Publications by authors named "Chuan Hou"

37 Publications

Author Correction: Perceptual learning with dichoptic attention tasks improves attentional modulation in V1 and IPS and reduces interocular suppression in human amblyopia.

Sci Rep 2022 Jun 27;12(1):10884. Epub 2022 Jun 27.

The Smith-Kettlewell Eye Research Institute, San Francisco, CA, 94115, USA.

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http://dx.doi.org/10.1038/s41598-022-15265-9DOI Listing
June 2022

Perceptual learning with dichoptic attention tasks improves attentional modulation in V1 and IPS and reduces interocular suppression in human amblyopia.

Sci Rep 2022 Jun 11;12(1):9660. Epub 2022 Jun 11.

The Smith-Kettlewell Eye Research Institute, San Francisco, CA, 94115, USA.

Long-term and chronic visual suppression to the non-preferred eye in early childhood is a key factor in developing amblyopia, as well as a critical barrier to treat amblyopia. To explore the relationship between selective visual attention and amblyopic suppression and its role in the success of amblyopic training, we used EEG source-imaging to show that training human adults with strabismic and anisometropic amblyopia with dichoptic attention tasks improved attentional modulation of neural populations in the primary visual cortex (V1) and intraparietal sulcus (IPS). We also used psychophysics to show that training reduced interocular suppression along with visual acuity and stereoacuity improvements. Importantly, our results revealed that the reduction of interocular suppression by training was significantly correlated with the improvement of selective visual attention in both training-related and -unrelated tasks in the amblyopic eye, relative to the fellow eye. These findings suggest a relation between interocular suppression and selective visual attention bias between eyes in amblyopic vision, and that dichoptic training with high-attention demand tasks in the amblyopic eye might be an effective way to treat amblyopia.
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http://dx.doi.org/10.1038/s41598-022-13747-4DOI Listing
June 2022

Bilirubin-induced neurotoxicity and visuocortical dysfunction.

J Perinatol 2022 May 26. Epub 2022 May 26.

Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.

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http://dx.doi.org/10.1038/s41372-022-01417-2DOI Listing
May 2022

Excitatory Contribution to Binocular Interactions in Human Visual Cortex Is Reduced in Strabismic Amblyopia.

J Neurosci 2021 10 25;41(41):8632-8643. Epub 2021 Aug 25.

Smith-Kettlewell Eye Research Institute, San Francisco, California 94115.

Binocular summation in strabismic amblyopia is typically reported as being absent or greatly reduced in behavioral studies and is thought to be because of a preferential loss of excitatory interactions between the eyes. Here, we studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with strabismic and anisometropic amblyopia in both sexes, using source-imaged steady-state visual evoked potentials (SSVEP) over a wide range of relative contrast between the two eyes. Dichoptic parallel grating stimuli modulated at unique temporal frequencies in each eye allowed us to quantify spectral response components associated with monocular inputs (self-terms) and the response components because of interaction of the inputs of the two eyes [intermodulation (IM) terms]. Although anisometropic amblyopes revealed a similar pattern of responses to normal-vision observers, strabismic amblyopes exhibited substantially reduced IM responses across cortical regions of interest (V1, V3a, hV4, hMT+ and lateral occipital cortex), indicating reduced interocular interactions in visual cortex. A contrast gain control model that simultaneously fits self- and IM-term responses within each cortical area revealed different patterns of binocular interactions between individuals with normal and disrupted binocularity. Our model fits show that in strabismic amblyopia, the excitatory contribution to binocular interactions is significantly reduced in both V1 and extra-striate cortex, whereas suppressive contributions remain intact. Our results provide robust electrophysiological evidence supporting the view that disruption of binocular interactions in strabismus or amblyopia is because of preferential loss of excitatory interactions between the eyes. We studied how excitatory and suppressive interactions contribute to binocular contrast interactions along the visual cortical hierarchy of humans with normal and amblyopic vision, using source-imaged SSVEP and frequency-domain analysis of dichoptic stimuli over a wide range of relative contrast between the two eyes. A dichoptic contrast gain control model was used to characterize these interactions in amblyopia and provided a quantitative comparison to normal vision. Our model fits revealed different patterns of binocular interactions between normal and amblyopic vision. Strabismic amblyopia significantly reduced excitatory contributions to binocular interactions, whereas suppressive contributions remained intact. Our results provide robust evidence supporting the view that the preferential loss of excitatory interactions disrupts binocular interactions in strabismic amblyopia.
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http://dx.doi.org/10.1523/JNEUROSCI.0268-21.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513700PMC
October 2021

Feature Counting Is Impaired When Shifting Attention Between the Eyes in Adults With Amblyopia.

Front Neurosci 2021 20;15:674146. Epub 2021 May 20.

Smith-Kettlewell Eye Research Institute, San Francisco, CA, United States.

Background: Feature counting requires rapid shifts of attention in the visual field and reflects higher-level cortical functions. This process is drastically impaired in the amblyopic eye of strabismic amblyopes. In this study, we hypothesized that feature counting performance in anisometropic and strabismic amblyopes is further impaired when shifts in attention is required between the eyes.

Materials And Methods: Through a mirror stereoscope, highly visible Gabor patches were presented to the same eye within a block or randomly presented to the left eye or to the right eye with an equal probability within a block. The task was to report the number of Gabors (3 to 9) as accurately as possible. Counting performance was compared between the amblyopes and the normal-vision observers and between the viewing conditions (shifting attention between the eyes versus maintaining attention in the same eye).

Results: When attention was maintained in the same eye, the amblyopic eye of both anisometropic and strabismic groups undercounted the number of Gabors, but achieved near-perfect performance with their fellow eye, compared to normal-vision observers. In contrast, when shifting attention randomly to the left or to the right eye, the amblyopic eye further undercounted the number of Gabors. Undercounting was also found in the fellow eye of strabismic amblyopes, but was not in the fellow eye of anisometropic amblyopes. Performance in normal-vision observers did not differ between shifting attention between the eyes and maintaining attention in the same eye.

Conclusion: Our data showed that the amblyopic eye of both anisometropic and strabismic amblyopes further undercounted features when shifting attention between the eyes, compared to when maintaining attention in the same eye. This suggests that the ability to quickly redirect attention, particularly under interocular suppression, is impaired in amblyopia. The fellow eye of strabismic amblyopes also undercounted features when shifting attention between the eyes. However, such fellow eye abnormality was not found in anisometropic amblyopes, suggesting that different patterns of visual deficits are associated with amblyopia of different etiologies. The inability to count multiple features accurately reflects dysfunctions of high-level cortices in the amblyopic brain.
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http://dx.doi.org/10.3389/fnins.2021.674146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174661PMC
May 2021

Feature Counting Under Dichoptic Viewing in Anisometropic and Strabismic Amblyopia.

Transl Vis Sci Technol 2020 05 16;9(6):13. Epub 2020 May 16.

Smith-Kettlewell Eye Research Institute, San Francisco, CA, USA.

Purpose: While using their amblyopic eye, individuals with strabismic amblyopia count inaccurately and underestimate the number of features. These deficits are attributed to limitations in high-level cortical functions and attention. In the current study, we examined whether feature counting is affected in strabismic and anisometropic amblyopia during dichoptic viewing, a setup that can better capture binocular function disruptions.

Methods: Through a mirror stereoscope, Gabor patches were presented for 200 msec (Experiment 1) or 350 msec (Experiment 2) in both the left eye and the right eye of observers, who were required to combine the percepts and report the total number of patches. Counting performance and errors were compared across amblyopic groups and normal-sighted observers. The contribution and relation of each eye to performance was also evaluated.

Results: Anisometropic and strabismic amblyopia groups counted inaccurately and underestimated the number of features compared to the normal-sighted group. In both amblyopic groups, the amblyopic eye contributed less in comparison to the fellow eye. The strabismic group exhibited worse performance, and a more pronounced difference in eye contribution, in comparison to the anisometropic group.

Conclusions: Overall, our results support the view of higher-level cortical and binocular function deficits in amblyopia.

Translational Relevance: The current study bridges the gap between research on high-cortical function deficits and clinical binocular function disruptions in amblyopia, which can help us better understand the neural mechanism of amblyopia and inform clinical therapeutic tasks and strategies.
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http://dx.doi.org/10.1167/tvst.9.6.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408935PMC
May 2020

Contrast Normalization Accounts for Binocular Interactions in Human Striate and Extra-striate Visual Cortex.

J Neurosci 2020 03 14;40(13):2753-2763. Epub 2020 Feb 14.

Smith-Kettlewell Eye Research Institute, San Francisco, California 94115.

During binocular viewing, visual inputs from the two eyes interact at the level of visual cortex. Here we studied binocular interactions in human visual cortex, including both sexes, using source-imaged steady-state visual evoked potentials over a wide range of relative contrast between two eyes. The ROIs included areas V1, V3a, hV4, hMT, and lateral occipital cortex. Dichoptic parallel grating stimuli in each eye modulated at distinct temporal frequencies allowed us to quantify spectral components associated with the individual stimuli from monocular inputs (self-terms) and responses due to interaction between the inputs from the two eyes (intermodulation [IM] terms). Data with self-terms revealed an interocular suppression effect, in which the responses to the stimulus in one eye were reduced when a stimulus was presented simultaneously to the other eye. The suppression magnitude varied depending on visual area, and the relative contrast between the two eyes. Suppression was strongest in V1 and V3a (50% reduction) and was least in lateral occipital cortex (20% reduction). Data with IM terms revealed another form of binocular interaction, compared with self-terms. IM response was strongest at V1 and was least in hV4. Fits of a family of divisive gain control models to both self- and IM-term responses within each cortical area indicated that both forms of binocular interaction shared a common gain control nonlinearity. However, our model fits revealed different patterns of binocular interaction along the cortical hierarchy, particularly in terms of excitatory and suppressive contributions. Using source-imaged steady-state visual evoked potentials and frequency-domain analysis of dichoptic stimuli, we measured two forms of binocular interactions: one is associated with the individual stimuli that represent interocular suppression from each eye, and the other is a direct measure of interocular interaction between inputs from the two eyes. We demonstrated that both forms of binocular interactions share a common gain control mechanism in striate and extra-striate cortex. Furthermore, our model fits revealed different patterns of binocular interaction along the visual cortical hierarchy, particularly in terms of excitatory and suppressive contributions.
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http://dx.doi.org/10.1523/JNEUROSCI.2043-19.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096139PMC
March 2020

Detection of Amblyopia Using Sweep VEP Vernier and Grating Acuity.

Invest Ophthalmol Vis Sci 2018 03;59(3):1435-1442

Department of Psychology, Stanford University, Stanford, California, United States.

Purpose: Vernier and grating acuity can be measured with swept-parameter visual evoked potentials (sVEP). However, whether sVEP Vernier and grating acuities are comparable in predicting letter acuity has not been systematically evaluated. This study evaluated the validity and reliability of sVEP Vernier and grating acuity for the detection of amblyopia in adults.

Methods: Three types of acuity were measured in 36 adults with amblyopia and 36 age-matched normal-vision controls. Letter acuity was measured with a logMAR chart. Both Vernier and grating acuity were estimated by sVEP and psychophysics for the same stimuli. Regression analyses were performed between the perceptual and electrophysiologic acuity measurements.

Results: SVEP Vernier and grating acuities were significantly correlated with their corresponding psychophysical acuities (P < 0.001). Both the sVEP Vernier (P < 0.0001) and grating (P < 0.01) acuities were also significantly correlated with letter acuity. However, Vernier acuity more precisely reflected the magnitude of the letter acuity loss than did grating acuity for both sVEP and psychophysical measures. Repeating sVEP grating acuity tests with different temporal frequencies and modulation types indicated good reliability of sVEP acuity measures.

Conclusions: SVEP Vernier acuity has a 1:1 relationship with letter acuity, but sVEP grating acuity does not. SVEP Vernier acuity thus provides a better characterization of the magnitude of the amblyopic acuity loss than does sVEP grating acuity. Nonetheless, each of the sVEP measurements can be used to predict letter acuity and because they can be made without a behavioral response, they may be useful measures of visual function in pre- and nonverbal patients.
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http://dx.doi.org/10.1167/iovs.17-23021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858252PMC
March 2018

Cortical sources of Vernier acuity in the human visual system: An EEG-source imaging study.

J Vis 2017 06;17(6)

The Smith-Kettlewell Eye Research Institute, San Francisco, CA, USA.

Vernier acuity determines the relative position of visual features with a precision better than the sampling resolution of cone receptors in the retina. Because Vernier displacement is thought to be mediated by orientation-tuned mechanisms, Vernier acuity is presumed to be processed in striate visual cortex (V1). However, there is considerable evidence suggesting that Vernier acuity is dependent not only on structures in V1 but also on processing in extrastriate cortical regions. Here we used functional magnetic resonance imaging-informed electroencephalogram source imaging to localize the cortical sources of Vernier acuity in observers with normal vision. We measured suprathreshold and near-threshold responses to Vernier onset/offset stimuli at different stages of the visual cortical hierarchy, including V1, hV4, lateral occipital cortex (LOC), and middle temporal cortex (hMT+). These responses were compared with responses to grating on/off stimuli, as well as to stimuli that control for lateral motion in the Vernier task. Our results show that all visual cortical regions of interest (ROIs) responded to both suprathreshold Vernier and grating stimuli. However, thresholds for Vernier displacement (Vernier acuity) were lowest in V1 and LOC compared with hV4 and hMT+, whereas all visual ROIs had identical thresholds for spatial frequency (grating acuity) and for relative motion. The cortical selectivity of sensitivity to Vernier displacement provides strong evidence that LOC, in addition to V1, is involved in Vernier acuity processing. The robust activation of LOC might be related to the sensitivity to the relative position of features, which is common to Vernier displacement and to some kinds of texture segmentation.
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http://dx.doi.org/10.1167/17.6.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460987PMC
June 2017

HER-2, ER, PR status concordance in primary breast cancer and corresponding metastatic lesion in lymph node in Chinese women.

Pathol Res Pract 2016 Apr 1;212(4):252-7. Epub 2016 Feb 1.

Department of Pathology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, China. Electronic address:

Aims And Background: To compare the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in the primary site and the metastatic lesion of lymph nodes in invasive breast cancer for investigating whether the expression of these biomarkers in the primary site could act as a surrogate to the lymphatic metastatic lesion in the same patient.

Methods: In lymphatic metastatic lesion and corresponding primary lesion of 107 cases of invasive breast cancer, ER and PR statuses were assessed by immunohistochemistry (IHC). HER-2 expression level was evaluated by IHC and/or fluorescence in situ hybridization (FISH).

Results: In the primary lesions, 43.9% were ER positive; 46.7% were PR positive; 34.6% were HER-2 positive. In corresponding lymphatic metastatic lesions, the HER-2 status was concordant in 90 patients; 9 patients were diagnosed positive in metastatic lesion while negative in primary lesion; 8 patients were negative in metastatic lesion while positive in primary site (agreement, 84.1%; κ=0.647). A change in ER status was observed in 24 cases: 17 cases positive in metastatic site while negative in primary site; 7 cases negative in metastatic site while positive in primary site (agreement, 77.6%; κ=0.534). PR status discordance between the primary lesion and the metastatic regional lymph nodes was reported in 19 cases (agreement, 82.2%; κ=0.640).

Conclusions: This study revealed that there was only a moderate concordance of ER, PR and HER-2 status between primary tumors and metastatic lymph nodes. These results indicate that it was inappropriate to predict the status of ER, PR and HER-2 in metastatic lymph nodes based on the results of evaluation of that in primary lesions.
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http://dx.doi.org/10.1016/j.prp.2015.11.019DOI Listing
April 2016

Degraded attentional modulation of cortical neural populations in strabismic amblyopia.

J Vis 2016 ;16(3):16

Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI-informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye.
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http://dx.doi.org/10.1167/16.3.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757464PMC
June 2016

Downregulation of survivin inhibits proliferation and migration of human gastric carcinoma cells.

Int J Clin Exp Pathol 2015 1;8(2):1731-6. Epub 2015 Feb 1.

Department of Pathology, The Affiliated Hospital, Xi'an Medical University Xi'an, China.

Gastric cancer is the second leading cause of cancer-related death worldwide. Survivin overexpressed in many human cancers as a member of the inhibitor of apoptosis protein family. We found that all samples of normal gastric tissues did not express the protein of survivin, and however, 65% human gastric cancer samples expressed survivin. Positive expression of survivin correlated with differentiation. The proliferation and migration of gastric cancer decreased after downregulation of surviving by RNA interference. Furthermore, downregulation of survivin caused the cell cycle arrest. These suggest that survivin play an important role in gastric cancer and the use of survivin siRNA might become an effective approach to cancer therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396289PMC
February 2016

Hemodynamic changes of the middle hepatic vein in patients with pulmonary hypertension using echocardiography.

PLoS One 2015 30;10(3):e0121408. Epub 2015 Mar 30.

Department of Ultrasound Diagnosis, Affiliated Hospital of Jilin Medical College, Jilin, Jilin Province, China.

The aim of this study was to analyze the changes of the middle hepatic vein (MHV) spectra in patients with pulmonary hypertension (PH) caused by congenital heart disease (CHD) and determine the proper parameters of MHV to predict PH. Eighty patients with CHD were included, whose pulmonary artery pressure was measured via right heart catheterization, and the MHV spectra were detected via echocardiography. The peak value of velocity (V) and velocity time integral (VTI) of the waves, including S wave, D wave and A wave, were measured at the end of inspiration. The values of the MHV parameters that were predictive of PH were evaluated and their cut-off points were determined. Compared with the control group, V of S wave (S), VTI of S wave (SVTI), V of D wave (D), VTI of D wave (DVTI) decreased and V of A wave (A), VTI of A wave (AVTI), A/S, AVTI/SVTI, A/(S+D), AVTI/ (SVTI+DVTI) increased in the PH group. These differences were statistically significant (P<0.05). A correlation analysis determined that the ratios of A/S, A/(S+D), AVTI/(SVTI+DVTI) were positively correlated with pulmonary artery mean pressure (r=0.529,0.575,0.438,P<0.001). An ROC curve analysis determined that the diagnostic effect of A/(S+D) was superior to the other two parameters. On the ROC curve, when the ratio of A/(S+D) was 0.30, the sensitivity was 85.37% and specificity was 75.00% for predicting PH. The spectral parameters of MHV, including the ratios of A/S, A/(S+D) and AVTI/(SVTI+DVTI), increased with increasing pulmonary pressure in CHD patients. When the ratio of A/(S+D) was 0.30 in MHV spectra, it had sufficient sensitivity and specificity for diagnosing PH, and this method could be used as a new non-invasive complementary echocardiographic parameter for predicting PH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0121408PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4379104PMC
March 2016

Visuocortical bilirubin-induced neurological dysfunction.

Semin Fetal Neonatal Med 2015 Feb 8;20(1):37-41. Epub 2015 Jan 8.

Smith-Kettlewell Eye Research Institute, 2318 Fillmore St, San Francisco, CA 94115, USA.

This review addresses the question whether elevated levels of total serum/plasma bilirubin (TB) cause measurable neurological effects, specifically to visuocortical functioning. Past research in the area of vision and its relation to jaundice has taken advantage of flash visual-evoked potentials (VEPs). Using a steady state VEP, we developed preliminary data suggesting that children who had jaundice with TB levels between 10 and 25mg/dL, but who did not have kernicterus, have measurable changes in visual function, when compared to control infants who did not have jaundice. This non-invasive test offers information about vision thresholds, signal amplitudes, and suprathreshold changes after brain exposure to bilirubin. Here, we review this novel tool, the steady state VEP, and data suggesting that neurological changes occur in infants with moderately elevated TB levels.
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http://dx.doi.org/10.1016/j.siny.2014.12.007DOI Listing
February 2015

Visuocortical function in infants with a history of neonatal jaundice.

Invest Ophthalmol Vis Sci 2014 Sep 2;55(10):6443-9. Epub 2014 Sep 2.

Smith-Kettlewell Eye Research Institute, San Francisco, California, United States.

Purpose: High concentrations of unconjugated bilirubin are neurotoxic and cause brain damage in newborn infants. However, the exact level of bilirubin that may be neurotoxic in a given infant is unknown. The aim of this study was to use a quantitative measure of neural activity, the swept parameter visual evoked potential (sVEP) to determine the relationship between neonatal bilirubin levels and visual responsivity several months later.

Methods: We compared sVEP response functions over a wide range of contrast, spatial frequency, and Vernier offset sizes in 16 full-term infants with high bilirubin levels (>10 mg/dL) and 18 age-matched infants with no visible neonatal jaundice, all enrolled at 14 to 22 weeks of age. The group means of sVEP thresholds and suprathreshold response amplitudes were compared. The correlation between individual sVEP thresholds and bilirubin levels in jaundiced infants was studied.

Results: Infants who had a history of neonatal jaundice showed lower response amplitudes (P < 0.05) and worse or immeasurable sVEP thresholds compared with control infants for all three measures (P < 0.05). Swept parameter visual evoked potential thresholds for Vernier offset were correlated with bilirubin level (P < 0.05), but spatial acuity and contrast sensitivity measures in the infants with neonatal jaundice were not (P > 0.05).

Conclusions: These results indicate that elevated neonatal bilirubin levels affect measures of visual function in infancy up to at least 14 to 22 weeks of postnatal age.
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http://dx.doi.org/10.1167/iovs.14-14261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197714PMC
September 2014

Acuity-independent effects of visual deprivation on human visual cortex.

Proc Natl Acad Sci U S A 2014 Jul 14;111(30):E3120-8. Epub 2014 Jul 14.

Department of Psychology, Stanford University, Stanford, CA 94305.

Visual development depends on sensory input during an early developmental critical period. Deviation of the pointing direction of the two eyes (strabismus) or chronic optical blur (anisometropia) separately and together can disrupt the formation of normal binocular interactions and the development of spatial processing, leading to a loss of stereopsis and visual acuity known as amblyopia. To shed new light on how these two different forms of visual deprivation affect the development of visual cortex, we used event-related potentials (ERPs) to study the temporal evolution of visual responses in patients who had experienced either strabismus or anisometropia early in life. To make a specific statement about the locus of deprivation effects, we took advantage of a stimulation paradigm in which we could measure deprivation effects that arise either before or after a configuration-specific response to illusory contours (ICs). Extraction of ICs is known to first occur in extrastriate visual areas. Our ERP measurements indicate that deprivation via strabismus affects both the early part of the evoked response that occurs before ICs are formed as well as the later IC-selective response. Importantly, these effects are found in the normal-acuity nonamblyopic eyes of strabismic amblyopes and in both eyes of strabismic patients without amblyopia. The nonamblyopic eyes of anisometropic amblyopes, by contrast, are normal. Our results indicate that beyond the well-known effects of strabismus on the development of normal binocularity, it also affects the early stages of monocular feature processing in an acuity-independent fashion.
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http://dx.doi.org/10.1073/pnas.1404361111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121844PMC
July 2014

Piecing it together: infants' neural responses to face and object structure.

J Vis 2012 Dec 6;12(13). Epub 2012 Dec 6.

Department of Psychology, Stanford University, Stanford, CA, USA.

Integration of local elements into a coherent global form is a fundamental aspect of visual object recognition. How the different hierarchically organized stages of visual analysis develop in order to support object representation in infants remains unknown. The aim of this study was to investigate structural encoding of natural images in 4- to 6-month-old infants and adults. We used the steady-state visual evoked potential (ssVEP) technique to measure cortical responses specific to the global structure present in object and face images, and assessed whether differential responses were present for these image categories. This study is the first to apply the ssVEP method to high-level vision in infants. Infants and adults responded to the structural relations present in both image categories, and topographies of the responses differed based on image category. However, while adult responses to face and object structure were localized over occipitotemporal scalp areas, only infant face responses were distributed over temporal regions. Therefore, both infants and adults show object category specificity in their neural responses. The topography of the infant response distributions indicates that between 4 and 6 months of age, structure encoding of faces occurs at a higher level of processing than that of objects.
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http://dx.doi.org/10.1167/12.13.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587016PMC
December 2012

Spatial contrast sensitivity vision loss in children with cortical visual impairment.

Invest Ophthalmol Vis Sci 2012 Nov 19;53(12):7730-4. Epub 2012 Nov 19.

Smith-Kettlewell Eye Research Institute, San Francisco, California 94115, USA.

Purpose: Although cortical visual impairment (CVI) is the leading cause of bilateral vision impairment in children in Western countries, little is known about the effects of CVI on visual function. The aim of this study was to compare visual evoked potential measures of contrast sensitivity and grating acuity in children with CVI with those of age-matched typically developing controls.

Methods: The swept parameter visual evoked potential (sVEP) was used to measure contrast sensitivity and grating acuity in 34 children with CVI at 5 months to 5 years of age and in 16 age-matched control children. Contrast thresholds and spatial frequency thresholds (grating acuities) were derived by extrapolating the tuning functions to zero amplitude. These thresholds and maximal suprathreshold response amplitudes were compared between groups.

Results: Among 34 children with CVI, 30 had measurable but reduced contrast sensitivity with a median threshold of 10.8% (range 5.0%-30.0% Michelson), and 32 had measurable but reduced grating acuity with median threshold 0.49 logMAR (9.8 c/deg, range 5-14 c/deg). These thresholds were significantly reduced, compared with age-matched control children. In addition, response amplitudes over the entire sweep range for both measures were significantly diminished in children with CVI compared with those of control children.

Conclusions: Our results indicate that spatial contrast sensitivity and response amplitudes are strongly affected by CVI. The substantial degree of loss in contrast sensitivity suggests that contrast is a sensitive measure for evaluating vision deficits in patients with CVI.
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http://dx.doi.org/10.1167/iovs.12-9775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501833PMC
November 2012

Effect of Grade I and II intraventricular hemorrhage on visuocortical function in very low birth weight infants.

Seeing Perceiving 2012 ;25(2):143-54

Stanford University School of Medline, Stanford, CA 94305, USA.

The neurological outcome for infants with Grade I/II intraventricular hemorrhage (IVH) is debated. The aim of this study was to determine whether very low birth weight infants (VLBW, <1500 g) with Grade I/II (IVH) have altered visuocortical activity compared with infants with no IVH. We assessed the quantitative swept parameter visual evoked potential (sVEP) responses evoked by three different visual stimuli. Data from 52 VLBW infants were compared with data from 13 infants with Grade I or II IVH, enrolled at 5-7 months corrected age. Acuity thresholds and suprathreshold response amplitudes were compared. Grating acuity (GA), contrast sensitivity (CS) and vernier acuity (VA) were each worse in the Grade I/II IVH compared with the no IVH groups (8.24 cpd in IVH group vs. 13.07 cpd in no IVH group for GA; 1.44% vs. 1.18% for CS and 1.55 arcmin vs. 0.58 arcmin for VA). The slopes of the response amplitude for CS and VA were significantly lower in IVH infants. The spatial frequency tuning function was shifted downward on the spatial frequency axis, without a change in slope. These results indicate that Grade I/II IVH are associated with deleterious effects on cortical vision development and function.
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http://dx.doi.org/10.1163/187847612X626381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500802PMC
August 2012

Electrochemical behavior of azithromycin at graphene and ionic liquid composite film modified electrode.

Talanta 2011 Oct 8;86:227-32. Epub 2011 Sep 8.

College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, PR China.

An electrochemical method has been successfully demonstrated for sensitive determination of azithromycin (Azi) with room temperature ionic liquid (IL) of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF(6)) - graphene (Gr) composite modified glassy carbon electrode (GCE). The cyclic voltammetric results indicate that Gr/IL/GCE can remarkably enhance electrocatalytic activity towards the oxidation of Azi in neutral solutions. Azi produce an anodic peak at about 0.82 V at this electrode. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Azi determination by differential-pulse voltammetry (DPV). Under optimized conditions, the concentration range and detection limit were 0.49-28.57 μg ml(-1) and 0.19 μg ml(-1) (S/N=3) respectively for Azi. The method was successfully applied assay of the drug in the pharmaceutical dosage forms.
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http://dx.doi.org/10.1016/j.talanta.2011.09.005DOI Listing
October 2011

Visual cortical function in very low birth weight infants without retinal or cerebral pathology.

Invest Ophthalmol Vis Sci 2011 Nov 25;52(12):9091-8. Epub 2011 Nov 25.

The Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, CA, USA.

Purpose: Preterm infants are at high risk of visual and neural developmental deficits. However, the development of visual cortical function in preterm infants with no retinal or neurologic morbidity has not been well defined. To determine whether premature birth itself alters visual cortical function, swept parameter visual evoked potential (sVEP) responses of healthy preterm infants were compared with those of term infants.

Methods: Fifty-two term infants and 58 very low birth weight (VLBW) infants without significant retinopathy of prematurity or neurologic morbidities were enrolled. Recruited VLBW infants were between 26 and 33 weeks of gestational age, with birth weights of less than 1500 g. Spatial frequency, contrast, and vernier offset sweep VEP tuning functions were measured at 5 to 7 months' corrected age. Acuity and contrast thresholds were derived by extrapolating the tuning functions to 0 amplitude. These thresholds and suprathreshold response amplitudes were compared between groups.

Results: Preterm infants showed increased thresholds (indicating decreased sensitivity to visual stimuli) and reductions in amplitudes for all three measures. These changes in cortical responsiveness were larger in the <30 weeks ' gestational age subgroup than in the ≥30 weeks' gestational age subgroup.

Conclusions: Preterm infants with VLBW had measurable and significant changes in cortical responsiveness that were correlated with gestational age. These results suggest that premature birth in the absence of identifiable retinal or neurologic abnormalities has a significant effect on visual cortical sensitivity at 5 to 7 months' of corrected age and that gestational age is an important factor in visual development.
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http://dx.doi.org/10.1167/iovs.11-7458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231847PMC
November 2011

[Effects of monocular visual deprivation on parameters of GLuRs in visual cortex in developing kittens].

Sichuan Da Xue Xue Bao Yi Xue Ban 2010 Jan;41(1):111-3

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

Objective: To explore the molecular mechanism of the development of amplyopia.

Methods: Lid suture was performed on 5 kittens at 3 weeks of age to produce monocular visual deprivation. Six kittens were used as controls without any treatment. Three months later, the characteristics of [3,4-3H]-glutamate binding to the visual cortical membranes of the kittens were studied using radiolabelled ligand receptor binding assay.

Results: The kittens with monocular deprivation had decreased GluRs binding sites in the visual cortex as compared with the controls (P < 0.001). The kittens with monocular deprivation had greater value of KD than the controls (P < 0.001), indicating a decrease in the affinify of GluRs. The Hill coefficients of all of the kittens were close to 1, indicating that [3,4-3H]1-glutamate binded to a single-site receptor, obeying mass action law. Even if there were multi binding sites in GluRs, the affinity of these sites to [3,4-3H]1-glutamate was almost identical. Neither positive nor negative interactive effects existed.

Conclusion: Monocular deprivation does affect the binding parameters (KD and Bmax) of GluRs, which may be a molecular mechanism of the development of amblyopia.
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January 2010

Connecting the dots: how local structure affects global integration in infants.

J Cogn Neurosci 2010 Jul;22(7):1557-69

The Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.

Glass patterns are moirés created from a sparse random-dot field paired with its spatially shifted copy. Because discrimination of these patterns is not based on local features, they have been used extensively to study global integration processes. Here, we investigated whether 4- to 5.5-month-old infants are sensitive to the global structure of Glass patterns by measuring visual-evoked potentials. Although we found strong responses to the appearance of the constituent dots, we found sensitivity to the global structure of the Glass patterns in the infants only over a very limited range of spatial separation. In contrast, we observed robust responses in the infants when we connected the dot pairs of the Glass pattern with lines. Moreover, both infants and adults showed differential responses to exchanges between line patterns portraying different global structures. A control study varying luminance contrast in adults suggests that infant sensitivity to global structure is not primarily limited by reduced element visibility. Together our results suggest that the insensitivity to structure in conventional Glass patterns is due to inefficiencies in extracting the local orientation cues generated by the dot pairs. Once the local orientations are made unambiguous or when the interpolation span is small, infants can integrate these signals over the image.
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http://dx.doi.org/10.1162/jocn.2009.21323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2853753PMC
July 2010

Evidence for visual compromise in preverbal children with orbital vascular birthmarks.

Am J Ophthalmol 2009 Apr 4;147(4):679-682.e1. Epub 2009 Feb 4.

Smith-Kettlewell Eye Research Institute, San Francisco, California 94115, USA.

Purpose: To learn whether electrophysiological changes indicating amblyopia occur even in the absence of clinically recognizable amblyopia.

Design: Prospective study.

Methods: Four consecutive infants between 7 and 19 months of age with unilateral periocular vascular lesions that intermittently obstructed vision in the affected eye and no clinical evidence of amblyopia were evaluated. No child had anisometropia greater than 0.50 diopter in the greatest meridian or strabismus. Sweep visual evoked potential vernier acuity was measured under monocular viewing conditions with the fellow eye tested as the control.

Results: Response amplitudes and acuity thresholds were significantly diminished in the affected eyes. A phase analysis showed slowing of the response in the affected eyes compared with the control eyes.

Conclusions: An amblyopia-like effect on vernier acuity occurred in infants with unilateral periocular vascular birthmarks when the lesion caused intermittent occlusion of the eye. Whether long-term effects will occur is unknown, but children with no clinically apparent amblyopia in the setting of a vascular mark or other cause of intermittent occlusion of the visual axis should be followed, since these electrophysiology findings suggest amblyopia may be present.
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http://dx.doi.org/10.1016/j.ajo.2008.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399829PMC
April 2009

Abnormalities of coherent motion processing in strabismic amblyopia: Visual-evoked potential measurements.

J Vis 2008 Apr 8;8(4):2.1-12. Epub 2008 Apr 8.

Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.

Coherent motion responses of patients with mild to moderate strabismic amblyopia were compared to those of normals using visual-evoked potentials (VEPs). Responses were elicited by dynamic random-dot kinematograms that alternated at 0.83 Hz between globally coherent (left-right) and incoherent (random) motion states. Tuning curves were measured at the first harmonic of the global motion update rate (0.83 Hz) and at the first harmonic of the dot update rate (20 Hz) for spatial displacements 3.1 to 27.9 arcmin (1.6 to 9.3 deg/s). Responses locked to the changes in the global organization of the local direction vectors were an inverted U-shaped function of displacement/speed in the normal-vision observers and in the fellow eyes of the strabismus patients while the tuning function of the amblyopic eyes was shifted to larger displacements/higher speeds. Responses at the dot update rate were reduced in amplitude and altered in timing in both eyes of the patients. The results are consistent with both local and global deficits in motion processing in strabismic amblyopia.
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http://dx.doi.org/10.1167/8.4.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386923PMC
April 2008

Validation study of VEP vernier acuity in normal-vision and amblyopic adults.

Invest Ophthalmol Vis Sci 2007 Sep;48(9):4070-8

Smith-Kettlewell Eye Research Institute, San Francisco, California 94115, USA.

Purpose: Vernier displacement thresholds can be measured with swept-parameter visual evoked potentials (sVEPs) and may therefore be useful in pre- or nonverbal subjects. This study was conducted to test whether sVEP vernier thresholds are valid measures of the visibility of vernier offsets in two different settings.

Methods: Vernier acuity thresholds were measured psychophysically and electrophysiologically using square-wave gratings containing vernier displacements modulated at 3.76 Hz. The detectability of the vernier alignment cue was degraded by introducing either gaps or standing offsets in the stimulus. These manipulations were performed in normal-vision observers. In a second experiment, psychophysical and sVEP vernier acuity were measured in amblyopic observers.

Results: sVEP thresholds and overall amplitudes in normal observers were strongly affected by the introduction of gaps or standing offsets, as were psychophysical thresholds. Psychophysical and sVEP vernier offset thresholds were significantly correlated in the amblyopic eyes, as were sVEP and optotype interocular threshold differences. sVEP amplitudes of patients with strabismus were lower than those of patients with anisometropic amblyopia, even though optotype acuities were the same in the two groups.

Conclusions: Vernier acuity thresholds derived from the sVEP tap mechanisms that are specific for the relative position of stimulus elements, and they correlate with perceptual visibility in normal and amblyopic observers. Because of this correlation and because sVEP thresholds can be measured without the need for instruction or behavioral responses, they may be useful in assessing visual function in pre- and nonverbal patients.
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http://dx.doi.org/10.1167/iovs.06-1368DOI Listing
September 2007

[Study on crossed and uncrossed disparity evoked potential of dynamic random dot stereogram].

Zhonghua Yan Ke Za Zhi 2006 Oct;42(10):878-82

Department of Ophthalmology, Huaxi Hospital, Sichuan University, Chengdu 610041, China.

Objective: To analyze the disparity evoked potentials (DEP) of fine disparities, coarse disparities, crossed disparities and uncrossed disparities and provide parameters of impersonal examining stereopsis.

Methods: A software package for generating dynamic random dot stereogram (DRDS) was developed as a visual stimulus to elicit DEP in 30 normal subjects. The DEP of every subject was recorded in different crossed and uncrossed disparity stimuli (4', 8', 15', 23', 30', 45', 53', 60', 72', 87', 102', 124', 150' of arc).

Results: (1) the constant negative-positive complex wave was observed in different disparity stimuli. (2) The N wave's latency of -45' was the longest, the N wave's latency of -150' was the shortest among crossed disparities. The N wave's latency of 4', 23' was the longest, the N wave's latency of 124' was the shortest among uncrossed disparities. (3) The amplitude peak of P wave occurred at -23', -60', -150' among crossed disparities. The amplitude peak of P wave occurred at 15', 45', 72' among uncrossed disparities. (4) All characteristic crossed disparities were smaller than the uncrossed disparities. The change orderliness of small crossed disparities was different from that of small uncrossed disparities.

Conclusions: The N wave's latency and the P wave's amplitude can be used as parameters to impersonally examine stereopsis. These results suggest that stereopsis can be divided into fine crossed stereopsis, fine uncrossed stereopsis, coarse crossed stereopsis, and coarse uncrossed stereopsis.
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October 2006

Sweep visual evoked potential grating acuity thresholds paradoxically improve in low-luminance conditions in children with cortical visual impairment.

Invest Ophthalmol Vis Sci 2006 Jul;47(7):3220-4

Smith Kettlewell Eye Research Institute, San Francisco, California 94115, USA.

Purpose: Children with cortical or cerebral visual impairment (CVI) often experience photophobia. In a study conducted to test whether this clinical phenomenon affects visual function, the sweep visual evoked potential (VEP) was used to evaluate cortical responses to grating stimuli in two luminance conditions: low and normal.

Methods: Twenty children (age range, 7 months to 4 years 10 months) with CVI and 17 age-matched control subjects were examined. Testing conditions consisted of a swept grating stimulus shown against a normal background luminance (109 cd/m2) and against a low-luminance background (20 cd/m2). Thresholds in these two luminance conditions were compared. Response amplitudes across the spatial frequency domain were also compared.

Results: Children with CVI paradoxically have improved grating acuity thresholds when the stimulus is shown using a low-luminance background (P=0.006). Response amplitudes are also increased in low luminance. In control children, luminance had no significant effect on response amplitudes or thresholds.

Conclusions: Increased luminance causes a worsening of acuity thresholds in children with CVI. Response amplitudes are also diminished in normal luminance. This finding has implications for optimal viewing and learning conditions for children with CVI.
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http://dx.doi.org/10.1167/iovs.05-1252DOI Listing
July 2006

Neural correlates of shape-from-shading.

Vision Res 2006 Mar;46(6-7):1080-90

The Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.

Visual evoked potentials were recorded during presentation of a single stimulus that generated bi-stable perceptual alternation between two different three-dimensional percepts. One interpretation (asymmetric) changed depth structure from flat to corrugated in depth and the other (symmetric) had the appearance of a flat surface translating laterally behind a set of apertures. Responses during perception of the asymmetric three-dimensional structure contained larger negative components than did responses during perception of the symmetric three-dimensional structure. Control experiments suggest that the interpretation of depth structure is selected after junction information caused by the interplay between shading and object shape is extracted.
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http://dx.doi.org/10.1016/j.visres.2005.10.017DOI Listing
March 2006

Delayed visual attention caused by high myopic refractive error.

Strabismus 2005 Jun;13(2):75-7

Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, CA 94115, USA.

Delayed visual maturation (DVM) is usually a retrospective diagnosis given to infants who are born with no or poor visually-directed behavior, despite normal acuity on objective testing, but who recover months later. This condition can be organized into several types based on associated neurodevelopmental or ocular findings, but the etiology of DVM is probably complex and involves multiple possible origins. Here we report two infants who presented with delayed visual maturation (attention). They were visually unresponsive at birth but were later found to have high myopic errors. Patient 1 had -4 D right eye, -5 D left eye. Patient 2 had -9 D o.u. Upon spectacle correction at 5 and 4 months, respectively, both infants immediately displayed visually-directed behavior, suggesting that a high refractive error was the cause of inattention in these patients. These findings could add to knowledge surrounding DVM and the diagnosis of apparently blind infants. Findings presented here also indicate the importance of prompt refractive error measurement in such cases.
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http://dx.doi.org/10.1080/09273970590935066DOI Listing
June 2005
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