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Oliveira-Abreu, Klausen, Nathalia Silva-dos-Santos, Andrelina Coelho-de-Souza, Francisco Ferreira-da-Silva, Kerly Silva-Alves, Ana Cardoso-Teixeira, José Cipolla-Neto, and José Leal-Cardoso. "Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential." International Journal of Molecular Sciences 20, no. 11 (May 28, 2019): 2611. http://dx.doi.org/10.3390/ijms20112611.
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Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N0) and with (Ninf) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N0 neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (Ninf) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01–1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitive—EMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitive—EMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (Rin), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt)max of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1–1000.0 nM) induced no alteration of (dV/dt)max of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N0 neurons shows that this substance has a greater pharmacological potency on Ninf neurons. We suggest that melatonin has important physiological function related to Ninf neurons and this is likely to bear a potential relevant therapeutic use, since Ninf neurons are related to nociception.
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Warren, S., H. A. Hamalainen, and E. P. Gardner. "Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys." Journal of Neurophysiology 56, no. 3 (September 1, 1986): 598–622. http://dx.doi.org/10.1152/jn.1986.56.3.598.
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In order to classify movement-sensitive neurons in SI cortex, and to estimate their relative distribution, we have developed a new simple method for controlled motion of textured surfaces across the skin, as well as a set of objective criteria for determining direction selectivity. Moving stimuli were generated using 5 mm thick precision gear wheels, whose teeth formed a grafting. They were mounted on the shafts of low-torque potentiometers (to measure the speed and direction of movement) and rolled manually across the skin using the potentiometer shaft as an axle. As the grafting wheel was advanced, its ridges sequentially contacted a specific set of points on the skin, leaving gaps of defined spacing that were unstimulated. This stimulus was reproducible from trial to trial and produced little distention of the skin. Three objective criteria were used to categorize responses: the ratio of responses to motion in the most and least preferred directions [direction index (DI)], the difference between mean firing rates in the two directions divided by the average standard deviation [index of discriminability (delta'e)], and statistical tests. Neurons were classified as direction sensitive if DI greater than 35, delta's greater than or equal to 1.35 (equivalent to 75% correct discrimination by an unbiased observer), and firing rates in most- and least-preferred directions were significantly different (P less than 0.05). Good agreement was found between the three classification schemes. Recordings were made from 1,020 cortical neurons in the hand and forearm regions of primary somatosensory cortex (areas 3b, 1 and 2) of five macaque monkeys. Tangential motion across the skin was found to be an extremely effective stimulus for SI cortical neurons. Two hundred eighty six of 757 tactile neurons (38%) responded more vigorously to moving stimuli than to pressure or tapping the skin. One hundred twenty-one cells were tested with moving gratings and were classified according to their ability to differentiate movement in longitudinal and transverse directions. Responses to the moving gratings resembled those observed when stroking the skin with brushed, edges, or blunt probes. Three major types of firing patterns were found: motion sensitive, direction sensitive, and orientation sensitive. Motion-sensitive neurons (37%) responded to movement in both longitudinal and transverse directions with only slight difference in firing rates and interval distributions. Responses throughout the field were fairly uniform, and no clear point of maximum sensitivity was apparent. Direction-sensitive neurons (60%) displayed clear preferences for movement in one or more directions.4
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Pastori, Valentina, Alessia D’Aloia, Stefania Blasa, and Marzia Lecchi. "Serum-deprived differentiated neuroblastoma F-11 cells express functional dorsal root ganglion neuron properties." PeerJ 7 (October 30, 2019): e7951. http://dx.doi.org/10.7717/peerj.7951.
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The isolation and culture of dorsal root ganglion (DRG) neurons cause adaptive changes in the expression and regulation of ion channels, with consequences on neuronal excitability. Considering that not all neurons survive the isolation and that DRG neurons are heterogeneous, it is difficult to find the cellular subtype of interest. For this reason, researchers opt for DRG-derived immortal cell lines to investigate endogenous properties. The F-11 cell line is a hybridoma of embryonic rat DRG neurons fused with the mouse neuroblastoma line N18TG2. In the proliferative condition, F-11 cells do not display a gene expression profile correspondent with specific subclasses of sensory neurons, but the most significant differences when compared with DRGs are the reduction of voltage-gated sodium, potassium and calcium channels, and the small amounts of TRPV1 transcripts. To investigate if functional properties of mature F-11 cells showed more similarities with those of isolated DRG neurons, we differentiated them by serum deprivation. Potassium and sodium currents significantly increased with differentiation, and biophysical properties of tetrodotoxin (TTX)-sensitive currents were similar to those characterized in small DRG neurons. The analysis of the voltage-dependence of calcium currents demonstrated the lack of low threshold activated components. The exclusive expression of high threshold activated Ca2+ currents and of TTX-sensitive Na+ currents correlated with the generation of a regular tonic electrical activity, which was recorded in the majority of the cells (80%) and was closely related to the activity of afferent TTX-sensitive A fibers of the proximal urethra and the bladder. Responses to capsaicin and substance P were also recorded in ~20% and ~80% of cells, respectively. The percentage of cells responsive to acetylcholine was consistent with the percentage referred for rat DRG primary neurons and cell electrical activity was modified by activation of non-NMDA receptors as for embryonic DRG neurons. These properties and the algesic profile (responses to pH5 and sensitivity to both ATP and capsaicin), proposed in literature to define a sub-classification of acutely dissociated rat DRG neurons, suggest that differentiated F-11 cells express receptors and ion channels that are also present in sensory neurons.
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Warren, S., H. A. Hamalainen, and E. P. Gardner. "Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys." Journal of Neurophysiology 57, no. 1 (January 1, 1987): 1. http://dx.doi.org/10.1152/jn.1987.57.1.1-a.
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S. Warren, H. A. Hamalainen, and E. P. Gardner, “Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys.” It was incorrectly stated that Orban and co-workers ( J. Neurophysiol. 45: 1059–1073, 1981) attributed direction selectivity to cortical neurons having a direction index (DI)≥20. Orban et al. actually used a weighted average of DIs and defined cells with a mean DI (MDI) above 50 as direction selective. Their criterion for direction selectivity was stricter and not less stringent, as stated in the paper. This error does not alter any of the data or conclusions of Warren et al.
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Warren, S., H. A. Hamalainen, and E. P. Gardner. "Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys." Journal of Neurophysiology 57, no. 6 (June 1, 1987): 1. http://dx.doi.org/10.1152/jn.1987.57.6.1-a.
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S. Warren, H. A. Hamalainen, and E. P. Gardner, “Objective classification of motion- and direction-sensitive neurons in primary somatosensory cortex of awake monkeys.” It was incorrectly stated that Orban and co-workers(J. Neurophysiol. 45: 1059–1073, 1981) attributed direction selectivity to cortical neurons having a direction index (DI) ge 20. Orban et al. actually used a weighted average of DIs and defined cells with a mean DI (MDI) above 50 as direction selective. Their criterion for direction selectivity was stricter and not less stringent, as stated in the paper. This error does not alter any of the data or conclusions of Warren et al.
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Mohren, Thomas L., Thomas L. Daniel, Steven L. Brunton, and Bingni W. Brunton. "Neural-inspired sensors enable sparse, efficient classification of spatiotemporal data." Proceedings of the National Academy of Sciences 115, no. 42 (September 13, 2018): 10564–69. http://dx.doi.org/10.1073/pnas.1808909115.
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Sparse sensor placement is a central challenge in the efficient characterization of complex systems when the cost of acquiring and processing data is high. Leading sparse sensing methods typically exploit either spatial or temporal correlations, but rarely both. This work introduces a sparse sensor optimization that is designed to leverage the rich spatiotemporal coherence exhibited by many systems. Our approach is inspired by the remarkable performance of flying insects, which use a few embedded strain-sensitive neurons to achieve rapid and robust flight control despite large gust disturbances. Specifically, we identify neural-inspired sensors at a few key locations on a flapping wing that are able to detect body rotation. This task is particularly challenging as the rotational twisting mode is three orders of magnitude smaller than the flapping modes. We show that nonlinear filtering in time, built to mimic strain-sensitive neurons, is essential to detect rotation, whereas instantaneous measurements fail. Optimized sparse sensor placement results in efficient classification with approximately 10 sensors, achieving the same accuracy and noise robustness as full measurements consisting of hundreds of sensors. Sparse sensing with neural-inspired encoding establishes an alternative paradigm in hyperefficient, embodied sensing of spatiotemporal data and sheds light on principles of biological sensing for agile flight control.
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Campbell, Robert A. A., Jan W. H. Schnupp, Akhil Shial, and Andrew J. King. "Binaural-Level Functions in Ferret Auditory Cortex: Evidence for a Continuous Distribution of Response Properties." Journal of Neurophysiology 95, no. 6 (June 2006): 3742–55. http://dx.doi.org/10.1152/jn.01155.2005.
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Many previous studies have subdivided auditory neurons into a number of physiological classes according to various criteria applied to their binaural response properties. However, it is often unclear whether such classifications represent discrete classes of neurons or whether they merely reflect a potentially convenient but ultimately arbitrary partitioning of a continuous underlying distribution of response properties. In this study we recorded the binaural response properties of 310 units in the auditory cortex of anesthetized ferrets, using an extensive range of interaural level differences (ILDs) and average binaural levels (ABLs). Most recordings were from primary auditory fields on the middle ectosylvian gyrus and from neurons with characteristic frequencies >5 kHz. We used simple multivariate statistics to quantify a fundamental coding feature: the shapes of the binaural response functions. The shapes of all 310 binaural response surfaces were represented as points in a five-dimensional principal component space. This space captured the underlying shape of all the binaural response surfaces. The distribution of binaural level functions was not homogeneous because some shapes were more common than others. Despite this, clustering validation techniques revealed no evidence for the existence of discrete, or partially overlapping, clusters that could serve as a basis for an objective classification of binaural-level functions. We also examined the gradients of the response functions for the population of units; these gradients were greatest near the midline, which is consistent with free-field data showing that cortical neurons are most sensitive to changes in stimulus location in this region of space.
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Esteky, H., and H. D. Schwark. "Responses of rapidly adapting neurons in cat primary somatosensory cortex to constant-velocity mechanical stimulation." Journal of Neurophysiology 72, no. 5 (November 1, 1994): 2269–79. http://dx.doi.org/10.1152/jn.1994.72.5.2269.
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1. The responses of rapidly adapting (RA) neurons to constant-velocity ramp stimulation were studied in the forepaw representation of primary somatosensory cortex (SI) of anesthetized cats. Single probe stimuli were used to indent the skin or to move hair parallel to the skin surface. The velocity of the moving stimulus probe was varied to determine the rate sensitivity of the neurons. 2. The cortical RA neurons were classified into four categories identified as G1/F1, Gint/Fint, G2/F2, and complex classes. The primary bases for classification in the present experiments were the pattern of response during ramp stimulation, velocity threshold, and directional sensitivity. 3. Of the RA neurons recorded in SI, 84% (49/58) could be assigned to one of the three response classes with little ambiguity. The remaining neurons showed more complex responses. The form of the complex responses suggested that they arose from a combination of inputs of different response classes. Some of these appeared to arise from a combination of different RA input classes, whereas others had components that resembled responses previously described for C mechanoreceptors. 4. Increased ramp velocity resulted in increased average firing frequency in 87% of the RA neurons. This relationship, which could be fitted with a power function, varied with response class. G1/F1 neurons were more sensitive to stimulus rate than G2/F2 neurons. Significant differences between response classes also were seen in the relationship between ramp velocity and their number of evoked action potentials and in their spontaneous firing rates. 5. The results demonstrate that a discrete SI neuron population is sensitive to the rate of stimulus movement. This observation is consistent with psychophysical studies reporting effects of stimulus indentation rates on perception of single probe stimuli. The appearance of complex responses in a small proportion of SI neurons provides evidence of convergence in somatosensory pathways to SI.
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Chittajallu, Siva K., Mathew J. Palakal, and Donald Wong. "Analysis and classification of delay-sensitive cortical neurons based on response to temporal parameters in echolocation signals." Hearing Research 84, no. 1-2 (April 1995): 157–66. http://dx.doi.org/10.1016/0378-5955(95)00022-v.
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Cvijanovic, Milan, Miroslav Ilin, Petar Slankamenac, Sofija Banic-Horvat, and Zita Jovin. "The sensitivity of electromyoneurography in the diagnosis of diabetic polyneuropathy." Medical review 64, no. 1-2 (2011): 11–14. http://dx.doi.org/10.2298/mpns1102011c.
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Diabetic polyneuropathy is a complex set of clinical syndromes, which deplete various regions of the nervous system. The process leading to diabetic neuropathy is multi-factorial. Its symptoms are paresthesia, dysesthesia and pain. The signs of damage to the peripheral neurons are hypoesthesia, hypoalgesia, hyperesthesia and hyperalgesia, decreased tendon reflexes, and, possibly, weakness and muscle atrophy. There is no universal classification. Electromyoneurography is indispensable in the diagnosis of diabetic polyneuropathy. However, there is no agreement on the most sensitive parameter for an early diagnosis. One hundred patients with diabetes mellitus were examined in order to investigate the sensitivity of different electromyographic parameters. Electromyographic techniques proved to be entirely sensitive for the early diagnosis of diabetic polyneuropathy. Some of the parameters are more suitable for an early detection of peripheral nerve damage, and others, which are not so sensitive but easy to use and stable, are suitable to follow up the course of diabetic polyneuropathy.
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Stüttgen, Maik C., Stephanie Kullmann, and Cornelius Schwarz. "Responses of Rat Trigeminal Ganglion Neurons to Longitudinal Whisker Stimulation." Journal of Neurophysiology 100, no. 4 (October 2008): 1879–84. http://dx.doi.org/10.1152/jn.90511.2008.
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Responses of rat trigeminal ganglion neurons to longitudinal whisker stimulation. Rats use their mobile set of whiskers to actively explore their environment. Parameters that play a role to generate movement dynamics of the whisker shaft within the follicle, thus activating primary afferents, are manifold: among them are mechanical properties of the whiskers (curvature, elasticity and taper), active movements (head, body, and whiskers), and finally, object characteristics (surface, geometry, position, and orientation). Hence the whisker system is confronted with forces along all three axes in space. Movements along the two latitudinal axes of the whisker (horizontal and vertical) have been well studied. Here we focus on movement along the whisker's longitudinal axis that has been neglected so far. We employed ramp-and-hold movements that pushed the whisker shaft toward the skin and quantified the resulting activity in trigeminal first-order afferents in anesthetized rats. Virtually all recorded neurons were highly sensitive to longitudinal movement. Neurons could be perfectly segregated into two groups according to their modulation by stimulus amplitude and velocity, respectively. This classification regimen correlated perfectly with the presence or absence of slowly adapting responses in longitudinal stimulation but agreed with classification derived from latitudinal stimulation only if the whisker was engaged in its optimal direction and set point. We conclude that longitudinal stimulation is an extremely effective means to activate the tactile pathway and thus is highly likely to play an important role in tactile coding on the ascending somatosensory pathway. In addition, compared with latitudinal stimulation, it provides a reliable and easy to use method to classify trigeminal first-order afferents.
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Blanchard, Tommy C., Steven T. Piantadosi, and Benjamin Y. Hayden. "Robust mixture modeling reveals category-free selectivity in reward region neuronal ensembles." Journal of Neurophysiology 119, no. 4 (April 1, 2018): 1305–18. http://dx.doi.org/10.1152/jn.00808.2017.
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Classification of neurons into clusters based on their response properties is an important tool for gaining insight into neural computations. However, it remains unclear to what extent neurons fall naturally into discrete functional categories. We developed a Bayesian method that models the tuning properties of neural populations as a mixture of multiple types of task-relevant response patterns. We applied this method to data from several cortical and striatal regions in economic choice tasks. In all cases, neurons fell into only two clusters: one multiple-selectivity cluster containing all cells driven by task variables of interest and another of no selectivity for those variables. The single cluster of task-sensitive cells argues against robust categorical tuning in these areas. The no-selectivity cluster was unanticipated and raises important questions about what distinguishes these neurons and what role they play. Moreover, the ability to formally identify these nonselective cells allows for more accurate measurement of ensemble effects by excluding or appropriately down-weighting them in analysis. Our findings provide a valuable tool for analysis of neural data, challenge simple categorization schemes previously proposed for these regions, and place useful constraints on neurocomputational models of economic choice and control. NEW & NOTEWORTHY We present a Bayesian method for formally detecting whether a population of neurons can be naturally classified into clusters based on their response tuning properties. We then examine several data sets of reward system neurons for variables and find in all cases that neurons can be classified into only two categories: a functional class and a non-task-driven class. These results provide important constraints for neural models of the reward system.
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Betts, Lisa R., and Hugh R. Wilson. "Heterogeneous Structure in Face-selective Human Occipito-temporal Cortex." Journal of Cognitive Neuroscience 22, no. 10 (October 2010): 2276–88. http://dx.doi.org/10.1162/jocn.2009.21346.
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It is well established that the human visual system contains a distributed network of regions that are involved in processing faces, but our understanding of how faces are represented within these face-sensitive brain areas is incomplete. We used fMRI to investigate whether face-sensitive brain areas are solely tuned for whole faces, or whether they contain heterogeneous populations of neurons tuned to individual components of the face as well as whole faces, as suggested by physiological investigations in nonhuman primates. The middle fusiform gyrus (fusiform face area, or FFA) and the inferior occipital gyrus (occipital face area, or OFA) produced robust BOLD activation to synthetic whole face stimuli, but also to the internal facial features and head outlines. BOLD responses to whole face stimuli in FFA were significantly reduced after adaptation to whole faces, but not after adaptation to features or head outlines, whereas activation to head outlines was reduced after adaptation to both whole faces and head outlines. OFA showed no significant adaptation effects for matching adaptation and test conditions, but did exhibit cross-adaptation between whole faces and head outlines. The internal face features did not produce any significant adaptation within either FFA or OFA. Our results are consistent with a model in which independent populations of whole face-, feature-, and head outline-tuned neurons exist within face-sensitive regions of human occipito-temporal cortex, which in turn would support tasks such as viewpoint processing, emotion classification, and identity discrimination.
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Karim, Ahmad M., Hilal Kaya, Mehmet Serdar Güzel, Mehmet R. Tolun, Fatih V. Çelebi, and Alok Mishra. "A Novel Framework Using Deep Auto-Encoders Based Linear Model for Data Classification." Sensors 20, no. 21 (November 9, 2020): 6378. http://dx.doi.org/10.3390/s20216378.
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This paper proposes a novel data classification framework, combining sparse auto-encoders (SAEs) and a post-processing system consisting of a linear system model relying on Particle Swarm Optimization (PSO) algorithm. All the sensitive and high-level features are extracted by using the first auto-encoder which is wired to the second auto-encoder, followed by a Softmax function layer to classify the extracted features obtained from the second layer. The two auto-encoders and the Softmax classifier are stacked in order to be trained in a supervised approach using the well-known backpropagation algorithm to enhance the performance of the neural network. Afterwards, the linear model transforms the calculated output of the deep stacked sparse auto-encoder to a value close to the anticipated output. This simple transformation increases the overall data classification performance of the stacked sparse auto-encoder architecture. The PSO algorithm allows the estimation of the parameters of the linear model in a metaheuristic policy. The proposed framework is validated by using three public datasets, which present promising results when compared with the current literature. Furthermore, the framework can be applied to any data classification problem by considering minor updates such as altering some parameters including input features, hidden neurons and output classes.
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Caron-Guyon, Jeanne, Julien Corbo, Yoh’i Zennou-Azogui, Christian Xerri, Anne Kavounoudias, and Nicolas Catz. "Neuronal Encoding of Multisensory Motion Features in the Rat Associative Parietal Cortex." Cerebral Cortex 30, no. 10 (June 4, 2020): 5372–86. http://dx.doi.org/10.1093/cercor/bhaa118.
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Abstract Motion perception is facilitated by the interplay of various sensory channels. In rodents, the cortical areas involved in multisensory motion coding remain to be identified. Using voltage-sensitive-dye imaging, we revealed a visuo–tactile convergent region that anatomically corresponds to the associative parietal cortex (APC). Single unit responses to moving visual gratings or whiskers deflections revealed a specific coding of motion characteristics strikingly found in both sensory modalities. The heteromodality of this region was further supported by a large proportion of bimodal neurons and by a classification procedure revealing that APC carries information about motion features, sensory origin and multisensory direction-congruency. Altogether, the results point to a central role of APC in multisensory integration for motion perception.
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Luna-Perejón, Francisco, Juan Manuel Montes-Sánchez, Lourdes Durán-López, Alberto Vazquez-Baeza, Isabel Beasley-Bohórquez, and José L. Sevillano-Ramos. "IoT Device for Sitting Posture Classification Using Artificial Neural Networks." Electronics 10, no. 15 (July 29, 2021): 1825. http://dx.doi.org/10.3390/electronics10151825.
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Nowadays, the percentage of time that the population spends sitting has increased substantially due to the use of computers as the main tool for work or leisure and the increase in jobs with a high office workload. As a consequence, it is common to suffer musculoskeletal pain, mainly in the back, which can lead to both temporary and chronic damage. This pain is related to holding a posture during a prolonged period of sitting, usually in front of a computer. This work presents a IoT posture monitoring system while sitting. The system consists of a device equipped with Force Sensitive Resistors (FSR) that, placed on a chair seat, detects the points where the user exerts pressure when sitting. The system is complemented with a Machine Learning model based on Artificial Neural Networks, which was trained to recognize the neutral correct posture as well as the six most frequent postures that involve risk of damage to the locomotor system. In this study, data was collected from 12 participants for each of the seven positions considered, using the developed sensing device. Several neural network models were trained and evaluated in order to improve the classification effectiveness. Hold-Out technique was used to guide the training and evaluation process. The results achieved a mean accuracy of 81% by means of a model consisting of two hidden layers of 128 neurons each. These results demonstrate that is feasible to distinguish different sitting postures using few sensors allocated in the surface of a seat, which implies lower costs and less complexity of the system.
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Atallah, Elias, Stavropoula I. Tjoumakaris, Robert H. Rosenwasser, and Pascal Jabbour. "118 Lessons Learned After 500 Cases of Intra-Arterial Chemotherapy for Retinoblastoma." Neurosurgery 64, CN_suppl_1 (August 24, 2017): 225–26. http://dx.doi.org/10.1093/neuros/nyx417.118.
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Abstract INTRODUCTION Intra-arterial chemotherapy has been used in early-childhood retinoblastoma. We present some pearls and pitfalls of this technique in a sizable cohort of retinoblastoma patients. METHODS A retrospective, non-comparative cohort of 500 patients with retinoblastoma was grouped between January 2009 and September 2016. Melphalan was infused under fluoroscopic guidance through the ophthalmic artery with supplementary topotecan or carboplatin or both, for a mean of 3 cycles. The mean follow-up was 20.3 months(SD = 11.3). The International Classification of Retinoblastoma (ICRB) was implemented in the assessment of ocular globe preservation and of the tumor's response to treatment. Grade E patients were almost always treated concomitantly with IV chemotherapy. RESULTS >Of 500 patients (mean of age 35 months), we treated 520 eyes. (n1 = 236; [(67) A, (83) B, (48) C, (18) D and (20) E]) received a primary treatment, (n2 = 95) were treated for their advanced disease, (n3 = 67) had bilateral retinoblastoma and (n4 = 55) were treated for a recurrence after conventional intravenous chemotherapy. Globe preservation was achieved in 87% of primary-treated cases(A [100%]; B [100%]; C [100%]; D [92%]; E [46%]) and in 69% of secondary-treated patients. Postprocedural complications were vitreous hemorrhage (3.2%), retinal artery branch occlusion (0.75%), ophthalmic artery (OA) occlusion (1.7%) and spasm (2.2%), limited choroidal ischemia (1.8%) and optic neuropathy (0.7%). 478(92%) patients had complete regression: small tumors 99%[201/203]; well-defined tumors 97%[173/178] and poorly defined tumors 92%[88/97]. There was no motor, sensitive or ictal complications after the intervention. Patients manifested none of the systemic side effects of the dispensed chemotherapy. CONCLUSION Selective intra-ophtalmic chemotherapy has become a gold standard in the treatment of retinoblastoma, with very low mortality, morbidity related to the procedure and a very high cure rate.
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Goddard, Erin, Samuel G. Solomon, and Thomas A. Carlson. "Dynamic population codes of multiplexed stimulus features in primate area MT." Journal of Neurophysiology 118, no. 1 (July 1, 2017): 203–18. http://dx.doi.org/10.1152/jn.00954.2016.
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The middle-temporal area (MT) of primate visual cortex is critical in the analysis of visual motion. Single-unit studies suggest that the response dynamics of neurons within area MT depend on stimulus features, but how these dynamics emerge at the population level, and how feature representations interact, is not clear. Here, we used multivariate classification analysis to study how stimulus features are represented in the spiking activity of populations of neurons in area MT of marmoset monkey. Using representational similarity analysis we distinguished the emerging representations of moving grating and dot field stimuli. We show that representations of stimulus orientation, spatial frequency, and speed are evident near the onset of the population response, while the representation of stimulus direction is slower to emerge and sustained throughout the stimulus-evoked response. We further found a spatiotemporal asymmetry in the emergence of direction representations. Representations for high spatial frequencies and low temporal frequencies are initially orientation dependent, while those for high temporal frequencies and low spatial frequencies are more sensitive to motion direction. Our analyses reveal a complex interplay of feature representations in area MT population response that may explain the stimulus-dependent dynamics of motion vision. NEW & NOTEWORTHY Simultaneous multielectrode recordings can measure population-level codes that previously were only inferred from single-electrode recordings. However, many multielectrode recordings are analyzed using univariate single-electrode analysis approaches, which fail to fully utilize the population-level information. Here, we overcome these limitations by applying multivariate pattern classification analysis and representational similarity analysis to large-scale recordings from middle-temporal area (MT) in marmoset monkeys. Our analyses reveal a dynamic interplay of feature representations in area MT population response.
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Semple, M. N., and L. M. Kitzes. "Binaural processing of sound pressure level in the inferior colliculus." Journal of Neurophysiology 57, no. 4 (April 1, 1987): 1130–47. http://dx.doi.org/10.1152/jn.1987.57.4.1130.
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The central auditory system could encode information about the location of a high-frequency sound source by comparing the sound pressure levels at the ears. Two potential computations are the interaural intensity difference (IID) and the average binaural intensity (ABI). In this study of the central nucleus of the inferior colliculus (ICC) of the anesthetized gerbil, we demonstrate that responses of 85% of the 97 single units in our sample were jointly influenced by IID and ABI. For a given ABI, discharge rate of most units is a sigmoidal function of IID, and peak rates occur at IIDs favoring the contralateral ear. Most commonly, successive increments of ABI cause successive shifts of the IID functions toward IIDs favoring the ipsilateral ear. Neurons displaying this behavior include many that would conventionally be classified EI (receiving predominantly excitatory input arising from one ear and inhibitory input from the other), many that would be classified EE (receiving predominantly excitatory input arising from each ear), and all that are responsive only to contralateral stimulation. The IID sensitivity of a very few EI neurons is unaffected by ABI, except near threshold. Such units could provide directional information that is independent of source intensity. A few EE neurons are very sensitive to ABI, but are minimally sensitive to IID. Nevertheless, our data indicate that responses of most EE units in ICC are strongly dominated by excitation of contralateral origin. For some units, discharge rate is nonmonotonically related to IID and is maximal when the stimuli at the two ears are of comparable sound pressure. This preference for zero IID is common for all binaural levels. Many EI neurons respond nonmonotonically to ABI. Discharge rates are greater for IIDs representative of contralateral space and are maximal at a single best ABI. For a subset of these neurons, the influence arising from the ipsilateral ear is comprised of a mixture of excitation and inhibition. As a consequence, discharge rates are nonmonotonically related not only to ABI but also to IID. This dual nonmonotonicity creates a clear focus of peak response at a particular ABI/IID combination. Because of their mixed monaural influences, such units would be ascribed to different classes of the conventional (EE/EI) binaural classification scheme depending on the binaural level presented. Several response classes were identified in this study, and each might contribute differently to the encoding of spatial information.(ABSTRACT TRUNCATED AT 400 WORDS)
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Arun, Pattathal V., and Arnon Karnieli. "Deep Learning-Based Phenological Event Modeling for Classification of Crops." Remote Sensing 13, no. 13 (June 25, 2021): 2477. http://dx.doi.org/10.3390/rs13132477.
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Classification of crops using time-series vegetation index (VI) curves requires appropriate modeling of phenological events and their characteristics. The current study explores the use of capsules, a group of neurons having an activation vector, to learn the characteristic features of the phenological curves. In addition, joint optimization of denoising and classification is adopted to improve the generalizability of the approach and to make it resilient to noise. The proposed approach employs reconstruction loss as a regularizer for classification, whereas the crop-type label is used as prior information for denoising. The activity vector of the class capsule is applied to sample the latent space conditioned on the cell state of a Long Short-Term Memory (LSTM) that integrates the sequences of the phenological events. Learning of significant phenological characteristics is facilitated by adversarial variational encoding in conjunction with constraints to regulate latent representations and embed label information. The proposed architecture, called the variational capsule network (VCapsNet), significantly improves the classification and denoising results. The performance of VCapsNet can be attributed to the suitable modeling of phenological events and the resilience to outliers and noise. The maxpooling-based capsule implementation yields better results, particularly with limited training samples, compared to the conventional implementations. In addition to the confusion matrix-based accuracy measures, this study illustrates the use of interpretability-based evaluation measures. Moreover, the proposed approach is less sensitive to noise and yields good results, even at shallower depths, compared to the main existing approaches. The performance of VCapsNet in accurately classifying wheat and barley crops indicates that the approach addresses the issues in crop-type classification. The approach is generic and effectively models the crop-specific phenological features and events. The interpretability-based evaluation measures further indicate that the approach successfully identifies the crop transitions, in addition to the planting, heading, and harvesting dates. Due to its effectiveness in crop-type classification, the proposed approach is applicable to acreage estimation and other applications in different scales.
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Gegenfurtner, Karl R., Daniel C. Kiper, and Jonathan B. Levitt. "Functional Properties of Neurons in Macaque Area V3." Journal of Neurophysiology 77, no. 4 (April 1, 1997): 1906–23. http://dx.doi.org/10.1152/jn.1997.77.4.1906.
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Gegenfurtner, Karl R., Daniel C. Kiper, and Jonathan B. Levitt. Functional properties of neurons in macaque area V3. J. Neurophysiol. 77: 1906–1923, 1997. We investigated the functional properties of neurons in extrastriate area V3. V3 receives inputs from both magno- and parvocellular pathways and has prominent projections to both the middle temporal area (area MT) and V4. It may therefore represent an important site for integration and transformation of visual signals. We recorded the activity of single units representing the central 10° in anesthetized, paralyzed macaque monkeys. We measured each cell's spatial, temporal, chromatic, and motion properties with the use of a variety of stimuli. Results were compared with measurements made in V2 neurons at similar eccentricities. Similar to area V2, most of the neurons in our sample (80%) were orientation selective, and the distribution of orientation bandwidths was similar to that found in V2. Neurons in V3 preferred lower spatial and higher temporal frequencies than V2 neurons. Contrast thresholds of V3 neurons were extremely low. Achromatic contrast sensitivity was much higher than in V2, and similar to that found in MT. About 40% of all neurons showed strong directional selectivity. We did not find strongly directional cells in layer 4 of V3, the layer in which the bulk of V1 and V2 inputs terminate. This property seems to be developed within area V3. An analysis of the responses of directionally selective cells to plaid patterns showed that in area V3, as in MT and unlike in V1 and V2, there exist cells sensitive to the motion of the plaid pattern rather than to that of the components. The exact proportion of cells classified as being selective to color depended to a large degree on the experiment and on the criteria used for classification. With the use of the same conditions as in a previous study of V2 cells, we found as many (54%) color-selective cells as in V2 (50%). Furthermore, the responses of V3 cells to colored sinusoidal gratings were well described by a linear combination of cone inputs. The two subpopulations of cells responsive to color and to motion overlapped to a large extent, and we found a significant proportion of cells that gave reliable and directional responses to drifting isoluminant gratings. Our results show that there is a significant interaction between color and motion processing in area V3, and that V3 cells exhibit the more complex motion properties typically observed at later stages of visual processing.
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Miltiadous, Andreas, Katerina D. Tzimourta, Nikolaos Giannakeas, Markos G. Tsipouras, Theodora Afrantou, Panagiotis Ioannidis, and Alexandros T. Tzallas. "Alzheimer’s Disease and Frontotemporal Dementia: A Robust Classification Method of EEG Signals and a Comparison of Validation Methods." Diagnostics 11, no. 8 (August 9, 2021): 1437. http://dx.doi.org/10.3390/diagnostics11081437.
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Dementia is the clinical syndrome characterized by progressive loss of cognitive and emotional abilities to a degree severe enough to interfere with daily functioning. Alzheimer’s disease (AD) is the most common neurogenerative disorder, making up 50–70% of total dementia cases. Another dementia type is frontotemporal dementia (FTD), which is associated with circumscribed degeneration of the prefrontal and anterior temporal cortex and mainly affects personality and social skills. With the rapid advancement in electroencephalogram (EEG) sensors, the EEG has become a suitable, accurate, and highly sensitive biomarker for the identification of neuronal and cognitive dynamics in most cases of dementia, such as AD and FTD, through EEG signal analysis and processing techniques. In this study, six supervised machine-learning techniques were compared on categorizing processed EEG signals of AD and FTD cases, to provide an insight for future methods on early dementia diagnosis. K-fold cross validation and leave-one-patient-out cross validation were also compared as validation methods to evaluate their performance for this classification problem. The proposed methodology accuracy scores were 78.5% for AD detection with decision trees and 86.3% for FTD detection with random forests.
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Smith, D. V., H. Liu, and M. B. Vogt. "Responses of gustatory cells in the nucleus of the solitary tract of the hamster after NaCl or amiloride adaptation." Journal of Neurophysiology 76, no. 1 (July 1, 1996): 47–58. http://dx.doi.org/10.1152/jn.1996.76.1.47.
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1. The responses of single nucleus of the solitary tract (NST) neurons in the hamster were recorded to an array of Na+ and non-Na+ stimuli under each of three adaptation conditions: distilled H2O, 0.032 M NaCl, and 10 microM amiloride. Each adapting solution flowed for 60 s before delivery of one of seven test stimuli: 0.032 M NaCl, NaNO3, and Na-gluconate, 0.1 M KCl and sucrose, 1 mM HCl, and 3 mM quinine hydrochloride (QHCl). Stimuli were dissolved in distilled H2O (H2O and NaCl adaptation conditions) or 10 microM amiloride (amiloride adaptation condition). 2. Both amiloride treatment and NaCl adaptation reduced responses to the Na+ stimuli. The effects of NaCl adaptation were generally greater than those of amiloride, and the responses to the Na+ salts were reduced by NaCl adaptation in every cell that responded to NaCl, regardless of its best-stimulus classification. Amiloride treatment suppressed the responses to Na+ salts with larger anions (NaNO3 and Na-gluconate) more than the response to NaCl. 3. Unlike amiloride treatment, NaCl adaptation also reduced responses to several non-Na+ stimuli (KCl, HCl, and QHCl). This effect occurred primarily in the NaCl-best neurons that were most highly responsive to NaCl and that showed a postexcitatory suppression after NaCl. This suppression has been observed in recordings from the chorda tympani nerve in both rats and hamsters and in taste receptor cell responses recorded in situ in the rat. If it is a receptor phenomenon, these data would imply that some NaCl-sensitive receptor cells are also responsive to these non-Na+ electrolytes. 4. The effects of amiloride on the responses to Na+ stimuli were not limited to NaCl-best neurons, but occurred in sucrose-best cells as well. These results suggest that the sucrose-best cells in the NST receive converging input from sucrose- and NaCl-best chorda tympani fibers, because there is little Na+ sensitivity in the peripheral sucrose-best fibers and the amiloride sensitivity is restricted to NaCl-best chorda tympani fibers. The responses to NaCl in the few HCl- and QHCl-best NST neurons were not affected by amiloride. 5. Rinsing the tongue with amiloride for 60 s resulted in a reduction in the baseline response rate of NST cells. This effect occurred primarily in NaCl- and sucrose-best NST neurons and implies that much of the spontaneous activity in these brain stem cells arises from amiloride-sensitive channel activity in the peripheral receptor cells. 6. The results of human psychophysical studies show very different effects of NaCl adaptation and amiloride treatment. Adaptation to NaCl produces a robust and specific reduction in the saltiness of all salts. The present results show that NaCl adaptation reduces the responses of all cells sensitive to NaCl. Treatment of the human tongue with amiloride produces a proportionately smaller reduction in the response to NaCl than it does in rodents, and it appears to have no effect on saltiness. Rather, amiloride has been shown to specifically reduce the sour side taste of NaCl, Nagluconate, and LiCl. Therefore conclusions about the effects of amiloride on taste quality based on rodent electrophysiology are questionable.
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WAFFORD, K. A., and D. B. SATTELLE. "L-Glutamate Receptors on the Cell Body Membrane of an Identified Insect Motor Neurone." Journal of Experimental Biology 144, no. 1 (July 1, 1989): 449–62. http://dx.doi.org/10.1242/jeb.144.1.449.
Full textAbstract:
Current-clamp experiments on an identified neurone have demonstrated the presence of L-glutamate receptors in the insect central nervous system. The cell body of the fast coxal depressor motor neurone (Df) in the metathoracic ganglion of the cockroach Periplaneta americana exhibits a hyperpolarizing response to L-glutamate, accompanied by an increase in membrane conductance. The response is dependent on both intracellular and extracellular chloride concentration, but is not affected by changes in potassium concentration. The hyperpolarization reverses at −82mV (the equilibrium potential for chloride), is mimicked by the action of L-aspartate, blocked by the antagonists picrotoxin and γ-D-glutamylglycine (γ-DGG) at high concentrations (1.0×10−4mol l−1), and is enhanced by L-amino phosphonobutyrate (L-APB). The response is insensitive to glutamate diethyl ester (GDEE), cis-2,3-piperazine dicarboxylic acid (cis-2,3- PDA) and D-amino phosphonobutyrate (D-APB). The 1-glutamate-activated increase in chloride conductance does not cross-desensitize with the γ-aminobutyric acid (GAB A) response on the same cell. It is less sensitive than the GAB Aresponse to block by picrotoxin. In addition, γ-DGG specifically blocks the L-glutamate receptor. A depolarizing response is elicited by kainate and quisqualate; it is associated with an increase in conductance, and exhibits a much slower time course than the response to 1-glutamate, indicating a different underlying mechanism. L-Cysteate produces a small depolarizing response of similar time course to that produced by 1-glutamate. L-Homocysteate and N-methyl-D-aspartate (NMDA) are ineffective on the cell body membrane when applied at concentrations up to 1.0×10−3mol l−1. This first detailed description of the properties of L-glutamate receptors on an identified insect neurone reveals that they are not readily accommodated in the existing classification of receptor subtypes, based on vertebrate pharmacology.
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Thavabalasingam, Sathesan, Edward B. O’Neil, Jonathan Tay, Adrian Nestor, and Andy C. H. Lee. "Evidence for the incorporation of temporal duration information in human hippocampal long-term memory sequence representations." Proceedings of the National Academy of Sciences 116, no. 13 (March 12, 2019): 6407–14. http://dx.doi.org/10.1073/pnas.1819993116.
Full textAbstract:
There has been much interest in how the hippocampus codes time in support of episodic memory. Notably, while rodent hippocampal neurons, including populations in subfield CA1, have been shown to represent the passage of time in the order of seconds between events, there is limited support for a similar mechanism in humans. Specifically, there is no clear evidence that human hippocampal activity during long-term memory processing is sensitive to temporal duration information that spans seconds. To address this gap, we asked participants to first learn short event sequences that varied in image content and interval durations. During fMRI, participants then completed a recognition memory task, as well as a recall phase in which they were required to mentally replay each sequence in as much detail as possible. We found that individual sequences could be classified using activity patterns in the anterior hippocampus during recognition memory. Critically, successful classification was dependent on the conjunction of event content and temporal structure information (with unsuccessful classification of image content or interval duration alone), and further analyses suggested that the most informative voxels resided in the anterior CA1. Additionally, a classifier trained on anterior CA1 recognition data could successfully identify individual sequences from the mental replay data, suggesting that similar activity patterns supported participants’ recognition and recall memory. Our findings complement recent rodent hippocampal research, and provide evidence that long-term sequence memory representations in the human hippocampus can reflect duration information in the order of seconds.
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Ramachandran, Ramnarayan, Kevin A. Davis, and Bradford J. May. "Single-Unit Responses in the Inferior Colliculus of Decerebrate Cats I. Classification Based on Frequency Response Maps." Journal of Neurophysiology 82, no. 1 (July 1, 1999): 152–63. http://dx.doi.org/10.1152/jn.1999.82.1.152.
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This study proposes a classification system for neurons in the central nucleus of the inferior colliculus (ICC) that is based on excitation and inhibition patterns of single-unit responses in decerebrate cats. The decerebrate preparation allowed extensive characterization of physiological response types without the confounding effects of anesthesia. The tone-driven discharge rates of individual units were measured across a range of frequencies and levels to map excitatory and inhibitory response areas for contralateral monaural stimulation. The resulting frequency response maps can be grouped into the following three populations: type V maps exhibit a wide V-shaped excitatory area and no inhibition; type I maps show a more restricted I-shaped region of excitation that is flanked by inhibition at lower and higher frequencies; and type O maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Units that produce a type V map typically have a low best frequency (BF: the most sensitive frequency), a low rate of spontaneous activity, and monotonic rate-level functions for both BF tones and broadband noise. Type I and type O units have BFs that span the cat’s range of audible frequencies and high rates of spontaneous activity. Like type V units, type I units are excited by BF tones and noise at all levels, but their rate-level functions may become nonmonotonic at high levels. Type O units are inhibited by BF tones and noise at high levels. The existence of distinct response types is consistent with a conceptual model in which the unit types receive dominant inputs from different sources and shows that these functionally segregated pathways are specialized to play complementary roles in the processing of auditory information.
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Qin, Shanshan, Qianyi Li, Chao Tang, and Yuhai Tu. "Optimal compressed sensing strategies for an array of nonlinear olfactory receptor neurons with and without spontaneous activity." Proceedings of the National Academy of Sciences 116, no. 41 (September 23, 2019): 20286–95. http://dx.doi.org/10.1073/pnas.1906571116.
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There are numerous different odorant molecules in nature but only a relatively small number of olfactory receptor neurons (ORNs) in brains. This “compressed sensing” challenge is compounded by the constraint that ORNs are nonlinear sensors with a finite dynamic range. Here, we investigate possible optimal olfactory coding strategies by maximizing mutual information between odor mixtures and ORNs’ responses with respect to the bipartite odor-receptor interaction network (ORIN) characterized by sensitivities between all odorant–ORN pairs. For ORNs without spontaneous (basal) activity, we find that the optimal ORIN is sparse—a finite fraction of sensitives are zero, and the nonzero sensitivities follow a broad distribution that depends on the odor statistics. We show analytically that sparsity in the optimal ORIN originates from a trade-off between the broad tuning of ORNs and possible interference. Furthermore, we show that the optimal ORIN enhances performances of downstream learning tasks (reconstruction and classification). For ORNs with a finite basal activity, we find that having inhibitory odor–receptor interactions increases the coding capacity and the fraction of inhibitory interactions increases with the ORN basal activity. We argue that basal activities in sensory receptors in different organisms are due to the trade-off between the increase in coding capacity and the cost of maintaining the spontaneous basal activity. Our theoretical findings are consistent with existing experiments and predictions are made to further test our theory. The optimal coding model provides a unifying framework to understand the peripheral olfactory systems across different organisms.
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Sanchez-Armass, S., D. C. Merz, and P. Drapeau. "Distinct receptors, second messengers and conductances underlying the dual responses to serotonin in an identified leech neurone." Journal of Experimental Biology 155, no. 1 (January 1, 1991): 531–47. http://dx.doi.org/10.1242/jeb.155.1.531.
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1. Pressure-sensitive mechanosensory (P) neurones of the leech Hirudo medicinalis produce two responses to serotonin (5-HT): activation of a Cl- conductance and of a non-selective monovalent cation conductance. The effects of channel blockers, the receptor pharmacology and the second-messenger dependence of these responses were studied in voltage-clamped P cells in culture. Antagonists were applied by superfusion and agonists by pressure ejection. 2. Zn2+ (100 mumol l-1) and H+ (pH 6.5 and lower) reversibly reduced the Cl- conductance activated by 5-HT. The cation conductance was impermeant to calcium ions and was reduced by micromolar concentrations of the Na+ channel inhibitors amiloride and 3,4-dichlorobenzamil. 3. High concentrations of antagonists or agonists of 5-HT1 receptors and an antagonist of 5-HT3 receptors had no effect on either response of P cells to 5-HT. Micromolar concentrations of ketanserin or cyproheptadine, which selectively antagonize 5-HT2 receptors, reduced the cation but not the Cl- conductance. From these results, the receptor underlying the cation conductance appears to be of the 5-HT2 subtype, whereas the receptor activating the Cl- conductance does not fit within the mammalian classification scheme. 4. Brief (less than 500 ms) application of membrane-permeant agonists of the second messenger cyclic AMP elicited a Cl- conductance, whereas antagonists of cyclic-AMP-dependent protein kinase A reversibly suppressed the Cl- conductance elicited by 5-HT and by cyclic AMP agonists. Compounds affecting other second messenger pathways were without effect on the Cl- conductance. It therefore appears that the Cl- conductance is activated by cyclic-AMP-dependent protein kinase A. 5. Cyclic nucleotide agonists and antagonists were without effect on the cation conductance. However, brief application of phorbol esters, which activate protein kinase C, elicited an amiloride-sensitive cation current. An inhibitor of protein kinase C reduced the cation conductance activated by 5-HT and by phorbol esters. Therefore, the cation conductance appears to depend on activation of protein kinase C. 6. We conclude that 5-HT activates two types of receptor coupled to separate ionic channels via different second messenger pathways in P cells. A receptor that is distinct from the mammalian subtypes activates Cl- channels via cyclic-AMP-dependent protein kinase A. 5-HT2 receptors appear to activate cation channels by means of protein kinase C.
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Edwards, Robin, Dengke Xiao, Christian Keysers, Peter Földiák, and David Perrett. "Color Sensitivity of Cells Responsive to Complex Stimuli in the Temporal Cortex." Journal of Neurophysiology 90, no. 2 (August 2003): 1245–56. http://dx.doi.org/10.1152/jn.00524.2002.
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The inferotemporal (IT) cortex of the monkey lies at the head of the ventral visual pathway and is known to mediate object recognition and discrimination. It is often assumed that color plays a minor role in the recognition of objects and faces because discrimination remains highly accurate with black-and-white images. Furthermore it has been suggested that for rapid presentation and reaction tasks, object classification may be based on a first wave of feedforward visual information, which is coarse and achromatic. The fine detail and color information follows later, allowing similar stimuli to be discriminated. To allow these theories to be tested, this study investigates whether the presence of color affects the response of IT neurons to complex stimuli, such as faces, and whether color information is delayed with respect to information about stimulus form in these cells. Color, achromatic, and false-color versions of effective stimuli were presented using a rapid serial visual presentation paradigm, and responses recorded from single cells in IT of the adult monkey. Achromatic images were found to evoke significantly reduced responses compared with color images in the majority of neurons (70%) tested. Differential activity for achromatic and colored stimuli was evident from response onset with no evidence to support the hypothesis that information about object color is delayed with respect to object form. A negative correlation ( P < 0.01) was found between cell latency and color sensitivity, with the most color-sensitive cells tending to respond earliest. The results of this study suggest a strong role for color in familiar object recognition and provide no evidence to support the idea of a first wave of form processing in the ventral stream based on purely achromatic information.
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Lochy, Aliette, Corentin Jacques, Louis Maillard, Sophie Colnat-Coulbois, Bruno Rossion, and Jacques Jonas. "Selective visual representation of letters and words in the left ventral occipito-temporal cortex with intracerebral recordings." Proceedings of the National Academy of Sciences 115, no. 32 (July 23, 2018): E7595—E7604. http://dx.doi.org/10.1073/pnas.1718987115.
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We report a comprehensive cartography of selective responses to visual letters and words in the human ventral occipito-temporal cortex (VOTC) with direct neural recordings, clarifying key aspects of the neural basis of reading. Intracerebral recordings were performed in a large group of patients (n = 37) presented with visual words inserted periodically in rapid sequences of pseudofonts, nonwords, or pseudowords, enabling classification of responses at three levels of word processing: letter, prelexical, and lexical. While letter-selective responses are found in much of the VOTC, with a higher proportion in left posterior regions, prelexical/lexical responses are confined to the middle and anterior sections of the left fusiform gyrus. This region overlaps with and extends more anteriorly than the visual word form area typically identified with functional magnetic resonance imaging. In this region, prelexical responses provide evidence for populations of neurons sensitive to the statistical regularity of letter combinations independently of lexical responses to familiar words. Despite extensive sampling in anterior ventral temporal regions, there is no hierarchical organization between prelexical and lexical responses in the left fusiform gyrus. Overall, distinct word processing levels depend on neural populations that are spatially intermingled rather than organized according to a strict postero-anterior hierarchy in the left VOTC.
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Kuśmierek, Paweł, Michael Ortiz, and Josef P. Rauschecker. "Sound-identity processing in early areas of the auditory ventral stream in the macaque." Journal of Neurophysiology 107, no. 4 (February 15, 2012): 1123–41. http://dx.doi.org/10.1152/jn.00793.2011.
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Auditory cortical processing is thought to be accomplished along two processing streams. The existence of a posterior/dorsal stream dealing, among others, with the processing of spatial aspects of sound has been corroborated by numerous studies in several species. An anterior/ventral stream for the processing of nonspatial sound qualities, including the identification of sounds such as species-specific vocalizations, has also received much support. Originally discovered in anterolateral belt cortex, most recent work on the anterior/ventral pathway has been performed on far anterior superior temporal (ST) areas and on ventrolateral prefrontal cortex (VLPFC). Regions of the anterior/ventral stream near its origin in early auditory areas have been less explored. In the present study, we examined three early auditory regions with different anteroposterior locations (caudal, middle, and rostral) in awake rhesus macaques. We analyzed how well classification based on sound-evoked activity patterns of neuronal populations replicates the original stimulus categories. Of the three regions, the rostral region (rR), which included core area R and medial belt area RM, yielded the greatest classification success across all stimulus classes or between classes of natural sounds. Starting from ∼80 ms past stimulus onset, clustering based on the population response in rR became clearly more successful than clustering based on responses from any other region. Our study demonstrates that specialization for sound-identity processing can be found very early in the auditory ventral stream. Furthermore, the fact that this processing develops over time can shed light on underlying mechanisms. Finally, we show that population analysis is a more sensitive method for revealing functional specialization than conventional types of analysis.
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Sossi, Vesna, Raúl de la Fuente-Fernández, James E. Holden, Doris J. Doudet, Jess McKenzie, A. J. Stoessl, and T. J. Ruth. "Increase in Dopamine Turnover Occurs Early in Parkinson's Disease: Evidence from a New Modeling Approach to PET 18F-Fluorodopa Data." Journal of Cerebral Blood Flow & Metabolism 22, no. 2 (February 2002): 232–39. http://dx.doi.org/10.1097/00004647-200202000-00011.
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An increase in dopamine turnover has been hypothesized to occur early in Parkinson's disease (PD) as a compensatory mechanism for dopaminergic neuronal loss. A new approach to the determination of dopamine turnover was developed using 4-hour-long 18F-fluorodopa (FD) positron emission tomography (PET) data. An effective dopamine turnover, an estimate of dopamine turnover, has been measured using its inverse, the effective dopamine distribution volume (EDV). This new method is based on a reversible tracer approach and determines the EDV using a graphical method. Six healthy subjects and 10 subjects with very early PD underwent a 4-hour-long FD scan. The EDV and the plasma uptake rate constant Ki, a marker of dopamine synthesis and storage, were compared according to their ability to separate the PD group from the healthy group. The EDV was the better discriminator (93.8% correct classification versus 81.3% for Ki). Effective dopamine distribution volume decreased by 65% in the PD group relative to the healthy group, whereas the decrease in Ki was 39%. These results show that changes in EDV are measurable with PET earlier than changes in the dopamine synthesis and storage rate, indicating that EDV is a sensitive marker for early PD and that a dopamine turnover increase likely serves as an early compensatory mechanism.
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Rigotti, DJ, A. Gass, L. Achtnichts, M. Inglese, JS Babb, Y. Naegelin, J. Hirsch, M. Amann, L. Kappos, and O. Gonen. "Multiple Sclerosis Severity Scale and whole-brain N-acetylaspartate concentration for patients’ assessment." Multiple Sclerosis Journal 18, no. 1 (September 15, 2011): 98–107. http://dx.doi.org/10.1177/1352458511415142.
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Background: The ability to predict the course of multiple sclerosis (MS) is highly desirable but lacking. Objective: To test whether the MS Severity Scale (MSSS) and global neuronal viability, assessed through the quantification of the whole-brain N-acetylaspartate concentration (WBNAA), concur or complement the assessment of individual patients’ disease course. Methods: The MSSS and average WBNAA loss rate (ΔWBNAA, extrapolated based on one current measurement and the assumption that at disease onset neural sparing was similar to healthy controls, obtained with proton magnetic resonance (MR) spectroscopy and magnetic resonance imaging (MRI)) from 61 patients with MS (18 male and 43 female) with long disease duration (15 years or more) were retrospectively examined. Some 27 patients exhibited a ‘benign’ disease course, characterized by an Expanded Disability Status Scale score (EDSS) of 3.0 or less, and 34 were ‘non-benign’: EDSS score higher than 3.0. Results: The two cohorts were indistinguishable in age and disease duration. Benign patients’ EDSS and MSSS (2.1 ± 0.7, 1.15 ± 0.60) were significantly lower than non-benign (4.6 ± 1.0, 3.6 ± 1.2; both p < 10−4). Their respective average ΔWBNAA, 0.10 ± 0.16 and 0.11 ± 0.12 mM/year, however, were not significantly different ( p > 0.7). While MSSS is both sensitive to (92.6%) and specific for (97.0%) benign MS, ΔWBNAA is only sensitive (92.6%) but not specific (2.9%). Conclusion: Since the WBNAA loss rate is similar in both phenotypes, the only difference between them is their clinical classification, characterized by MSSS and EDSS. This may indicate that ‘benign’ MS probably reflects fortuitous sparing of clinically eloquent brain regions and better utilization of brain plasticity.
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Perez-Pinzon, Miguel A., R. Anne Stetler, and Gary Fiskum. "Novel Mitochondrial Targets for Neuroprotection." Journal of Cerebral Blood Flow & Metabolism 32, no. 7 (March 28, 2012): 1362–76. http://dx.doi.org/10.1038/jcbfm.2012.32.
Full textAbstract:
Mitochondrial dysfunction contributes to the pathophysiology of acute neurologic disorders and neurodegenerative diseases. Bioenergetic failure is the primary cause of acute neuronal necrosis, and involves excitotoxicity-associated mitochondrial Ca2+ overload, resulting in opening of the inner membrane permeability transition pore and inhibition of oxidative phosphorylation. Mitochondrial energy metabolism is also very sensitive to inhibition by reactive O2 and nitrogen species, which modify many mitochondrial proteins, lipids, and DNA/RNA, thus impairing energy transduction and exacerbating free radical production. Oxidative stress and Ca2+-activated calpain protease activities also promote apoptosis and other forms of programmed cell death, primarily through modification of proteins and lipids present at the outer membrane, causing release of proapoptotic mitochondrial proteins, which initiate caspase-dependent and caspase-independent forms of cell death. This review focuses on three classifications of mitochondrial targets for neuroprotection. The first is mitochondrial quality control, maintained by the dynamic processes of mitochondrial fission and fusion and autophagy of abnormal mitochondria. The second includes targets amenable to ischemic preconditioning, e.g., electron transport chain components, ion channels, uncoupling proteins, and mitochondrial biogenesis. The third includes mitochondrial proteins and other molecules that defend against oxidative stress. Each class of targets exhibits excellent potential for translation to clinical neuroprotection.
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Fursova, A. Zh, Yu A. Gamza, M. Yu Zubkova, A. S. Derbeneva, O. B. Doronina, K. S. Doronina, N. V. Bulatova, and A. S. Belgibaeva. "Ophthalmic examination in the debut and during progression of neurodegenerative diseases." Russian Ophthalmological Journal 14, no. 1 (March 20, 2021): 104–10. http://dx.doi.org/10.21516/2072-0076-2021-14-1-104-110.
Full textAbstract:
Neurodegenerative diseases (NDD) are a group of nosological forms, caused by excessive formation of protein molecules and their aggregates and leading to the death of brain cells. Classical pathophysiological mechanisms are associated with the accumulation of extracellular amyloid b -protein (A b) in Alzheimer's disease (AD) and a -synuclein protein in Parkinson's disease (PD), which are markers of neurodegenerative process. Signs of functional disorders in NDD include decreasing visual acuity, lower contrast light sensitivity with the most significant changes at the highest spatial frequencies (18 and 12 cycles per degree), and reduced color vision. These disorders correlate with the severity of cognitive impairment and duration of the disease. Changes in the indicators of psychophysical tests are accompanied by lower central retinal thickness (CRT), which is a consequence of inner layers degeneration. NDD progression is characterized by the stability of psychophysical tests, significant thinning of the peripapillary retinal nerve fiber layer (RNFL) and CRT thickening, which correlates with cognitive disfunction. A b and a -synuclein deposits in artery walls cause lumen narrowing and occlusion of blood vessels, reduced optic nerve disk perfusion density, superficial and deep capillary plexus depletion, expansion of the avascular foveolar zone. Microcirculatory disorders lead to retinal changes, which were proven to correlate negatively with the thickness of inner retinal layers and duration of the disease. An ever-growing need in the identification of specific and sensitive biomarkers at the preclinical stage of NDDs, differentiation of their causes, precise subtype classification, and assessment of progression risk is an evidence of the relevance of studying and identifying functional and structural changes in retinal neurons and axons. Non-invasive and informative methods of multimodal imaging appear to be valuable for NDD diagnosis and monitoring.
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Kasper, J., R. H. Schor, B. J. Yates, and V. J. Wilson. "Three-dimensional sensitivity and caudal projection of neck spindle afferents." Journal of Neurophysiology 59, no. 5 (May 1, 1988): 1497–509. http://dx.doi.org/10.1152/jn.1988.59.5.1497.
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1. We recorded from neck muscle spindle afferents in the C2 dorsal root ganglion of the decerebrate cat using floating electrodes. The afferents presumably innervated mainly ventral and ventrolateral perivertebral muscles, and sternocleidomastoid. Stimuli consisted of combinations of rotatory head movements about the roll/pitch or pitch/yaw axes. An important difference from our earlier experiments (10) was the addition of yaw movement to the stimulus paradigm making possible a three-dimensional analysis of afferent behavior. 2. For each afferent we determined the most effective direction of tilt (orientation of the response vector) in three dimensions by using sinusoidal stimuli that combined pitch and roll, or pitch and yaw, or by measuring the gains to responses to roll, pitch, and yaw rotation. 3. Most afferents were sensitive to rotation around all three axes; pitch and yaw were usually more effective than roll. There was no indication of clustering of response vectors, as might be expected if the receptors were located in a small number of muscles each of which has receptors aligned in a homogeneous direction. 4. The responses of afferents were further studied using sinusoidal and trapezoidal stimuli aligned as closely as possible with the orientation of their response vector. The availability of the yaw stimulus made receptor classification based on response linearity, gain, and dynamic index more reliable than in our earlier experiments (10). 5. Muscle spindle responses were divided into three categories: A, B, and ambiguous. The evidence suggests that category A are probably spindle primary receptors and category B are secondaries. Ambiguous receptors have intermediate properties. 6. The caudal projection of spindle afferents was examined by delivering antidromic stimuli with a movable electrode on the surface of the ipsilateral dorsal column. Eighteen percent of the afferents projected to C4, and 14% as far as C5. Long caudal projections can be found in A, B, and ambiguous receptors with a range of directional sensitivities. 7. The evidence suggests that C2 spindle afferents make synapses in the midcervical segments with interneurons and propriospinal neurons that are part of the intraspinal pathway of the tonic neck reflex.
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Machida, Nozomu, Masanori Terashima, Keisei Taku, Takashi Daimon, Masashi Kimura, Akihisa Sugimoto, Hirofumi Yasui, et al. "A prospective multicenter trial of S-1 with lafutidine vs S-1 as adjuvant chemotherapy for gastric cancer in Japan: AEOLUS." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 91. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.91.
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91 Background: From the result of ACTS-GC study, adjuvant chemotherapy with S-1 for one year is standard therapy of gastric cancer in Japan. In this study, completion rate of pre-planned S-1 treatment was 65.8% and there is still room for improvement on this rate. Lafutidine is a H2 blocker and enhances submucosal blood flow via capsaicin-sensitive afferent neurons. Alleviating effect of lafutidine on toxicity of 5FU leading to discontinuation of adjuvant treatment could be expected. Methods: Patients with histologically confirmed stage II (excluding T1 cases), IIIA, or IIIB (Japanese Classification of Gastric Carcinoma 13th) who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 with lafutidine(L) or S-1 (S). All patients were given S-1 (40mg/m2) for 4 weeks with 2 weeks rest, repeated for 1 year after surgery. Patients of L group received lafutidine (20mg/day) every day for 1 year with S-1. The primary end point was treatment completion rate (TCR) of S-1. Definition of treatment completion was S-1 continuation for 1 year with over 70% planned dose. The secondary end points were toxicity (CTCAE v3.0) and relative total administration dose (RD) of S-1. Results: We randomly assigned 101 patients to the L group and 101 patients to the S group between February 2010 and December 2012 from 17 centers in Japan. After randomization, two patients were found to be ineligible in L group (the absence of cytologic examination of the peritoneal fluid, stageIB) and 1 in S group (allocation violation). TCR was 68.3% in the L group and 60.4% in the S group (p = 0.072, Cochran-Mantel-Haenzel test at a pre-specified one-sided significance level of 0.1). Adverse events of grade 3/4 excluding ineligible example was 30.0% in the L group, and 36.0% in the S group. Patients who require a dose reduction and/or delay of S-1 was 41.6% in the L group, and 51.5% in the S group. RD was 83.9% (range: 1.6-103.7) in the L group, and 84.0% (range: 1.7-103.8) in the S group. No any toxicity of lafutidine was observed. Conclusions: Lafutidine may increase a completion rate of adjuvant chemotherapy using S-1 within a 30% dose reduction for gastric cancer. This result need to be confirmed in double-blind placebo control study. Clinical trial information: UMIN000002703.
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Pruett, J. R., R. J. Sinclair, and H. Burton. "Response Patterns in Second Somatosensory Cortex (SII) of Awake Monkeys to Passively Applied Tactile Gratings." Journal of Neurophysiology 84, no. 2 (August 1, 2000): 780–97. http://dx.doi.org/10.1152/jn.2000.84.2.780.
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This experiment explored the effects of controlled manipulations of three parameters of tactile gratings, groove width (1.07–2.53 mm), contact force (30–90 g), and scanning speed (40–120 mm/s), on the responses of cells in second somatosensory cortex (SII) of awake monkeys that were performing a groove-width classification task with passively presented stimuli. A previous experiment involving an active touch paradigm demonstrated that macaque SII cells code groove-width and hand-movement parameters in their average firing rates. The present study used a passive-touch protocol to remove somatosensory activation related to hand movements that accompany haptic exploration of surfaces. Monkeys maintained a constant hand position while a robotic device delivered stimulation with tactile gratings to a single stabilized finger pad. Single-unit recordings isolated 216 neurons that were retrospectively assigned to SII on histological criteria. Firing patterns for 86 of these SII cells were characterized in detail, while monkeys classified gratings as rough (1.90 and 2.53 mm groove widths) or smooth (1.07 and 1.42 mm groove widths), with trial-wise random, parametric manipulation of force or speed; the monkeys compared 1.07 versus 1.90 mm and 1.42 versus 2.53 mm in alternating blocks of trials. We studied 33 cells with systematic variation of groove width and force, 49 with groove width and speed, and four with all three variables. Sixty-three cells were sensitive to groove width, 43 to force (effects of random force in speed experiments contributed to N), and 34 to speed. Relatively equal numbers of cells changed mean firing rates as positive or negative functions of increasing groove width, force, and/or speed. Cells typically changed mean firing rates for two or three of the independent variables. Effects of groove width, force, and speed were additive or interactive. The variety of response functions was similar to that found in a prior study of primary somatosensory cortex (SI) that used passive touch. The SII sample population showed correlated changes (both positive and negative) in firing rates with increasing groove width and force and to a lesser degree, with increasing groove width and speed. This correlation is consistent with human psychophysical studies that found increasing groove width and force increase perceived roughness magnitude, and it strengthens the argument for SII's direct involvement in roughness perception.
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Stabler, S. E., A. R. Palmer, and I. M. Winter. "Temporal and mean rate discharge patterns of single units in the dorsal cochlear nucleus of the anesthetized guinea pig." Journal of Neurophysiology 76, no. 3 (September 1, 1996): 1667–88. http://dx.doi.org/10.1152/jn.1996.76.3.1667.
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1. We examined the temporal and mean rate discharge characteristics of 514 single units recorded extracellularly from the dorsal cochlear nucleus (DCN) of anesthetized guinea pigs. A mean rate response area (receptive field) was measured for the majority of units in this study. Each response area was placed in one of seven categories (type I to type V and the intermediate types I/III and IV-T) as defined by previous workers. The shape of the best frequency (BF) rate-level function has been used to aid in the distinction between type IV and type IV-T units, and the classification of type II units is based on their relative response to noise and tone bursts. 2. The threshold of single units was normalized to the cochlear action potential (CAP) threshold (a negative relative threshold indicates that the unit's threshold was more sensitive than the corresponding CAP threshold). There were significant differences (P < 0.05; 1-way analysis of variance--Duncan test) between the mean relative thresholds of type IV units (-12 dB) and those of type I (-6.52 dB), type II (-3 dB), and type I/III units (-4.25 dB). There were also significant differences between the relative thresholds of types III and IV-T and those of types I/III and II. 3. Rate-level functions at a unit's BF were divided into groups according to shape and degree of nonmonotonicity. Six units responded with a decrease in firing rate at all suprathreshold sound levels. However, most units increased their discharge rate over approximately the first 20 dB above BF threshold. Units were further subdivided by the change in slope 20 dB above BF threshold. The majority of units (60%) showed monotonic increases in discharge rate with sound level: some rate-level functions clearly resembled the sloping saturation rate-level functions observed in intermediate-threshold auditory nerve fibers. An unexpected finding was the relatively large number of nonmonotonic rate-level functions (40%). Among a relatively homogenous group of projection neurons (predominantly type IV and pause/build units) with nonmonotonic rate-level functions, the range of "best intensities" (the sound level evoking the highest discharge rate) was < 50 dB. This range of best intensities is narrower than found in higher auditory nuclei. 4. Units were also classified by their temporal activity pattern in response to suprathreshold BF tones. The most common pattern identified is the pause/build pattern (n = 294). This temporal activity pattern has been associated with the principal output neuron of the DCN, the fusiform cell. Our definition of pause/build units includes units with an almost constant steady-state discharge rate. Nonmonotonic rate-level functions were observed in 42% (99 of 233) of pause/build units. A measure of discharge regularity (the SD of the interspike interval/mean interspike interval: coefficient of variation, CV) revealed that the majority (82%) of units classified as pause/build and with steady-state discharge rates > 75 spikes/s (n = 142) were characterized by regular discharge patterns (CV = 0.41 +/- 0.15, mean +/- SD). 5. Units characterized by chopper or onset-type discharges were the next most frequently encountered units. The chopper units (n = 75) showed a regular discharge (CV = 0.39 +/- 0.17) similar to that found in recordings from the ventral division of the cochlear nucleus (VCN). One difference between many chopper units in the DCN compared with those recorded in the VCN was the relatively high value (> 5 ms) of the mean interspike interval (and thus the low steady-state discharge rate). The majority (44 of 59; 75%) of chopper units had monotonic rate-level functions. Onset units (n = 47) may represent several response types, linked by the predominance of discharges in response to stimulus onset, and the majority of onset units reported here bear little resemblance to onset units recorded in the VCN of the guinea pig. Approximately 10% of units did not fit easily into any of th
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Di Re, Jessica, Wei-Chun J. Hsu, Cihan B. Kayasandik, Nickolas Fularczyk, T. F. James, Miroslav N. Nenov, Pooran Negi, et al. "Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability." Frontiers in Molecular Neuroscience 14 (June 30, 2021). http://dx.doi.org/10.3389/fnmol.2021.643860.
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The axon initial segment (AIS) is a highly regulated subcellular domain required for neuronal firing. Changes in the AIS protein composition and distribution are a form of structural plasticity, which powerfully regulates neuronal activity and may underlie several neuropsychiatric and neurodegenerative disorders. Despite its physiological and pathophysiological relevance, the signaling pathways mediating AIS protein distribution are still poorly studied. Here, we used confocal imaging and whole-cell patch clamp electrophysiology in primary hippocampal neurons to study how AIS protein composition and neuronal firing varied in response to selected kinase inhibitors targeting the AKT/GSK3 pathway, which has previously been shown to phosphorylate AIS proteins. Image-based features representing the cellular pattern distribution of the voltage-gated Na+ (Nav) channel, ankyrin G, βIV spectrin, and the cell-adhesion molecule neurofascin were analyzed, revealing βIV spectrin as the most sensitive AIS protein to AKT/GSK3 pathway inhibition. Within this pathway, inhibition of AKT by triciribine has the greatest effect on βIV spectrin localization to the AIS and its subcellular distribution within neurons, a phenotype that Support Vector Machine classification was able to accurately distinguish from control. Treatment with triciribine also resulted in increased excitability in primary hippocampal neurons. Thus, perturbations to signaling mechanisms within the AKT pathway contribute to changes in βIV spectrin distribution and neuronal firing that may be associated with neuropsychiatric and neurodegenerative disorders.
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Fogo, Garrett M., Anthony R. Anzell, Kathleen J. Maheras, Sarita Raghunayakula, Joseph M. Wider, Katlynn J. Emaus, Timothy D. Bryson, et al. "Machine learning-based classification of mitochondrial morphology in primary neurons and brain." Scientific Reports 11, no. 1 (March 4, 2021). http://dx.doi.org/10.1038/s41598-021-84528-8.
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AbstractThe mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.
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Nistal, Dominic A., Michael L. Martini, Trevor Hardigan, Nicolas Fernandez, Seunghee Kim-Schulze, Rui Song, Natalia Romano Spica, Julianne Kleitsch, J. D. Mocco, and Christopher P. Kellner. "Elucidating a Proteomic Signature for the Detection of Intracerebral Aneurysms." Neurosurgery 66, Supplement_1 (August 20, 2019). http://dx.doi.org/10.1093/neuros/nyz310_170.
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Abstract INTRODUCTION Intracranial aneurysms (IA) occur in approximately 2% of the general population and are the leading cause for spontaneous subarachnoid hemorrhage (SAH). Recent studies have shown that inflammatory and cell adhesion molecules are associated with the formation and progression of aneurysmal growth. In this study, we utilized proteomic data from patients with known intracranial aneurysms and age, sex, and comorbidity matched controls to identify a proteomic signature that is highly consistent with the presence of an intracranial aneurysm. METHODS A total of 56 patients were prospectively enrolled in this study, 28 of which had unruptured intracranial aneurysms. Protein was isolated from peripheral blood samples and sent for Proseek multiplex immunoassay processing. Of the 92 analytes in the selected Olink Inflammatory Panel, 70 had variable expression across our cohort and were included for analyses. Multivariate regression models were constructed to predict the presence of an aneurysm. Support Vector Machine (SVM) learning and naïve Bayes algorithms were developed with an 80/20: training/test data separation to determine the precision and reliability of the proteomic signature. RESULTS Of the 28 patients, 82.1% (n = 23) were female, with a mean aneurysm size of 8.9 mm. Logistic regression analysis revealed 8 highly sensitive analytes that were predictive of the presence of an aneurysm at a threshold of P < .0001. The support vector machine learning and naïve Bayes classification algorithms performed well with a positive predictive value of 100% and 85.7% and a sensitivity of 100% and 100%, respectively (Brier score = 0.032, 0.083). CONCLUSION This study leveraged individualized data from patients with IA to identify specific protein analytes that predict the presence of an aneurysm. To our knowledge this is the first proteomic signature developed for the purpose of identifying IA’s prior to rupture. Future research with increased sample size will allow for the validation and strengthening of this predictive signature.
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Eckerdt, Frank D., Jonathan B. Bell, Christopher Gonzalez, Michael S. Oh, Ricardo E. Perez, Candice Mazewski, Mariafausta Fischietti, Stewart Goldman, Ichiro Nakano, and Leonidas C. Platanias. "Combined PI3Kα-mTOR Targeting of Glioma Stem Cells." Scientific Reports 10, no. 1 (December 2020). http://dx.doi.org/10.1038/s41598-020-78788-z.
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AbstractGlioblastoma (GBM) is the most common and lethal primary intrinsic tumour of the adult brain and evidence indicates disease progression is driven by glioma stem cells (GSCs). Extensive advances in the molecular characterization of GBM allowed classification into proneural, mesenchymal and classical subtypes, and have raised expectations these insights may predict response to targeted therapies. We utilized GBM neurospheres that display GSC characteristics and found activation of the PI3K/AKT pathway in sphere-forming cells. The PI3Kα selective inhibitor alpelisib blocked PI3K/AKT activation and inhibited spheroid growth, suggesting an essential role for the PI3Kα catalytic isoform. p110α expression was highest in the proneural subtype and this was associated with increased phosphorylation of AKT. Further, employing the GBM BioDP, we found co-expression of PIK3CA with the neuronal stem/progenitor marker NES was associated with poor prognosis in PN GBM patients, indicating a unique role for PI3Kα in PN GSCs. Alpelisib inhibited GSC neurosphere growth and these effects were more pronounced in GSCs of the PN subtype. The antineoplastic effects of alpelisib were substantially enhanced when combined with pharmacologic mTOR inhibition. These findings identify the alpha catalytic PI3K isoform as a unique therapeutic target in proneural GBM and suggest that pharmacological mTOR inhibition may sensitize GSCs to selective PI3Kα inhibition.
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Ebrahimzadeh, Elias, Mostafa Asgarinejad, Sarah Saliminia, Sarvenaz Ashoori, and Masoud Seraji. "PREDICTING CLINICAL RESPONSE TO TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION USING TIME-FREQUENCY EEG SIGNAL PROCESSING." Biomedical Engineering: Applications, Basis and Communications, August 14, 2021, 2150048. http://dx.doi.org/10.4015/s1016237221500484.
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Repetitive transcranial magnetic stimulation (rTMS) is defined as a noninvasive technique of brain stimulation conducted for both diagnostic and therapeutic purposes. rTMS can effectively excite the brain neurons and increase brain plasticity, which becomes particularly useful in psychiatric and neurological fields. Biomarkers that predict clinical outcomes in depression are essential for increasing the precision of treatments and clinical outcomes. The electroencephalogram (EEG) is a noninvasive neurophysiological test that is promising as a biomarker sensitive to treatment effects. The aim of our study was to investigate a novel nonlinear index of the resting state EEG activity as a predictor of clinical outcome and compare its predictive capacity to traditional frequency-based indices. EEG was recorded from 50 patients with treatment resistant depression (TRD) and 24 healthy comparison (HC) subjects. TRD patients were treated with excitatory rTMS to the dorsolateral prefrontal cortex (DLPFC) for 4–6 weeks. EEG signals were first decomposed using the ICA algorithm and the extracted components were then processed by time-frequency analysis. We then go on to compare the participants’ depression severity before, after, and 2 months after finishing the last treatment session using the proposed rTMS therapy. Absolute powers (APs), band powers (BPs), and theta and beta band entropies (BAs), which were extracted from the EEG, are used as features for the classification of changes in patients and normal cases after applying rTMS. Accordingly, we can go beyond the Beck score and clinically classify the EEG signal into two classes: depression and normal. The results demonstrated 78.37%, 74.32%, and 82.43% accuracy for artificial neural network (ANN), [Formula: see text]-nearest neighbor (KNN), and support vector machine (SVM) classifiers, respectively, indicating the superiority of the proposed method to those mentioned in similar studies. Also, the electrophysiological changes are shown to be evident in patients with major depression. Our data show that the time-frequency index yields superior outcome prediction performance compared to the traditional frequency band indices. Our findings warrant further investigation of EEG-based biomarkers in depression.