Dissecting unsupervised learning through hidden Markov modeling in electrophysiological data.

Unsupervised, data-driven methods are commonly used in neuroscience to automatically decompose data into interpretable patterns. These patterns differ from one another depending on the assumptions of the models. How these assumptions affect specific data decompositions in practice, however, is often unclear, which hinders model applicability and interpretability. For instance, the hidden Markov model (HMM) automatically detects characteristic, recurring activity patterns (so-called states) from time series data. States are defined by a certain probability distribution, whose state-specific parameters are estimated from the data. But what specific features, from all of those that the data contain, do the states capture? That depends on the choice of probability distribution and on other model hyperparameters. Using both synthetic and real data, we aim to better characterize the behavior of two HMM types that can be applied to electrophysiological data. Specifically, we study which differences in data features (such as frequency, amplitude, or signal-to-noise ratio) are more salient to the models and therefore more likely to drive the state decomposition. Overall, we aim at providing guidance for the appropriate use of this type of analysis on one- or two-channel neural electrophysiological data and an informed interpretation of its results given the characteristics of the data and the purpose of the analysis.NEW & NOTEWORTHY Compared with classical supervised methods, unsupervised methods of analysis have the advantage to be freer of subjective biases. However, it is not always clear what aspects of the data these methods are most sensitive to, which complicates interpretation. Focusing on the hidden Markov model, commonly used to describe electrophysiological data, we explore in detail the nature of its estimates through simulations and real data examples, providing important insights about what to expect from these models.

The role of hippocampal mossy cells in novelty detection.

At the encounter with a novel environment, contextual memory formation is greatly enhanced, accompanied with increased arousal and active exploration. Although this phenomenon has been widely observed in animal and human daily life, how the novelty in the environment is detected and contributes to contextual memory formation has lately started to be unveiled. The hippocampus has been studied for many decades for its largely known roles in encoding spatial memory, and a growing body of evidence indicates a differential involvement of dorsal and ventral hippocampal divisions in novelty detection. In this brief review article, we discuss the recent findings of the role of mossy cells in the ventral hippocampal moiety in novelty detection and put them in perspective with other novelty-related pathways in the hippocampus. We propose a mechanism for novelty-driven memory acquisition in the dentate gyrus by the direct projection of ventral mossy cells to dorsal dentate granule cells. By this projection, the ventral hippocampus sends novelty signals to the dorsal hippocampus, opening a gate for memory encoding in dentate granule cells based on information coming from the entorhinal cortex. We conclude that, contrary to the presently accepted functional independence, the dorsal and ventral hippocampi cooperate to link the novelty and contextual information, and this dorso-ventral interaction is crucial for the novelty-dependent memory formation.

Ventro-dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.

Novelty facilitates memory formation and is detected by both the dorsal and ventral hippocampus. Although dentate granule cells (GCs) in the dorsal hippocampus are known to mediate the formation of novelty-induced contextual memories, the required pathways and mechanisms remain unclear. Here we demonstrate that a powerful excitatory pathway from mossy cells (MCs) in the ventral hippocampus to dorsal GCs is necessary and sufficient for driving dorsal GC activation in novel environment exploration. In vivo Ca2+ imaging in freely moving mice indicated that this pathway relays environmental novelty. Furthermore, manipulation of ventral MC activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MC activity gates contextual memory formation through an intra-hippocampal interaction activated by environmental novelty.

Supraglottoplasty for laryngomalacia: The experience from Concepcion, Chile.

OBJECTIVE: To review the clinical manifestations and outcomes of supraglottoplasty in patients with moderate to severe laryngomalacia at Guillermo Grant Benavente Hospital between January 2015 and January 2017. METHODS: Retrospective study of patients with laryngomalacia who underwent CO2 laser supraglottoplasty at a tertiary referral center. A review of medical records of these patients was performed. Epidemiological data along with symptoms, comorbidities, morphological type of laryngomalacia, synchronous airway lesions, surgery outcomes and satisfaction of parents after the procedure were recorded. Surgical success was defined as the resolution of the criteria of severity of laryngomalacia. RESULTS: Twenty-four patients were operated, 1 was excluded due to prior tracheostomy. Twenty-three patients were included, the median age at the time of surgery was 5.5 months. All the patients had stridor, 87% presented feeding difficulties, 34.8 % had cyanosis and 21.7% had failure to thrive. Six cases had congenital anomalies and four cases had nongenetic comorbidities. Fifteen patients (65.2%) had synchronous airway lesions. 17.4% had type I laryngomalacia and 82.6% were type 2. The postoperative average hospital stay was 1.3 days. The average follow-up was 14 months and no complications were reported. The overall success rate of surgery was 95%. CONCLUSIONS: Patients with laryngomalacia and any symptom of severity should undergo a full airway evaluation, to rule out synchronous airway lesions, and supraglottoplasty if needed, as it has been shown to be a safe and effective technique for the management of these patients.

Nontraumatic Laryngeal Fractures: Report of Two Cases and Review of the Literature.

Laryngeal fractures occur mainly in the context of cervical trauma, hanging, or strangulation. Nontraumatic laryngeal fractures are rare and there are few reports in the literature. We present two cases of nontraumatic laryngeal fractures evaluated in our service.

Endoscopic management of bilateral vocal fold paralysis in newborns and infants.

INTRODUCTION: Bilateral vocal cord paralysis in adducted position (BVCPAd) is a severe cause of airway obstruction and usually debuts with stridor and airway distress necessitating immediate intervention. Tracheostomy has long been the gold standard for treating this condition, but has significant associated morbidity and mortality in pediatric patients. New conservative procedures have emerged to treat this condition thus avoiding tracheostomy, like endoscopic anterior and posterior cricoid split (EAPCS). The objective of this paper was to review our experience with EAPCS in newborns and infants. METHODS: Prospective study involving patients undergoing endoscopic EAPCS for symptomatic BVCPAd. The primary outcomes were tracheostomy avoidance and resolution of airway symptoms. RESULTS: Three patients underwent EAPCS between January 2016 and December 2016. All patients stayed at least 7 days in the Intensive Care Unit (ICU) intubated. All patients presented complete resolution of their symptoms due to airway obstruction, without the need for tracheostomy. CONCLUSION: EAPCS is a novel and effective alternative to treat BVCPAd in patients under 1 year old. Our study is an initial experience; more cases are required to identify the real impact and benefits of this technique and to determine the proper selection of patients.

Visual Outcomes after Endoscopic Pituitary Surgery in Patients Presenting with Preoperative Visual Deficits.

Introduction Pituitary adenomas represent 15% of primary brain tumors. Visual disturbance is a common clinical manifestation of these neoplasms due, among other factors, to local mass effect on the optic system. Objective To evaluate changes of the visual fields in patients undergoing endoscopic endonasal approach (EEA) for pituitary adenomas and to find predictive factors for successful visual field outcome. Material and Methods This is a cross-sectional study. A review was conducted of medical records of consecutive patients with tumors of the sellar region undergoing EEA between January 2008 and December 2012 at the Skull Base Unit of Guillermo Grant Benavente Hospital, University of Concepción, Concepción, Chile, and who had undergone pre- and postoperative visual field evaluation. Results A total of 35 patients, with a mean age of 50.2 years, fulfilled the inclusion criteria. All patients had objective visual field disturbances before the surgery. Following surgery, 25 patients (71.4%) had favorable outcomes, whereas 8 (22.8%) had no change and 2 (5.8%) had an unfavorable outcome. Complete tumor removal was associated with a better visual outcome than those obtained after a subtotal removal. Discussion The EEA for pituitary tumors is particularly effective for visual field disturbances, with reported improvement rates ranging from 50 to 90%. Our series show similar results, with a 71.4% improvement of visual field disturbances. Conclusion This study adds further evidence to the current belief that EEA for pituitary adenomas is a safe and effective technique to improve visual field alterations. Complete removal of the tumor during surgery seems to be a predictive factor for a good visual outcome.

Potential Effect of Leukocyte-Platelet-Rich Fibrin in Bone Healing of Skull Base: A Pilot Study.

BACKGROUND: Reconstruction of surgical defects following cranial base surgery is challenging. Others have demonstrated that leukocyte-platelet-rich fibrin (L-PRF) stimulates tissue healing and bone regeneration. However, these studies have addressed mostly maxillofacial surgical wounds. OBJECTIVE: The objective of this study was to assess the possible adjuvant role of L-PRF in inducing neoossification of the surgical bone defect in anterior skull base surgery. METHODS: We identified patients who had undergone an endoscopic endonasal surgery of the anterior skull base in which L-PRF membranes were used for the reconstruction of the bone defect and who were followed up with postoperative CT scans. CT findings were then correlated with baseline scans and with the CT scans of a patient who had undergone imaging and histologic analysis after maxillofacial surgery in which L-PRF was used and in which we demonstrated bone formation. RESULTS: Five patients fulfilled the inclusion criteria. In four patients, the CT scan demonstrated closure of the bony defect by neoosteogenesis; however, the bone appeared less dense than the surrounding normal bone. A comparison with the control patient yielded similar radiological features. CONCLUSION: This case series suggests that L-PRF may induce bone healing and regeneration at the surgical site defect. Multi-institutional studies with a larger series of patients are required to confirm this possibility.

Spatial organization of the pigeon tectorotundal pathway: an interdigitating topographic arrangement.

The retinotectofugal system is the main visual pathway projecting upon the telencephalon in birds and many other nonmammalian vertebrates. The ascending tectal projection arises exclusively from cells located in layer 13 of the optic tectum and is directed bilaterally toward the thalamic nucleus rotundus. Although previous studies provided evidence that different types of tectal layer 13 cells project to different subdivisions in Rt, apparently without maintaining a retinotopic organization, the detailed spatial organization of this projection remains obscure. We reexamined the pigeon tectorotundal projection using conventional tracing techniques plus a new method devised to perform small deep-brain microinjections of crystalline tracers. We found that discrete injections involving restricted zones within one subdivision retrogradely label a small fraction of layer 13 cells that are distributed throughout the layer, covering most of the tectal representation of the contralateral visual field. Double-tracer injections in one subdivision label distinct but intermingled sets of layer 13 neurons. These results, together with the tracing of tectal axonal terminal fields in the rotundus, lead us to propose a novel "interdigitating" topographic arrangement for the tectorotundal projection, in which intermingled sets of layer 13 cells, presumably of the same particular class and distributed in an organized fashion throughout the surface of the tectum, terminate in separate regions within one subdivision. This spatial organization has significant consequences for the understanding of the physiological and functional properties of the tectofugal pathway in birds.

The mapping of the visual field onto the dorso-lateral tectum of the pigeon (Columba livia) and its relations with retinal specializations.

Most of the physiological studies of the pigeon retino-tectal visual pathway have investigated the accessible tectum, a small dorso-lateral tectal section that can be easily accessed by a simple craniotomy. However, at present we lack a detailed study of the topographical arrangement between the visual field, the retina and the accessible tectum. In particular, it is not known which section of the visual field is mapped onto the accessible tectum, and which of the specialized retinal areas mediates this projection. Here we determined, using local field potential (LFP) recordings and reverse retinoscopy, the shape, size and position in the visual space of the portion of the visual field mapped onto the accessible tectum (called here the accessible visual field, or AVF). Using this data and the mapping of Nalbach et al. [Vis. Res. 30 (4) (1990) 529], the retinal area corresponding to the AVF was determined. Such retinal area was also directly delimited by means of retrograde transport of DiI. The results indicate that the AVF is a triangular perifoveal zone encompassing only 15% of total visual field. The retinal region corresponding to the AVF has the shape of an elongated triangle that runs parallel to the visual equator and contains the fovea, the tip of the pecten, a perifoveal region of the yellow field and a small crescent of the red field. In agreement with this anatomical heterogeneity, visual evoked potentials measured in different parts of the accessible tectum present steep variations in shape and size. These results are helpful to better design and interpret anatomical and physiological experiments involving the pigeon's visual system.

The habenulo-raphe serotonergic circuit encodes an aversive expectation value essential for adaptive active avoidance of danger.

Anticipation of danger at first elicits panic in animals, but later it helps them to avoid the real threat adaptively. In zebrafish, as fish experience more and more danger, neurons in the ventral habenula (vHb) showed tonic increase in the activity to the presented cue and activated serotonergic neurons in the median raphe (MR). This neuronal activity could represent the expectation of a dangerous outcome and be used for comparison with a real outcome when the fish is learning how to escape from a dangerous to a safer environment. Indeed, inhibiting synaptic transmission from vHb to MR impaired adaptive avoidance learning, while panic behavior induced by classical fear conditioning remained intact. Furthermore, artificially triggering this negative outcome expectation signal by optogenetic stimulation of vHb neurons evoked place avoidance behavior. Thus, vHb-MR circuit is essential for representing the level of expected danger and behavioral programming to adaptively avoid potential hazard.

Does nocturnality drive binocular vision? Octodontine rodents as a case study.

Binocular vision is a visual property that allows fine discrimination of in-depth distance (stereopsis), as well as enhanced light and contrast sensitivity. In mammals enhanced binocular vision is structurally associated with a large degree of frontal binocular overlap, the presence of a corresponding retinal specialization containing a fovea or an area centralis, and well-developed ipsilateral retinal projections to the lateral thalamus (GLd). We compared these visual traits in two visually active species of the genus Octodon that exhibit contrasting visual habits: the diurnal Octodon degus, and the nocturnal Octodon lunatus. The O. lunatus visual field has a prominent 100° frontal binocular overlap, much larger than the 50° of overlap found in O. degus. Cells in the retinal ganglion cell layer were 40% fewer in O. lunatus (180,000) than in O. degus (300,000). O. lunatus has a poorly developed visual streak, but a well developed area centralis, located centrally near the optic disk (peak density of 4,352 cells/mm(2)). O. degus has a highly developed visual streak, and an area centralis located more temporally (peak density of 6,384 cells/mm(2)). The volumes of the contralateral GLd and superior colliculus (SC) are 15% larger in O. degus compared to O. lunatus. However, the ipsilateral projections to GLd and SC are 500% larger in O. lunatus than in O. degus. Other retinorecipient structures related to ocular movements and circadian activity showed no statistical differences between species. Our findings strongly suggest that nocturnal visual behavior leads to an enhancement of the structures associated with binocular vision, at least in the case of these rodents. Expansion of the binocular visual field in nocturnal species may have a beneficial effect in light and contrast sensitivity, but not necessarily in stereopsis. We discuss whether these conclusions can be extended to other mammalian and non-mammalian amniotes.

Bilateral and ipsilateral ascending tectopulvinar pathways in mammals: a study in the squirrel (Spermophilus beecheyi).

The mammalian pulvinar complex is a collection of dorsal thalamic nuclei related to several visual and integrative processes. Previous studies have shown that the superficial layers of the superior colliculus project to multiple divisions of the pulvinar complex. Although most of these works agree about the existence of an ipsilateral tectopulvinar projection arising from the stratum griseum superficialis, some others report a bilateral projection originating from this same tectal layer. We investigated the organization of the tectopulvinar projections in the Californian ground squirrel using cholera toxin B (CTb). We confirmed previous studies showing that the caudal pulvinar of the squirrel receives a massive bilateral projection originating from a specific cell population located in the superficial collicular layers (SGS3, also called the "lower SGS" or "SGSL"). We found that this projection shares striking structural similarities with the tectorotundal pathway of birds and reptiles. Morphology of the collicular cells originating this projection closely corresponds to that of the bottlebrush tectal cells described previously for chickens and squirrels. In addition, we found that the rostral pulvinar receives an exclusively ipsilateral projection from a spatially separate population of collicular cells located at the base of the stratum opticum, deeper than the cells projecting to the caudal pulvinar. These results strongly support, at a structural level, the homology of the pathway originating in the SGS3 collicular cells upon the caudal pulvinar with the tectorotundal pathway of nonmammalian amniotes and contribute to clarifying the general organization of the tectopulvinar pathways in mammals.

Topographic arrangement of the rotundo-entopallial projection in the pigeon (Columba livia).

The tectofugal pathway (retina--optic tectum--nucleus rotundus--entopallium) is a prominent route mediating visual discrimination in diurnal birds. Several lines of evidence have shown that at the tecto-rotundal stage this pathway is composed of multiple parallel channels. Anatomical studies show that the nucleus rotundus is composed of at least four subdivisions, according to differences in cytoarchitectonic, histochemical, and hodological properties. Each of these subdivisions is in receipt of a highly convergent, nontopographic tectal projection, originating from a distinct subset of tecto-rotundal neurons. Physiological studies show that neurons of different subdivisions respond specifically to different visual dimensions, such as color, luminance, two-dimensional motion, and in-depth motion. At present it is less clear whether or to what extent this channel segregation is preserved at the telencephalic stage of the tectofugal pathway. The entopallium shows no obvious subdivisions or laminations. Nevertheless, tract-tracing experiments show that separate portions of the entopallium receive efferent projections from different rotundal subdivisions, in a way that maintains the rostrocaudal order of these subdivisions. In the present study we investigate in detail the topography of the rotundo-entopallial projection by means of anterograde and retrograde neuronal tracers. Our results confirm the zonal topography proposed by previous studies and indicate that each zone in the entopallium receives a direct and topographically organized projection from its corresponding rotundal subdivision. These results suggest that the spatial arrangement of the different rotundal functional modules is preserved at the entopallial level.