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PubMed2004

Recent advances in laryngeal sensorimotor control for voice, speech and swallowing.

PURPOSE OF REVIEW: This article reviews advances in knowledge on laryngeal sensorimotor control affecting the assessment, understanding, and treatment of laryngeal motor control disorders in voice, speech, and swallowing. Three topics are covered: new knowledge on laryngeal innervation and central nervous system control from basic research studies, the role of laryngeal sensation in normal swallowing and dysphagia in patients, and new approaches to the restoration of laryngeal motor control after recurrent laryngeal nerve disorders. RECENT FINDINGS: A significant advance this year was tracing the efferent pathways from the cortex to the brainstem in monkeys. This provided new information on subcortical and brainstem connections in the laryngeal efferent pathways. Laryngeal sensory feedback continued to receive attention, and the role of sensory feedback in the control of the pharyngeal phase of swallowing is now well established. Further developments in neuromotor monitoring of the recurrent laryngeal nerve during thyroidectomy were seen, and a large case series recommended that these techniques become standard practice for surgery for thyroid benign recurrence or malignancy. Finally, the first tissue engineering papers in the field of vocal fold tissue and nerve restoration were published this year, beginning an exciting new approach to restoration of laryngeal motor control. SUMMARY: Considerable attention has been given to laryngeal muscle physiology, denervation, and sensation in neurolaryngology. Relatively limited understanding is available regarding the central nervous system integrative control of laryngeal function for speech, respiration, and swallowing.

Animals↗
PubMed1990

On the determination of input sound frequencies by the auditory central processor.

There are two schools of thought with regard to how the auditory central processor achieves good frequency resolution. The first is based on the steep 300 dB/oct rolloff; the second on the fact that the action potential (AP) output of neurons associated with hair cells is partially synchronized to the incoming fin or its subharmonics. The main objection to this proposal is that synchronization seems to fail for high-frequency audio inputs. It is shown that this failure may be due to experimental difficulties. It is impossible to avoid trauma to the cochlea and/or auditory nerve. To study synchronization at 10,000 Hz, the interspike-interval (ISI) histogram requires a timing accuracy of 4 microseconds or better despite input AP's that have a rise time of 200 microseconds. Synthetic AP ISI histograms are derived for a) unstimulated; b) fully synchronized; c) low-frequency; and d) high-frequency audio input conditions. The latter are compared with typical experimentally derived data. Hypothetical processing by reverberatory neurons is also considered.

Cochlea↗
PubMed2001

Neuro-fuzzy extraction of angular information from muscle afferents for ankle control during standing in paraplegic subjects: an animal model.

This paper is part of a project whose aim is the implementation of closed-loop control of ankle angular position during functional electrical stimulation (FES) assisted standing in paraplegic subjects using natural sensory information. In this paper, a neural fuzzy (NF) model is implemented to extract angular position information from the electroneurographic signals recorded from muscle afferents using cuff electrodes in an animal model. The NF model, named dynamic nonsingleton fuzzy logic system is a Mamdani-like fuzzy system, implemented in the framework of recurrent neural networks. The fuzzification procedure implemented was the nonsingleton technique which has been shown in previous works to be able to take into account the uncertainty in the data. The proposed algorithm was tested in different situations and was able to predict reasonably well the ankle angular trajectories especially for small excursions (as during standing) and when the stimulation sites are far from the registration sites. This suggests it may be possible to use activity from muscle afferents recorded with cuff electrodes for FES closed-loop control of ankle position during quite standing.

Algorithms↗
PubMed2005

Recruitment of local excitatory circuits in the superior colliculus following deafferentation and the regeneration of retinocollicular inputs.

The local synaptic connectivity in the superficial gray layer of the superior colliculus (SC) was assessed following retinal ganglion cell axonal regeneration through a peripheral nerve graft into the SC of Lister Hooded rats, using in vitro brain slice techniques. Repair was effected between the ipsilateral eye and SC, following bilateral lesion of optic nerves and ablation of ipsilateral occipital cortex. Deafferentation surgery alone resulted in a complete loss of synaptic potentials of extrinsic origin, once both retinal and cortical inputs were removed. Stimulation of graft insertion sites elicited synaptic responses comprising monosynaptic and network-mediated depolarising events. This activity, together with similar spontaneous bursts of depolarising events and action potential firing, was generated by the activation of non-N-methyl-D-aspartate glutamate receptors. This behaviour may reflect the development of a local recurrent synaptic connectivity following the repair surgery, as both evoked and spontaneous responses developed into large long-lasting bursts of excitatory activity when inhibition mediated by GABA receptors was blocked. These results suggest that the ultrastructural changes in the superficial layers of the SC resulting from deafferentation are reflected functionally at the synaptic level in the target structure even after repair. Such changes are likely to compromise the ability of the target structure to function normally during information processing. Therefore, although axons regenerating along peripheral nerve grafts can make functional synaptic connections, their efficacy in activating the target structure will probably be compromised by local changes in synaptic connectivity.

Action Potentials↗
PubMed2004

Functional organization of respiratory neurones: a brief review of current questions and speculations.

This article presents a short overview of current knowledge about the medullary respiratory neurones and the generation of breathing rhythm. The background respiratory neurophysiology of the medulla and pons is briefly reviewed, with some current ideas about the organization of the pontine-medullary respiratory control system and its development. Questions and speculations about the organization and generation of respiratory rhythm are included, with a view to stimulating experiments to provide answers.

Animals↗
PubMed2006

Brainstem circuits regulating gastric function.

Brainstem parasympathetic circuits that modulate digestive functions of the stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus of the vagus (DMV). A large body of evidence has shown that neuronal communications between the NTS and the DMV are plastic and are regulated by the presence of a variety of neurotransmitters and circulating hormones as well as the presence, or absence, of afferent input to the NTS. These data suggest that descending central nervous system inputs as well as hormonal and afferent feedback resulting from the digestive process can powerfully regulate vago-vagal reflex sensitivity. This paper first reviews the essential "static" organization and function of vago-vagal gastric control neurocircuitry. We then present data on the opioidergic modulation of NTS connections with the DMV as an example of the "gating" of these reflexes, i.e., how neurotransmitters, hormones, and vagal afferent traffic can make an otherwise static autonomic reflex highly plastic.

Animals↗
PubMed2005

Chemical activation of pre-Bötzinger complex in vivo reduces respiratory network complexity.

In the in vivo anesthetized adult cat model, multiple patterns of inspiratory motor discharge have been recorded in response to chemical stimulation and focal hypoxia of the pre-Bötzinger complex (pre-BötC), suggesting that this region may participate in the generation of complex respiratory dynamics. The complexity of a signal can be quantified using approximate entropy (ApEn) and multiscale entropy (MSEn) methods, both of which measure the regularity (orderliness) in a time series, with the latter method taking into consideration temporal fluctuations in the underlying dynamics. The current investigation was undertaken to examine the effects of pre-BötC-induced excitation of phasic phrenic nerve discharge, which is characterized by high-amplitude, rapid-rate-of-rise, short-duration bursts, on the complexity of the central inspiratory neural controller in the vagotomized, chloralose-anesthetized adult cat model. To assess inspiratory neural network complexity, we calculated the ApEn and MSEn of phrenic nerve bursts during eupneic (basal) discharge and during pre-BötC-induced excitation of phasic inspiratory bursts. Chemical stimulation of the pre-BötC using DL-homocysteic acid (DLH; 10 mM; 10-20 nl; n=10) significantly reduced the ApEn from 0.982+/-0.066 (mean+/-SE) to 0.664+/-0.067 (P<0.001) followed by recovery ( approximately 1-2 min after DLH) of the ApEn to 1.014+/-0.067; a slightly enhanced magnitude reduction in MSEn was observed. Focal pre-BötC hypoxia (induced by sodium cyanide; NaCN; 1 mM; 20 nl; n=2) also elicited a reduction in both ApEn and MSEn, similar to those observed for the DLH-induced response. These observations demonstrate that activation of the pre-BötC reduces inspiratory network complexity, suggesting a role for the pre-BötC in regulation of complex respiratory dynamics.

Animals↗
PubMed1994

Distributed actions and dynamic associations in respiratory-related neuronal assemblies of the ventrolateral medulla and brain stem midline: evidence from spike train analysis.

1. Considerable evidence indicates that neurons in the brain stem midline and ventrolateral medulla participate in the control of breathing. This work was undertaken to detect and evaluate evidence for functional links that coordinate the parallel operations of neurons distributed in these two domains. 2. Data were from 51 Dial-urethan-anesthetized, bilaterally vagotomized, paralyzed, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor simultaneously spike trains in two or three of the following regions: n. raphe obscurus-n. raphe pallidus, n. raphe magnus, rostral ventrolateral medulla, and caudal ventrolateral medulla. Efferent phrenic nerve activity was recorded to indicate the phases of the respiratory cycle. Electrodes in the ventral spinal cord (C3) were used in antidromic stimulation tests for spinal projections of neurons. 3. Spike trains of 1,243 neurons were tested for respiratory modulated firing rates with cycle-triggered histograms and an analysis of variance with the use of a subjects-by-treatments experimental design. Functional associations were detected and evaluated with cross-correlograms, snowflakes, and the gravity method. 4. Each of 2,310 pairs of neurons studied included one neuron monitored within 0.6 nm of the brain stem midline and a second cell recorded in the ventrolateral medulla; 117 of these pairs (5%) included a neuron with a spinal projection, identified with antidromic stimulation methods, that extended to at least the third cervical segment. Short-time scale correlations were detected in 110 (4.7%) pairs of neurons. Primary cross-correlogram features included 40 central peaks, 47 offset peaks, 4 central troughs, and 19 offset troughs. 5. In 14 data sets, multiple short-time scale correlations were found among three or more simultaneously recorded neurons distributed between both midline and ventrolateral domains. The results suggested that elements of up to three layers of interneurons were monitored simultaneously. Evidence for concurrent serial and parallel regulation of impulse synchrony was detected. Gravitational representations demonstrated respiratory-phase dependent synchrony among neurons distributed in both brain stem regions. 6. The results support a model of the brain stem respiratory network composed of coordinated distributed subassemblies and provide evidence for several hypotheses. 1) Copies of respiratory drive information from rostral ventrolateral medullary (RVLM) respiratory neurons are transmitted to midline neurons. 2) Midline neurons act on respiratory-related neurons in the RVLM to modulate phase timing. 3) Impulse synchrony of midline neurons is influenced by concurrent divergent actions of both midline and ventrolateral neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Altered respiratory activity and respiratory regulations in adult monoamine oxidase A-deficient mice.

The abnormal metabolism of serotonin during the perinatal period alters respiratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flores et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied the respiratory activity and regulations in adult C3H and Tg8 mice. First, plethysmographic and pneumotachographic analyses of breathing patterns revealed weaker tidal volumes and shorter inspiratory durations in Tg8 than in C3H mice. Second, electrophysiological studies showed that the firing activity of inspiratory medullary neurons and phrenic motoneurons is higher in Tg8 mice and that of the intercostal motoneurons in C3H mice. Third, histological studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. dl-p-chlorophenyl-alanine treatments applied to Tg8 mice depress the high serotonin level present during adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not significantly affected. Therefore in Tg8 mice the high serotonin level occurring during the perinatal period alters respiratory network maturation and produces a permanent respiratory dysfunction, whereas the high serotonin level present in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the respiratory network and in both the respiratory activity and the respiratory regulations.

Animals↗
PubMed1985

[Pathogenesis of diabetic neuropathies].

There are two types of diabetic neuropathy: on the one hand, mononeuritis and, on the other hand, the symmetric polyneuropathy with a glove and stocking distribution and autonomic polyneuropathy. Mononeuritis (or mononeuritis multiplex) seems to be the result of ischaemia due to intrinsic or extrinsic (altered coagulability) vascular disease. Polyneuropathy is probably due to metabolic factors related to chronic hyperglycaemia: abnormal nerve energy metabolism, impaired axonal transport, increased activity of the sorbitol pathway, non-enzymatic nerve protein glucosylation and abnormal myo-inositol metabolism. The respective roles of these different factors in the pathogenesis of polyneuropathy are discussed.

Animals↗
PubMed1985

[Cephalic insulin secretion--neuromorphologic findings].

The paper presented deals with the electron microscopy bases of experimental results, which show a cephalic insulin secretion. The B cell-producing insulin--is a highly innervated endocrine cell. Several nerve endings often form synaptic connexions at a single B cell. The synaptic clefts are usually 20-25 nm. The nerve endings cause an evident impression of the cell membrane. The narrow neuro-cellular connexions form a structural bases of the cephalic insulin response. The interruption of this reflex loop caused by vagotomy eliminates cephalic mechanism. However, the innervation of the islets (electron microscopic examination) remains unaffected. Therefore the intramural nervous mechanism seems to be not excluded by vagotomy.

Animals↗
PubMed1995

Simulation of oculomotor post-inhibitory rebound burst firing using a Hodgkin-Huxley model of a neuron.

A number of theories have been reported on post saccade phenomenon describing dynamic overshoot, glissadic overshoot and undershoot, and undershoot, all naturally and frequently occurring saccadic eye movements. Electrophysiological evidence for post-inhibitory rebound burst firing activity during saccadic eye movements is prevalent in the literature. However, the cause for the phenomenon is not known. Marked inhibition of neurons within the Paramedian Pontine Reticular Formation often results in post-inhibitory rebound burst firing activity at the beginning and end of a saccade. In this paper, post-inhibitory rebound burst firing activity after marked hyperpolarization is postulated to occur in the Paramedian Pontine Reticular Formation due to a low membrane threshold voltage. With this biophysical property, a single neuron is capable of firing at high rates automatically and without stimulation when released from inhibition. Simulations using the Hodgkin-Huxley model of a neuron demonstrate that a single neuron is capable of firing at high rates automatically without stimulation when released from inhibition.

Electrophysiology↗
PubMed1999

Immunohistochemical evidence for the brevican-tenascin-R interaction: colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain.

Brevican is one of the most abundant chondroitin sulfate proteoglycans in the adult rat brain. We have recently shown that the C-type lectin domain of brevican binds fibronectin type III domains 3-5 of tenascin-R. Here we report strong evidence for a physiological basis for this interaction. Substantial brevican immunoreactivity was detected in a number of nuclei and in the reticular formations throughout the midbrain and hindbrain, including, but not limited to, the deep cerebellar nuclei, the trapezoid body, the red nucleus, the oculomotor nucleus, the vestibular nucleus, the cochlear nucleus, the gigantocellular reticular nucleus, the motor trigeminal nucleus, and the lateral superior olive. Most of the brevican immunoreactivity exhibited pericellular and reticular staining patterns. In almost all of these sites, brevican immunoreactivity colocalized with that of tenascin-R, which was also substantially codistributed with versican, another member of the lectican family. Detailed analysis revealed that the pericellular staining of brevican resembled that in perineuronal nets in which tenascin-R has been localized. Immunoelectron microscopy identified brevican immunoreactivity in the intercellular spaces surrounding presynaptic boutons and on their surfaces, but not in the synaptic clefts or in their immediate vicinity, a distribution pattern consistent with perineuronal nets. Taken together, our results provide strong evidence that the previously reported interactions between brevican and tenascin-R may play a functional role within the perineuronal nets.

Age Factors↗
PubMed1987

Extracellular ATP modulates calcium uptake and transmitter release at the neuromuscular junction.

Adenosine, AMP, ADP, and ATP were tested for their ability to modulate evoked quantal transmitter release at excitor-opener nerve terminals in the crayfish walking leg. Only ATP was found to have a significant effect, inhibiting release by 43%. To determine whether the effects of extracellular ATP on transmitter release were related to changes in free Ca2+ levels in the nerve terminal, net 45Ca uptake was measured in regions of the nerve near the terminal; although resting 45Ca uptake was increased by 5 mM exogenous ATP. Thus, extracellular ATP normally inhibits evoked transmitter release; this is associated with reduced stimulation-induced net Ca2+ uptake into the synaptic terminal. To explore the possibility that metabolic factors might be involved, nerve ATP levels were reduced by greater than or equal to 50% by omitting glucose from the bathing solution. Although quantal content and synaptic delay were unaffected by reduced intracellular ATP, under these conditions 5 mM exogenous ATP failed to reduce quantal release. Five millimolars of ATP did increase synaptic facilitation, however, which is consistent with a reduced ability to regulate intracellular free Ca2+. Therefore, under conditions of reduced intracellular ATP, the increased resting Ca2+ uptake produced by 5 mM ATP is not buffered completely. This leads to elevated free Ca2+ levels in the nerve terminal, increasing the amount of transmitter released following an action potential.

Acetylcholine↗
PubMed2001

Perineuronal nets in the rat medial nucleus of the trapezoid body surround neurons immunoreactive for various amino acids, calcium-binding proteins and the potassium channel subunit Kv3.1b.

Perineuronal nets (PNs) are known as chondroitin sulfate-rich, lattice-like coatings of the extracellular matrix ensheathing mainly GABAergic, parvalbumin-containing neurons especially in the cerebral cortex. PNs have also been detected around GABA-immunonegative cells which were shown to be not aminergic, cholinergic, nitrinergic or peptidergic in various brain regions of some mammalian species. To find out whether glycine and aspartate may occur in net-bearing neurons the present study was focused on the rat medial nucleus of the trapezoid body (MNTB) which contains a large portion of cells immunoreactive for these amino acids, but appears to be devoid of GABA-immunoreactive cell bodies. PNs were detected around many glycine- and aspartate-immunopositive neurons in the MNTB by carbocyanine double labeling and confocal laser scanning microscopy. An additional finding was that the lectin-cytochemically stained extracellular matrix surrounds the calretinin-immunoreactive calyces of Held known as giant glutamatergic endbulbs which cover glycinergic principal cells in the MNTB. As elucidated by triple fluorescence labeling, the vast majority of somata co-expressed the calcium-binding proteins parvalbumin and calbindin, but not calretinin. The observed co-localization of PNs and immunoreactivity for the voltage-dependent potassium channel Kv3.1b - as an established marker of fast-firing parvalbumin-containing neurons - supports the assumed function of PNs as a cation exchanger ensuring rapid ion transport as required by highly active nerve cells.

Amino Acids↗
PubMed2002

Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory.

Brevican is a brain-specific proteoglycan which is found in specialized extracellular matrix structures called perineuronal nets. Brevican increases the invasiveness of glioma cells in vivo and has been suggested to play a role in central nervous system fiber tract development. To study the role of brevican in the development and function of the brain, we generated mice lacking a functional brevican gene. These mice are viable and fertile and have a normal life span. Brain anatomy was normal, although alterations in the expression of neurocan were detected. Perineuronal nets formed but appeared to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect. Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles.

Animals↗