A Novel Source-Filter Stochastic Model for Voice Production.

The novel stochastic model to produce voiced sounds proposed in this paper uses the source-filter Fant theory to generate voice signals and, consequently, it does not consider the coupling between the vocal tract and the vocal folds. Two novelties are proposed in the paper. The first one is the new model obtained from the unification of two other deterministic one mass-spring-damper models obtained from the literature and the second one is to build a stochastic model which can generate and control the level of jitter resulting even in hoarse voice signals or with pathological characteristics but using a simpler model than those ones discussed in the literature. An inverse stochastic problem is then solved for two cases, considering a normal voice and other obtained from a case of paralysis on the vocal folds. The parameters of the model are identified in the two cases allowing the validation of the model.

Stochastic mechanical model of vocal folds for producing jitter and for identifying pathologies through real voices.

Jitter, in voice production applications, is a random phenomenon characterized by the deviation of the glottal cycle length with respect to a mean value. Its study can help in identifying pathologies related to the vocal folds according to the values obtained through the different ways to measure it. This paper aims to propose a stochastic model, considering three control parameters, to generate jitter based on a deterministic one-mass model for the dynamics of the vocal folds and to identify parameters from the stochastic model taking into account real voice signals experimentally obtained. To solve the corresponding stochastic inverse problem, the cost function used is based on the distance between probability density functions of the random variables associated with the fundamental frequencies obtained by the experimental voices and the simulated ones, and also on the distance between features extracted from the voice signals, simulated and experimental, to calculate jitter. The results obtained show that the model proposed is valid and some samples of voices are synthesized considering the identified parameters for normal and pathological cases. The strategy adopted is also a novelty and mainly because a solution was obtained. In addition to the use of three parameters to construct the model of jitter, it is the discussion of a parameter related to the bandwidth of the power spectral density function of the stochastic process to measure the quality of the signal generated. A study about the influence of all the main parameters is also performed. The identification of the parameters of the model considering pathological cases is maybe of all novelties introduced by the paper the most interesting.

Effects of bicuculline application on the somatosensory responses of secondary vestibular neurons.

Limb somatosensory signals modify the discharge of vestibular neurons and elicit postural reflexes, which stabilize the body position. The aim of this study was to investigate the contribution of the γ-amino-butyric-acid (GABA) to the responsiveness of vestibular neurons to somatosensory inputs. The activity of 128 vestibular units was recorded in anesthetized rats in resting conditions and during sinusoidal foreleg rotation around the elbow or shoulder joints (0.026-0.625Hz, 45° peak amplitude). None of the recorded units was influenced by elbow rotation, while 40% of them responded to shoulder rotation. The selective GABAA antagonist receptor, bicuculline methiodine (BIC), was applied by microiontophoresis on single vestibular neurons and the changes in their activity at rest and during somatosensory stimulation was studied. In about half of cells the resting activity increased after the BIC application: 75% of these neurons showed also an increased response to somatosensory inputs whereas 17% exhibited a decrease. Changes in responsiveness in both directions were detected also in the units whose resting activity was not influenced by BIC. These data suggest that the responses of vestibular neurons to somatosensory inputs are modulated by GABA through a tonic release, which modifies the membrane response to the synaptic current. It is also possible that a phasic release of GABA occurs during foreleg rotation, shaping the stimulus-elicited current passing through the membrane. If this is the case, the changes in the relative position of body segments would modify the GABA release inducing changes in the vestibular reflexes and in learning processes that modify their spatio-temporal development.

Acetyl-L-carnitine affects nonassociative learning processes in the leech Hirudo medicinalis.

Acetyl-L-carnitine is a natural molecule widely distributed in vertebrate and invertebrate nervous system. It is known to have significant effects on neuronal activity playing a role as neuroprotective and anti-nociceptive agent, as well as neuromodulatory factor. About its capability of affecting learning processes the available data are controversial. In the present study, we utilized the simplified model system of the leech Hirudo medicinalis to analyze the effects of acetyl-L-carnitine, assessing whether and how it might affect elementary forms of nonassociative learning processes. In leeches with the head ganglion disconnected from the first segmental ganglion, repetitive application of weak electrical shocks onto the caudal portion of the body wall induces habituation of swim induction whereas brush strokes on the dorsal skin produces sensitization or dishabituation when the nociceptive stimulus is delivered on previously habituated animals. Herein, the effects of different concentrations of acetyl-L-carnitine (2 mM - 0.05 mM) have been tested at different times on both sensitization and dishabituation. The results show that a single treatment of acetyl-L-carnitine blocked the onset of sensitization in a dose- and time-dependent manner. In fact, the most effective concentration able to block this process was 2 mM, which induced its major effects 11 days after the treatment, whereas 0.05 mM was unable to affect the sensitization process at all considered time points. On the contrary, acetyl-L-carnitine did not completely abolish dishabituation at the tested concentrations and at every time point. Finally, acetyl-L-carnitine also impaired the habituation of swim induction, but only 11 days after treatment.

Acetyl-L-carnitine induces a sustained potentiation of the afterhyperpolarization.

Acetyl-L-carnitine is known to improve many aspects of the neural activity even if its exact role in neurotransmission is still unknown. This study investigates the effects of acetyl-L-carnitine in T segmental sensory neurons of the leech Hirudo medicinalis. These neurons are involved in some forms of neural plasticity associated with learning processes. Their physiological firing is accompanied by a large afterhyperpolarization that is mainly due to the Na+/K+ ATPase activity and partially to a Ca2+ -dependent K+ current. A clear-cut hyperpolarization and a significant increase of the afterhyperpolarization have been recorded in T neurons of leeches injected with 2 mM acetyl-L-carnitine some days before. Acute treatments of 50 microM acetyl-L-carnitine induced similar effects in T cells of naive animals. In the presence of apamin, a pharmacological blocker of Ca2+ -dependent K+ channel, acetyl-L-carnitine still enhanced the residual afterhyperpolarization, suggesting an effect of the drug on the Na+/K+ATPase. Acetyl-L-carnitine also increased the hyperpolarization induced by intracellular injection of Na+ ions. Therefore, acetyl-L-carnitine seems to be able to exert a positive sustained effect on the Na+/K+ ATPase activity in leech T sensory neurons. Moreover, in these cells, widely arborized, the afterhyperpolarization seems to play an important role in determining the action potential transmission at neuritic bifurcations. A computational model of a T cell has been previously developed considering detailed data for geometry and the modulation of the pump current. Herein, we showed that to a larger afterhyperpolarization, due to the acetyl-L-carnitine-induced effects, corresponds a decrement in the number of action potentials reaching synaptic terminals.

Nonassociative learning in the leech Hirudo medicinalis.

In the present study we examined nonassociative learning of the induction of swimming which was evoked by weak electrical stimulation in the leech Hirudo medicinalis. The behavioural response to stimuli applied repeatedly to the body wall at an inter-trial interval (ITI) of 1 min decreased, eventually ceased, and then recovered spontaneously. More rapid reduction of the behavioural response occurred in repeated training sessions. This decrement of response conformed to the operational definition of habituation. Moreover, a noxious stimulus (i.e. brushing on the skin) facilitated the decremented response (dishabituation). In addition, we compared response decrement in naive animals with decrement in dishabituated and in sensitized animals. The analysis of the best fitting functions of the habituation, the habituation of dishabituation and the habituation of sensitization revealed interesting differences in these processes.

Enhancement of bone ingrowth into collagen/HA composite implants using e-PTFE membranes.

The objective of this investigation was to study the effectiveness of expanded polytetrafluoroethylene (e-PTFE) membranes for enhancement of bone ingrowth through subperiosteally implanted collagen/HA composite blocks. Twelve rabbits aged 12-15 months served as the experimental animals in this study. Two compressed Collagen/HA composite blocks in the shape of two attached cylinders of different diameters were inserted into two defects of each rabbit calvarium, the smaller cylinder being intrabony, the larger subperiosteal in location. One of the two implants was covered with non-resorbable e-PTFE membrane. The other implant was left uncovered. Specimens were obtained at 4, 8, and 12 weeks. While the implant specimens on the membrane side showed progressive bone formation between and around HA particles at the subperiosteal extrabony locations, the HA particles on the non-membrane side were surrounded and separated by dense fibrous tissue. At intraosseous sites, HA particles were surrounded by new bone throughout the defect on the membrane side, but new bone formation occurred only along the periphery on the non-membrane side. It appears that guided tissue regeneration may be used to enhance new bone formation around and between subperiosteally implanted HA particles.

The effect of N-nitrosonornicotine on the buccal mucosa of Syrian hamsters.

PURPOSE: The carcinogens in smokeless tobacco have been identified as the tobacco-specific nitrosamines and the effect of one of these, N-Nitrosonornicotine (NNN), on the buccal mucosa of the Syrian hamster was studied. MATERIALS AND METHODS: Buccal pouches of 36 Syrian hamsters were painted five times per week for 24 weeks with 10 mg/mL 98% pure NNN in suspension with mineral oil. Animals were killed at 6, 8, 12, and 24 weeks. RESULTS: At 6 weeks, the buccal pouch mucosa of the experimental animals appeared clinically more hyperemic than those of the controls. From 12 weeks onward, all experimental animals showed epithelial hyperplasia and inflammation on histologic examination. Three animals killed at 24 weeks showed mild epithelial dysplasia. CONCLUSIONS: Exposure of Syrian hamster buccal mucosa to NNN, five times per week for 24 weeks, did not result in clinical or histologic cancerous changes. NNN may require other factors for cancer production, such as a cocarcinogen, a higher concentration, or a longer period of application.