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The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates-macaque, marmoset and human-but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

BACKGROUND: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein-to-vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study-III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single-unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. RESULTS: Data on VLBW infants (n = 254) who received one or more single-unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post-transfusion hemoglobin increments were associated with RBC units donated by female donors (-0.24 g/dL [95% confidence interval (CI) -0.57, -0.02]; p = .04) and donors <25 years old (-0.57 g/dL [95% CI -1.02, -0.11]; p = .02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p < .01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post-transfusion hemoglobin increments. CONCLUSION: Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants.

Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of neurological disorders.

© 2020 Elsevier Inc. Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.

BackgroundRecent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin (Hb) levels in patients after red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes.Study design and methodsWe linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined Hb increments and subsequent transfusion requirements after single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors.ResultsWe linked data on 4038 transfusion recipients who received one or more single-unit RBC transfusions (n = 5086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n = 326), Hb increments were reduced after transfusion of gamma-irradiated units (0.76 g/dL; p = 0.033) but not unirradiated units (1.04 g/dL; p = 0.54) compared to those from nonsmokers (1.01 g/dL; n = 4760). In parallel with changes in Hb levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (odds ratio [OR], 2.49; p = 0.01) but not unirradiated RBC units (OR, 1.10; p = 0.52).ConclusionDonor smoking was associated with reduced Hb increments and the need for additional transfusions in recipients of gamma-irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion.

Marilyn T Nedumcheril,1,2 Robert A DeSimone,1 Sabrina E Racine-Brzostek,1 Ok Kyong Chaekal,1,3 Ljiljana V Vasovic1 1Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA; 2New York Blood Center Enterprises, New York, NY, USA; 3Department of Medicine/Division of Hematology-Oncology New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USACorrespondence: Ljiljana V VasovicDepartment of Pathology and Laboratory Medicine, New York-Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, Box 251, New York, NY, 10065, USATel +1 212 746 6106Fax +1 212 746 8435Email ljv9004@med.cornell.eduAbstract: Daratumumab, a monoclonal antibody therapeutic, is highly efficacious and widely used in all stages of multiple myeloma and amyloidosis and has promising activity in other hematologic disorders. Daratumumab interacts with red blood cells, interfering with pre-transfusion testing. This interference can lead to compromising transfusion safety, extensive blood bank work ups and delays in provision of compatible units. Several methods have been developed to negate daratumumab interference with indirect antiglobulin testing. They are based on i) standard blood bank techniques including dithiothreitol and enzymatic treatment of reagent cells, using reagent red blood cells negative for CD38, ii) blocking CD38 antigens on reagent or donor cells, iii) neutralization of anti-CD38 antibody in patient plasma prior to testing, and iv) extended antigen typing of patient red blood cells in conjunction with provision of phenotypically matched units for transfusion. Implementation of those methods by the blood bank should be a planned effort coordinated with the patient’s clinical team. Timely involvement of blood bank and transfusion services and educational efforts by both blood banks and clinical providers can improve the overall daratumumab safety profile in regard to blood transfusion.K

© 2020 Landman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Vocal communication in animals often involves taking turns vocalizing. In humans, turn-taking is a fundamental rule in conversation. Among non-human primates, the common marmoset is known to engage in antiphonal calling using phee calls and trill calls. Calls of the trill type are the most common, yet difficult to study, because they are not very loud and uttered in conditions when animals are in close proximity to one another. Here we recorded trill calls in captive pair-housed marmosets using wearable microphones, while the animals were together with their partner or separated, but within trill call range. Trills were exchanged mainly with the partner and not with other animals in the room. Animals placed outside the home cage increased their trill call rate and uttered more trills in response to their partner compared to strangers. The fundamental frequency, F0, of trills increased when animals were placed outside the cage. Our results indicate that trill calls can be monitored using wearable audio equipment and that minor changes in social context affect trill call interactions and spectral properties of trill calls.

The lateral prefrontal cortex (LPFC) of primates plays an important role in executive control, but how it interacts with the rest of the cortex remains unclear. To address this, we densely mapped the cortical connectome of LPFC, using electrical microstimulation combined with functional MRI (EM-fMRI). We found isomorphic mappings between LPFC and five major processing domains composing most of the cerebral cortex except early sensory and motor areas. An LPFC grid of ∼200 stimulation sites topographically mapped to separate grids of activation sites in the five domains, coarsely resembling how the visual cortex maps the retina. The temporal and parietal maps largely overlapped in LPFC, suggesting topographically organized convergence of the ventral and dorsal streams, and the other maps overlapped at least partially. Thus, the LPFC contains overlapping, millimeter-scale maps that mirror the organization of major cortical processing domains, supporting LPFC's role in coordinating activity within and across these domains., NEI (Grant R01-EY029666)

© 2019, The Author(s). When searching for an object in a cluttered scene, we can use our memory of the target object features to guide our search, and the responses of neurons in multiple cortical visual areas are enhanced when their receptive field contains a stimulus sharing target object features. Here we tested the role of the ventral prearcuate region (VPA) of prefrontal cortex in the control of feature attention in cortical visual area V4. VPA was unilaterally inactivated in monkeys performing a free-viewing visual search for a target stimulus in an array of stimuli, impairing monkeys’ ability to find the target in the array in the affected hemifield, but leaving intact their ability to make saccades to targets presented alone. Simultaneous recordings in V4 revealed that the effects of feature attention on V4 responses were eliminated or greatly reduced while leaving the effects of spatial attention on responses intact. Altogether, the results suggest that feedback from VPA modulates processing in visual cortex during attention to object features.

© 2020 Elsevier Inc. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of neurological disorders.

Affective judgment and decision-making are strongly modulated by the pregenual anterior cingulate (pACC) and caudal orbitofrontal (cOFC) cortical regions. By combining MRI-guided electrical microstimulation with viral tracing methods in non-human primates, we demonstrate that circumscribed pACC and cOFC microstimulation sites that induce negative decision-making preferentially project to striosomes in the anterior striatum. These results outline a behaviorally important circuit from pACC/cOFC to striosomes causally modulating decision-making under emotional conflict. Keywords: anterior cingulate cortex; approach–avoidance; microstimulation; orbitofrontal cortex; striatum, National Institute of Neurological Disorders and Stroke (Grant R01 NS025529), United States. Office of Naval Research (Grant N00014‐07‐1‐0903), United States. Army Research Office (Grant W911NF‐16‐1‐0474)

Musical training confers advantages in speech-sound processing, which could play an important role in early childhood education. To understand the mechanisms of this effect, we used event-related potential and behavioral measures in a longitudinal design. Seventy-four Mandarin-speaking children aged 4–5 y old were pseudorandomly assigned to piano training, reading training, or a no-contact control group. Six months of piano training improved behavioral auditory word discrimination in general as well as word discrimination based on vowels compared with the controls. The reading group yielded similar trends. However, the piano group demonstrated unique advantages over the reading and control groups in consonant-based word discrimination and in enhanced positive mismatch responses (pMMRs) to lexical tone and musical pitch changes. The improved word discrimination based on consonants correlated with the enhancements in musical pitch pMMRs among the children in the piano group. In contrast, all three groups improved equally on general cognitive measures, including tests of IQ, working memory, and attention. The results suggest strengthened common sound processing across domains as an important mechanism underlying the benefits of musical training on language processing. In addition, although we failed to find far-transfer effects of musical training to general cognition, the near-transfer effects to speech perception establish the potential for musical training to help children improve their language skills. Piano training was not inferior to reading training on direct tests of language function, and it even seemed superior to reading training in enhancing consonant discrimination.

In cluttered scenes, we can use feature-based attention to quickly locate a target object. To understand how feature attention is used to find and select objects for action, we focused on the ventral prearcuate (VPA) region of prefrontal cortex. In a visual search task, VPA cells responded selectively to search cues, maintained their feature selectivity throughout the delay and subsequent saccades, and discriminated the search target in their receptive fields with a time course earlier than in FEF or IT cortex. Inactivation of VPA impaired the animals' ability to find targets, and simultaneous recordings in FEF revealed that the effects of feature attention were eliminated while leaving the effects of spatial attention in FEF intact. Altogether, the results suggest that VPA neurons compute the locations of objects with the features sought and send this information to FEF to guide eye movements to those relevant stimuli., National Eye Institute (Grant EY017921), National Science Foundation (U.S.) (Grant CCF 1317348)

Cognition requires the dynamic modulation of effective connectivity, i.e., the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backward to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.

This protocol describes a large-volume illuminator, which was developed for optogenetic manipulations in the non-human primate brain. The illuminator is a modified plastic optical fiber with etched tip, such that the light emitting surface area is > 100x that of a conventional fiber. In addition to describing the construction of the large-volume illuminator, this protocol details the quality-control calibration used to ensure even light distribution. Further, this protocol describes techniques for inserting and removing the large volume illuminator. Both superficial and deep structures may be illuminated. This large volume illuminator does not need to be physically coupled to an electrode, and because the illuminator is made of plastic, not glass, it will simply bend in circumstances when traditional optical fibers would shatter. Because this illuminator delivers light over behaviorally-relevant tissue volumes (≈ 10 mm 3 ) with no greater penetration damage than a conventional optical fiber, it facilitates behavioral studies using optogenetics in non-human primates., National Institutes of Health (U.S.) (Grant NIH 2R44NS070453-03A1), National Institutes of Health (U.S.) (Grant NIH EY017292)

A large body of previous neuroimaging studies suggests that multiple languages are processed and organized in a single neuroanatomical system in the bilingual brain, although differential activation may be seen in some studies because of different proficiency levels and/or age of acquisition of the two languages. However, one important possibility is that the two languages may involve interleaved but functionally independent neural populations within a given cortical region, and thus, distinct patterns of neural computations may be pivotal for the processing of the two languages. Using functional magnetic resonance imaging (fMRI) and multivariate pattern analyses, we tested this possibility in Chinese-English bilinguals when they performed an implicit reading task. We found a broad network of regions wherein the two languages evoked different patterns of activity, with only partially overlapping patterns of voxels in a given region. These regions, including the middle occipital cortices, fusiform gyri, and lateral temporal, temporoparietal, and prefrontal cortices, are associated with multiple aspects of language processing. The results suggest the functional independence of neural computations underlying the representations of different languages in bilinguals.

Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (~70 nm) imaging of cells and mammalian tissues on conventional microscopes., United States. National Institutes of Health (1R01GM104948), United States. National Institutes of Health (1DP1NS087724), United States. National Institutes of Health ( NIH 1R01EY023173), United States. National Institutes of Health (1U01MH106011)

The ventro-lateral pulvinar is reciprocally connected with the visual areas of the ventral stream that are important for object recognition. To understand the mechanisms of attentive stimulus processing in this pulvinar-cortex loop, we investigated the interactions between the pulvinar, area V4, and IT cortex in a spatial-attention task. Sensory processing and the influence of attention in the pulvinar appeared to reflect its cortical inputs. However, pulvinar deactivation led to a reduction of attentional effects on firing rates and gamma synchrony in V4, a reduction of sensory-evoked responses and overall gamma coherence within V4, and severe behavioral deficits in the affected portion of the visual field. Conversely, pulvinar deactivation caused an increase in low-frequency cortical oscillations, often associated with inattention or sleep. Thus, cortical interactions with the ventro-lateral pulvinar are necessary for normal attention and sensory processing and for maintaining the cortex in an active state. The pulvinar is often proposed to modulate cortical processing with attention. Zhou et al. find that beyond any role in attention, the pulvinar input to cortex seems necessary to maintain the cortex in an active state., National Institutes of Health (U.S.) (Grant R01 EY017292)

Optogenetic methods have been highly effective for suppressing neural activity and modulating behavior in rodents, but effects have been much smaller in primates, which have much larger brains. Here, we present a suite of technologies to use optogenetics effectively in primates and apply these tools to a classic question in oculomotor control. First, we measured light absorption and heat propagation in vivo, optimized the conditions for using the red-light–shifted halorhodopsin Jaws in primates, and developed a large-volume illuminator to maximize light delivery with minimal heating and tissue displacement. Together, these advances allowed for nearly universal neuronal inactivation across more than 10 mm³ of the cortex. Using these tools, we demonstrated large behavioral changes (i.e., up to several fold increases in error rate) with relatively low light power densities (≤100 mW/mm²) in the frontal eye field (FEF). Pharmacological inactivation studies have shown that the FEF is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear from earlier work, however, whether FEF activity during each epoch is necessary for memory-guided saccade execution. By harnessing the temporal specificity of optogenetics, we found that FEF contributes to memory-guided eye movements during every epoch of the memory-guided saccade task (the visual, delay, and motor periods)., United States. National Institutes of Health (2R44NS070453-03A1), United States. National Institutes of Health (EY017292)

Cognition requires the dynamic modulation of effective connectivity, i.e., the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backward to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.

Groups of neurons tend to synchronize in distinct frequency bands. Within a given frequency band, synchronization is defined as the consistency of phase relations between site pairs, over time. This synchronization has been investigated in numerous studies and has been found to be modulated by sensory stimulation or cognitive conditions. Here, we investigate local field potentials (LFPs) and multi-unit activity (MUA) recorded from area V4 of two monkeys performing a selective visual attention task. We show that phase relations, that are consistent over time, are typically diverse across site pairs. That is, across site pairs, mean phase relations differ substantially and this across-site-pair phase-relation diversity (SPHARED, for Spatial PHAse RElation Diversity) is highly reliable. Furthermore, we show that visual stimulation and selective attention can shift the pattern of phase relations across site pairs. These shifts are again diverse and this across-site-pair phase-relation-shift diversity (SPHARESD) is again highly reliable. We find SPHARED for LFP–LFP, LFP–MUA and MUA–MUA pairs, stimulus-induced SPHARESD for LFP–LFP and LFP–MUA pairs, and attention-induced SPHARESD for LFP–LFP pairs. SPHARESD is a highly interesting signal from the perspective of impact on downstream neuronal activity. We provide several pieces of evidence for such a role., National Institute of Mental Health (U.S.). Intramural Research Program, National Institutes of Health (U.S.) (Grant R01-EY017292)

It has been known that monkeys will repeatedly press a bar for electrical stimulation in several different brain structures. We explored the possibility of using electrical stimulation in one such structure, the nucleus accumbens, as a substitute for liquid reward in animals performing a complex task, namely visual search. The animals had full access to water in the cage at all times on days when stimulation was used to motivate them. Electrical stimulation was delivered bilaterally at mirror locations in and around the accumbens, and the animals’ motivation to work for electrical stimulation was quantified by the number of trials they performed correctly per unit of time. Acute mapping revealed that stimulation over a large area successfully supported behavioral performance during the task. Performance improved with increasing currents until it reached an asymptotic, theoretically maximal level. Moreover, stimulation with chronically implanted electrodes showed that an animal's motivation to work for electrical stimulation was at least equivalent to, and often better than, when it worked for liquid reward while on water control. These results suggest that electrical stimulation in the accumbens is a viable method of reward in complex tasks. Because this method of reward does not necessitate control over water or food intake, it may offer an alternative to the traditional liquid or food rewards in monkeys, depending on the goals and requirements of the particular research project., National Institutes of Health (U.S.) (Grant EY017921)

Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific., National Institute of Mental Health (U.S.). Intramural Research Program, National Institutes of Health (U.S.) (Grant R01EY017292)

Background: Recording and manipulating neural activity in awake behaving animal models requires long-term implantation of cranial implants that must address a variety of design considerations, which include preventing infection, minimizing tissue damage, mechanical strength of the implant, and MRI compatibility. New method: Here we address these issues by designing legless, custom-fit cranial implants using structural MRI-based reconstruction of the skull and that are made from carbon-reinforced PEEK. Results: We report several novel custom-fit radiolucent implant designs, which include a legless recording chamber, a legless stimulation chamber, a multi-channel microdrive and a head post. The fit to the skull was excellent in all cases, with no visible gaps between the base of the implants and the skull. The wound margin was minimal in size and showed no sign of infection or skin recession. Comparison with existing methods: Cranial implants used for neurophysiological investigation in awake behaving animals often employ methyl methacrylate (MMA) to serve as a bonding agent to secure the implant to the skull. Other designs rely on radially extending legs to secure the implant. Both of these methods have significant drawbacks. MMA is toxic to bone and frequently leads to infection while radially extending legs cause the skin to recede away from the implant, ultimately exposing bone and proliferating granulation tissue. Conclusions: These radiolucent implants constitute a set of technologies suitable for reliable long-term recording, which minimize infection and tissue damage., National Eye Institute (EY017291), National Eye Institute (EY017292), National Institutes of Health (U.S.) (National Research Service Award, EY020692)

Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ∼60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a prestimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma-synchronized as strongly as with visual stimulation. These analyses reveal the cell-type-specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level., National Institute of Mental Health (U.S.). Intramural Research Program, National Institutes of Health (U.S.) (Grant R01-EY017292)

It is widely held that the frontal eye field (FEF) in prefrontal cortex (PFC) modulates processing in visual cortex with attention, although the evidence that it is necessary is equivocal. To help identify critical sources of attentional feedback to area V4, we surgically removed the entire lateral PFC, including the FEF, in one hemisphere and transected the corpus callosum and anterior commissure in two macaques. This deprived V4 of PFC input in one hemisphere while keeping the other hemisphere intact. In the absence of PFC, attentional effects on neuronal responses and synchrony in V4 were substantially reduced and the remaining effects of attention were delayed in time, indicating a critical role for PFC. Conversely, distracters captured attention and influenced V4 responses. However, because the effects of attention in V4 were not eliminated by PFC lesions, other sources of top-down attentional control signals to visual cortex must exist outside of PFC., National Institute of Mental Health (U.S.). Intramural Research Program, National Institutes of Health (U.S.) (Grant R01EY017292)

In primates, visual stimuli with social and emotional content tend to attract attention. Attention might be captured through rapid, automatic, subcortical processing or guided by slower, more voluntary cortical processing. Here we examined whether irrelevant faces with varied emotional expressions interfere with a covert attention task in macaque monkeys. In the task, the monkeys monitored a target grating in the periphery for a subtle color change while ignoring distracters that included faces appearing elsewhere on the screen. The onset time of distracter faces before the target change, as well as their spatial proximity to the target, was varied from trial to trial. The presence of faces, especially faces with emotional expressions interfered with the task, indicating a competition for attentional resources between the task and the face stimuli. However, this interference was significant only when faces were presented for greater than 200 ms. Emotional faces also affected saccade velocity and reduced pupillary reflex. Our results indicate that the attraction of attention by emotional faces in the monkey takes a considerable amount of processing time, possibly involving cortical–subcortical interactions. Intranasal application of the hormone oxytocin ameliorated the interfering effects of faces. Together these results provide evidence for slow modulation of attention by emotional distracters, which likely involves oxytocinergic brain circuits., Simons Foundation, National Institutes of Health (U.S.) (Grant EY017292)

When we search for a target in a crowded visual scene, we often use the distinguishing features of the target, such as color or shape, to guide our attention and eye movements. To investigate the neural mechanisms of feature-based attention, we simultaneously recorded neural responses in the frontal eye field (FEF) and area V4 while monkeys performed a visual search task. The responses of cells in both areas were modulated by feature attention, independent of spatial attention, and the magnitude of response enhancement was inversely correlated with the number of saccades needed to find the target. However, an analysis of the latency of sensory and attentional influences on responses suggested that V4 provides bottom-up sensory information about stimulus features, whereas the FEF provides a top-down attentional bias toward target features that modulates sensory processing in V4 and that could be used to guide the eyes to a searched-for target., National Institutes of Health (U.S.) (NIH EY017921), National Institutes of Health (U.S.) (NIH 5P30EY2621-33)

Many experiments in neuroscience have compared the strength of association between neural spike trains and rhythms present in local field potential (LFP) recordings. The measure employed in these comparisons, “spike-field coherence”, is a frequency dependent measure of linear association, and is shown to depend on overall neural activity (Lepage et al., 2011). Dependence upon overall neural activity, that is, dependence upon the total number of spikes, renders comparison of spike-field coherence across experimental context difficult. In this paper, an inferential procedure based upon a generalized linear model is shown to be capable of separating the effects of overall neural activity from spike train-LFP oscillatory coupling. This separation provides a means to compare the strength of oscillatory association between spike train-LFP pairs independent of differences in spike counts. Following a review of the generalized linear modelling framework of point process neural activity a specific class of generalized linear models are introduced. This model class, using either a piece-wise constant link function, or an exponential function to relate an LFP rhythm to neural response, is used to develop hypothesis tests capable of detecting changes in spike train-LFP oscillatory coupling. The performance of these tests is validated, both in simulation and on real data. The proposed method of inference provides a principled statistical procedure by which across-context change in spike train-LFP rhythmic association can be directly inferred that explicitly handles between-condition differences in total spike count., National Institute of Neurological Disorders and Stroke (U.S.) (R01NS073118), National Institute of Neurological Disorders and Stroke (U.S.) (R01NS072023), Grant EY017292, Grant EY017921

When a sensory stimulus repeats, neuronal firing rate and functional MRI blood oxygen level-dependent responses typically decline, yet perception and behavioral performance either stay constant or improve. An additional aspect of neuronal activity is neuronal synchronization, which can enhance the impact of neurons onto their postsynaptic targets independent of neuronal firing rates. We show that stimulus repetition leads to profound changes of neuronal gamma-band (∼40–90 Hz) synchronization. Electrocorticographic recordings in two awake macaque monkeys demonstrated that repeated presentations of a visual grating stimulus resulted in a steady increase of visually induced gamma-band activity in area V1, gamma-band synchronization between areas V1 and V4, and gamma-band activity in area V4. Microelectrode recordings in area V4 of two additional monkeys under the same stimulation conditions allowed a direct comparison of firing rates and gamma-band synchronization strengths for multiunit activity (MUA), as well as for isolated single units, sorted into putative pyramidal cells and putative interneurons. MUA and putative interneurons showed repetition-related decreases in firing rate, yet increases in gamma-band synchronization. Putative pyramidal cells showed no repetition-related firing rate change, but a decrease in gamma-band synchronization for weakly stimulus-driven units and constant gamma-band synchronization for strongly driven units. We propose that the repetition-related changes in gamma-band synchronization maintain the interareal stimulus signaling and sharpen the stimulus representation by gamma-synchronized pyramidal cell spikes., Human Frontier Science Program (Strasbourg, France) (Organization Grant RGP0070/2003), Volkswagen Foundation (Grant I/79876), European Science Foundation (European Young Investigator Award Program), European Union (HEALTH-F2-2008-200728 Grant), State Offensive for Development of Scientific and Economic Excellence (program grant “Neuronale Koordination Forschungsschwerpunkt Frankfurt”), Netherlands. Ministry of Economic Affairs (Smart Mix Programme), Netherlands. Ministry of Education, Culture, and Science (BrainGain), Netherlands Organization for Scientific Research (Grant 452-03-344)

The claustrum is a surprisingly large, sheet-like neuronal structure hidden beneath the inner surface of the neocortex. We found that the portions of the claustrum connected with V4 appear to overlap considerably with those portions connected with other cortical visual areas, including V1, V2, MT, MST and FST, TEO and TE. We found extensive reciprocal connections between V4 and the ventral portion of the claustrum (vCl), which extended through at least half of the rostrocaudal extent of the structure. Additionally, in approximately 75% of the cases, we found reciprocal connections between V4 and a more restricted region located farther dorsal, near the middle of the structure (mCl). Both vCl and mCl appear to have at least a crude topographic organization. Based on the projection of these claustrum subdivisions to the amygdala, we propose that vCl and mCl are gateways for the transmission of visual information to the memory system. In addition to these crude visuotopically organized regions, there are other parts of the claustrum that obey the topographical proximity principle, with considerable overlap of their connections. There is only an overall segregation of claustrum regions reciprocally connected to the occipital, parietal, temporal and frontal lobes. The portion of the claustrum connected to the visual cortex is located ventral and posterior; the one connected to the auditory cortex is located dorsal and posterior; the one connected to the somatosensory cortex is located dorsal and medial; the one connected to the frontal premotor and motor cortices is located dorsal and anterior; while the one connected to the temporal cortex is located ventral and anterior. The extensive reciprocal connections of the claustrum with almost the entire neocortex and its projections to the hippocampus, amygdala and basal ganglia prompt us to propose its role as a gateway for perceptual information to the memory system., National Institute of Mental Health (U.S.) (NIMH Intramural Research Program), National Eye Institute (NEI (NIH) grant RO1EY017292)

To investigate the subcortical efferent connections of visual area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the fovea representation as well as representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that V2 projects topographically to different portions of the inferior and lateral pulvinar and to the superficial and intermediate layers of the superior colliculus. Within the pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the strongest projection being in P2. Central visual field injections in V2 labeled projection zones in P1 and P2, whereas peripheral field injections labeled P1, P2, and P4. No projections were found in P3. Both central and peripheral field injections in V2 projected topographically to the superficial and intermediate layers of the superior colliculus. Projections from V2 to the pulvinar and the superior colliculus constituted cortical–subcortical loops through which circuits serving spatial attention are activated., National Institutes of Health (U.S.) (EY017292), Conselho Nacional de Pesquisas (Brazil), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro

It is well established that stellar effective temperatures determined from photometry and spectroscopy yield systematically different results. We describe a new, simple method to correct spectroscopically derived temperatures ("excitation temperatures") of metal-poor stars based on a literature sample with –3.3 < [Fe/H] < –2.5. Excitation temperatures were determined from Fe I line abundances in high-resolution optical spectra in the wavelength range of ~3700-~7000 Å, although shorter wavelength ranges, up to 4750-6800 Å, can also be employed, and compared with photometric literature temperatures. Our adjustment scheme increases the temperatures up to several hundred degrees for cool red giants, while leaving the near-main-sequence stars mostly unchanged. Hence, it brings the excitation temperatures in good agreement with photometrically derived values. The modified temperature also influences other stellar parameters, as the Fe I-Fe II ionization balance is simultaneously used to determine the surface gravity, while also forcing no abundance trend on the absorption line strengths to obtain the microturbulent velocity. As a result of increasing the temperature, the often too low gravities and too high microturbulent velocities in red giants become higher and lower, respectively. Our adjustment scheme thus continues to build on the advantage of deriving temperatures from spectroscopy alone, independent of reddening, while at the same time producing stellar chemical abundances that are more straightforwardly comparable to studies based on photometrically derived temperatures. Hence, our method may prove beneficial for comparing different studies in the literature as well as the many high-resolution stellar spectroscopic surveys that are or will be carried out in the next few years., Brazil. National Council for Scientific and Technological Development (CNPq, grant number 55.0003/2011-8), Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ, grant number E-26/110.905/2013)

Electrical recordings in humans and monkeys show attentional enhancement of evoked responses and gamma synchrony in ventral stream cortical areas. Does this synchrony result from intrinsic activity in visual cortex or from inputs from other structures? Using paired recordings in the frontal eye field (FEF) and area V4, we found that attention to a stimulus in their joint receptive field leads to enhanced oscillatory coupling between the two areas, particularly at gamma frequencies. This coupling appeared to be initiated by FEF and was time-shifted by about 8 to 13 milliseconds across a range of frequencies. Considering the expected conduction and synaptic delays between the areas, this time-shifted coupling at gamma frequencies may optimize the postsynaptic impact of spikes from one area upon the other, improving cross-area communication with attention., Grant EY017292, Grant EY17921

Shifts of gaze and shifts of attention are closely linked and it is debated whether they result from the same neural mechanisms. Both processes involve the frontal eye fields (FEF), an area which is also a source of top-down feedback to area V4 during covert attention. To test the relative contributions of oculomotor and attention-related FEF signals to such feedback, we recorded simultaneously from both areas in a covert attention task and in a saccade task. In the attention task, only visual and visuomovement FEF neurons showed enhanced responses, whereas movement cells were unchanged. Importantly, visual, but not movement or visuomovement cells, showed enhanced gamma frequency synchronization with activity in V4 during attention. Within FEF, beta synchronization was increased for movement cells during attention but was suppressed in the saccade task. These findings support the idea that the attentional modulation of visual processing is not mediated by movement neurons., National Eye Institute (Grant 5R01EY017921)

Cognition requires the dynamic modulation of effective connectivity, i.e. the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backwards to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.

Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications., Helen Hay Whitney Foundation, National Institutes of Health (U.S.) (NIH K99MH085944), McGovern Institute Neurotechnology (MINT) Program, National Institutes of Health (U.S.) (Director’s New Innovator Award 1DP2OD002002, 1R01DA029639, 1R43NS070453, 1RC2DE020919, 1R01NS067199), National Science Foundation (U.S.) (NSF (EFRI 0835878)), National Science Foundation (U.S.) (DMS 0848804), United States. Dept. of Defense, Brain & Behavior Research Foundation, Alfred P. Sloan Foundation, Dr. Gerald Burnett and Marjorie Burnett, SFN Research Award for Innovation in Neuroscience, Massachusetts Institute of Technology. Media Laboratory, McGovern Institute for Brain Research at MIT, Benesse Foundation, Massachusetts Institute of Technology (Neurotechnology Fund), Wallace H. Coulter Foundation

This chapter reviews the concept of dynamic coordination, its mechanistic implementation in brain circuits, and the extent to which dynamic coordination, and specific manifestations of it, have the power to account for functions performed by interacting brain systems. In our discussions, we addressed how on-the- y changes in coupling between neural subpopulations might enable the brain to handle the fast-changing recombination of processing elements thought to underlie cognition. Such changes in coupling should be apparent, rst and foremost, in the statistical relationship between activity in interconnected brain systems, rather than in the individual ring patterns of each subsystem. Dynamic coordination may manifest itself through a variety of mechanisms, of which oscillation-based synchronization is likely to play an important but not exclusive role. Also discussed is how modulation of phase relationships of oscillations in different brain systems, in neocortex and hippocampus of the mammalian brain, may change functional coupling, and how such changes may play a role in routing of signals at cross sections between cortical areas and hippocampal subdivisions. Possible mechanisms for oscillation-based synchronization, particularly in the gamma frequency range, are explored. It is acknowledged that the brain is likely capable of producing zero-phase lag between spatially dispersed cell populations by way of rather simple coupling mechanisms, primarily when neuronal groups are coupled symmetrically. Synchronization with remote areas may be most ef cient with phase differences that match the conduction delays. Fast-conducting, long-range projecting interneurons are identi ed as a potential substrate for synchronizing one neural circuit with another. A number of research strategies are identi ed to enhance our understanding of dynamic coordination of brain systems and how it might contribute to the implementation of the functions of those systems.

Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications., Helen Hay Whitney Foundation, National Institutes of Health (U.S.) (NIH K99MH085944), McGovern Institute Neurotechnology (MINT) Program, National Institutes of Health (U.S.) (Director’s New Innovator Award 1DP2OD002002, 1R01DA029639, 1R43NS070453, 1RC2DE020919, 1R01NS067199), National Science Foundation (U.S.) (NSF (EFRI 0835878)), National Science Foundation (U.S.) (DMS 0848804), United States. Dept. of Defense, Brain & Behavior Research Foundation, Alfred P. Sloan Foundation, Dr. Gerald Burnett and Marjorie Burnett, SFN Research Award for Innovation in Neuroscience, Massachusetts Institute of Technology. Media Laboratory, McGovern Institute for Brain Research at MIT, Benesse Foundation, Massachusetts Institute of Technology (Neurotechnology Fund), Wallace H. Coulter Foundation

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks. ChR2 was safely expressed, and could mediate optical neuromodulation, in primate neocortex over many months. These findings highlight a methodology for investigating the causal role of specific cell types in nonhuman primate neural computation, cognition, and behavior, and open up the possibility of a new generation of ultraprecise neurological and psychiatric therapeutics via cell-type-specific optical neural control prosthetics., Helen Hay Whitney Foundation (Fellowship), National Institutes of Health (U.S.) (NIH-EY002621-31), McGovern Institute for Brain Research at MIT (Neurotechnology Award), National Institutes of Health (U.S.) (Grant NIH-EY12848), National Institutes of Health (U.S.) (Grant NIH-EY017292), National Institutes of Health (U.S.) (NIH Director's New Innovator Award (DP2 OD002002-01)), Brain & Behavior Research Foundation, United States. Dept. of Defense, National Science Foundation (U.S.), Alfred P. Sloan Foundation, Dr. Gerald Burnett and Marjorie Burnett, SFN Research Award for Innovation in Neuroscience, Massachusetts Institute of Technology. Media Laboratory, Benesse Foundation, Wallace H. Coulter Foundation

Attention to a stimulus enhances both neuronal responses and gamma frequency synchrony in visual area V4, both of which should increase the impact of attended information on downstream neurons. To determine whether gamma synchrony is common throughout the ventral stream, we recorded from neurons in the superficial and deep layers of V1, V2, and V4 in two rhesus monkeys. We found an unexpected striking difference in gamma synchrony in the superficial vs. deep layers. In all three areas, spike-field coherence in the gamma (40–60 Hz) frequency range was largely confined to the superficial layers, whereas the deep layers showed maximal coherence at low frequencies (6–16 Hz), which included the alpha range. In the superficial layers of V2 and V4, gamma synchrony was enhanced by attention, whereas in the deep layers, alpha synchrony was reduced by attention. Unlike these major differences in synchrony, attentional effects on firing rates and noise correlation did not differ substantially between the superficial and deep layers. The results suggest that synchrony plays very different roles in feedback and feedforward projections., National Eye Institute (Grant EY017292), National Eye Institute (Grant EY017921)

Recognizing objects in cluttered scenes requires attentional mechanisms to filter out distracting information. Previous studies have found several physiological correlates of attention in visual cortex, including larger responses for attended objects. However, it has been unclear whether these attention-related changes have a large impact on information about objects at the neural population level. To address this question, we trained monkeys to covertly deploy their visual attention from a central fixation point to one of three objects displayed in the periphery, and we decoded information about the identity and position of the objects from populations of ∼200 neurons from the inferior temporal cortex using a pattern classifier. The results show that before attention was deployed, information about the identity and position of each object was greatly reduced relative to when these objects were shown in isolation. However, when a monkey attended to an object, the pattern of neural activity, represented as a vector with dimensionality equal to the size of the neural population, was restored toward the vector representing the isolated object. Despite this nearly exclusive representation of the attended object, an increase in the salience of nonattended objects caused “bottom-up” mechanisms to override these “top-down” attentional enhancements. The method described here can be used to assess which attention-related physiological changes are directly related to object recognition, and should be helpful in assessing the role of additional physiological changes in the future., National Science Foundation (U.S.) (Grant NSF-0640097), National Science Foundation (U.S.) (grant NSF-0827427), National Eye Institute (Grant R01EY017292), United States. Defense Advanced Research Projects Agency, Adobe Systems, American Honda Motor Company, King Abdullah University of Science and Technology, United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellow), Herbert Schoemaker (Firm)

The visual processing of behaviorally relevant stimuli is enhanced through top-down attentional feedback. One possibility is that feedback targets early visual areas first and the attentional enhancement builds up at progressively later stages of the visual hierarchy. An alternative possibility is that the feedback targets the higher-order areas first and the attentional effects are communicated “backward” to early visual areas. Here, we compared the magnitude and latency of attentional enhancement of firing rates in V1, V2, and V4 in the same animals performing the same task. We found a reverse order of attentional effects, such that attentional enhancement was larger and earlier in V4 and smaller and later in V1, with intermediate results in V2. These results suggest that attentional mechanisms operate via feedback from higher-order areas to lower-order ones., National Institutes of Health (U.S.) (Grant EY017292), National Institutes of Health (U.S.) (Grant EY017921), National Institutes of Health (U.S.) (Grant MH072034)

Recognizing objects in cluttered scenes requires attentional mechanisms to filter out distracting information. Previous studies have found several physiological correlates of attention in visual cortex, including larger responses for attended objects. However, it has been unclear whether these attention-related changes have a large impact on information about objects at the neural population level. To address this question, we trained monkeys to covertly deploy their visual attention from a central fixation point to one of three objects displayed in the periphery, and we decoded information about the identity and position of the objects from populations of ∼200 neurons from the inferior temporal cortex using a pattern classifier. The results show that before attention was deployed, information about the identity and position of each object was greatly reduced relative to when these objects were shown in isolation. However, when a monkey attended to an object, the pattern of neural activity, represented as a vector with dimensionality equal to the size of the neural population, was restored toward the vector representing the isolated object. Despite this nearly exclusive representation of the attended object, an increase in the salience of nonattended objects caused “bottom-up” mechanisms to override these “top-down” attentional enhancements. The method described here can be used to assess which attention-related physiological changes are directly related to object recognition, and should be helpful in assessing the role of additional physiological changes in the future., National Science Foundation (U.S.) (Grant NSF-0640097), National Science Foundation (U.S.) (grant NSF-0827427), National Eye Institute (Grant R01EY017292), United States. Defense Advanced Research Projects Agency, Adobe Systems, American Honda Motor Company, King Abdullah University of Science and Technology, United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellow), Herbert Schoemaker (Firm)

A complex visual scene will typically contain many different objects, few of which are currently relevant to behavior. Thus, attentional mechanisms are needed to select the relevant objects from the scene and to reject the irrelevant ones. Neurophysiological studies in monkeys have identified some of the neural mechanisms of attentional selection within the ventral, ldquoobject recognitionrdquo, stream of the cortex, which begins with area V1 and continues through areas V2, V4, and IT cortex. At each stage along this stream, attended, or behaviorally relevant, stimuli are processed preferentially compared to irrelevant distracters. The source of the attentional feedback to visual cortex seems to originate in parietal and prefrontal cortex. We proposed some years ago that this attentional feedback biased competitive interactions among neurons in visual cortex, in favor of neuronal responses to the most behaviorally relevant stimulus. More recent work indicates that these competitive interactions are one aspect of a more general visual mechanism for contrast normalization, which is present in most or all visual areas. By providing the appropriate input to this normalization mechanism, feedback from parietal and prefrontal cortex appears to shift the balance of visual cortical responses towards the attended stimulus.

Rhythms occur both in neuronal activity and in behavior. Behavioral rhythms abound at frequencies at or below 10 Hz. Neuronal rhythms cover a very wide frequency range, and the phase of neuronal low-frequency rhythms often rhythmically modulates the strength of higher-frequency rhythms, particularly of gamma-band synchronization (GBS). Here, we study stimulus-induced GBS in awake monkey areas V1 and V4 in relation to a specific form of spontaneous behavior, namely microsaccades (MSs), small fixational eye movements. We found that MSs occur rhythmically at a frequency of ~3.3 Hz. The rhythmic MSs were predicted by the phase of the 3.3 Hz rhythm in V1 and V4 local field potentials. In turn, the MSs modulated both visually induced GBS and the speed of visually triggered behavioral responses. Fast/slow responses were preceded by a specific temporal pattern of MSs. These MS patterns induced perturbations in GBS that in turn explained variability in behavioral response speed. We hypothesize that the 3.3 Hz rhythm structures the sampling and exploration of the environment through building and breaking neuronal ensembles synchronized in the gamma-frequency band to process sensory stimuli., 7th European Community Framework Programme (FP7/2007-2013), Beca Presidente de la República, Gobierno de Chile (C.A.B.)