SUMMARY Despite the fact that strong trial-to-trial correlated variability in responses has been reported in many cortical areas, recent evidence suggests that neuronal correlations are much lower than previously thought. Here, we used multicontact laminar probes to revisit the issue of correlated variability in primary visual (V1) cortical circuits. We found that correlations between neurons depend strongly on local network context—whereas neurons in the input (granular) layers showed virtually no correlated variability, neurons in the output layers (supragranular and infragranular) exhibited strong correlations. The laminar dependence of noise correlations is consistent with recurrent models in which neurons in the granular layer receive intracortical inputs from nearby cells, whereas supragranular and infragranular layer neurons receive inputs over larger distances. Contrary to expectation that the output cortical layers encode stimulus information most accurately, we found that the input network offers superior discrimination performance compared to the output networks.

It is generally believed that attention enhances the processing of sensory information during perception and learning. Here we report that, contrary to common belief, attention limits the degree of plasticity induced by repeated exposure to image features. Specifically, daily exposure to oriented stimuli that are not linked to a specific task causes an orientation-specific improvement in perceptual performance along the "exposed" axes. This effect is modulated by attention: human subjects showed a larger improvement in orientation discrimination when attention is directed toward the location where stimuli are presented. However, the capacity to perform discriminations away from the exposed orientation is enhanced when the exposure stimuli are unattended. Importantly, the improvement in orientation discrimination at the unattended location leads to a robust enhancement in the discrimination of complex stimuli, such as natural texture images, with orientation components along the exposed axes, whereas the improvement in orientation discrimination at the attended location exhibits only weak transfer to complex stimuli. These results indicate that sensory adaptation by passive stimulus exposure should be viewed as a form of perceptual learning that is complementary to practice-based learning in that it reduces constraints on generalization.

A fundamental feature of information processing in neocortex is the ability of individual neurons to adapt to changes in incoming stimuli. It is increasingly being understood that cortical adaptation is a phenomenon that requires network interactions. The fact that the structure of local networks depends critically on cortical layer raises the possibility that adaptation could induce specific effects in different layers. Here we show that brief exposure (300 ms) to a stimulus of fixed orientation modulates the strength of synchronization between individual neurons and local population activity in the gamma-band frequency (30-80 Hz) in macaque primary visual cortex (V1) and influences the ability of individual neurons to encode stimulus orientation. Using laminar probes, we found that although stimulus presentation elicits a large increase in the gamma synchronization of rhythmic neuronal activity in the input (granular) layers of V1, adaptation caused a pronounced increase in synchronization in the cortical output (supragranular) layers. The increase in gamma synchronization after adaptation was significantly correlated with an improvement in neuronal orientation discrimination performance only in the supragranular layers. Thus, synchronization between the spiking activity of individual neurons and their local population may enhance sensory coding to optimize network processing across laminar circuits.A fundamental issue in our understanding of brain circuits is how networks in different layers of the cerebral cortex encode information. Cortical layers are ubiquitous structures throughout neocortex (1, 2) that consist of highly recurrent local networks that communicate among each other to possibly influence the information encoded in population activity. In recent years, significant progress has been made in our understanding of the differences in response properties of neurons across cortical layers (3, 4), yet there is still a great deal to learn about whether and how neuronal populations encode information in a layerspecific manner. A measure of the activity of a local population (or ensemble) of neurons (5) is captured by local field potentials (LFPs), which are composed of low-frequency extracellular voltage fluctuations, including local excitatory and inhibitory intracortical inputs (6) believed to originate from within 250-500 μm of the recording site (7,8). In visual cortex, it has been found that neuronal groups exhibit strong responses in the gammaband frequency (30-80 Hz) (9-11) and that single neurons synchronize their responses with the local population activity (12, 13). Synchronization in visual cortex, particularly in the gammaband, has been found to be critically involved in sensory processing (9,11,14), grouping (9, 11; but see refs. 15-17), attention (10,(18)(19)(20), working memory (5), and behavioral reaction times (20). The results of these studies support the hypothesis that efficient information transmission would occur whenever two networks are synchronous in their excitability peaks, wh...

The ability to detect moving objects is an ethologically salient function. Direction-selective neurons have been identified in the retina, thalamus, and cortex of many species, but their homology has remained unclear. For instance, it is unknown whether direction-selective retinal ganglion cells (DSGCs) exist in primates and, if so, whether they are the equivalent to mouse and rabbit DSGCs. Here, we used a molecular/circuit approach in both sexes to address these issues. In mice, we identify the transcription factor Satb2 (special AT-rich sequence-binding protein 2) as a selective marker for three RGC types: On-Off DSGCs encoding motion in either the anterior or posterior direction, a newly identified type of Off-DSGC, and an Off-sustained RGC type. In rabbits, we find that expression of Satb2 is conserved in On-Off DSGCs; however, it has evolved to include On-Off DSGCs encoding upward and downward motion in addition to anterior and posterior motion. Next, we show that macaque RGCs express Satb2 most likely in a single type. We used rabies virus-based circuitmapping tools to reveal the identity of macaque Satb2-RGCs and discovered that their dendritic arbors are relatively large and monostratified. Together, these data indicate Satb2-expressing On-Off DSGCs are likely not present in the primate retina. Moreover, if DSGCs are present in the primate retina, it is unlikely that they express Satb2.

The rapidly advancing field of digital health technologies provides a great opportunity to radically transform the way clinical trials are conducted and to shift the clinical trial paradigm from a site-centric to a patientcentric model. Merck & Co., Inc.'s (Kenilworth, NJ, USA) digitally-enabled clinical trial initiative is focused on introduction of digital technologies into the clinical trial paradigm to reduce patient burden, improve drug adherence, provide a means of more closely engaging with the patient, and enable higher quality, faster, and Accepted Article This article is protected by copyright. All rights reserved more frequent data collection. This paper will describe the following four key areas of focus from Merck & Co., Inc.'s (Kenilworth, NJ, USA) digitally-enabled clinical trials initiative, along with corresponding enabling technologies: (1) use of technologies that can monitor and improve drug adherence (smart dosing), (2) collection of pharmacokinetic, pharmacodynamic, and biomarker samples in an outpatient setting (patientcentric sampling), (3) use of digital devices to collect and measure physiological and behavioral data (digital biomarkers), and (4) use of data platforms that integrate digital data streams, visualize data in real-time, and provide a means of greater patient engagement during the trial (digital platform). Furthermore, this paper will discuss the synergistic power in implementation of these approaches jointly within a trial to enable better understanding of adherence, safety, efficacy, pharmacokinetics, pharmacodynamics, and corresponding exposure-response relationships of investigational therapies as well as reduced patient burden for clinical trial participation. Obstacle and challenges to adoption and full realization of the vision of patient-centric, digitally-enabled trials will also be discussed.