Closed-Loop Targeted Memory Reactivation during Sleep Improves Spatial Navigation

Sounds associated with newly learned information that are replayed during non-rapid eye movement (NREM) sleep can improve recall in simple tasks. The mechanism for this improvement is presumed to be reactivation of the newly learned memory during sleep when consolidation takes place. We have developed an EEG-based closed-loop system to precisely deliver sensory stimulation at the time of down-state to up-state transitions during NREM sleep. Here, we demonstrate that applying this technology to participants performing a realistic navigation task in virtual reality results in a significant improvement in navigation efficiency after sleep that is accompanied by increases in the spectral power especially in the fast (12\u201315 Hz) sleep spindle band. Our results show promise for the application of sleep-based interventions to drive improvement in real-world tasks

Dynamics In Primary Somatosensory Cortex: A Role For SI In The Processing Of Tactile Information

Traditional views of primary somatosensory cortex (SI) and its role in the processing of tactile information have limited its function as a dynamic component in the somatosensory pathway. Here I present evidence that the response in SI to stimuli at a given skin site is systematically modified with changes in the stimulus parameters and displays considerable dynamics. Optical intrinsic signal (OIS) imaging was used to study the responses (in vivo) evoked by 25 Hz (flutter) vertical skin displacement stimuli to the forelimb of squirrel monkey and cat. Responses to electrical stimulation were also measured in rat sensorimotor cortical slices using OIS imaging and local field potential (LFP) recordings. Results indicate that, contrary to traditional views, the intensive but not spatial attributes of the SI response are modified by increases in stimulus amplitude. Increasing the duration of flutter stimulation evokes increases in response magnitude in cortical regions near to the maximally responding center and simultaneous decreases in surrounding cortical regions; the net effect of this is the spatial sharpening of the SI response during prolonged stimulation. The distribution of decreased absorbance in surrounding cortex was non-uniform, indicating the possibility of stronger intracortical inhibition along the proximodistal axis of the body representation. Cortical slices in the sagital and coronal planes of the rat somatosensory cortex demonstrated a similar anisotropy in the distribution and impact of GABAergic inhibition on the horizontal spread of activity, and lend support to the idea that the non-uniformity observed in vivo may contain functional relevance. Bilateral stimulation of both forelimbs demonstrated that, although input to SI has been traditionally regarded as exclusively contralateral, not only can the response to an ipsilateral stimulus be measured in SI, but when stimulation is applied bilaterally the spatiotemporal characteristics of the evoked response cannot be accounted for by the responses of either stimulus alone or by the linear summation of the pair. All of these results taken together present a strong case for the necessity of strong dynamics in SI and the role of SI as an important site of cortical information processing in the somatosensory pathway

Response of SI cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: While SII cortex is considered to be the first cortical stage of the pathway that integrates tactile information arising from both sides of the body, SI cortex is generally not considered as a region in which neuronal response is modulated by simultaneous stimulation of bilateral (and mirror-image) skin sites. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of SI and SII in the same hemisphere to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally (simultaneously) to the central pads of the forepaws. A localized increase in absorbance in both SI and SII occurred in response to both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but little or no change in SI absorbance. In the forepaw representational region of SI, however, bilateral stimulation of the central pads evoked a response substantially smaller (approximately 30–35% smaller) than the response to flutter stimulation of the contralateral central pad. CONCLUSION: The finding that the response of SI cortex to bilateral central pad flutter stimulation is substantially smaller than the response evoked by a contralateral flutter stimulus, together with the recently published observation that a region located posteriorly in SII responds with a substantially larger response to a bilateral flutter stimulus than the response evoked from the contralateral central pad, lead us to propose that the SI activity evoked by contralateral skin stimulation is suppressed/inhibited (via corticocortical connections between SII and SI in the same hemisphere) by the activity a simultaneous ipsilateral skin stimulus evokes in posterior SII

Temporal fluctuations of waves in weakly nonlinear disordered media

We consider the multiple scattering of a scalar wave in a disordered medium with a weak nonlinearity of Kerr type. The perturbation theory, developed to calculate the temporal autocorrelation function of scattered wave, fails at short correlation times. A self-consistent calculation shows that for nonlinearities exceeding a certain threshold value, the multiple-scattering speckle pattern becomes unstable and exhibits spontaneous fluctuations even in the absence of scatterer motion. The instability is due to a distributed feedback in the system "coherent wave + nonlinear disordered medium". The feedback is provided by the multiple scattering. The development of instability is independent of the sign of nonlinearity.Comment: RevTeX, 15 pages (including 5 figures), accepted for publication in Phys. Rev.

What Do Unions Do for Economic Performance?

Twenty years have passed since Freeman and Medoff's What Do Unions Do? This essay assesses their analysis of how unions in the U.S. private sector affect economic performance - productivity, profitability, investment, and growth. Freeman and Medoff are clearly correct that union productivity effects vary substantially across workplaces. Their conclusion that union effects are on average positive and substantial cannot be sustained, subsequent evidence suggesting an average union productivity effect near zero. Their speculation that productivity effects are larger in more competitive environments appears to hold up, although more evidence is needed. Subsequent literature continues to find unions associated with lower profitability, as noted by Freeman and Medoff. Unions are found to tax returns stemming from market power, but industry concentration is not the source of such returns. Rather, unions capture firm quasi-rents arising from long-lived tangible and intangible capital and from firm-specific advantages. Lower profits and the union tax on asset returns leads to reduced investment and, subsequently, lower employment and productivity growth. There is little evidence that unionization leads to higher rates of business failure. Given the decline in U.S. private sector unionism, I explore avenues through which individual and collective voice might be enhanced, focusing on labor law and workplace governance defaults. Substantial enhancement of voice requires change in the nonunion sector and employer as well as worker initiatives. It is unclear whether labor unions would be revitalized or further marginalized by such an evolution

Response of SII cortex to ipsilateral, contralateral and bilateral flutter stimulation in the cat

BACKGROUND: A distinctive property of SII is that it is the first cortical stage of the somatosensory projection pathway that integrates information arising from both sides of the body. However, there is very little known about how inputs across the body mid-line are processed within SII. RESULTS: Optical intrinsic signal imaging was used to evaluate the response of primary somatosensory cortex (SI and SII in the same hemisphere) to 25 Hz sinusoidal vertical skin displacement stimulation ("skin flutter") applied contralaterally, ipsilaterally, and bilaterally to the central pads of the forepaws. A localized increase in absorbance in both SI and SII was evoked by both contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation evoked a localized increase in absorbance in SII, but not in SI. The SII region that responded with an increase in absorbance to ipsilateral stimulation was posterior to the region in which absorbance increased maximally in response to stimulation of the contralateral central pad. Additionally, in the posterior SII region that responded maximally to ipsilateral stimulation of the central pad, bilateral central pad stimulation approximated a linear summation of the SII responses to independent stimulation of the contralateral and ipsilateral central pads. Conversely, in anterior SII (the region that responded maximally to contralateral stimulation), bilateral stimulation was consistently less than the response evoked from the contralateral central pad. CONCLUSIONS: The results indicate that two regions located at neighboring, but distinctly different A-P levels of the anterior ectosylvian gyrus process input from opposite sides of the body midline in very different ways. The results suggest that the SII cortex, in the cat, can be subdivided into at least two functionally distinct regions and that these functionally distinct regions demonstrate a laterality preference within SII

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Amplitude-dependency of response of SI cortex to flutter stimulation

BACKGROUND: It is established that increasing the amplitude of a flutter stimulus increases its perceived intensity. Although many studies have examined this phenomenon with regard to the responding afferent population, the way in which the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains unclear. RESULTS: Optical intrinsic signal (OIS) imaging was used to study the evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50 sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and different amplitudes were interleaved. Control levels of activity were measured in the absence of stimulation, and used to compare with activation levels evoked by the different stimulus amplitudes. Stimulation of a discrete skin site on the forelimb evoked a prominent increase in absorbance within the forelimb representational region in cytoarchitectonic areas 3b and 1 of the contralateral hemisphere. An increase in stimulus amplitude led to a proportional increase in the magnitude of the absorbance increase in this region of areas 3b and 1 while surrounding cortex underwent a decrease in absorbance. Correlation maps revealed that as stimulus amplitude is increased, the spatial extent of the activated region in SI remains relatively constant, and the activity within this region increases progressively. Additionally, as stimulus amplitude is increased to suprathreshold levels, activity in the surround of the activated SI territory decreases, suggesting an increase in inhibition of neuronal activity within these regions. CONCLUSION: Increasing the amplitude of a flutter stimulus leads to a proportional increase in absorbance within the forelimb representational region of SI. This most likely reflects an increase in the firing rate of neurons in this region of SI. The relatively constant spatial extent of this stimulus-evoked increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin stimulus does not evoke a larger area of SI neuronal activation due to an amplitude-dependent lateral inhibitory effect that spatially funnels the responding SI neuronal population

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin