Advances in Pediatric Neurorehabilitation: What Works in Vision Rehabilitation?
Glen Prusky, Ph.D.
April 2016, Course, Blythedale Children’s Hospital, Valhalla, NY, USA
Visual dysfunction as the result of developmental disorders or acquired brain injury is a major source of disability in children. There are limited means to reliably measure visual dysfunction, or to treat visual dysfunction in children. At present, the only visual assessment procedure that has attained a Good Quality rating for Body-of-Evidence, and is Strongly Recommended for verbal children, is a modified Snellen chart using child-friendly, standardized ototypes. There is no methodology that meets these criteria for non-verbal children. For visual dysfunction, the only childhood visual disease that has a valid treatment protocol is amblyopia: Uncorrectable decrease in vision in one or both eyes due to altered visual experience early in life, affecting 2%-4% of the population. The only treatment for amblyopia that meets a Good Quality rating for Body-of-Evidence, and is Strongly Recommended is intermittent patching of the amblyopic eye before the age of 10. Promising assessment and treatment paradigms are in the pipeline for non-verbal children, and for brain injured children with cerebral visual impairment.
Translating Visual Neuroscience into Clinical Practice
Glen Prusky, Ph.D.
August 2016, Research Seminar, Canadian Centre for Behavioural Neuroscience, Lethbridge, Alberta, Canada
My lab has made progress in translating basic visual science into clinical application on 2 fronts. First, we have modified a methodology to measure spatial visual thresholds in rodents (OptoMotry) for use in non-verbal humans (OptokineSys) who cannot participate in traditional visual assessments. OptokineSys utilizes eye-tracking technology to measure smooth eye movements while a subject is reflexively following moving visual scenes. Psychophysical procedures, quantitative stimulus manipulations, and musical feedback are utilized to identify the limits of spatial visual function. The system represents a novel way to measure visual thresholds in intact humans, as well as in brain injured subjects who are unable to effectively communicate. Second, we have identified in animal studies a peptide-based strategy to improve retinal mitochondrial function, and have used to reverse diabetic visual decline and age related visual decline. The same strategy has now passed Phase 2 human clinical studies for use with Diabetic Retinal Edema, and a clinical study for Age-related Macular Degeneration is being planned.
Novel automated method to quantify vision in children with brain injury who cannot follow commands
Melis Suner, M.D.
September 2016, Research Presentation, Burke Medical Research Institute Annual Retreat, Skytop, PA, USA
Measuring vision in brain-injured children is difficult since patients often have cognitive impairments that preclude the use of traditional visual assessment procedures. We addressed this problem by designing a computer-based system that measures vision in children based on the reflexive tracking of spatially defined visual stimuli. We tested children with brain injury that varied in cognitive function. In the majority of children, the system was able to detect eye movements and determine thresholds of visual ability. Measures in healthy children and children with brain injury who can follow commands, showed that tracking thresholds correlated well with classical measures of vision.
Novel automated method to quantify vision in children with brain injury who cannot follow commands
Melis Suner, M.D., Glen Prusky, Ph.D., Jeremy N. Hill, D.Phil., and Jason B. Carmel, M.D., Ph.D.
October 2016, Platform Presentation, 45th Annual Child Neurology Society Meeting, Vancouver, Canada
Cerebral visual impairment (CVI) is a leading cause of disability in children. Diagnosing CVI is difficult, however, since patients often have cognitive impairments that preclude the use of traditional visual assessment procedures. We addressed this problem by designing a computer-based system that measures vision in children based on the reflexive tracking of spatially defined visual stimuli. Visual stimuli are moved horizontally across a large computer screen while an eye tracker measures the gaze position of a subject facing the screen. An algorithm determines in real time whether the eyes are smoothly following stimulus movement. When the algorithm detects smooth tracking, which confirms that the subject can see, the behavior is rewarded with musical feedback. To determine visual thresholds, such as acuity and contrast sensitivity, the system automatically adjusts the stimulus characteristics until the limit of ability is identified. We tested children with brain injury that varied in cognitive function. In the majority of children, the system was able to detect eye movements and determine thresholds of visual ability. Measures in healthy children and children with brain injury who can follow commands, showed that tracking thresholds correlated well with classical measures of vision. Our system enables the detection and quantification of CVI from patients who lack the verbal or cognitive skills to participate in standard visual assessment procedures. The measurement of visual thresholds in children with brain injury should enable future studies to determine incidence, natural history and treatment of CVI.
OptokineSys: an automated method of quantifying visual function, even in people who cannot follow commands
Jeremy N. Hill, D.Phil., Melis Suner, M.D., Jason B. Carmel, M.D., Ph.D., and Glen Prusky, Ph.D.
November 2016, Poster Presentation, Society for Neuroscience 46TH Annual Meeting, San Diego, CA, USA
Brain injury may lead to cerebral visual impairment (CVI), a leading cause of disability in children. Diagnosing CVI is difficult, as brain injury often also leads to cognitive impairments that preclude traditional vision assessment methods. To address this, we developed an automated system to measure vision based on the smooth tracking of moving visual stimuli. Our system, called OptokineSys, moves visual stimuli smoothly across a large computer screen while an eye-tracker measures gaze position. Our algorithm determines in real time whether the eyes smoothly follow stimulus movement. It rewards smooth tracking by playing music of the subject's or caregiver's choice, to motivate continued engagement with the task. The algorithm tolerates reverse saccades, catch-up saccades and changes of direction, but interruptions longer than these cause the system to pause the music. Smooth tracking in the correct direction and approximately correct speed is evidence that the subject can see the stimulus. An adaptive procedure uses this evidence to alter contrast and spatial frequency and determine a threshold of visuomotor function. Our use of OptokineSys as a vision assessment tool is based on the principle that, given intact smooth pursuit, these tracking thresholds reflect the subjects' spatial vision. We used OptokineSys to vary the contrast of a band-limited visual noise stimulus, to measure contrast thresholds as a function of spatial frequency. We also adapted spatial frequency at a fixed contrast level, to obtain spatial frequency thresholds as a single acuity measure. In healthy adult subjects, we found: (1) That the system worked robustly and without needing per-subject calibration; (2) that the resulting contrast sensitivity functions had an inverted-U shape, as expected of a true measure of spatial vision; (3) that contrast sensitivity measures were highly repeatable within and across subjects; (4) that spatial-frequency thresholds were well correlated with eye-chart acuity (LogMAR). In children with brain injury, we found (5) that OptokineSys engages children even when they are unable to follow verbal instructions, and (6) that it provides objective information about visual function, including repeatable spatial-frequency thresholds, even in children who cannot communicate and hence cannot otherwise be measured. We conclude that our system is a promising tool for assessing spatial vision, even for people who cannot follow commands. Efficient, objective measurement of visual thresholds in people with brain injury should enable future studies to determine incidence, natural history, and treatment of CVI.
Extraction of motor spatial patterns in children with movement disorders via joint decomposition of brain and muscle activity
Alexandre Barachant, Ph.D., Jason B. Carmel, M.D., Ph.D., Kathleen Friel, Ph.D., Andrew Gordon, Ph.D., Disha Gupta, Ph.D.
November 2016, Poster Presentation, Society for Neuroscience 46TH Annual Meeting, San Diego, CA, USA
In children with neuromotor disorders such as in cerebral palsy (CP), electroencephalography (EEG) based motor spatial patterns can provide valuable information for functional motor connectivity assessment. However, conducting cue-based EEG motor paradigms in people with CP has 3 main challenges: First, they can have difficulty initiating, maintaining and stopping a movement, which means movement is not time-locked to cue stimuli, which is essential for extracting invariant spatial patterns. Second, their EEG motor patterns maybe weaker than background noise, which requires many more trials than healthy subjects, which can be challenging especially for children. Third, the brain injury that leads to CP causes reorganization of the cortical control signals, leading to atypical motor spatial patterns that are not trivial to interpret. To overcome these challenges, we describe here a novel semi- supervised method that does not rely on cue based data epoching, but jointly decomposes the brain (EEG) and muscle (EMG) signals in the Riemannian space. It has the advantage of being objective, simpler and generalizable to signals of varying complexity, as compared to other recent methods such as SPoC and mSPoC that are quite complex and designed to handle a specific type of input signal. We demonstrate the method with the analysis of EEG and EMG data from 23 children with CP, to ascertain their reorganized functional motor connectivity. Subjects participated in an EMG-feedback based videogame experiment, where they controlled the lateral movement of a spaceship by pinching the index finger of either hand. In this way, the subject was engaged and focused and rewarded for being calm, while synchronized EEG and EMG was being acquired from hundreds of movement trials. The cue in this case was continuous rather than discrete. EEG and EMG covariance matrices were estimated and projected in their respective Riemannian tangent space and vectorized. Then a Canonical Partial Least Square was applied to find vector rotations in the tangent space to extract a latent variable that explains the maximum variation between EEG and EMG. Rotation coefficients were back-projected and diagonalized to produce a set of spatial patterns ranked by their importance. This method can enable the use of EEG based neurophysiological assessment of functional motor connectivity in people, especially children, with neuromotor disorders. A better understanding of brain physiology can help guide the development of more effective therapies. (Software implementation of this method is made available as an open-source python toolbox called pyRiemann).
Assessment of proprioception impairments in children with unilateral spastic cerebral palsy using a marker-less motion capture system
David Putrino, P.T., Ph.D., Karen Chin, M.A., Behdad Dehbandi, Ph.D., Victor Nwankwo, Ph.D., Andrew M. Gordon, Ph.D., Kathleen M. Friel, Ph.D.
November 2016, Poster Presentation, Society for Neuroscience 46TH Annual Meeting, San Diego, CA, USA
Background/Objective: Proprioception – the ability to sense the position of a limb in space without visual feedback – is an important contributor to motor control. Deficits in proprioception can impede a person’s ability to accurately perform motor skills. Although it is known that neurological impairment often causes proprioception deficits, there are no reliable, quantitative scales that can accurately and affordably measure proprioception. We developed a proprioception assessment platform that can easily, non-invasively quantify proprioception in children with unilateral spastic cerebral palsy (USCP). Design: Prospective cohort study. Participants & Setting: 13 children with UsCP (6.8-19y, 8 females), university laboratory. Methods: Our proprioception assessment used a Microsoft Kinect 2. The child was seated 1m from the front of the Kinect. During testing, the child was blindfolded. Children were asked to perform three different tasks. In each task, the experimenter first moved the child’s arm (model arm) to a raised position lateral to the trunk. The child would hold the model arm in position for three seconds. During this interval, the Kinect would capture xyz coordinates of each of the child’s upper body joints. In task 1 (ipsilateral remembered), after the child held the model arm in position for three seconds, the child would relax the arm to the side of the body, and then reposition the same arm (test arm), in the same position as the model arm had been placed. In task 2 (contralateral remembered), after the child held the model arm in position for three seconds, the child would relax the arm to the side of the body, and then position the contralateral arm (test arm) in a position that mirrored the model arm position. In task 3 (match), after the child held the model arm in position for three seconds, the child would maintain the position of the model arm, and position the contralateral arm (test arm) to mirror the position of the model arm. During each of these tasks, the Kinect would capture coordinates of the test arm after the child had positioned the arm. Both the more- and less-impaired arms were used, in turn, as the model and test arm for each task. Kinect files were processed offline in MATLAB. Differences in joint positions of the model vs. test arm were quantified. We measured unimanual hand movement speed using the Jebsen-Taylor Test of Hand Function (JTTHF) of each child. A blinded physical therapist also scored proprioception of each child using a clinical rating. Results: All children showed substantial deficits in proprioception. Proprioception scores were similar for each child for the three tasks, and were similar whether the more- or less-impaired arm was used as the model or test arm. There was not a correlation between JTTHF score and proprioception. Our platform could be easily used to test children with USCP, and provides quantified assessments of proprioception. Conclusions/Significance: Proprioception is an important component of motor control, but has been difficult in the past to quantify. We have developed a system that can quantify proprioception in children with USCP using low-cost technology. This tool can be used to further understand proprioception in children with CP.
Sensory connectivity and lesion type predict hand function in children with unilateral spastic cerebral palsy
Disha Gupta, Ph.D., Alexandre Barachant, Ph.D., Andrew Gordon, Ph.D., Hsing-Ching Cuo, Ph.D., Jason B. Carmel, M.D., Ph.D., Kathleen Friel, Ph.D.
November 2016, Poster Presentation, Society for Neuroscience 46TH Annual Meeting, San Diego, CA, USA
The goal of this study was to examine the predictive value of sensory and motor system connectivity and lesion type on hand function in children with unilateral spastic cerebral palsy (USCP). In typically developing children, sensory and motor functions are primarily mediated via crossed (contralateral) connections, as opposed to same-sided (ipsilateral) connections. In children with USCP, an early brain injury often leads to sensory-motor reorganization, where ipsilateral motor connections on the lesioned side are seen to persist. Ipsilateral sensory connections are less common. Given the large scale adaptation in the motor system to unilateral brain injury and smaller scale adaptation in the sensory system, we hypothesized that loss of crossed sensory connections would be more predictive of hand function than loss of crossed motor connections. In addition, sensory circuits being established early in development has been shown to be more affected by cortical lesions than periventricular (PV) lesions. Thus, we hypothesized that cortical lesions would cause greater hand impairment than PV lesions. 23 children with USCP participated in anatomical, physiological and behavior testing of the sensory and motor systems. Anatomically, lesions were denned using MRI, and principal sensory and motor pathways were reconstructed using DTI. Physiologically, somatosensory evoked potentials (SSEPs) were recorded in response to vibrotactile stimulation of the index fingers; and EMG responses to motor cortex stimulation with TMS were recorded. For behavior, sensory hand function was tested with the Cooper stereognosis test and two-point discrimination; while motor hand function was assessed with the Jebsen-Taylor Test and box and blocks. We found that for the impaired hand, presence of significantly discriminable SSEP in the contralateral hemisphere, and a preserved contralateral sensory tract in DTI were both highly predictive of good hand motor and sensory function (Cohen’s kappa agreement between group of subjects with good hand function and testing modality = 0.83 and 0.48 respectively, with kappa > 0.75 being strong agreement, and kappa < 0.40 poor). Lesion type was also predictive of hand function (kappa = 0.47). By contrast, the presence of contralateral motor connections—both physiological from TMS and anatomical from DTI—was less predictive of hand function (kappa = 0.24 and 0.32 respectively). Thus, sensory connectivity is more predictive of hand function in children with USCP than motor connectivity. This indicates that therapies to restore anatomical and physiological sensory connectivity may be important for recovery of sensory-motor function.
Cognitive Impairment after Acquired Brain Injury: What Is Known about the Mechanisms and Effective Therapeutic Interventions
Sudhin Shah, Ph.D.
November 2016, Neuroscience, Weill Cornell Medicine, New York, NY, USA
Traumatic brain injury (TBI) is one of the most common causes of childhood disability worldwide. Several studies have shown that survivors of TBI suffer long-term functional impairments. Cognitive functions such as attention, memory and executive are the most prominently affected with debilitating consequences to emotional and behavioral development. Currently, the mechanisms underlying this impairment have not been characterized, limiting prognosis and development of targeted therapies. Methods: This presentation will discuss what is known about the mechanisms underlying these cognitive deficits. The latest evidence based cognitive rehab interventions will also be presented. Results: Future research must focus on cognitive rehab approaches that utilize knowledge of pathophysiology to alleviate the devastating long-term consequences after TBI. Conclusions: TBI is expected to soon be the leading cause of disability and death worldwide by the World health organization. The long-term sequelae of cognitive impairments are well known but currently very little is known about the underlying mechanisms and limited therapeutic interventions exist.