A subcortical magnocellular pathway is responsible for the fast processing of topological properties of objects: A transcranial magnetic stimulation study.

Rapid object recognition has survival significance. The extraction of topological properties (TP) is proposed as the starting point of object perception. Behavioral evidence shows that TP processing takes precedence over other geometric properties and can accelerate object recognition. However, the mechanism of the fast TP processing remains unclear. The magnocellular (M) pathway is well known as a fast route to convey "coarse" information, compared with the slow parvocellular (P) pathway. Here, we hypothesize that the fast processing of TP occurs in a subcortical M pathway. We applied single-pulse transcranial magnetic stimulation (TMS) over the primary visual cortex to temporarily disrupt cortical processing. Besides, stimuli were designed to preferentially engage M or P pathways (M- or P-biased conditions). We found that, when TMS disrupted cortical function at the early stages of stimulus processing, non-TP shape discrimination was strongly impaired in both M- and P-biased conditions, whereas TP discrimination was not affected in the M-biased condition, suggesting that early M processing of TP is independent of the visual cortex, but probably occurs in a subcortical M pathway. Using an unconscious priming paradigm, we further found that early M processing of TP can accelerate object recognition by speeding up the processing of other properties, e.g., orientation. Our findings suggest that the human visual system achieves efficient object recognition by rapidly processing TP in the subcortical M pathway.

Delayed administration of nafamostat mesylate inhibits thrombin-mediated blood-spinal cord barrier breakdown during acute spinal cord injury in rats.

BACKGROUND: Nafamostat mesylate (nafamostat, NM) is an FDA-approved serine protease inhibitor that exerts anti-neuroinflammation and neuroprotective effects following rat spinal cord injury (SCI). However, clinical translation of nafamostat has been limited by an unclear administration time window and mechanism of action. METHODS: Time to first dose of nafamostat administration was tested on rats after contusive SCI. The optimal time window of nafamostat was screened by evaluating hindlimb locomotion and electrophysiology. As nafamostat is a serine protease inhibitor known to target thrombin, we used argatroban (Arg), a thrombin-specific inhibitor, as a positive control in the time window experiments. Western blot and immunofluorescence of thrombin expression level and its enzymatic activity were assayed at different time points, as well its receptor, the protease activated receptor 1 (PAR1) and downstream protein matrix metalloproteinase-9 (MMP9). Blood-spinal cord barrier (BSCB) permeability leakage indicator Evans Blue and fibrinogen were analyzed along these time points. The infiltration of peripheral inflammatory cell was observed by immunofluorescence. RESULTS: The optimal administration time window of nafamostat was 2-12 h post-injury. Argatroban, the thrombin-specific inhibitor, had a similar pattern. Thrombin expression peaked at 12 h and returned to normal level at 7 days post-SCI. PAR1, the thrombin receptor, and MMP9 were significantly upregulated after SCI. The most significant increase of thrombin expression was detected in vascular endothelial cells (ECs). Nafamostat and argatroban significantly downregulated thrombin and MMP9 expression as well as thrombin activity in the spinal cord. Nafamostat inhibited thrombin enrichment in endothelial cells. Nafamostat administration at 2-12 h after SCI inhibited the leakage of Evans Blue in the epicenter and upregulated tight junction proteins (TJPs) expression. Nafamostat administration 8 h post-SCI effectively inhibited the infiltration of peripheral macrophages and neutrophils to the injury site. CONCLUSIONS: Our study provides preclinical information of nafamostat about the administration time window of 2-12 h post-injury in contusive SCI. We revealed that nafamostat functions through inhibiting the thrombin-mediated BSCB breakdown and subsequent peripheral immune cells infiltration.

Topological change induces an interference effect in visual working memory.

The "irrelevant-change distracting effect" refers to the effect of changes in irrelevant features on the performance of the target feature, which has frequently been used to study information processing in visual working memory (VWM). In the current study, we reported a novel interference effect in VWM: the topological-change interference effect (TCIE). In a series of six experiments, we examined the influence of topological and nontopological changes as irrelevant features on VWM using a color change detection paradigm. The results revealed that only topological changes, although task irrelevant, could produce a significant interference effect. In contrast, nontopological changes did not produce any evident interference effect. Moreover, the TCIE was a stable and lasting effect, regardless of changes in locations, reporting methods, particular stimulus figures, the other salient feature dimensions and delay interval times. Therefore, our results support the notion that topological invariance that defines perceptual objects plays an essential role in maintaining representations in VWM.

Perceptual learning modifies the functional specializations of visual cortical areas.

Training can improve performance of perceptual tasks. This phenomenon, known as perceptual learning, is strongest for the trained task and stimulus, leading to a widely accepted assumption that the associated neuronal plasticity is restricted to brain circuits that mediate performance of the trained task. Nevertheless, learning does transfer to other tasks and stimuli, implying the presence of more widespread plasticity. Here, we trained human subjects to discriminate the direction of coherent motion stimuli. The behavioral learning effect substantially transferred to noisy motion stimuli. We used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the transfer of learning. The TMS experiment revealed dissociable, causal contributions of V3A (one of the visual areas in the extrastriate visual cortex) and MT+ (middle temporal/medial superior temporal cortex) to coherent and noisy motion processing. Surprisingly, the contribution of MT+ to noisy motion processing was replaced by V3A after perceptual training. The fMRI experiment complemented and corroborated the TMS finding. Multivariate pattern analysis showed that, before training, among visual cortical areas, coherent and noisy motion was decoded most accurately in V3A and MT+, respectively. After training, both kinds of motion were decoded most accurately in V3A. Our findings demonstrate that the effects of perceptual learning extend far beyond the retuning of specific neural populations for the trained stimuli. Learning could dramatically modify the inherent functional specializations of visual cortical areas and dynamically reweight their contributions to perceptual decisions based on their representational qualities. These neural changes might serve as the neural substrate for the transfer of perceptual learning.

Visual working memory representation as a topological defined perceptual object.

The question of what the basic unit is of visual working memory remains one of the most fundamental and controversial issues. In the current study, we proposed a unique perspective based on early topological perception to describe the nature of representation in visual working memory. In a series of updating change-detection tasks, the repetition-benefit effect on color memory was not affected when items in the second memory array underwent massive changes of nontopological features from the first memory array. However, when the topological properties of an item changed, the repetition-benefit effect was destroyed, suggesting that the item was perceived as a new object impairing the original memory. Hence, our results suggest that a perceptual object defined by its topological invariance might be a unique perspective from which to describe representations of visual working memory.

Topology-defined units in numerosity perception.

What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.

What determines the object-level visual masking: The bottom-up role of topological change.

Object substitution masking (OSM) is said to occur on an object level without a close spatiotemporal proximity of target and mask. An influential account for OSM is "object updating," which espouses that OSM occurs when the target is updated by the mask as they share a single object representation. However, it is unclear what attribute determines whether the mask shares the same object representation as the target. We hypothesize that topological property determines whether a new object representation is built, and hence topological perception modulates object-level masking. We systematically manipulated the similarity between the target and the mask by changing a topological property (number of holes), color, shape, and orientation. We found that the topological change between the target and the mask reduced masking effects of all the other properties. Changing color, shape, or orientation, however, did not affect the masking effect of any other property. The global effect of the topological change remained across a variety of temporal and spatial distances between the target and the mask and was not limited to masking paradigms. Thus, our results suggest that the object representation, constrained by its topological properties, serves as a higher and global level of OSM, influencing the ongoing visual processing of features that are at a lower and local level.

Objective measurement of gestalts: Quantifying grouping effect by tilt aftereffect.

The importance of holistic perception is described by Gestalt psychology and its principles. Gestalt psychologists have promoted a formal and testable framework for these principles. Quantitative measurements have been introduced from Gestalt psychology in order to complement traditional phenomenal descriptions. Here we demonstrated a new method of measuring grouping effects objectively and quantitatively, by means of tilt aftereffect (TAE) from visual adaptation. Experiment 1 validated the method by measuring grouping based on either proximity or color similarity. Experiments 2 and 3 verified that this paradigm is also effective with dimotif lattices in which different perceptual organizations compete. The novel TAE-based paradigm is an objective and effective method for studying perceptual organization, especially the relationship between different Gestalt principles.

Neural activities in V1 create the bottom-up saliency map of natural scenes.

A saliency map is the bottom-up contribution to the deployment of exogenous attention. It, as well as its underlying neural mechanism, is hard to identify because of the influence of top-down signals. A recent study showed that neural activities in V1 could create a bottom-up saliency map (Zhang et al. in Neuron 73(1):183-192, 2012). In this paper, we tested whether their conclusion can generalize to complex natural scenes. In order to avoid top-down influences, each image was presented with a low contrast for only 50 ms and was followed by a high contrast mask, which rendered the whole image invisible to participants (confirmed by a forced-choice test). The Posner cueing paradigm was adopted to measure the spatial cueing effect (i.e., saliency) by an orientation discrimination task. A positive cueing effect was found, and the magnitude of the cueing effect was consistent with the saliency prediction of a computational saliency model. In a following fMRI experiment, we used the same masked natural scenes as stimuli and measured BOLD signals responding to the predicted salient region (relative to the background). We found that the BOLD signal in V1, but not in other cortical areas, could well predict the cueing effect. These results suggest that the bottom-up saliency map of natural scenes could be created in V1, providing further evidence for the V1 saliency theory (Li in Trends Cogn Sci 6(1):9-16, 2002).

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.

Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain.

Global versus local: double dissociation between MT+ and V3A in motion processing revealed using continuous theta burst transcranial magnetic stimulation.

The functional properties of motion selective areas in human visual cortex, including V3A, MT+, and intraparietal sulcus (IPS) are not fully understood. To examine the functional specialization of these areas for global and local motion processing, we used off-line, neuronavigated, continuous theta burst (cTBS) transcranial magnetic stimulation to temporarily alter neural activity within unilateral V3A, MT+, and IPS. A within-subjects design was employed and stimulation sessions were separated by at least 24 h. In each session, subjects were asked to discriminate the global motion directions of successively presented random dot kinematograms (RDKs) before and after cTBS. RDKs were presented at either 100 or 40 % coherence in either the left or right visual field. We found that V3A stimulation selectively impaired discrimination of 100 % coherent motion, while MT+ stimulation selectively impaired discrimination of 40 % coherent motion. IPS stimulation impaired discrimination of both motion stimuli. All cTBS effects were specific to stimuli presented contralaterally to the stimulation site and vertex stimulation had no effect. The double dissociation between the cTBS effects on MT+ and V3A indicates distinct roles for these two regions in motion processing. Judging the direction of 100 % coherent motion can rely on local motion processing because every dot moves in the same direction. However, judging the global direction of 40 % coherent motion requires global processing. Thus, our results suggest separate, parallel processing of local and global motion in V3A and MT+, respectively, with the outputs of these two areas being combined within the IPS.

Topological change disturbs object continuity in attentive tracking.

The question of what is a perceptual object is one of the most central and also controversial issues in cognitive science. According to the topological approach to perceptual organization, the core intuitive notion of an object--the holistic identity preserved over shape-changing transformations--may be characterized precisely as topological invariance. Here we show that, across a series of multiple-object tracking tasks, performance was not disrupted when the moving items underwent massive featural changes. However, performance was significantly impaired when the items changed their topological properties of holes, demonstrating that topological invariance constrains what counts as an object in the first place. Consistent with previous findings, fMRI studies indicated that the anterior temporal lobe may be involved in the formation of object representation defined by topological constraints.

Brain Cognition-Inspired Dual-Pathway CNN Architecture for Image Classification.

Inspired by the global-local information processing mechanism in the human visual system, we propose a novel convolutional neural network (CNN) architecture named cognition-inspired network (CogNet) that consists of a global pathway, a local pathway, and a top-down modulator. We first use a common CNN block to form the local pathway that aims to extract fine local features of the input image. Then, we use a transformer encoder to form the global pathway to capture global structural and contextual information among local parts in the input image. Finally, we construct the learnable top-down modulator where fine local features of the local pathway are modulated by global representations of the global pathway. For ease of use, we encapsulate the dual-pathway computation and modulation process into a building block, called the global-local block (GL block), and a CogNet of any depth can be constructed by stacking a necessary number of GL blocks one after another. Extensive experimental evaluations have revealed that the proposed CogNets have achieved the state-of-the-art performance accuracies on all the six benchmark datasets and are very effective for overcoming the "texture bias" and the "semantic confusion" problems faced by many CNN models.

Form Properties of Moving Targets Bias Smooth Pursuit Target Selection in Monkeys.

During natural viewing, we often recognize multiple objects, detect their motion, and select one object as the target to track. It remains to be determined how such behavior is guided by the integration of visual form and motion perception. To address this, we studied how monkeys made a choice to track moving targets with different forms by smooth pursuit eye movements in a two-target task. We found that pursuit responses were biased toward the motion direction of a target with a hole. By computing the relative weighting, we found that the target with a hole exhibited a larger weight for vector computation. The global hole feature dominated other form properties. This dominance failed to account for changes in pursuit responses to a target with different forms moving singly. These findings suggest that the integration of visual form and motion perception can reshape the competition in sensorimotor networks to guide behavioral selection.

Neural representation of gestalt grouping and attention effect in human visual cortex.

BACKGROUND: The brain aggregates meaningless local sensory elements to form meaningful global patterns in a process called perceptual grouping. Current brain imaging studies have found that neural activities in V1 are modulated during visual grouping. However, how grouping is represented in each of the early visual areas, and how attention alters these representations, is still unknown. NEW METHOD: We adopted MVPA to decode the specific content of perceptual grouping by comparing neural activity patterns between gratings and dot lattice stimuli which can be grouped with proximity law. Furthermore, we quantified the grouping effect by defining the strength of grouping, and assessed the effect of attention on grouping. RESULTS: We found that activity patterns to proximity grouped stimuli in early visual areas resemble these to grating stimuli with the same orientations. This similarity exists even when there is no attention focused on the stimuli. The results also showed a progressive increase of representational strength of grouping from V1 to V3, and attention modulation to grouping is only significant in V3 among all the visual areas. COMPARISON WITH EXISTING METHODS: Most of the previous work on perceptual grouping has focused on how activity amplitudes are modulated by grouping. Using MVPA, the present work successfully decoded the contents of neural activity patterns corresponding to proximity grouping stimuli, thus shed light on the availability of content-decoding approach in the research on perceptual grouping. CONCLUSIONS: Our work found that the content of the neural activity patterns during perceptual grouping can be decoded in the early visual areas under both attended and unattended task, and provide novel evidence that there is a cascade processing for proximity grouping through V1 to V3. The strength of grouping was larger in V3 than in any other visual areas, and the attention modulation to the strength of grouping was only significant in V3 among all the visual areas, implying that V3 plays an important role in proximity grouping.

LC-MS/MS-based arachidonic acid metabolomics in acute spinal cord injury reveals the upregulation of 5-LOX and COX-2 products.

Arachidonic acid (AA) plays a critical role in inflammatory regulation and secondary injury after spinal cord injury (SCI). However, the overall AA metabolism profile in the acute phase of SCI remains elusive. Here we quantified AA metabolomics by High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Method (LC-MS/MS) using spinal cord tissue collected at 4 h, 24 h and 48 h after contusive SCI in rats. Remarkably, Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4) were significantly increased throughout the acute SCI. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), the key enzymes involved in the production of PGE2 and LTB4, were elevated in the lesioned spinal cord tissue, validated by both western blot and immunofluorecnce. The spatial-temporal changes of COX-2 and 5-LOX mainly occurs in neurons both in epicenter and rostral and caudal spinal cord segments after SCI. Our study sheds light on the dynamic microenvironment changes in acute SCI by characterizing the profile of AA metabolism. The COX-2 and 5-LOX may be promising therapeutic target for SCI.

Edaravone Modulates Neuronal GPX4/ACSL4/5-LOX to Promote Recovery After Spinal Cord Injury.

The FDA-approved drug edaravone has a neuroprotective effect on spinal cord injury (SCI) and many other central nervous system diseases. However, its molecular mechanism remains unclear. Since edaravone is a lipid peroxidation scavenger, we hypothesize that edaravone exerts its neuroprotective effect by inhibiting ferroptosis in SCI. Edaravone treatment after SCI upregulates glutathione peroxidase 4 (GPX4) and system Xc-light chain (xCT), which are anti-ferroptosis proteins. It downregulates pro-ferroptosis proteins Acyl-CoA synthetase long-chain family member 4 (ACSL4) and 5-lipoxygenase (5-LOX). The most significant changes in edaravone treatment occur in the acute phase, two days post injury. Edaravone modulates neuronal GPX4/ACSL4/5-LOX in the spinal segment below the lesion, which is critical for maintaining locomotion. Moreover, the GPX4/ACSL4/5-LOX in motor neuron is also modulated by edaravone in the spinal cord. Therefore, secondary injury below the lesion site is reversed by edaravone via ferroptosis inhibition. The cytokine array revealed that edaravone upregulated some anti-inflammatory cytokines such as IL-10, IL-13, and adiponectin. Edaravone reduced microgliosis and astrogliosis, indicating reduced neuroinflammation. Edaravone has a long-term effect on neuronal survival, spinal cord tissue sparing, and motor function recovery. In summary, we revealed a novel mechanism of edaravone in inhibiting neuronal ferroptosis in SCI. This mechanism may be generalizable to other neurological diseases.

Probing quantum many-body correlations by universal ramping dynamics.

Ramping a physical parameter is one of the most common experimental protocols in studying a quantum system, and ramping dynamics has been widely used in preparing a quantum state and probing physical properties. Here, we present a novel method of probing quantum many-body correlation by ramping dynamics. We ramp a Hamiltonian parameter to the same target value from different initial values and with different velocities, and we show that the first-order correction on the finite ramping velocity is universal and path-independent, revealing a novel quantum many-body correlation function of the equilibrium phases at the target values. We term this method as the non-adiabatic linear response since this is the leading order correction beyond the adiabatic limit. We demonstrate this method experimentally by studying the Bose-Hubbard model with ultracold atoms in three-dimensional optical lattices. Unlike the conventional linear response that reveals whether the quasi-particle dispersion of a quantum phase is gapped or gapless, this probe is more sensitive to whether the quasi-particle lifetime is long enough such that the quantum phase possesses a well-defined quasi-particle description. In the Bose-Hubbard model, this non-adiabatic linear response is significant in the quantum critical regime where well-defined quasi-particles are absent. And in contrast, this response is vanishingly small in both superfluid and Mott insulators which possess well-defined quasi-particles. Because our proposal uses the most common experimental protocol, we envision that our method can find broad applications in probing various quantum systems.

Cortical dynamics underlying face completion in human visual system.

In natural images, visual objects are typically occluded by other objects. A remarkable ability of our visual system is to complete occluded objects effortlessly and see whole, uninterrupted objects. How object completion is implemented in the visual system is still largely unknown. In this study, using a backward masking paradigm, we combined psychophysics and functional magnetic resonance imaging to investigate the temporal evolvement of face completion at different levels of the visual processing hierarchy. Human subjects were presented with two kinds of stimuli that were designed to elicit or not elicit the percept of a completed face, although they were physically very similar. By contrasting subjects' behavioral and blood oxygenation level-dependent (BOLD) responses to completed and noncompleted faces, we measured the psychophysical time course of the face completion and its underlying cortical dynamics. We found that face completion manifested its effect between 50 and 250 ms after stimulus onset. Relative to noncompleted faces, completed faces induced weaker BOLD response at early processing phases in retinotopic visual areas V1 and V2 and stronger BOLD response at late processing phases in occipital face area and fusiform face area. Attending away from the stimuli largely abolished these effects. These findings suggest that face completion consists of two synergetic phases: early suppression in lower visual areas and late enhancement in higher visual areas; moreover, attention is necessary to these neural events.