Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin-Film Electronics for High-Resolution Cortical Mapping.

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro-electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin-film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental-ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time-division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. In vivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8 mm2 . The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain-machine interfaces.

Reactivity to pseudorandom environmental patterns in woodlice: Effects of hydric deprivation and light exposure.

Exploratory activity is an essential component of animal behavior, including among invertebrate species. This study examined the effects of hydric deprivation and their possible modulation by light exposure on locomotion and rearing-up behavior in two woodlice species, Porcellio scaber (Latreille 1804) and Armadillidium vulgare (Latreille 1804). It was also an attempt to replicate previous findings on the stimulation of these behaviors in P. scaber, exposed to (pseudo)random vs. regular visual and tactile patterns in a small enclosure. In Experiment 1, two groups of P. scaber and two groups of A. vulgare were exposed to randomly vs. regularly distributed visual (black and white) and tactile (grained and smooth) patterns for approximately 20 min. No rewards were present in the environment and the woodlice were tested without preliminary hydric deprivation. In Experiment 2, the same procedure was used but the woodlice were tested following a 20-min hydric deprivation under a bottle cap (darkness). Experiment 3 replicated this procedure with the 20-min hydric deprivation spent in a plastic cup (light exposure). The results of Experiments 1 and 3 provide partial replication with A. vulgare, but not P. scaber, of the previous findings: Random patterns stimulate rearing-up behavior on the apparatus' vertical walls more than regular patterns. Also, a more aversive stimulation in Experiment 3 compared to Experiment 2, increased locomotion, especially in the random environment. The role of hydric deprivation and light exposure in the process of escaping from a hostile environment is discussed, as well as the effects of the treatments used in these experiments.

Influence of excessive sucrose consumption on exploratory behaviour in rats - Possible implications for the brain reward system.

Due to the low cost of production and the strong evolutionary preference for sweet taste in humans, sugar is added to many food products. This leads to often involuntary overconsumption of high amounts of sugar. Yet, growing evidence indicates that high-sugar diets impact brain function and impair cognitive ability. It may be due to physiological changes in specific regions of the brain or/and maladaptive changes in dopamine signalling similar to those observed in the etiology of addiction. In our study, rats from the experimental group were kept on a feeding protocol involving intermittent access to sucrose solution for eight weeks. Then, the animals underwent a spontaneous exploration test in an experimental arena divided into three zones where stationary and movable objects were placed. Studying the rats' exploratory behaviour allowed us to assess the impact of the sucrose diet on a broad spectrum of behaviours related to the general functioning of the organism in its environment. Analyses showed differences in reaction to novelty between different diet groups which had been placed in different experimental setups. Rats from the sugar-fed group responded to change with more pronounced exploratory behaviours directed at the source of the novel stimuli and the surrounding environment. These results may indicate a lower reward value of novelty resulting from diminished responsiveness of the reward system in the sugar-diet group. We have not found evidence for memory and/or learning impairments in rats on the sugar-rich diet.

Rat's response to a novelty and increased complexity of the environment resulting from the introduction of movable vs. stationary objects in the free exploration test.

Most animals, including rats, show a preference for more complex environments. This is demonstrated particularly well when complexity increases due to the addition of new elements to the environment. The aim of the study was to investigate the reaction to novelty, understood as a change in environmental properties that involve both changes in complexity and controllability. Controllability may allow for dealing with challenges of an environment of low predictability in a way that the animal's own activity reduces the uncertainty of environmental events. In our study, the animals underwent a spontaneous exploration test in low-stress conditions. After a period of habituation to the experimental arena, additional stationary (increased complexity) and/or movable (increased complexity and controllability) tunnels were introduced, and the reaction of the rats to the novel objects was measured. The results of the study confirmed that an increase in the complexity of the environment through the addition of objects triggers a more intensive exploratory activity in rats. However, an increased spatial complexity combined with the movability of the novel objects seems to result in increased caution towards the novelty after an initial inspection of the changed objects. It suggests that the complexity of the novelty may trigger both neophilia and neophobia depending on the level of the predictability of the novel environment and that the movability of newly introduced objects is not independent of other parameters of the environment.

Decrease in the rewarding value of spatial novelty due to the contamination of the stimulus field with light - Evidence from a free exploration test involving rats.

It has been shown that rearranging the spatial properties of a familiar environment consistently elicits a positive response in rats directed toward the source of novelty. Previous studies have been conducted under red light or darkness. The purpose of this study was to test the effect of rearranging the spatial properties of a familiar environment in conjunction with a change in lighting conditions. The results have shown specific effects of the light presence and its intensity on different behavioral measures. We propose that this study provides a basis for hypothesizing a two-way mechanism of the behavioral response to light regulation in rats. The first is based on ON/OFF states. This level may be related to fundamental, evolutionarily early, emergent components of behavioral antipredator adaptations. Another level of behavioral regulation involves mechanisms sensitive to light intensity. These appear to be involved in the regulation of more advanced behavioral acts, such as exploratory responses. This may suggest that light intensity analysis may require the involvement of more advanced cognitive components in the behavioral regulation system.

Research culture: science from bench to society.

Research is a long process in which the collaboration between stakeholders involved in academia, industry and governments is crucial. Ideally, these stakeholders should work together to better align the innovation process with the values, needs and expectations of the research community. Reflecting on how we perform research and how our discoveries can benefit society is therefore of the utmost importance. The complete system of shared values concerning the research process is embedded in the concept of research culture, which has been gaining more attention in recent years. With the hope of increasing awareness of research culture among established scientists and early-career professionals, in this manuscript we discuss what research culture is, what it consists of and how it can positively influence scientific developments.

Response to novelty induced by change in size and complexity of familiar objects in Lister-Hooded rats, a follow-up of 2019 study.

This study examines the relationship between the change in size and change in complexity of well-known/familiarized objects and exploratory activity regulation in rats. In our experiment, the rats were exposed to three types of environmental novelty in a well-familiarized chamber: (1) addition of new tunnels to the chamber, (2) increased size of a familiarized tunnel, and (3) increased complexity of the existing tunnels. The animals responded to the addition of new tunnels with a significant behavioural shift involving increased exploration of the newly installed tunnels. This effect was stable across all three test trials. The rats exposed to a change in size of the familiar object initially reacted with a behavioural shift towards the enlarged tunnel but then re-focused on the unchanged one. There was also a significant increase in the frequency of moving between the zones of the chamber. The experimental group exposed to an increased complexity of familiar objects responded with a pronounced behavioural shift towards the complex tunnel and then slightly intensified their exploration of the unchanged one. A decrease was also observed in the frequency of moving between the zones of the chamber in the first and second test trials. In the effect size analysis, no differences were found in any of the three groups, which suggests that all manipulations had similar impact. The data obtained in this study supports the view that in rats, curiosity is at least two-dimensional: activational and cognitive. The activational aspect of curiosity may be explained by novelty-related arousal processes, while the cognitive processes are activated at longer time intervals in response to more complex stimulation. The validation of this hypothesis requires further research involving manipulations with a recently standardized protocol for measuring free exploration.

Can the Hole-Board Test Predict a Rat's Exploratory Behavior in a Free-Exploration Test?

This study focuses on the rat activity in a hole-board setting that we considered a type of exploratory behavior. The general hypothesis is based on the claim that a motivational mechanism is central to both the response to novelty in a highly familiarized environment and the activity in the hole-board apparatus. Our sample consisted of 80 experimentally naive Lister Hooded rats. All rats were tested in the hole-board apparatus. Twenty individuals with the highest hole-board scores and twenty subjects with the lowest hole-board scores subsequently underwent an established free-exploration test. In our study, the scores obtained in the hole-board test had little predictive value for the rats' activity in the free-exploration test. Based on our previous experience in studying exploratory behavior in the free-exploration test and the data presented in this paper, we suggest that the hole-board test is not an appropriate tool for measuring exploratory behavior in laboratory rodents.

Optogenetic fUSI for brain-wide mapping of neural activity mediating collicular-dependent behaviors.

Neuronal cell types are arranged in brain-wide circuits that guide behavior. In mice, the superior colliculus innervates a set of targets that direct orienting and defensive actions. We combined functional ultrasound imaging (fUSI) with optogenetics to reveal the network of brain regions functionally activated by four collicular cell types. Stimulating each neuronal group triggered different behaviors and activated distinct sets of brain nuclei. This included regions not previously thought to mediate defensive behaviors, for example, the posterior paralaminar nuclei of the thalamus (PPnT), which we show to play a role in suppressing habituation. Neuronal recordings with Neuropixels probes show that (1) patterns of spiking activity and fUSI signals correlate well in space and (2) neurons in downstream nuclei preferentially respond to innately threatening visual stimuli. This work provides insight into the functional organization of the networks governing innate behaviors and demonstrates an experimental approach to explore the whole-brain neuronal activity downstream of targeted cell types.

Left ventricular diastolic dysfunction and diseases severity contribute to impaired exercise capacity in systemic lupus erythematosus.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have a higher risk of myocardial involvement, which can result in ventricular dysfunction. The aim of our study was to estimate potential relationship between exercise capacity assessed by six minute walk test (6MWT) and echocardiographic parameters of left and right ventricular function in SLE patients. METHODS: We prospectively studied 66 SLE patients (57 F, age 44 (20-75) years) and 27 age matched healthy subjects. In addition to routine evaluation, 6MWT and transthoracic echocardiography including LV diastolic dysfunction parameters (E/A, E/É) were performed. RESULTS: While E/A was similar in both groups, E/E' was higher in patients with SLE than in controls, 7.5 (4-22) vs 6.8 (1.6-9.4), p = 0.018. The mean 6MWT distance was significantly shorter in SLE (561.6 ± 150.7 vs 682.6 ± 98.1 m, p < 0.002). Among SLE patients only 53 (80.3%) were capable to walk at least 450 m, while in controls 27 (100%) (p = 0.013). We observed significant correlations between 6MWT distance and SLICC/ACR-DI (rho=-0.44, p < 0.001), E/A (rho = 0.30, p = 0.004), E/E' (rho=-0.36, p < 0.001) in SLE patients. Univariable logistic regression models revealed that SLICC/ACR-DI, E/E', tricuspid regurgitant peak gradient (TRPG), and right ventricular systolic pressure (RVSP) were associated with 6MWT distance lower than < 450 m. ROC curves shown high predictive value of E/E' ratio, TRPG, RVSP in the prediction for 6MWT distance < 450 m. CONCLUSION: Impaired exercise tolerance seems to result mainly from the severity of SLE and LV diastolic dysfunction.

Variability of enriched environment does not enhance the enrichment effect on food neophobia in rats (Rattus norvegicus).

Many studies report differences between animals raised in an enriched environment and those living in standard conditions. Animals reared in enriched conditions demonstrate better memory and learning abilities, increased activity, reduced level of anxiety, etc. However, there is a shortage of studies investigating the impact of environmental variability on animal behaviour, and few studies on this topic focus on animals with different initial anxiety levels. This study was conducted on laboratory rats. Prior to the experiment, the rats were kept in three types of rearing conditions: an enriched stable environment; an enriched variable environment; and in standard laboratory conditions. The environment was enriched by providing a cognitively and physically stimulating living space. The variability of the environment involved altering the arrangement of the enriching objects on a daily basis. The level of reaction to food novelty was measured with a food neophobia test. The study demonstrates that an enriched environment has a significant impact on reducing food neophobia. However, our findings suggest that the variability of the environment is not necessary and does not enhance the positive impact of enrichment on these aspects of behaviour.

Influence of disease severity and cardiac autonomic tone on ventricular repolarization and dispersion in electrocardiographic assessment of patients with systemic lupus erythematosus.

BACKGROUND: There are no data on the influence of disease severity and cardiac autonomic tone on ventricular repolarization and dispersion in 24-hour Holter monitoring in systemic lupus erythematosus (SLE). METHODS: Consecutive 92 SLE and 51 healthy subjects were studied. The standard 12-lead electrocardiography (ECG), Holter monitoring with heart rate turbulence (HRT) and QT, Tp-e and Tp-e/QT ratio assessment (including corrected values) were performed. Subjects with conditions causing repolarization abnormalities or insufficient number of beats suitable for QT evaluation were excluded (17 SLE and 8 controls). RESULTS: Finally, 75 SLE and 43 sex- and age-matched controls were included to the study. In SLE patients, the median disease severity score (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)) was 3.0. The mean values of QTc, cTp-e and cTp-e/QTc were significantly higher in SLE patients than in controls. QTc ≥ 460 ms was observed in 18.7% of patients using standard ECG and in 58.7% using Holter monitoring. With Holter monitoring, patients with SLICC/ACR-DI >3.0 presented longer QTc than those with SLICC/ACR-DI ≤3.0 (418±15 vs. 409 ± 16, p = 0.04), while cTp-e and cTp-e/QTc values were similar. Patients with abnormal HRT presented longer cTp-e and higher cTp-e/QTc than those with normal HRT (92 ± 52 vs. 71 ± 16 ms, p = 0.04; 0.244 ± 0.126 vs. 0.187 ± 0.035, p = 0.03), while QTc values were similar. No differences in QT and Tp-e parameters were observed according to disease duration. CONCLUSION: In SLE patients, Holter monitoring revealed QTc prolongation more frequently than standard ECG. Longer QTc values were observed in patients with more advanced disease, while increased cTp-e and cTp-e/QTc were related to cardiac autonomic dysfunction expressed by abnormal HRT.

Behavioural Response to the Environmental Changes of Various Types in Lister-Hooded Male Rats.

The animal preference for complexity is most clearly demonstrated when the environmental change takes the form of an increase in complexity. Therefore, one of the potential difficulties in interpretation is that the preference for perceptual novelty may be confounded with the change in environmental complexity. In this study, the environmental complexity was controlled by manipulating with tunnels inside the experimental chamber. Adding new tunnels triggered a very profound change in behaviour, which was demonstrated by the animals' prolonged stay in the proximity of the novel objects, sniffing, touching, and climbing on top of the tunnels. The removal of the tunnels from the test arena turned out to have the least influence on behaviour compared to the other manipulations used in this study. The reduction of complexity of the tunnels had a moderate effect on rat behavior. Tunnels are important elements in the rats' environment, since they provide various possibilities for hiding, resting or moving inside the tunnel. They may be treated as a good example of affordances in rat-environment interactions. The results of this study may therefore serve as a basis for constructing a modified theory of animal curiosity which could incorporate the concept of ecological psychology.

Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary circulation in patients with systemic sclerosis.

PURPOSE: Pulmonary hypertension (PH) is an ominous complication in systemic sclerosis patients (SSc) and echocardiography is a screening tool for its detection. The goal of this study was to assess the reliability of resting and exercise echo Doppler parameters with data obtained by right heart catheterization (RHC). MATERIAL AND METHODS: We included 91 patients (84 F, 53.3 ± 15.2 years) with SSc. Transthoracic echocardiography followed by exercise Doppler-echocardiography (EDE) were performed. A positive EDE was defined as a ≥20 mmHg increase in tricuspid regurgitation peak gradient (TRPG). RHC with exercise was performed in positive EDE patients and/or in subjects with resting TRPG > 31 mmHg. RESULTS: Finally, RHC was performed in 20 patients. The correlation for the echocardiography and invasive measurement of systolic (sPAP) and mean (mPAP) pulmonary artery pressure was r = 0.66 (p = 0.001) and r = 0.7 (p = 0.001), respectively. We also found significant correlation between echocardiography and invasive measurement of exercise sPAP r = 0.68 (p = 0.001) and exercise mPAP r = 0.67 (p = 0.002). There was a correlation between pulmonary vascular resistance (PVR) assessed by echocardiography and measured by RHC r = 0.49, p = 0.027. The equation derived within our population was: PVR by echocardiography = 9.6*TRV/TVIRVOT+0.068. We also performed ROC analysis to predict PVR > 2 WU. Our results highlight that sPAP has the highest AUC (0.802, 95% CI 0.585-1). CONCLUSION: Doppler resting and exercise echocardiography may provide a reliable, noninvasive method for determining resting and exercise sPAP, mPAP, and PVR in SSc patients, although it may underestimate or overestimate these values in some individuals. Doppler echocardiography does not replace RHC for definite hemodynamic assessment of suspected PH.

The application of the supported liquid membrane and molecularly imprinted polymers as solid acceptor phase for selective extraction of biochanin A from urine.

An efficient sample clean-up and preconcentration procedure for phytoestrogens analysis in urine has been developed. It was based on a combination of solid phase extraction with hollow-fiber supported liquid membrane and molecularly imprinted beads (MIPs-HF-SLM-SPE). The molecularly imprinted polymers (MIPs) were synthesized by precipitation polymerization technique with biochanin A (BCA) as a template, giving narrowly dispersed microspheres with a regular shape. As the functional monomer, (dimethylamino)ethyl methacrylate (-DEM) turned out to be better than methacrylic acid (MAA) to get the best-imprinted effects. The MIPs used as sorbents in the MIPs-HF-SLM-SPE extraction process exhibited excellent binding selectivity for BCA, in comparison to non-imprinted polymers as well as its structural analogs (genistein and daidzein). Finally, the developed method was used to detect BCA in urine. Under optimal extraction conditions, the recovery of BCA in urine samples (using 4.5 mL sample spiked with 10 µg L-1) was over 41%, with a coefficient of variation (CV) < 6.6% (n = 5). The detection limit (LOD) and quantification limit (LOQ) for BCA analysis in urine were 0.41 and 1.36 µg L-1, respectively.

Volumes of brain structures in captive wild-type and laboratory rats: 7T magnetic resonance in vivo automatic atlas-based study.

Selective breeding of laboratory rats resulted in changes of their behavior. Concomitantly, the albino strains developed vision related pathologies. These alterations certainly occurred on the background of modifications in brain morphology. The aim of the study was to assess and compare volumes of major structures in brains of wild-captive, laboratory albino and laboratory pigmented rats. High resolution T2-weighted images of brains of adult male Warsaw Wild Captive Pisula-Stryjek rats (WWCPS, a model of wild type), laboratory pigmented (Brown Norway strain, BN) and albino rats (Wistar strain, WI) were obtained with a 7T small animal-dedicated magnetic resonance tomograph. Volume quantification of whole brains and 50 brain structures within each brain were performed with the digital Schwarz rat brain atlas and a custom-made MATLAB/SPM8 scripts. Brain volumes were scaled to body mass, whereas volumes of brain structures were normalized to individual brain volumes. Normalized brain volume was similar in WWCPS and BN, but lower in WI. Normalized neocortex volume was smaller in both laboratory strains than in WWCPS and the visual cortex was smaller in albino WI rats than in WWCPS and BN. Relative volumes of phylogenetically older structures, such as hippocampus, amygdala, nucleus accumbens and olfactory nuclei, also displayed certain strain-related differences. The present data shows that selective breeding of laboratory rats markedly affected brain morphology, the neocortex being most significantly altered. In particular, albino rats display reduced volume of the visual cortex, possibly related to retinal degeneration and the development of blindness.

The impact of changeability of enriched environment on exploration in rats.

Although the positive effect of environmental enrichment on animals' cognitive capacities is well-known, it remains unclear what role changeability plays in this context. Our study aims to analyse the impact of environmental changeability on the level of exploration and the rate of habituation to novelty. Prior to the experiment, the animals were housed in three settings: enriched stable conditions, enriched changing conditions and standard conditions. Environmental changeability was introduced by re-arranging objects in the housing pen. A test was conducted to measure the level of exploration in adult individuals. The study results suggest that rats housed in standard conditions exhibit a higher demand for interactions with the new environment. However, once novelty is introduced, rats from the enriched environments spend more time than their standard counterparts exploring the new objects. No significant differences have been observed in the behaviour of rats from the stable and changeable conditions. It may be concluded, therefore, that in a setting characterised by long-lasting environmental enrichment, the changeability of the environment plays no major role, at least with respect to exploration, general activity and the rate of habituation to novelty. It may be linked to the relatively quick extinguishment of behaviours reinforced by intrinsic reinforcement.

Comparison of non-invasive assessment of arrhythmias, conduction disturbances and cardiac autonomic tone in systemic sclerosis and systemic lupus erythematosus.

Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are connective tissue diseases presenting cardiac complications including different arrhythmias, then direct electrocardiographic comparison may be useful in everyday clinical decision making. We examined 86 adult SSc patients, 76 with SLE and 45 healthy controls. Among other examinations all subjects underwent 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence evaluation. Patients with various co-existing conditions which might markedly influence arrhythmias and autonomic modulation were excluded from further analysis (SSc n = 12, SLE n = 6). Finally, 76 SSc and 70 SLE subjects were eligible for this study, mean age 51.9 ± 13.1 and 46.5 ± 12.7 years (p = 0.11), with median disease duration 6.0 and 8.5 years (p = 0.15), respectively. As compared to SLE, patients with SSc were characterised by more frequent incidence of various supraventricular and ventricular arrhythmias. As compared to SSc, patients with SLE presented prolonged corrected QT intervals and also significant correlations between corrected QT length and heart rate variability indices. Both SSc and SLE subjects presented impaired sympathetic cardiac autonomic modulation, while indices associated with parasympathetic activity in SLE were not diminished. Disease duration was not associated with arrhythmias' occurrence (except for ventricular tachycardia in SSc, p = 0.02) and also with autonomic function in both groups of patients. Patients with SSc and SLE differ in terms of arrhythmias, conduction disturbances and cardiac autonomic tone. Regular Holter monitoring should be considered as a part of routine evaluation in connective tissue diseases patients, especially in systemic sclerosis.

Social environment as a factor affecting exploration and learning in pre-juvenile rats.

Stress associated with social isolation in early life can lead to disturbances in the emotional regulation in adult rats. However, there are no reports on the impact of isolation from the mother while providing contact with peers. Under such conditions, young individuals have the opportunity to interact with others, are able to develop social behaviour, etc. Yet, there is no stimulation and care provided by the mother. We examined the relative impact of maternal contact and sibling contact in the rarely studied pre-juvenile (3rd and 4th week post birth) period on subsequent development. An experiment was designed to compare the impact of different social environments on the animals' behaviour in adulthood. There were three breeding conditions: young with mother, young with peers, and standard breeding conditions. Adult rats were subjected to a T-Maze test to measure the level of exploratory behaviour. Spatial learning was assessed by placing water bottles in the side corridors. The analysis revealed that a distorted environment during the development process has a negative impact on the rats' emotional regulation and a subtle effect on related aspects of adaptive behaviours (i.e. exploration). In the pre-juvenile period, to some degree, contact with peers may be complementary to the mother's influence.

Higher visuo-Attentional Demands of Multiple Object Tracking (MOT) Lead to A Lower Precision in Pointing Movements.

Multiple object tracking (MOT) requires visually attending to dynamically moving targets and distractors. This cognitive ability is based on perceptual-attentional processes that are also involved in goal-directed movements. This study aimed to test the hypothesis that MOT affects the motor performance of aiming movements. Therefore, the participants performed pointing movements using their fingers or a computer mouse that controlled the movements of a cursor directed at the targets in the MOT task. The precision of the pointing movements was measured, and it was predicted that a higher number of targets and distractors in the MOT task would result in a lower pointing precision. The results confirmed this hypothesis, indicating that MOT might influence the performance of motor actions. The potential factors underlying this influence are discussed.