once a
week?
6. Has that person ever been the closest person (or the second
closest) to you?
7. Has your acquaintance with that person affected your life?
9. Was your acquaintance with that person significant for you?
12. Is your acquaintance with that person still affecting you
today?
13. Have you experienced significant events with that person?
15. Was that person present in any significant event you have
experienced?
18. Has that person ever appeared in your dreams?
19. Have you ever felt closeness to that person?
[0079] Rating questions (on a scale of 1-5).
3. How much is this person in your life (Physically or not)? [Very
much=5; not at all=1].
4. Rate the level of your closeness with that person. [Very much=5;
not at all=1].
5. Rate the maximal level of closeness you have ever had with that
person in the past [Very much=5; not at all=1].
8. Rate how much your acquaintance with that person affected your
life [Very much=5; not at all=1].
10. Rate how significant your acquaintance with that person was to
you [Very significant=5; not at all=1].
11. Rate how significant this person was to you at the time he was
most significant for you. [Very significant=5; not at all=1].
14. Rate how intense the most intense experiences you have ever
experienced with that person were. [Very intense=5; not at
all=1].
17. Rate how often you find yourself thinking about this person.
[Very often=5; not at all=1].
20. How often does this person come to your mind? [3 or more times
a day=5; never=1]
21. How often do you think about this person? [All the time=5;
never=1].
22. How significant is this person to you? [Very much=5; not at
all=1].
23. How much has this person affected your life? [Very much=5; not
at all=1].
24. How much do you like this person? [Very much=5; not at
all=0].
25. What is the duration of your acquaintance? [All of my life=5;
just one coincidental meeting=1].
26. How often do you see each other on your initiative? [Every
day=5; never=1].
Factor 2:
[0080] Yes\No questions
27. Would you prefer if you never met that person?
28. Has that person ever frustrated you?
30. Do you remember having any fights or quarrels with that
person?
31. Has that person ever hurt you?
33. Have you ever hurt that person?
35. Have you ever hated that person?
36. Were you ever angry at that person?
Rating questions (on a scale of 1-5).
29. Rate how much frustration this person has ever caused you.
[Very much=5; not at all=1].
32. Rate how much you were hurt by that person. [Very much=5; not
at all=1].
34. Rate how much you have hurt that person. [Very much=5; not at
all=1].
37. How often does this person make you nervous? [Very often=5; not
at all=1].
38. How much do you dislike this person? [Very much=5; not at
all=0].
39. In case you are not in contact with that person right now: rate
how significant your acquaintance was at the time you were in
contact. [Very significant=5; not at all=1].
Factor 3:
[0081] Yes/No questions
40. Did the relationship end abruptly?
In case the participant doesn't see that person any more:
41. Has the relationship ended in a way you were not satisfied
with, or in a traumatic way?
42. Do you remember your last meeting?
45. Has the relationship ended during the last 5 years?
46. Would you like to renew contacts with that person?
Rating questions (on a scale of 1-5).
43. In case you are not in contact right now--rate how intense your
last meeting with that person was (if you can remember it). [Very
intense=5; not at all=1].
44. In case you are not in contact right now--rate the intensity of
your separation [very painful, I could not avoid thinking about
this person all the time=5; I haven't even noticed the
separation=1].
[0082] Although the invention has been described in detail,
nevertheless changes and modifications, which do not depart from
the teachings of the present invention, will be evident to those
skilled in the art. Such changes and modifications are deemed to
come within the purview of the present invention and the appended
claims.
* * * * *