Direct contribution of the sensory cortex to the judgment of stimulus duration.

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding.

Tactile cognition in rodents.

Since the discovery 50 years ago of the precisely ordered representation of the whiskers in somatosensory cortex, the rodent tactile sensory system has been a fertile ground for the study of sensory processing. With the growing sophistication of touch-based behavioral paradigms, together with advances in neurophysiological methodology, a new approach is emerging. By posing increasingly complex perceptual and memory problems, in many cases analogous to human psychophysical tasks, investigators now explore the operations underlying rodent problem solving. We define the neural basis of tactile cognition as the transformation from a stage in which neuronal activity encodes elemental features, local in space and in time, to a stage in which neuronal activity is an explicit representation of the behavioral operations underlying the current task. Selecting a set of whisker-based behavioral tasks, we show that rodents achieve high level performance through the workings of neuronal circuits that are accessible, decodable, and manipulatable. As a means towards exploring tactile cognition, this review presents leading psychophysical paradigms and, where known, their neural correlates.

Prevalence of Central Venous Stenosis among Black and White ESKD Patients with Dysfunctional Dialysis Access.

In the United States, significant racial and ethnic disparities exist in chronic kidney disease (CKD) and its management. Hemodialysis constitutes the main stay of renal replacement therapy for end-stage kidney disease (ESKD), which is initiated using central venous catheters (CVC) in most CKD patients in the United States. Black ESKD patients have higher usage and greater time on CVC for hemodialysis compared to White patients. This trend places Black patients at a potentially higher risk for CVC-related complications such as central venous stenosis (CVS). We posited that Black patients would have a higher prevalence and a greater risk of CVS. A retrospective review was performed of ESKD patients who underwent a fistulogram for dialysis access malfunction. CVS was defined as > 50% stenosis in the central veins. Fistulograms of 428 ESKD patients were adjudicated, and CVS was noted in 167 of these patients. Of the entire cohort, 370 fistulograms belonged to self-reported unique Black and White ESKD patients, of whom 137 patients were noted to have CVS. There was no difference in the of CVS between Black (40%) and White (41%) ESKD patients. However, a higher severity of stenosis (>70%) (P = 0.03) was noted in White ESKD patients. An unadjusted model showed a significant association between CVS and cardiovascular disease and the use of CVCs. The risk-adjusted model showed a significant association between diabetes and CVS. Unlike arterial stenotic lesions, this work for the first time demonstrated higher prevalence of severe venous stenotic lesions in White ESKD patients and linked diabetes to stenotic venous disease. This work paves the way for future studies investigating the risk and influence of race and ethnicity on CVS using a larger and diverse data set.

Time coding in rat dorsolateral striatum.

To assess the role of dorsolateral striatum (DLS) in time coding, we recorded neuronal activity in rats tasked with comparing the durations of two sequential vibrations. Bayesian decoding of population activity revealed a representation of the unfolding of the trial across time. However, further analyses demonstrated a distinction between the encoding of trial time and perceived time. First, DLS did not show a privileged representation of the stimulus durations compared with other time spans. Second, higher intensity vibrations were perceived as longer; however, time decoded from DLS was unaffected by vibration intensity. Third, DLS did not encode stimulus duration differently on correct versus incorrect trials. Finally, in rats trained to compare the intensities of two sequential vibrations, stimulus duration was encoded even though it was a perceptually irrelevant feature. These findings lead us to posit that temporal information is inherent to DLS activity irrespective of the rat's ongoing percept.

Conserved visual capacity of rats under red light.

Recent studies examine the behavioral capacities of rats and mice with and without visual input, and the neuronal mechanisms underlying such capacities. These animals are assumed to be functionally blind under red light, an assumption that might originate in the fact that they are dichromats who possess ultraviolet and green cones, but not red cones. But the inability to see red as a color does not necessarily rule out form vision based on red light absorption. We measured Long-Evans rats' capacity for visual form discrimination under red light of various wavelength bands. Upon viewing a black and white grating, they had to distinguish between two categories of orientation: horizontal and vertical. Psychometric curves plotting judged orientation versus angle demonstrate the conserved visual capacity of rats under red light. Investigations aiming to explore rodent physiological and behavioral functions in the absence of visual input should not assume red-light blindness.

A sensory integration account for time perception.

The connection between stimulus perception and time perception remains unknown. The present study combines human and rat psychophysics with sensory cortical neuronal firing to construct a computational model for the percept of elapsed time embedded within sense of touch. When subjects judged the duration of a vibration applied to the fingertip (human) or whiskers (rat), increasing stimulus intensity led to increasing perceived duration. Symmetrically, increasing vibration duration led to increasing perceived intensity. We modeled real spike trains recorded from vibrissal somatosensory cortex as input to dual leaky integrators-an intensity integrator with short time constant and a duration integrator with long time constant-generating neurometric functions that replicated the actual psychophysical functions of rats. Returning to human psychophysics, we then confirmed specific predictions of the dual leaky integrator model. This study offers a framework, based on sensory coding and subsequent accumulation of sensory drive, to account for how a feeling of the passage of time accompanies the tactile sensory experience.

Spine Surgery in Italy in the COVID-19 Era: Proposal for Assessing and Responding to the Regional State of Emergency.

In December 2019, coronavirus disease 2019 (COVID-19) was discovered in Wuhan, Hubei province, from where it spread rapidly worldwide. COVID-19 characteristics (increased infectivity, rapid spread, and general population susceptibility) pose a great challenge to hospitals. Infectious disease, pulmonology, and intensive care units have been strengthened and expanded. All other specialties have been compelled to suspend or reduce clinical and elective surgical activities. The profound effects on spine surgery call for systematic approaches to optimizing the diagnosis and treatment of spinal diseases. Based on the experience of one Italian region, we draw an archetype for assessing the current and predicted level of stress in the health care system, with the aim of enabling hospitals to make better decisions during the pandemic. Further, we provide a framework that may help guide strategies for adapting surgical spine care to the conditions of epidemic surge.

State-Dependent Changes in Perception and Coding in the Mouse Somatosensory Cortex.

An animal's behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animal's choice. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease in correlation across neurons in high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system.

White matter structure and myelin-related gene expression alterations with experience in adult rats.

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins involved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms.

Making sense of sensory evidence in the rat whisker system.

In natural environments, choices frequently must be made on the basis of complex and ambiguous streams of sensory input. There are advantages inherent to rapid decision making. Choices are better grounded, however, if information is acquired and accumulated over time. In primate visual motion perception, sensory evidence is accumulated up to a limit, at which point the brain commits to a choice. Recalling the models evoked for primate visual perception, recent studies in the rat vibrissal sensorimotor system, using a number of behavioral paradigms, show that perceptual decision making is characterized by the integration of sensory evidence over time. In this integrative process, vibrissal primary somatosensory cortex (vS1 and vS2) act not as the integrator, but as the distributor of sensory information to downstream regions.

Perceptual uncertainty.

The number of the distinct tactile percepts exceeds the number of receptor types in the skin, signifying that perception cannot be explained by a one-to-one mapping from a single receptor channel to a corresponding percept. The abundance of touch experiences results from multiplexing (the coexistence of multiple codes within a single channel, increasing the available information content of that channel) and from the mixture of receptor channels by divergence and convergence. When a neuronal representation emerges through the combination of receptor channels, perceptual uncertainty can occur-a perceptual judgment is affected by a stimulus feature that would be, ideally, excluded from the task. Though uncertainty seems at first glance to reflect nonoptimality in sensory processing, it is actually a consequence of efficient coding mechanisms that exploit prior knowledge about objects that are touched. Studies that analyze how perceptual judgments are "fooled" by variations in sensory input can reveal the neuronal mechanisms underlying the tactile experience.

Neuronal Correlates of Tactile Working Memory in Prefrontal and Vibrissal Somatosensory Cortex.

Tactile working memory engages a broad network of cortical regions in primates. To assess whether the conclusions drawn from primates apply to rodents, we examined the vibrissal primary somatosensory cortex (vS1) and the prelimbic cortex (PL) in a delayed comparison task. Rats compared the speeds of two vibrissal vibrations, stimulus1 and stimulus2, separated by a delay of 2 s. Neuronal firing rates in vS1 and PL encode both stimuli in real time. Across the delay, the stimulus1 representation declines more precipitously in vS1 than in PL. Theta-band local field potential (LFP) coherence between vS1 and PL peaks at trial onset and remains elevated during the interstimulus interval; simultaneously, vS1 spikes become phase locked to PL LFP. Phase locking is stronger on correct (versus error) trials. Tactile working memory in rats appears to be mediated by a posterior (vS1) to anterior (PL) flow of information, with performance facilitated through coherent LFP oscillation.

Rats Generate Vibrissal Sensory Evidence until Boundary Crossing Triggers a Decision.

Behaviors in which primates collect externally generated streams of sensory evidence, such as judgment of random dot motion direction, are explained by a bounded integration decision model. Does this model extend to rodents, and does it account for behavior in which the motor system generates evidence through interactions with the environment? In this study, rats palpated surfaces to identify the texture before them, showing marked trial-to-trial variability in the number of touches prior to expressing their choice. By high-speed video, we tracked whisker kinematic features and characterized how they encoded the contacted texture. Next, we quantified the evidence for each candidate texture transmitted on each touch by the specified whisker kinematic features. The instant of choice was well fit by modeling the brain as an integrator that gives the greatest weight to vibrissal evidence on first touch and exponentially less weight to evidence on successive touches; according to this model, the rat makes a decision when the accumulated quantity of evidence for one texture reaches a boundary. In summary, evidence appears to be accumulated within the brain until sufficient to support a well-grounded choice. These findings extend the framework of bounded sensory integration from primates to rodents and from passively received evidence to evidence that is actively generated by the sensorimotor system.

Texture Identification by Bounded Integration of Sensory Cortical Signals.

Recent work demonstrated that when a rat palpates a surface to identify its texture, signals generated by whisker kinematics are integrated by the brain, one touch at a time, until the accumulated evidence supports a well-grounded choice. The framework of decision making through bounded integration, previously attributed to primates, thus extends to rodents. In the present study, we ask whether vibrissal somatosensory cortex (vS1 and vS2) functions as the integrator of incoming evidence or, alternatively, as a relay of evidence to a downstream integrator. Rats carried out 1-6 touches per trial to discriminate among candidate textures. We calculated the evidence for each texture, per touch, carried by the firing rates of sets of neurons in vS1 and vS2. The quantity of information within vS1 and vS2 did not grow progressively; instead, the decision was accounted for by modeling a downstream integrator that accumulated packets of vS1 and vS2 texture information until the total quantity of evidence for one texture reached a boundary. In this behavioral task, vibrissal somatosensory cortex appears to act as a sensory relay. Bounded integration is likely to take place in regions targeted by somatosensory cortex.

Supralinear and Supramodal Integration of Visual and Tactile Signals in Rats: Psychophysics and Neuronal Mechanisms.

To better understand how object recognition can be triggered independently of the sensory channel through which information is acquired, we devised a task in which rats judged the orientation of a raised, black and white grating. They learned to recognize two categories of orientation: 0° ± 45° ("horizontal") and 90° ± 45° ("vertical"). Each trial required a visual (V), a tactile (T), or a visual-tactile (VT) discrimination; VT performance was better than that predicted by optimal linear combination of V and T signals, indicating synergy between sensory channels. We examined posterior parietal cortex (PPC) and uncovered key neuronal correlates of the behavioral findings: PPC carried both graded information about object orientation and categorical information about the rat's upcoming choice; single neurons exhibited identical responses under the three modality conditions. Finally, a linear classifier of neuronal population firing replicated the behavioral findings. Taken together, these findings suggest that PPC is involved in the supramodal processing of shape.

Posterior parietal cortex represents sensory history and mediates its effects on behaviour.

Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics: it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is not relevant to the current task at hand. Nevertheless, the neural mechanisms and regions of the brain that are necessary for computing and using such prior experience are unknown. Here we report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. We trained rats in an auditory parametric working memory task, and found that they displayed substantial and readily quantifiable behavioural effects of sensory-stimulus history, similar to those observed in humans and monkeys. Earlier proposals that the PPC supports working memory predict that optogenetic silencing of this region would impair behaviour in our working memory task. Contrary to this prediction, we found that silencing the PPC significantly improved performance. Quantitative analyses of behaviour revealed that this improvement was due to the selective reduction of the effects of prior sensory stimuli. Electrophysiological recordings showed that PPC neurons carried far more information about the sensory stimuli of previous trials than about the stimuli of the current trial. Furthermore, for a given rat, the more information about previous trial sensory history in the neural firing rates of the PPC, the greater the behavioural effect of sensory history, suggesting a tight link between behaviour and PPC representations of stimulus history. Our results indicate that the PPC is a central component in the processing of sensory-stimulus history, and could enable further neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.

A Fluorescent Dye Method Suitable for Visualization of One or More Rat Whiskers.

Visualization and tracking of the facial whiskers is critical to many studies of rodent behavior. High-speed videography is the most robust methodology for characterizing whisker kinematics, but whisker visualization is challenging due to the low contrast of the whisker against its background. Recently, we showed that fluorescent dye(s) can be applied to enhance visualization and tracking of whisker(s) ( Rigosa et al., 2017 ), and this protocol provides additional details on the technique.