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.
Background
The increasing use of fresh blood group O whole blood in acute trauma medicine makes it important to reevaluate the issue of hemolytic reactions related to the transfusion of ...ABO‐incompatible plasma.
STUDY DESIGN AND METHODS
This review summarizes and evaluates published articles and case reports concerning hemolytic reactions in connection with the transfusion of group O whole blood or blood products to nongroup O recipients.
Results
In 1945‐1986, 15 nonmilitary publications reported hemolytic transfusion reactions with group O blood/blood products. All patients recovered except for two fatalities. Late in World War II and during the Korean and Vietnam wars and onward in Iraq and Afghanistan only “low anti‐A, anti‐B titer” group O whole blood has been used as universal blood. In spite of a large number of units transfused, there are no reports of hemolytic reactions. Twenty‐five publications report hemolytic reactions after transfusion of group O platelets to nongroup O recipients. In all patients but one, the titer of the implicated A‐ or B‐antibody was >100 (saline) or >400 (antiglobulin) and all cases with an infused volume of incompatible plasma <200 mL were related to anti‐A or anti‐B antiglobulin titers >1000.
Conclusion
In emergency lifesaving resuscitation, the risk of hemolytic transfusion reactions from transfusion of group O blood to nongroup O recipients constitutes risk that is outweighed by the benefits. A low titer of anti‐A/B will minimize the risk for a hemolytic reaction, particularly if the screening is repeated after an immunization episode, e.g., blood transfusion, vaccination, or pregnancy.
Salient objects grab attention because they stand out from their surroundings. Whether this phenomenon is accomplished by bottom-up sensory processing or requires top-down guidance is debated. We ...tested these alternative hypotheses by measuring how early and in which cortical layer(s) neural spiking distinguished a target from a distractor. We measured synaptic and spiking activity across cortical columns in mid-level area V4 of male macaque monkeys performing visual search for a color singleton. A neural signature of attentional capture was observed in the earliest response in the input layer 4. The magnitude of this response predicted response time and accuracy. Errant behavior followed errant selection. Because this response preceded top-down influences and arose in the cortical layer not targeted by top-down connections, these findings demonstrate that feedforward activation of sensory cortex can underlie attentional priority.
•Cognitive EEG production was accurately modeled from empirically measured cortical activity in macaques.•V4 laminar activity can generate a well-known attention-related EEG signal.•Models ...demonstrate the importance of biophysical geometry in cognitive EEG production.•Biophysical and computational contributions are dissociable.
Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.
Cognitive operations are widely studied by measuring electric fields through EEG and ECoG. However, despite their widespread use, the neural circuitry giving rise to these signals remains unknown ...because the functional architecture of cortical columns producing attention-associated electric fields has not been explored. Here, we detail the laminar cortical circuitry underlying an attention-associated electric field measured over posterior regions of the brain in humans and monkeys. First, we identified visual cortical area V4 as one plausible contributor to this attention-associated electric field through inverse modeling of cranial EEG in macaque monkeys performing a visual attention task. Next, we performed laminar neurophysiological recordings on the prelunate gyrus and identified the electric-field-producing dipoles as synaptic activity in distinct cortical layers of area V4. Specifically, activation in the extragranular layers of cortex resulted in the generation of the attention-associated dipole. Feature selectivity of a given cortical column determined the overall contribution to this electric field. Columns selective for the attended feature contributed more to the electric field than columns selective for a different feature. Last, the laminar profile of synaptic activity generated by V4 was sufficient to produce an attention-associated signal measurable outside of the column. These findings suggest that the top-down recipient cortical layers produce an attention-associated electric field that can be measured extracortically with the relative contribution of each column depending upon the underlying functional architecture.
Firms operate today in a rapidly changing and risky environment, where such factors as market and technology are inevitably shrouded in uncertainties. They must make design and operating decisions to ...satisfy several conflicting goals such as maximizing expected profit, minimizing risk, and sustaining long-term viability and competitiveness. Proper formulation is both essential and critical for finding appropriate solutions to such problem. We show how one can formulate this problem as a Markov decision process with recourse that considers decision making throughout the process life cycle and at different hierarchical levels. This formulation incorporates multiple kinds of uncertainties such as market conditions and technology evolution. It allows decision-makers to provide multiple criteria—such as expected profit, expected downside risk, and process lifetime—that reflect various conflicting or incommensurable goals. The formulation integrates design decisions and future planning by constructing a multi-period decision process in which one makes decisions sequentially at each period. The decision process explicitly incorporates both the upper-level investment decisions and lower-level production decisions as a two-stage optimization problem. This problem formulation leads to a multi-objective Markov decision problem, searching for Pareto optimal design strategies that prescribe design decisions for each state the environment and process could occupy. We can often recast this class of problem in order to exploit a rigorous multi-objective stochastic dynamic programming algorithm. This approach decomposes the problem into a sequence of single-period subproblems, each of which is a two-stage stochastic program with recourse. We show how one can solve these subproblems to obtain and propagate the Pareto optimal solutions set recursively backward in time. A small illustrative example appears throughout the paper to demonstrate the formulation and solution issues. The scalability of the rigorous algorithm is limited due to the “curse of dimensionality”, suggesting the need for approximating approaches to solve realistic problems.
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.
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.
Background. Fibroblast growth factor-23 (FGF23) is a circulating factor that regulates the renal reabsorption of inorganic phosphate (Pi) and is increased in chronic kidney disease (CKD). The aim of ...the current investigation was to study the regulation of FGF23 in CKD subjects with various degree of renal function. As such, we analysed the relationship between FGF23, Pi, calcium, parathyriod hormone (PTH), 25(OH) vitamin D3(25(OH)D3), 1,25(OH)2 vitamin D3(1,25(OH)2D3) and estimated glomerular filtration rate (eGFR). Methods. Intact FGF23 and other biochemical variables were analysed in 72 consecutive adult out-patients with various stages of CKD (eGFR ranging from 4–96 ml/min.) Association studies were performed using linear univariate and multivariate analysis. Results. FGF23 was significantly elevated at CKD stage 4 (266 ± 315 pg/ml, P < 0.001) and 5 (702 ± 489 pg/ml, P < 0.001) compared with CKD 1–2 (46 ± 43 pg/ml). In CKD 4–5 an independent association between log FGF23 and Pi (P < 0.001), 25(OH)D3 (P < 0.05) as well as eGFR (P < 0.01) was observed. In contrast, in CKD 1–3 log PTH (P < 0.05) was the only independent predictor of log FGF23 in multivariate analysis. In CKD 1–5, Pi (P < 0.00001) and log PTH (P < 0.01) were explanatory variables for log FGF23 in multivariate analysis. Conclusions: We conclude that serum FGF23 increases in CKD 4–5, in parallel with the emerging hyperphosphataemia. Serum Pi is the most important predictor of FGF23 when GFR is less than 30 ml/min. In contrast, our data suggest that Pi may not be an important determinant of FGF23 in normophosphataemic CKD subjects. Finally, the association between FGF23 and PTH in CKD may suggest a co-regulation that remains to be further elucidated.
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.
Display omitted
•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
PDF
