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The superior colliculus is an evolutionarily conserved midbrain region that is thought to mediate spatial orienting, including saccadic eye movements and covert spatial attention. Here, we reveal a role for the superior colliculus in higher-order cognition, independent of its role in spatial orienting. We trained rhesus macaques to perform an abstract visual categorization task that involved neither instructed eye movements nor differences in covert attention. We compared neural activity in the superior colliculus and the posterior parietal cortex, a region previously shown to causally contribute to abstract category decisions. The superior colliculus exhibits robust encoding of learned visual categories, which is stronger than in the posterior parietal cortex and arises at a similar latency in the two areas. Moreover, inactivation of the superior colliculus markedly impaired animals' category decisions. These results demonstrate that the primate superior colliculus mediates abstract, higher-order cognitive processes that have traditionally been attributed to the neocortex., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Populations of neurons produce activity with two central features. First, neuronal responses are very diverse - specific stimuli or behaviors prompt some neurons to emit many action potentials, while other neurons remain relatively silent. Second, the trial-to-trial fluctuations of neuronal response occupy a low dimensional space, owing to significant correlations between the activity of neurons. These two features define the quality of neuronal representation. We link these two aspects of population response using a recurrent circuit model and derive the following relation: the more diverse the firing rates of neurons in a population, the lower the effective dimension of population trial-to-trial covariability. This surprising prediction is tested and validated using simultaneously recorded neuronal populations from numerous brain areas in mice, non-human primates, and in the motor cortex of human participants. Using our relation we present a theory where a more diverse neuronal code leads to better fine discrimination performance from population activity. In line with this theory, we show that neuronal populations across the brain exhibit both more diverse mean responses and lower-dimensional fluctuations when the brain is in more heightened states of information processing. In sum, we present a key organizational principle of neuronal population response that is widely observed across the nervous system and acts to synergistically improve population representation.

Gamma oscillations (30 to 80 Hz) have been hypothesized to play an important role in feature binding, based on the observation that continuous long bars induce stronger gamma in the visual cortex than bars with a small gap. Recently, many studies have shown that natural images, which have discontinuities in several low-level features, do not induce strong gamma oscillations, questioning their role in feature binding. However, the effect of different discontinuities on gamma has not been well studied. To address this, we recorded spikes and local field potential from 2 monkeys while they were shown gratings with discontinuities in 4 attributes: space, orientation, phase, or contrast. We found that while these discontinuities only had a modest effect on spiking activity, gamma power drastically reduced in all cases, suggesting that gamma could be a resonant phenomenon. An excitatory-inhibitory population model with stimulus-tuned recurrent inputs showed such resonant properties. Therefore, gamma could be a signature of excitation-inhibition balance, which gets disrupted due to discontinuities., Competing Interests: The authors have declared that no competing interests exist.

Biomonitoring wearable sensors based on two-dimensional nanomaterials have recently elicited keen research interest and potential for a new range of flexible nanoelectronic devices. Practical nanomaterial-based devices suited for real-world service, which exhibit first-rate performance while being an attractive accessory, are still distant. We report a multifunctional flexible wearable sensor fabricated using an ultrathin percolative layer of graphene nanosheets on laser-patterned gold circular interdigitated electrodes for monitoring vital human physiological parameters. This graphene on laser-patterned electrode (GLE) sensor displays an excellent strain resolution of 245 με (0.024%) and a record high gauge factor of 6.3 × 10 7 , with exceptional stability and repeatability in its operating range. The sensor was tested for human physiological monitoring like measurement of heart rate, breathing rate, body temperature, and hydration level, which are vital health parameters, especially considering the current pandemic scenario. The sensor also served in applications such as a pedometer, limb movement tracker, and control switch for human interaction. The innovative laser-etch process used to pattern gold thin-film electrodes, with the multifunctional incognizable graphene layer, provides a technique for integrating multiple sensors in a wearable band. The reported work marks a giant leap from the conventional banal devices to a highly marketable multifunctional sensor array as a biomonitoring fashion accessory.

Flexible strain sensors are emerging rapidly and overcoming the drawbacks of traditional strain sensors. However, many flexible sensors failed to balance the sensitivity, response time, and the desired sensing range. This work proposes a novel and cost-effective strain sensor which simultaneously achieved high sensitivity, fast response, and a good sensing range. It illustrates a prototype strain sensor realized with a nanocomposite constituting reduced graphene oxide and palladium as the primary sensing elements. These sensors were fabricated with manual screen-printing technology. The sensor exhibited an outstanding performance for the different strains ranging from 0.1% to 45%. As a result, a substantially high gauge factor around 1523 at a strain of as high as 45% and a rapid response time of 47 ms was obtained. This work demonstrated potential applications like real-time monitoring of pulse and respiration, and other physical movement detection, which become crucial parameters to be measured continuously during the COVID-19 pandemic., (© 2021 IOP Publishing Ltd.)

The discovery of stable two-dimensional (2D) materials has effectuated a rapid evolution of skin conformal sensors for health monitoring via epidermal electronics. Among the newly discovered 2D materials, MXene stands out as a solution-processable 2D material allowing easy fabrication of highly conductive thin films with the potential to realize flexible skin conformal sensors. Here, we present a successful demonstration of a Ti 3 C 2 -MXene resistor as an extremely sensitive strain sensor in the form an ultrathin skin mountable temporary tattoo. The skin conformability and form factor afforded by the sensor promises inconspicuous and continuous monitoring of vital health parameters of an individual, like the pulse rate, respiration rate, and surface electromyography. The sensor serves as a single conduit for sensing the respiration rate and pulse, dispensing with the need of mounting multiple sensors. Its remarkably high sensitivity with a gauge factor of ∼7400 has been ascribed to development of nanocracks and their propagation through the film upon application of strain. The fast response and highly repeatable sensor follows easy fabrication steps and can be patterned into any shape and size using a laser.

Reduced graphene oxide (rGO) attracts great popularity as an alternative to pristine graphene because of the facile synthesis process of its precursor, graphene oxide (GO). Electrical conduction of GO is tunable, subject to the extent of reduction of oxygen functional groups in it. This work for the first time demonstrates rapid reduction of GO using spark at ambient conditions. A stream of spark generated by applying high electric potential across two electrodes, when passed through a film of GO deposited on a porous substrate, reduces it into rGO. Upon sparking, the electrical resistance of the GO film drops down by an order of six within a second, making the reduction process instantaneous. X-ray photoelectron spectroscopy and Raman spectra of spark-reduced graphene oxide (SrGO) films revealed a high C/O ratio with an increase in the domain of sp 2 -hybridized carbon. The electromechanical properties of SrGO were practically examined by testing it as a flex sensor by incorporating its films with commercially available gloves. It showed high sensitivity for bending and good repeatability while offering an easy route for textile integration, making an impactful statement about the potential of sparking as a cost-effective method to reduce GO on a large scale.

We report a novel strain sensor based on reduced graphene oxide (rGO) with palladium (Pd) nano-composite. The sensor was fabricated on the SS304 stainless-steel substrate using a screen-printing method. Graphene oxide was synthesized using a modified Hummer's method and reduced using a chemical route. Field emission-scanning electron microscope, x-ray diffraction and Raman spectroscopy were used to characterize the as-synthesized nano-composite. The as-fabricated strain sensor was tested for tensile strain using Micro-universal Test Machine and the change in resistance for different strains was recorded. The sensor response was observed to be stable and linear within the applied strain range of 0-3000 microstrains, and an average gauge factor of 42.69 was obtained in this range.

This paper presents development and performance assessment of an innovative and a highly potent graphene-electrolyte capacitive sensor (GECS) based on the supercapacitor model. Although graphene has been widely researched and adapted in supercapacitors as electrode material, this combination has not been applied in sensor technology. A low base capacitance, generally the impeding factor in capacitive sensors, is addressed by incorporating electric double layer capacitance in GECS, and a million-fold increase in base capacitance is achieved. The high base capacitance (∼22.0 μF) promises to solve many inherent issues pertaining to capacitive sensors. GECS is fabricated by using thermally reduced microwave exfoliated graphene oxide material to form interdigitated electrodes coated with solid-state electrolyte which forms the double layer capacitance. The capacitance response of GECS on subjecting to strain is examined and an enormous operating range (∼300 nF) is seen, which is the salient feature of this sensor. The GECS showed an impressive device sensitivity of 11.24 nF kPa-1 and good immunity towards noise i.e. lead capacitance and stray capacitance. Two regimes of operation are identified based on the procedure of device fabrication. The device can be applied to varied applications and one such biomedical application of breath pattern monitoring is demonstrated.

Gamma oscillations (∼30-80 Hz) are a prominent signature of electrophysiological signals, with a purported role in natural vision. Previous studies in the primary visual cortex (area V1) have shown that achromatic gratings or gabor stimuli generate salient gamma oscillations, whose strength and frequency depend on stimulus properties such as their size, contrast, and orientation. Surprisingly, although natural images are rarely achromatic, the effect of chromatic input on gamma has not been thoroughly investigated. Recording from primate V1, we show that gamma oscillations of extremely high magnitude (peak increase of ∼300-fold in some cases), far exceeding the gamma generated by optimally tuned achromatic gratings, are induced in the local field potentials by full-field color stimuli of different hues. Furthermore, gamma oscillations are sensitive to the hue of the chromatic input, with the strongest oscillations for long-wavelength (reddish) hues and another, smaller gamma response peak for hues in the short-wavelength (bluish) range, which lie approximately on the two cardinal chromatic response axes of the upstream lateral geniculate nucleus neurons. These oscillations depended critically on the purity of the hue, decreasing with hue desaturation, but remained robust for pure hue stimuli even at reduced luminance. Importantly, the magnitude of gamma oscillations was highly correlated with positive L-M cone contrast produced by the stimuli, suggesting that gamma could be a marker of the specific mechanisms underlying this computation. These findings provide insights into the generation of gamma oscillations, as well as the processing of color along the visual pathway., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Recent studies have shown the existence of two gamma rhythms in the hippocampus subserving different functions but, to date, primate studies in primary visual cortex have reported a single gamma rhythm. Here, we show that large visual stimuli induce a slow gamma (25-45 Hz) in area V1 of two awake adult female bonnet monkeys and in the EEG of 15 human subjects (7 males and 8 females), in addition to the traditionally known fast gamma (45-70 Hz). The two rhythms had different tuning characteristics for stimulus orientation, contrast, drift speed, and size. Further, fast gamma had short latency, strongly entrained spikes and was coherent over short distances, reflecting short-range processing, whereas slow gamma appeared to reflect long-range processing. Together, two gamma rhythms can potentially provide better coding or communication mechanisms and a more comprehensive biomarker for diagnosis of mental disorders. SIGNIFICANCE STATEMENT Gamma rhythm has been associated with high-level cognitive functions such as attention and feature binding and has been reported to be abnormal in brain disorders such as autism and schizophrenia. Unlike previous studies that have shown a single gamma rhythm in the primate visual cortex, we found that large visual gratings induce two distinct gamma oscillations in both monkey LFP and human EEG. These rhythms, termed slow (25-45 Hz) and fast (45-70 Hz), exhibited distinct tuning preferences, latencies, and coherence profiles, potentially reflecting processing at two different ranges. Multiple gamma oscillations in visual cortex may provide a richer representation of external visual stimuli and could be used for developing brain-machine interfacing applications and screening tests for neuropsychiatric disorders., (Copyright © 2018 Murty et al.)

Brain signals are often analyzed in the spectral domain, where the power spectral density (PSD) and phase differences and consistency can reveal important information about the network. However, for proper interpretation, it is important to know whether these measures depend on stimulus/behavioral conditions or the reference scheme used to analyze data. We recorded local field potential (LFP) from an array of microelectrodes chronically implanted in area V1 of monkeys under different stimulus/behavioral conditions and computed PSD slopes, coherence, and phase difference between LFPs as a function of frequency and interelectrode distance while using four reference schemes: single wire, average, bipolar, and current source density. PSD slopes were dependent on reference scheme at low frequencies (below 200 Hz) but became invariant at higher frequencies. Average phase differences between sites also depended critically on referencing, switching from 0 degrees for single-wire to 180 degrees for average reference. Results were consistent across different stimulus/behavioral conditions. We were able to account for these results based on the coherence profile across sites and properties of the spectral estimator. Our results show that using different reference schemes can have drastic effects on phase differences and PSD slopes and therefore must be interpreted carefully to gain insights about network properties.

A simple method for the simultaneous assay of both substrate utilization and product formation by Bordetella pertussis adenylate cyclase has been developed. This method involves measurement of ATP remaining in the reaction mixture and cyclic 3',5'-AMP (cAMP) formation by 31p-NMR spectroscopy. No separation of the nucleotides is required. The measurement of the rate of cAMP formation compared very well with other methods that require separation of product from the substrate. With this method it has been possible to show calmodulin activation of B. pertussis adenylate cyclase and to demonstrate an inhibition of calmodulin activation by melittin. The inhibition of calmodulin-activated adenylate cyclase by melittin is not permanent and can be overcome by long-term incubation.

We have determined the comparative activities of peroxisomal proliferators, ciprofibrate and clofibric acid on various hepatic parameters associated with endoplasmic reticulum, mitochondria and peroxisomes in primary cultures of rat hepatocytes. We have measured the activities of carnitine acetyltransferase and fatty acylCoA oxidase, and the amount of 60 and 80 kD polypeptides as biochemical markers of the peroxisomal function; laurate hydroxylase and cytochrome P-450 as markers of the endoplasmic reticulum; and carnitine palmitoyltransferase as a marker of mitochondria in primary cultures of hepatocytes. Ciprofibrate (0.01 to 0.3 mM) and clofibric acid (0.1 to 3 mM) produced similar changes in several components of cultured hepatocytes within 72 hr. Increases of protein (18 and 11%), carnitine palmitoyltransferase (23 and 97%), cytochrome P-450 (37 and 49%), carnitine acetyltransferase (484 and 614%), fatty acylCoA oxidase (529 and 931%) and laurate hydroxylase (624 and 671%) were obtained in hepatocytes after a 72-hr exposure to 0.1 mM ciprofibrate and 1.0 mM clofibric acid, respectively. In cultured hepatocytes, ciprofibrate was about 30-fold more active than clofibric acid for the stimulation of carnitine acetyltransferase, laurate hydroxylase and fatty acylCoA oxidase activities. Ciprofibrate was also more potent than clofibric acid as an inducer of the 60 and 80 kD proteins in hepatocytes. The maximal drug-induced increases in carnitine acetyltransferase activity were not additive, and the induction of carnitine acetyltransferase by ciprofibrate was blocked by addition (1 micrograms per ml) of cycloheximide or actinomycin D. Changes in protein and RNA synthesis preceded the drug-induced increases of carnitine acetyltransferase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Tunicamycin caused a dose and time dependent decrease in cytochrome P-450 in rat liver. A dose of 50 micrograms/kg caused a decrease of about 50% in 72 hours. A similar decrease in the activities of rat liver microsomal aniline hydroxylase, aminopyrine N-demethylase and ethoxycoumarin O-deethylase were also seen after the tunicamycin treatment. Tunicamycin also suppressed food and water intake but the decrease in cytochrome P-450 was not related to these effects. NADPH cytochrome c reductase was not markedly decreased by tunicamycin. A decrease in cytochrome P-450 was also observed in cultured rat hepatocytes treated with tunicamycin. It decreased incorporation of [35S]-methionine into total proteins as well as into various cytochrome P-450 isozymes of rat hepatocytes. This indicates that a decrease in protein synthesis may be responsible for the tunicamycin-induced decrease in cytochrome P-450 and drug metabolism.

Daunomycin and adriamycin are widely used antitumor agents which induce dose-dependent cardiotoxicity. The mechanisms by which daunomycin causes cardiotoxicity have been investigated in neonatal rat cardiac myocytes maintained in tissue culture. Daunomycin inhibited the uptake of adenine, amino acids, and deoxyglucose in a dose-dependent fashion. The uptake of both adenine and methionine was inhibited without any delay while the glucose uptake (deoxyglucose) was inhibited after a delay of 2 hr. Since daunomycin affected the uptake of both adenine and amino acids without any delay and since daunomycin did not affect the incorporation of adenine into nucleotide and amino acids into proteins once these were transported into the cell, it is possible the daunomycin exerted these effects by acting directly on the cell membrane. Thus, one of the early toxic manifestations of anthracycline antibiotics may be on the transport of nutrients such as amino acids, glucose, and adenine.

A simple, sensitive method has been developed for evaluating cell injury noninvasively in monolayer cells in culture. The cell ATP pool was radiolabeled by incubating the cells with [14C]adenine. The uptake and incorporation of [14C]adenine was shown to proportional to the number of cells. As determined by HPLC, about 65-70% of the incorporated 14C label was in the ATP pool, 15-20% was in the ADP pool, and the rest was in the 5'-AMP pool. When prelabeled cells were exposed to toxic drugs (acetaminophen, calcium ionophore A-23187, or daunomycin) there was a marked decrease in cell ATP with a concomitant increase in leakage of labeled nucleotides, mainly 5'-AMP and 5'IMP. We have shown that leakage of 14C label into the medium from the prelabeled cells may be employed for quantitation of cell injury. This new measure of toxicity was shown to correlate very well with LDH leakage from the cells, which is a well accepted measure of cell injury. The leakage of 5'-[14C]AMP also correlated very well with the reduction of cell ATP in cardiac myocytes. This method has been used for monitoring drug-induced toxicity in liver cells, cardiac myocytes, and LB cells.

In rat hepatocytes maintained in culture, cytochrome P-450 and NADPH cytochrome c reductase activities were decreased by tunicamycin in a dose and time dependent fashion. The effect of tunicamycin was mainly due to inhibition of protein synthesis. Tunicamycin decreased L-[35S] methionine incorporation into many proteins, including a 52 kDa cytochrome P-450 isozyme. Tunicamycin also reduced RNA synthesis. These results indicate that tunicamycin decreased cytochrome P-450 levels in hepatocytes by inhibiting protein and RNA synthesis.

Neonatal rat cardiac myocytes maintained in tissue culture were utilized to screen cardiotoxicity induced by a number of adriamycin and daunomycin analogs. Cell toxicity was assessed by leakage of cytoplasmic enzymes and was confirmed by electron microscopy. A number of modifications of structure of adriamycin and daunomycin markedly altered the incidence of toxicity caused by these drugs. Even though some of these structural alterations markedly altered lipid solubility or reactivity of quinone function, these changes did not always account for the differences in the toxicity induced by anthracycline analogs. The cardiomyocyte culture system used in this simple screening technique should be useful in the development of active anthracycline analog with least cardiotoxic potential.