Probabilistic discrimination of relative stimulus features in mice.

During perceptual decision-making, the brain encodes the upcoming decision and the stimulus information in a mixed representation. Paradigms suitable for studying decision computations in isolation rely on stimulus comparisons, with choices depending on relative rather than absolute properties of the stimuli. The adoption of tasks requiring relative perceptual judgments in mice would be advantageous in view of the powerful tools available for the dissection of brain circuits. However, whether and how mice can perform a relative visual discrimination task has not yet been fully established. Here, we show that mice can solve a complex orientation discrimination task in which the choices are decoupled from the orientation of individual stimuli. Moreover, we demonstrate a typical discrimination acuity of 9°, challenging the common belief that mice are poor visual discriminators. We reached these conclusions by introducing a probabilistic choice model that explained behavioral strategies in 40 mice and demonstrated that the circularity of the stimulus space is an additional source of choice variability for trials with fixed difficulty. Furthermore, history biases in the model changed with task engagement, demonstrating behavioral sensitivity to the availability of cognitive resources. In conclusion, our results reveal that mice adopt a diverse set of strategies in a task that decouples decision-relevant information from stimulus-specific information, thus demonstrating their usefulness as an animal model for studying neural representations of relative categories in perceptual decision-making research.

Many Roads Lead to Rome: Differential Learning Processes for the Same Perceptual Improvement.

Repeatedly exercising a perceptual ability usually leads to improvement, yet it is unclear whether the mechanisms supporting the same perceptual learning could be flexibly adjusted according to the training settings. Here, we trained adult observers in an orientation-discrimination task at either a single (focused) retinal location or multiple (distributed) retinal locations. We examined the observers' discriminability (N = 52) and bias (N = 20) in orientation perception at the trained and untrained locations. The focused and distributed training enhanced orientation discriminability by the same amount and induced a bias in perceived orientation at the trained locations. Nevertheless, the distributed training promoted location generalization of both practice effects, whereas the focused training resulted in specificity. The two training tactics also differed in long-term retention of the training effects. Our results suggest that, depending on the training settings of the same task, the same discrimination learning could differentially engage location-specific and location-invariant representations of the learned stimulus feature.

V1 neurons encode the perceptual compensation of false torsion arising from Listing's law.

We try to deploy the retinal fovea to optimally scrutinize an object of interest by directing our eyes to it. The horizontal and vertical components of eye positions acquired by goal-directed saccades are determined by the object's location. However, the eccentric eye positions also involve a torsional component, which according to Donder's law is fully determined by the two-dimensional (2D) eye position acquired. According to von Helmholtz, knowledge of the amount of torsion provided by Listing's law, an extension of Donder's law, alleviates the perceptual interpretation of the image tilt that changes with 2D eye position, a view supported by psychophysical experiments he pioneered. We address the question of where and how Listing's law is implemented in the visual system and we show that neurons in monkey area V1 use knowledge of eye torsion to compensate the image tilt associated with specific eye positions as set by Listing's law.

Human visual processing during walking: Dissociable pre- and post-stimulus influences.

Walking influences visual processing but the underlying mechanism remains poorly understood. In this study, we investigated the influence of walking on pre-stimulus and stimulus-induced visual neural activity and behavioural performance in a discrimination task while participants were standing or freely walking. The results showed dissociable pre- and post-stimulus influences by the movement state. Walking was associated with a reduced pre-stimulus alpha power, which predicted enhanced N1 and decreased P3 components during walking. This pre-stimulus alpha activity was additionally modulated by time on the task, which was paralleled by a similar behavioural modulation. In contrast, the post-stimulus alpha power was reduced in its modulation due to stimulus onset during walking but showed no evidence of modulation by time on the task. Additionally, stimulus parameters (eccentricity, laterality, distractor presence significantly influenced post-stimulus alpha power, whereas the visually evoked components showed no evidence of such an influence. There was further no evidence of a correlation between pre-stimulus and post stimulus alpha power. We conclude that walking has two dissociable influences on visual processing: while the walking induced reduction in alpha power suggests an attentional state change that relates to visual awareness, the post-stimulus influence on alpha power modulation indicates changed spatial visual processing during walking.

A Sparse Probabilistic Code Underlies the Limits of Behavioral Discrimination.

The cortical code that underlies perception must enable subjects to perceive the world at time scales relevant for behavior. We find that mice can integrate visual stimuli very quickly (<100 ms) to reach plateau performance in an orientation discrimination task. To define features of cortical activity that underlie performance at these time scales, we measured single-unit responses in the mouse visual cortex at time scales relevant to this task. In contrast to high-contrast stimuli of longer duration, which elicit reliable activity in individual neurons, stimuli at the threshold of perception elicit extremely sparse and unreliable responses in the primary visual cortex such that the activity of individual neurons does not reliably report orientation. Integrating information across neurons, however, quickly improves performance. Using a linear decoding model, we estimate that integrating information over 50-100 neurons is sufficient to account for behavioral performance. Thus, at the limits of visual perception, the visual system integrates information encoded in the probabilistic firing of unreliable single units to generate reliable behavior.

Mental health and substance use among women and men at the intersections of identities and experiences of discrimination: insights from the intersectionality framework.

BACKGROUND: Intersectionality theory focuses on how one's human experiences are constituted by mutually reinforcing interactions between different aspects of one's identities, such as race, class, gender, and sexual orientation. In this study, we asked: 1) Do associations between intersecting identities (race and sexual orientation) and mental health (depressive symptoms) and substance use (alcohol, tobacco, and marijuana) differ between men and women? and 2) How do single or intersecting self-reports of perceived racial and/or sexual orientation discrimination influence mental health and substance use outcomes for men and women? We compared results of assessing identities versus experiences of discrimination. METHODS: Multivariable regressions were conducted on cross-sectional data from 2315 Black and White college students. Predictors included measures of sociodemographic characteristics and experiences of discrimination. Outcomes included past 2-week depressive symptoms (PHQ-9), past 30-day alcohol use, past 30-day tobacco use, and past 30-day marijuana use. RESULTS: Intersecting identities and experience of discrimination had different associations with outcomes. Among women, self-reporting both forms of discrimination was associated with higher depressive symptoms and substance use. For example, compared to women experiencing no discrimination, women experiencing both forms of discrimination had higher depressive symptoms (B = 3.63, CI = [2.22-5.03]), alcohol use (B = 1.65, CI = [0.56-2.73]), tobacco use (OR = 3.45, CI = [1.97-6.05]), and marijuana use (OR = 3.38, CI = [1.80-6.31]). However, compared to White heterosexual women, White sexual minority women had higher risks for all outcomes (B = 3.16 and CI = [2.03-4.29] for depressive symptoms, B = 1.45 and CI = [0.58-2.32] for alcohol use, OR = 2.21 and CI = [1.32-3.70] for tobacco use, and OR = 3.01 and CI = [1.77-5.12] for marijuana use); while Black sexual minority women had higher tobacco (OR = 2.64, CI = [1.39-5.02]) and marijuana use (OR = 2.81, CI = [1.33-5.92]) only. Compared to White heterosexual men, White sexual minority men had higher depressive symptoms (B = 1.90, CI = [0.52-3.28]) and marijuana use (OR = 2.37, CI = [1.24-4.49]). CONCLUSIONS: Our results highlight the deleterious impacts of racial discrimination and sexual orientation discrimination on health, in particular for women. Future studies should distinguish between and jointly assess intersecting social positions (e.g., identities) and processes (e.g., interpersonal experience of discrimination or forms of structural oppression).

Experimental confirmation of a character-facing bias in literacy development.

When learning to write, children often mirror-reverse individual letters. For children learning to use the Latin alphabet, in a left-to-right writing culture, letters that appear to face left (such as J and Z) seem to be more prone to reversal than those that appear to face right (such as B and C). It has been proposed that, because most asymmetrical Latin letters face right, children statistically learn this general regularity and are subsequently biased to write any letter rightward. The evidence for this character-facing bias is circumstantial, however, because letter-facing direction is confounded with other factors that could affect error rates; for instance, J and Z are left-facing, but they are also infrequent. We report the first controlled experimental test of the character-facing bias. We taught 43 Scottish primary schoolchildren (aged 4.8-5.8 years) four artificial, letter-like characters, two of which were left-facing and two of which were right-facing. The characters were novel and so were not subject to prior exposure effects, and alternate groups of children were assigned to identical but mirror-reflected character sets. Children were three times more likely to mirror-write a novel character they had learned in a left-facing format than to mirror-write one they had learned in a right-facing format. This provides the first experimental confirmation of the character-facing bias in literacy development and suggests that implicit knowledge acquired from exposure to written language is readily generalized to novel letter-like forms.

Differential aversive learning enhances orientation discrimination.

A number of recent studies have documented rapid changes in behavioural sensory acuity induced by aversive learning in the olfactory and auditory modalities. The effect of aversive learning on the discrimination of low-level features in the visual system of humans remains unclear. Here, we used a psychophysical staircase procedure to estimate discrimination thresholds for oriented grating stimuli, before and after differential aversive learning. We discovered that when a target grating orientation was conditioned with an aversive loud noise, it subsequently led to an improvement of discrimination acuity in nearly all subjects. However, no such change was observed in a control group conditioned to an orientation shifted by ±90° from the target. Our findings cannot be explained by contextual learning or sensitisation factors. The results converge with those reported in the olfactory modality and provide further evidence that early sensory systems can be rapidly modified by recently experienced reinforcement histories.

Mice Can Use Second-Order, Contrast-Modulated Stimuli to Guide Visual Perception.

Visual processing along the primate ventral stream takes place in a hierarchy of areas, characterized by an increase in both complexity of neuronal preferences and invariance to changes of low-level stimulus attributes. A basic type of invariance is form-cue invariance, where neurons have similar preferences in response to first-order stimuli, defined by changes in luminance, and global features of second-order stimuli, defined by changes in texture or contrast. Whether in mice, a now popular model system for early visual processing, visual perception can be guided by second-order stimuli is currently unknown. Here, we probed mouse visual perception and neural responses in areas V1 and LM using various types of second-order, contrast-modulated gratings with static noise carriers. These gratings differ in their spatial frequency composition and thus in their ability to invoke first-order mechanisms exploiting local luminance features. We show that mice can transfer learning of a coarse orientation discrimination task involving first-order, luminance-modulated gratings to the contrast-modulated gratings, albeit with markedly reduced discrimination performance. Consistent with these behavioral results, we demonstrate that neurons in area V1 and LM are less responsive and less selective to contrast-modulated than to luminance-modulated gratings, but respond with broadly similar preferred orientations. We conclude that mice can, at least in a rudimentary form, use second-order stimuli to guide visual perception. SIGNIFICANCE STATEMENT: To extract object boundaries in natural scenes, the primate visual system does not only rely on differences in local luminance but can also take into account differences in texture or contrast. Whether the mouse, which has a much simpler visual system, can use such second-order information to guide visual perception is unknown. Here we tested mouse perception of second-order, contrast-defined stimuli and measured their neural representations in two areas of visual cortex. We find that mice can use contrast-defined stimuli to guide visual perception, although behavioral performance and neural representations were less robust than for luminance-defined stimuli. These findings shed light on basic steps of feature extraction along the mouse visual cortical hierarchy, which may ultimately lead to object recognition.

Beyond blindsight: properties of visual relearning in cortically blind fields.

Damage to the primary visual cortex (V1) or its immediate afferents results in a dense scotoma, termed cortical blindness (CB). CB subjects have residual visual abilities, or blindsight, which allow them to detect and sometimes discriminate stimuli with high temporal and low spatial frequency content. Recent work showed that with training, discriminations in the blind field can become more reliable, and even reach consciousness. However, the narrow spatiotemporal bandwidth of blindsight limits its functional usefulness in everyday vision. Here, we asked whether visual training can induce recovery outside the spatiotemporal bandwidth of blindsight. Specifically, could human CB subjects learn to discriminate static, nonflickering stimuli? Can such learning transfer to untrained stimuli and tasks, and does double training with moving and static stimuli provide additional advantages relative to static training alone? We found CB subjects capable of relearning static orientation discriminations following single as well as double training. However, double training with complex, moving stimuli in a separate location was necessary to recover complex motion thresholds at locations trained with static stimuli. Subjects trained on static stimuli alone could only discriminate simple motion. Finally, both groups had approximately equivalent, incomplete recovery of fine orientation and direction discrimination thresholds, as well as contrast sensitivity. These results support two conclusions: (1) from a practical perspective, complex moving stimuli and double training may be superior training tools for inducing visual recovery in CB, and (2) the cortically blind visual system can relearn to perform a wider range of visual discriminations than predicted by blindsight alone.

Decision-related activity in sensory neurons may depend on the columnar architecture of cerebral cortex.

Many studies have reported correlations between the activity of sensory neurons and animals' judgments in discrimination tasks. Here, we suggest that such neuron-behavior correlations may require a cortical map for the task relevant features. This would explain why studies using discrimination tasks based on disparity in area V1 have not found these correlations: V1 contains no map for disparity. This scheme predicts that activity of V1 neurons correlates with decisions in an orientation-discrimination task. To test this prediction, we trained two macaque monkeys in a coarse orientation discrimination task using band-pass-filtered dynamic noise. The two orientations were always 90° apart and task difficulty was controlled by varying the orientation bandwidth of the filter. While the trained animals performed this task, we recorded from orientation-selective V1 neurons (n = 82, n = 31 for Monkey 1, n = 51 for Monkey 2). For both monkeys, we observed significant correlation (quantified as "choice probabilities") of the V1 activity with the monkeys' perceptual judgments (mean choice probability 0.54, p = 10(-5)). In one of these animals, we had previously measured choice probabilities in a disparity discrimination task in V1, which had been at chance (0.49, not significantly different from 0.5). The choice probabilities in this monkey for the orientation discrimination task were significantly larger than those for the disparity discrimination task (p = 0.032). These results are predicted by our suggestion that choice probabilities are only observed for cortical sensory neurons that are organized in maps for the task-relevant feature.

Interocular transfer of perceptual skills after sleep.

Several studies suggest that sleep improves perceptual skills in the visual texture discrimination task (TDT). Here we report that besides consolidation, sleep also generalizes the learned perceptual abilities to the untrained eye. Healthy volunteers (n = 32) were trained on the TDT, in which they had to discriminate between horizontal and vertical target textures briefly presented in the periphery of the visual field (left upper quadrant). After a 10-hr interval filled with either sleep or wakefulness, they were retested first on the trained eye in the trained quadrant and then on the untrained eye and quadrant. In line with prior findings, visual discrimination was globally higher after sleep than after wakefulness, as compared to performance levels at the end of training. Furthermore, discrimination performance was significantly improved only in the sleep condition for the untrained eye in the same quadrant, but also showed a trend to generalize to the untrained eye and untrained quadrant. Our results suggest that sleep-dependent perceptual skills continue developing at a later visual-process stage than the V1 area, where learning is not monocular anymore.

A new approach to measure interocular suppression in amblyopia and strabismus.

Interocular suppression is commonly estimated by the contrast "balance point" between the eyes in individuals with amblyopia, in which the depth of suppression is defined as the increased contrast in the amblyopic eye that is perceptually matched to the fellow eye. However, this method may not be suitable for individuals with strabismus who have normal or even better contrast sensitivity in the non-fixating eye. In this study, I introduced a new approach that can be used for measuring interocular suppression for both amblyopia and strabismus without balancing contrasts between the eyes. The method consists of the following components: •The stimuli have equal contrasts in both eyes.•The percepts of objects seen monocularly and binocularly are compared.•Interocular suppression is defined as the percept of object in the amblyopic eye is suppressed when an object is presented in the fellow eye.

Spatiotopic perceptual learning mediated by retinotopic processing and attentional remapping.

Visual processing takes place in both retinotopic and spatiotopic frames of reference. Whereas visual perceptual learning is usually specific to the trained retinotopic location, our recent study has shown spatiotopic specificity of learning in motion direction discrimination. To explore the mechanisms underlying spatiotopic processing and learning, and to examine whether similar mechanisms also exist in visual form processing, we trained human subjects to discriminate an orientation difference between two successively displayed stimuli, with a gaze shift in between to manipulate their positional relation in the spatiotopic frame of reference without changing their retinal locations. Training resulted in better orientation discriminability for the trained than for the untrained spatial relation of the two stimuli. This learning-induced spatiotopic preference was seen only at the trained retinal location and orientation, suggesting experience-dependent spatiotopic form processing directly based on a retinotopic map. Moreover, a similar but weaker learning-induced spatiotopic preference was still present even if the first stimulus was rendered irrelevant to the orientation discrimination task by having the subjects judge the orientation of the second stimulus relative to its mean orientation in a block of trials. However, if the first stimulus was absent, and thus no attention was captured before the gaze shift, the learning produced no significant spatiotopic preference, suggesting an important role of attentional remapping in spatiotopic processing and learning. Taken together, our results suggest that spatiotopic visual representation can be mediated by interactions between retinotopic processing and attentional remapping, and can be modified by perceptual training.

Variability in training unlocks generalization in visual perceptual learning through invariant representations.

Stimulus and location specificity are long considered hallmarks of visual perceptual learning. This renders visual perceptual learning distinct from other forms of learning, where generalization can be more easily attained, and therefore unsuitable for practical applications, where generalization is key. Based on the hypotheses derived from the structure of the visual system, we test here whether stimulus variability can unlock generalization in perceptual learning. We train subjects in orientation discrimination, while we vary the amount of variability in a task-irrelevant feature, spatial frequency. We find that, independently of task difficulty, this manipulation enables generalization of learning to new stimuli and locations, while not negatively affecting the overall amount of learning on the task. We then use deep neural networks to investigate how variability unlocks generalization. We find that networks develop invariance to the task-irrelevant feature when trained with variable inputs. The degree of learned invariance strongly predicts generalization. A reliance on invariant representations can explain variability-induced generalization in visual perceptual learning. This suggests new targets for understanding the neural basis of perceptual learning in the higher-order visual cortex and presents an easy-to-implement modification of common training paradigms that may benefit practical applications.

Flexible information representation to stabilize sensory perception despite minor external input variations.

Sensory information about the environment constantly changes or varies depending on circumstances. However, once we repeatedly experience objects, our brain can perceive and recognize them as identical, even if they are slightly altered or include some diversity. We can stably perceive things without interference from minor external changes or variety. Our recent study focusing on visual perception showed that repeatedly viewing the same oriented grating stimuli enables information representation for low-contrast (or weak-intensity) orientations in the primary visual cortex. We observed low contrast-preferring neurons, whose firing rates increased by reducing the luminance contrast. The number of such neurons increased after the experience, and the neuronal population, including such neurons, can represent even low-contrast orientations. This study indicated that experience leads to flexible information representations that continuously respond to inputs of various strengths at the neuronal population level in the primary sensory cortex. In this perspective article, in addition to the above mechanism, I would discuss alternative mechanisms for perceptual stabilization. The primary sensory cortex represents external information faithfully without alterations, as well as in a state distorted by experience. Both sensory representations may cooperatively and dynamically affect hierarchical downstream, resulting in stable perception.

A flexible Python-based touchscreen chamber for operant conditioning reveals improved visual perception of cardinal orientations in mice.

Natural scenes are composed of a wide range of edge angles and spatial frequencies, with a strong overrepresentation of vertical and horizontal edges. Correspondingly, many mammalian species are much better at discriminating these cardinal orientations compared to obliques. A potential reason for this increased performance could be an increased number of neurons in the visual cortex that are tuned to cardinal orientations, which is likely to be an adaptation to the natural scene statistics. Such biased angular tuning has recently been shown in the mouse primary visual cortex. However, it is still unknown if mice also show a perceptual dominance of cardinal orientations. Here, we describe the design of a novel custom-built touchscreen chamber that allows testing natural scene perception and orientation discrimination performance by applying different task designs. Using this chamber, we applied an iterative convergence towards orientation discrimination thresholds for cardinal or oblique orientations in different cohorts of mice. Surprisingly, the expert discrimination performance was similar for both groups but showed large inter-individual differences in performance and training time. To study the discrimination of cardinal and oblique stimuli in the same mice, we, therefore, applied, a different training regime where mice learned to discriminate cardinal and oblique gratings in parallel. Parallel training revealed a higher task performance for cardinal orientations in an early phase of the training. The performance for both orientations became similar after prolonged training, suggesting that learning permits equally high perceptual tuning towards oblique stimuli. In summary, our custom-built touchscreen chamber offers a flexible tool to test natural visual perception in rodents and revealed a training-induced increase in the perception of oblique gratings. The touchscreen chamber is entirely open-source, easy to build, and freely available to the scientific community to conduct visual or multimodal behavioral studies. It is also based on the FAIR principles for data management and sharing and could therefore serve as a catalyst for testing the perception of complex and natural visual stimuli across behavioral labs.

Effect of Transcranial Electrical Stimulation over the Posterior Parietal Cortex on Tactile Spatial Discrimination Performance.

The intraparietal sulcus region, which is part of the posterior parietal cortex (PPC), has been shown to play an important role in discriminating object shapes using the fingers. Transcranial random noise stimulation (tRNS) and anodal transcranial pulsed current stimulation (tPCS) are noninvasive strategies widely used to modulate neural activity in cortical regions. Therefore, we investigated the effects of tRNS and anodal tPCS applied to left or right PPC on the tactile discrimination performance of the right index finger in 20 neurologically healthy subjects. A grating orientation task (GOT) was performed before and immediately after delivering tRNS (stimulus frequency 0.1-640 Hz) in Experiment 1 or anodal tPCS (pulse width 50 ms and inter-pulse interval 5 ms) in Experiment 2. Performing tRNS over the right PPC significantly improved discrimination performance on the GOT. Subjects were classified into low and high baseline performance groups. Conducting tRNS over the left PPC significantly reduced the GOT discrimination performance in the high-performance group. By contrast, anodal tPCS delivered to the PPC of the left and right hemispheres had no significant effect on the tactile GOT discrimination performance of the right hand. We show that transcranial electric stimulation over the PPC may improve tactile perception but the effect depends on stimulus modality, parameters, and on the stimulated hemisphere.

Grating orientation task trial numbers for short- and long-term tactile discrimination learning.

Perceptual learning generally improves with training intensity, but the number of training trials sufficient for transient and long-term improvement in tactile grating orientation task (GOT) discrimination has not been systematically studied. To define reliable trial numbers for tactile discrimination learning, we compared tactile orientation discrimination performance of the right-finger following 200 and 400 training trials. Fifty-one neurologically healthy subjects were recruited. Tactile spatial acuity for orientation (parallel or orthogonal to the long axis of the finger) across different grating frequencies was assessed before, immediately after, 30 min after, and 24 h after sessions consisting of 200 training trials (50/block × 4 blocks), 400 training trials (50/block × 8 blocks), or no training (sham control). Both the 200- and 400-trial training conditions reduced the grating orientation discrimination threshold at 24 h after training. In contrast, the control condition had no effect on the grating orientation discrimination threshold. There was a negative correlation between the baseline grating orientation discrimination threshold and training-induced change in threshold (improvement) following both 200 and 400 trials. Fewer GOT trials (200) substantially prolong tactile discrimination learning, presumably by promoting the consolidation of the underlying neuroplastic mechanisms. In this widely used perceptual learning paradigm, 200 and 400 training trials appear effective for inducing short-term and long-term perceptual memory.

Time Course of Perceived Visual Distortion and Axial Length Growth in Myopic Children Undergoing Orthokeratology.

Purpose: To establish the time course of the subjective visual function changes during the first month of orthokeratology treatment in myopic children, and to investigate how the time course variations are associated with the objective optical quality changes and the axial length growth (ALG) after 1 year of treatment. Methods: A total of 58 myopic children aged from 8 to 16 years participated in this self-controlled prospective study. All subjects were fitted with designed spherical four-zone orthokeratology lenses. Subjective visual function was evaluated with orientation discrimination threshold (ODT), and objective optical quality was quantified with the high-order aberration root-mean-square (HOA-RMS) and the changing speed of HOA. The measurements were done before the lens fitting and 1 day, 1-, 2-, and 4-weeks after lens wear. Axial length was obtained at baseline and 1-year follow-up, and ALG was defined as the difference. One-way ANOVA was conducted to compare the difference for statistical analysis. Results: After lens fitting, the ODT time courses peaked on day 1 in 28 children, 1 week in 15 children, 2 weeks in 11 children, and 4 weeks in 4 children. In contrast, the HOA-RMS steadily rose during the first month, and the changing speed of HOA was only transiently elevated on day 1 after the initial lens wear. The ALG was 0.12 ± 0.20 mm in subjects whose ODT peaked at day 1, 0.08 ± 0.09 mm in subjects whose ODT peaked on 1-week, and 0.12 ± 0.15 mm in subjects whose ODT peaked on 2-week or later. There was no difference in axial growth among the subjects whose ODT peaked at different days (P = 0.734). Conclusion: While half ODT time course resembled the changing speed of HOA with a transient elevation on day 1, about a quarter of the ODT time course resemble the steadily rising of HOA-RMS, and the rest was located in the middle. The ALGs in children with different types of ODT time courses were similar.