Patent Abstract:
typical neurological examinations focus on qualitative and subjective assessments , including obtaining a patient history , assessing the patient &# 39 ; s cognitive status , motor and sensory skills , and cranial nerve functionality . a quantitative assessment of neurological condition includes recording a subject performing a visuomotor task and processing the performance data to determine a level of complexity in the task activity and determine a complexity index . for a sample healthy population , a baseline level of complexity and baseline complexity index can be determined . a patient &# 39 ; s complexity index can be compared to this baseline complexity index as an indication of disease or disability . a baseline complexity index can be determined for a patient at part of a health maintenance examination and used as the baseline complexity to detect disease or disability in the future based on lower complexity index values in future examinations .

Detailed Description:
the present invention is directed to methods and systems for providing quantitative neurological assessments and neuro - diagnostic evaluations . in accordance with various embodiments of the invention , a subject is asked to perform a task that is intended to test a specific neurologic function and a system tracks and records the subject &# 39 ; s performance of the task . the task data can be analyzed using a neuromotor index . this index can include a multiscale complexity analysis in order to determine a quantitative assessment , such as a complexity index ( ci ) which can be compared to a standard or baseline index for the subject to detect disease or disability , or the ci can be compared to prior performance data and ci values for the subject to assess effectiveness of treatment or therapy . the neuromotor index can also include timing parameters , such as the cumulative micropause duration , which is an indicator of motion submovement concatenation and percent time in target region . a further detailed description of the data processing is included below . in accordance with embodiments of the present invention , mathematical methods derived from the theory of nonlinear systems can be used quantify the complexity of a signal derived from tracking a subject performing a task . the signal to be quantified can be one or more of the following : 1 ) the recorded trajectory ; 2 ) the residual signal defined as the difference between the recorded trajectory and the actual ( task target ) trajectory ; 3 ) any signal derived from each of two previously mentioned , such as those obtained by computing their first and second derivatives , representing velocity and acceleration , respectively . in accordance with the invention , the methods used to quantify the signal include , entropy - based algorithms such as multiscale entropy , sample entropy , approximate entropy , algorithms that quantify the fractal properties of a signal such as detrended fluctuation analysis , time domain parameters such as the moments of a distribution ( mean , variance , skewness , etc . ), and methods of frequency analysis such as fourier and huang - hilbert transforms . fig1 shows a diagram of a system 100 according to the present invention . the system 100 can include a computer or data processing system 110 connected to a task monitoring device 120 . the connection can be a wired or wireless connection ( e . g , wifi , bluetooth , zigbee , etc .). the computer system 110 can include one or more processors 112 and associated memory devices 114 , 116 ( e . g ., volatile and non - volatile memory devices ) and one or more user input and output devices 118 ( e . g ., display devices , keyboards , mice , etc .). the computer system 110 can also include software ( e . g ., operating systems and application programs ) to facilitate the operation of the system and for receiving , storing and processing data . the task monitoring device 120 can take many forms and can include one or more sensors for recording subject motion data while the subject is performing a requested task . in accordance with one embodiment of the invention , the task monitoring device 120 can include a touch sensitive display screen 122 that can display objects 130 , 132 and images on the screen and sense a subject making contact with the screen . fig2 and 3 show diagrams of an example of a task according to some embodiments of the present invention . in accordance with the invention , a subject is provided with a task monitoring device 120 and asked to perform a task . in one embodiment , the subject is asked to place their finger ( or a stylus ) on an object 132 ( e . g ., a dot or a box ) on the screen and maintain their finger in the center of the box as the box moves around the circle 130 , as indicated by the arrow shown . in accordance with the invention , one or more software application programs can be executed by the processor 112 to cause the circle and the object to appear on the screen . other indicia ( not shown ), such as instructions and a count - down timer can be provided to assist the subject in performing the task . the subject can be instructed to perform the task of following the object around the circle and the task monitoring device 120 can sense the position of the subject &# 39 ; s finger ( or a pointing device , such as a stylus ) and transfer this information to the computer system 110 . the computer system 110 , under software application control can record the position information along with time synchronization information . the subject can be asked to repeat the task ( e . g ., 4 revolutions around the circle ) and / or perform the task in different directions and / or at different speeds . a sequence of tasks can be presented , for example , including different directions and / or different paths ( e . g ., circles , ovals , lines , polygons , spirals , etc .). in some embodiments , the path can move into or out of the screen ( e . g ., a driving simulation task ). these tasks can be implemented under software application program control . in some embodiments , the data can be collected and processed in real - time in order to provide feedback to the user . for example , symbol , such as a box or a circle on the display can change colors to provide an indication of performance or size of the object can be enlarged or reduced as a function of performance . the information and / or data collected can be used to produce a time series of data representing the task motion recorded . for example , the data recorded can represent the position of the subject &# 39 ; s finger on the screen at predefined sampling intervals and time series representing the difference between the actual position and target position ( e . g ., the object , dot , or box on the path ) can be determined . next , the degree of complexity or irregularity can be quantified using an entropy measure , such as sampen , for example , resulting in a multiscale entropy ( mse ) plot of sampen at various scale factors . in accordance with one embodiment of the invention , a complexity index ( ci ) can be determined as the area under the mse curve for a predefined range of scale factors . the complexity index can be used as the neuromotor index ( ni ) or combined with other measures to form the neuromotor index . in accordance with embodiments of the present invention , one or more of the ni values for a given subject can be stored and used to evaluate neuromotor function of the subject . an initial ni value can be used as a baseline from which to evaluate the subject to indicate the existence of disease or disability . during treatment and therapy , further subsequent evaluations in accordance with the invention can be compared with one or more prior evaluations ( ni values ) to assess the effectiveness of the treatment and / or therapy . in accordance with some embodiments of the invention , the ni indicates a level of complexity or adaptability of a subject given their state at the time of assessment . it is expected that with a healthy subject the complexity level for a given task will be higher than when the subject is fighting a disease or upon initially acquiring a disability . the efficacy of treatment or therapy can be assessed according to embodiments of the invention by comparing current ni values with prior ni values to determine whether current ni values are greater , indicating increased complexity and a return to healthy state . in accordance with embodiments of the present invention , an integrative neuromotor index can be calculated as a function of one or more of the neuromotor performance signals or indices . these parameters can be directly combined through addition , by comparing a vector , or through implementation of a model . in one embodiment , this model can be developed using principal component analysis , support vector machines , neural networks , or other machine learning algorithm . similar to the ci , the values for a given subject can be stored and used to evaluate neuromotor function of the subject . in accordance with other embodiments of the invention , the tracking system can include a display ( which could be a monitor or a projected image ) and an eye - tracking system . in this embodiment , the task can include the subject following an object as it moves along a predefined or random path with their eyes . the eye tracking system can determine the location or position on the display of the subject &# 39 ; s gaze over time . the gaze position sequence can be used as described herein to determine ni values . in accordance with other embodiments of the invention , the tracking system can employ a motion capture system to obtain the body motion over time of the subject &# 39 ; s entire body or elements of the subject &# 39 ; s body ( e . g ., head , arms , hands , legs and feet ). the body motion can be captured using well known motion caption devices and methods including , but not limited to , remote sensing devices such as cameras and reflective sensor ( e . g ., mm and high frequency sensing ) and subject worn sensing devices , such as , accelerometers , gyroscopes , magnetometers , force sensitive resistors , inertial navigation devices , and combinations of remote sensing devices and body worn sensing devices . in accordance with other embodiments of the invention , the tracking system can a light sensing target and the subject can move a pointing laser to trace the motion of the moving target . the target can be moved by a simple mechanism , such as a rotating disk or a more complex system , multi degree - of - freedom actuator , such as a robotic arm . the target can include one or more sensors that can be used to determine the position of the laser image ( laser spot ) on the target and the deviation of the image from a center or reference point on the target . the target can include an array of light sensors that become illuminated by laser image projected by the subject on the target . a time sequence of positions on the target can be used to track the movement and the residual signal can be determined as a function of the distance from a target point ( e . g ., a center point ) of the target array and the brightest point ( e . g . highest signal intensity ) on the array illuminate by the subject . alternatively a single sensor or array of sensors can be used and the residual signal can be determined as a function of signal intensity . the position to be tracked could also be on a display screen . the speed of the target object ( e . g ., a red line , a circle or a square , fig3 ) around the circle was selected through testing , with the goal of achieving a speed of motion of the object that was slow enough to allow for microcontrol adaptations ( error corrections ), but not so slow that the subject would consciously stop and wait for the target to move . in accordance with one embodiment , a speed of 18 deg / sec around a circle with a 400 pixel diameter was selected . ( the tablet used in this study had a screen size of 8 . 25 × 6 . 125 in , with a resolution of 125 ppi .) other speeds can be selected based on the resolution of the position sensing device , in this example , the touch screen . the data collection software can output the coordinates for both the target and the subject &# 39 ; s actual position . the sampling frequency can be 31 . 25 hz , a value that was chosen taking into consideration the target speed and the pixel size . in order to measure micropauses where the velocity is zero , the sampling frequency and speed can be selected to detect motion from one sensing position to the next , with limited overlap , thus sampling too slow or having large pixels would result in an inaccurate detection of micropause duration . in accordance with some embodiments of the invention , a method and system for measuring a neuromotor tracking function can be provided in a way that is simple , accurate , quantitative and inexpensive . the outputs can include measurements referred to herein the neuromotor index ( ni ). ni can reflect a combination of features useful for a physiologic system to be adaptive . these features can include 1 ) correlations across multiple time scales , 2 ) accuracy , and 3 ) fluidity . for example , these features can be analogized to the properties that are universally understood to underlie great works of classical music . from a practical , clinical point of view , a measure of these features can be reflected in the neuromotor index by employing one or more methods designed to analyze series of data points ( time series ) derived from tracking or monitoring motion . in accordance with some embodiments of the invention , the system or method can include measuring the mean and standard deviation of the error of patient position , the complexity index ( ci ) of the residual signal , the percentage of time within the designated region , and the number of micropauses . the task tracking system monitors the movement of the subject , records the raw values , and can determine a predicted age of the subject based on the measures and stored baseline measures . the value can also be compared to a previous baseline measure recording . in some embodiments of the invention , the desired position of the user can be actually a region of a circle . if ( x c , y c ) are the coordinates of the center of the circle and ( x s , y s ) are the coordinates of the stylus at a recorded time point , then the instantaneous error at that time point can be defined as instantaneous error =√{ square root over (( x s − x c ) 2 +( y s − y c ) 2 )}{ square root over (( x s − x c ) 2 +( y s − y c ) 2 )}− r ( 1 ) where r is the radius of the circle . the error time series is then the sequence of instantaneous errors or micro - errors . to account for initiation and termination effects , the first and last quarter or other portion of the circle can be removed . thus , in this embodiment , the system can analyze , for example , a total of 3 . 5 revolutions out of the 4 revolutions collected . the mean and standard deviation of the residual can be calculated using standard methods . as shown in fig4 , in accordance with various embodiments of the invention , the error or residual values can be determined in one or more different ways . for example , the residual value r 1 can be determined as the difference between the actual stylus position ( x a , y a ) and the path being traced , which , for a circular path , extends along a line drawn between the actual stylus position ( x a , y a ) and the center of the circle ( x c , y c ). this residual value is independent of changes in speed . alternatively , the residual value r 2 can be determined as the distance ( e . g ., euclidean distance ) between the actual stylus position ( x a , y a ) and the target position ( x t , y t ). for example , sqrt (( x a − x t ) 2 +( y a − y t ) 2 ). this residual value reflects changes in speed . in accordance with some embodiments of the invention , the residual signal can include a sequence of residual values determined at consecutive points in time . fig5 shows a diagram of an example of a target path , an actual path and a residual signal . this micro - error signal can also be calculated by determining the difference between the stylus position and the target region . in some embodiments of the invention , the micro - error signal can include position ( angular or cartesian coordinates ) and / or velocity error . in other embodiments of the invention , the micro - error signal can include time error ( e . g ., the difference in time between actual arrival at a position and the expected arrival at a position ). the original mse method was derived for the analysis of stationary time series . since these tracking time series are highly non - stationary , the system and method according to the invention can use a detrending algorithm prior to calculating the ci values . for detrending , a moving average with a window of , for example , 21 points can be used . as described in detail elsewhere ( costa et al ., 2005 ), the mse comprises two steps : 1 ) deriving a set of coarse - grained time series that capture system dynamics over different time scales and 2 ) measuring the information content of each of the coarse - grained time series use sample entropy ( sampen ). the mse curves are the sampen value plotted against the scale factor . the ci in one embodiment can be defined as the sum of the sampen values for scales 1 through 4 based on the data collection rate , resolution of the tablet , and the total number of points recorded . the target region can be defined at each of the generated time points by computing the rays from the circle origin to the boundaries of the moving target region , as shown in fig6 . if the cursor , represented by the ball , touches or falls within the target region , the time point can be considered within the region . the time increments associated with the pixels in the region can be summed to determine a total time in the region , as well as to verify the total task time . the percent time in the target region ( pttr ) can be determined by dividing the total time in the region by the total task time . micropauses can be defined as occurring when the position of the stylus did not change between two consecutive time points , thus where ( x , y ) i and ( x , y ) i + 1 are the stylus coordinates at time i and i + 1 , respectively . the cumulative micropause duration is then the summation of the time increments associated with the repeated stylus coordinates . this parameter is limited only when the stylus location is not sampled frequently enough as pauses would be missed . if the data are sampled at higher rates , the cumulative micropause duration would not be affected . in some embodiments of the invention , it may be appropriate to combine multiple parameters in the assessment of adaptability . these parameters may be combined in many ways , including machine learning algorithms ( e . g . support vector machines , neural networks , hidden markov models , etc .). additional embodiments for analyzing the correlations across multiple time scales and information content can be assessed with a variety of entropy - based analyses , including but not limited to : multiscale entropy ( mse ), sample entropy ( sampen ), approximate entropy ( apen ), tsallis entropy , kolmogorov entropy , and diffusion entropy . each of these methodologies can be applied to the micro - error signal as defined previously . complementary techniques that measure correlation properties of time series are fractal and multifractal analyses , including those based on detrended fluctuation analysis , box - counting or wavelet analysis . these methods can be applied to the raw data or micro - error data . the multiscale entropy ( mse ) method discussed in the preferred embodiment has certain attractive features for capturing correlations across time scales and information content in that it explicitly measures the entropy , not only of the original signal , but also of a family of signals derived therefrom , which represent multiple time scales . this technique allows one to distinguish highly variable signals without correlations ( e . g ., white noise ) from more physiologic types of 1 / f noise seen in the output of complex adaptive systems . in additional embodiments , the accuracy of the tracking motions can be assessed with a number of measures in the time domain , including mean , standard deviation and higher moments of the histogram / probability distribution . these methods can be applied to the raw signal , micro - errors , velocity , acceleration , or other function of the raw signal . additional embodiments can assess the fluidity of motion by detecting oscillations that indicate the presence of a characteristic time scale associated with a pathologic process . for example , parkinson &# 39 ; s disease is associated with distinctive oscillations ( tremor ) at a frequency of around 5 hz . these periodic dynamics can be detected and quantified using frequency domain analyses , including fourier or wavelet - based methods , and methods based on the hilbert - huang transform ( hht ) and empirical mode decomposition ( emd ). each of these methods can be applied to the raw signal , micro - errors , velocity , acceleration , or other function of the raw signal . the assessment of fluidity ( or lack thereof ) of motion can also be assessed using measures of micropauses described previously . the greater the number of pauses and the longer their duration , the less fluid the motions are . with these outcome measures , a model of the system can be developed using support vector machines ( svm ) ( chang and lin , 2001 ), which are a method of supervised learning used for classification . in order to develop a model , a set of training data with known classifications is required . once trained , the model can be tested and used with different datasets . here , a c - support vector classification formulation of the quadratic minimization problem ( chang and lin , 2001 ; boser et al ., 1992 ; cortes and vapnik , 1995 ) with a radial basis function ( rbf ) can be used , implementing the “ one - against - one ” approach for multi - class classification ( chang and lin , 2001 ; knerr et al . 1990 ; hsu and lin , 2002 ), and a five - fold cross - validation model to minimize over - fitting the model . in accordance with one embodiment of the invention , training parameters include the tracing outcome measures for n - trials for the dominant hand , along with the corresponding subject gender . during the model development , there are two unknown parameters that must be solved , c , an error penalty parameter in the optimization , and γ , a rbf kernel parameter . the parameters c and γ can be determined , for example , by performing the cross - validation training optimization using a coarse grid search , then refine the search to obtain a better solution . the model can be trained with the best c and γ parameters . using this model , the probability that a new data point falls within a particular age group can be estimated . knowing a subjects &# 39 ; actual age , the system and method according to the invention can be used to assess whether their visuomotor skill falls above , below , or at their actual age . the apparatus and method previously described can be implemented for the following applications : neurological assessment , including standard neurological exams and those in particularly affected groups such as the elderly , those with parkinson &# 39 ; s disease , multiple sclerosis , traumatic brain injury , micro traumatic brain injury , musculoskeletal injury , stroke , diabetes , cerebral palsy , etc . baseline quantitative values can be determined from a sample healthy population and used as a threshold for detecting disease or disability . the data obtained from repeated assessments taken over time can be compared to determine how the patient progresses through healing , rehabilitation , training , therapy , etc . these measures can also be used to determine the efficacy of a drug dosage , or presence of side effects , for a particular diagnosis in providing an appropriate degree of motion adaptability . current concussion sideline assessment techniques use a very general scale that is affected by the person administrating the exam and the person responding to the questions . methods and systems according to the present invention can provide a quantitative evaluation with appropriate resolution that is not limited by the subject interpretation of the person administering the test . for example , for athletic subject evaluation , such as in sports , evaluations according to the present invention can be given pre - season to establish a baseline and then after each game and / or potential injury , a more detailed understanding of the neuromotor pathways can be developed . thus , if an athletic subject receives a concussion or other neuromotor injury , an evaluation according to the present invention can be used to determine the extent of the injury , the subject &# 39 ; s progress through treatment and rehabilitation and when the subject has recovered back to their baseline measures . similarly , embodiments of the present invention can be applied in other contexts , including , for example , military deployments , high speed activities , such as autoracing , and space travel . more generally , the evaluation according to the present invention can be performed during a standard physical and then can later be used for any person reporting head trauma . methods and systems according to embodiments of the invention can be used to develop a sobriety test . in accordance with embodiments of the invention , as a person increases their alcohol intake , their motion become less complex and less adaptable to perturbations , which can be quantitatively evaluated in accordance with the present invention . given a baseline , evaluations according to the present invention can provide information on how able the person is to perform motor tasks . implantable neurological stimulators and implantable drug pumps continue to show promise in the treatment of a variety of diseases and ailments . setting therapeutic levels and dosages is still difficult because it often relies on a clinician &# 39 ; s observation of symptoms , or patient &# 39 ; s self report of symptoms ( such as tremor , etc . ), during a dosage setting paradigm that can take hours , weeks , or months . methods and systems according to embodiments of the present invention can be used quickly and precisely assess neuromotor adaptability and complexity would significantly improve the ability to tune these devices for individual needs . hydrocephalus , and its related disorders , involves the increase of cranial pressures from a build up of cerebral - spinal fluid around the brain . typically excess fluid is normally drained to maintain cerebral pressure but in some cases this mechanism is faulty and cranial pressure can rise , leading to brain injury and neuromotor and cognitive dysfunction . often the symptoms of an increase in cranial pressure are not apparent until the pressure reaches dangerous levels . cerebral spinal shunts are often placed to drain excess fluid when the natural mechanisms fail but can clog and become nonfunctional over time . assessment of cerebral pressure and shunt performance is typically invasive and expensive . methods and systems according to embodiments of the present invention can be used to identify changes in neuromotor performance that indicate a dangerous change in pressure affecting neuromotor performance and cognition . research is ongoing in the field of electrical and mechanical assistance for improving pathologies associated with motor control . methods and systems according to embodiments of the present invention can be used to provide information regarding the patient &# 39 ; s neuromotor control with and without the assistive device . this additional information can be used for clinical assessment and evaluation of the efficacy of new assistive devices , including the objective assessment of the optimal range of parameters for a given individual . a wide range of exercise and therapy protocols have been proposed for aging adults to enhance their motor control adaptability , including yoga , tai chi , strength training , etc . methods and systems according to embodiments of the present invention can used to provide valuable quantitative information on the comparative efficacy of these exercise interventions in improving motor control adaptability . during certain types of neurosurgery , the patient is kept awake and tested to confirm which parts of the brain are being affected . in accordance with embodiments of the invention , for example , eye - tracking based embodiment , can be used to monitor neuromotor ability , while still keeping the patient immobile . in accordance with various embodiments of the present invention , emotion - based assessment , including assessment for depression treatment , post - traumatic stress disorder , combat fatigue , etc can be provided . with increased emotional stress , the body is less able to adapt , thus their motor tracking complexity should decrease . methods and systems according to embodiments of the present invention can be used as a diagnostic to determine if a patient improves from a baseline measurement condition , or degrades when the baseline is during a neutral state . chronic or acute sleep deprivation can cause fatigue , decrease cognitive functionality , and decrease motor control . while drivers are not permitted to drive when under the influence of alcohol , there are no legal limitations on the permissibility of driving while fatigued . methods and systems according to embodiments of the present invention can used to determine if a driver is alert and adaptable enough to drive . embodiments of the invention can be incorporated into a car dash device or program . this embodiment might be especially useful for transit workers , rail works , long haul truck drivers , surgeons , and medical residents . embodiments of the present invention can also be used for clinical assessment of the neuromotor pathway associated with fatigue and can be used to help with drug dosing . methods and systems according to embodiments of the present invention can also be used to analyze a robot performing similar tracking tasks . embodiments of the present invention can be used to determine whether the robot is adaptable to perturbations in a similar manner as a healthy human . the present invention can be used to detect defective sensors , actuators and / or communication pathways . in some applications , it may be appropriate to combine multiple parameters in the assessment of adaptability . these parameters may be combined in many ways , including machine learning algorithms ( e . g . support vector machines , neural networks , hidden markov models , etc .). other embodiments are within the scope and spirit of the invention . for example , due to the nature of software , functions described above can be implemented using software , hardware , firmware , hardwiring , or combinations of any of these . features implementing functions may also be physically located at various positions , including being distributed such that portions of functions are implemented at different physical locations . further , while the description above refers to the invention , the description may include more than one invention . the following references are incorporated herein by reference in their entirety 1 . kessler r c , berglund p , demler o , jin r , koretz d , merikangas k r et al . the epidemiology of major depressive disorder : results from the national comorbidity survey replication ( ncs - 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