FIELD OF THE INVENTION

The present invention relates to a system and method for assessment of and rehabilitation from peripheral nerve damage. More specifically, a unique stereognosis training system and methodology is disclosed. In a preferred embodiment, closed loop vagus nerve stimulation (CL VNS) is paired with assessment of and/or rehabilitation from tactile sensory dysfunction in a patient.

BACKGROUND OF THE INVENTION

Nerve damage is a debilitating neurological disorder that affects over one hundred million people worldwide. Most traumatic nerve injuries occur in the upper extremities, resulting in profound motor and sensory loss and chronic dysfunction of the arm and hand, which can severely reduce quality of life. Despite advances in surgical repair and scaffolding techniques that promote regeneration, long-term prognosis for most patients remains poor. There is a clear and present need to develop interventional strategies that target alternative mechanisms beyond nerve regeneration to restore function in patients after nerve injury.

Immediately after traumatic nerve damage, physical disconnection results in loss of motor and sensory function. This peripheral damage precipitates lasting changes throughout the central nervous system. One consequence of nerve disruption is a sudden and dramatic imbalance of synaptic activity in regions of the brain and spinal cord that control motor and sensory function. This transient perturbation generates profound, long-lasting reorganization as these central networks attempt to compensate for altered peripheral connectivity. Pioneering studies conducted over three decades ago demonstrated that synaptic connections from spared circuits strengthen and dominate central network activity in the absence of competition from the denervated circuits. Over time, injured axons in the damaged nerve sprout, regrow, and establish new connections with targets in the periphery. Despite reconnection of peripheral axons to end targets (e.g., reinnervated muscle fibers and sensory receptors), chronic dysfunction of motor control and sensation often persists. The inability for weakened reinnervated networks to overcome maladaptive central plasticity may contribute to lasting dysfunction.

Indirect evidence supports the role of insufficient central plasticity in chronic dysfunction following nerve injury. Compared to adults, children often display greater recovery despite a similar degree of reinnervation inaccuracies after nerve injury, an effect partially attributed to a greater capacity for plasticity in children. Moreover, imaging studies in humans reveal long-term changes in brain structure and network function that associate with functional impairment. If insufficient central plasticity after nerve damage contributes to chronic dysfunction after nerve damage, then techniques to enhance plasticity and reestablish central network signaling should improve function, even in the absence of changes to the damaged nerve itself.

Sensory impairment of the hand is common after peripheral nerve damage, stroke, spinal cord injury, multiple sclerosis and other neurological conditions. Impaired proprioception, stereognosis and tactile sensation are common after stroke and are associated with poor functional outcomes.

Stereognosis, also known as haptic perception or tactile gnosis, is the ability to perceive and recognize the form of an object, in the absence of visual and auditory information, by using tactile information to provide cues from texture, size, spatial properties, and temperature, etc. Astereognosis is the failure to identify or recognize objects by palpation in the absence of visual or auditory information, even though tactile, proprioceptive, and thermal sensations may be unaffected. Astereognosis can be caused by damage to the posterior association areas of the parietal, temporal, or occipital lobes, or the postcentral gyms of either hemisphere.

Tactile sensory function is driven by the somatosensory system which processes stimulus such as texture, temperature, pressure etc. The somatosensory system is a complex system of sensory receptors that respond to internal or external stimulus and send sensory information to the brain. Somatosensory receptors are classified into five primary receptor modalities, mechanoreceptors (touch), nociceptors (pain), thermoreceptors (temperature), proprioceptors (position and movement), and chemoreceptors (taste and smell). Proprioceptors are sensitive to the stretch and tension of muscles, tendons, and joints. These receptors allow us to calculate weight and movement.

Mechanoreceptors are found in the dermis or epidermis and are generally associated with the sensation of touch. Mechanoreceptors are broken up into four specialized sensory receptor sub-modalities, Meissner corpuscle, Pacinian corpuscles, Ruffini endings, and Merkel's disks. Meissner corpuscles are sensitive to fine tactile touch and are used to help determine texture. Pacinian corpuscles are sensitive to fast stimulus, such as a jolt, fluttering or vibrating sensations. Ruffini endings are sensitive to skin stretching or movement and give the feeling of object slippage and finger position and control. Merkel's disks are responsive to deep and slow pressure and help determine shapes and edges.

There is no established method to restore tactile sensation after peripheral nerve damage, stroke, spinal cord injury, multiple sclerosis and other neurological conditions. It is widely believed that patients receive inadequate sensory training to promote clinically significant recovery of sensory function. Daily sensory training with a therapist or clinician is prohibitively expensive and requires significant time to travel to and from the clinic.

U.S. Pat. No. 8,489,185 to Kilgard, et al. discloses timing control for paired plasticity. Kilgard discloses a closed loop timing control that is communicably connected to a neural stimulation system and a sensor.

U.S. Pat. No. 8,700,145 to Kilgard, et al. discloses methods, systems, and devices for pairing vagus nerve stimulation with motor therapy in stroke patients. Kilgard discloses a system that may be arranged in a closed loop fashion so that stimulation is automatic, or arranged in an open loop fashion where a therapist is required to intercede before stimulation.

U. S. Publication No. 2018/0221666 to Rennaker, I I, et al. discloses systems and methods for optimizing targeted neuroplasticity. Rennaker discloses a closed loop system for optimizing learning having a vagus nerve stimulator configured to stimulate a vagus nerve of a person with an electrical pulse train; a controller configured to alter one or more parameters of the electrical pulse train while maintaining other parameters of the electrical pulse train constant; and a monitoring device configured to monitor skill learning, where the controller receives feedback from the monitoring device and alters the parameters of the electrical pulse train of the vagus nerve stimulator.

SUMMARY OF THE INVENTION

Millions of people suffer from chronic problems caused by nerve damage, including loss of motor control and paresthesia. These symptoms often persist even after the reestablishment of nerve connectivity, suggesting that denervation alone cannot fully account for dysfunction. It is well-known that nerve damage generates maladaptive neuroplasticity in central networks attempting to compensate for the loss of peripheral connectivity. However, it is not known whether this pathological homeostasis is a critical feature responsible for the expression of peripheral neuropathy symptoms. If pathological central changes contribute to dysfunction, then it is conceived that reversing the changes in central networks should restore motor and sensory function even in the absence of peripheral changes.

Embodiments of this disclosure employ a strategy using brief bursts of closed-loop vagus nerve stimulation (CL-VNS) paired with a well-defined rehabilitation and/or regeneration to reverse the pathological plasticity caused by severe nerve damage. Reversal of aberrant central plasticity results in substantial recovery of motor and sensory function without changes in the nerve or muscle, such that plasticity in brain and spinal networks mediate recovery. Anatomical and physiological studies reveal that CL-VNS therapy drives extensive synaptic reorganization in central networks. Depletion of acetylcholine in the brain blocks plasticity and subsequently eliminates functional recovery. These findings demonstrate that manipulations to enhance plasticity in central networks improves motor and sensory recovery and define CL-VNS therapy as a novel and readily translatable therapy to restore function after nerve damage.

Rehabilitation for astereognosis and tactile sensory dysfunction in the clinic is expensive and produces insufficient numbers of trials per week. At home therapy can be effective with or without the addition of adjuvant therapies such as vagus nerve stimulation (VNS). The present invention allows patients to improve sensory and motor function through stereognosis practice enhanced by the use of mobile technology.

In one aspect of the invention, a method and system of treatment for peripheral nerve damage of a subject includes targeting reversal of maladaptive central network plasticity resulting from the peripheral nerve damage by enhancing plasticity in at least one of a motor or a sensory network of the subject. This treatment releases cortical acetylcholine during rehabilitative training to enhance plasticity in the motor or the sensory network.

In another aspect of the invention, a method and system for treatment for peripheral nerve damage applies a closed-loop vagus nerve stimulation during a rehabilitation of the damaged peripheral nerve wherein a vagus nerve stimulation signal is applied coincidentally with the rehabilitation. In yet another aspect, the rehabilitation comprises applying a stimulus to the sensory network of the subject.

In a further aspect of the invention, a method and system of treatment for peripheral nerve damage wherein a closed-loop vagus nerve stimulation is applied coincidentally upon completing a successful rehabilitative task. The successful rehabilitative task comprises specific movements or exercises during rehabilitation of the damaged peripheral nerve that meet specified quantitative or qualitative criteria pre-defined by a therapist or a measurement system. In one aspect, the method and system comprises pairing the step of applying a closed-loop vagus nerve stimulation with a regenerative therapy of the peripheral nerve damage wherein the regenerative therapy is as any strategy that promotes nerve regrowth or reinnervation. In another aspect, the regenerative therapy comprises at least one of surgical techniques, nerve conduits, treatment with growth factors, electrical stimulation of the damaged nerve, or pharmacological treatments.

A stereognosis training system for a patient is disclosed comprising a set of objects categorized by tactile sensory function wherein an obstruction visually obscures the set of objects from the patient. In an aspect of the present invention, an interactive device in the system is configured to select a test object, direct the patient to identify and grasp the test object from the set of objects and determine if the patent correctly identified and grasped the test object.

The set of objects of the present invention have many different features and aspects. For example, the set of objects have different feature sizes and/or different colors based on tactile sensory function. One important feature of the set of objects is that subsets of objects can be chosen to stimulate a particular tactile sensory function. In another aspect, the set of objects includes subsets of objects that stimulate a selected receptor group of the somatosensory system or multiple receptor groups of the somatosensory system. The receptor groups may be selected, for example, from cutaneous receptors, mechanoreceptors, nociceptors and thermoreceptors.

In another aspect, the particular tactile sensory functions include size, texture, heat conductance, temperature, weight, density, ductility, flexibility, yield-strength, compliance, homogeneity, vibration, friction, viscosity, stickiness, orientation stability and pain.

In other aspects, a subset of objects is chosen to have a common fixed feature. For example, the subset of objects have the same weight. In yet other aspects, a subset of objects have common varying features. For example, subsets of objects have varying ability to stimulate pain, have varying texture or have varying size. In yet other aspects, a subset of objects have one of more common fixed features for a set of tactile sensory functions while also having one or more common varying features for a different set of tactile sensory functions. For example, the subset of objects have the same size, shape and texture but vary in density.

In one embodiment of the stereognosis training system, an obstruction is provided that visually obscures the set of objects from the patient such as a blindfold. In other embodiments of the stereognosis training system, the obstruction that visually obscures the set of objects from the patient is a curtain or a solid obstruction between the patient's eyes and the set of objects. In each case, the patient's hands remain free to grasp the set of objects.

In another embodiment of the stereognosis training system, the obstruction that visually obscures the set of objects from the patient is a box comprising a set of solid walls, a floor and an opening or penetrable wall sufficient for a hand of the patient to be inserted into the box while obscuring the inside of the box from view of the patient.

In other embodiments, the stereognosis training system is configured to automatically distribute the set of objects on the floor of the box. For example, in one embodiment, the floor is sloping away from the penetrable wall so that the set of objects are distributed away from the penetrable wall so that the patient is better able to locate all of the blocks within the box. In another embodiment, the set of objects are automatically distributed with random placement inside the box utilizing, for example, a guide for loading and distributing the set of objects inside the box.

In another aspect of the present invention it is conceived that the interactive device be a smart phone or other computer device. There are many features and programmable aspects of smart phones and computer devices useful to the present invention. For example, the interactive device is further configured to visually identify a test object to the patient for the patient to retrieve from the box. In another aspect, the interactive device is configured to audibly identify a test object to the patient for the patient to retrieve from the box.

In yet another embodiment of the stereognosis training system, an attachment is included for holding the interactive device. Examples of an attachment may be a transparent shelf attached to the walls of the box or a transparent shelf attached to a self-supporting structure further attached to or sitting upon a desk on which the box is placed.

In another feature of the present invention, the interactive device is further configured to accept at least one of a screen tap or an audible sound to determine if the patient correctly identifies and grasps the test object. In a related feature, the interactive device is further configured to automatically determine if the patient correctly identifies and grasps the test object without requiring the patient to touch the interactive device or create an audible sound for the interactive device.

In other aspects of the present invention, the interactive device is further configured to determine an ability of the patient to correctly identify and grasp a test object in response to a request to retrieve the test object. In yet another aspect, the interactive device is further configured to determine an elapsed time from when the patient inserts their hand into the box in response to a request to retrieve a test object until when the patient correctly identifies and grasps the test object and to further record the elapsed time as the ability of the patient to correctly identify and grasp the test object. In a further aspect, the interactive device is configured to record the determination that the patient correctly identified and grasped the test object as a score and transmit the score to a second device.

In another embodiment, the system is configured to measure and record the interaction time that the patient interacts with the interactive device, for example when the patient touches the screen of the interactive device or moves their hand into or out of the field of view of a camera of the interactive device. Such a measure and recording of the interaction time may also provide a measure and recording of the rate of movement outside the box, and a measure and recording of when the hand moves from inside the box to the field of view of the camera. In yet another aspect, the system measures and records the speed of movement and hand position during object exploration.

In another embodiment of the present invention, the stereognosis training system further comprises a stimulation device for the patient wherein the stimulation device is communicatively attached to the interactive device. It is further conceived that the interactive device be configured to determine whether or not the patient's hand is inserted into the box and stimulates the patient with the stimulation device while the patient's hand is inserted into the box. In another aspect of the stimulation feature, the stimulation device is configured to stimulate the vagus nerve of the patient.

The present invention includes an embodiment for a method for improving tactile sensory function in a patient using a stereognosis training system for a patient having a set of objects categorized by tactile sensory function wherein an obstruction visually obscures the set of objects from the patient and having an interactive device in the system configured to select a test object, direct the patient to identify and grasp the test object from the set of objects and determine if the patent correctly identified and grasped the test object. The method for improving tactile sensory function comprises the step of assessing tactile recognition with the stereognosis training system to determine a set of tactile sensory deficits and a tactile sensory score. The method further comprises directing the patient to practice tactile recognition with the stereognosis training system based on the set of tactile sensory deficits.

In another embodiment, the method for improving tactile sensory function in a patient further comprises the steps of targeting a target sensory deficit in the set of tactile sensory deficits for rehabilitation based on the assessment; selecting a subset of the set of objects based on the target sensory deficit; directing the patient via the interactive device to retrieve at least one object from the subset of the set of objects; determining whether the patient retrieved the at least one object; and, determining a tactile function score based on whether the patient retrieved the at least one object.

In a further embodiment, the rehabilitation is adjusted by re-selecting the target sensory deficit for rehabilitation based on the tactile function score. Then the method for improving tactile sensory function is repeated beginning with the step of selecting a subset of the set of objects based on the (different) target sensory deficit.

Other embodiments of the method for improving tactile sensory function in a patient include recording minutes per day of practice with the stereognosis training system, plotting usage history of the stereognosis training system, tracking a history of tactile sensory scores, sending a reminder message to the patient reminding the patient to practice therapy, triggering simultaneous vagus nerve stimulation based on tactile sensor scores, quantifying hand position and speed of movement during haptic exploration and retrieval of the at least one object, providing instructions for using the stereognosis training system. In yet another embodiment a step of tracking a history of tactile sensory scores and determining improvement in tactile sensory function of the patient is included. In yet another embodiment, feedback is provided to the patient based on the improvement in tactile sensory function and the history of tactile sensory scores.

In another aspect of the present invention, the foregoing steps of the method for improving tactile sensory function and the various embodiments can be performed by the interactive device.

Another embodiment is conceived wherein the method for improving tactile sensory function comprises sensing the patient's hand position and causing a stimulator device to stimulate the vagus nerve of the patient based on the patient's hand position.

Objects used in stereognosis training are easily identified visually but challenging for a stroke or spinal cord injury patient to identify by touch alone. Object sets have been conceived that have different levels of difficulty for identification by touch (active exploration, stereognosis). The most distinct objects differ in multiple tactile sensory functions (dimensions). Difficult contrasts in stereognosis will be of a single tactile sensory function (dimension). For example, objects sets are conceived to challenge individual dimensions such as length, curvature, texture roughness and weight.

Object weight and center of gravity can be adjusted by producing hollow spaces in 3D printed objects or by adding weights to hollow spaces. Differences in weight and associated momentum change (during movements) will allow for mass estimation.

It is also conceived that placement of objects in specific locations would be advantageous for use and assessment of tactile memory. This becomes more important when a greater number of objects and greater level of difficulty in training is required.

For example, the objects in each set are a different color so it is easy to ensure the right objects for a particular tactile sensory function are in each set and returned there after each discrimination. Additionally, each object is optionally labeled with a number (that cannot be felt). Object sets of real world objects are also conceived such as a brush, a spoon, a set of keys, a tube of toothpaste or pair of eye glasses (for example). For severely impaired individuals, object sets are conceived to have an upward facing handle or putty (which adheres to the shape of the hand when grasping).

In addition to object sets, a system and method is disclosed for the patient to assign tasks, interact with an object set and complete tasks with the object set is conceived. For example, a box to obscure vision is provided without obscuring hand access wherein the box can be loaded from above so locations of the objects are not known at the beginning of each task.

An interactive device is integrated with the stereognosis training system to direct, monitor and provide feedback for patient activity. In an illustrative embodiment, a smart phone operating a programmed application uses an on-board camera to detect that the patient's hand has entered the box. The box (or another embodiment of stereognosis apparatus) is modified to hold the phone and angle the camera appropriately to make observations and allow for patient interaction. Such an event can be time-stamped and utilized to trigger time-coordinated external stimulation, such as vagus nerve stimulation. In one embodiment, an easily identifiable object is worn on the hand (for example colored bracelet) to confirm when the hand of the patient is engaged with the object set. In another embodiment, the pattern of the patient's active hand exploration is determined to analyze stimulation timing.

A clinical tool is conceived to confirm improvement in stereognosis and tactile sensory function by measuring individual dimensions of density, texture, compliance, shape, and so forth. Repeated testing and use of quantitative measures (average time required to identify objects with specific physical differences) will yield more reliable and more sensitive assessments of sensory function compared to current clinical methods.

The stereognosis system of the present invention provides a much needed improvement in the art of stereognosis assessment, rehabilitation and treatment in that: it is inexpensive from a hardware/software and treatment perspectives (no therapist is required), it is transportable with potentially lightweight construction and easy setup, it can provide challenging and directed practice for the patient in individual dimensions and in dual or multiple physical dimensions, it can utilize real world objects, the objects sets are color coded, the objects cover a wide range of difficulty to cover the wide range of impairment from easy to grasp objects to more difficult, it blocks visual cues during object exploration but provides clear visual feedback when needed using an interactive device, it can provide motivating encouragement and reminders through the interactive device, it is practical for home use and the treatment can be paired with external stimulation (for example vagus nerve stimulation) using the interactive device, it can reduce inactivity and contractures through grasp-search-release-repeat structure, it can detect and record history of practice time and assess progress in training, it is normed to real tactile sensory function data to set appropriately difficult tasks as the patient progresses, video and audio advice are provided to the patient to guide therapy based on performance.

A stereognosis training system comprises: a box with a hand access opening; a camera with a lens; a computing device with a video input coupled to the camera; an interior surface within the box that is reachable by a patient via the hand access opening; and a set of objects located within the box and on the interior surface; wherein at least one of the set of objects is optically tracked using the camera and the computing device to generate a time domain stream of data on at least one of location, rotation, and vibration for the at least one object of the object set. In a preferred embodiment, the computing device has a signal output to trigger a closed loop nerve stimulation to the patient. In a preferred embodiment, a mirror is optically coupled between the lens of the camera and the interior surface. In a preferred embodiment, the camera and the computing device are integrated components of a mobile device such as a smart phone, tablet or laptop. In a preferred embodiment, the mobile device is mechanically connected to an adaptor that is mechanically coupled to the enclosure to hold the mobile device and optically couple the lens of the camera to the mirror. In a preferred embodiment, the enclosure has an arm rest positioned beneath the hand access opening. Optionally, the arm rest can be removable. In a preferred embodiment, the enclosure has a chute to introduce the object set onto the interior surface.

A method of stereognosis training comprises: cuing a patient to identify and retrieve at least one member of an object set; and optically tracking a hand of the patient and the at least one member of the object set using computing device having a camera and a microprocessor to generate a time domain stream of data on the hand of the patient and the at least one member of the object set. In a preferred embodiment, the method comprises automatically triggering a vagus nerve stimulation (CL VNS) to the patient with a signal output from the computing device.

In a preferred embodiment, the system and method comprise providing within the box a set of objects (object set) where each of the objects is characterized by a different color. In this way, the camera and microprocessor can track each of the objects. Tracking can include recognizing and locating. This recognizing and locating by color can be verified based on the pixels that the camera associates with the color. In this way, each object can be identified by a color and a number of pixels. Each of the pixels can have three or four component intensities such as red, green, and blue, or cyan, magenta, yellow, and black.

In an alternative embodiment, the system and method comprise providing at least one fiducial on each of the plurality of objects that uniquely identifies each object and that indicates both scalar position of each object and directional orientation of each object. The use of at least one fiducial on each of the objects enables readily available augmented reality tools for mobile devices to generate a time domain stream of data on at least one of position, rotation, and vibration for each of the objects of the object set.

A nerve stimulation signal can be triggered based on the time domain stream of data meeting criterion associated with a performance threshold. The performance threshold can be moving the object that was cued and/or removing the object that was cued from the box (from the view of the camera). In a preferred embodiment, the signal is automatically handled in a closed loop from the microprocessor to an implanted vagus nerve stimulator via a network interface and a wireless local area network. The time domain stream of data can be reported to a remote device such as a clinical device monitored by a therapist or an application server that is connected to a database. The determination of whether the time domain stream of data meets the criterion associated with the performance threshold can be performed with software by the computing device and/or the remote device, without the need for a therapist or clinician. This is an important advantage of the invention because obviating the need for a therapist or clinician dramatically reduces costs. It also makes the determination more objective and less subjective.

In an embodiment of the present invention, the computer is configured to detect and measure hand insertion into the stereognosis system. The tablet computer also detects and measures duration times for a patient searching for an object and/or retrieving the object from the box.

It is an object of the present invention to engage the patient in practice of stereognosis leading to rehabilitation of tactile sensory function. In so doing, an interactive device records minutes of use per day, number of attempts and number of successes.

