Dependence of Contextual Modulation in Macaque V1 on Interlaminar Signal Flow.

In visual cortex, neural correlates of subjective perception can be generated by modulation of activity from beyond the classical receptive field (CRF). In macaque V1, activity generated by nonclassical receptive field (nCRF) stimulation involves different intracortical circuitry than activity generated by CRF stimulation, suggesting that interactions between neurons across V1 layers differ under CRF and nCRF stimulus conditions. We measured border ownership modulation within large populations of V1 neurons. We found that neurons in single columns preferred the same side of objects located outside of the CRF. In addition, we found that interactions between pairs of neurons situated across feedback/horizontal and input layers differed between CRF and nCRF stimulation. Furthermore, the magnitude of border ownership modulation was predicted by greater information flow from feedback/horizontal to input layers. These results demonstrate that the flow of signals between layers covaries with the degree to which neurons integrate information from beyond the CRF.

Common and distinct neural mechanisms of attention.

Despite a constant deluge of sensory stimulation, only a fraction of it is used to guide behavior. This selective processing is generally referred to as attention, and much research has focused on the neural mechanisms controlling it. Recently, research has broadened to include more ways by which different species selectively process sensory information, whether due to the sensory input itself or to different behavioral and brain states. This work has produced a complex and disjointed body of evidence across different species and forms of attention. However, it has also provided opportunities to better understand the breadth of attentional mechanisms. Here, we summarize the evidence that suggests that different forms of selective processing are supported by mechanisms both common and distinct.

Functional interactions among neurons within single columns of macaque V1.

Recent developments in high-density neurophysiological tools now make it possible to record from hundreds of single neurons within local, highly interconnected neural networks. Among the many advantages of such recordings is that they dramatically increase the quantity of identifiable, functional interactions between neurons thereby providing an unprecedented view of local circuits. Using high-density, Neuropixels recordings from single neocortical columns of primary visual cortex in nonhuman primates, we identified 1000s of functionally interacting neuronal pairs using established crosscorrelation approaches. Our results reveal clear and systematic variations in the synchrony and strength of functional interactions within single cortical columns. Despite neurons residing within the same column, both measures of interactions depended heavily on the vertical distance separating neuronal pairs, as well as on the similarity of stimulus tuning. In addition, we leveraged the statistical power afforded by the large numbers of functionally interacting pairs to categorize interactions between neurons based on their crosscorrelation functions. These analyses identified distinct, putative classes of functional interactions within the full population. These classes of functional interactions were corroborated by their unique distributions across defined laminar compartments and were consistent with known properties of V1 cortical circuitry, such as the lead-lag relationship between simple and complex cells. Our results provide a clear proof-of-principle for the use of high-density neurophysiological recordings to assess circuit-level interactions within local neuronal networks.

Highland Barley and Its By-Products Enriched with Phenolic Compounds for Inhibition of Pyrraline Formation by Scavenging α-Dicarbonyl Compounds.

Pyrraline, a typical kind of advanced glycation end product, has been found to contribute to the development of pathologies associated with ageing and diabetes mellitus. In the study, phenolic compounds extracted from highland barley whole grain (HBWG) and vinasse (HBVN) were used to inhibit pyrraline formation in a simulated food. The optimal extraction condition for HBWG and HBVN was using 8 mL of 50% acetone solution at 50 °C for 60 min. The extraction and identification of phenolic compounds from HBWG and HBVN were performed by UPLC-PAD-MS/MS. The inhibitory effects of pyrraline in the simulated food were 52.03% and 49.22% by HBVN and HBWG, respectively. The diphenyl picrylhydrazyl radical- and ferric-reducing ability of plasma assays was used to evaluate the antioxidant activity of the extracts. The main inhibition pathways and molecular mechanism of phenolic compounds on pyrraline regulation were explored by scavenging α-dicarbonyl compounds. The study demonstrated that highland barley and its by-products can potentially be used as a functional food to regulate pyrraline formation during food processing.

Multi-View Broad Learning System for Primate Oculomotor Decision Decoding.

Multi-view learning improves the learning performance by utilizing multi-view data: data collected from multiple sources, or feature sets extracted from the same data source. This approach is suitable for primate brain state decoding using cortical neural signals. This is because the complementary components of simultaneously recorded neural signals, local field potentials (LFPs) and action potentials (spikes), can be treated as two views. In this paper, we extended broad learning system (BLS), a recently proposed wide neural network architecture, from single-view learning to multi-view learning, and validated its performance in decoding monkeys' oculomotor decision from medial frontal LFPs and spikes. We demonstrated that medial frontal LFPs and spikes in non-human primate do contain complementary information about the oculomotor decision, and that the proposed multi-view BLS is a more effective approach for decoding the oculomotor decision than several classical and state-of-the-art single-view and multi-view learning approaches.

Frontal eye field neurons selectively signal the reward value of prior actions.

The consequences of individual actions are typically unknown until well after they are executed. This fact necessitates a mechanism that bridges delays between specific actions and reward outcomes. We looked for the presence of such a mechanism in the post-movement activity of neurons in the frontal eye field (FEF), a visuomotor area in prefrontal cortex. Monkeys performed an oculomotor gamble task in which they made eye movements to different locations associated with dynamically varying reward outcomes. Behavioral data showed that monkeys tracked reward history and made choices according to their own risk preferences. Consistent with previous studies, we observed that the activity of FEF neurons is correlated with the expected reward value of different eye movements before a target appears. Moreover, we observed that the activity of FEF neurons continued to signal the direction of eye movements, the expected reward value, and their interaction well after the movements were completed and when targets were no longer within the neuronal response field. In addition, this post-movement information was also observed in local field potentials, particularly in low-frequency bands. These results show that neural signals of prior actions and expected reward value persist across delays between those actions and their experienced outcomes. These memory traces may serve a role in reward-based learning in which subjects need to learn actions predicting delayed reward.

Parietal Cortex Regulates Visual Salience and Salience-Driven Behavior.

Unique stimuli stand out. Despite an abundance of competing sensory stimuli, the detection of the most salient ones occurs without effort, and that detection contributes to the guidance of adaptive behavior. Neurons sensitive to the salience of visual stimuli are widespread throughout the primate visual system and are thought to shape the selection of visual targets. However, a neural source of salience remains elusive. In an attempt to identify a source of visual salience, we reversibly inactivated parietal cortex and simultaneously recorded salience signals in prefrontal cortex. Inactivation of parietal cortex not only caused pronounced and selective reductions of salience signals in prefrontal cortex but also diminished the influence of salience on visually guided behavior. These observations demonstrate a causal role of parietal cortex in regulating salience signals within the brain and in controlling salience-driven behavior.

Inactivation of Medial Frontal Cortex Changes Risk Preference.

Humans and other animals need to make decisions under varying degrees of uncertainty. These decisions are strongly influenced by an individual's risk preference; however, the neuronal circuitry by which risk preference shapes choice is still unclear [1]. Supplementary eye field (SEF), an oculomotor area within primate medial frontal cortex, is thought to be an essential part of the neuronal circuit underlying oculomotor decision making, including decisions under risk [2-5]. Consistent with this view, risk-related action value and monitoring signals have been observed in SEF [6-8]. However, such activity has also been observed in other frontal areas, including orbitofrontal [9-11], cingulate [12-14], and dorsal-lateral frontal cortex [15]. It is thus unknown whether the activity in SEF causally contributes to risky decisions, or whether it is merely a reflection of neural processes in other cortical regions. Here, we tested a causal role of SEF in risky oculomotor choices. We found that SEF inactivation strongly reduced the frequency of risky choices. This reduction was largely due to a reduced attraction to reward uncertainty and high reward gain, but not due to changes in the subjective estimation of reward probability or average expected reward. Moreover, SEF inactivation also led to increased sensitivity to differences between expected and actual reward during free choice. Nevertheless, it did not affect adjustments of decisions based on reward history.

Dissonant Representations of Visual Space in Prefrontal Cortex during Eye Movements.

We used local field potentials (LFPs) and spikes to investigate representations of visual space in prefrontal cortex and the dynamics of those representations during eye movements. Spatial information contained in LFPs of the frontal eye field (FEF) was differentially distributed across frequencies, with a majority of that information being carried in alpha and high-gamma bands and minimal signal in the low-gamma band. During fixation, spatial information from alpha and high-gamma bands and spiking activity was robust across cortical layers. Receptive fields (RFs) derived from alpha and high-gamma bands were retinocentrically organized, and they were spatially correlated both with each other and with spiking RFs. However, alpha and high-gamma RFs probed before eye movements were dissociated. Whereas high-gamma and spiking RFs immediately converged toward the movement goal, alpha RFs remained largely unchanged during the initial probe response, but they converged later. These observations reveal possible mechanisms of dynamic spatial representations that underlie visual perception during eye movements.

Effects of Highland Barley Bran Extract Rich in Phenolic Acids on the Formation of Nε-Carboxymethyllysine in a Biscuit Model.

Highland barley, a staple food in northwest China, is a well-known source of bioactive phytochemicals, including phenolic compounds. This study evaluated the inhibitory effects of highland barley bran extract (HBBE) on the advanced glycation end product (AGE) levels in a biscuit model, as measured by Nε-carboxymethyllysine (CML) content. CML was detected in all inhibition models using HBBE extracted with different solvents. Under optimal conditions, CML formation in the heated model system composed of glucose/lysine/linoleic acid was effectively inhibited by HBBE. This inhibition effect using extracts from 60% acetone solution was 45.58%. Five major phenolic acids from HBBE (ferulic, syringic, sinapic, p-coumaric, and caffeic acids) were further tested for their trapping and scavenging abilities of glyoxal, a reactive carbonyl species and a key intermediate compound for forming CML. This study has demonstrated that HBBE can potentially control CML formation during food processing, therefore effectively reducing glycation in foods and benefiting those with chronic diseases.

Graphene oxide-sensitized molecularly imprinted opto-polymers for charge-transfer fluorescent sensing of cyanoguanidine.

The hierarchical structuring of materials offers exciting opportunities to construct functional sensors. Multiple processes were combined to create complex materials for the selective detection of cyanoguanidine (CYA) using graphene oxide-sensitized molecularly imprinted opto-polymers (MIOP). Molecular imprinting was used to construct molecular-scale analyte-selective cavities, graphene oxide was introduced to provide a platform for the polymerization, and increase the stability and binding kinetic properties, and 3-methacryloxy propyl trimethoxy silane-modified quantum dots were combined with a functional monomer to increase the fluorescence quantum yield. Polymer cross-linking and fluorescence intensity were optimized for molecular recognition and opto-sensing detection. Selective and sensitive, fluorescence sensing of CYA was possible at concentrations as low as to 1.6µM. It could be applied to the rapid and cost-effective monitoring of CYA in infant formula. The approach is generic and applicable to many molecules and conventional opto-sensors, based on molecularly imprinted polymer formulations, individually or in multiplexed arrays.

Core-Shell Metal-Organic Frameworks/Molecularly Imprinted Nanoparticles as Absorbents for the Detection of Pyrraline in Milk and Milk Powder.

A novel core-shell metal-organic framework coated with a dummy template molecularly imprinted polymer (MOF@DMIP) was synthesized by one-pot bulk polymerization for the detection of pyrraline in food samples. The pyrraline analogue pyrrolidine-3-carboxylic acid was used as the template because of its lower cost, and MIL-101 was used as the MOF core owing to its numerous inherent advantages, including high chemical and hydrothermal stabilities. MIL-101@DMIP was used to detect trace pyrraline in foods by solid-phase extraction combined with high-performance liquid chromatography. It exhibited the advantages of faster mass transport, excellent sensitivity, and selectivity. Under optimum conditions, the detection limit of this system was 40.7 µg L-1, and a linear range was from 5 × 10-7 to 2 × 10-3 mol L-1, within relative standard deviations of 4.46-6.87%. The recoveries ranged from 92.23 to 103.87%, indicating the excellent ability of the prepared MIL-101@DMIP to recognize pyrraline in complex food matrices and its potential for application in pyrraline detection.

Application of Quantum Dot-Molecularly Imprinted Polymer Core-Shell Particles Sensitized with Graphene for Optosensing of N(ε)-Carboxymethyllysine in Dairy Products.

Hydrophobic CdSe/ZnS quantum dots (QDs) coated with a molecularly imprinted polymer (MIP) sensitized with graphene (Gra-QDs@MIP) were prepared through a one-pot reverse microemulsion polymerization at room temperature. Gra-QDs@MIP was used as a molecular recognition element to construct a N(ε)-carboxymethyllysine (CML) optosensor. Graphene was used as a polymerization platform to increase the stability and kinetic binding properties of the system. Reverse microemulsion polymerization can anchor silica spheres on the surface of the QDs. This provides functional groups on the surface of Gra-QDs@MIP, which can bind CML and improve the fluorescence stability. Selective and sensitive optosensing of CML is possible at concentrations down to 3.0 µg L(-1) using Gra-QDs@MIP. Gra-QDs@MIP can be applied to dairy samples, as a recognition and response element for determining CML concentrations. The optosensing method was validated by high-performance liquid chromatography-mass spectrometry. The optosensor is economically and easily prepared, and the method is simple, fast, accurate, and reproducible.

Sequential selection of economic good and action in medial frontal cortex of macaques during value-based decisions.

Value-based decisions could rely either on the selection of desired economic goods or on the selection of the actions that will obtain the goods. We investigated this question by recording from the supplementary eye field (SEF) of monkeys during a gambling task that allowed us to distinguish chosen good from chosen action signals. Analysis of the individual neuron activity, as well as of the population state-space dynamic, showed that SEF encodes first the chosen gamble option (the desired economic good) and only ~100 ms later the saccade that will obtain it (the chosen action). The action selection is likely driven by inhibitory interactions between different SEF neurons. Our results suggest that during value-based decisions, the selection of economic goods precedes and guides the selection of actions. The two selection steps serve different functions and can therefore not compensate for each other, even when information guiding both processes is given simultaneously.

Mechanisms underlying the influence of saliency on value-based decisions.

Objects in the environment differ in their low-level perceptual properties (e.g., how easily a fruit can be recognized) as well as in their subjective value (how tasty it is). We studied the influence of visual salience on value-based decisions using a two alternative forced choice task, in which human subjects rapidly chose items from a visual display. All targets were equally easy to detect. Nevertheless, both value and salience strongly affected choices made and reaction times. We analyzed the neuronal mechanisms underlying these behavioral effects using stochastic accumulator models, allowing us to characterize not only the averages of reaction times but their full distributions. Independent models without interaction between the possible choices failed to reproduce the observed choice behavior, while models with mutual inhibition between alternative choices produced much better results. Mutual inhibition thus is an important feature of the decision mechanism. Value influenced the amount of accumulation in all models. In contrast, increased salience could either lead to an earlier start (onset model) or to a higher rate (speed model) of accumulation. Both models explained the data from the choice trials equally well. However, salience also affected reaction times in no-choice trials in which only one item was present, as well as error trials. Only the onset model could explain the observed reaction time distributions of error trials and no-choice trials. In contrast, the speed model could not, irrespective of whether the rate increase resulted from more frequent accumulated quanta or from larger quanta. Visual salience thus likely provides an advantage in the onset, not in the processing speed, of value-based decision making.

Supplementary motor area exerts proactive and reactive control of arm movements.

Adaptive behavior requires the ability to flexibly control actions. This can occur either proactively to anticipate task requirements, or reactively in response to sudden changes. Here we report neuronal activity in the supplementary motor area (SMA) that is correlated with both forms of behavioral control. Single-unit and multiunit activity and intracranial local field potentials (LFPs) were recorded in macaque monkeys during a stop-signal task, which elicits both proactive and reactive behavioral control. The LFP power in high- (60-150 Hz) and low- (25-40 Hz) frequency bands was significantly correlated with arm movement reaction time, starting before target onset. Multiunit and single-unit activity also showed a significant regression with reaction time. In addition, LFPs and multiunit and single-unit activity changed their activity level depending on the trial history, mirroring adjustments on the behavioral level. Together, these findings indicate that neuronal activity in the SMA exerts proactive control of arm movements by adjusting the level of motor readiness. On trials when the monkeys successfully canceled arm movements in response to an unforeseen stop signal, the LFP power, particularly in a low (10-50 Hz) frequency range, increased early enough to be causally related to the inhibition of the arm movement on those trials. This indicated that neuronal activity in the SMA is also involved in response inhibition in reaction to sudden task changes. Our findings indicate, therefore, that SMA plays a role in the proactive control of motor readiness and the reactive inhibition of unwanted movements.

[In vivo extracellular neural recording for the study of cortical plasticity].

Neural network plasticity is fundamental for learning and memory. Its abnormal change underlies some neural diseases. Measurement of the plasticity of cortex can help understand the mechanism of plasticity, and provide a quantitative way to observe the neural process of natural aging and neurodegenerative diseases, which may lead to a new approach for evaluation of anti-aging drugs and new medical treatments for neurodegenerative diseases. In this study, a systematic method was established based on whisker pairing (WP) experiment to measure the network plasticity in the barrel cortex in rat. WP experiment is a classical experiment to study the effect of innocuous bias of the flow of sensory activity from the whiskers for certain periods in awake and behaving rats on the receptive field organization in S1 barrel cortex neurons. In the experiment, one pair of adjacent whiskers D2 and D3 remained intact while others were being trimmed throughout a certain period. After that, receptive fields of single cells in the contralateral barrel were analyzed by post-stimulus time histogram after certain days of WP and compared with the controls. In the control group, response magnitudes to surrounding whiskers D1 and D3 deflection were not significantly different. However, after WP, a bias occurred in response to paired surrounding whisker D3 relative to the opposite trimmed surrounding whisker D1. In this study, by comparing the bias degree in rats in different groups after WP, a quantitative method was established to compare cortical plasticity. Example of corical plasticity comparison between adolescent and mature rats was employed in this paper to illustrate our method. The key techniques of this method such as the identification of D2 barrels, supragranular (L2-3) and barrel layer (L4) in real-time were described in details. The feasibility of this approach was further verified by compendious report of results and our previous study regarding cortical plasticity comparison between adolescent and mature rats.