key: cord-0275957-ltukxzy3 authors: Roberts, Mariel; Carrasco, Marisa title: Exogenous attention generalizes location transfer of perceptual learning in adults with amblyopia date: 2021-09-24 journal: bioRxiv DOI: 10.1101/2021.04.27.441700 sha: d22b6382d09e14255ac6e404b392756d2b233ccb doc_id: 275957 cord_uid: ltukxzy3 Visual perceptual learning (VPL), or improved visual performance after practice, is a behavioral manifestation of the impressive neuroplasticity in the brain. However, its practical effectiveness is limited because improvements are often specific to the trained conditions and require significant time and effort. Thus, it is critical to understand the conditions that promote learning and its transfer. Covert endogenous (voluntary) and exogenous (involuntary) spatial attention help overcome VPL location and feature specificity in neurotypical adults, but whether they can also do so for people with atypical visual development is unknown. This is the first study to investigate the role of exogenous attention during VPL in a special population of adults. Here we show that exogenous attention helps generalize learning beyond trained spatial locations in adults with amblyopia, an ideal population for investigation given their asymmetrically developed, but highly plastic, visual cortex. Our findings provide insight into the mechanisms underlying changes in neuro(a)typical brain plasticity. Further, they reveal that attention can enhance the effectiveness of perceptual learning during rehabilitation of visual disorders. Visual perceptual learning (VPL) refers to enhancements in perceptual sensitivity or discriminability A corresponding analysis of median RT, our secondary variable, showed a significant main effect Given that the 4-way ANOVA did not reveal a main effect of eye, we collapsed across the 167 amblyopic and fellow eye data for the following analyses. show learning at the trained conditions. But to retain as many observers as possible to maximize 219 our statistical power, we performed a complementary series of analyses to understand how 220 precluding observers who got worse would impact our results. We converted observers' normalized 221 change in d' at the trained diagonal (collapsing across the two eyes) into z-scores (relative to each 222 observer's assigned group mean) and ranked observers in ascending order from those who 223 learned the least to most. We conducted the analyses three different times, in which we 224 systematically precluded the one (Figure 3) , two ( Figure S4 ), or three ( Figure S5 ) observers who 225 learned the least from each group. The statistical results were always the same (see Table S2 ). Therefore, in the following two paragraphs we only summarize the detailed results for the analysis Table S2 . To assess whether training with exogenous attention promotes generalization to untrained spatial 236 locations, we conducted a 3-way (Session: pre-test, post-test X Diagonal: trained, untrained X Group: Neutral, Attention) mixed ANOVA of d' in each group (Figure 3, qCSF. To assess potential changes in observers' broadband contrast sensitivity at the fovea, we 283 had them perform a 4-AFC orientation discrimination task that incorporated the quick Contrast Sensitivity Function (qCSF) procedure on days 2 and 16 (before and after training) (see Figure 285 S6). The qCSF is a Bayesian adaptive procedure that uses a trial-by-trial information gain strategy 286 to estimate and detect changes in the underlying contrast sensitivity functions of neurotypical (e.g., A Pearson's correlation matrix analysis revealed that, aside from the truncation parameter that did We also assessed whether and to what extent training reduced the interocular difference in visual 366 acuity (also known as amblyopic depth), a common metric for quantifying amblyopia severity. We There is evidence that covert spatial attention remains functionally intact in amblyopia (Roberts et Thus, the fact that both groups show similar performance at the trained diagonal but differential 487 improvement at the untrained can only be attributed to differences in exogenous attentional 488 allocation during training. These findings are encouraging, as they demonstrate that neuroplasticity 489 in the adult amblyopic brain may extend further than previously known. Complementary measures of broadband contrast sensitivity improvements at the fovea. Contrast 503 sensitivity improvements measured by the qCSF were largely driven by changes in the peak gain 504 (sensitivity) of the contrast sensitivity function, rather than the spatial frequency corresponding to 505 the peak, or increased sensitivity to lower or higher spatial frequencies (see group means in Table 506 S4 and detailed ANOVA results in Figure S7 ). Our observers trained on a 6-cpd Gabor, a 507 challenging spatial frequency for amblyopes, but not close to their spatial frequency cutoff. A VPL 508 study in which amblyopic observers showed increased sensitivity to higher spatial frequencies had 509 observers train on a contrast sensitivity task near their individual SF cutoffs (Huang et al., 2008) . Both groups also showed modest increases in the AULCSF, similar in magnitude to another VPL 534 Improvements in stereoacuity. Given the controversy that monocular training while patching the 535 fellow eye may promote interocular suppression over binocularity (Hess et al., 2015) , it is 536 encouraging that stereoacuity thresholds improved (decreased) in both groups (Figure 4 , Table S3 537 & Figure S11 for individual scatter plots). This finding reflects changes to observers' typical 538 binocular vision even when not wearing an eye patch, consistent with evidence that latent 539 binocularity remains in the amblyopic brain, and can be at least partially recovered given the right We also found a correlation between improvements in crowding and visual acuity, although The mechanisms underlying crowding in amblyopic foveal vision may be more similar to crowding Optimal amount of training. There is evidence that the number of training hours that it takes for an 608 observer to achieve asymptotic performance directly scales with the severity of their deficit (Li et al. Training protocol. Our visual training task was relatively demanding; observers were required to 617 discriminate a peripheral target while maintaining fixation within a relatively tight fixation window. If 618 their eye moved outside of the window, the trial would be cancelled, and they would have to redo 619 the trial at the end of the block. As some observers suffered from greater fixational instability, 620 especially those with the strabismic ("lazy eye") or mixed subtypes of amblyopia, not all could 621 complete the same number of training blocks each day before becoming fatigued. In these few 622 cases (5 out of 20), we had to spread the 80 training blocks across more than ten sessions. other. Another source of variability was the different number of days that passed between training 627 sessions. We strongly recommended that no more than two days pass between training sessions, difference) between the two groups (see Table S1 ). Across all visual tasks and observers, the 642 amblyopic eye was worse than the fellow eye, providing confirmatory evidence for observers' 643 amblyopia diagnosis, and that the amblyopic contrast sensitivity deficit extends into the parafovea. As expected, all observers required more contrast in their amblyopic eye than fellow eye to 645 complete the task with similar performance; but most importantly, the required stimulus contrast for 646 each eye did not significantly differ between groups. Amblyopia subtypes. It has been proposed that the various subtypes of amblyopia (i.e., In the present study we employed peripheral exogenous precues during an orientation 726 Levi, 2020) . Thus, as in other amblyopia VPL studies (e.g., Li and Levi, 2008) , visual training may 727 have acted to reduce this elevated internal noise and retune observer's perceptual templates. There are several conceptual (e.g., Maniglia and Seitz, 2018) The Reverse hierarchy theory postulates that VPL is a top-down guided process that begins with The Integrated Reweighting Theory explains transfer across retinotopic locations by incorporating Fernández and Carrasco, 2020) and altered the distribution of VPL changes to be biased towards 778 higher brain areas whose responses are less tuned to specific spatial locations, features and/or 779 eyes. VPL for any task is widespread, likely involving several areas, and the pattern of VPL Conclusions. This study reveals that exogenous attention generalizes the effects of perceptual 814 training to untrained spatial locations in adults with amblyopia. Limitations of the study. Due to the COVID lockdown, we were unable to collect the post-test 817 data for one observer in the Attention group for all tasks in the visual battery. We were also unable 818 to bring observers back for a 6-month follow-up to see how much of the learning was retained after 819 an extended period, as we had originally planned. This study did not generate new unique reagents. Data and code availability. • Any additional information required to reanalyze the data reported in this paper is available 889 from the lead contact upon request. The observers who had been prescribed refractive correction from their personal eye doctor were 895 required to wear either the exact same pair of glasses or contacts that they would typically wear 896 throughout the entire study. Before training, we confirmed that observers exhibited a ≥ two-line disease were included in the study (see Table S1 for demographic and clinical information 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160 1161 1162 1163 1164 1165 1166 1167 Table S4 , related to Figure S7 . Task difficulty and the specificity of perceptual learning Reverse hierarchies and sensory 1289 learning Strabismic amblyopia. Part 1. Psychophysics. Clin Can perceptual learning be used to treat 1294 amblyopia beyond the critical period of visual development? Visual acuity testing. From the laboratory to the clinic Enhancing attentional control: lessons from action video 1301 games Controlling the false discovery rate: a practical and powerful 1304 approach to multiple testing The optimal correction for estimating extreme discriminability Visual attention: The past 25 years Spatial covert attention: Perceptual modulation How attention affects spatial resolution Covert attention accelerates the rate of visual information 1317 processing Spatial covert attention increases contrast 1320 sensitivity across the CSF: support for signal enhancement Visual recovery in cortical blindness is limited by high internal noise Endogenous spatial attention during perceptual learning 1332 facilitates location transfer Exogenous attention 1335 facilitates perceptual learning in visual acuity to untrained stimulus locations and features Exogenous attention facilitates location transfer of 1339 perceptual learning Visual perceptual learning and models Differential impact of endogenous 1345 and exogenous attention on activity in human visual cortex Attention reorients periodically Extinguishing exogenous attention via transcranial magnetic 1352 stimulation Adult visual cortical plasticity On the automaticity and flexibility of covert 1358 attention: a speed-accuracy trade-off analysis Exogenous spatial attention: evidence for intact functioning in adults with autism spectrum 1362 disorder Endogenous spatial attention: evidence for intact functioning in adults with autism Effects of monocular perceptual learning on binocular visual processing in adolescent and 1370 adult amblyopia. iScience Crowding" in normal and amblyopic vision assessed 1373 with Gaussian and Gabor C's Generalized perceptual learning in the absence of 1377 sensory adaptation Amblyopia and the binocular approach to its therapy qCSF in 1386 clinical application: efficient characterization and classification of contrast sensitivity functions in 1387 amblyopia Degraded attentional modulation of cortical 1390 neural populations in strabismic amblyopia Evaluating the 1393 performance of the quick CSF method in detecting contrast sensitivity function changes Broad bandwidth of perceptual learning in the visual 1397 system of adults with anisometropic amblyopia Prolonged training at threshold promotes robust retinotopic 1401 specificity in perceptual learning Perceptual learning reduces crowding 1405 in amblyopia and in the normal periphery Specificity of perceptual learning increases 1409 with increased training Task precision at transfer determines 1412 specificity of perceptual learning The effects of 1415 monocular training on binocular functions in anisometropic amblyopia Recurrent processing drives perceptual plasticity Differential impact of exogenous and endogenous attention on the 1423 contrast sensitivity function across eccentricity Neuroimaging of amblyopia and binocular vision: a review Cortical correlates of amblyopia Visual processing in amblyopia: human studies Linking assumptions in amblyopia Rethinking amblyopia 2020 Stereopsis and amblyopia: A mini-review Perceptual learning as a potential treatment for amblyopia: a mini-1450 review Prolonged perceptual learning of positional acuity in adult 1453 amblyopia: perceptual template retuning dynamics Transient attention enhances perceptual performance and 1457 FMRI response in human visual cortex Comparing the time course and efficacy of spatial and 1461 feature-based attention The therapeutic impact of perceptual 1464 learning on juvenile amblyopia with or without previous patching treatment Spatial attention: Different mechanisms for central and peripheral 1468 temporal precues? 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We used only valid peripheral cues, and not Main task stimuli. Observers were asked to fixate on a black cross (1° across) at the center of the 1017 screen throughout the trial (Figure 1a) . The target and distractor stimuli were both 3.2°-wide, 6-cpd The stimulus display screen was flipped, then presented onto a mirror 114 cm away from the 1080 observer to simulate presenting the task at 228 cm, the necessary distance for displaying letters of We designed our task to evaluate changes in orientation sensitivity (d'). Observers were 1107 encouraged to be as accurate as possible. Median RTs for correct trials served as a secondary 1108 variable to assess potential speed-accuracy tradeoffs. RTs were measured relative to the 1109 simultaneous onset of the Gabor stimuli and response cue (Figure 1a) , which remained onscreen 1110 for 123 ms. The Gabors disappeared, leaving only the response cue, and observers had to wait an 1111 additional 78 ms before they were allowed to respond within a 5-s window, to further encourage 1112 observers to be as accurate rather than as fast as possible. In our experimental design, as in many 1113 tasks that measure RT as the primary dependent variable (e.g., Wang et al., 2015) , it was 1114 impossible to distinguish the degree to which reaction time (RT) differences reflected changes in 1115 speed of processing, discriminability, response criterion, and/or motor learning (e.g., Carrasco and We conducted all ANOVAs in R with ezANOVA using the Type-III sums of squares approach. We 1119 always included Observer as a random factor, Eye (amblyopic, fellow), Diagonal (trained, 1120 untrained) and Session (pre-test, post-test) as fixed within-subjects factors, and Group (Neutral, 1121 Attention) as a fixed between-subjects factor. Planned comparisons were two-tailed paired t-tests, 1122 and the Benjamini-Hochberg adjustment (Benjamini and Hochberg, 1995) was applied to correct 1123 for multiple comparisons as it controls for the false discovery rate. All reports of variability represent 1124 ±1 standard error of the mean.