A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia During COVID-19.

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and following inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational in vitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen levels generated in vivo. Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. In analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection compared to young animals. To investigate oxygen levels during a respiratory viral infection, we intratracheally infected nine aged (3-year-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2 infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days post infection (dpi). SARS-CoV-2 infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen levels in lung tissue. At 4 dpi, oxygen levels in lung tissue were significantly lower (mean %O2 of 3.89 ≙ ≈ 27.78 mmHg) compared to the negative control group (mean %O2 of 8.65 ≙ ≈ 61.4 mmHg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). .

Anaesthetic-sparing effect of the anxiolytic drug tasipimidine in Beagle dogs.

OBJECTIVE: To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia. STUDY DESIGN: Placebo-controlled, randomized, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months. METHODS: The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 µg kg-1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 µg kg-1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg-1 IV. TMPD: tasipimidine 30 µg kg-1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by a dexmedetomidine constant rate infusion of 1 µg kg-1 hour-1. Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MACNM) were determined. A mixed-model analysis or the Friedman and Mann-Whitney test were used; p-value < 0.05. RESULTS: Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MACNM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MACNM was reduced by 35%. CONCLUSIONS AND CLINICAL RELEVANCE: An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan.

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs.

OBJECTIVE: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. STUDY DESIGN: Prospective, placebo-controlled, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. METHODS: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 µg kg-1 orally and placebo IV; TMP: tasipimidine 30 µg kg-1 orally and methadone 0.2 mg kg-1 IV; and TMPD: tasipimidine 30 µg kg-1 orally with methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by 1 µg kg-1 hour-1. Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. RESULTS: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

Case studies in neuroscience: reversible signatures of edema following electric and piezoelectric craniotomy drilling in macaques.

In vivo electrophysiology requires direct access to brain tissue, necessitating the development and refinement of surgical procedures and techniques that promote the health and well-being of animal subjects. Here, we report a series of findings noted on structural magnetic resonance imaging (MRI) scans in monkeys with MRI-compatible implants following small craniotomies that provide access for intracranial electrophysiology. We found distinct brain regions exhibiting hyperintensities in T2-weighted scans that were prominent underneath the sites at which craniotomies had been performed. We interpreted these hyperintensities as edema of the neural tissue and found that they were predominantly present following electric and piezoelectric drilling, but not when manual, hand-operated drills were used. Furthermore, the anomalies subsided within 2-3 wk following surgery. Our report highlights the utility of MRI-compatible implants that promote clinical examination of the animal's brain, sometimes revealing findings that may go unnoticed when incompatible implants are used. We show replicable differences in outcome when using electric versus mechanical devices, both ubiquitous in the field. If electric drills are used, our report cautions against electrophysiological recordings from tissue directly underneath the craniotomy for the first 2-3 wk following the procedure due to putative edema.NEW & NOTEWORTHY Close examination of structural MRI in eight nonhuman primates following craniotomy surgeries for intracranial electrophysiology highlights a prevalence of hyperintensities on T2-weighted scans following surgeries conducted using electric and piezoelectric drills, but not when using mechanical, hand-operated drills. We interpret these anomalies as edema of neural tissue that resolved 2-3 wk postsurgery. This finding is especially of interest as electrophysiological recordings from compromised tissue may directly influence the integrity of collected data immediately following surgery.

Attentional sampling of visual and auditory objects is captured by theta-modulated neural activity.

Recent evidence suggests that visual attention alternately samples two behaviourally relevant objects at approximately 4 Hz, rhythmically shifting between the objects. Whether similar attentional rhythms exist in other sensory modalities, however, is not yet clear. We therefore adapted and extended an established paradigm to investigate visual and potential auditory attentional rhythms, as well as possible interactions, on both a behavioural (detection performance, N = 33) and a neural level (EEG, N = 18). The results during unimodal attention demonstrate that both visual- and auditory-target detection fluctuate at frequencies of approximately 4-8 Hz, confirming that attentional rhythms are not specific to visual processing. The EEG recordings provided evidence of oscillatory activity that underlies these behavioural effects. At right and left occipital EEG electrodes, we detected counter-phasic theta-band activity (4-8 Hz), mirroring behavioural evidence of alternating sampling between the objects presented right and left of central fixation, respectively. Similarly, alpha-band activity as a signature of relatively suppressed sensory encoding showed a theta-rhythmic, counter-phasic change in power. Moreover, these theta-rhythmic changes in alpha power were predictive of behavioural performance in both sensory modalities. Overall, the present findings provide a new perspective on the multimodal rhythmicity of attention.

Neural Basis of Biased Competition in Development: Sensory Competition in Visual Cortex of School-Aged Children.

The fundamental receptive field (RF) architecture in human visual cortex becomes adult-like by age 5. However, visuo-spatial functions continue to develop until teenage years. This suggests that, despite the early maturation of the RF structure, functional interactions within and across RFs may mature slowly. Here, we used fMRI to investigate functional interactions among multiple stimuli in the visual cortex of school children (ages 8 to 12) in the context of biased competition theory. In the adult visual system, multiple objects presented in the same visual field compete for neural representation. These competitive interactions occur at the level of the RF and are therefore closely linked to the RF architecture. Like in adults, we found suppression of evoked responses in children's visual cortex when multiple stimuli were presented simultaneously. Such suppression effects were modulated by the spatial distance between the stimuli as a function of RF size across the visual system. Our findings suggest that basic competitive interactions in the visual cortex of children above age 8 operate in an adult-like manner, with subtle differences in early visual areas and area MT. Our study establishes a paradigm and provides baseline data to investigate the neural basis of visuo-spatial processing in typical and atypical development.

Nasal and tracheobronchial nitric oxide production and its influence on oxygenation in horses undergoing total intravenous anaesthesia.

BACKGROUND: The present study aimed to investigate the effect of endotracheal intubation on nasal and tracheal endogenous NO concentrations, gas exchange and oxygenation in horses undergoing general anaesthesia. In many species a major part of physiological nitric oxide (NO) production takes place in the nasopharynx. Inhaled NO acts as a pulmonary vasodilator and regulates lung perfusion and endotracheal intubation bypasses the nasopharynx. Six horses were randomly assigned to either the "intubated" (INT) or the "non-intubated" (nINT) treatment group. Horses were premedicated with dexmedetomidine (5 µg/kg IV). Anaesthesia was induced with 2.5 mg/kg ketamine and 0.05 mg/kg diazepam IV, and it was maintained by administration of a triple-drip (100 mg/kg/h guaifenesin, 4 mg/kg/h ketamine, 7 µg/kg/h dexmedetomidine). The horses were spontaneously breathing room air. Heart rate, cardiac output, arterial blood pressure, pulmonary arterial blood pressures and respiratory rate were recorded during a 100-min anaesthesia period. Arterial, venous and mixed venous blood samples were taken every 10 minutes and analysed for partial pressure of oxygen (PO2) and carbon dioxide (PCO2), oxygen saturation and haemoglobin content. Standard oxygenation indices were calculated. Nasal and tracheal endogenous NO concentration was determined by chemiluminescence. RESULTS: Cardiovascular variables, respiratory rate, PO2, PCO2, oxygen saturation, haemoglobin content, CaO2, O2ER, P(a-ET)CO2 and Qs/Qt did not differ significantly between the two treatment groups. The P(A-a)O2 was significantly higher in INT (6.1 ± 0.3 kPa) compared to nINT (4.9 ± 0.1 kPa) (p = 0.045), respectively. The nasal (8.0 ± 6.2 ppb) and tracheal (13.0 ± 6.3 ppb) endogenous NO concentration differed significantly in INT (p = 0.036), but not in nINT (nasal: 16.9 ± 9.0 ppb; tracheal: 18.5 ± 9.5 ppb) (p = 0.215). CONCLUSION: Endotracheal intubation reduces the nasal and tracheal endogenous NO concentration. The influence on pulmonary gas exchange and oxygenation is negligible in horses breathing room air.

Clinical effect of buprenorphine or butorphanol, in combination with detomidine and diazepam, on sedation and postoperative pain after cheek tooth extraction in horses.

The objective of this study was to compare effects of butorphanol (BUT) or buprenorphine (BUP), in combination with detomidine and diazepam, on the sedation quality, surgical conditions, and postoperative pain control after cheek tooth extraction in horses, randomly allocated to 2 treatment groups (BUT: n = 20; BUP: n = 20). A bolus of detomidine (15 µg/kg, IV) was followed by either BUP (7.5 µg/kg, IV) or BUT (0.05 mg/kg, IV). After 20 min, diazepam (0.01 mg/kg, IV) was administered and sedation was maintained with a detomidine IV infusion (20 µg/kg/h), with rate adjusted based on scores to 5 variables. All horses received a nerve block (maxillary or mandibular), and gingival infiltration with mepivacaine. Sedation quality was assessed by the surgeon from 1 (excellent) to 10 (surgery not feasible). A pain scoring system (EQUUS-FAP) was used to assess postoperative pain. Serum cortisol concentrations and locomotor activity (pedometers) were measured. Horses in BUP and BUT required a median detomidine infusion rate of 30.2 µg/kg/h (20 to 74.4 µg/kg/h) and 32.2 µg/kg/h (20 to 48.1 µg/kg/h), respectively (P = 0.22). Horses in the BUP group had better sedation quality (P < 0.05) during surgery and higher step counts (P < 0.001) postoperatively. Buprenorphine combined with detomidine provided a more reliable sedation than butorphanol. However, the EQUUS-FAP pain scale became unreliable because of BUP-induced excitement behavior.

Effet clinique de la buprénorphine ou du butorphanol, en association avec la détomidine et le diazépam, sur la sédation et la douleur postopératoire après extraction de dents jugales chez le cheval. L'objectif de cette étude était de comparer les effets du butorphanol (BUT) ou de la buprénorphine (BUP), en association avec la détomidine et le diazépam, sur la qualité de la sédation, les conditions chirurgicales et la gestion de la douleur postopératoire après extraction des dents jugales chez les chevaux, répartis au hasard dans deux groupes de traitement (BUT : n = 20; BUP : n = 20). Un bolus de détomidine (15 µg/kg, IV) a été suivi soit de BUP (7,5 µg/kg, IV) soit de BUT (0,05 mg/kg, IV). Après 20 min, du diazépam (0,01 mg/kg, IV) a été administré et la sédation a été maintenue avec une perfusion IV de détomidine (20 µg/kg/h), avec un taux ajusté en fonction des scores de cinq variables. Tous les chevaux ont reçu un bloc nerveux (maxillaire ou mandibulaire) et une infiltration gingivale avec de la mépivacaïne. La qualité de la sédation a été évaluée par le chirurgien de 1 (excellent) à 10 (chirurgie impossible). Un système de notation de la douleur (EQUUS-FAP) a été utilisé pour évaluer la douleur postopératoire. Les concentrations sériques de cortisol et l'activité locomotrice (podomètres) ont été mesurées.Les chevaux en BUP et BUT ont nécessité un débit médian de perfusion de détomidine de 30,2 µg/kg/h (20 à 74,4 µg/kg/h) et 32,2 µg/kg/h (20 à 48,1 µg/kg/h), respectivement (P = 0,22). Les chevaux du groupe BUP avaient une meilleure qualité de sédation (P < 0,05) pendant la chirurgie et un nombre de pas plus élevé (P < 0,001) après l'opération. La buprénorphine associée à la détomidine a fourni une sédation plus fiable que le butorphanol. Cependant, l'échelle de douleur EQUUS-FAP est devenue peu fiable en raison du comportement d'excitation induit par le BUP.(Traduit par Dr Serge Messier).

Overlapping Neuronal Population Responses in the Human Parietal Cortex during Visuospatial Attention and Arithmetic Processing.

Engagement of posterior parietal cortex (PPC) in visuospatial attention and arithmetic processing has been extensively documented using neuroimaging methods. Numerous studies have suggested a close connection between visuospatial attention and arithmetic processing. However, the extant evidence in humans stems from neuroimaging methods that have relied on group analyses without much knowledge about the profile of neurophysiological engagement within localized neuronal populations at the individual brain level. Hence, it has remained unclear if the overlap of two functions in the PPC is the product of averaging, or they truly stem from a common profile of activity within the same neuronal populations in the human PPC. In the current study, we leveraged the anatomical precision and high signal-to-noise ratio of intracranial electrocorticography and probed the engagement of discrete PPC neuronal populations in seven neurosurgical patients (n = 179 total PPC sites covered; 26 sites on average per individual participant). We aimed to study the extent of parietal activations within each individual brain during visuospatial attention versus arithmetic tasks and the profile of electrophysiological responses within a given recording site during these tasks. Our findings indicated that about 40% of PPC sites did not respond to either visuospatial attention or arithmetic stimuli-or episodic memory conditions that were used as an adjunct control condition. Of those that were activated during either visuospatial attention or arithmetic conditions, a large majority showed overlapping responses during both visuospatial attention and arithmetic conditions. Most interestingly, responses during arithmetic processing were greatest in sites along the intraparietal sulcus region showing preference to contralateral, instead of ipsilateral, visual probes in the visuospatial attention task. Our results provide novel data about the relationship between numerical and spatial orientation at the neuronal population level and shed light on the complex functional organization of the PPC that could not be attained with noninvasive methods.

International primate neuroscience research regulation, public engagement and transparency opportunities.

Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care ("culture of care") and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research.

In vivo oxygen measurement in cerebrospinal fluid of pigs to determine physiologic and pathophysiologic oxygen values during CNS infections.

During infection and inflammation, a reduced oxygen level clearly affects cellular functions. Oxygen levels during CNS infections are unknown. Here we established and evaluated an in vivo measurement system to characterize the oxygen level in parallel with bacterial numbers (CFU/mL), the cell number and pH level inside the CSF of healthy compared to Streptococcus suis-infected pigs. The animals were anesthetized over a seven-hour period with isoflurane in air/oxygen at physiologic arterial partial pressure of oxygen. Oxygen levels in CSF of anesthetized pigs were compared to euthanized pigs. The detected partial pressure of oxygen in the CSF remained constant in a range of 47-63 mmHg, independent of the infection status (bacterial or cell number). In contrast, the pH value showed a slight drop during infection, which correlated with cell and bacterial number in CSF. We present physiologic oxygen and pH values in CSF during the onset of bacterial meningitis.

Development of spatial biases in school-aged children.

In the adult brain, biases in the allocation of spatial attention can be measured using a line bisection task and are directly relatable to neural attention signals in the fronto-parietal attention network. Behavioral studies on the development of spatial biases have yielded a host of inconsistent results, likely due to variance in sample size, definition of experimental groups, and motor confounds introduced by using a paper-and-pencil version of a line bisection task. Here, we used a perceptual, computerized version of this task and examined the development of spatial biases in 459 children from grades 1-8 and 61 college freshmen. We found that children in early elementary grades exerted a significant leftward bias that gradually diminished with advancing grade level. We further show that among children in early elementary school grades, the degree of leftward spatial bias predicted better performance on a rapid automatized naming test, a predictor of reading ability. Significant leftward biases in early elementary school grades may be due to reading experience, thereby reflecting an interaction of the attention network with the evolving reading network.

Functional Specialization in the Attention Network.

Spatial attention is comprised of neural mechanisms that boost sensory processing at a behaviorally relevant location while filtering out competing information. The present review examines functional specialization in the network of brain regions that directs such preferential processing. This attention network includes both cortical (e.g., frontal and parietal cortices) and subcortical (e.g., the superior colliculus and the pulvinar nucleus of the thalamus) structures. Here, we piece together existing evidence that these various nodes of the attention network have dissociable functional roles by synthesizing results from electrophysiology and neuroimaging studies. We describe functional specialization across several dimensions (e.g., at different processing stages and within different behavioral contexts), while focusing on spatial attention as a dynamic process that unfolds over time. Functional contributions from each node of the attention network can change on a moment-to-moment timescale, providing the necessary cognitive flexibility for sampling from highly dynamic environments.

Ischaemic postconditioning reduces apoptosis in experimental jejunal ischaemia in horses.

BACKGROUND: Ischaemic postconditioning (IPoC) refers to brief periods of reocclusion of blood supply following an ischaemic event. This has been shown to ameliorate ischaemia reperfusion injury in different tissues, and it may represent a feasible therapeutic strategy for ischaemia reperfusion injury following strangulating small intestinal lesions in horses. The objective of this study was to assess the degree cell death, inflammation, oxidative stress, and heat shock response in an equine experimental jejunal ischaemia model with and without IPoC. METHODS: In this randomized, controlled, experimental in vivo study, 14 horses were evenly assigned to a control group and a group subjected to IPoC. Under general anaesthesia, segmental ischaemia with arterial and venous occlusion was induced in 1.5 m jejunum. Following ischaemia, the mesenteric vessels were repeatedly re-occluded in group IPoC only. Full thickness intestinal samples and blood samples were taken at the end of the pre-ischaemia period, after ischaemia, and after 120 min of reperfusion. Immunohistochemical staining or enzymatic assays were performed to determine the selected variables. RESULTS: The mucosal cleaved-caspase-3 and TUNEL cell counts were significantly increased after reperfusion in the control group only. The cleaved-caspase-3 cell count was significantly lower in group IPoC after reperfusion compared to the control group. After reperfusion, the tissue myeloperoxidase activity and the calprotectin positive cell counts in the mucosa were increased in both groups, and only group IPoC showed a significant increase in the serosa. Tissue malondialdehyde and superoxide dismutase as well as blood lactate levels showed significant progression during ischaemia or reperfusion. The nuclear immunoreactivity of Heat shock protein-70 increased significantly during reperfusion. None of these variables differed between the groups. The neuronal cell counts in the myenteric plexus ganglia were not affected by the ischaemia model. CONCLUSIONS: A reduced apoptotic cell count was found in the group subjected to IPoC. None of the other tested variables were significantly affected by IPoC. Therefore, the clinical relevance and possible protective mechanism of IPoC in equine intestinal ischaemia remains unclear. Further research on the mechanism of action and its effect in clinical cases of strangulating colic is needed.

Pharmacodynamics and plasma concentrations of dexmedetomidine with or without vatinoxan as a constant-rate infusion in horses anaesthetized with isoflurane-A pilot study.

The aim was to determine the effects of vatinoxan on dexmedetomidine plasma concentrations and effects on cardiovascular and intestinal tissue pharmacodynamics. In a prospective randomized study, six horses were premedicated intravenously with dexmedetomidine 3.5 µg kg-1 followed by a constant-rate infusion of 7 µg kg-1  h-1 (group DEX) and six horses with dexmedetomidine of the same dose (bolus and constant-rate infusion) combined with vatinoxan 130 µg kg-1 followed by 40 µg kg-1  h-1 (group VAT). Anaesthesia was induced with ketamine and diazepam and maintained with isoflurane. Venous blood samples were withdrawn before and at predefined points in time after drug application. During sedation and anaesthesia, cardiopulmonary variables, gastrointestinal tissue perfusion and oxygenation were recorded. Data were analysed using two-way-ANOVA, unpaired-t-test and Dunnett's-t-test (p < 0.05). Group VAT had significantly higher oxygen delivery and lower oxygen extraction ratio, venous admixture, alveolar dead space and alveolar-arterial-oxygen difference. Tissue perfusion of buccal mucosa was reduced during anaesthesia in group DEX. Plasma concentrations of dexmedetomidine in group VAT (n = 6) and group DEX (n = 5) were comparable between groups. In the present pilot study, co-administration of vatinoxan with dexmedetomidine did not alter plasma concentrations of dexmedetomidine but ameliorated tissue perfusion and global oxygenation variables.

Temporal Dynamics and Response Modulation across the Human Visual System in a Spatial Attention Task: An ECoG Study.

The selection of behaviorally relevant information from cluttered visual scenes (often referred to as "attention") is mediated by a cortical large-scale network consisting of areas in occipital, temporal, parietal, and frontal cortex that is organized into a functional hierarchy of feedforward and feedback pathways. In the human brain, little is known about the temporal dynamics of attentional processing from studies at the mesoscopic level of electrocorticography (ECoG), that combines millisecond temporal resolution with precise anatomical localization of recording sites. We analyzed high-frequency broadband responses (HFB) responses from 626 electrodes implanted in 8 epilepsy patients who performed a spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system. HFB responses showed high spatial selectivity and tuning, constituting ECoG response fields (RFs), within and outside the topographic visual system. In accordance with monkey physiology studies, both RF widths and onset latencies increased systematically across the visual processing hierarchy. We used the spatial specificity of HFB responses to quantitatively study spatial attention effects and their temporal dynamics to probe a hierarchical top-down model suggesting that feedback signals back propagate the visual processing hierarchy. Consistent with such a model, the strengths of attentional modulation were found to be greater and modulation latencies to be shorter in posterior parietal cortex, middle temporal cortex and ventral extrastriate cortex compared with early visual cortex. However, inconsistent with such a model, attention effects were weaker and more delayed in anterior parietal and frontal cortex.SIGNIFICANCE STATEMENT In the human brain, visual attention has been predominantly studied using methods with high spatial, but poor temporal resolution such as fMRI, or high temporal, but poor spatial resolution such as EEG/MEG. Here, we investigate temporal dynamics and attention effects across the human visual system at a mesoscopic level that combines precise spatial and temporal measurements by using electrocorticography in epilepsy patients performing a classical spatial attention task. Electrode locations were reconstructed using a probabilistic atlas of the human visual system, thereby relating them to topography and processing hierarchy. We demonstrate regional differences in temporal dynamics across the attention network. Our findings do not fully support a top-down model that promotes influences on visual cortex by reversing the processing hierarchy.

Effects of isoflurane, remifentanil and dexmedetomidine on selected EEG parameters derived from a Narcotrend Monitor before and after nociceptive stimulation at different MAC multiples in cats.

BACKGROUND: The aim of this prospective and complete cross-over study was to evaluate the effects of isoflurane, remifentanil and dexmedetomidine on EEG parameters derived from the Narcotrend® Monitor before and after nociceptive stimulation at different isoflurane MAC (minimal alveolar concentration) multiples. Seven adult European Domestic Short Hair cats were used. Each cat went through 3 experimental treatments. Group I received isoflurane, group IR received isoflurane and a constant rate infusion (CRI) of remifentanil (18 µg/kg/h IV), and group ID received isoflurane and a CRI of dexmedetomidine (3 µg/kg/h IV). The isoflurane MAC in each group was determined via supramaximal electrical stimulation. The EEG parameters were derived by a Narcotrend Monitor at specific time points before and after nociceptive stimulation at 0.75, 1.0 and 1.5 MAC. The depth of anaesthesia was also assessed by a clinical score. RESULTS: The mean MAC sparing effects in group IR and group ID were 9.8 and 55.2%, respectively. The best correlation of EEG and MAC multiples was found for the Narcotrend Index (NI) in group I (r = - 0.67). The NI was also able to differentiate between 0.75 MAC and 1.5 MAC in group IR. Spectral edge frequency had a lower correlation with MAC multiples in group I (r = - 0.62) but was able to differentiate between 0.75 MAC and 1.5 MAC in groups I and IR, and between 1.0 MAC and 1.5 MAC in group IR. Narcotrend Index, SEF 95 and MF increased significantly after nociceptive stimulation at 1.0 MAC in group I, and SEF 95 increased significantly at 0.75 MAC in group ID. The clinical score correlated closer than any of the EEG parameters with MAC in all groups, with highest correlation values in group I (r = - 0.89). Noxious stimulation led to a significant increase of the clinical score at 0.75 MAC and 1.0 MAC in group I. CONCLUSIONS: The EEG parameters derived from the Narcotrend Monitor show correlation to isoflurane MAC multiples in cats, but the anaesthetic protocol and especially the addition of dexmedetomidine have great influence on the reliability. The Narcotrend Monitor can be used as an additional tool to assess anesthetic depth in cats.

Comparison between head-tail-rope assisted and unassisted recoveries in healthy horses undergoing general anesthesia for elective surgeries.

OBJECTIVE: To compare attempts to stand, duration, quality, and occurrence of injuries between head-tail rope assistance and unassisted recoveries in healthy horses undergoing general anesthesia for elective surgeries. STUDY DESIGN: Randomized, prospective, clinical trial. METHODS: Three hundred one healthy horses undergoing elective surgeries were randomly assigned to recover with head-tail rope assistance (group A) or unassisted (group U); 305 recoveries (group A, n = 154; group U, n = 151) were analyzed. Anesthesia was maintained with isoflurane and triple drip. For each recovery, attempts to stand, duration, quality, and recovery-associated injuries were recorded. Data were analyzed by linear regression and analysis of covariance. RESULTS: Anesthesia duration was similar between groups (mean ± SD, 70 ± 29 minutes). Compared with group U, group A had fewer attempts to stand (median [range], group A = 1 [1-7] vs group U = 3 [1-34]) and shorter duration of recovery (mean ± SD, A = 36 ± 12 minutes vs U = 41 ± 15 minutes). Recovery quality in group A (28 points [15-70]) was better than that in group U (38 points [11-87]). More horses had recovery-associated injuries in group U (9 horses) compared with group A (2 horses). One horse per group was euthanized. CONCLUSION: Head-tail rope assistance reduced standing attempts, shortened recovery duration, improved recovery quality, and reduced recovery-associated minor injuries after general anesthesia for elective surgery in healthy horses. Fatalities could not be prevented. CLINICAL SIGNIFICANCE: Head-tail rope assistance may improve recovery in healthy horses after short-duration elective surgeries with isoflurane and triple drip.