Patent Application: US-201113083335-A

Abstract:
a method of interpreting cognitive response to a stimulus is disclosed . the method includes collecting baseline neural activity data from a subject absent a stimulus . neural activity data is collected while the subject is being stimulated through exposure to a stimulus . a unique three - dimensional cognitive engram is then plotted representative of cerebral regions of stimulated neural activity caused by the stimulus . a novel graphical representation is plotted in three dimensions to indicate the brain region response unique to that stimulus .

Description:
the present invention has utility in producing a cognitive engram representation of neuroimaging data associated with the neurophysiological changes that are responsible for storage of a specific memory element in the brain . the present invention finds utility in settings such as interrogation , national security , criminal investigation , marketing and pharmacology . while a memory engram is known to one skilled in the art as a term that refers to the physical changes in the brain that accompany learning , as used herein the term “ cognitive engram ” is defined as a multidimensional representation of neuroimaging data of neurophysiological changes that are responsible for storage of a specific memory element or concept in the brain . a subset of a cognitive engram is appreciated herein to include truth / deception indications . a “ subject ” is defined herein to include a human ; non - human mammals such as monkeys , chimps , rats , mice , rabbits , dogs , cats , pigs , sheep and cows ; and birds such as pigeons and chickens . according to the present invention , cognitive engrams are described that capture memories of persons , places , events , concepts , intentions or thoughts from the brain of a subject and as such are readily adapted to discerning hidden agendas , past criminal activities , plans for the future , collaborative names , crime scene locations and other information that for instance is relevant to criminal investigations . it is appreciated that interrogation uses of the present invention are facilities by exposing a subject to stimulus while the subject is sedated , sleeping , or unconscious . additionally , application of various stimuli to a given subject are applied directly onto the appropriate receptor organ ( ear , eyes , etc .) or via direct brain stimulation to better illustrate the methods of the present invention for locating and uncoding cognitive data , the conceptual phrase “ i took the car to the atm and withdrew some cash ” entails at least three images , namely an individual standing by an atm machine , an image of a vehicle , and a cognitive image of currency . this conceptual phrase has numerous equivalent alternative phrases illustratively including “ i took the car to the atm , withdrew some cash ”; “ i got in the jeep , took some money from the atm ”; “ i got a ride to the bank for money ”; and “ drove to atm ”. if the exemplary conceptual phrase “ i took the car to the atm and withdrew some cash ” were translated into a standard binary code , the resulting string of zeros and ones would not be readily understandable to a human . however , if every time a person &# 39 ; s memory area is imaged while they are viewing an image of an atm machine results in a string of values x , then this code represents a unique cognitive engram , in this case for an atm machine . additionally , according to the present invention it is not necessary to know how the representation is made so long as it is unique , repeatable and identifiable . as the brain represents a three - dimensional neuronal structure , the data necessary to derive a cognitive engram is not present in a single plane through the brain , but rather is found to be distributed through various portions of the brain and as such only a three - dimensional construction of a neural activation map is operative to display data indicative of , in the exemplary case , an atm machine . referring now to fig1 the schematic process for the determination of a cognitive engram is provided . in fig1 the image 10 shown to a subject is that of a car and specifically a jaguar brand vehicle . before the subject is shown the image 10 , a baseline mri and functional mri is taken of the test subject to provide baseline imaging 12 of the subject . representative two - dimensional baseline scan images are shown at 14 . the presentation of the image 10 in front of the subject 16 occurs while functional mri test imaging 18 is collected . representative two - dimensional mri images are shown generally at 22 during image presentation 16 . for each respective test slice 22 , a compensation as detailed further below with respect to corresponding image 14 results in a series of two - dimensional numerical matrices representative of raw data 20 . the raw data 20 is then combined and analyzed to provide a cognitive image engram 24 representative of the image 10 . a representative engram for the car depicted in image 10 is shown at 26 and more specifically is unique not just for a car but for a jaguar brand of vehicle . software for the analysis of raw imaging data 20 to identify unique cognitive engrams is surprisingly not critical with the proviso that like processing is used for subsequent experiments . according to the present invention , manipulation of imaging data is as simple as subtracting a baseline image from each test scan from a subject brain . alternatively , baseline two - dimensional mri images and test two - dimensional view images are scanned for common patterns of data among groups of subjects exposed to the same or similar stimuli . in this way , a database of cognitive engrams can be developed common across populations in response to a particular stimulus . while the present invention has been detailed with respect to functional mri data collection , it is appreciated that such data is optionally supplemented with ct , pet , meg or eeg data . such supplemental data is particularly helpful in constructing cognitive engrams representative of common responses to similar or identical stimulus . it is appreciated that conventional software routines are operative herein to construct spatially localized images and correlate concepts and items introduced via subject senses . such software routines illustratively include subtracting test images 22 from corresponding baseline images 14 , cryptography software , motion direction software that involves use of moving overlap , correlation across various imaging techniques , neural network software , statistical parametric mapping software , analysis of functional neuroimages ( afni software ), holographic routines and combinations thereof . gradient imaging is also optionally used to fluctuate the magnetic gradient of the mri signal to enhance the resolution and content of the signal data . pet - mri image registration is used to correlate images and data in both structural and functional terms . although such data is obtained from separate scans with separate techniques , the resulting data extracted from the different scans on the same individual afford common structural and functional information . ct - mri image fusion analysis is also operative herein to correlate images and data with both structural and functional components . this is analogous to pet - mri image registration . in another embodiment , the comparison of dynamic mri imaging with dynamic double arterial phase helical computer tomography is used to evaluate the structure and function of blood supply and perfusion and its relation to the encoding of memory . virtual mri constructions of finer resolution are appreciated to correlate functionally active regions of a subject brain to specific concept encoding . the resulting patterns are correlated through the stimulus a subject is being subjected to during neuroimaging . in other embodiment , three - dimensional image correlation of ct , magnetic resonance and pet studies are compared to further enhance structural and functional correlations within a subject brain and categorize those correlations with a stimulus or thought . in still another embodiment , a functional magnetic resonance imaging in real - time ( fire ) uses sliding - window correlation analysis and reference - vector optimization of imaging data to understand encoding of specific stimulus as concepts within the subject brain in a mechanistic fashion . in another embodiment , arterial spin labeling and dynamic susceptibility weighted contrast enhanced magnetic resonance imaging are used to discern , identify and match two - dimensional brain imaging data to the concepts being stored in a subject brain . in another embodiment , comparison of conventional , magnetization transfer and diffusion - tensor magnetic resonance imaging findings is used with whole brain tissue histogram analysis to discern , identify and match two - dimensional brain imaging data to concepts being stored in a subject brain . additionally , activation areas of a subject brain by groups of continuous voxels and by individual voxels are compared between individuals and within the same individual for multiple runs of the same stimulus . additionally , windowing can be used to further simplify analysis such that instead of , for example , simply using maximal intensity by looking only at subject brain regions having for instance greater than 90 % activity or only activity between 60 % and 80 %, a cognitive engram is more rapidly produced . the net result of these varied image processing techniques that are applied in the generation and analysis of raw data is to discern a data storage pattern within the brain and prepare a rosetta stone for the identification and matching of brain imaging scan data with a given stimulus without the need for understanding the rules of stimulus encoding within a subject brain . optionally , prior to determination of a cognitive engram , image corrections known to the art are performed to remove - image noise . such additional techniques illustratively include correcting for subject movement artifact , reprocessing sequential images , digital noise subtraction , blood oxygen level dependency consideration , statistical deformation modeling ( sdm ), and analysis algorithms well known to one skilled in the art for mri data that exploits differences in data signals not requiring functional mri or blood oxygen level dependent techniques . an additional aspect of the present invention is the development of movement artifact overlap harvesting in which additional data removed by software to correct for movement artifact is harvested and processed to fill in detail from spatial areas between imaging slices and as such increases the total data set . the inventive technique of movement artifact overlap harvesting spatially plots conventional motion correction artifacts to create partial pseudoslices intermediate between adjacent mri imaging slices . the present invention is further detailed with respect to the following non - limiting examples . recent scientific publications utilizing fmri to study neurocognitive functions were located by searching the national library of medicine . publications which detailed the specific coordinates of activation areas for visual objects were selected , and are described below . three - dimensional graphical surface and bubble point representations of the activation maps were constructed by plotting the xyz coordinates . the xyz coordinates were supplied by all three sets of investigators using the normalized space of the talairach and tournoux brain atlas ( 1988 ). all of the publications whose data was reprocessed presented test objects to test subjects while lying in an mri scanner , using a flat panel display situated to allow visibility during scanning . bernard et al . ( 2004 ) studied the presentation and processing of visual imaging of famous and non - famous faces . the study used an event - related fmri design , utilized a 4 - t mri system , with stimuli consisting of 80 black and white pictures of adult faces , half of famous and half of non - famous people . the xyz coordinates of the activation areas were supplied in table 1 of the bernard et al . publication . when the three - dimensional representation of bernard et al . was prepared , the following cognitive engrams were determined . when bernard 2004 data was processed to create three - dimensional activation maps , two cognitive engrams were developed , one for famous and one for non - famous faces . it is apparent that by viewing these activation patterns , a determination of famous versus non - famous could be determined . the data regenerated from bernard et al . into cognitive engrams demonstrate the potential to distinguish whether specific faces are recognizable , and whether they are famous or non - famous . differences between three classes of objects ( face , chair , house ), and familiar and non - familiar words can also be distinguished by the pattern of the cognitive engrams generated . with the development of more detailed activation maps , from a larger number of individuals , with a more detailed graphical representation of concepts , a rosetta stone forming a database of cognitive engrams for individual faces , objects , places , and concepts ( hate , intent to deceive , etc .) is being developed . such a database allows the two - way interpretation of cognitive engrams , allowing the identification of the presence of specific thoughts ( persons , places , intents ) in an individual &# 39 ; s brain . a 3 - t general electric signa excite scanner with whole head coil is used . changes in the blood oxygen level dependent t2 *- weighted mri signal are measured using a gradient - echo echoplanar sequence . in each time series , 18 ( 128 × 128 ) or 28 ( 64 × 64 ) contiguous axial slices are obtained . there are three sets of scans performed per experiment : localizer , mri for functional data , and high resolution anatomic . the subject lies in the mri scanner , wearing a phased array mri head coil as part of the regular head scan . mounted on the head coil is a 45 degree mirror , allowing them to see down toward their feet and view the test images . displayed near the bottom of the subject &# 39 ; s feet is a large photo , or a white blank paper board , which can have a large x marked across it , which is totally within the field of view of the test subject lying in the scanner . other means of presentation of visual test images include a goggle image projection set , and use of an mri - compatible video monitor . the functional mri scans last between 110 to 220 seconds total ; after a 6 second lead - in time , the blank is displayed for 6 to 8 seconds , then the picture for 6 to 8 seconds , blank , picture , for a total of 5 to 10 repetitions . in a separate scan , high - resolution full volume structural images are obtained for each subject , using fast spgr imaging ( 146 , 1 . 0 - mm thick axial slices , no spaces , tr = 8 , te = 3 . 2 , fov = 24 cm , 256 × 256 matrix ). these t1 - weighted images provided detailed anatomical information for registration and three - dimensional normalization to the talairach and tournoux atlas ( 1988 ), as described below . there were about eight runs per person for these first few scans : imaging data is analyzed in two ways : conventional and raw data . conventional analysis refers to the generation of activation maps correlated with anatomical representative images . modeling of raw imaging data involves the manipulation of the basic output from the scanner itself , using techniques such as neural networks . voxels can be individually compared with the properties of intensity of activation and corrected spatial localization . the following paragraphs explain the conventional analysis procedure . the fmri scan volumes are motion - corrected and spatially smoothed in - plane . mri data files are analyzed using medx to determine the location of activated voxels — defined as voxels from a brain region that respond differentially to the test ( visual ) stimuli . voxels are selected that show an overall increase in activity for meaningful stimuli , for example , a positive regression weight for the contrast between a test photo and control ( blank page ) stimuli . the uncorrected probability is & gt ; 0 . 05 , meaning every voxel showing activation with the probability of more than 95 % is selected in the analysis . activated voxels are then segregated into clusters according to the category of objects that evoke the maximal response . for a conventional analysis , clusters of seven or more contiguous voxels are considered significant . in separate analyses , activated voxel data can also be parsed on the basis of degree of activation . the anatomical locations of clusters of voxels showing significant differences between responses are determined by superimposing the statistical maps on coplanar high - resolution structural images . the partial volume structural images are registered with the full volume high - resolution images using automated image registration ( woods , mazziotta & amp ; cherry , 1993 ). the full volume high - resolution images are normalized to the talairach and tournoux atlas ( 1988 ) using medx . both transformations ( registration and normalization ) are then applied to the statistical maps , in order to obtain the talairach coordinates of brain regions that respond maximally to the test stimuli to generate a cognitive engram . functional mri experiments were performed on normal subjects , while they were looking at photos . as an example , the following activation map data points were created when viewing photos of president bush and a grieving woman kneeling at grave site are detailed in tables 1 and 2 , respectively . cognitive engrams derived from scans of a subject brain while viewing photos of president bush , a grieving woman kneeling at a graveside , and saddam hussein are shown in fig3 , and 5 , respectively . the fmris from the same individual , viewing these images are shown in fig6 where similar areas of general visual activation arte noted , and also areas that are indicative of specific differentiating areas . by using an activation map composed of xyz coordinates and intensity windows , such as areas with greater than 90 % activity , 60 to 80 % activity ; etc . a fourth dimension of activity intensity topography is overlapped onto an inventive cognitive engram . background information is obtained on the subject &# 39 ; s name , age , sex , ssn , birth city , medications , current and past illnesses , psych history , criminal history , accusation . then , a basic set of standard images is presented to the test subject while undergoing neuroimaging , in order to obtain a background pattern of activation . individual responses to questions are recorded via a number of techniques , including verbal and pressing of buttons on handgrips . the test subject is presented with between ten to twenty test questions , and asked to supply intentionally deceptive and intentionally truthful responses to each question . the test subject is presented with case - specific questions , with accompanying images / displays of words and phrases concerning : facts about their own personal life , name , sex , age , ssn , residence , criminal history ; and specific photos / questions / statements relating to the subject at issue , including potentially the specific crime , intention , conspiracy collaborators , locations , objects . the raw imaging data ( structure and function ) is analyzed and three - dimensional activation and anatomical maps are created . the pattern of activation is correlated with specific responses to images and concepts , as part of a correlative dictionary ( rosetta stone ) between three - dimensional fmri activation maps and concepts / images presented . the activation map is analyzed according to example 2 to create the optimum correlation between activation areas and truthful / deceptive responses on control and question images / concepts . using the internal controls on individual patients , and accumulated group controls , an interpretation on truthfulness is made for : responses to individual questions ; and recognition of individual presented images and concepts . use of fmri to predict neurologic adverse effects of interferon used to treat patients with hepatitis c brain activation cognitive engrams of individuals who have been selected to receive interferon therapy are produced , before and after 4 - 6 weekly injections of interferon . standard medical questioning and written evaluation tools of depression such as beck depression scale are employed at baseline and weekly to detect the development of inf - associated depression . individuals who require treatment of interferon - induced depression ( receive an antidepressant such as ssri medication ) undergo repeat fmri after an appropriate therapeutic interval , in order to evaluate changes in activation map which can correlate with a therapeutic antidepressive response . immediate follow - up studies include dose - response of interferon to fmri indices of clinical depression , and response of depression , as shown by fmri indices of depression , to antidepressant drugs . the immediate benefit of this is to develop an objective method of predicting a depressive response to depressant side effects of essential medications . the response predictive protocol is provided in table 3 . the study subjects undergo continual mri neuroimaging while viewing test stimuli in order to capture structural and functional data as detailed in example 2 . these data are analyzed for the presence of neuroimaging activation that has been shown to correspond to cognition and depression . test visual stimuli are chosen to induce a strong depressive response in the viewer . a normal test subject was shown photos of president bush , saddam hussein , and of a grieving woman kneeling at a grave as detailed in example 2 . the photo of the grieving woman was used to generate a feeling of sadness . this person showed activation in the right inferior and middle temporal gyrus , and in the fusiform gyrus , areas known to correlate with the provocation of sadness in normal individuals . this activation was only noted when viewing the grieving woman , not for the test photos of president bush and saddam hussein . individuals scoring as depressed on the beck depression scale showed varying degrees of activation in these cerebral regions for all three images . beauchamp m h et al . dynamic functional changes associated with cognitive skill learning of an adapted version of the tower of london task . neuroimage . 2003 november ; 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