Biology subjects

Salinas, E.

Publications and source records attributed to Salinas, E..

16 recordsLinked to original sources

bioRxiv2026

Multisensory integration of stimulus-driven and goal-driven signals during urgent saccadic choices

The ability to orient or attend to sensory events is generally greater in response to visual and auditory cues occurring together than in response to single-modality cues occurring alone. In such cases the perceptual fusion of cross-modal stimuli (multisensory integration) depends on low-level features (e.g., location, intensity) and follows well established principles. However, less is known about multisensory integration mechanisms when behavioral responses are less direct and require top-down control. Here we investigate this in human participants using an urgent multisensory choice task that effectively dissociates stimulus-driven and goal-driven contributions to performance based on their distinct temporal signatures. Task conditions varied the modality of the cues (auditory, visual, or both), their location (left or right), and the rule defining the correct choice (look toward or away from a given cue). When spatially coincident cues were associated with the same response rule ("look away"), we observed multisensory enhancement and performance remained close to a statistical expectation as the choice process unfolded. However, when spatially disparate cues were associated with different rules but the same target, one cue dominated performance and the other produced crossmodal capture, i.e., low-level competition. The results indicate that the efficacy of multisensory integration is dictated by the stimulus-and goal-driven signals produced by each cue, with all four factors rapidly interacting in accordance to the dynamics of spatial attention. Significance StatementAuditory and visual stimuli located near each other in space and time are typically bound into a single sensory percept that draws attention most effectively. However, it is unclear whether such "multisensory integration" occurs during behaviors that go beyond directly attending or orienting to cue stimuli and require top-down control. We investigated this using a novel task design with which stimulus-driven and goal-driven contributions to performance can be accurately identified. We found that multisensory enhancement depends not so much on the complexity of the requested cue-response associations, but rather on the timing and alignment of the stimulus-and goal-driven signals derived from each cue (auditory and visual) -- similar to the way that such signals dictate the allocation of spatial attention.

neuroscience↗

bioRxiv2025

Contributions of distinct attention mechanisms to saccadic choices in a gamified, dynamic environment

Visuospatial attention is key for parsing visual information and selecting targets to look at. Based on regimented laboratory tasks, it is now well established that three types of mechanism determine when and where attention is deployed; these are stimulus-driven (exogenous), goal-driven (endogenous), and history-driven (reflecting recent experience). It is unclear, however, how these distinct attentional signals interact and contribute in visual environments that are more akin to natural scanning, when stimuli may change rapidly and no fixation requirements are imposed. Here, we investigate this via a gamified task in which participants (male and female) make continuous saccadic choices at a rapid pace -- and yet, perceptual performance can be accurately tracked over time as the choice process unfolds. The results reveal unequivocal markers of exogenous capture toward salient stimuli; endogenous guidance toward valuable targets and relevant locations; and history-driven effects, which produce large, involuntary modulations in processing capacity. Under dynamic conditions, success probability is dictated by temporally precise interplay between different forms of spatial attention, with recent history making a particularly prominent contribution. Significance StatementVisuospatial attention comprises a collection of mental mechanisms that allow us to focus on (or look at) specific objects or parts of space and ignore others. The next target to be inspected is generally selected based on how much it stands out (salience), its relevance to current goals, and recent experience. We designed a gamified visual scanning task in which all such forms of attentional control interact rapidly, more akin to real life situations (e.g., driving through traffic). Each mechanism affected in characteristic ways the probability that participants would look to the correct target at each moment in time. Most notably, we found that the history of recently seen stimuli determines visual processing capacity much more strongly than previously thought.

neuroscience↗

bioRxiv2024

Brain structure and activity predicting cognitive maturation in adolescence

Cognitive abilities of primates, including humans, continue to improve through adolescence 1,2. While a range of changes in brain structure and connectivity have been documented 3,4, how they affect neuronal activity that ultimately determines performance of cognitive functions remains unknown. Here, we conducted a multilevel longitudinal study of monkey adolescent neurocognitive development. The developmental trajectory of neural activity in the prefrontal cortex accounted remarkably well for working memory improvements. While complex aspects of activity changed progressively during adolescence, such as the rotation of stimulus representation in multidimensional neuronal space, which has been implicated in cognitive flexibility, even simpler attributes, such as the baseline firing rate in the period preceding a stimulus appearance had predictive power over behavior. Unexpectedly, decreases in brain volume and thickness, which are widely thought to underlie cognitive changes in humans 5 did not predict well the trajectory of neural activity or cognitive performance changes. Whole brain cortical volume in particular, exhibited an increase and reached a local maximum in late adolescence, at a time of rapid behavioral improvement. Maturation of long-distance white matter tracts linking the frontal lobe with areas of the association cortex and subcortical regions best predicted changes in neuronal activity and behavior. Our results provide evidence that optimization of neural activity depending on widely distributed circuitry effects cognitive development in adolescence.

neuroscience↗

bioRxiv2024

Location- and feature-based selection histories make independent, qualitatively distinct contributions to urgent visuomotor performance

Attention mechanisms guide visuomotor behavior by weighing physical salience and internal goals to prioritize stimuli as choices for action. Although less well studied, selection history, which reflects multiple facets of experience with recent events, is increasingly recognized as a distinct source of attentional bias. To examine how selection history impacts saccadic choices, we trained two macaque monkeys to perform an urgent version of an oddball search task in which a red target appeared among three green distracters, or vice versa. By imposing urgency, performance could be tracked continuously as it transitioned from uninformed guesses to informed choices as a function of processing time. This, in turn, permitted assessment of attentional control as manifest in motor biases, processing speed, and asymptotic accuracy. Here, we found that the probability of making a correct choice was strongly modulated by the histories of preceding target locations and target colors. Crucially, although both effects were gated by success (or reward), their dynamics were clearly distinct: whereas location history promoted a motor bias, color history modulated perceptual sensitivity, and these influences acted independently. Thus, combined selection histories can give rise to enormous swings in visuomotor performance even in simple tasks with highly discriminable stimuli. Impact statementDuring visual search, the choice of where to look next is biased to a remarkable degree by the location and color histories of recently viewed target stimuli.

neuroscience↗

bioRxiv2024

Coupling of saccade plans to endogenous attention during urgent choices

The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location necessarily activates a corresponding saccade plan remains unclear. One problem is that attention and saccades are both automatically driven by salient sensory events; another is that the underlying processes unfold within tens of milliseconds only. Here, we use an urgent task design to resolve the evolution of a visuomotor choice on a moment-by-moment basis while independently controlling the endogenous (goal-driven) and exogenous (salience-driven) contributions to performance. Human participants saw a peripheral cue and, depending on its color, either looked at it (prosaccade) or looked at a diametrically opposite, uninformative non-cue (antisaccade). By varying the luminance of the stimuli, the exogenous contributions could be cleanly dissociated from the endogenous process guiding the choice over time. According to the measured timecourses, generating a correct antisaccade requires about 30 ms more processing time than generating a correct prosaccade based on the same perceptual signal. The results indicate that saccade plans elaborated during fixation are biased toward the location where attention is endogenously deployed, but the coupling is weak and can be willfully overridden very rapidly.

neuroscience↗

bioRxiv2024

CD4+ and CD8+ T cells are required to prevent SARS-CoV-2 persistence in the nasal compartment

SARS-CoV-2 is the causative agent of COVID-19 and continues to pose a significant public health threat throughout the world. Following SARS-CoV-2 infection, virus-specific CD4+ and CD8+ T cells are rapidly generated to form effector and memory cells and persist in the blood for several months. However, the contribution of T cells in controlling SARS-CoV-2 infection within the respiratory tract are not well understood. Using C57BL/6 mice infected with a naturally occurring SARS-CoV-2 variant (B.1.351), we evaluated the role of T cells in the upper and lower respiratory tract. Following infection, SARS-CoV-2-specific CD4+ and CD8+ T cells are recruited to the respiratory tract and a vast proportion secrete the cytotoxic molecule Granzyme B. Using antibodies to deplete T cells prior to infection, we found that CD4+ and CD8+ T cells play distinct roles in the upper and lower respiratory tract. In the lungs, T cells play a minimal role in viral control with viral clearance occurring in the absence of both CD4+ and CD8+ T cells through 28 days post-infection. In the nasal compartment, depletion of both CD4+ and CD8+ T cells, but not individually, results in persistent and culturable virus replicating in the nasal compartment through 28 days post-infection. Using in situ hybridization, we found that SARS-CoV-2 infection persisted in the nasal epithelial layer of tandem CD4+ and CD8+ T cell-depleted mice. Sequence analysis of virus isolates from persistently infected mice revealed mutations spanning across the genome, including a deletion in ORF6. Overall, our findings highlight the importance of T cells in controlling virus replication within the respiratory tract during SARS-CoV-2 infection.

immunology↗

bioRxiv2023

Intrinsic p53 Activation Restricts Gammaherpesvirus-Driven Germinal Center B Cell Expansion during Latency Establishment

Gammaherpesviruses (GHV) are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68), this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center (GC) B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined. Using a small-animal model of GHV pathogenesis, we demonstrate in vivo that tumor suppressor p53 is activated specifically in B cells that are latently infected by MHV68. In the absence of p53, the early expansion of MHV68 latency was greatly increased, especially in GC B cells, a cell-type whose proliferation was conversely restricted by p53. We identify the B cell-specific latency gene M2, a viral promoter of GC B cell differentiation, as a viral protein sufficient to elicit a p53-dependent anti-proliferative response caused by Src-family kinase activation. We further demonstrate that EBV-encoded latent membrane protein 1 (LMP1) similarly triggers a p53 response in primary B cells. Our data highlight a model in which GHV latency gene-expression programs that promote B cell proliferation and differentiation to facilitate viral colonization of the host trigger aberrant cellular proliferation that is controlled by p53. IMPORTANCEGammaherpesviruses cause lifelong infections of their hosts, commonly referred to as latency, that can lead to cancer. Latency establishment benefits from the functions of viral proteins that augment and amplify B cell activation, proliferation, and differentiation signals. In uninfected cells, off-schedule cellular differentiation would typically trigger anti-proliferative responses by effector proteins known as tumor suppressors. However, tumor suppressor responses to gammaherpesvirus manipulation of cellular processes remain understudied, especially those that occur during latency establishment in a living organism. Here we identify p53, a tumor suppressor commonly mutated in cancer, as a host factor that limits virus-driven B cell proliferation and differentiation, and thus, viral colonization of a host. We demonstrate that p53 activation occurs in response to viral latency proteins that induce B cell activation. This work informs a gap in our understanding of intrinsic cellular defense mechanisms that restrict lifelong GHV infection.

microbiology↗

bioRxiv2023

Conditional independence as an assessment of evidence integration processes

Intuitively, combining multiple sources of evidence should lead to more accurate decisions than considering single sources of evidence individually. In practice, however, the proper computation may be difficult, or may require additional data that are inaccessible. Here, based on the concept of conditional independence, we consider expressions that can serve either as recipes for integrating evidence based on limited data, or as statistical benchmarks for characterizing evidence integration processes. Consider three events, A, B, and C. We find that, if A and B are conditionally independent with respect to C, then the probability that C occurs given that both A and B are known, P (C|A, B), can be easily calculated without the need to measure the full three-way dependency between A, B, and C. This simplified approach can be used in two general ways: to generate predictions by combining multiple (conditionally independent) sources of evidence, or to test whether separate sources of evidence are functionally independent of each other. These applications are demonstrated with four computer-simulated examples, which include detecting a disease based on repeated diagnostic testing, inferring biological age based on multiple biomarkers of aging, discriminating two spatial locations based on multiple cue stimuli (multisensory integration), and examining how behavioral performance in a visual search task depends on selection histories. Besides providing a sound prescription for predicting outcomes, this methodology may be useful for analyzing experimental data of many types.

neuroscience↗

bioRxiv2022

Waning and boosting of functional humoral immunity to SARS-CoV-2

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

immunology↗

bioRxiv2022

Exogenous capture accounts for fundamental differences between prosaccade and antisaccade performance

Oculomotor circuits generate eye movements based on the physical salience of objects and current behavioral goals, exogenous and endogenous influences, respectively. However, the interactions between exogenous and endogenous mechanisms and their dynamic contributions to target selection have been difficult to resolve because they evolve extremely rapidly. In a recent study (Salinas et al., 2019), we achieved the necessary temporal precision using an urgent variant of the antisaccade task wherein motor plans are initiated early and choice accuracy depends sharply on when exactly the visual cue information becomes available. Empirical and modeling results indicated that the exogenous signal arrives [~]80 ms after cue onset and rapidly accelerates the (incorrect) plan toward the cue, whereas the informed endogenous signal arrives [~]25 ms later to favor the (correct) plan away from the cue. Here, we scrutinize a key mechanistic hypothesis about this dynamic, that the exogenous and endogenous signals act at different times and independently of each other. We test quantitative model predictions by comparing the performance of human participants instructed to look toward a visual cue versus away from it under high urgency. We find that, indeed, the exogenous response is largely impervious to task instructions; it simply flips its sign relative to the correct choice, and this largely explains the drastic differences in psychometric performance between the two tasks. Thus, saccadic choices are strongly dictated by the alignment between salience and behavioral goals.

neuroscience↗

bioRxiv2021

The spatial signal in area LIP is not an obligatory correlate of perceptual evidence during informed saccadic choices

The lateral intraparietal area (LIP) contains spatially selective neurons that are partly responsible for determining where to look next and are thought to serve a variety of sensory, motor planning, and cognitive control functions within this role1,2,3. Notably, according to numerous studies in monkeys4,5,6,7,8,9,10,11,12, area LIP implements a fundamental perceptual process, the gradual accumulation of sensory evidence in favor of one choice (e.g., look left) over another (look right), which manifests as a slowly developing spatial signal during a motion discrimination task. However, according to recent inactivation experiments13,14, this signal is unnecessary for accurate task performance. Here we reconcile these contradictory findings. We designed an urgent version of the motion discrimination task in which there is no systematic lag between the perceptual evaluation and the motor action reporting it, and such that the evolution of the subjects choice can be tracked millisecond by millisecond15,16,17,18. We found that while choice accuracy increased steeply with increasing sensory evidence, at the same time, the spatial selection signal in LIP became progressively weaker, as if it hindered performance. In contrast, in a similarly urgent task in which the discriminated stimuli and the choice targets were spatially coincident, this neural signal seemed to facilitate performance. The data suggest that the LIP activity traditionally interpreted as evidence accumulation may correspond to a slow, post-decision shift of spatial attention from one location (where the motion occurs) to another (where the eyes land).

neuroscience↗

bioRxiv2019

Perceptual modulation of parietal activity during urgent saccadic choices

The lateral intraparietal cortex (LIP) contributes to visuomotor transformations for determining where to look next. However, its spatial selectivity can signify attentional priority, motor planning, perceptual discrimination, or other mechanisms. Resolving how this LIP signal influences a perceptually guided choice requires knowing exactly when such signal arises and when the perceptual evaluation informs behavior. To achieve this, we recorded single-neuron activity while monkeys performed an urgent choice task for which the perceptual evaluations progress can be tracked millisecond by millisecond. The evoked presaccadic responses were strong, exhibited modest motor preference, and were only weakly modulated by sensory evidence. This modulation was remarkable, though, in that its time course preceded and paralleled that of behavioral performance (choice accuracy), and it closely resembled the statistical definition of confidence. The results indicate that, as the choice process unfolds, LIP dynamically combines attentional, motor, and perceptual signals, the former being much stronger than the latter.

neuroscience↗

bioRxiv2018

Urgency reveals an attentional vortex during antisaccade performance

In the antisaccade task, which is considered a sensitive assay of cognitive function, a salient visual cue appears and the participant must look away from it. This requires sensory, motor-planning, and cognitive neural mechanisms. But what are the unique contributions of these mechanisms to performance, and when exactly are they engaged? By introducing an urgency requirement into the antisaccade task, we track the evolution of the choice process with millisecond resolution and find a singular, nonlinear dependence on cue exposure: when viewed briefly ([~]100-140 ms), the cue captures attention so powerfully that looking at it (erroneously) is virtually inevitable, but as the cue viewing time increases, the probability of success quickly rises and saturates. The psychophysical and modeling results reveal concerted interactions between reflexive and voluntary cognitive mechanisms that (1) unfold extremely rapidly, (2) are qualitatively consistent across participants, and (3) are nevertheless quantitatively distinctive of each individuals perceptual capacities

neuroscience↗

bioRxiv2018

Pardon the interruption: saccadic inhibition enables the rapid deployment of alternate oculomotor plans

Diverse psychophysical and neurophysiological results show that oculomotor networks are continuously active, such that plans for making the next eye movement are always ongoing. So, when new visual information arrives unexpectedly, how are those plans affected? At what point can the new information start guiding an eye movement, and how? Here, based on modeling and simulation results, we make two observations that are relevant to these questions. First, we note that many experiments, including those investigating the phenomenon known as \"saccadic inhibition,\" are consistent with the idea that sudden-onset stimuli briefly interrupt the gradual rise in neural activity associated with the preparation of an impending saccade. And second, we show that this stimulus-driven interruption is functionally adaptive, but only if perception is fast. In that case, putting on hold an ongoing saccade plan toward location A allows the oculomotor system to initiate a concurrent, alternative plan toward location B (where a stimulus just appeared), deliberate (briefly) on the priority of each target, and determine which plan should continue. Based on physiological data, we estimate that the actual advantage of this strategy, relative to one in which any plan once initiated must be completed, is of several tens of milliseconds.

neuroscience↗

bioRxiv2017

Motor selection dynamics in FEF explain the reaction time variance of saccades to single targets

In studies of voluntary movement, a most elemental quantity is the reaction time (RT) between the onset of a visual stimulus and a saccade toward it. However, this RT demonstrates extremely high variability, which in spite of extensive research remains unexplained. It is well established that, when a visual target appears, oculomotor activity gradually builds up until a critical level is reached, at which point a saccade is triggered. Here, we further characterize the dynamics of this rise-to-threshold process based on computational work and single-neuron recordings from the frontal eye field (FEF) of behaving monkeys. We find that the baseline activity, build-up rate, and threshold level show strong, nonlinear co-dependencies that explain the distinct RT distributions observed experimentally. The results indicate that intrinsic randomness contributes little to saccade variance, which results mainly from an intricate, fundamentally deterministic mechanism of motor conflict resolution that has subtle yet highly characteristic manifestations.

neuroscience↗

bioRxiv2017

FireCloud, a scalable cloud-based platform for collaborative genome analysis: Strategies for reducing and controlling costs

FireCloud, one of three NCI Cloud Pilots, is a collaborative genome analysis platform built on a cloud computing infrastructure. FireCloud aims to solve the many challenges presented by the increasingly large data sets and computing requirements employed in cancer research. However, cost uncertainty associated with cloud computings pay-as-you-go model is proving to be a barrier to adoption of cloud computing. In this paper we present guidelines for optimizing workflows to minimize cost and reduce latency. Our guidelines include: (i) dynamic disk sizing to efficiently utilize virtual disks; (ii) tuned provisioning of virtual machines (VMs) using a performance monitoring tool; (iii) taking advantage of steep price discounts of preemptible VMs; and (iv) utilizing the optimal parallelization of a tasks workload.

bioinformatics↗