November 2019
Volume 60, Issue 14
Open Access
Eye Movements, Strabismus, Amblyopia and Neuro-ophthalmology  |   November 2019
Abnormal Monocular and Dichoptic Temporal Synchrony in Adults with Amblyopia
Author Affiliations & Notes
  • Chunwen Tao
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Yidong Wu
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Ling Gong
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Shijia Chen
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Yu Mao
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Yiya Chen
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Jiawei Zhou
    School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
  • Pi-Chun Huang
    Department of Psychology, National Cheng Kung University, Tainan, Taiwan
  • Correspondence: Jiawei Zhou, School of Ophthalmology and Optometry, Affiliated Eye Hospital, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou Medical University, 270 Xueyuan Xi Road, Wenzhou, Zhejiang 325000, China; zhoujw@mail.eye.ac.cn
  • Pi-Chun Huang, Department of Psychology, National Cheng Kung University, 1 University Road, Tainan City 701, Taiwan; pichun_huang@mail.ncku.edu.tw
Investigative Ophthalmology & Visual Science November 2019, Vol.60, 4858-4864. doi:https://doi.org/10.1167/iovs.19-27893
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      Chunwen Tao, Yidong Wu, Ling Gong, Shijia Chen, Yu Mao, Yiya Chen, Jiawei Zhou, Pi-Chun Huang; Abnormal Monocular and Dichoptic Temporal Synchrony in Adults with Amblyopia. Invest. Ophthalmol. Vis. Sci. 2019;60(14):4858-4864. doi: https://doi.org/10.1167/iovs.19-27893.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: We investigate temporal synchrony within one eye and between both eyes in adults with amblyopia.

Methods: Eight adult amblyopes (range, 19.88–27.81 years old; median, 22.86 years old) and 12 age-matched adults with normal vision (range, 21.2–50.30 years old; median, 23.78 years old) participated in the experiment. We showed two pairs of Gaussian blobs flickering at 1 Hz as visual stimuli, one pair with the same temporal phase modulation (i.e., the reference) and another pair with a distinct temporal phase (i.e., the signal). We employed the constant stimuli method to measure the minimum degree of temporal phase (temporal synchrony threshold), at which participants were able to discriminate the signal pair under binocular, monocular, and dichoptic viewing configurations.

Results: The temporal synchrony threshold was different across the six configurations (P = 0.001). There was also an interaction between the configuration and the group (P = 0.004). The synchrony threshold was significantly higher in amblyopes than in controls under the configurations where two pairs of blobs were presented to the amblyopic eye (136.52 ± 50.19 vs. 97.08 ± 22.02 ms, P = 0.027) and where the paired blobs were presented to different eyes (163.15 ± 80.85 vs. 111.61 ± 22.46 ms, P = 0.049). The visual deficits in these two configurations were significantly correlated (r = 0.824, P = 0.012).

Conclusions: The threshold for detecting temporal asynchrony increased when the stimuli were presented only to the amblyopic eye and when they were dichoptically presented to the amblyopic and fellow eyes.

Amblyopia affects 0.5% to 3.6% of the population1,2 and is one of the most common causes of vision deficit in children.3 Extensive evidence has demonstrated that amblyopes have poor spatial vision, including visual acuity, vernier acuity, grating acuity, contrast sensitivity,4 binocular combination,5 stereoacuity,6 second-order motion perception,7 and global form integration8 in the amblyopic eye. Apart from the spatial visual deficits, amblyopes also experience temporal visual deficit. For example, the amblyopic eye has trouble in detecting a movement or a flicker at a temporal frequency of 0.5 to 8 Hz,9 discriminating global motion direction,10 and segregating temporally defined figure–ground signals.11 Huang and colleagues12 also reported that the amblyopic eye's temporal synchrony sensitivity, which is defined as the minimum degree of temporal phase difference that enables participants to discriminate that the target is flickering asynchronously in time, was considerably higher than that of the fellow eye. These visual deficits in spatial and temporal processes are considered to be from some abnormalities in the developed visual system in the brain1318 rather than those in the eye. Since the problems reside in the neural circuitry rather than anatomy of the eye, they cannot be directly corrected optically.4,19 
In most studies, researchers have studied the visual deficit from amblyopia monocularly to determine the difference between the amblyopic eye and the fellow eye. The binocular visual deficit in amblyopia has been receiving more recognition,5,2026 namely, the role of interocular suppression from the fellow eye to the amblyopic eye.5,20,22,23,27,28 The importance of interocular suppression has been well documented in various binocular spatial visual processes, including binocular phase combination,5,7 binocular contrast combination,23 binocular global form integration,29 and binocular rivalry.30 These binocular visual deficits have been studied using suprathreshold visual stimuli. This indicates that the deficits cannot be accounted for only by monocular spatial visual loss of the amblyopes and that interocular suppression was involved in binocular processing. 
However, the extent of the visual deficits in binocular temporal visual processes in amblyopia, especially the relationship between monocular (within the eye) and dichoptic (between eyes) temporal visual deficits, has not been fully understood. We developed a paradigm that measures the ability to discriminate temporal asynchrony based on a previous study12 and measured the temporal synchrony sensitivity of amblyopes under binocular, monocular, and dichoptic viewing configurations. We demonstrated that there are temporal synchrony deficits within the eye and between eyes in amblyopia. 
Methods
Participants
Eight adults with anisometropic or mixed amblyopia (AMB group; range, 19.88–27.81 years old; average, 23.68 ± 2.86 years old, mean ± standard deviation [SD]; median, 22.86 years old) and 12 age-matched (U = 60, P = 0.384; Mann-Whitney U test) controls with emmetropia (EMM group; range, 21.20–50.30 years old; average, 26.49 ± 7.77 years old; median, 23.78 years old) participated in the study. Participants in the EMM group had spherical equivalent refractive errors between +0.75 and −0.50 diopter (D) and normal or corrected to normal visual acuity (no worse than 0.00 logMAR). Amblyopia was defined according to the Preferred Practice Patterns of the American Academy of Ophthalmology31 with a best-corrected visual acuity in the amblyopic eye between 0.10 (logMAR) and 1.00 (logMAR) and 0.05 (logMAR) or a better vision in the fellow eye. The details of the AMB group are provided in the Table. Participants' refractive errors, if any, were fully corrected during data collection. Participants were naive to the purpose of the study. This study followed the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Wenzhou Medical University. 
Table
 
Clinical Details of Amblyopes
Table
 
Clinical Details of Amblyopes
Apparatus
Stimuli were generated using a Macintosh laptop (Apple Inc., Cupertino, CA, USA) equipped with Matlab (Mathworks, Natick, MA, USA) and Psychtoolbox 3.0.14.32,33 We dichoptically displayed the stimuli on gamma-corrected head-mounted three-dimensional goggles (Goovis Pro; NED Optics, Shenzhen, China). The goggles had a resolution of 1600 × 900 pixels (corresponding to 46° × 26°) and a refresh rate of 60 Hz in each eye. The maximal luminance of the OLED goggles was 150 cd/m2
Stimuli
The stimuli consisted of four Gaussian blobs flickering at 1 Hz. One pair of Gaussian blobs was presented above the fixation cross at the center, and the other pair was presented below the fixation. One pair flickered synchronously; it served as a reference. The other pair flickered asynchronously; it acted as a signal. Observers were asked to determine the position of signal blobs (i.e., above or below the fixation). The extent of the asynchrony was manipulated by varying the temporal phase difference between flickering blobs. The two blobs in each pair were presented diagonally with a separation of 2.46° horizontally and vertically. The center of the two blobs was 4.3° above or below the fixation. Between the trials, the SD of each Gaussian blob randomly varied from 0.28° to 0.46°, and their luminance contrast ranged from 0.4 to 0.8 to prevent participants from using local cues to complete the task. 
All stimuli were presented within a binocular square frame (23° × 23°). To enable a better fusion, we dichoptically presented a cross as a fixation point (size: 1.16° × 0.58°) at the center of the frame and a short vertical line (0.58°) at the edge of the frame to the two eyes (Fig. 1). During the beginning of the test, participants were asked to adjust the position of the frames to align the two eyes. 
Figure 1
 
Illustration of the experimental design. The stimuli consisted of four Gaussian blobs flickering at 1 Hz. One pair of Gaussian blobs was presented above the fixation cross at the center, and the other pair was presented below the fixation cross. One pair flickered synchronously and served as reference blobs (Reference). The other pair flickered asynchronously and acted as signal blobs (Signal). Observers were asked to determine the position of the signal blobs (i.e., above or below the fixation). We measured the synchrony threshold of the participants in (a) binocular viewing configuration, where the signal and reference blobs were presented to both eyes (Bi); (b, c) monocular viewing configurations, where the signal blobs were presented to the amblyopic eye (MA) or the fellow eye (MF), and the reference blobs were presented to the same eye; (d, e) partially dichoptic viewing configurations, where the signal blobs were presented to the amblyopic eye (D2A) or the fellow eye (D2F), and the reference blobs were presented to the other eye; and (f) pure dichoptic viewing configuration, where both the signal and reference blobs were presented to different eyes (Di). These six configurations were tested using an order randomized for individual participants. AE, amblyopic eye; FE, fellow eye.
Figure 1
 
Illustration of the experimental design. The stimuli consisted of four Gaussian blobs flickering at 1 Hz. One pair of Gaussian blobs was presented above the fixation cross at the center, and the other pair was presented below the fixation cross. One pair flickered synchronously and served as reference blobs (Reference). The other pair flickered asynchronously and acted as signal blobs (Signal). Observers were asked to determine the position of the signal blobs (i.e., above or below the fixation). We measured the synchrony threshold of the participants in (a) binocular viewing configuration, where the signal and reference blobs were presented to both eyes (Bi); (b, c) monocular viewing configurations, where the signal blobs were presented to the amblyopic eye (MA) or the fellow eye (MF), and the reference blobs were presented to the same eye; (d, e) partially dichoptic viewing configurations, where the signal blobs were presented to the amblyopic eye (D2A) or the fellow eye (D2F), and the reference blobs were presented to the other eye; and (f) pure dichoptic viewing configuration, where both the signal and reference blobs were presented to different eyes (Di). These six configurations were tested using an order randomized for individual participants. AE, amblyopic eye; FE, fellow eye.
Design
We tested the synchrony threshold of participants in six configurations: Bi (Fig. 1a), binocular viewing, where the signal and reference blobs were presented to both eyes; MA (Fig. 1b), monocular amblyopic viewing (controls: monocular nondominant eye viewing), where both signal and reference blobs were presented to the amblyopic (nondominant) eye; MF (Fig. 1c), monocular fellow eye viewing (controls: monocular dominant eye viewing), where both signal and reference blobs were presented to the fellow (dominant) eye; D2A (Fig. 1d), dichoptic amblyopic viewing, where the signal blobs were presented to the amblyopic eye, and the reference blobs were presented to the fellow eye; D2F (Fig. 1e), dichoptic fellow eye viewing, where the signal blobs were presented to the fellow eye, and the reference blobs were presented to the amblyopic eye; Di (Fig. 1f), pure dichoptic viewing, where both the signal and reference blobs were presented to different eyes. These six configurations were tested using an order randomized for all participants. An illustration of these six configurations is provided in Figure 1
Procedure
A constant stimuli method was used to measure the minimum degree of asynchrony. Eight levels of temporal lag (i.e., temporal phase difference between the pairs of asynchronous blobs) with a rate ranging from 33.33 to 266.67 ms and an interval of 33.33 ms were tested for each viewing configuration. In each trial, the stimuli were presented for 1 second. Participants were asked to determine the position of signal blobs (i.e., whether they were above or below the fixation, two-alternative forced choice, 2AFC). The next trial started 750 ms after participants' response. The six viewing configurations and eight levels of temporal lag were tested using an order randomized in various trials. Each observer completed 960 trials totally in two sections. Each section included 480 trials with 10 trials tested for each condition (six configurations and eight temporal lags). Participants were allowed to take a break for every 144 trials and started the experiment whenever they were ready to proceed. 
Data Analysis
For each participant, we combined all trials and plotted the psychometric function, which was defined as the proportion correct against the temporal lag (i.e., the temporal phase difference between the pairs of asynchronous blobs, in ms). The psychometric functions of the six configurations were fitted using Palamedes 1.8.1.34 Each psychometric function was fitted based on the following equation:  
\(\def\upalpha{\unicode[Times]{x3B1}}\)\(\def\upbeta{\unicode[Times]{x3B2}}\)\(\def\upgamma{\unicode[Times]{x3B3}}\)\(\def\updelta{\unicode[Times]{x3B4}}\)\(\def\upvarepsilon{\unicode[Times]{x3B5}}\)\(\def\upzeta{\unicode[Times]{x3B6}}\)\(\def\upeta{\unicode[Times]{x3B7}}\)\(\def\uptheta{\unicode[Times]{x3B8}}\)\(\def\upiota{\unicode[Times]{x3B9}}\)\(\def\upkappa{\unicode[Times]{x3BA}}\)\(\def\uplambda{\unicode[Times]{x3BB}}\)\(\def\upmu{\unicode[Times]{x3BC}}\)\(\def\upnu{\unicode[Times]{x3BD}}\)\(\def\upxi{\unicode[Times]{x3BE}}\)\(\def\upomicron{\unicode[Times]{x3BF}}\)\(\def\uppi{\unicode[Times]{x3C0}}\)\(\def\uprho{\unicode[Times]{x3C1}}\)\(\def\upsigma{\unicode[Times]{x3C3}}\)\(\def\uptau{\unicode[Times]{x3C4}}\)\(\def\upupsilon{\unicode[Times]{x3C5}}\)\(\def\upphi{\unicode[Times]{x3C6}}\)\(\def\upchi{\unicode[Times]{x3C7}}\)\(\def\uppsy{\unicode[Times]{x3C8}}\)\(\def\upomega{\unicode[Times]{x3C9}}\)\(\def\bialpha{\boldsymbol{\alpha}}\)\(\def\bibeta{\boldsymbol{\beta}}\)\(\def\bigamma{\boldsymbol{\gamma}}\)\(\def\bidelta{\boldsymbol{\delta}}\)\(\def\bivarepsilon{\boldsymbol{\varepsilon}}\)\(\def\bizeta{\boldsymbol{\zeta}}\)\(\def\bieta{\boldsymbol{\eta}}\)\(\def\bitheta{\boldsymbol{\theta}}\)\(\def\biiota{\boldsymbol{\iota}}\)\(\def\bikappa{\boldsymbol{\kappa}}\)\(\def\bilambda{\boldsymbol{\lambda}}\)\(\def\bimu{\boldsymbol{\mu}}\)\(\def\binu{\boldsymbol{\nu}}\)\(\def\bixi{\boldsymbol{\xi}}\)\(\def\biomicron{\boldsymbol{\micron}}\)\(\def\bipi{\boldsymbol{\pi}}\)\(\def\birho{\boldsymbol{\rho}}\)\(\def\bisigma{\boldsymbol{\sigma}}\)\(\def\bitau{\boldsymbol{\tau}}\)\(\def\biupsilon{\boldsymbol{\upsilon}}\)\(\def\biphi{\boldsymbol{\phi}}\)\(\def\bichi{\boldsymbol{\chi}}\)\(\def\bipsy{\boldsymbol{\psy}}\)\(\def\biomega{\boldsymbol{\omega}}\)\(\def\bupalpha{\unicode[Times]{x1D6C2}}\)\(\def\bupbeta{\unicode[Times]{x1D6C3}}\)\(\def\bupgamma{\unicode[Times]{x1D6C4}}\)\(\def\bupdelta{\unicode[Times]{x1D6C5}}\)\(\def\bupepsilon{\unicode[Times]{x1D6C6}}\)\(\def\bupvarepsilon{\unicode[Times]{x1D6DC}}\)\(\def\bupzeta{\unicode[Times]{x1D6C7}}\)\(\def\bupeta{\unicode[Times]{x1D6C8}}\)\(\def\buptheta{\unicode[Times]{x1D6C9}}\)\(\def\bupiota{\unicode[Times]{x1D6CA}}\)\(\def\bupkappa{\unicode[Times]{x1D6CB}}\)\(\def\buplambda{\unicode[Times]{x1D6CC}}\)\(\def\bupmu{\unicode[Times]{x1D6CD}}\)\(\def\bupnu{\unicode[Times]{x1D6CE}}\)\(\def\bupxi{\unicode[Times]{x1D6CF}}\)\(\def\bupomicron{\unicode[Times]{x1D6D0}}\)\(\def\buppi{\unicode[Times]{x1D6D1}}\)\(\def\buprho{\unicode[Times]{x1D6D2}}\)\(\def\bupsigma{\unicode[Times]{x1D6D4}}\)\(\def\buptau{\unicode[Times]{x1D6D5}}\)\(\def\bupupsilon{\unicode[Times]{x1D6D6}}\)\(\def\bupphi{\unicode[Times]{x1D6D7}}\)\(\def\bupchi{\unicode[Times]{x1D6D8}}\)\(\def\buppsy{\unicode[Times]{x1D6D9}}\)\(\def\bupomega{\unicode[Times]{x1D6DA}}\)\(\def\bupvartheta{\unicode[Times]{x1D6DD}}\)\(\def\bGamma{\bf{\Gamma}}\)\(\def\bDelta{\bf{\Delta}}\)\(\def\bTheta{\bf{\Theta}}\)\(\def\bLambda{\bf{\Lambda}}\)\(\def\bXi{\bf{\Xi}}\)\(\def\bPi{\bf{\Pi}}\)\(\def\bSigma{\bf{\Sigma}}\)\(\def\bUpsilon{\bf{\Upsilon}}\)\(\def\bPhi{\bf{\Phi}}\)\(\def\bPsi{\bf{\Psi}}\)\(\def\bOmega{\bf{\Omega}}\)\(\def\iGamma{\unicode[Times]{x1D6E4}}\)\(\def\iDelta{\unicode[Times]{x1D6E5}}\)\(\def\iTheta{\unicode[Times]{x1D6E9}}\)\(\def\iLambda{\unicode[Times]{x1D6EC}}\)\(\def\iXi{\unicode[Times]{x1D6EF}}\)\(\def\iPi{\unicode[Times]{x1D6F1}}\)\(\def\iSigma{\unicode[Times]{x1D6F4}}\)\(\def\iUpsilon{\unicode[Times]{x1D6F6}}\)\(\def\iPhi{\unicode[Times]{x1D6F7}}\)\(\def\iPsi{\unicode[Times]{x1D6F9}}\)\(\def\iOmega{\unicode[Times]{x1D6FA}}\)\(\def\biGamma{\unicode[Times]{x1D71E}}\)\(\def\biDelta{\unicode[Times]{x1D71F}}\)\(\def\biTheta{\unicode[Times]{x1D723}}\)\(\def\biLambda{\unicode[Times]{x1D726}}\)\(\def\biXi{\unicode[Times]{x1D729}}\)\(\def\biPi{\unicode[Times]{x1D72B}}\)\(\def\biSigma{\unicode[Times]{x1D72E}}\)\(\def\biUpsilon{\unicode[Times]{x1D730}}\)\(\def\biPhi{\unicode[Times]{x1D731}}\)\(\def\biPsi{\unicode[Times]{x1D733}}\)\(\def\biOmega{\unicode[Times]{x1D734}}\)\begin{equation}{\rm{\psi }}\left( {{\rm{x}};{\rm{\alpha }},{\rm{\beta }},{\rm{\gamma }},{\rm{\lambda }}} \right) = {\rm{\gamma }} + \left( {1 - {\rm{\gamma }} - {\rm{\lambda }}} \right){\rm{F}}\left( {{\rm{x}};{\rm{\alpha }},{\rm{\beta }}} \right) = {\rm{\gamma }} + \left( {1 - {\rm{\gamma }} - {\rm{\lambda }}} \right)\left[ {1 - {\rm{exp}}\left( { - {{\left( {{\rm{\ x}}/{\rm{\alpha }}} \right)}^{\rm{\beta }}}} \right)} \right]\end{equation}
 
In which F (x; α, β) is the Weibull function; x is the temporal lag; α is the threshold; β is a free parameter related to the slope of the function; γ is the guessed rate; and λ is the lapse rate. During our fitting, we set γ at 0.5 and constrained the λ to a fixed value (ranging from 0 to 0.06) for each participant. We also assumed the slopes were the same for the six configurations. (For most of our participants, this reduced model with same slopes for the six configurations produced statistically equivalent accounts as the full model with varied slopes for the six configurations, except one amblyope and two emmetropic subjects; applying full model fitting for these three participants generated similar thresholds and the same conclusions with the present version.) We used the method of maximum likelihood to estimate the threshold and slope of the psychometric function. 
Results
In Figure 2, we plotted the proportion correct in discriminating signals as a function of the temporal phase lag for the eight amblyopes. Most of the performances of the amblyopes under the six configurations, as plotted by distinct colored dots in each part of the figure, were inconsistent. A 2-way within-subject repeated-measures analysis of variance (ANOVA), with the configuration (six levels) and temporal lag (eight levels) selected as within-subject factors, revealed no significant interaction between temporal lag and configuration (F[5.270, 36.891] = 1.210, P = 0.324). The effects of both the temporal lag (F[6.721, 73.935] = 1.431, P = 0.208). The effect of temporal lag was significant (F[2.946, 32.401] = 185.058, P < 0.001), whereas the effect of configuration was insignificant (F[5,55] = 1.524, P = 0.197). were significant. These results suggest that the synchrony thresholds were different under the six configurations. 
Figure 2
 
The proportion correct in discriminating temporal asynchrony signals as a function of temporal lag for amblyopes. The data of the eight amblyopes are presented in separate parts of the figure. In each, the vertical axis represents the proportion correct (in percentage) and the horizontal axis represents the temporal lag (in ms). Distinct colored symbols represent the results of the six configurations that we list in Figure 1, namely, plus sign, circle, asterisk, pentastar, square, and triangle, which represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. The associated lines represent the best-fitting psychometric functions obtained with Palamedes 1.8.1.34
Figure 2
 
The proportion correct in discriminating temporal asynchrony signals as a function of temporal lag for amblyopes. The data of the eight amblyopes are presented in separate parts of the figure. In each, the vertical axis represents the proportion correct (in percentage) and the horizontal axis represents the temporal lag (in ms). Distinct colored symbols represent the results of the six configurations that we list in Figure 1, namely, plus sign, circle, asterisk, pentastar, square, and triangle, which represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. The associated lines represent the best-fitting psychometric functions obtained with Palamedes 1.8.1.34
The psychometric functions of the 12 normal controls in discriminating the asynchrony signals under six configurations are plotted in Figure 3. The performances of controls were relatively consistent under the six configurations. A 2-way within-subject repeated-measures ANOVA with the configuration (six levels) and temporal lag (eight levels) selected as within-subject factors also revealed no interaction between temporal lag and configuration (F[6.721, 73.935] = 1.431, P = 0.208). The effect of temporal lag was significant (F[2.946, 32.401] = 185.058, P < 0.001), whereas the effect of configuration was insignificant (F[5,55] = 1.524, P = 0.197). These results indicate that the synchrony thresholds under the six configurations were consistent in normal controls. 
Figure 3
 
Proportion correct in discriminating temporal synchrony signals as a function of temporal lag for controls with emmetropia. The data of the 12 controls with emmetropia are displayed in separate parts of the figure. These are organized in the same way as in Figure 2.
Figure 3
 
Proportion correct in discriminating temporal synchrony signals as a function of temporal lag for controls with emmetropia. The data of the 12 controls with emmetropia are displayed in separate parts of the figure. These are organized in the same way as in Figure 2.
To better demonstrate the difference in temporal asynchrony discrimination between the two groups, we plotted the averaged temporal synchrony thresholds under the six configurations in Figure 4 for both groups. A mixed repeated-measures ANOVA on temporal synchrony thresholds with group as the between-subjects factor (two levels: EMM and AMB) and configuration as the within-subject factor (six levels) revealed that the effect of configuration was significant (F[2.37, 42.661] = 7.228, P = 0.001), and the interaction between group and configuration was significant (F[2.37, 42.661] = 5.853, P = 0.004). We subsequently conducted pairwise post hoc contrasts to further analyze this effect. The results are summarized as follows: (1) In the emmetropic group, the only significant threshold differences were observed between the MA and MF configurations (P = 0.024) and between the MA and D2A configurations (P = 0.034), and the differences among the other configurations were insignificant (for all, P ≥ 0.128; Fig. 4A, left). (2) In the amblyopic group, the threshold difference between MA and D2A configurations was insignificant (P = 0.617), and it was insignificant among Bi, MF, and D2F configurations (for all, P ≥ 0.508); however, it was significant among the other configurations (for all, P ≤ 0.033; Fig. 4A, right). (3) The threshold differences between the two groups were significant under the MA (P = 0.027) and Di (P = 0.049) configurations but not under the other configurations (for all, P ≥ 0.169; Fig. 4B). We also conducted independent sample t-tests to compare the slopes of the psychometric functions between the two groups and noted no significant difference between the groups (t[18] = 1.242, P = 0.230). 
Figure 4
 
Mean temporal synchrony thresholds of the two groups. The differences between the six configurations within a group were plotted in panel A and the differences between groups were plotted in panel B. The open columns represent the result of the emmetropic group, and the solid columns represent the result of the amblyopic group. Each color represents a different configuration. From the left to the right, green, red, carmine, blue, turquoise, and black represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. Error bars represent the standard errors. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 4
 
Mean temporal synchrony thresholds of the two groups. The differences between the six configurations within a group were plotted in panel A and the differences between groups were plotted in panel B. The open columns represent the result of the emmetropic group, and the solid columns represent the result of the amblyopic group. Each color represents a different configuration. From the left to the right, green, red, carmine, blue, turquoise, and black represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. Error bars represent the standard errors. *P < 0.05; **P < 0.01; ***P < 0.001.
In summary, we demonstrate that amblyopes have deficits in discriminating temporal asynchrony signals when the stimuli are shown solely to one eye (MA versus MF) and between eyes (D2A versus D2F, and Di compared to the rest of the configurations). Compared with the control group, the amblyopic group exhibited relatively poor performance in MA and Di configurations. 
Whether a relationship exists between the temporal synchrony threshold under the dichoptic viewing configuration (i.e., between-eyes deficits) and the monocular synchrony thresholds in the amblyopic eye (i.e., within-eye deficits) is of interest. In Figure 5, we plot the temporal synchrony thresholds of amblyopies under the dichoptic viewing configuration as a function of their monocular synchrony thresholds in the amblyopic eyes. A 2-tailed Pearson correlation analysis indicated that there was a significant and strong correlation between the thresholds of MA and Di viewing configurations in amblyopes (r = 0.824, P = 0.012). 
Figure 5
 
Relationship between temporal synchrony thresholds in Di and MA viewing configurations in amblyopes. Temporal synchrony threshold of amblyopes under the dichoptic viewing configuration was plotted as a function of the temporal synchrony threshold in the amblyopic eye. Each dot represents the results of one amblyope. The average results of the controls were plotted with the open square symbol; error bars represent standard errors.
Figure 5
 
Relationship between temporal synchrony thresholds in Di and MA viewing configurations in amblyopes. Temporal synchrony threshold of amblyopes under the dichoptic viewing configuration was plotted as a function of the temporal synchrony threshold in the amblyopic eye. Each dot represents the results of one amblyope. The average results of the controls were plotted with the open square symbol; error bars represent standard errors.
Discussion
In the present study, we found that amblyopes have a higher temporal synchrony threshold when discriminating the asynchronous pair of signal blobs presented to the amblyopic eye (Fig. 4A) under the monocular and dichoptic viewing configurations (Fig. 4B). 
For amblyopes, the temporal synchrony thresholds of the amblyopic eye (i.e., MA) were significantly higher than those of the fellow eye (i.e., MF; Fig. 4A). Using a similar paradigm, Huang et al.12 investigated the temporal synchrony deficit in amblyopia under the monocular viewing configuration (MA and MF). They compared the temporal deficit in strabismic and nonstrabismic amblyopia and the temporal deficit in foveal and peripheral vision. They reported that nonstrabismic amblyopes also had a higher temporal synchrony threshold in the amblyopic eye (116.39 ms) than in the fellow eye (68.81 ms) when discriminating temporal asynchrony blobs whose separation was 2.5° of visual angle. Comparing our results with a similar target separation and the types of amblyopia in the previous study, we show that the temporal synchrony threshold in the amblyopic eye is 136.52 ms and that in fellow eye is 97.08 ms. The difference in the synchrony thresholds between the two studies might be caused by the methodologies. Huang et al.12 used a 4-AFC odd-man-out paradigm with a staircase method; in this method, subjects were asked to detect which blob flickered asynchronously. However, we used a 2-AFC paradigm with the constant stimuli method; in this method, subjects were asked to detect which pair flickered asynchronously. Another explanation could be interocular suppression. Interocular suppression is typically chronic.35,36 When the monocular viewing configuration is conducted by occluding one eye, the interocular suppression is minimized. This might explain our study's findings, which show higher temporal synchrony thresholds at the pure dichoptic configuration (i.e., Di). 
Several studies have reported the existence of the temporal deficit in the amblyopic eye. Many of the studies concerned the temporal dependence in contrast detection ability. For example, the contrast sensitivity gets reduced at all temporal frequencies in the amblyopic eye.9,37 This form of deficit has also been revealed with a weak magnitude in visually evoked potential38 and a delayed hemodynamic response function in the early visual cortex that receives input from the amblyopic eye.39 These deficits can be explained by the deficit in spatiotemporal contrast sensitivity. Our study, in contrast, addresses the temporal processing deficit per se by measuring the temporal synchrony threshold with a suprathreshold stimulus. The temporal synchrony of neurons has been thought of as the underlying mechanism for binding different features into one object.40 A reduced synchrony of firing in the amblyopic eye in cats has been found when the contrast and spatial tunings in the amblyopic eye are normal.41 Our experimental results are consistent with the findings that show higher synchrony thresholds in the amblyopic eye. The reduced synchrony might contribute to the spatiotemporal deficit in amblyopia.41 
Notably, amblyopes also exhibited poor performance when discriminating temporal asynchrony signals that were dichoptically presented to the two eyes (i.e., the Di viewing configuration; Fig. 4B). The temporal synchrony thresholds under the dichoptic viewing configuration were significantly higher than those under the monocular viewing configuration in amblyopes but not in normal adults (Fig. 4A). One might argue that the temporal synchrony deficit found in the Di viewing configuration was due to the difference in the perceived luminance or contrast between eyes.24,42 In our study, we randomized the luminance contrast of each blob independently; thus the cues for using the luminance contrast between eyes were reduced but not excluded. Whether the perceived luminance between eyes modulates the temporal synchrony process or not (or the temporal synchrony between eyes alternates the perceived luminance) needs to be resolved in future studies. Nevertheless, we show that the temporal synchrony thresholds under the Di viewing condition were significantly higher but correlated with those under the MA viewing condition (Fig. 5). These results indicate that amblyopes had additional between-eyes deficits in processing the temporal asynchrony signals and that such deficits could not be totally accounted for by the within-eye deficits in processing the temporal synchrony signals. 
Data and the current models that describe the visual deficit of amblyopes in binocular spatial processing show that amblyopes have both monocular and interocular deficits in binocular processing. The models include, for example, the two-stage model,21 the multipathway contrast-gain control model,23 and the gain-control and gain-enhancement model.43 We further report that temporal synchrony thresholds follow a similar pattern with both within-eye and between-eyes deficits. Our findings provide new insight on how interocular suppression can be involved in temporal binocular processing. 
In conclusion, we demonstrate temporal synchrony deficits within the eye and between eyes in amblyopia. Although the best-corrected visual acuity of the amblyopic eye is the main outcome in clinical trials and clinical practice regarding amblyopia, recent studies have suggested that best-corrected visual acuity of the amblyopic eye might not be the main reason for the poor life quality of amblyopes.44,45 The relationship between temporal synchrony deficits within the eye and between eyes in amblyopia and patients' quality of life will need to be further studied. In addition, accumulating evidence indicates that the poor visual performance of amblyopes in spatial visual processing can be improved by refractive correction, patching, atropine, perceptual learning, and other methods.2 A future study should investigate whether the patient visual deficits in temporal processing observed in this study can also be treated by these methods. 
Acknowledgments
Supported by National Natural Science Foundation of China Grants NSFC 31970975 and 81500754 and a Wenzhou Medical University Grant QTJ16005 (JZ), and a MOST 104-2628-H-006-001-MY3 Grant (P-CH). This manuscript was edited by Wallace Academic Editing and Seung Hyun (Sam) Min. 
Disclosure: C. Tao, None; Y. Wu, None; L. Gong, None; S. Chen, None; Y. Mao, None; Y. Chen, None; J. Zhou, None; P.-C. Huang, None 
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Figure 1
 
Illustration of the experimental design. The stimuli consisted of four Gaussian blobs flickering at 1 Hz. One pair of Gaussian blobs was presented above the fixation cross at the center, and the other pair was presented below the fixation cross. One pair flickered synchronously and served as reference blobs (Reference). The other pair flickered asynchronously and acted as signal blobs (Signal). Observers were asked to determine the position of the signal blobs (i.e., above or below the fixation). We measured the synchrony threshold of the participants in (a) binocular viewing configuration, where the signal and reference blobs were presented to both eyes (Bi); (b, c) monocular viewing configurations, where the signal blobs were presented to the amblyopic eye (MA) or the fellow eye (MF), and the reference blobs were presented to the same eye; (d, e) partially dichoptic viewing configurations, where the signal blobs were presented to the amblyopic eye (D2A) or the fellow eye (D2F), and the reference blobs were presented to the other eye; and (f) pure dichoptic viewing configuration, where both the signal and reference blobs were presented to different eyes (Di). These six configurations were tested using an order randomized for individual participants. AE, amblyopic eye; FE, fellow eye.
Figure 1
 
Illustration of the experimental design. The stimuli consisted of four Gaussian blobs flickering at 1 Hz. One pair of Gaussian blobs was presented above the fixation cross at the center, and the other pair was presented below the fixation cross. One pair flickered synchronously and served as reference blobs (Reference). The other pair flickered asynchronously and acted as signal blobs (Signal). Observers were asked to determine the position of the signal blobs (i.e., above or below the fixation). We measured the synchrony threshold of the participants in (a) binocular viewing configuration, where the signal and reference blobs were presented to both eyes (Bi); (b, c) monocular viewing configurations, where the signal blobs were presented to the amblyopic eye (MA) or the fellow eye (MF), and the reference blobs were presented to the same eye; (d, e) partially dichoptic viewing configurations, where the signal blobs were presented to the amblyopic eye (D2A) or the fellow eye (D2F), and the reference blobs were presented to the other eye; and (f) pure dichoptic viewing configuration, where both the signal and reference blobs were presented to different eyes (Di). These six configurations were tested using an order randomized for individual participants. AE, amblyopic eye; FE, fellow eye.
Figure 2
 
The proportion correct in discriminating temporal asynchrony signals as a function of temporal lag for amblyopes. The data of the eight amblyopes are presented in separate parts of the figure. In each, the vertical axis represents the proportion correct (in percentage) and the horizontal axis represents the temporal lag (in ms). Distinct colored symbols represent the results of the six configurations that we list in Figure 1, namely, plus sign, circle, asterisk, pentastar, square, and triangle, which represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. The associated lines represent the best-fitting psychometric functions obtained with Palamedes 1.8.1.34
Figure 2
 
The proportion correct in discriminating temporal asynchrony signals as a function of temporal lag for amblyopes. The data of the eight amblyopes are presented in separate parts of the figure. In each, the vertical axis represents the proportion correct (in percentage) and the horizontal axis represents the temporal lag (in ms). Distinct colored symbols represent the results of the six configurations that we list in Figure 1, namely, plus sign, circle, asterisk, pentastar, square, and triangle, which represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. The associated lines represent the best-fitting psychometric functions obtained with Palamedes 1.8.1.34
Figure 3
 
Proportion correct in discriminating temporal synchrony signals as a function of temporal lag for controls with emmetropia. The data of the 12 controls with emmetropia are displayed in separate parts of the figure. These are organized in the same way as in Figure 2.
Figure 3
 
Proportion correct in discriminating temporal synchrony signals as a function of temporal lag for controls with emmetropia. The data of the 12 controls with emmetropia are displayed in separate parts of the figure. These are organized in the same way as in Figure 2.
Figure 4
 
Mean temporal synchrony thresholds of the two groups. The differences between the six configurations within a group were plotted in panel A and the differences between groups were plotted in panel B. The open columns represent the result of the emmetropic group, and the solid columns represent the result of the amblyopic group. Each color represents a different configuration. From the left to the right, green, red, carmine, blue, turquoise, and black represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. Error bars represent the standard errors. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 4
 
Mean temporal synchrony thresholds of the two groups. The differences between the six configurations within a group were plotted in panel A and the differences between groups were plotted in panel B. The open columns represent the result of the emmetropic group, and the solid columns represent the result of the amblyopic group. Each color represents a different configuration. From the left to the right, green, red, carmine, blue, turquoise, and black represent Bi, MA, MF, D2A, D2F, and Di configurations, respectively. Error bars represent the standard errors. *P < 0.05; **P < 0.01; ***P < 0.001.
Figure 5
 
Relationship between temporal synchrony thresholds in Di and MA viewing configurations in amblyopes. Temporal synchrony threshold of amblyopes under the dichoptic viewing configuration was plotted as a function of the temporal synchrony threshold in the amblyopic eye. Each dot represents the results of one amblyope. The average results of the controls were plotted with the open square symbol; error bars represent standard errors.
Figure 5
 
Relationship between temporal synchrony thresholds in Di and MA viewing configurations in amblyopes. Temporal synchrony threshold of amblyopes under the dichoptic viewing configuration was plotted as a function of the temporal synchrony threshold in the amblyopic eye. Each dot represents the results of one amblyope. The average results of the controls were plotted with the open square symbol; error bars represent standard errors.
Table
 
Clinical Details of Amblyopes
Table
 
Clinical Details of Amblyopes
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