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In neuroscience, numerous experimental procedures in animal models require surgical interventions, such as the implantation of recording electrodes or cannulas before main experiments. These surgeries can take several hours and should rely on principles that are common in the field of research and medicine. Considering the characteristics of the avian respiratory physiology, the development of a safe and replicable protocol for birds is necessary to minimize side effects of anesthetic agents, circumvent technical limitations due to the insufficient availability of patient monitoring, and to maintain stable intraoperative anesthesia. Through the consistent and responsible implementation of the three R principle of animal welfare in science (“Replace, Reduce, Refine”), we aimed to optimize experimental methods to minimize the burden on pigeons (Columba livia) during surgical procedures. Here, surgeries were conducted under balanced anesthesia and perioperative monitoring of heart rate, oxygen saturation, body temperature, and the reflex state. The protocol we developed is based on the combination of injectable and inhalative anesthetic drugs [ketamine, xylazine, and isoflurane, supported by the application of an opiate for analgesia (e.g., butorphanol, buprenorphine)]. The combination of ketamine and xylazine with a pain killer is established in veterinary medicine across a vast variety of species. Practicability was verified by survival of the animals, fast and smooth recovery quantified by clinical examination, sufficiency, and stability of anesthesia. Independent of painful stimuli like incision or drilling, or duration of surgery, vital parameters were within known physiological ranges for pigeons. Our approach provides a safe and conservative protocol for surgeries of extended duration for scientific applications as well as for veterinary medicine in pigeons which can be adapted to other bird species.

In order to continuously monitor the intensity and position of an electron beam of a few hundred pA, a system of resonant cavities has been set up. The current measurement relies on signals of a few fW power extracted out of a cylindrical resonator, excited at its TM_{010} mode. The demodulated cavity pickup signal allows the reconstruction of the beam current with a precision of a few pA. For beam position measurements, we designed two resonators, one each for the horizontal and vertical plane. They are excited at their TM_{110} dipole modes, the signal strength vanishing with the beam passing on their symmetry axis. Commercial digital lock-in amplifiers perform a phase-sensitive detection of the position signals, separating them from background noise. A frequency mixing scheme was applied to transform the signals into the passband of the amplifiers. Great care was taken to prevent cross talk by using special shielding. With these techniques, a relative beam position resolution of 50 μm was achieved. The position readings are sampled with a maximum rate of 9 Hz. A standard PC is used to read out the lock-in amplifiers. It transfers the measured raw data as well as processed values to the accelerator control system for graphical display.

In neuroscience, numerous experimental procedures in animal models require surgical interventions, such as the implantation of recording electrodes or cannulas before main experiments. These surgeries can take several hours and should rely on principles that are common in the field of research and medicine. Considering the characteristics of the avian respiratory physiology, the development of a safe and replicable protocol for birds is necessary to minimize side effects of anesthetic agents, circumvent technical limitations due to the insufficient availability of patient monitoring, and to maintain stable intraoperative anesthesia. Through the consistent and responsible implementation of the three R principle of animal welfare in science ("Replace, Reduce, Refine"), we aimed to optimize experimental methods to minimize the burden on pigeons ( Columba livia ) during surgical procedures. Here, surgeries were conducted under balanced anesthesia and perioperative monitoring of heart rate, oxygen saturation, body temperature, and the reflex state. The protocol we developed is based on the combination of injectable and inhalative anesthetic drugs [ketamine, xylazine, and isoflurane, supported by the application of an opiate for analgesia (e.g., butorphanol, buprenorphine)]. The combination of ketamine and xylazine with a pain killer is established in veterinary medicine across a vast variety of species. Practicability was verified by survival of the animals, fast and smooth recovery quantified by clinical examination, sufficiency, and stability of anesthesia. Independent of painful stimuli like incision or drilling, or duration of surgery, vital parameters were within known physiological ranges for pigeons. Our approach provides a safe and conservative protocol for surgeries of extended duration for scientific applications as well as for veterinary medicine in pigeons which can be adapted to other bird species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Serir, Tuff, Rook, Fongaro, Schreiber, Peus, Güntürkün, Manahan-Vaughan, Rose and Pusch.)

Many cognitive neuroscientists believe that both a large brain and an isocortex are crucial for complex cognition. Yet corvids and parrots possess non-cortical brains of just 1-25 g, and these birds exhibit cognitive abilities comparable with those of great apes such as chimpanzees, which have brains of about 400 g. This opinion explores how this cognitive equivalence is possible. We propose four features that may be required for complex cognition: a large number of associative pallial neurons, a prefrontal cortex (PFC)-like area, a dense dopaminergic innervation of association areas, and dynamic neurophysiological fundaments for working memory. These four neural features have convergently evolved and may therefore represent 'hard to replace' mechanisms enabling complex cognition., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Working memory is the cognitive capability to maintain and process information over short periods. Behavioral and computational studies have shown that visual information is associated with working memory performance. However, the underlying neural correlates remain unknown. To identify how visual information affects working memory performance, we conducted behavioral experiments in pigeons (Columba livia) and single unit recordings in the avian prefrontal analog, the nidopallium caudolaterale (NCL). Complex pictures featuring luminance, spatial and color information, were associated with higher working memory performance compared to uniform gray pictures in conjunction with distinct neural coding patterns. For complex pictures, we found a multiplexed neuronal code displaying visual and value-related features that switched to a representation of the upcoming choice during a delay period. When processing gray stimuli, NCL neurons did not multiplex and exclusively represented the choice already during stimulus presentation and throughout the delay period. The prolonged representation possibly resulted in a decay of the memory trace ultimately leading to a decrease in performance. In conclusion, we found that high stimulus complexity is associated with neuronal multiplexing of the working memory representation possibly allowing a facilitated read-out of the neural code resulting in enhancement of working memory performance., (© 2023. The Author(s).)

Purpose: Pathogenic fusion events involving neurotrophic receptor tyrosine kinase (NTRK) have been described in ~ 2% of differentiated thyroid cancer (DTC). The selective tropomyosin receptor kinase (TRK) inhibitors entrectinib and larotrectinib have been approved in a tumor agnostic manner based on phase 1/2 clinical trials. In a real-world setting at five referral centers, we aimed to describe the prevalence of NTRK gene fusions and the efficacy and safety of TRK inhibitor treatment for non-medullary, advanced thyroid cancer (TC)., Methods: A total of 184 TC patients with testing for NTRK gene fusions were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method in six patients with NTRK fusion-positive TC who underwent TRK inhibitor therapy., Results: 8/184 (4%) patients harbored NTRK gene fusions. Six patients with radioiodine (RAI)-refractory TC harboring NTRK1 (n = 4) and NTRK3 (n = 2) gene fusions were treated with larotrectinib. Five patients (83%) had received ≥ 1 prior systemic therapy and one patient did not receive prior systemic therapy. All patients had morphologically progressive disease before treatment initiation. Objective response rate was 83%, including two complete remissions. Median PFS from start of TRK inhibitor treatment was 23 months (95% confidence interval [CI], 0-57.4) and median OS was not reached (NR) (95% CI, NR). Adverse events were of grade 1-3., Conclusion: The prevalence of NTRK gene fusions in our cohort of RAI-refractory TC is slightly higher than reported for all TC patients. Larotrectinib is an effective treatment option in the majority of NTRK gene fusion-positive advanced TC patients after prior systemic treatment and has a favorable safety profile., (© 2023. The Author(s).)

Birds are excellent model organisms to study perceptual categorization and concept formation. The renewed focus on avian neuroscience has sparked an explosion of new data in the field. At the same time, our understanding of sensory and particularly visual structures in the avian brain has shifted fundamentally. These recent discoveries have revealed how categorization is mediated in the avian brain and has generated a theoretical framework that goes beyond the realm of birds. We review the contribution of avian categorization research-at the methodical, behavioral, and neurobiological levels. To this end, we first introduce avian categorization from a behavioral perspective and the common elements model of categorization. Second, we describe the functional and structural organization of the avian visual system, followed by an overview of recent anatomical discoveries and the new perspective on the avian 'visual cortex'. Third, we focus on the neurocomputational basis of perceptual categorization in the bird's visual system. Fourth, an overview of the avian prefrontal cortex and the prefrontal contribution to perceptual categorization is provided. The fifth section outlines how asymmetries of the visual system contribute to categorization. Finally, we present a mechanistic view of the neural principles of avian visual categorization and its putative extension to concept learning., (© 2022. The Author(s).)

In the past 12 months a plethora of relevant novel data for the treatment of metastatic HER2 positive breast cancer were published. To bring this new evidence into a clinical perspective, a group of Austrian breast cancer specialists updated their previously published treatment algorithm for those patients. For this consensus paper a total of eight scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated. Consensus was established by detailed discussions of each scenario and by reaching full consensus., (© 2022. The Author(s).)

Pigeons are classic model animals to study perceptual category learning. To achieve a deeper understanding of the cognitive mechanisms of categorization, a careful consideration of the employed stimulus material and a thorough analysis of the choice behavior is mandatory. In the present study, we combined the use of "virtual phylogenesis", an evolutionary algorithm to generate artificial yet naturalistic stimuli termed digital embryos and a machine learning approach on the pigeons' pecking responses to gain insight into the underlying categorization strategies of the animals. In a forced-choice procedure, pigeons learned to categorize these stimuli and transferred their knowledge successfully to novel exemplars. We used peck tracking to identify where on the stimulus the animals pecked and further investigated whether this behavior was indicative of the pigeon's choice. Going beyond the classical analysis of the binary choice, we were able to predict the presented stimulus class based on pecking location using a k-nearest neighbor classifier, indicating that pecks are related to features of interest. By analyzing error trials with this approach, we further identified potential strategies of the pigeons to discriminate between stimulus classes. These strategies remained stable during category transfer, but differed between individuals indicating that categorization learning is not limited to a single learning strategy., (© 2022. The Author(s).)

Discriminating between object categories (e.g., conspecifics, food, potential predators) is a critical function of the primate and bird visual systems. We examined whether a similar hierarchical organization in the ventral stream that operates for processing faces in monkeys also exists in the avian visual system. We performed electrophysiological recordings from the pigeon Wulst of the thalamofugal pathway, in addition to the entopallium (ENTO) and mesopallium ventrolaterale (MVL) of the tectofugal pathway, while pigeons viewed images of faces, scrambled controls, and sine gratings. A greater proportion of MVL neurons fired to the stimuli, and linear discriminant analysis revealed that the population response of MVL neurons distinguished between the stimuli with greater capacity than ENTO and Wulst neurons. While MVL neurons displayed the greatest response selectivity, in contrast to the primate system no neurons were strongly face-selective and some responded best to the scrambled images. These findings suggest that MVL is primarily involved in processing the local features of images, much like the early visual cortex., (© 2022. The Author(s).)

Cognitive functions are similar in birds and mammals. So, are therefore pallial cellular circuits and neuronal computations also alike? In search of answers, we move in from bird's pallial connectomes, to cortex-like sensory canonical circuits and connections, to forebrain micro-circuitries and finally to the avian "prefrontal" area. This voyage from macro- to micro-scale networks and areas reveals that both birds and mammals evolved similar neural and computational properties in either convergent or parallel manner, based upon circuitries inherited from common ancestry. Thus, these two vertebrate classes evolved separately within 315 million years with highly similar pallial architectures that produce comparable cognitive functions., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Extinction learning, the process of ceasing an acquired behavior in response to altered reinforcement contingencies, is not only essential for survival in a changing environment, but also plays a fundamental role in the treatment of pathological behaviors. During therapy and other forms of training involving extinction, subjects are typically exposed to several sessions with a similar structure. The effects of this repeated exposure are not well understood. Here, we studied the behavior of pigeons across several sessions of a discrimination-learning task in context A, extinction in context B, and a return to context A to test the context-dependent return of the learned responses (ABA renewal). By focusing on individual learning curves across animals, we uncovered a session-dependent variability of behavior: (1) during extinction, pigeons preferred the unrewarded alternative choice in one-third of the sessions, predominantly during the first one. (2) In later sessions, abrupt transitions of behavior at the onset of context B emerged, and (3) the renewal effect decayed as sessions progressed. We show that the observed results can be parsimoniously accounted for by a computational model based only on associative learning between stimuli and actions. Our work thus demonstrates the critical importance of studying the trial-by-trial dynamics of learning in individual sessions, and the power of "simple" associative learning processes., (© 2021. The Author(s).)

Reward prediction errors (RPEs) have been suggested to drive associative learning processes, but their precise temporal dynamics at the single-neuron level remain elusive. Here, we studied the neural correlates of RPEs, focusing on their trial-by-trial dynamics during an operant extinction learning paradigm. Within a single behavioral session, pigeons went through acquisition, extinction and renewal - the context-dependent response recovery after extinction. We recorded single units from the avian prefrontal cortex analogue, the nidopallium caudolaterale (NCL) and found that the omission of reward during extinction led to a peak of population activity that moved backwards in time as trials progressed. The chronological order of these signal changes during the progress of learning was indicative of temporal shifts of RPE signals that started during reward omission and then moved backwards to the presentation of the conditioned stimulus. Switches from operant choices to avoidance behavior (and vice versa) coincided with changes in population activity during the animals' decision-making. On the single unit level, we found more diverse patterns where some neurons' activity correlated with RPE signals whereas others correlated with the absolute value during the outcome period. Finally, we demonstrated that mere sensory contextual changes during the renewal test were sufficient to elicit signals likely associated with RPEs. Thus, RPEs are truly expectancy-driven since they can be elicited by changes in reward expectation, without an actual change in the quality or quantity of reward., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Although optogenetics has revolutionized rodent neuroscience, it is still rarely used in other model organisms as the efficiencies of viral gene transfer differ between species and comprehensive viral transduction studies are rare. However, for comparative research, birds offer valuable model organisms as they have excellent visual and cognitive capabilities. Therefore, the following study establishes optogenetics in pigeons on histological, physiological, and behavioral levels. We show that AAV1 is the most efficient viral vector in various brain regions and leads to extensive anterograde and retrograde ChR2 expression when combined with the CAG promoter. Furthermore, transient optical stimulation of ChR2 expressing cells in the entopallium decreases pigeons' contrast sensitivity during a grayscale discrimination task. This finding demonstrates causal evidence for the involvement of the entopallium in contrast perception as well as a proof of principle for optogenetics in pigeons and provides the groundwork for various other methods that rely on viral gene transfer in birds.

Animal-fMRI is a powerful method to understand neural mechanisms of cognition, but it remains a major challenge to scan actively participating small animals under low-stress conditions. Here, we present an event-related functional MRI platform in awake pigeons using single-shot RARE fMRI to investigate the neural fundaments for visually-guided decision making. We established a head-fixated Go/NoGo paradigm, which the animals quickly learned under low-stress conditions. The animals were motivated by water reward and behavior was assessed by logging mandibulations during the fMRI experiment with close to zero motion artifacts over hundreds of repeats. To achieve optimal results, we characterized the species-specific hemodynamic response function. As a proof-of-principle, we run a color discrimination task and discovered differential neural networks for Go-, NoGo-, and response execution-phases. Our findings open the door to visualize the neural fundaments of perceptual and cognitive functions in birds-a vertebrate class of which some clades are cognitively on par with primates.

In this article, we present PixelClipper, a tool built for facilitating data engagement events. PixelClipper supports conversations around visualizations in public settings through annotation and commenting capabilities. It is recognized that understanding data is important for an informed society. However, even when visualizations are available on the web, open data is not yet reaching all audiences. Public facilitated events centered around data visualizations may help bridge this gap. PixelClipper is designed to promote discussion and engagement with visualizations in public settings. It allows viewers to quickly and expressively extract visual clippings from visualizations and add comments to them. Ambient and facilitator displays attract attention by showing clippings. They function as entry points to the full visualizations while supporting deeper conversations about the visualizations and data. We describe the design goals of PixelClipper, share our experiences from deploying it, and discuss its future potential in supporting data visualization engagement events.