Feature variability determines specificity and transfer in multiorientation feature detection learning.

Historically, in many perceptual learning experiments, only a single stimulus is practiced, and learning is often specific to the trained feature. Our prior work has demonstrated that multi-stimulus learning (e.g., training-plus-exposure procedure) has the potential to achieve generalization. Here, we investigated two important characteristics of multi-stimulus learning, namely, roving and feature variability, and their impacts on multi-stimulus learning and generalization. We adopted a feature detection task in which an oddly oriented target bar differed by 16° from the background bars. The stimulus onset asynchrony threshold between the target and the mask was measured with a staircase procedure. Observers were trained with four target orientation search stimuli, either with a 5° deviation (30°-35°-40°-45°) or with a 45° deviation (30°-75°-120°-165°), and the four reference stimuli were presented in a roving manner. The transfer of learning to the swapped target-background orientations was evaluated after training. We found that multi-stimulus training with a 5° deviation resulted in significant learning improvement, but learning failed to transfer to the swapped target-background orientations. In contrast, training with a 45° deviation slowed learning but produced a significant generalization to swapped orientations. Furthermore, a modified training-plus-exposure procedure, in which observers were trained with four orientation search stimuli with a 5° deviation and simultaneously passively exposed to orientations with high feature variability (45° deviation), led to significant orientation learning generalization. Learning transfer also occurred when the four orientation search stimuli with a 5° deviation were presented in separate blocks. These results help us to specify the condition under which multistimuli learning produces generalization, which holds potential for real-world applications of perceptual learning, such as vision rehabilitation and expert training.

Contour integration deficits at high spatial frequencies in children treated for anisometropic amblyopia.

Purpose: This study was conducted to reexamine the question of whether children treated for anisometropic amblyopia have contour integration deficits. To do so, we used psychophysical methods that require global contour processing while minimizing the influence of low-level deficits: visibility, shape perception, and positional uncertainty. Methods: Thirteen children with anisometropic amblyopia (age: 10.1 ± 1.8 years) and thirteen visually normal children (age: 10.8 ± 2.0 years) participated in this study. The stimuli were closed figures made up of Gabor patches either in noise or on a blank field. The contrast thresholds to detect a circular contour on a blank field, as well as the thresholds of aspect ratio and contour element number to discriminate a circular or elliptical contour in noise, were measured at Gabor spatial frequencies of 1.5, 3, and 6 cpd for amblyopic eyes (AEs), fellow eyes (FEs), and normal control eyes. Visual acuities and contrast sensitivity functions for AEs and FEs and the Randot stereoacuity were measured before testing. Results: The AEs showed contrast deficits and degraded shape perception compared to the FEs at higher spatial frequencies (6 cpd). When the influence of abnormal contrast sensitivity and shape perception were minimized, the AEs showed contour integration deficits at spatial frequencies 3 and 6 cpd. These deficits were not related to basic losses in contrast sensitivity and acuity, stereoacuity, and visual crowding. Besides, no significant difference was found between the fellow eyes of the amblyopic children and the normal control eyes in the performance of contour integration. Conclusion: After eliminating or compensating for the low-level deficits, children treated for anisometropic amblyopia still show contour integration deficits, primarily at higher spatial frequencies, which might reflect the deficits in global processing caused by amblyopia. Contour integration deficits are likely independent of spatial vision deficits. Refractive correction and/or occlusion therapies may not be sufficient to fully restore contour integration deficits, which indicates the need for the development of clinical treatments to recover these deficits.

The impact of training on the inner-outer asymmetry in crowding.

Inner-outer asymmetry, where the outer flanker induces stronger crowding than the inner flanker, is a hallmark property of visual crowding. It is unclear the contribution of inner-outer asymmetry to the pattern of crowding errors (biased predominantly toward the flanker identities) and the role of training on crowding errors. In a typical radial crowding display, 20 observers were asked to report the orientation of a target Gabor (7.5° eccentricity) flanked by either an inner or outer Gabor along the horizontal meridian. The results showed that outer flanker conditions induced stronger crowding, accompanied by assimilative errors to the outer flanker for similar target/flanker elements. In contrast, the inner flanker condition exhibited weaker crowding, with no significant patterns of crowding errors. A population coding model showed that the flanker weights in the outer flanker condition were significantly higher than those in the inner flanker condition. Nine observers continued to train the outer flanker condition for four sessions. Training reduced inner-outer asymmetry and reduced flanker weights to the outer flanker. The learning effects were retained over 4 to 6 months. Individual differences in the appearance of crowding errors, the strength of inner-outer asymmetry, and the training effects were evident. Nevertheless, our findings indicate that different crowding mechanisms may be responsible for the asymmetric crowding effects induced by inner and outer flankers, with the outer flankers dominating the appearance more than the inner ones. Training reduces inner-outer asymmetry by reducing target/flanker confusion, and learning is persistent over months, suggesting that perceptual learning has the potential to improve visual performance by promoting neural plasticity.

Classification and Interpretation for 11 FBN1 Variants Responsible for Marfan Syndrome and Pre-implantation Genetic Testing (PGT) for Two Families Successfully Blocked Transmission of the Pathogenic Mutations.

Background: The lifespan of Marfan Syndrome (MFS) patients is shortened, especially in patients without early diagnostics, preventive treatment, and elective surgery. Clinically, MFS diagnosis is mainly dependent on phenotypes, but for children, sporadic cases, or suspicious MFS patients, molecular genetic testing, and mainly FBN1 mutation screening, plays a significant role in the diagnosis of MFS. PGT-M gives couples that had a family history of monogenic disorders the opportunity to avoid the occurrence of MFS. Methods: In this study, 11 families with MFS were recruited and complete clinical features were collected. Variants were classified and interpreted through pedigree analysis according to guidelines. Two families chose to undergo PGT-M; 16 blastocysts were biopsied and amplified. Haplotype analysis was performed to deduce the embryo's genotype by using single nucleotide polymorphisms (SNPs) identified in each sample. Results: We identified 11 potential disease-causing FBN1 variants, six of which are novel. All variants were assessed with prediction tools to assess mutation pathogenicity, population databases to evaluate population allele frequency, literature databases to identify whether the variant had been reported in MFS patients, and multiple sequence alignment to carry out conservative analysis. Finally, nine variants were classified as likely pathogenic/pathogenic variants. Among 11 variants, eight variants were missense, and seven of them were located in the Ca-binding EGF-like motifs, moreover, half of them substituted conserved Cysteine residues. We also identified a splice site variant, a frameshift variant, and a synonymous variant. There are two variants that are de novo variants. PGT-M helped two MFS families give birth to a healthy baby not carrying the FBN1 mutation. Conclusions: In the present study, the FBN1 mutation spectrum was enriched, and may help further elucidate the pathogenesis, benefiting clinical diagnosis and management of MFS. We make use of a reliable PGT-M method for the successful birth of healthy babies to two MFS families.

Dichoptic Perceptual Training in Children With Amblyopia With or Without Patching History.

Purpose: Dichoptic training is becoming a popular tool in amblyopia treatment. Here we investigated the effects of dichoptic demasking training in children with amblyopia who never received patching treatment (NPT group) or were no longer responsive to patching (PT group). Methods: Fourteen NPT and thirteen PT amblyopes (6-16.5 years; 24 anisometropic, two strabismus, and one mixed) received dichoptic demasking training for 17 to 22 sessions. They used the amblyopic eye (AE) to practice contrast discrimination between a pair of Gabors that were dichoptically masked by a band-filtered noise pattern simultaneously presented in the fellow eye (FE). Dichoptic learning was quantified by the increase of maximal tolerable noise contrast (TNC) for AE contrast discrimination. Computerized visual acuities and contrast sensitivity functions for both eyes and the Randot stereoacuity were measured before and after training. Results: Training improved maximal TNC by six to eight times in both groups, along with a boost of AE acuities by 0.15 logMAR (P < 0.001) in the NPT group and 0.06 logMAR (P < 0.001) in the PT group. This visual acuity improvement was significantly dependent on the pretraining acuity. Stereoacuity was significantly improved by 41.6% (P = 0.002) in the NPT group and 64.2% (P < 0.001) in the PT group. The stereoacuity gain was correlated to the pretraining interocular acuity difference (r = -0.49, P = 0.010), but not to the interocular acuity difference change (r = -0.28, P = 0.15). Training improved AE contrast sensitivity in the NPT group (P = 0.009) but not the PT group (P = 0.76). Moreover, the learning effects in 12 retested observers were retained for 10 to 24 months. Conclusions: Dichoptic training can improve, and sometimes even restore, the stereoacuity of amblyopic children, especially those with mild amblyopia (amblyopic VA ≦0.28 logMAR). The dissociation of stereoacuity gain and the interocular acuity difference change suggests that the stereoacuity gain may not result from a reduced interocular suppression in most amblyopes. Rather, the amblyopes may have learned to attend to, or readout, the stimulus information to improve stereopsis.

Dichoptic De-Masking Learning in Adults With Amblyopia and Its Mechanisms.

Purpose: Recently, we reported that dichoptic de-masking training can further boost stereoacuity, but not visual acuity, in adults with amblyopia after extensive monocular perceptual training. Here, we investigated whether this dichoptic training targets on interocular suppression directly, or improves vision through high-level brain mechanisms. Methods: Eleven adults with amblyopia first used amblyopic eyes (AEs) to perform contrast (n = 6) or orientation (n = 5) discrimination training, while resisting dichoptic noise masking from fellow eyes (FEs). Learning was indicated by increased maximal tolerable noise contrast (TNC) for AE contrast/orientation discrimination. After dichoptic training, six observers continued to use AEs to perform monocular training for nine sessions. Results: (1) Training of dichoptic de-masking doubled maximal TNC, but learning did not transfer much to the same task at an orthogonal orientation or a different task, showing orientation/task specificities. (2) Following a training-plus-exposure (TPE) protocol, AEs then received exposure of the orthogonal orientation by performing the other orientation/contrast discrimination task at the orthogonal orientation. After this TPE training, dichoptic learning with the original discrimination task transferred to the orthogonal orientation. (3) Dichoptic training improved AE's acuity (1.2 lines), stereoacuity (60.2%), and contrast sensitivity (mainly at higher spatial frequencies). (4) Additional monocular training did not produce further acuity and stereoacuity gains. Conclusions: The initial orientation/task specificities exclude the possibility that dichoptic training reduces physiological interocular suppression. The later transfer of learning to an orthogonal orientation with TPE training suggests improvement in high-level brain processing. Dichoptic training may strengthen top-down attention to AEs to counter the impacts of attentional bias to FEs and/or physiological interocular suppression and improve stereoacuity.

Occurrence, Distribution, and Potential Sources of Organophosphate Esters in Urban and Rural Surface Water in Shanghai, China.

In this study, the occurrence and distribution patterns of eight organophosphate esters (OPEs) were investigated in urban and rural surface water in a typical cosmopolitan city: Shanghai, China. In addition, concentration levels and removal efficiencies of seven sewage treatment plants were analyzed. The OPEs concentrations detected in urban rivers were significantly higher than those detected in rural rivers. Total OPEs ranged from 185.4 to 321 ng L-1 in rural surface water and from 340 to 1688.7 ng L-1 in urban, with an average of 221.8 ng L-1 and 850.2 ng L-1, respectively. Compared with other studies published in the world, the OPEs contamination in surface river water in Shanghai was at a moderate level. Furthermore, the potential sources of OPEs in urban surface water were investigated, and the results indicated that OPEs in urban surface water mainly came from three potential sources. In rural surface water, the OPE concentrations were uniformly distributed, so OPEs in rural surface water may came from nonpoint source pollution. Last, a preliminary environmental risk assessment and health risk assessment were conducted. The results showed low environmental risks at all sampling sites (except for sampling point R7: medium risk for algae) for the three aquatic organisms (algae, daphnia, and fish). Health risk assessment indicated a noncarcinogenic risk for diverse human groups for Æ©OPEs.

Vernier learning with short- and long-staircase training and its transfer to a new location with double training.

We previously demonstrated that perceptual learning of Vernier discrimination, when paired with orientation learning at the same retinal location, can transfer completely to untrained locations (Wang, Zhang, Klein, Levi, & Yu, 2014; Zhang, Wang, Klein, Levi, & Yu, 2011). However, Hung and Seitz (2014) reported that the transfer is possible only when Vernier is trained with short staircases, but not with very long staircases. Here we ran two experiments to examine Hung and Seitz's conclusions. The first experiment confirmed the transfer effects with short-staircase Vernier training in both our study and Hung and Seitz's. The second experiment revealed that long-staircase training only produced very fast learning at the beginning of the pretraining session, but with no further learning afterward. Moreover, the learning and transfer effects differed insignificantly with a small effect size, making it difficult to support Hung and Seitz's claim that learning with long-staircase training cannot transfer to an untrained retinal location.

Dichoptic training in adults with amblyopia: Additional stereoacuity gains over monocular training.

Dichoptic training is a recent focus of research on perceptual learning in adults with amblyopia, but whether and how dichoptic training is superior to traditional monocular training is unclear. Here we investigated whether dichoptic training could further boost visual acuity and stereoacuity in monocularly well-trained adult amblyopic participants. During dichoptic training the participants used the amblyopic eye to practice a contrast discrimination task, while a band-filtered noise masker was simultaneously presented in the non-amblyopic fellow eye. Dichoptic learning was indexed by the increase of maximal tolerable noise contrast for successful contrast discrimination in the amblyopic eye. The results showed that practice tripled maximal tolerable noise contrast in 13 monocularly well-trained amblyopic participants. Moreover, the training further improved stereoacuity by 27% beyond the 55% gain from previous monocular training, but unchanged visual acuity of the amblyopic eyes. Therefore our dichoptic training method may produce extra gains of stereoacuity, but not visual acuity, in adults with amblyopia after monocular training.

Bottom-up and top-down influences at untrained conditions determine perceptual learning specificity and transfer.

Perceptual learning is often orientation and location specific, which may indicate neuronal plasticity in early visual areas. However, learning specificity diminishes with additional exposure of the transfer orientation or location via irrelevant tasks, suggesting that the specificity is related to untrained conditions, likely because neurons representing untrained conditions are neither bottom-up stimulated nor top-down attended during training. To demonstrate these top-down and bottom-up contributions, we applied a "continuous flash suppression" technique to suppress the exposure stimulus into sub-consciousness, and with additional manipulations to achieve pure bottom-up stimulation or top-down attention with the transfer condition. We found that either bottom-up or top-down influences enabled significant transfer of orientation and Vernier discrimination learning. These results suggest that learning specificity may result from under-activations of untrained visual neurons due to insufficient bottom-up stimulation and/or top-down attention during training. High-level perceptual learning thus may not functionally connect to these neurons for learning transfer.

Perceptual learning of basic visual features remains task specific with Training-Plus-Exposure (TPE) training.

Visual perceptual learning is known to be specific to the trained retinal location, feature, and task. However, location and feature specificity can be eliminated by double-training or TPE training protocols, in which observers receive additional exposure to the transfer location or feature dimension via an irrelevant task besides the primary learning task Here we tested whether these new training protocols could even make learning transfer across different tasks involving discrimination of basic visual features (e.g., orientation and contrast). Observers practiced a near-threshold orientation (or contrast) discrimination task. Following a TPE training protocol, they also received exposure to the transfer task via performing suprathreshold contrast (or orientation) discrimination in alternating blocks of trials in the same sessions. The results showed no evidence for significant learning transfer to the untrained near-threshold contrast (or orientation) discrimination task after discounting the pretest effects and the suprathreshold practice effects. These results thus do not support a hypothetical task-independent component in perceptual learning of basic visual features. They also set the boundary of the new training protocols in their capability to enable learning transfer.

The transfer of motion direction learning to an opposite direction enabled by double training: A reply to Liang et al. (2015).

A recent paper from our lab (Zhang & Yang, 2014) reports that perceptual learning of motion-direction discrimination, which is known to be specific to the trained direction, can transfer significantly, and sometimes completely, to an opposite direction, provided that the observers receive additional exposure of the opposite direction via an irrelevant task. However, in a newly published study, Zili Liu and collaborators claim that they cannot replicate our original double training results using identical procedures (Liang, Fahle, & Liu, 2015). Here we point out that the relevant data in Liang et al. (2015) are actually not very different from those in Zhang and Yang (2014). We thus pool data from both studies to obtain a more precise estimate of the transfer rate, which is over 75% of the learning effect.

Perceptual Learning at a Conceptual Level.

Humans can learn to abstract and conceptualize the shared visual features defining an object category in object learning. Therefore, learning is generalizable to transformations of familiar objects and even to new objects that differ in other physical properties. In contrast, visual perceptual learning (VPL), improvement in discriminating fine differences of a basic visual feature through training, is commonly regarded as specific and low-level learning because the improvement often disappears when the trained stimulus is simply relocated or rotated in the visual field. Such location and orientation specificity is taken as evidence for neural plasticity in primary visual cortex (V1) or improved readout of V1 signals. However, new training methods have shown complete VPL transfer across stimulus locations and orientations, suggesting the involvement of high-level cognitive processes. Here we report that VPL bears similar properties of object learning. Specifically, we found that orientation discrimination learning is completely transferrable between luminance gratings initially encoded in V1 and bilaterally symmetric dot patterns encoded in higher visual cortex. Similarly, motion direction discrimination learning is transferable between first- and second-order motion signals. These results suggest that VPL can take place at a conceptual level and generalize to stimuli with different physical properties. Our findings thus reconcile perceptual and object learning into a unified framework. SIGNIFICANCE STATEMENT: Training in object recognition can produce a learning effect that is applicable to new viewing conditions or even to new objects with different physical properties. However, perceptual learning has long been regarded as a low-level form of learning because of its specificity to the trained stimulus conditions. Here we demonstrate with new training tactics that visual perceptual learning is completely transferrable between distinct physical stimuli. This finding indicates that perceptual learning also operates at a conceptual level in a stimulus-invariant manner.

Development and validation of an UFLC-MS/MS method for enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study.

A chiral UFLC-MS/MS method was established and validated for quantifying d-threo-methylphenidate (d-threo-MPH), l-threo-methylphenidate (l-threo-MPH), d-threo-ethylphenidate (d-threo-EPH), l-threo-ethylphenidate (l-threo-EPH) and d,l-threo-ritalinic acid (d,l-threo-RA) in rat plasma over the linearity range of 1-500ng/mL. Chiral separation was performed on an Astec Chirobiotic V2 column (5µm, 250×2.1mm) with isocratic elution using methanol containing 0.003% ammonium acetate (w/v) and 0.003% trifluoroacetic acid (v/v) at a flow of 0.3mL/min. All analytes and IS were extracted from rat plasma by a one-step liquid-liquid extraction (LLE) method. The intra- and inter-run accuracies were within 85-115%, and the intra- and inter-run precision were <10% for all analytes. Extraction recoveries were 55-62% for d-threo-MPH, 54-60% for l-threo-MPH, 55-60% for d-threo-EPH, 53-57% for l-threo-EPH and 25-30% for d,l-threo-RA. The validated UFLC-MS/MS method successfully applied to the pharmacokinetic interaction study of oral d-threo-MPH and l-threo-MPH (alone or in combination) in female Sprague Dawley rats. The EPH was not detected in rat plasma following oral administrated MPH without EtOH. As far as it is known to the authors, this study is the first one step liquid-liquid extraction method to extract and UFLC-MS/MS method to quantify d-threo-MPH, l-threo-MPH, d-threo-EPH, l-threo-EPH and d,l-threo-RA simultaneously.

Perceptual learning eases crowding by reducing recognition errors but not position errors.

When an observer reports a letter flanked by additional letters in the visual periphery, the response errors (the crowding effect) may result from failure to recognize the target letter (recognition errors), from mislocating a correctly recognized target letter at a flanker location (target misplacement errors), or from reporting a flanker as the target letter (flanker substitution errors). Crowding can be reduced through perceptual learning. However, it is not known how perceptual learning operates to reduce crowding. In this study we trained observers with a partial-report task (Experiment 1), in which they reported the central target letter of a three-letter string presented in the visual periphery, or a whole-report task (Experiment 2), in which they reported all three letters in order. We then assessed the impact of training on recognition of both unflanked and flanked targets, with particular attention to how perceptual learning affected the types of errors. Our results show that training improved target recognition but not single-letter recognition, indicating that training indeed affected crowding. However, training did not reduce target misplacement errors or flanker substitution errors. This dissociation between target recognition and flanker substitution errors supports the view that flanker substitution may be more likely a by-product (due to response bias), rather than a cause, of crowding. Moreover, the dissociation is not consistent with hypothesized mechanisms of crowding that would predict reduced positional errors.

Vernier perceptual learning transfers to completely untrained retinal locations after double training: a "piggybacking" effect.

Perceptual learning, a process in which training improves visual discrimination, is often specific to the trained retinal location, and this location specificity is frequently regarded as an indication of neural plasticity in the retinotopic visual cortex. However, our previous studies have shown that "double training" enables location-specific perceptual learning, such as Vernier learning, to completely transfer to a new location where an irrelevant task is practiced. Here we show that Vernier learning can be actuated by less location-specific orientation or motion-direction learning to transfer to completely untrained retinal locations. This "piggybacking" effect occurs even if both tasks are trained at the same retinal location. However, piggybacking does not occur when the Vernier task is paired with a more location-specific contrast-discrimination task. This previously unknown complexity challenges the current understanding of perceptual learning and its specificity/transfer. Orientation and motion-direction learning, but not contrast and Vernier learning, appears to activate a global process that allows learning transfer to untrained locations. Moreover, when paired with orientation or motion-direction learning, Vernier learning may be "piggybacked" by the activated global process to transfer to other untrained retinal locations. How this task-specific global activation process is achieved is as yet unknown.

Perceptual learning of contrast discrimination under roving: the role of semantic sequence in stimulus tagging.

Perceptual learning may occur when multiple contrasts are practiced in a fixed, but not in a roving (random), temporal sequence. However, learning may escape roving disruption when each contrast is assigned a letter tag (i.e., A, B, C, D). Because these letter tags carry not only stimulus identity information, but also semantic sequence information, here we investigated whether the semantic sequence information is necessary for learning of tagged contrasts under the roving condition. We found that assigning number tags (i.e., 1, 2, 3, 4), which also contained both identity and semantic sequence information, to four roving contrasts enabled significant learning of discrimination of each contrast, confirming previous data. However, learning became insignificant when the contrast tags were replaced with Greek letters that were familiar to our Chinese observers except their sequence or Chinese characters that carried no sequence information. In addition, assigning orientation tags, which carried no sequence information either, to roving contrasts was ineffective as well because learning occurred only with sequenced but not roving contrasts. These results suggest that semantic sequence information is necessary for stimulus tagging to effectively enable perceptual learning of multiple contrast discrimination under roving.

Perceptual learning improves adult amblyopic vision through rule-based cognitive compensation.

PURPOSE: We investigated whether perceptual learning in adults with amblyopia could be enabled to transfer completely to an orthogonal orientation, which would suggest that amblyopic perceptual learning results mainly from high-level cognitive compensation, rather than plasticity in the amblyopic early visual brain. METHODS: Nineteen adults (mean age = 22.5 years) with anisometropic and/or strabismic amblyopia were trained following a training-plus-exposure (TPE) protocol. The amblyopic eyes practiced contrast, orientation, or Vernier discrimination at one orientation for six to eight sessions. Then the amblyopic or nonamblyopic eyes were exposed to an orthogonal orientation via practicing an irrelevant task. Training was first performed at a lower spatial frequency (SF), then at a higher SF near the cutoff frequency of the amblyopic eye. RESULTS: Perceptual learning was initially orientation specific. However, after exposure to the orthogonal orientation, learning transferred to an orthogonal orientation completely. Reversing the exposure and training order failed to produce transfer. Initial lower SF training led to broad improvement of contrast sensitivity, and later higher SF training led to more specific improvement at high SFs. Training improved visual acuity by 1.5 to 1.6 lines (P < 0.001) in the amblyopic eyes with computerized tests and a clinical E acuity chart. It also improved stereoacuity by 53% (P < 0.001). CONCLUSIONS: The complete transfer of learning suggests that perceptual learning in amblyopia may reflect high-level learning of rules for performing a visual discrimination task. These rules are applicable to new orientations to enable learning transfer. Therefore, perceptual learning may improve amblyopic vision mainly through rule-based cognitive compensation.

Perceptual learning of motion direction discrimination transfers to an opposite direction with TPE training.

Motion direction learning is known to be specific to the trained direction. However, in this study we used our recently developed TPE (training-plus-exposure) method to demonstrate that motion direction learning can transfer to an opposite direction. Specifically, we first replicated the strict direction specificity of motion direction learning with a group of moving dots. However, when the participants were exposed to the opposite direction in an irrelevant dot number discrimination task, either simultaneously with motion direction training or at a later time, but not in a reversed order, motion direction learning transferred to the opposite direction significantly and sometimes completely. These results suggest that motion direction learning may be a high-level process in which the brain learns the potentially transferrable rules of reweighting the motion direction inputs. However, we speculate that high-level learning may not functionally connect to sensory neurons that are tuned to other directions but are not stimulated during training, which leads to direction specificity. It is the stimulus exposure in TPE training that connects high-level learning to the exposed opposite direction to enable learning transfer.