Offline transcranial direct current stimulation improves the ability to perceive crowded targets.

The deleterious effect of nearby flankers on target identification in the periphery is known as visual crowding. Studying visual crowding can advance our understanding of the mechanisms of visual awareness and object recognition. Alleviating visual crowding is one of the major ways to improve peripheral vision. The aim of the current study was to examine whether transcranial direct current stimulation (tDCS) was capable of alleviating visual crowding at different visual eccentricities and with different visual tasks. In the present single-blind sham-controlled study, subjects were instructed to perform an orientation discrimination task or a letter identification task with isolated and crowded targets in the periphery, before and after applying 20 minutes of 2 mA anodal tDCS to visual cortex of the hemisphere contralateral or ipsilateral to visual stimuli. Contralateral tDCS significantly alleviated the orientation crowding effect at two different eccentricities and the letter crowding effect. This alleviation was absent after sham or ipsilateral stimulation and could not be fully explained by the performance improvement with the isolated targets. These findings demonstrated that offline tDCS was effective in alleviating visual crowding across different visual eccentricities and tasks, therefore providing a promising way to improve spatial vision rapidly in crowded scenes.

Spatial summation revealed in the earliest visual evoked component C1 and the effect of attention on its linearity.

In natural scenes, multiple objects are usually presented simultaneously. How do specific areas of the brain respond to multiple objects based on their responses to each individual object? Previous functional magnetic resonance imaging (fMRI) studies have shown that the activity induced by a multiobject stimulus in the primary visual cortex (V1) can be predicted by the linear or nonlinear sum of the activities induced by its component objects. However, there has been little evidence from electroencephelogram (EEG) studies so far. Here we explored how V1 responded to multiple objects by comparing the EEG signals evoked by a three-grating stimulus with those evoked by its two components (the central grating and 2 flanking gratings). We focused on the earliest visual component C1 (onset latency of ∼50 ms) because it has been shown to reflect the feedforward responses of neurons in V1. We found that when the stimulus was unattended, the amplitude of the C1 evoked by the three-grating stimulus roughly equaled the sum of the amplitudes of the C1s evoked by its two components, regardless of the distances between these gratings. When the stimulus was attended, this linear spatial summation existed only when the three gratings were far apart from each other. When the three gratings were close to each other, the spatial summation became compressed. These results suggest that the earliest visual responses in V1 follow a linear summation rule when attention is not involved and that attention can affect the earliest interactions between multiple objects.

Two-stage perceptual learning to break visual crowding.

When a target is presented with nearby flankers in the peripheral visual field, it becomes harder to identify, which is referred to as crowding. Crowding sets a fundamental limit of object recognition in peripheral vision, preventing us from fully appreciating cluttered visual scenes. We trained adult human subjects on a crowded orientation discrimination task and investigated whether crowding could be completely eliminated by training. We discovered a two-stage learning process with this training task. In the early stage, when the target and flankers were separated beyond a certain distance, subjects acquired a relatively general ability to break crowding, as evidenced by the fact that the breaking of crowding could transfer to another crowded orientation, even a crowded motion stimulus, although the transfer to the opposite visual hemi-field was weak. In the late stage, like many classical perceptual learning effects, subjects' performance gradually improved and showed specificity to the trained orientation. We also found that, when the target and flankers were spaced too finely, training could only reduce, rather than completely eliminate, the crowding effect. This two-stage learning process illustrates a learning strategy for our brain to deal with the notoriously difficult problem of identifying peripheral objects in clutter. The brain first learned to solve the "easy and general" part of the problem (i.e., improving the processing resolution and segmenting the target and flankers) and then tackle the "difficult and specific" part (i.e., refining the representation of the target).

Attention-dependent early cortical suppression contributes to crowding.

Crowding, the identification difficulty for a target in the presence of nearby flankers, is ubiquitous in spatial vision and is considered a bottleneck of object recognition and visual awareness. Despite its significance, the neural mechanisms of crowding are still unclear. Here, we performed event-related potential and fMRI experiments to measure the cortical interaction between the target and flankers in human subjects. We found that the magnitude of the crowding effect was closely associated with an early suppressive cortical interaction. The cortical suppression was reflected in the earliest event-related potential component (C1), which originated in V1, and in the BOLD signal in V1, but not other higher cortical areas. Intriguingly, spatial attention played a critical role in the manifestation of the suppression. These findings provide direct and converging evidence that attention-dependent V1 suppression contributes to crowding at a very early stage of visual processing.

pH-Sensitive nanoparticles as smart carriers for selective intracellular drug delivery to tumor.

Herein, a smart pH-sensitive nanoparticle (DGL-PEG-Tat-KK-DMA-DOX) was prepared to achieve the selective intracellular drug delivery. In this nanoparticle, a PEG-grafted cell penetrating peptide (PEG-Tat-KK) was designed and acted as the cell penetrating segment. By introducing the pH-sensitive amide bonds between the peptide and blocking agent (2,3-dimethylmaleic anhydride, DMA), the controllable moiety (PEG-Tat-KK-DMA) endowed the nanoparticle with a charge-switchable shell and temporarily blocked penetrating function, thus improving the specific internalization. Besides, dendrigraft poly-L-lysine (DGL) used as the skeleton can greatly improve the drug loading because of the highly dendritic framework. Under the stimuli of acidic pH, this nanoparticle exhibited a remarkable charge-switchable property. The drug release showed an expected behavior with little release in the neutral pH media but relatively fast release in the acidic media. The in vitro experiments revealed that the cellular uptake and cytotoxicity were significantly enhanced after the pH was decreased. In vivo biodistribution and antitumor research indicated that the nanoparticle had noteworthy specificity and antitumor efficacy with a tumor inhibition rate of 79.7%. These results verified this nanoparticle could efficiently improve the selective intracellular delivery and possessed a great potential in tumor treatment.