Repetitive visual stimulation profoundly changes sensory processing in the primary visual cortex (V1). We show how the associated adaptive changes are linked to an altered flow of synaptic activation ...across the V1 laminar microcircuit. Using repeated visual stimulation, we recorded layer-specific responses in V1 of two fixating monkeys. We found that repetition-related spiking suppression was most pronounced outside granular V1 layers that receive the main retinogeniculate input. This repetition-related response suppression was robust to alternating stimuli between the eyes, in line with the notion that repetition-related adaptation is predominantly of cortical origin. Most importantly, current source density (CSD) analysis, which provides an estimate of local net depolarization, revealed that synaptic processing during repeated stimulation was most profoundly affected within supragranular layers, which harbor the bulk of cortico-cortical connections. Direct comparison of the temporal evolution of laminar CSD and spiking activity showed that stimulus repetition first affected supragranular synaptic currents, which translated into a reduction of stimulus-evoked spiking across layers. Together, these results suggest that repetition induces an altered state of intracortical processing that underpins visual adaptation.
Our survival depends on our brains rapidly adapting to ever changing environments. A well-studied form of adaptation occurs whenever we encounter the same or similar stimuli repeatedly. We show that this repetition-related adaptation is supported by systematic changes in the flow of sensory activation across the laminar cortical microcircuitry of primary visual cortex. These results demonstrate how adaptation impacts neuronal interactions across cortical circuits.
Most binocular vision models assume that the two eyes sum incompletely. However, some facilitatory cortical neurons fire for only one eye, but amplify their firing rates if both eyes are stimulated. ...These 'binocular gate' neurons closely resemble subthreshold multisensory neurons. Binocular amplification for binocular gate neurons follows a power law, with a compressive exponent. Unexpectedly, this rule also applies to facilitatory true binocular neurons; although driven by either eye, binocular neurons are well modeled as gated amplifiers of their strongest monocular response, if both eyes are stimulated. Psychophysical data follows the same power law as the neural data, with a similar exponent; binocular contrast sensitivity can be modeled as a gated amplification of the more sensitive eye. These results resemble gated amplification phenomena in multisensory integration, and other non-driving modulatory interactions that affect sensory processing. Models of incomplete summation seem unnecessary for V1 facilitatory neurons or contrast sensitivity. However, binocular combination of clearly visible monocular stimuli follows Schrödinger's nonlinear magnitude-weighted average. We find that putatively suppressive binocular neurons closely follow Schrödinger's equation. Similar suppressive multisensory neurons are well documented but seldom studied. Facilitatory binocular neurons and mildly suppressive binocular neurons are likely neural correlates of binocular sensitivity and binocular appearance respectively.
Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely ...unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7-14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.
Sepsis is a life-threatening condition caused by a dysregulated response to infection, affecting millions of people worldwide. Early diagnosis and treatment are critical for managing sepsis and ...reducing morbidity and mortality rates.
A systematic design approach was employed to build a model that predicts sepsis, incorporating clinical feedback to identify relevant data elements. XGBoost was utilized for prediction, and interpretability was achieved through the application of Shapley values. The model was successfully deployed within a widely used Electronic Medical Record (EMR) system.
The developed model demonstrated robust performance pre-operations, with a sensitivity of 92%, specificity of 93%, and a false positive rate of 7%. Following deployment, the model maintained comparable performance, with a sensitivity of 91% and specificity of 94%. Notably, the post-deployment false positive rate of 6% represents a substantial reduction compared to the currently deployed commercial model in the same health system, which exhibits a false positive rate of 30%.
These findings underscore the effectiveness and potential value of the developed model in improving timely sepsis detection and reducing unnecessary alerts in clinical practice. Further investigations should focus on its long-term generalizability and impact on patient outcomes.
Most of the mammalian neocortex is comprised of a highly similar anatomical structure, consisting of a granular cell layer between superficial and deep layers. Even so, different cortical areas ...process different information. Taken together, this suggests that cortex features a canonical functional microcircuit that supports region-specific information processing. For example, the primate primary visual cortex (V1) combines the two eyes' signals, extracts stimulus orientation, and integrates contextual information such as visual stimulation history. These processes co-occur during the same laminar stimulation sequence that is triggered by the onset of visual stimuli. Yet, we still know little regarding the laminar processing differences that are specific to each of these types of stimulus information. Univariate analysis techniques have provided great insight by examining one electrode at a time or by studying average responses across multiple electrodes. Here we focus on multivariate statistics to examine response patterns across electrodes instead. Specifically, we applied multivariate pattern analysis (MVPA) to linear multielectrode array recordings of laminar spiking responses to decode information regarding the eye-of-origin, stimulus orientation, and stimulus repetition. MVPA differs from conventional univariate approaches in that it examines patterns of neural activity across simultaneously recorded electrode sites. We were curious whether this added dimensionality could reveal neural processes on the population level that are challenging to detect when measuring brain activity without the context of neighboring recording sites. We found that eye-of-origin information was decodable for the entire duration of stimulus presentation, but diminished in the deepest layers of V1. Conversely, orientation information was transient and equally pronounced along all layers. More importantly, using time-resolved MVPA, we were able to evaluate laminar response properties beyond those yielded by univariate analyses. Specifically, we performed a time generalization analysis by training a classifier at one point of the neural response and testing its performance throughout the remaining period of stimulation. Using this technique, we demonstrate repeating (reverberating) patterns of neural activity that have not previously been observed using standard univariate approaches.
During binocular rivalry (BR) only one eye’s view is perceived. Neural underpinnings of BR are debated. Recent studies suggest that primary visual cortex (V1) initiates BR. One trigger might be ...response suppression across most V1 neurons at the onset of BR. Here, we utilize a variant of BR called binocular rivalry flash suppression (BRFS) to test this hypothesis. BRFS is identical to BR, except stimuli are shown with a ∼1s delay. If V1 response suppression was required to initiate BR, it should occur during BRFS as well. To test this, we compared V1 spiking in two macaques observing BRFS. We found that BRFS resulted in response facilitation rather than response suppression across V1 neurons. However, BRFS still reduces responses in a subset of V1 neurons due to the adaptive effects of asynchronous stimulus presentation. We argue that this selective response suppression could serve as an alternate initiator of BR.
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•The role of primary visual cortex (V1) for binocular rivalry (BR) is unclear•V1 population spiking is reduced at the onset of BR, providing a potential trigger•However, this broad spiking suppression does not occur for a variant of BR•The BR variant reduces subpopulation responses, a potential alternate trigger
Cellular neuroscience; Sensory neuroscience
Neurons in the primary visual cortex (V1) of primates play a key role in combining monocular inputs to form a binocular response. Although much has been gleaned from studying how V1 responds to ...discrepant (dichoptic) images, equally important is to understand how V1 responds to concordant (dioptic) images in the two eyes. Here, we investigated the extent to which concordant, balanced, zero-disparity binocular stimulation modifies V1 responses to varying stimulus contrast using intracranial multielectrode arrays. On average, binocular stimuli evoked stronger V1 activity than their monocular counterparts. This binocular facilitation scaled most proportionately with contrast during the initial transient. As V1 responses evolved, additional contrast-mediated dynamics emerged. Specifically, responses exhibited longer maintenance of facilitation for lower contrast and binocular suppression at high contrast. These results suggest that V1 processes concordant stimulation of both eyes in at least two sequential steps: initial response enhancement followed by contrast-dependent control of excitation.
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•Binocular facilitation in primary visual cortex (V1) is contrast dependent•Lower contrasts result in greater binocular facilitation overall•Suppression follows initial facilitation of binocular response in V1•Contrast modulates both facilitation duration and suppression magnitude
Biological sciences; Neuroscience; Behavioral neuroscience
The dorsal lateral geniculate nucleus of the thalamus (LGN) receives the main outputs of both eyes and relays those signals to the visual cortex. Each retina projects to separate layers of the LGN so ...that each LGN neuron is innervated by a single eye. In line with this anatomical separation, visual responses of almost all of LGN neurons are driven by one eye only. Nonetheless, many LGN neurons are sensitive to what is shown to the other eye as their visual responses differ when both eyes are stimulated compared to when the driving eye is stimulated in isolation. This, predominantly suppressive, binocular modulation of LGN responses might suggest that the LGN is the first location in the primary visual pathway where the outputs from the two eyes interact. Indeed, the LGN features several anatomical structures that would allow for LGN neurons responding to one eye to modulate neurons that respond to the other eye. However, it is also possible that binocular response modulation in the LGN arises indirectly as the LGN also receives input from binocular visual structures. Here we review the extant literature on the effects of binocular stimulation on LGN spiking responses, highlighting findings from cats and primates, and evaluate the neural circuits that might mediate binocular response modulation in the LGN.
Our brains combine the signals from the two eyes to create a singular view. Where the separate streams from the two eyes meet in the primate brain is unclear, with debate centering on whether the signals from the two eyes remain separate within the main target of retinal projections, the lateral geniculate nucleus (LGN). Here we review the effects of binocular stimulation on LGN neurons and evaluate neural circuits that might mediate binocular interactions in this structure.
In humans and other primates, sensory signals from each eye remain separated until they arrive in the primary visual cortex (V1), but their exact meeting point is unknown. In V1, some neurons respond ...to stimulation of only one eye (monocular neurons), while most neurons respond to stimulation of either eye (binocular neurons). The main input layers of V1 contain most of the monocular neurons while binocular neurons dominate the layers above and below. This observation has given rise to the idea that the two eyes’ signals remain separate until they converge outside V1’s input layers. Here, we show that, despite responding to only one eye, monocular neurons in all layers, including the input layers, of V1 discriminate between stimulation of their driving eye alone and stimulation of both eyes. Some monocular V1 neurons’ responses were significantly enhanced, or facilitated, when both eyes were stimulated. Binocular facilitation within V1’s input layers tended to occur at the onset of the visual response, which could be explained by converging thalamocortical inputs. However, most V1 monocular neurons were significantly reduced, or suppressed, to binocular stimulation. In contrast to facilitation, binocular suppression occurred several milliseconds following the onset of the visual response, suggesting that the bulk of binocular modulation involves cortical inhibition. These findings, combined, suggest that binocular signals arise at an earlier processing stage than previously appreciated, as even so-called monocular neurons in V1’s input layers encode what is shown to both eyes.
•Monocular neurons in primate V1 layer 4C encode binocular inputs•Firing rates of most monocular V1 neurons are suppressed under binocular viewing•A neuron’s ocularity and its binocular modulation are linearly related
Dougherty et al. evaluate to which degree neurons across V1 layers encode inputs to both eyes. So-called monocular neurons in the primary input layers of V1 modulate under binocular viewing, suggesting binocular signals arise at the input stage of V1.
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