Perception of visual variance is mediated by subcortical mechanisms.

Variance characterizes the structure of the environment. This statistical concept plays a critical role in evaluating the reliability of evidence for human decision-making. The present study examined the involvement of subcortical structures in the processing of visual variance. To this end, we used a stereoscope to sequentially present two circle arrays in a dichoptic or monocular fashion while participants compared the perceived variance of the two arrays. In Experiment 1, two arrays were presented monocularly to the same eye, dichopticly to different eyes, or binocularly to both eyes. The variance judgment was less accurate in different-eye condition than the other conditions. In Experiment 2, the first circle array was split into a large-variance and a small-variance set, with either the large-variance or small-variance set preceding the presentation of the second circle array in the same eye. The variance of the first array was judged larger when the second array was preceded by the large-variance set in the same eye, showing that the perception of variance was modulated by the visual variance processed in the same eye. Taken together, these findings provide evidence for monocular processing of visual variance, suggesting that subcortical structures capture the statistical structure of the visual world.

Nonadditive integration of visual information in ensemble processing.

Statistically summarizing information from a stimulus array into an ensemble representation (e.g., the mean) improves the efficiency of visual processing. However, little is known about how the brain computes the ensemble statistics. Here, we propose that ensemble processing is realized by nonadditive integration, rather than linear averaging, of individual items. We used a linear regression model approach to extract EEG responses to three levels of information: the individual items, their local interactions, and their global interaction. The local and global interactions, representing nonadditive integration of individual items, elicited rapid and independent neural responses. Critically, only the neural representation of the global interaction predicted the precision of the ensemble perception at the behavioral level. Furthermore, spreading attention over the global pattern to enhance ensemble processing directly promoted rapid neural representation of the global interaction. Taken together, these findings advocate a global, nonadditive mechanism of ensemble processing in the brain.

Brain Protection Effects of Mild Hypothermia Combined with Distant Ischemic Postconditioning and Thrombolysis in Patients with Acute Ischemic Stroke.

To assess the effectiveness and molecular mechanisms of mild hypothermia and remote ischemic postconditioning (RIPC) in patients with acute ischemic stroke (AIS) who have undergone thrombolysis therapy. A total of 58 AIS patients who received recombinant tissue plasmin activator (rt-PA) intravenous thrombolysis were included in this prospective study. Participants were randomly allocated to the experimental group (rt-PA intravenous thrombolysis plus mild hypothermic ice cap plus remote ischemic brain protection, n = 30) and the control group (rt-PA intravenous thrombolysis plus 0.9% saline, n = 28). The RIPC was performed for 14 consecutive days on both upper limb arteries spaced 2 minutes apart. Five cycles of ischemia-reperfusion were performed sequentially (2-2, 3-3, 4-4, 5-5, 5-0 minutes, respectively). The outcome measures of the National Institute of Health stroke scale (NIHSS) score, volume of cerebral infarction, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1ß, tumor necrosis factor α, nuclear factors kappa B (NF-κB), and NOD-1ike receptor pyrin 3 (NLRP3) were evaluated at different time points after treatment. Similarly, the 90-day modified Rankin Scale (mRS) scores were compared between the two groups. After treatment, the NIHSS score, MDA, NF-κB, and NLRP3 levels in the experimental group were significantly lower than those in the control group (p < 0.05). While the SOD in the experimental group was significantly higher than in the control group (p < 0.05), the NIHSS scores decreased within groups (all p < 0.05) in both experimental and control groups. The 90-day mRS score (0-2 points) in the experimental group was significantly higher than that in the control group (73.33% vs. 53.57%, p < 0.05) and no significant differences were observed in the safety indices between the two groups (all p > 0.05). Our study shows that combining mild hypothermia and RIPC has a positive effect on brain protection and can significantly reduce the oxidative stress and associated outburst of inflammatory response. The Clinical Trial Registration number is ChiCTR2300073136.

Subcortical encoding of summary statistics in humans.

Statistical encoding compresses redundant information from multiple items into a single summary metric (e.g., mean). Such statistical representation has been suggested to be automatic, but at which stage it is extracted is unknown. Here, we examined the involvement of the subcortex in the processing of summary statistics. We presented an array of circles dichoptically or monocularly while matching the number of perceived circles after binocular fusion. Experiments 1 and 2 showed that interocularly suppressed, invisible circles were automatically involved in the summary statistical representation, but only when they were presented to the same eye as the visible circles. This same-eye effect was further observed for consciously processed circles in Experiment 3, in which the estimated mean size of the circles was biased toward the information transmitted by monocular channels. Together, we provide converging evidence that the processing of summary statistics, an assumed high-level cognitive process, is mediated by subcortical structures.

Ensemble size perception: Its neural signature and the role of global interaction over individual items.

To efficiently process complex visual scenes, the visual system often summarizes statistical information across individual items and represents them as an ensemble. However, due to the lack of techniques to disentangle the representation of the ensemble from that of the individual items constituting the ensemble, whether there exists a specialized neural mechanism for ensemble processing and how ensemble perception is computed in the brain remain unknown. To address these issues, we used a frequency-tagging EEG approach to track brain responses to periodically updated ensemble sizes. Neural responses tracking the ensemble size were detected in parieto-occipital electrodes, revealing a global and specialized neural mechanism of ensemble size perception. We then used the temporal response function to isolate neural responses to the individual sizes and their interactions. Notably, while the individual sizes and their local and global interactions were encoded in the EEG signals, only the global interaction contributed directly to the ensemble size perception. Finally, distributed attention to the global stimulus pattern enhanced the neural signature of the ensemble size, mainly by modulating the neural representation of the global interaction between all individual sizes. These findings advocate a specialized, global neural mechanism of ensemble size perception and suggest that global interaction between individual items contributes to ensemble perception.

The dynamics of microsaccade amplitude reflect shifting of covert attention.

Attention flexibly shifts between spatial locations to accommodate task demands. The present study examined if the dynamics of attentional shifting are seen in microsaccades whose direction has been shown to accompany the shifts of covert attention. In a spatial cueing task, the cue predicted the target location on 100%, 75%, or 50% of the trials. The results revealed that microsaccade rate and amplitude were both reduced following cue onset and then rebounded. Both microsaccade rate and amplitude were biased towards the opposite direction of the cue and then returned to the cued direction. Importantly, the cue validity modulated the temporal profile of microsaccade amplitude but had little impact on the temporal profile of microsaccade rate. In line with this, the cueing effect measured with target response accuracy was correlated with the microsaccade amplitude only. These results indicate that the temporal dynamics of microsaccade amplitude reflect shifting of covert attention.

Alpha-Band Phase Modulates Bottom-up Feature Processing.

Recent studies reveal that attention operates in a rhythmic manner, that is, sampling each location or feature alternatively over time. However, most evidence derives from top-down tasks, and it remains elusive whether bottom-up processing also entails dynamic coordination. Here, we developed a novel feature processing paradigm and combined time-resolved behavioral measurements and electroencephalogram (EEG) recordings to address the question. Specifically, a salient color in a multicolor display serves as a noninformative cue to capture attention and presumably reset the oscillations of feature processing. We then measured the behavioral performance of a probe stimulus associated with either high- or low-salient color at varied temporal lags after the cue. First, the behavioral results (i.e., reaction time) display an alpha-band (~8 Hz) profile with a consistent phase lag between high- and low-salient conditions. Second, simultaneous EEG recordings show that behavioral performance is modulated by the phase of alpha-band neural oscillation at the onset of the probes. Finally, high- and low-salient probes are associated with distinct preferred phases of alpha-band neural oscillations. Taken together, our behavioral and neural results convergingly support a central function of alpha-band rhythms in feature processing, that is, features with varied saliency levels are processed at different phases of alpha neural oscillations.

Electrophysiological correlates of the somatotopically organized tactile duration aftereffect.

Adaptation to sensory events of long or short duration leads to a negative aftereffect, in which a new target event (of median duration) following the adaptation will be perceived to be shorter or longer than is actually the case. This illusion has been observed in visual, auditory, and tactile modalities. This study used event-related potentials (ERPs) to examine the tactile duration aftereffect, using the contingent negative variation (CNV) and the late positive component (LPC) as a way to characterize the temporal processes. The tactile duration adaptation was found to induce a significant aftereffect within a somatotopic framework. Moreover, the CNV in the contralateral scalp and the LPC in the fronto-central scalp were both modulated by the tactile duration adaptation. Specifically, adaptation to a short tactile duration increased the CNV and LPC amplitudes, whereas adaptation to a long tactile duration decreased them. This modulation was contingent on the topographic distance between fingers, which was only observed when the adapting and test fingers were consistent or adjacent, but not homologous. In sum, these results reveal a coherent behavioral-electrophysiological link in the somatotopically organized tactile duration aftereffect.

Competing rhythmic neural representations of orientations during concurrent attention to multiple orientation features.

When a feature is attended, all locations containing this feature are enhanced throughout the visual field. However, how the brain concurrently attends to multiple features remains unknown and cannot be easily deduced from classical attention theories. Here, we recorded human magnetoencephalography signals when subjects concurrently attended to two spatially overlapping orientations. A time-resolved multivariate inverted encoding model was employed to track the ongoing temporal courses of the neural representations of the attended orientations. We show that the two orientation representations alternate with each other and undergo a theta-band (~4 Hz) rhythmic fluctuation over time. Similar temporal profiles are also revealed in the orientation discrimination performance. Computational modeling suggests a tuning competition process between the two neuronal populations that are selectively tuned to one of the attended orientations. Taken together, our findings reveal for the first time a rhythm-based, time-multiplexing neural machinery underlying concurrent multi-feature attention.

Beta and alpha desynchronizations underlie reconsolidation-mediated episodic memory updating.

Reactivation returns a consolidated memory to a plastic state, opening a window for the existing memory to be updated. For episodic memory, learning of competing information upon reactivation either integrates the new information into the reactivated memory or disrupts the reactivated memory directly, but the two effects were found in distinct experimental paradigms and their neural mechanisms are largely unknown. The current study explored the effects and neural mechanisms of episodic memory reactivation using behavioural and MEG techniques. Taking advantage of an independent-cue retrieval procedure, we revealed both the integration and the forgetting effects by a single post-reactivation interference paradigm. However, while the integration effect followed the reconsolidation window, the forgetting effect did not, suggesting only the integration effect being caused by memory reconsolidation. MEG measurements further revealed beta-band power decrease during reactivation and alpha-band power decrease during post-reactivation interference, both of which parametrically predicted the degree of memory integration. But neither the beta nor the alpha desynchronization was related to the forgetting of the original memory. Our results suggest original memory forgetting and new information integration happen in different time periods after memory reactivation, and beta and alpha desynchronizations underlie reconsolidation-mediated episodic memory updating.

Selective spatial attention involves two alpha-band components associated with distinct spatiotemporal and functional characteristics.

Attention is crucial for efficiently coordinating resources over multiple objects in a visual scene. Recently, a growing number of studies suggest that attention is implemented through a temporal organization process during which resources are dynamically allocated over a multitude of objects, yet the associated neural evidence, particularly in low-level sensory areas, is still limited. Here we used EEG recordings in combination with a temporal response function (TRF) approach to examine the spatiotemporal characteristics of neuronal impulse response in covert selective attention. We demonstrate two distinct alpha-band components - one in post-central parietal area and one in contralateral occipital area - that are involved in coordinating neural representations of attended and unattended stimuli. Specifically, consistent with previous findings, the central alpha-band component showed enhanced activities for unattended versus attended stimuli within the first 200 ms temporal lag of TRF response, suggesting its inhibitory function in attention. In contrast, the contralateral occipital component displayed relatively earlier activation for the attended than unattended one in the TRF response. Furthermore, the central component but not the occipital component was correlated with attentional behavioral performance. Finally, the parietal area exerted directional influences on the occipital activity through alpha-band rhythm. Taken together, spatial attention involves two hierarchically organized alpha-band components that are associated with distinct spatiotemporal characteristics and presumably play different functions.

[Temporal structure and dynamic neural mechanism in visual attention].

Attention shapes what we see and what we act upon by allocating limited resources to certain parts of visual display in a selective and adaptive manner. While most previous studies in visual attention mainly focused on the attentional distribution over space or features, recent studies have revealed that temporal dynamics also plays a crucial function in visual attention. This paper reviews the representation, function and neural mechanism of temporal dynamics in visual attention from the following four aspects: (1) Tracking dynamic structure of external stimulus by attention; (2) Intrinsic dynamic characteristics of attention; (3) Time-based multiple object representation; (4) Relationship between visual dynamics and classical attentional phenomena. We propose that the dynamic structure and temporal organization are fundamental to visual attention, and the research on it might provide new solutions to many unresolved issues in visual attention research.

Fast-backward replay of sequentially memorized items in humans.

Storing temporal sequences of events (i.e., sequence memory) is fundamental to many cognitive functions. However, it is unknown how the sequence order information is maintained and represented in working memory and its behavioral significance, particularly in human subjects. We recorded electroencephalography (EEG) in combination with a temporal response function (TRF) method to dissociate item-specific neuronal reactivations. We demonstrate that serially remembered items are successively reactivated during memory retention. The sequential replay displays two interesting properties compared to the actual sequence. First, the item-by-item reactivation is compressed within a 200 - 400 ms window, suggesting that external events are associated within a plasticity-relevant window to facilitate memory consolidation. Second, the replay is in a temporally reversed order and is strongly related to the recency effect in behavior. This fast-backward replay, previously revealed in rat hippocampus and demonstrated here in human cortical activities, might constitute a general neural mechanism for sequence memory and learning.

Have you ever played the 'Memory Maze Challenge' game, or its predecessor from the 1980s, 'Simon'? Players must memorize a sequence of colored lights, and then reproduce the sequence by tapping the colors on a pad. The sequence becomes longer with each trial, making the task more and more difficult. One wrong response and the game is over. Storing and retrieving sequences is key to many cognitive processes, from following speech to hitting a tennis ball to recalling what you did last week. Such tasks require memorizing the order in which items occur as well as the items themselves. But how do we hold this information in memory? Huang et al. reveal the answer by using scalp electrodes to record the brain activity of healthy volunteers as they memorize and then recall a sequence. Memorizing, or encoding, each of the items in the sequence triggered a distinct pattern of brain activity. As the volunteers held the sequence in memory, their brains replayed these activity patterns one after the other. But this replay showed two non-intuitive features. First, it was speeded up relative to the original encoding. In fact, the brain compressed the entire sequence into about 200 to 400 milliseconds. Second, the brain replayed the sequence backwards. The activity pattern corresponding to the last item was replayed first, while that corresponding to the first item was replayed last. This 'fast-backward' replay may explain why we tend to recall items at the end of a list better than those in the middle, a phenomenon known as the recency effect. The results of Huang et al. suggest that when we hold a list of items in memory, the brain does not replay the list in its original form, like an echo. Instead, the brain restructures and reorganizes the list, compressing and reversing it. This process, which is also seen in rodents, helps the brain to incorporate the list of items into existing neuronal networks for memory storage.

Sequential sampling of visual objects during sustained attention.

In a crowded visual scene, attention must be distributed efficiently and flexibly over time and space to accommodate different contexts. It is well established that selective attention enhances the corresponding neural responses, presumably implying that attention would persistently dwell on the task-relevant item. Meanwhile, recent studies, mostly in divided attentional contexts, suggest that attention does not remain stationary but samples objects alternately over time, suggesting a rhythmic view of attention. However, it remains unknown whether the dynamic mechanism essentially mediates attentional processes at a general level. Importantly, there is also a complete lack of direct neural evidence reflecting whether and how the brain rhythmically samples multiple visual objects during stimulus processing. To address these issues, in this study, we employed electroencephalography (EEG) and a temporal response function (TRF) approach, which can dissociate responses that exclusively represent a single object from the overall neuronal activity, to examine the spatiotemporal characteristics of attention in various attentional contexts. First, attention, which is characterized by inhibitory alpha-band (approximately 10 Hz) activity in TRFs, switches between attended and unattended objects every approximately 200 ms, suggesting a sequential sampling even when attention is required to mostly stay on the attended object. Second, the attentional spatiotemporal pattern is modulated by the task context, such that alpha-mediated switching becomes increasingly prominent as the task requires a more uniform distribution of attention. Finally, the switching pattern correlates with attentional behavioral performance. Our work provides direct neural evidence supporting a generally central role of temporal organization mechanism in attention, such that multiple objects are sequentially sorted according to their priority in attentional contexts. The results suggest that selective attention, in addition to the classically posited attentional "focus," involves a dynamic mechanism for monitoring all objects outside of the focus. Our findings also suggest that attention implements a space (object)-to-time transformation by acting as a series of concatenating attentional chunks that operate on 1 object at a time.

Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke.

Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.