Center for Visual and Neurocognitive Rehabilitation

VA, United States

Center for Visual and Neurocognitive Rehabilitation

VA, United States
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Gu X.,Emory University | Wei Z.Z.,Emory University | Wei Z.Z.,Center for Visual and Neurocognitive Rehabilitation | Espinera A.,Emory University | And 7 more authors.
Experimental Neurology | Year: 2015

Neonatal brain trauma is linked to higher risks of mortality and neurological disability. The use of mild to moderate hypothermia has shown promising potential against brain injuries induced by stroke and traumatic brain injury (TBI) in various experimental models and in clinical trials. Conventional methods of physical cooling, however, are difficult to use in acute treatments and in induction of regulated hypothermia. In addition, general anesthesia is usually required to mitigate the negative effects of shivering during physical cooling. Our recent investigations demonstrate the potential therapeutic benefits of pharmacologically induced hypothermia (PIH) using the neurotensin receptor (NTR) agonist HPI201 (formerly known as ABS201) in stroke and TBI models of adult rodents. The present investigation explored the brain protective effects of HPI201 in a P14 rat pediatric model of TBI induced by controlled cortical impact. When administered via intraperitoneal (i.p.) injection, HPI201 induced dose-dependent reduction of body and brain temperature. A 6-h hypothermic treatment, providing an overall 2-3. °C reduction of brain and body temperature, showed significant effect of attenuating the contusion volume versus TBI controls. Attenuation occurs whether hypothermia is initiated 15. min or 2. h after TBI. No shivering response was seen in HPI201-treated animals. HPI201 treatment also reduced TUNEL-positive and TUNEL/NeuN-colabeled cells in the contusion area and peri-injury regions. TBI-induced blood-brain barrier damage was attenuated by HPI201 treatment, evaluated using the Evans Blue assay. HPI201 significantly decreased MMP-9 levels and caspase-3 activation, both of which are pro-apototic, while it increased anti-apoptotic Bcl-2 gene expression in the peri-contusion region. In addition, HPI201 prevented the up-regulation of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6. In sensorimotor activity assessments, rats in the HPI201 treated group exhibited improved functional recovery after TBI versus controls. These data support that PIH therapy using our NTR agonist is effective in reducing neuronal and BBB damage, attenuating inflammatory response and detrimental cellular signaling, and promoting functional recovery after TBI in the developing brain, supporting its potential for further evaluation towards clinical development. © 2015 Elsevier Inc.

Zhou X.,Wenzhou University | Zhou X.,State Key Laboratory of Ophthalmology | Pardue M.T.,Georgia Institute of Technology | Pardue M.T.,Center for Visual and Neurocognitive Rehabilitation | And 3 more authors.
Progress in Retinal and Eye Research | Year: 2017

In the face of an "epidemic" increase in myopia over the last decades and myopia prevalence predicted to reach 2.5 billion people by the end of this decade, there is an urgent need to develop effective and safe therapeutic interventions to slow down this "myopia booming" and prevent myopia-related complications and vision loss. Dopamine (DA) is an important neurotransmitter in the retina and mediates diverse functions including retina development, visual signaling, and refractive development. Inspired by the convergence of epidemiological and animal studies in support of the inverse relationship between outdoor activity and risk of developing myopia and by the close biological relationship between light exposure and dopamine release/signaling, we felt it is timely and important to critically review the role of DA in myopia development. This review will revisit several key points of evidence for and against DA mediating light control of myopia: 1) the causal role of extracellular retinal DA levels, 2) the mechanism and action of dopamine D1 and D2 receptors and 3) the roles of cellular/circuit retinal pathways. We examine the experiments that show causation by altering DA, DA receptors and visual pathways using pharmacological, transgenic, or visual environment approaches. Furthermore, we critically evaluate the safety issues of a DA-based treatment strategy and some approaches to address these issues. The review identifies the key questions and challenges in translating basic knowledge on DA signaling and myopia from animal studies into effective pharmacological treatments for myopia in children. © 2017 The Authors.

Lacey S.,Emory University | Martinez M.,Emory University | McCormick K.,Emory University | Sathian K.,Emory University | Sathian K.,Center for Visual and Neurocognitive Rehabilitation
European Journal of Neuroscience | Year: 2016

Synesthesia is a phenomenon in which an experience in one domain is accompanied by an involuntary secondary experience in another, unrelated domain; in classical synesthesia, these associations are arbitrary and idiosyncratic. Cross-modal correspondences refer to universal associations between seemingly unrelated sensory features, e.g., auditory pitch and visual size. Some argue that these phenomena form a continuum, with classical synesthesia being an exaggeration of universal cross-modal correspondences, whereas others contend that the two are quite different, since cross-modal correspondences are non-arbitrary, non-idiosyncratic, and do not involve secondary experiences. Here, we used the implicit association test to compare synesthetes’ and non-synesthetes’ sensitivity to cross-modal correspondences. We tested the associations between auditory pitch and visual elevation, auditory pitch and visual size, and sound-symbolic correspondences between auditory pseudowords and visual shapes. Synesthetes were more sensitive than non-synesthetes to cross-modal correspondences involving sound-symbolic, but not low-level sensory, associations. We conclude that synesthesia heightens universally experienced cross-modal correspondences, but only when these involve sound symbolism. This is only partly consistent with the idea of a continuum between synesthesia and cross-modal correspondences, but accords with the idea that synesthesia is a high-level, post-perceptual phenomenon, with spillover of the abilities of synesthetes into domains outside their synesthesias. To our knowledge, this is the first demonstration that synesthetes, relative to non-synesthetes, experience stronger cross-modal correspondences outside their synesthetic domains. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd

Jamal Y.,Emory University | Lacey S.,Emory University | Nygaard L.,Emory University | Sathian K.,Emory University | Sathian K.,Center for Visual and Neurocognitive Rehabilitation
Multisensory Research | Year: 2017

Cross-modal correspondences refer to associations between apparently unrelated stimulus features in different senses. For example, high and low auditory pitches are associated with high and low visual elevations, respectively. Here we examined how this crossmodal correspondence between visual elevation and auditory pitch relates to auditory elevation. We used audiovisual combinations of high- or low-frequency bursts of white noise and a visual stimulus comprising a white circle. Auditory and visual stimuli could each occur at high or low elevations. These multisensory stimuli could be congruent or incongruent for three correspondence types: cross-modal featural (auditory pitch/visual elevation), within-modal featural (auditory pitch/auditory elevation) and cross-modal spatial (auditory and visual elevation). Participants performed a 2AFC speeded classification (high or low) task while attending to auditory pitch, auditory elevation, or visual elevation. We tested for modulatory interactions between the three correspondence types. Modulatory interactions were absent when discriminating visual elevation. However, the within-modal featural correspondence affected the cross-modal featural correspondence during discrimination of auditory elevation and pitch, while the reverse modulation was observed only during discrimination of auditory pitch. The cross-modal spatial correspondence modulated the other two correspondences only when auditory elevation was being attended, was modulated by the cross-modal featural correspondence only during attention to auditory pitch, and was modulated by the within-modal featural correspondence while performing discrimination of either auditory elevation or pitch. We conclude that the cross-modal correspondence between auditory pitch and visual elevation interacts strongly with auditory elevation. © 2017 by Koninklijke Brill NV, Leiden, The Netherlands.

Wei Z.Z.,Emory University | Wei Z.Z.,Center for Visual and Neurocognitive Rehabilitation | Yu S.P.,Emory University | Yu S.P.,Center for Visual and Neurocognitive Rehabilitation | And 7 more authors.
Cellular and Molecular Neurobiology | Year: 2014

Stem cell transplantation therapy has provided promising hope for the treatment of a variety of neurodegenerative disorders. Among challenges in developing disease-specific stem cell therapies, identification of key regulatory signals for neuronal differentiation is an essential and critical issue that remains to be resolved. Several lines of evidence suggest that JNK, also known as SAPK, is involved in neuronal differentiation and neural plasticity. It may also play a role in neurite outgrowth during neuronal development. In cultured mouse embryonic stem (ES) cells, we test the hypothesis that the JNK pathway is required for neuronal differentiation. After neural induction, the cells were plated and underwent differentiation for up to 5 days. Western blot analysis showed a dramatic increase in phosphorylated JNKs at 1-5 days after plating. The phosphorylation of JNK subsequently induced activation of STAT1 and STAT3 that lead to expressions of GAP-43, neurofilament, βIII-tubulin, and synaptophysin. NeuN-colabelled with DCX, a marker for neuroblast, was enhanced by JNK signaling. Neuronal differentiation of ES cells was attenuated by treatment with SP600125, which inhibited the JNK activation and decreased the activation of STAT1 and STAT3, and consequently suppressed the expressions of GAP-43, neurofilament, βIII-tubulin, and the secretion of VEGF. Data from immunocytochemistry indicated that the nuclear translocation of STAT3 was reduced, and neurites of ES-derived neurons were shorter after treatment with SP600125 compared with control cells. These results suggest that the JNK-STAT3 pathway is a key regulator required for early neuronal differentiation of mouse ES cells. Further investigation on expression of JNK isoforms showed that JNK-3 was significantly upregulated during the differentiation stage, while JNK-1 and JNK-2 levels decreased. Our study provided interesting information on JNK functions during ES cell neuronal differentiation. © 2014 Springer Science+Business Media.

PubMed | VA Palo Alto Health Care System, Center for Visual and Neurocognitive Rehabilitation and Emory University
Type: Journal Article | Journal: Military medicine | Year: 2017

Eye care in the Veterans Affairs Health Care System is challenged with increasing demand and higher prevalence of patients with complex ocular conditions. Understanding factors that impact eye care productivity and access is necessary for appropriate allocation of resources. The purpose of this study was to determine the impact of various eye clinic personnel on eye care provider productivity and patient access.Utilizing data from the Veterans Health Administration National Data Warehouse, workload and level of staffing were analyzed. Trends in the data were analyzed using descriptive and regression analyses employing both linear and curve fitting modeling methods.There was a significant positive correlation between ophthalmology technicians and ophthalmologist productivity (p < 0.001), number of unique patients seen per year per provider (p = 0.047), and total yearly number of office visits per provider (p < 0.001). Similarly, there was a significant positive correlation between number of ophthalmology residents and productivity (p = 0.046) and number of clinic visits per provider (p < 0.001) but not the number of unique patients seen. Positive correlation was found between optometry technicians and the number of unique patients seen by optometrists (p = 0.041) and total number of clinic visits per provider (p < 0.001) but not optometrist productivity. No significant correlations were present for nurses, nurse practitioners, physician assistants, or clerical staff.Eye care technicians provide a cost-effective multiplier effect for provider productivity, especially in ophthalmology clinics, allowing significant increases in total clinic visits and number of unique patients seen per year.

Chasan J.E.,Emory University | Delaune B.,Center for Visual and Neurocognitive Rehabilitation | Maa A.Y.,Emory University | Maa A.Y.,Atlanta Medical Center | And 2 more authors.
JAMA Ophthalmology | Year: 2014

IMPORTANCE: Telemedicine is a useful clinical method to extend health care to patients with limited access. Minimal information exists on the subsequent effect of telemedicine activities on eye care resources. OBJECTIVE: To evaluate the effect of a community-based diabetic teleretinal screening program on eye care use and resources. DESIGN, SETTING, AND PARTICIPANTS: The current studywas a retrospective medical record review of patients who underwent diabetic teleretinal screening in the community-based clinics of the Atlanta Veterans Affairs Medical Center from October 1, 2008, through March 31, 2009, and who were referred for an ophthalmic examination in the eye clinic. EXPOSURES: Clinical medical records were reviewed for a 2-year period after patients were referred from teleretinal screening. The following information was collected for analysis: patient demographics, referral and confirmatory diagnoses, ophthalmology clinic visits, diagnostic procedures, surgical procedures, medications, and spectacle prescriptions. MAIN OUTCOMES AND MEASURES: The accuracy between referring and final diagnoses and the eye care resources that were used in the care of referred patients. RESULTS: The most common referral diagnoses were nonmacular diabetic retinopathy (43.2%), nerve-related disease (30.8%), lens or media opacity (19.1%), age-related macular degeneration (12.9%), and diabetic macular edema (5.6%). The percentage of agreement among these 5 visually significant diagnoses was 90.4%, with a total sensitivity of 73.6%. Diabetic macular edema required the greatest number of ophthalmology clinic visits, diagnostic tests, and surgical procedures. Using Medicare cost data estimates, the mean cost incurred during a 2-year period per patient seen in the eye clinic was approximately $1000. CONCLUSIONS AND RELEVANCE: Although a teleretinal screening program can be accurate and sensitive for multiple visually significant diagnoses, measurable resource burdens should be anticipated to adequately prepare for the associated increase in clinical care. Copyright 2014 American Medical Association. All rights reserved.

Kelly R.,Georgia Institute of Technology | Mizelle J.C.,Georgia Institute of Technology | Mizelle J.C.,Center for Visual and Neurocognitive Rehabilitation | Wheaton L.A.,Georgia Institute of Technology
Neuropsychologia | Year: 2015

Prior work has demonstrated that perspective and handedness of observed actions can affect action understanding differently in right and left-handed persons, suggesting potential differences in the neural networks underlying action understanding between right and left-handed individuals. We sought to evaluate potential differences in these neural networks using electroencephalography (EEG). Right- and left-handed participants observed images of tool-use actions from egocentric and allocentric perspectives, with right- and left-handed actors performing the actions. Participants judged the outcome of the observed actions, and response accuracy and latency were recorded. Behaviorally, the highest accuracy and shortest latency was found in the egocentric perspective for right- and left-handed observers. Handedness of subject showed an effect on accuracy and latency also, where right-handed observers were faster to respond than left-handed observers, but on average were less accurate. Mu band (8-10. Hz) cortico-cortical coherence analysis indicated that right-handed observers have coherence in the motor dominant left parietal-premotor networks when looking at an egocentric right or allocentric left hands. When looking in an egocentric perspective at a left hand or allocentric right hand, coherence was lateralized to right parietal-premotor areas. In left-handed observers, bilateral parietal-premotor coherence patterns were observed regardless of actor handedness. These findings suggest that the cortical networks involved in understanding action outcomes are dependent on hand dominance, and notably right handed participants seem to utilize motor systems based on the limb seen performing the action. The decreased accuracy for right-handed participants on allocentric images could be due to asymmetrical lateralization of encoding action and motoric dominance, which may interfere with translating allocentric limb action outcomes. Further neurophysiological studies will determine the specific processes of how left- and right-handed participants understand actions. © 2015 Elsevier Ltd.

PubMed | Center for Visual and Neurocognitive Rehabilitation, University of Illinois at Chicago, Emory University and Georgia Institute of Technology
Type: | Journal: Experimental eye research | Year: 2016

Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30min of low-level electrical stimulation (4Aat 5Hz; n=10) or sham stimulation (Sham group; n=15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30min, and retinal tissue harvested at 1h and 24h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1h, but not 24h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.

Sathian K.,Emory University | Sathian K.,Center for Visual and Neurocognitive Rehabilitation
Journal of Neurophysiology | Year: 2016

Haptic sensing of objects acquires information about a number of properties. This review summarizes current understanding about how these properties are processed in the cerebral cortex of macaques and humans. Nonnoxious somatosensory inputs, after initial processing in primary somatosensory cortex, are partially segregated into different pathways. A ventrally directed pathway carries information about surface texture into parietal opercular cortex and thence to medial occipital cortex. A dorsally directed pathway transmits information regarding the location of features on objects to the intraparietal sulcus and frontal eye fields. Shape processing occurs mainly in the intraparietal sulcus and lateral occipital complex, while orientation processing is distributed across primary somatosensory cortex, the parietal operculum, the anterior intraparietal sulcus, and a parieto-occipital region. For each of these properties, the respective areas outside primary somatosensory cortex also process corresponding visual information and are thus multisensory. Consistent with the distributed neural processing of haptic object properties, tactile spatial acuity depends on interaction between bottom-up tactile inputs and topdown attentional signals in a distributed neural network. Future work should clarify the roles of the various brain regions and how they interact at the network level. © 2016 the American Physiological Society.

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