BY MEANS OF THE APPLICATION OF A COMBINATION OF STIMULI

OF DIFFERENT TYPE AND THE STUDY OF CORRESPONDING

REACTIONS

The present invention relates to a device for the analysis of the central nervous system by means of the application of a combination of stimuli of different type and the study of corresponding reactions.

More in detail, the invention relates to a device of the said kind, deriving from the need for studying through quantification, analysis and reproducibility methods some brain functions, in particular visual and visuomotor functions and the coordination of eye and hand movements during the execution of some specific tasks, by means of the registration of the movements of the eyes and at the same time the registration of the movements of the limbs, with particular reference to the upper limbs, after application of stimuli of different nature (visual, auditive, tactile and interferential) combined with each other, both under experimental conditions (preset experimental settings using previously validated visual, auditive, tactile and interferential stimuli), and under natural conditions, through the exploration of complex scenes (video, pictures, 3D) or during movement.

It is known that the system of vision constitutes the most important provider of senses to the brain. In fact, the human brain work, for more than 70%, in the elaboration of visual information, i.e. in processes regarding vision and its elaboration. This is particularly true when considering the, wide portion of cerebral cortex (from the occipital to the frontal areas) involved in the processing and elaboration of visual inputs.

In the last years, important progress was achieved in the comprehension of how the system of vision is organised and how it interacts with the other cerebral systems. The previous models based on block module schemes were withdrawn, and it was subsequently understood that the vision operates through multiple systems, in which it is possible to identify different "streams" linking to one another dynamically. Through this complex interaction, the brain can elaborate a visual signal and interpret it according to the internal conditions of the moment or the conditions of the environment and keep control of actions in correlation with the correct representation of the environment. The visual information is processed relatively slowly by the cortex areas of vision, therefore the system must filter the redundant information and information that are useless in that moment coming from the environment. Such a filtering requires that the system select a specific number (generally a definite number) of important perceptive stimuli. The process of attention can be considered as a macroscopic filter allowing for focusing our interest over specific areas of the surrounding environment. Neurophysiologic and psychophysical researches highlighted that the visual exploration of a picture does not occurs all together, but through small "quanta" of space and time. This mechanism occurs through a sequence of small fixations concentrating in the regions of interest of the picture itself and allowing for the foveation (foveal vision) of the detail of interest. However, during the visual "scanning", eyes move continuously; these are micromovements of fixation that do not reach a level of consciousness, but they are fundamental for the visual perception. The best visual perception occurs when a picture, or part of it, is kept fixed on an area of the retina called fovea. Different classes of eye movements are needed to keep a picture on the retina when moving the head or the picture or to pointing again the glaze on an object of interest. Form a functional point of view, two higher classes of eye movements are required for man: those stabilising the glaze and those moving the glaze. Under natural conditions, all different eye movements allow for the exploration of the visual scene. The sequence of fixations and saccades (rapid movements of displacement of the eyes from one point of interest to another) during the visual exploration, can be indicative of different cognitive processes; the use of standardised protocols with preset space and time variables allows for the study of specific cognitive processes, such as for example perception, attention, memory, preference, decision, choice.

The quantification of eye movements in physiological and pathological conditions can provide information on the functioning of the cortical cerebral motor program and on its control performed by subcortical structures.

From a dynamic point of view, a method for detecting different classes of eye movements is based on the identification of its slow and fast components by means of suitable detection systems.

As already anticipated, saccades and the nystagmus quick phase are the fastest eye movements and are needed for accelerating and decelerating the eye in order to modify the position of the glaze and put a new object of interest on the fovea. Saccadic movements include voluntary saccades, in response to visual, verbal, auditive or memory stimuli, and involuntary saccades, in response to visual stimuli of the peripheral retina or sounds, the fast phase of the vestibular and optokinetic nystagmus and fast eye movements occurring at sleeping (REM phase). The characteristic parameters of saccadic movements comprise: latency, speed, amplitude, duration and gain. The saccadic latency is the time interval passing from the appearance of the object of interest and the beginning of saccadic movement. Saccadic speed is the speed of execution of the saccade. Saccadic amplitude is the difference between the position of the eye at the beginning of the saccade and the position it has at the end of the saccadic impulse. Saccadic duration is the time interval passing from the beginning and the end of the saccadic movement. Saccadic eye movements show a correlation between their duration D (seconds) and their top speed Vp (degrees/second), correlation conventionally expressed as a function of the amplitude A (degrees). The saccadic gain, expressed as the ratio between the amplitude of the saccade and the amplitude of the target, estimate the saccadic accuracy.

On the other side, the three principal kind of movements of fixation of vision are tremor, drifts and microsaccades. Tremor, also called physiological nystagmus, is a movement of the eyes similar to a wave, aperiodical, with a frequency of about 90 Hz, independent in the two eyes. Drifts are slow eye movements, occurring simultaneously with tremor, occurring during intervals between microsaccades. Drifts can be both conjugated and non-conjugated. Microsaccades are small and quick eye movements, similar to a jump, occurring during voluntary fixation.

With reference to the systems for eye movement detecting and tracking, shortly EyeTracking, with reference to the prior art they can be divided essentially into two classes: 1) systems detecting eye movements on the base of the position it has with respect to the head, and 2) systems monitoring the position of the glaze in the space or "point of glaze".

Roughly 4 classes of instruments for measuring eye movements exist: electro-oculography (EOG) having electrodes in contact with the skin, intraocular contact lenses or search coil, video-oculography (VOG) and pupillary and corneal double reflection video-based systems using infrared CCD cameras. The firsts are contact systems, according to which the relative position of the eye with respect to the head is detected, the lasts are considered remote systems and evaluate the point of glaze in the space; they require the forced fixing of the head or the use of a head tracker in order to evaluate the exact position of the eye with respect to the head, but have the great advantage that they are not invasive and are accurate (about 1 ° of visual angle for 30° of visual range).

At present interactive multi-stimuli systems are not known, being capable of analysing a specific behaviour and obtaining from it information that can be useful to predict a future behaviour, thus allowing to modify the scene contingently and to interactively module the future movement.

In the light of the above, it is evident the need for an interactive multi-stimuli system responding to the need for studying and modelling, by testing the system of vision, the physio-critical behaviours of the central nervous system, with the aim of: making diagnosis; measuring the attention capability, learning capability memory and choice (decision) of normal subjects, for diagnosis and research; evaluating the attitudinal capabilities; providing an instrument of self-training in the video-spatial and cognitive rehabilitation.

In this context is positioned the solution according to the present invention, with the aim of providing for a device combining, in a multi- stimuli platform, a database of protocols and a system of analysis capable of managing the diagnostic cycle of a patient, in a closed way, by testing the system of vision and the coordination of eyes and upper limbs. In particular, the device according to the present invention provides for the definition and configuration of different stimuli (visual, auditive, tactile and interactive stimuli), such stimuli being specific for testing some functions of the nervous system (oculomotor, attentive, work memory, long-term memory, functional tasks), each test providing for some specific pointers, capable to give a specific vision of the tested function. The combination of the pointers allows depicting the model of the patient central nervous system and its state with reference to a group of healthy subjects.

These and other results are achieved according to the prese nt invention by proposing a device capable to define in an open manner its own tasks, choosing amongst those described in the literature and aiming to the verifying of specific clinical states.

An aim of the present invention is therefore that of realising a device allowing for overcoming the limits of the solutions according to the prior art and achieving the previously described technical results. A further aim of the invention is that said device can be realised with substantially reduced costs, as far as both the production costs and the operative costs is concerned.

Not last aim of the invention is that of realising a device that is 5 substantially simple, safe and reliable.

It is therefore a specific object of the present invention a device for the analysis of the central nervous system by means of the application of stimuli on a patient and the study of the reaction of the same patient, comprising a plurality of multi-sensorial stimulus apparatuses and ao plurality of reaction data acquisition apparatuses, combined together in order to realise a stimulus and data acquisition interface by means of a management and analysis interface and arranged on a support interface, wherein said data acquisition apparatuses comprise means for detecting the movements of the eyes and means for detecting the movements of the5 limbs.

According to the invention, said management and analysis interface further comprises means for computing the collected reaction data controlling said multi-sensorial stimulus apparatuses.

always according to the present invention, said means for detecting o the movements of the limbs can be linked to a force feedback device.

Moreover, according to the invention, said stimulus and data acquisition interface further comprises a stimuli protocols database.

Furthermore, always according to the invention, said management and analysis interface comprises a system of algorithms in order to extract5 the important parameters derived by the analysis, a database of stimuli management protocols and a database of cases modulating a high level analytic response.

Moreover, according to the invention, said support structure comprises a metal platform, transportable and adjustable and electrically o insulated, composed of an ergonomic module inside which the patient puts his head, an adjustment module for housing said data acquisition apparatuses, and a housing module for said multi-sensorial stimuli apparatuses.

It is evident the efficacy of the device of the present invention,5 which can find application in different fields, such as in particular in the diagnostic and therapeutic field, since it constitutes a non invasive aid that can support in the diagnosis of diseases of the brain or the eyes. In fact, the performing of validated tasks and the acquisition of reference data for eye movement or for the response required from a subject (for example the movement of a hand handling a joystick or clicking on a button) for each task, allows to quantify and repeat a single test. This can be used also for longitudinal studies not only evaluating the evolution of pathology, but also the response to a therapy.

The device can also be used in the field of rehabilitation, since it allows for using a user-friendly system that can be also be applied through a connection system between the location of a tutor and a remote location (the house of a patient). Thus, the patient can connect to the system by means of a keyword and performing the established tests and can also have a direct feed-back from the tutor, receiving explanations and evaluations. His data can further be input in the system database and be used for remote controls (follow-up) or for subsequent scientific applications.

The device of the invention provides for the possibility of using multisensory interferences for cognitive studies, for studies on basic or psyco-attitudinal neuroscience. In this application the subject performs a visual task or simply explores a scene and when performing the task some interferences are introduced of an acoustic, TMS or motor kind (selecting a button and/or operating on a force feedback device such as for example a joystick or another manual instrument, during the tasks of coordination between eye and hands). This multisensory interferential approach can find application in psycoattitudinal tests, for example to test driving attitude or in other situations in which a certain ability is required of the attentive shift or when it is required to keep the attention by inhibiting any shift of the attention.

The invention will now be described for illustrative, ma non limitative purposes, with reference in particular to some examples and to the enclosed drawings, wherein:

- figure 1 shows a scheme of the base architecture of a device according to the present invention,

- figure 2 shows a scheme of the dependencies of the modules of the device of figure 1,

- figure 3 shows a perspective view of the portion of the device specific for the housing of the user inside the support structure of a device according to the present invention, - figure 4 shows a perspective view of the portion of the device specific for the housing of the eye tracking apparatus inside the support structure of the device of figure 3,

- figure 5 shows a perspective view of the portion of the device specific for the housing of the visual stimuli apparatus inside the support structure of the device of figure 3,

- figure 6 shows a perspective view of the whole support structure of the device of figure 3,

- figure 7 shows a scheme of the architecture of the operative system of a device according to the present invention,

- figure 8 shows a view of a user interface for the generation and/or modification of stimuli generated by a device according to the present invention,

- figure 9 shows a view of a user interface for the generation and/or modification of the "gaze contingent" of a device according to the present invention,

- figure 10 shows a view of a user interface for the analysis of the acquisition signal of a device according to the present invention,

- figure 11 shows a view of a user interface for the analysis of saccades of a device according to the present invention,

- figure 12 shows a TMT (Trail Making Test) report obtained by means of the device according to the present invention,

- figure 13 shows a diagram of the square waves (Square jark) obtained as response from a patient undergoing an analysis performed by the device according to the present invention,

- figure 14 shows a trail making test (TMT) diagram obtained as response from a patient undergoing an analysis performed by the device according to the present invention,

- figure 15 shows a diagram of the map of transitions obtained as response from a patient undergoing an analysis performed by the device according to the present invention,

- figure 16 shows a diagram of the reference map of transitions,

- figure 17 shows a view of a user interface for the generation and or modification of stimuli constituted by timerised pictures sequences with an established frequency of the device according to the present invention, and

- figure 18 shows a view of a user interface for visualising the direction towards which the patient moves its gaze.

The key features of the device according to the present invention comprise firstly the possibility to produce stimuli (visual, auditive, tactile, interferential) on different apparatuses (TMS, Video, Sound) and with different modalities (inhibiting, exciting). To this end, the system exploits a database of protocols (stimulus mode) to generate a series of stimuli with time.

Other key features of the device are: the possibility of generating stimuli in an adaptive and real time manner; the possibility of collecting the signal and extracting the characteristic parameters; the possibility of analysing the characteristic parameters and providing an analytic response and a model of functions serving as an example of a behaviour.

The bases of the system are the patient work memory excitation and the detection of its reactions and the possibility of modifying interactively and real time (gaze contingent) the visual and tactile stimulus on the base of the patient's glaze and the dynamic features of the eye- hand movements. Interactivity does not relates only to the visual scene, that can be changed on the base of the dynamic fcharacteristics of eye movement, but also by means of a force feedback device operated by a joystick or other manual instrument, during the task of coordination between eye and hand. Such an analysis mode allows for detecting the level of attention (for civil and/or military purposes), evaluating the exploration capabilities (for diagnostic purposes), train the user (for rehabilitative purposes). Therefore, the device needs real time reactive protocols allowing for generating appropriate stimuli in order to memorise the patient's significant characteristics.

The device can be used mainly in diagnostic and therapeutic applications, since its aim is that of providing:

- a database of diagnostic protocols (for the evaluation of motion or cognitive functions, such as for example video-space attention) which can be implemented on the base of the validation of protocols and/or on the base of diagnostic and research needs. In particular, the device is intended for the developing and implementation of protocols making possible to evaluate the interaction between video-space attention and motion program during the video-space exploration;

- a database of functions for the analysis of oculo-motor parameters and a database of functions for the analysis of the dynamics of the inspected limb. It is a acquisition of pointers offering parameters of the tested function that . can be quantified and reproduced. The combination of pointers allows describing the model on the investigated cerebral function in a specific patient and its position with reference to healthy subjects. Moreover, the possibility of having quantitative and reproducible indicators allows for tracking the pathological evolution with time of a disease and the response to a specific therapy;

- a series of ergonomic complimentary devices (devices for housing the head of the patient and the used apparatuses, sensors of strength, accelerometers, sound or rhythmic devices, devices for the application of acoustic interferences and trans-cranial magnetic stimulation "TMS").

With reference to figures 1 and 2, the architecture of the device is divided in two main sub-systems: the stimulus and data acquisition interface A, the management and analyse interface B.

The stimulus and data acquisition interface, represented in the figures by the block A, is involved in receiving the patient in an ergonomic system, collecting eye tracking and manual response (joystick and/or keyboard) data and generating physical stimuli. Sue h interface is constituted by hardware elements such as: a support structure 10 for adjusting the position of the stimuli generating and response collecting and for insulating the patient (in the following shown in detail with reference to figures 3-6), a acquisition system 11 (which, in particular, can comprise an infrared camera 110 model ASL 500 and a joystick or other manual instrument (not shown) connected to a control apparatus 111 of the acquisition system) and a stimuli generating system 12 (video 120, audio 121 and apparatus 122 for trans-cranial magnetic stimulation TMS (directly applied on the patient's skull 100) linked to a control apparatus 123 of the stimuli generating system).

With reference to figures 3-6, the support structure is composed of a platform 60 realised of metal, transportable and adjustable and electrically insulated, suitable for housing the stimuli generating and response acquisition instruments. It is composed of an ergonomic module 30 inside which the patient puts his head, an adjustment module 40 suitable for housing an eye tracking apparatus, and a housing module 50 for the visual stimulation apparatus.

In particular, the ergonomic module 30 comprises all the elements needed for housing the patient, in particular a structure composed of a chin rest 31 , front rest 32, hand supports 33, an element 34 that can be adjusted in height and depth for the housing of an orthodontic bite and a connection element 35 for coupling with an adjustment module 40.

In its turn, the adjustment module 40 comprises a support 41 for the eye tracking apparatus, connected to a spherical knuckle joint 42 for the moving of the support 41 on three orthogonal axes x, y, z, a system of threaded bars 43 connected to elements 44 provided with corresponding threaded housings, for moving on the axes x and y, a handle 45 for controlling the moving on axis x, two handles 46 for controlling the moving on axis y and a passage 47 for the connection cables of the eye tracking apparatus.

The housing module 50 of the visual stimulation apparatus comprises a plurality of articulated support clamps 51 that can be used independently from one another, for example for the use of stimuli on curved panels, a mechanism 52 for adjusting the position of the upper clamps 51 along the axis y, a system of threaded bars 53 connected to elements 54 provided with corresponding threaded housings, for moving the position of the lower clamps 51 along the axis y, two handles 56 for controlling the moving on the axis y and a passage 57 for the connection cables of the visual stimulation apparatus.

All the modules are provided with adjusting mechanisms 61 for the height (axis z), foldable supports 62, bars 63 for connecting the modules having variable sizes.

The whole support structure is closed in a dark room, partially soundproof and painted with non reflective paint for avoiding external interferences.

As already seen with reference to figure 1 , the system for response acquisition 11 exploits an infrared camera 110 to detect the glaze and a controller 111 to collect the signal. Moreover, the system for response acquisition 11 comprises a software system for the setting of parameters and the acquisition of data. The infrared camera 110 exploits, for illustrative non limitative purposes, an infrared camera mo del ASL500 based on the reflection of the pupil and the cornea or as an alternative a EOG at 100Hz. The system can be widened by developing a acquisition driver able to extract real time the following characteristics: coordinate x, coordinate y, pupil size, time.

The stimuli generating system 12 is composed of: a visual stimulation apparatus (video 120), a stereo sound stimulation apparatus stereo (audio .121), an apparatus 122 for trans-cranial magnetic stimulation (TMS).

The trans-cranial magnetic stimulation apparatus 122 makes use of a temporised impulse controller by means of a parallel connector 25 pin standard producing a continuous or alternate electromagnetic impulse on the area where the magnet is applied (Barker AT, Jalinous R, Freeston IL. (May 1985). "Non-invasive magnetic stimulation of human motor cortex". The Lancet 1 (8437): 1106-1107. doi:10.1016/S0140-6736(85)92413-4. PMID 2860322).

With reference to figure 7, the management and analysis interface B is composed of a system of algoritms to obtain the significati parameters (latency, time, saccade, peak velocity, ROI), a database of protocols 71 to manage the stimulus and a database of cases 72 to offer a high level analytic response.

Always with reference to figure 7, the stimuli generating system 12 comprises a stimuli generating subsystem 73 providing for the software management of all the auditive, visual and magnetic interference stimuli the 100 undergoes. The stimuli generating subsystem 73 is connected to a stimulus interface 74, composed of some models such as drivers for audio, video or magnetic reproduction.

The stimuli generating subsystem 73 operates de facto as a multimedia player generating one or more stimuli stored in the database 72 and defined as templates.

Figure 8 shows an example of user interface for the generation and/or the modification of stimuli generated by a device according to the present invention. The frame 81 shows the features of the monitor to be used for the visualisation and execution of the test: distance, width, height and resolution. The frame 82 allows for selecting some "physical" properties of the point, such as: size (in pixels), colour, position on the display (expressed in degrees), the number of point to be inserted, the reference point.

The reference point is an essential parameter for the subsequent analysis of the collected data because it indicates which point must be used as a reference signal in the analysis of the collected data. It is obviously fundamental in the case of the contemporary presence of different points on the scene. In case only one point is present it is a reference point by default. The point has a further feature, which can be selected from .three different typologies proposed by the frame 83.

A dynamic point is a point that, once it is appeared on the display, is destined, after a preset time, to disappear from the scene. A dynamic point has a plurality of features that can be set by use of the frame 84: the main feature is the time of permanency on the scene (TIME ON), to which other features can be associated making it behave in different ways during the execution of the test: Blank before (option according to which, before the visualisation of the point, all the static points on the display are removed), Return Point (option according to which, after visualisation for the time TIME ON, the point automatically moves to the center of the display to remain there for the time indicated in the field Return Point), Flash Point (option according to which the point appears in the indicated point for the time set in the field FLASH ON, then goes off for the time set in the field FLASH OFF; the series of lighting on and off being performed for a number of repetitions indicated in the field N° of FLASH (with a maximum preset value of 5). These last three features of the point are optional. By default, the point disappears from the display after the time indicated in the field of the parameter TIME ON.

The static point, second option of the frame 83, has a substantial difference with respect to the dynamic point: it does not have a duration time, practically it remains on the display until the occurrence of a "Blank" event making it disappear. The limit of static points that can be managed on the scene is preset at 100. The appearing of a static point on the display implies a time of 20ms during which no other events can occur on the scene (appearing of other dynamic or static points, Blank event).

The Blank, third option of the frame 83, is a modality allowing for the cleaning of the whole display. This means that all the static points on the display are removed. Its minimum duration is 20ms, but, in this case, it can be set, by filling in the field of the frame 85, to maintain the scene without any point for a set time.

By means of the user interface shown in figure 8 it is also possible to set further features of the template, such as: TMS impulse, Cycle Test, View All Points, Random Sequence Allowed, Point in Movement.

If the value TMS impulse is selected in frame 86 when inserting appoint on the scene, when the point appears on the display it will correspond to a TMS impulse. The option Cycle Test, in frame 87, indicates the number of repetitions o f .the points introduced in the te mplate. If the te mplate is composed of 10 points, and the parameter Cycle Test is set at 2, the effective test is of 20 points (2 cycles of the list of points in the template).

The option View All Points, always in frame 87, if selected, is such that on the preview minidisplay 88 all the points comprised in the template are shown; otherwise only the last inserted point will be shown.

The option Random Sequence Allowed, also in the frame 87, if selected allows using the RANDOM function during the execution of the test, so to randomly generate the points in the template.

Lastly, the frame 89 contains the option for generating points in motion, to define these points it is needed to set the start position and the end position. The features of the moving point are the same of the dynamic point. The moving point speed is 307s.

In some cases, stimuli can react as a function of the patient's glaze (gaze contingent). In particular, the activation of specific sounds, pictures or modification of the same pict ures can be driven by defining some regions of interest and the consequent action to be activated. Table 1 shows a small extract of commands that can be activated.

Table 1

A specific description, with reference to figure 9, is deserved by the component "gaze contingent", which can show only a little portion of the picture centred on the point (x,y) the patient is looking at. Such a task can inhibit the peripheral vision, so to compel the user to explore a scene in such a way that he cannot use the peripheral attention (covert attention). The system further allows, by means of a protocol defined on a file, for activating some actions (sound, picture motion) when the user looks at some regions or after a set time passed.

With reference to figure 1 7, a user interface for the generation and/or the modification of stimuli is shown constituted by sequences of temporised pictures having a set frequency. The general concept on which this function is based is that a visual test lasts a time t composed of time slots repres ented by the graded bar s hown high on the mask. Three different time zoom levels are foreseen: Minutes/Seconds/20th of

Seconds, (the active level is indicated by the parameter Zoom Level). This means that, depending on the selected time zoom, every time slot of the bar represents 1 minute, 1 second or 0,20 seconds. However it is also possible to use time zoom levels smaller than a 0,20 seconds.

In figure 17, time scale is indicated by Zoom Level and each slot is represented as empty because it does not contain any element at any level of depth. To generate a template, once the general required information are given, the file Object will be used for introducing visual objects in the template.

In figure 17 the insertion of a visual object (local neutral smile) in a preset moment in the template (Time Template: 00:00,100, Zoom level: 20ms - 5° slot) in a set position x/y (250/250) is shown. The object remains on display for 200ms (Duration) and the TMS is not on (tms = off) at the same time neither a sound beep is emitted (beep =off). Using Insert object the operation is confirmed.

The proof of the insertion is shown in figure 17, wherein the slot contains the character "*" to indicate the start of the object visualisation and the subsequent slots contain the character "-" to indicate its permanence on the display.

To introduce another visual object it is sufficient to repeat the above described procedure by selecting the moment on the time scale for introducing the picture. It is always possible to go up of time level using the upward blue arrow positioned on the same bar.

With reference to figure 18, according to the present invention the system allows the operator to control the patient in real time during the execution of the experiment, both by using a camera shooting the scene but in particular by observing where the patient points the gaze (frame high on the right of figure 18 where the position of the patient's gaze during the experiment is shown.

In the first frame on top of the mask the typical information about the environment where the test is performed are reported. These data cannot be modified, as neither the name nor the description of the template. On the contrary it is needed t ogive a name to the undergoing test, its type (useful to group together the performed tests), the needed annotations. The values assigned to Display Time, Fixation, Exploration, Luminance and Eye are stored for future implementations. Repetition and Frequence show preset values in the step of template generation and cannot be modified during the execution of the test. It is further shown the indication of the presence or not of a joystick for the patient.

In the frame Patient Information the anagraphic information of the patient undergoing the test must be input.

Using the icon representing dices it is possible to activate the random sequence function. Such a function allows for randomly change the sequence of points presented during the visual test.

The lower frame allows selecting the following functions.

1) Runtime pupil diameter

It allows for visualising in the frame named pupil diameter the patient's pupil size during the execution of the test. The value is represented in digital and graphical mode. In order to limit the introduction of latencies during the execution of the test, such a value is represented for any 10 samplings.

2) Patient gaze on 2nd monitor

It allows for visualising on the side of the operator, in the frame high on the right, the position of the patient's pupil during the execution of the test. In order to limit the introduction of latencies during the execution of the test, such a value is represented for any 10 samplings.

3) View test on 2nd monitor

It allows for visualising on the side of the operator, in the frame high on the right, the monitor on the sideof the patient.

By making again reference to figure 7, the analysis subsystem 75 is a module that can analyse the signal coming from the acquisition interface 11 and provides for the following algorithms: analysis of the signal (the relative analysis interface is shown in figure 10); analysis of saccades and extraction of the main parameters (time, amplitude, gain, peak velocity, latency) (the relative analysis interface is shown in figure 11); application of a filter; analysis of the fixations and extraction of the main parameters (number of fixations, dispersion, time of fixation, points of fixation); analysis of the regions of interest (ROI) (points belonging to the ROIs, average time between ROIs, dispersion of fixations out of the ROIs ₁ inlet direction, outlet direction, average crossing error).

Analysis algorithms of the signal aiming at extracting saccades (Fischer, B., Biscaldi, M., and Otto, P.1993. Saccadic eye movements of dyslexic adults. Neuropsychologia, Vol. 31 , No 9, pp. 887-906) and fixations (Widdel, H. (1984). Operational problems in analysing eye movements. In A. G. Gale & F. Johnson (Eds.), Theoretical and Applied Aspects of Eye Movement Research. North-Holland: Elsevier Science Publishers B.V.) are based on typical parameters of velocity of saccades and minimum time of a fixation (Leigh R J, Zee D S. The neurology of eye movements. 4th ed. Oxford University Press. :598-725. (2006)).

The algorithm for extracting the saccades can extract: average velocity of the saccade, peak velocity, start time of the saccade and end time of the saccade, acceleration, deceleration, amplitude, time, eye saccadic movement trajectories, error α (defined as the module of the difference between the amplitude expressed in degrees of the target T and the amplitude of the saccade A, α=|T-A|), gain of the movement with respect to a target and latency of the saccade with respect to the presentation of a stimulus.

The algorithm for extracting the fixations can extract: centroid of the fixation, dispersion, time and invalid points.

The indicators for the saccadic oscillations are frequency, amplitude, velocity, time of the saccadic oscillation.

The indicators for micromovements are amplitude, velocity, time of the micromovement.

Other parameters are instead calculated as a function of the following formulas:

gain = saccade amplitude / amplitude of the stimulus

delay = |stimulus starting time -saccade starting time|

points belonging to the roi = {(x,y) ε fl} wherein fl=region circumscribed by a polygon

dispersion of fixations out of the ROI = min(δ ((Xf.yt) - (xa.ya)))

wherein (X _f ,y _f ) are the coordinates of the centroid of the fixation and (xa.ya) those of the center of the ROI and wherein δ is the euclidean distance direction = arctan((y _s - ya)/(x _s - XyO) = angle subtended by the entry saccade with respect to the center of the ROI

direction error = |entry direction - expected direction!

For saccades, beyond the indicators relating to the parameters of the movement dynamics, the correlations between the different dynamic parameters are calculated, such as for example the correlation between main sequence peak velocity-amplitude and time-amplitude, the functions representing the above indicated correlations are plotted on display. This allows for defining the motor features of the saccadic movements under normal and pathological conditions, in particular, the correlation peak velocity - average velocity allows for identifying morphologic features of the movements.

The final analysis is performer by means of a statistic tool that can compare the above described reference parameters with a database of healthy subjects. The final report is composed of a medical report that can be personalised, comparing the data obtained from the patient with the data of reference.

In some cases, such as for example the task trial making (Reitan RM (1958): validity of the Trail Making Test as indicator of organic brain damage. Percept Mot Skills;8:271-276), requiring for a multidimensional vision, it is possible to extract the scanpath obtained from a patient, such as for example that shown with reference to figure 12.

Lastly, the trail making test also requires the developing of a specific algorithm, capable of calculating the score of performing the task correctly. The algorithm gives a score of 1 for each correctly sampling made during the sequence 1-A-2-B-3-C-4-D-5-E.

Lastly, for the comparation of bidimensional video space explorations, the system can extract a map of transitions, that can compare the exploration of a healthy subject with the control values (reference can be made to figure 15, showing the map of transitions obtained for a patient and to figure 16, showing the control map of transitions). The map of transitions is defined as the probability of passing from a region to another. Regions are defined by dividing the picture in 5x5 squares for a total of 25 per 25 possible transitions.

Also with reference to figure 7, the mo delling subsystem 76 is composed of a graphical interface on the side of the operator for modelling the stimulus (pre-processing) and comparing obtained data and the performed analysis (post-processing) with the reference models and cases.

The stimulus modelling sub system uses graphical tools that can draw some geometric shapes, import videos, sounds and define regions of interest (ROI). Oncethey are defined, the objects are integrated by means of a designer that can define the timing or activation of stimuli on the base of the ROI.

The database of stimuli 72 contains the complete list of basic stimuli able to reproduce the stimulus. Some basic stimuli are shown in the following Table 2.

Table 2

The database of protocols 71 contains the temporised sequence of stimuli to be reproduced.

The database of models 77 contains the complete list of cases or saccadic models organised according to the type of protocol used for comparing the performed analysis.

Example 1. Sceneries and cases of system testing. Healthy patients

The system was tested on 40 healthy patients. Protocols GAP and antisaccade where used. The following table 3 shows the obtained data.

Table 3

Obtained data are consistent with those reported in literature.

Example 2. Sceneries and cases of system testing. Patients Affected by cerebellar atrophy of type 2

The s ystem was tested on six patien ts affected by SCA2 (rare disease). Protocols GAP and Antisaccade where used. The following table 4 shows the obtained data.

Table 4 In this case also the obtained data are consistent with those reported in literature.

Example 3. Sceneries and cases of system testing. Patient Affected by cerebellar atrophy of type 2 sguare wave jarks

The system was tested on a patient affected by SCA2 (rare disease) using potocols GAP and Antisaccade. Figure 13 and the following table 5 show the results of the analysis of the square waves, characteristic of saccadic intrusions. Table 5

Example 4. Sceneries and cases of system testing. Healthy patients and Patients Affected by cerebellar atrophy of type 2 - protocol TMT

The system was tested on 30 healthy patients and the protocol TMT was applied (Reitan RM (1958): validity of the Trail Making Test as indicator of organic brain damage. Percept Mot Skills;8:271-276). Th e results are shown with reference to figure 10. The system allowed for detecting that the direction error decreases during the execution of the test, confirming the patient's learning capabilities.

The device of the present invention was described with reference to a purely exemplificative embodiment. Any development of the device is possible and falls within the same inventive concept of the present invention. As an example, it is possible to provide for the integration of the device with systems for the detection of the movement of the head (EOG- differential; camera systems), in order to improve the system for response signal acquisition.

The present invention was described for illustrative non limitative purposes, according to its preferred embodiments, but it ha sto be understood that any variation and/or modification can be made by the skilled in the art without for this reason escape the pertaining scope of protection, as defined by the enclosed claims.