Os resultados do implante coclear em crianças portadoras de Neuropatia Auditiva: revisão de literatura The results of cochlear implants in children with Auditory Neuropathy: literature review

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Rafaela Carolina Lopez Silva

2007-09-01

Full Text Available A Neuropatia Auditiva é um distúrbio na condução do estímulo sonoro, provavelmente relacionado à alteração da mielinização das fibras do nervo auditivo. Os avanços tecnológicos têm levado ao aumento nos recursos de diagnóstico e intervenção nos casos de deficiência auditiva por etiologia de Neuropatia Auditiva. O objetivo do presente estudo foi pesquisar na literatura os resultados obtidos em crianças com Neuropatia Auditiva após implante coclear. Foi realizado um trabalho de revisão bibliográfica em livros, periódicos e internet dos últimos dez anos sobre crianças com Neuropatia Auditiva usuárias de implante coclear. As pesquisas sugerem que a estimulação elétrica é capaz de compensar a dessincronia do nervo e que o implante coclear é um recurso para a (rehabilitação da audição em crianças portadoras de Neuropatia Auditiva. O uso do implante coclear permite melhoria significativa nas habilidades da audição e da comunicação. No entanto, as habilidades adquiridas parecem sofrer influência de diversos fatores como: tempo de uso do dispositivo, existência de um processo terapêutico sistemático, época do diagnóstico e a idade da criança.Auditory Neuropathy is a disorder in the transmission of the sound stimulus, probably related to mielinization alterations of auditory nerve fibers. Technology advances have been increasing diagnostic and intervention resources in cases of hearing loss caused by auditory neuropathy. The aim of the present study was to research the available literature about the results obtained with children with Auditory Neuropathy after cochlear implants. An ample review was conducted on books, articles and the internet, over the last 10 years, regarding children with Auditory Neuropathy, users of cochlear implants. The available data suggest that electric stimulation can compensate neural asynchrony and that cochlear implants aid in the rehabilitation process of children with Auditory

IMPAIRED PROCESSING IN THE PRIMARY AUDITORY CORTEX OF AN ANIMAL MODEL OF AUTISM

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Renata eAnomal

2015-11-01

Full Text Available Autism is a neurodevelopmental disorder clinically characterized by deficits in communication, lack of social interaction and, repetitive behaviors with restricted interests. A number of studies have reported that sensory perception abnormalities are common in autistic individuals and might contribute to the complex behavioral symptoms of the disorder. In this context, hearing incongruence is particularly prevalent. Considering that some of this abnormal processing might stem from the unbalance of inhibitory and excitatory drives in brain circuitries, we used an animal model of autism induced by valproic acid (VPA during pregnancy in order to investigate the tonotopic organization of the primary auditory cortex (AI and its local inhibitory circuitry. Our results show that VPA rats have distorted primary auditory maps with over-representation of high frequencies, broadly tuned receptive fields and higher sound intensity thresholds as compared to controls. However, we did not detect differences in the number of parvalbumin-positive interneurons in AI of VPA and control rats. Altogether our findings show that neurophysiological impairments of hearing perception in this autism model occur independently of alterations in the number of parvalbumin-expressing interneurons. These data support the notion that fine circuit alterations, rather than gross cellular modification, could lead to neurophysiological changes in the autistic brain.

An animal model for tinnitus.

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Jastreboff, P J; Brennan, J F; Sasaki, C T

1988-03-01

Subjective tinnitus remains obscure, widespread, and without apparent cure. In the absence of a suitable animal model, past investigations took place in humans, resulting in studies that were understandably restricted by the nature of human investigation. Within this context, the development of a valid animal model would be considered a major breakthrough in this field of investigation. Our results showed changes in the spontaneous activity of single neurons in the inferior colliculus, consistent with abnormally increased neuronal activity within the auditory pathways after manipulations known to produce tinnitus in man. A procedure based on a Pavlovian conditioned suppression paradigm was recently developed that allows us to measure tinnitus behaviorally in conscious animals. Accordingly, an animal model of tinnitus is proposed that permits tests of hypotheses relating to tinnitus generation, allowing the accommodation of interventional strategies for the treatment of this widespread auditory disorder.

Perceptual consequences of disrupted auditory nerve activity.

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Zeng, Fan-Gang; Kong, Ying-Yee; Michalewski, Henry J; Starr, Arnold

2005-06-01

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique

Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

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Eric P. Davidson

2014-01-01

Full Text Available Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

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Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte

2010-01-01

of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist...... findings confirm measures of early information processing to show high resemblance between rodents and humans, and indicate that early postnatal PCP-treated rats show deficits in pre-attentional processing, which are distinct from those observed in schizophrenia patients.......The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages...

A Novel Rodent Model of Posterior Ischemic Optic Neuropathy

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Wang, Yan; Brown, Dale P.; Duan, Yuanli; Kong, Wei; Watson, Brant D.; Goldberg, Jeffrey L.

2014-01-01

Objectives To develop a reliable, reproducible rat model of posterior ischemic optic neuropathy (PION) and study the cellular responses in the optic nerve and retina. Methods Posterior ischemic optic neuropathy was induced in adult rats by photochemically induced ischemia. Retinal and optic nerve vasculature was examined by fluorescein isothiocyanate–dextran extravasation. Tissue sectioning and immunohistochemistry were used to investigate the pathologic changes. Retinal ganglion cell survival at different times after PION induction, with or without neurotrophic application, was quantified by fluorogold retrograde labeling. Results Optic nerve injury was confirmed after PION induction, including local vascular leakage, optic nerve edema, and cavernous degeneration. Immunostaining data revealed microglial activation and focal loss of astrocytes, with adjacent astrocytic hypertrophy. Up to 23%, 50%, and 70% retinal ganglion cell loss was observed at 1 week, 2 weeks, and 3 weeks, respectively, after injury compared with a sham control group. Experimental treatment by brain-derived neurotrophic factor and ciliary neurotrophic factor remarkably prevented retinal ganglion cell loss in PION rats. At 3 weeks after injury, more than 40% of retinal ganglion cells were saved by the application of neurotrophic factors. Conclusions Rat PION created by photochemically induced ischemia is a reproducible and reliable animal model for mimicking the key features of human PION. Clinical Relevance The correspondence between the features of this rat PION model to those of human PION makes it an ideal model to study the pathophysiologic course of the disease, most of which remains to be elucidated. Furthermore, it provides an optimal model for testing therapeutic approaches for optic neuropathies. PMID:23544206

Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia-Gating of auditory-evoked potentials and prepulse inhibition

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Broberg, Brian Villumsen; Oranje, Bob; Yding, Birte

2010-01-01

The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages...... of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist...... PCP on postnatal days 7, 9, and 11 reliably induce cognitive impairments resembling those presented by schizophrenia patients. Here we evaluate the potential of early postnatal PCP (20mg/kg) treatment in Lister Hooded rats to induce post-pubertal deficits in PPI and changes, such as reduced gating...

Herbal Medicine AC591 Prevents Oxaliplatin-Induced Peripheral Neuropathy in Animal Model and Cancer Patients

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Xiaolan Cheng

2017-06-01

Full Text Available Oxaliplatin is clinically compelling because of severe peripheral neuropathy. The side effect can result in dosage reductions or even cessation of chemotherapy, and no effective treatments are available. AC591 is a standardized extract of Huangqi Guizhi Wuwu decoction, an herbal formula recorded in “Synopsis of the Golden Chamber” for improving limb numbness and pain. In this study, we investigated whether AC591 could protect against oxaliplatin-induced peripheral neuropathy. To clarify it, a rat model of oxaliplatin-induced peripheral neuropathy was established, and neuroprotective effect of AC591 was studied. Our results showed that pretreatment with AC591 reduced oxaliplatin-induced cold hyperalgesia, mechanical allodynia as well as morphological damage of dorsal root ganglion. Microarray analysis indicated the neuroprotective action of AC591 depended on the modulation of multiple molecular targets and pathways involved in the downregulation of inflammation and immune response. Moreover, AC591 enhanced the antitumor activity of oxaliplatin to some extent in Balb/c mice bearing CT-26 carcinoma cells. The efficacy of AC591 is also investigated in 72 colorectal cancer patients. After four cycles of treatment, the percentage of grades 1–2 neurotoxicity in AC591-treated group (n = 36 was 25%, whereas in the control group the incidence was 55.55% (P < 0.01 (n = 36. No significant differences in the tumor response rate between the two groups were found. These evidences suggested that AC591 can prevent oxaliplatin-induced neuropathy without reducing its antitumor activity, and may be a promising adjuvant to alleviate sensory symptoms in clinical practice.

Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice.

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Amin, Sanjiv B; Wang, Hongyue; Laroia, Nirupama; Orlando, Mark

2016-06-01

This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex-Specific Brain Deficits in Auditory Processing in an Animal Model of Cocaine-Related Schizophrenic Disorders

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Patricia A. Broderick

2013-04-01

Full Text Available Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. We used this acoustic startle paradigm in female versus male Sprague-Dawley animals to discriminate possible sex differences in responses to startle. The startle method operates through auditory pathways in brain via a network of sensorimotor gating processes within auditory cortex, cochlear nuclei, inferior and superior colliculi, pontine reticular nuclei, in addition to mesocorticolimbic brain reward and nigrostriatal motor circuitries. This paper is the first to report sex differences to acoustic stimuli in Sprague-Dawley animals (Rattus norvegicus although such gender responses to acoustic startle have been reported in humans (Swerdlow et al. 1997 [1]. The startle method monitors pre-pulse inhibition (PPI as a measure of the loss of sensorimotor gating in the brain's neuronal auditory network; auditory deficiencies can lead to sensory overload and subsequently cognitive dysfunction. Cocaine addicts and schizophrenic patients as well as cocaine treated animals are reported to exhibit symptoms of defective PPI (Geyer et al., 2001 [2]. Key findings are: (a Cocaine significantly reduced PPI in both sexes. (b Females were significantly more sensitive than males; reduced PPI was greater in females than in males. (c Physiological saline had no effect on startle in

Mechanisms of Distal Axonal Degeneration in Peripheral Neuropathies

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Cashman, Christopher R.; Höke, Ahmet

2015-01-01

Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration. PMID:25617478

Auditory neuropathy/auditory dyssynchrony in children with cochlear implants Neuropatia auditiva/dessincronia auditiva em crianças usuárias de implante coclear

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Ana Claudia Martinho de Carvalho

2011-08-01

Full Text Available The electrical stimulation generated by the Cochlear Implant (CI may improve the neural synchrony and hence contribute to the development of auditory skills in patients with Auditory Neuropathy/Auditory Dyssynchrony (AN/AD. AIM: Prospective cohort cross-sectional study to evaluate the auditory performance and the characteristics of the electrically evoked compound action potential (ECAP in 18 children with AN/AD and cochlear implants. MATERIAL AND METHODS: The auditory perception was evaluated by sound field thresholds and speech perception tests. To evaluate ECAP's characteristics, the threshold and amplitude of neural response were evaluated at 80Hz and 35Hz. RESULTS: No significant statistical difference was found concerning the development of auditory skills. The ECAP's characteristics differences at 80 and 35Hz stimulation rate were also not statistically significant. CONCLUSIONS: The CI was seen as an efficient resource to develop auditory skills in 94% of the AN/AD patients studied. The auditory perception benefits and the possibility to measure ECAP showed that the electrical stimulation could compensate for the neural dyssynchrony caused by the AN/AD. However, a unique clinical procedure cannot be proposed at this point. Therefore, a careful and complete evaluation of each AN/AD patient before recommending a Cochlear Implant is advised. Clinical Trials: NCT01023932A estimulação elétrica gerada pelo Implante Coclear (IC pode ser capaz de melhorar a sincronia neural e contribuir para o desenvolvimento das habilidades auditivas de sujeitos portadores de Neuropatia Auditiva/Dessincronia Auditiva (NA/DA. OBJETIVO: Estudo de coorte prospectivo transversal para avaliar o desempenho auditivo e as características do Potencial de Ação Composto Eletricamente Evocado no Nervo Auditivo (ECAP em 18 crianças portadoras de NA/DA e usuárias de IC. MATERIAL E MÉTODOS: Percepção auditiva e características do ECAP foram avaliadas

Eletrococleografia extratimpânica na neuropatia/dessincronia auditiva Extratympanic electrocochleography in the diagnosis of auditory neuropathy/auditory dyssynchrony

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Adriana Ribeiro Tavares Anastasio

2008-02-01

Full Text Available O potencial evocado auditivo de tronco encefálico (PEATE vem sendo amplamente utilizado como método para avaliação da função coclear em indivíduos com diagnóstico de neuropatia/dessincronia auditiva (NA/DA. Na ausência das emissões otoacústicas, muitos casos de NA/DA foram diagnosticados pela presença do microfonismo coclear (MC identificado no PEATE. OBJETIVO: Demonstrar a aplicabilidade clínica da eletrococleografia extratimpânica (Ecog-ET no diagnóstico diferencial da NA/DA quando comparada ao PEATE. MATERIAL E MÉTODO: Uma criança com 4 anos de idade, com diagnóstico de NA/DA atendida no Centro de Pesquisas Audiológicas realizou a Ecog-ET com tone burst de 2000Hz nas polaridades de rarefação e condensação. RESULTADOS: Ilustrou-se o registro da Ecog-ET. Com a utilização de protocolo apropriado, o MC pode ser evidenciado e confirmado na Ecog, com qualidade de registro superior ao obtido no PEATE. CONCLUSÃO: A Ecog-ET permitiu uma análise mais detalhada do MC quando comparada ao PEATE tendo, portanto aplicabilidade clínica na investigação da função coclear na NA/DA.The brainstem auditory evoked potential (BAEP is being extensively used as a method for the evaluation of cochlear function in individuals with diagnosis of auditory neuropathy/auditory dyssynchrony (AN/AD. In the absence of otoacoustic emissions, many cases of AN/AD have been diagnosed by the presence of CM identified in the BAEP. AIM: to demonstrate the clinical applicability of extratympanic electrocochleography (ET-Ecochg in the differential diagnosis of AN/AD compared to the BAEP. METHOD: a 4-year-old child with a diagnosis of AN/AD seen at the Audiological Research Center was submitted to ET-Ecochg with a 2000 Hz tone burst in rarefaction and condensation polarities. RESULTS: the ET-Ecochg exam was illustrated. Using an appropriate protocol, it was possible to demonstrate CM and to confirm it in the Ecochg, with a recording quality superior to

The impact of bodyweight and body condition on behavioral testing for painful diabetic neuropathy in the streptozotocin rat model.

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Hoybergs, Yves M J J; Biermans, Ria L V; Meert, Theo F

2008-05-02

The streptozotocin (STZ)-induced diabetes model is widely used for the induction of neuropathy in the rat. In this model, diabetic animals often display chronic illness, which raises objections not only on ethical but also on scientific grounds. In this study, the investigators set out to determine the impact of bodyweight and body condition (BC) on behavioral testing in the rat. Animals were allocated to four different groups as a function of their bodyweight, in particular one control group and three experimental groups with different starting weights (low bodyweight [LBW], medium bodyweight [MBW] and high bodyweight [HBW]), the groups having been rendered diabetic with an intraperitoneal injection of STZ (65mg/kg). Bodyweight, blood glucose, body condition and thresholds for mechanical hyperalgesia and tactile allodynia were measured or evaluated over a 68-day period. Animals with a LBW at the start of the experiment showed a gradual increase in BW with a decrease in mechanical nociceptive thresholds, while MBW and HBW animals presented a decrease in both thresholds and BW. The body condition score (BCS) decreased in all STZ-treated groups over time. Since correlations between mechanical thresholds and BW were similar between the control group and the HBW and MBW groups, the loss in BW clearly contributed to the decrease in thresholds. In the LBW group, thresholds and BW correlated negatively, so that the decrease in thresholds was mainly caused by the development of a painful neuropathy. From an ethical and a scientific point of view, in the STZ-induced diabetic neuropathy model, animals should be chosen on the basis of bodyweight and it must also be ensured that STZ is correctly dosed.

A homozygous MYO7A mutation associated to Usher syndrome and unilateral auditory neuropathy spectrum disorder.

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Xia, Hong; Hu, Pengzhi; Yuan, Lamei; Xiong, Wei; Xu, Hongbo; Yi, Junhui; Yang, Zhijian; Deng, Xiong; Guo, Yi; Deng, Hao

2017-10-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by sensorineural hearing loss, progressive visual loss and night blindness due to retinitis pigmentosa (RP), with or without vestibular dysfunction. The purpose of this study was to detect the causative gene in a consanguineous Chinese family with USH. A c.3696_3706del (p.R1232Sfs*72) variant in the myosin VIIa gene (MYO7A) was identified in the homozygous state by exome sequencing. The co‑segregation of the MYO7A c.3696_3706del variant with the phenotype of deafness and progressive visual loss in the USH family was confirmed by Sanger sequencing. The variant was absent in 200 healthy controls. Therefore, the c.3696_3706del variant may disrupt the interaction between myosin VIIa and other USH1 proteins, and impair melanosome transport in retinal pigment epithelial cells. Notably, bilateral auditory brainstem responses were absent in two patients of the USH family, while distortion product otoacoustic emissions were elicited in the right ears of the two patients, consistent with clinical diagnosis of unilateral auditory neuropathy spectrum disorder. These data suggested that the homozygous c.3696_3706del variant in the MYO7A gene may be the disease‑causing mutation for the disorder in this family. These findings broaden the phenotype spectrum of the MYO7A gene, and may facilitate understanding of the molecular pathogenesis of the disease, and genetic counseling for the family.

Glucose control and diabetic neuropathy: lessons from recent large clinical trials.

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Ang, Lynn; Jaiswal, Mamta; Martin, Catherine; Pop-Busui, Rodica

2014-01-01

Diabetic peripheral and autonomic neuropathies are common complications of diabetes with broad spectrums of clinical manifestations and high morbidity. Studies using various agents to target the pathways implicated in the development and progression of diabetic neuropathy were promising in animal models. In humans, however, randomized controlled studies have failed to show efficacy on objective measures of neuropathy. The complex anatomy of the peripheral and autonomic nervous systems, the multitude of pathogenic mechanisms involved, and the lack of uniformity of neuropathy measures have likely contributed to these failures. To date, tight glycemic control is the only strategy convincingly shown to prevent or delay the development of neuropathy in patients with type 1 diabetes and to slow the progression of neuropathy in some patients with type 2 diabetes. Lessons learned about the role of glycemic control on distal symmetrical polyneuropathy and cardiovascular autonomic neuropathy are discussed in this review.

Phantom auditory sensation in rats: an animal model for tinnitus.

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Jastreboff, P J; Brennan, J F; Coleman, J K; Sasaki, C T

1988-12-01

In order to measure tinnitus induced by sodium salicylate injections, 84 pigmented rats, distributed among 14 groups in five experiments, were used in a conditioned suppression paradigm. In Experiment 1, all groups were trained with a conditioned stimulus (CS) consisting of the offset of a continuous background noise. One group began salicylate injections before Pavlovian training, a second group started injections after training, and a control group received daily saline injections. Resistance to extinction was profound when injections started before training, but minimal when initiated after training, which suggests that salicylate-induced effects acquired differential conditioned value. In Experiment 2 we mimicked the salicylate treatments by substituting a 7 kHz tone in place of respective injections, resulting in effects equivalent to salicylate-induced behavior. In a third experiment we included a 3 kHz CS, and again replicated the salicylate findings. In Experiment 4 we decreased the motivational level, and the sequential relation between salicylate-induced effects and suppression training was retained. Finally, no salicylate effects emerged when the visual modality was used. These findings support the demonstration of phantom auditory sensations in animals.

Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy.

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Turkiew, Elliot; Falconer, Debbie; Reed, Nicole; Höke, Ahmet

2017-09-01

Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study, we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development. © 2017 Peripheral Nerve Society.

Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

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Schendzielorz, Philipp; Vollmer, Maike; Rak, Kristen; Wiegner, Armin; Nada, Nashwa; Radeloff, Katrin; Hagen, Rudolf; Radeloff, Andreas

2017-10-01

A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy

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Daisuke Kawata

2017-09-01

Full Text Available Chemotherapy-induced peripheral neuropathy (CIPN is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3 or interleukin-10 (IL-10 from replication-defective herpes simplex virus (HSV-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2, and expression of the transgene was controlled by doxycycline (DOX. We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

Regulatable Transgene Expression for Prevention of Chemotherapy-Induced Peripheral Neuropathy.

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Kawata, Daisuke; Wu, Zetang

2017-09-15

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating complication associated with drug treatment of cancer for which there are no effective strategies of prevention or treatment. In this study, we examined the effect of intermittent expression of neurotophin-3 (NT-3) or interleukin-10 (IL-10) from replication-defective herpes simplex virus (HSV)-based regulatable vectors delivered by subcutaneous inoculation to the dorsal root ganglion (DRG) on the development of paclitaxel-induced peripheral neuropathy. We constructed two different tetracycline (tet)-on-based regulatable HSV vectors, one expressing NT-3 and the other expressing IL-10, in which the transactivator expression in the tet-on system was under the control of HSV latency-associated promoter 2 (LAP-2), and expression of the transgene was controlled by doxycycline (DOX). We examined the therapeutic effect of intermittent expression of the transgene in animals with paclitaxel-induced peripheral neuropathy modeled by intraperitoneal injection of paclitaxel (16 mg/kg) once a week for 5 weeks. Intermittent expression of either NT-3 or IL-10 3 days before and 1 day after paclitaxel administration protected animals against paclitaxel-induced peripheral neuropathy over the course of 5 weeks. These results suggest the potential of regulatable vectors for prevention of chemotherapy-induced peripheral neuropathy.

Effect of neonatal asphyxia on the impairment of the auditory pathway by recording auditory brainstem responses in newborn piglets: a new experimentation model to study the perinatal hypoxic-ischemic damage on the auditory system.

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Francisco Jose Alvarez

Full Text Available Hypoxia-ischemia (HI is a major perinatal problem that results in severe damage to the brain impairing the normal development of the auditory system. The purpose of the present study is to study the effect of perinatal asphyxia on the auditory pathway by recording auditory brain responses in a novel animal experimentation model in newborn piglets.Hypoxia-ischemia was induced to 1.3 day-old piglets by clamping 30 minutes both carotid arteries by vascular occluders and lowering the fraction of inspired oxygen. We compared the Auditory Brain Responses (ABRs of newborn piglets exposed to acute hypoxia/ischemia (n = 6 and a control group with no such exposure (n = 10. ABRs were recorded for both ears before the start of the experiment (baseline, after 30 minutes of HI injury, and every 30 minutes during 6 h after the HI injury.Auditory brain responses were altered during the hypoxic-ischemic insult but recovered 30-60 minutes later. Hypoxia/ischemia seemed to induce auditory functional damage by increasing I-V latencies and decreasing wave I, III and V amplitudes, although differences were not significant.The described experimental model of hypoxia-ischemia in newborn piglets may be useful for studying the effect of perinatal asphyxia on the impairment of the auditory pathway.

The uses of overlap: carer-child interaction involving a nine-year-old boy with auditory neuropathy.

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Anstey, Julie; Wells, Bill

2013-01-01

The subject of this single case study, Ricky, is a nine-year-old boy with a profound hearing loss arising from auditory neuropathy. Despite cochlear implantation at the age of two, his receptive language skills remain very restricted and his speech is unintelligible. Techniques of interactional linguistics are used to analyse recordings of Ricky and his mother during shared book reading. Both participants display competences in managing turn-taking and overlapping talk that enable them to progress the book-reading activity, to talk spontaneously on topically related matters and also to handle issues of phonetic and linguistic repair. Instances of both competitive and non-competitive overlap reveal that Ricky has access to interactionally important prosodic skills. The study thus reinforces the need, when assessing a child's potential to understand and use spoken language, to examine the child's talk from an interactional perspective. It further indicates that overlapping talk is not necessarily a problem; indeed it can be part of a solution to issues of interpersonal understanding that routinely arise in the course of talk-in-interaction.

Functional deficits in peripheral nerve mitochondria in rats with paclitaxel- and oxaliplatin-evoked painful peripheral neuropathy

OpenAIRE

Zheng, Huaien; Xiao, Wen Hua; Bennett, Gary J.

2011-01-01

Cancer chemotherapeutics like paclitaxel and oxaliplatin produce a dose-limiting chronic sensory peripheral neuropathy that is often accompanied by neuropathic pain. The cause of the neuropathy and pain is unknown. In animal models, paclitaxel-evoked and oxaliplatin-evoked painful peripheral neuropathies are accompanied by an increase in the incidence of swollen and vacuolated mitochondria in peripheral nerve axons. It has been proposed that mitochondrial swelling and vacuolation are indicati...

Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration.

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Petkov, Christopher I; Sutter, Mitchell L

2011-01-01

Auditory perceptual 'restoration' occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of 'auditory scene analysis' to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings. © 2010 Elsevier B.V. All rights reserved.

Auditory object perception: A neurobiological model and prospective review.

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Brefczynski-Lewis, Julie A; Lewis, James W

2017-10-01

Interaction with the world is a multisensory experience, but most of what is known about the neural correlates of perception comes from studying vision. Auditory inputs enter cortex with its own set of unique qualities, and leads to use in oral communication, speech, music, and the understanding of emotional and intentional states of others, all of which are central to the human experience. To better understand how the auditory system develops, recovers after injury, and how it may have transitioned in its functions over the course of hominin evolution, advances are needed in models of how the human brain is organized to process real-world natural sounds and "auditory objects". This review presents a simple fundamental neurobiological model of hearing perception at a category level that incorporates principles of bottom-up signal processing together with top-down constraints of grounded cognition theories of knowledge representation. Though mostly derived from human neuroimaging literature, this theoretical framework highlights rudimentary principles of real-world sound processing that may apply to most if not all mammalian species with hearing and acoustic communication abilities. The model encompasses three basic categories of sound-source: (1) action sounds (non-vocalizations) produced by 'living things', with human (conspecific) and non-human animal sources representing two subcategories; (2) action sounds produced by 'non-living things', including environmental sources and human-made machinery; and (3) vocalizations ('living things'), with human versus non-human animals as two subcategories therein. The model is presented in the context of cognitive architectures relating to multisensory, sensory-motor, and spoken language organizations. The models' predictive values are further discussed in the context of anthropological theories of oral communication evolution and the neurodevelopment of spoken language proto-networks in infants/toddlers. These phylogenetic

Vitamin D Supplementation for Prevention of Post-Traumatic Osteoarthritis: Evaluation in Animal and Clinical Models

Science.gov (United States)

2017-10-01

Science of Variation Group (Wolf JM, SVG group member). Variation in recommendation for surgical treatment for compressive neuropathy. J Hand... Goldberg Arthritis Grant Animal Model of Vitamin D Supplementation for Prevention of Osteoarthritis This project evaluates the potentially preventive

Amelioration of Auditory Response by DA9801 in Diabetic Mouse

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Yeong Ro Lee

2015-01-01

Full Text Available Diabetes mellitus (DM is a metabolic disease that involves disorders such as diabetic retinopathy, diabetic neuropathy, and diabetic hearing loss. Recently, neurotrophin has become a treatment target that has shown to be an attractive alternative in recovering auditory function altered by DM. The aim of this study was to evaluate the effect of DA9801, a mixture of Dioscorea nipponica and Dioscorea japonica extracts, in the auditory function damage produced in a STZ-induced diabetic model and to provide evidence of the mechanisms involved in enhancing these protective effects. We found a potential application of DA9801 on hearing impairment in the STZ-induced diabetic model, demonstrated by reducing the deterioration produced by DM in ABR threshold in response to clicks and normalizing wave I–IV latencies and Pa latencies in AMLR. We also show evidence that these effects might be elicited by inducing NGF related through Nr3c1 and Akt. Therefore, this result suggests that the neuroprotective effects of DA9801 on the auditory damage produced by DM may be affected by NGF increase resulting from Nr3c1 via Akt transformation.

Recent advances in regenerative medicine to treat enteric neuropathies: use of human cells.

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Stamp, L A; Young, H M

2017-01-01

As current options for treating most enteric neuropathies are either non-effective or associated with significant ongoing problems, cell therapy is a potential attractive possibility to treat congenital and acquired neuropathies. Studies using animal models have shown that following transplantation of enteric neural progenitors into the bowel of recipients, the transplanted cells migrate, proliferate, and generate neurons that are electrically active and receive synaptic inputs. Recent studies have transplanted human enteric neural progenitors into the mouse colon and shown engraftment. In this article, we summarize the significance of these recent advances and discuss priorities for future research that might lead to the use of regenerative medicine to treat enteric neuropathies in the clinic. © 2016 John Wiley & Sons Ltd.

Targeting the innate repair receptor to treat neuropathy

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Albert Dahan

2016-07-01

Full Text Available Abstract. The innate repair receptor (IRR is a heteromer of the erythropoietin receptor and the β-common (CD131 receptor, which simultaneously activates anti-inflammatory and tissue repair pathways. Experimental data suggest that after peripheral nerve injury, the IRR is upregulated in the spinal cord and modulates the neurogenic inflammatory response. The recently introduced selective IRR agonist ARA290 is an 11-amino acid peptide initially tested in animal models of neuropathy. After sciatic nerve injury, ARA290 produced a rapid and long-term relief of mechanical and cold allodynia in normal mice, but not in animals with a β-common receptor knockout phenotype. In humans, ARA290 has been evaluated in patients with small fiber neuropathy associated with sarcoidosis or type 2 diabetes (T2D mellitus. In patients with sarcoidosis, ARA290 significantly improved neuropathic and autonomic symptoms, as well as quality of life as assessed by the small fiber neuropathy screening list questionnaire. In addition, ARA290 treatment for 28 days initiated a regrowth of small nerve fibers in the cornea, but not in the epidermis. In patients with T2D, the results were similar to those observed in patients with sarcoidosis along with an improved metabolic profile. In both populations, ARA290 lacked significant adverse effects. These experimental and clinical studies show that ARA290 effectively reprograms a proinflammatory, tissue-damaging milieu into one of healing and tissue repair. Further clinical trials with long-term treatment and follow-up are needed to assess the full potential of IRR activation by ARA290 as a disease-modifying therapy in neuropathy of various etiologies.

Rapid measurement of auditory filter shape in mice using the auditory brainstem response and notched noise.

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Lina, Ioan A; Lauer, Amanda M

2013-04-01

The notched noise method is an effective procedure for measuring frequency resolution and auditory filter shapes in both human and animal models of hearing. Briefly, auditory filter shape and bandwidth estimates are derived from masked thresholds for tones presented in noise containing widening spectral notches. As the spectral notch widens, increasingly less of the noise falls within the auditory filter and the tone becomes more detectible until the notch width exceeds the filter bandwidth. Behavioral procedures have been used for the derivation of notched noise auditory filter shapes in mice; however, the time and effort needed to train and test animals on these tasks renders a constraint on the widespread application of this testing method. As an alternative procedure, we combined relatively non-invasive auditory brainstem response (ABR) measurements and the notched noise method to estimate auditory filters in normal-hearing mice at center frequencies of 8, 11.2, and 16 kHz. A complete set of simultaneous masked thresholds for a particular tone frequency were obtained in about an hour. ABR-derived filter bandwidths broadened with increasing frequency, consistent with previous studies. The ABR notched noise procedure provides a fast alternative to estimating frequency selectivity in mice that is well-suited to high through-put or time-sensitive screening. Copyright © 2013 Elsevier B.V. All rights reserved.

A Time-Frequency Auditory Model Using Wavelet Packets

DEFF Research Database (Denmark)

Agerkvist, Finn

1996-01-01

A time-frequency auditory model is presented. The model uses the wavelet packet analysis as the preprocessor. The auditory filters are modelled by the rounded exponential filters, and the excitation is smoothed by a window function. By comparing time-frequency excitation patterns it is shown...... that the change in the time-frequency excitation pattern introduced when a test tone at masked threshold is added to the masker is approximately equal to 7 dB for all types of maskers. The classic detection ratio therefore overrates the detection efficiency of the auditory system....

Mitochondrial dysfunction in an animal model of diabetic neuropathy is associated with a reduction of neurosteroid synthesis. [version 2; referees: 2 approved

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Stephen R. Humble

2018-03-01

Full Text Available Background: Recent work in a model of diabetic neuropathy revealed that layer 2/3 cortical pyramidal neurones of the pain pathway exhibited reduced endogenous neurosteroid modulation of the GABAAR and exogenously applied neurosteroids had an exaggerated impact. It is postulated that this is related to reduced precursor synthesis, due to mitochondrial dysfunction in diabetic neuropathy. Benzodiazepines are also known to activate neurosteroidogenesis by binding to mitochondrial translocator protein (TSPO. This study explored the differential effect of diazepam on GABAAR modulation via neurosteroidogenesis in diabetic and wild type (WT mice. Methods: Whole-cell patch-clamp technique was used on slices of neural tissue. Electrophysiological recordings were obtained from layer 2/3 cortical pyramidal neurons of the pain pathway from mice with type-II diabetic neuropathy (ob/ob and WT controls aged 60-80 days. Results: There was a key difference in the response of the WT and ob/ob cortical neurons to simultaneous incubation with diazepam and flumazenil. In contrast, diazepam and the 5a-reductase inhibitor finasteride, individually or in combination, produced the same response in both strains. Conclusions: The exaggerated effect of diazepam on GABAergic inhibitory tone in the ob/ob, despite the presence of the GABAAR benzodiazepine antagonist flumazenil is likely observed due to physiological upregulation of key neurosteroidogenic enzymes in response to the reduced pregnenolone synthesis by the mitochondria. By increasing pregnenolone via TSPO activation, it is possible to promote enhanced neurosteroidogenesis and increase GABAergic inhibitory tone via an alternate route. In diabetic neuropathy, mitochondrial dysfunction may play an important role. Enhancing the GABAergic neurosteroid tone could be of potential therapeutic benefit.

Inter-trial coherence as a marker of cortical phase synchrony in children with sensorineural hearing loss and auditory neuropathy spectrum disorder fitted with hearing aids and cochlear implants

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Nash-Kille, Amy; Sharma, Anu

2014-01-01

Objective Although brainstem dys-synchrony is a hallmark of children with auditory neuropathy spectrum disorder (ANSD), little is known about how the lack of neural synchrony manifests at more central levels. We used time-frequency single-trial EEG analyses (i.e., inter-trial coherence; ITC), to examine cortical phase synchrony in children with normal hearing (NH), sensorineural hearing loss (SNHL) and ANSD. Methods Single trial time-frequency analyses were performed on cortical auditory evoked responses from 41 NH children, 91 children with ANSD and 50 children with SNHL. The latter two groups included children who received intervention via hearing aids and cochlear implants. ITC measures were compared between groups as a function of hearing loss, intervention type, and cortical maturational status. Results In children with SNHL, ITC decreased as severity of hearing loss increased. Children with ANSD revealed lower levels of ITC relative to children with NH or SNHL, regardless of intervention. Children with ANSD who received cochlear implants showed significant improvements in ITC with increasing experience with their implants. Conclusions Cortical phase coherence is significantly reduced as a result of both severe-to-profound SNHL and ANSD. Significance ITC provides a window into the brain oscillations underlying the averaged cortical auditory evoked response. Our results provide a first description of deficits in cortical phase synchrony in children with SNHL and ANSD. PMID:24360131

A partial hearing animal model for chronic electro-acoustic stimulation

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Irving, S.; Wise, A. K.; Millard, R. E.; Shepherd, R. K.; Fallon, J. B.

2014-08-01

Objective. Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. Approach. This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. Main results. Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. Significance. This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual

Adult plasticity in the subcortical auditory pathway of the maternal mouse.

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Jason A Miranda

Full Text Available Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

Adult plasticity in the subcortical auditory pathway of the maternal mouse.

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Miranda, Jason A; Shepard, Kathryn N; McClintock, Shannon K; Liu, Robert C

2014-01-01

Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.

Pathogenesis of presbycusis in animal models: a review.

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Fetoni, Anna R; Picciotti, Pasqualina M; Paludetti, Gaetano; Troiani, Diana

2011-06-01

Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of curcumin in mice model of vincristine-induced neuropathy.

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Babu, Anand; Prasanth, K G; Balaji, Bhaskar

2015-06-01

Curcumin exhibits a wide spectrum of biological activities which include neuroprotective, antinociceptive, anti-inflammatory, and antioxidant activity. The present study evaluates the effect of curcumin in vincristine-induced neuropathy in a mice model. Vincristine sulfate (0.1 mg/kg, i.p. for 10 consecutive days) was administered to mice to induce neuropathy. Pain behavior was assessed at different days, i.e., 0, 7, 10, and 14 d. Sciatic nerve total calcium, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), nitric oxide (NO), and lipid peroxidation (LPO) were also estimated after the 14th day of study. Pregabalin (10 mg/kg, p.o.) and curcumin (15, 30, and 60 mg/kg, p.o.) were administered for 14 consecutive days. Curcumin at 60 mg/kg significantly attenuated the vincristine-induced neuropathic pain manifestations in terms of thermal hyperalgesia (p Curcumin at 30 and 60 mg/kg exhibited significant changes (p Curcumin at 30 and 60 mg/kg dose levels significantly attenuated vincristine-induced neuropathy which may be due to its multiple actions including antinociceptive, calcium inhibitory, and antioxidant effect.

An Auditory Model with Hearing Loss

DEFF Research Database (Denmark)

Nielsen, Lars Bramsløw

An auditory model based on the psychophysics of hearing has been developed and tested. The model simulates the normal ear or an impaired ear with a given hearing loss. Based on reviews of the current literature, the frequency selectivity and loudness growth as functions of threshold and stimulus...... level have been found and implemented in the model. The auditory model was verified against selected results from the literature, and it was confirmed that the normal spread of masking and loudness growth could be simulated in the model. The effects of hearing loss on these parameters was also...... in qualitative agreement with recent findings. The temporal properties of the ear have currently not been included in the model. As an example of a real-world application of the model, loudness spectrograms for a speech utterance were presented. By introducing hearing loss, the speech sounds became less audible...

Cochlear third window in the scala vestibuli: an animal model.

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Preis, Michal; Attias, Joseph; Hadar, Tuvia; Nageris, Ben I

2009-08-01

Pathologic third window has been investigated in both animals and humans, with a third window located in the vestibular apparatus, specifically, dehiscence of the superior semicircular canal, serving as the clinical model. The present study sought to examine the effect of a cochlear third window in the scala vestibuli on the auditory thresholds in fat sand rats that have a unique anatomy of the inner ear that allows for easy surgical access. The experiment included 7 healthy 6-month-old fat sand rats (a total of 10 ears). A pathologic third window was induced by drilling a hole in the bony labyrinth over the scala vestibuli, with preservation of the membranous labyrinth. Auditory brainstem responses to high- and low-frequency acoustic stimuli delivered via air and bone conduction were recorded before and after the procedure. In the preoperative auditory brainstem response recordings, air-conduction thresholds (ACTs) to clicks and tone bursts averaged 9 and 10 dB, respectively, and bone-conduction thresholds averaged 4.5 and 2.9 dB, respectively. Postfenestration ACTs averaged 41 and 42.2 dB, and bone-conduction thresholds averaged 1.1 and 4.3 dB. The change in ACT was statistically significant (p scala vestibuli affects auditory thresholds by causing a decrease in sensitivity to air-conducted sound stimuli. These findings agree with the theoretical model and clinical findings.

Music Genre Classification using an Auditory Memory Model

DEFF Research Database (Denmark)

Jensen, Kristoffer

2011-01-01

Audio feature estimation is potentially improved by including higher- level models. One such model is the Auditory Short Term Memory (STM) model. A new paradigm of audio feature estimation is obtained by adding the influence of notes in the STM. These notes are identified when the perceptual...... results, and an initial experiment with sensory dissonance has been undertaken with good results. The parameters obtained form the auditory memory model, along with the dissonance measure, are shown here to be of interest in genre classification....

The Role of Temporal Envelope and Fine Structure in Mandarin Lexical Tone Perception in Auditory Neuropathy Spectrum Disorder.

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Shuo Wang

Full Text Available Temporal information in a signal can be partitioned into temporal envelope (E and fine structure (FS. Fine structure is important for lexical tone perception for normal-hearing (NH listeners, and listeners with sensorineural hearing loss (SNHL have an impaired ability to use FS in lexical tone perception due to the reduced frequency resolution. The present study was aimed to assess which of the acoustic aspects (E or FS played a more important role in lexical tone perception in subjects with auditory neuropathy spectrum disorder (ANSD and to determine whether it was the deficit in temporal resolution or frequency resolution that might lead to more detrimental effects on FS processing in pitch perception. Fifty-eight native Mandarin Chinese-speaking subjects (27 with ANSD, 16 with SNHL, and 15 with NH were assessed for (1 their ability to recognize lexical tones using acoustic E or FS cues with the "auditory chimera" technique, (2 temporal resolution as measured with temporal gap detection (TGD threshold, and (3 frequency resolution as measured with the Q(10dB values of the psychophysical tuning curves. Overall, 26.5%, 60.2%, and 92.1% of lexical tone responses were consistent with FS cues for tone perception for listeners with ANSD, SNHL, and NH, respectively. The mean TGD threshold was significantly higher for listeners with ANSD (11.9 ms than for SNHL (4.0 ms; p < 0.001 and NH (3.9 ms; p < 0.001 listeners, with no significant difference between SNHL and NH listeners. In contrast, the mean Q(10dB for listeners with SNHL (1.8 ± 0.4 was significantly lower than that for ANSD (3.5 ± 1.0; p < 0.001 and NH (3.4 ± 0.9; p < 0.001 listeners, with no significant difference between ANSD and NH listeners. These results suggest that reduced temporal resolution, as opposed to reduced frequency selectivity, in ANSD subjects leads to greater degradation of FS processing for pitch perception.

Abnormal muscle afferent function in a model of Taxol chemotherapy-induced painful neuropathy

OpenAIRE

Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

2011-01-01

Despite muscle pain being a well-described symptom in patients with diverse forms of peripheral neuropathy, the role of neuropathic mechanisms in muscle pain have received remarkably little attention. We have recently demonstrated in a well-established model of chemotherapy-induced painful neuropathy (CIPN) that the anti-tumor drug paclitaxel (Taxol) produces mechanical hyperalgesia in skeletal muscle, of similar time course to and with shared mechanism with cutaneous symptoms. In the present...

Sensory Neuropathy Due to Loss of Bcl-w

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Courchesne, Stephanie L.; Karch, Christoph; Pazyra-Murphy, Maria F.; Segal, Rosalind A.

2010-01-01

Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons. Bcl-w −/− mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons. Bcl-w −/− sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establish bcl-w −/− mice as an animal model of small fiber sensory neuropathy, and provide new insight regarding the role of bcl-w and of mitochondria in preventing axonal degeneration. PMID:21289171

[Review of the recent literature on hereditary neuropathies].

Science.gov (United States)

Birouk, N

2014-12-01

The recent literature included interesting reports on the pathogenic mechanisms of hereditary neuropathies. The axonal traffic and its abnormalities in some forms of Charcot-Marie-Tooth (CMT) disease were particularly reviewed by Bucci et al. Many genes related to CMT disease code for proteins that are involved directly or not in intracellular traffic. KIF1B controls vesicle motility on microtubules. MTMR2, MTMR13 and FIG4 regulate the metabolism of phosphoinositide at the level of endosomes. The HSPs are involved in the proteasomal degradation. GDAP1 and MFN2 regulate the mitochondrial fission and fusion respectively and the mitochondial transport within the axon. Pareyson et al. reported a review on peripheral neuropathies in mitochondrial disorders. They used the term of "mitochondrial CMT" for the forms of CMT with abnormal mitochondrial dynamic or structure. Among the new entities, we can draw the attention to a proximal form of hereditary motor and sensory neuropathy with autosomal dominant inheritance, which is characterized by motor deficit with cramps and fasciculations predominating in proximal muscles. Distal sensory deficit can be present. The gene TFG on chromosome 3 has been recently identified to be responsible for this form. Another rare form of axonal autosomal recessive neuropathy due to HNT1 gene mutation is characterized by the presence of hands myotonia that appears later than neuropathy but constitute an interesting clinical hallmark to orientate the diagnosis of this form. In terms of differential diagnosis, CMT4J due to FIG4 mutation can present with a rapidly progressive and asymmetric weakness that resembles CIDP. Bouhy et al. made an interesting review on the therapeutic trials, animal models and the future therapeutic strategies to be developed in CMT disease. Copyright © 2014. Published by Elsevier Masson SAS.

A human model of small fiber neuropathy to study wound healing.

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Ben M W Illigens

Full Text Available The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter and deep (>3 millimeter punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (P<0.001 and day 14 (P<0.001. Deep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (P<0.01. In conclusion, topical application of capsaicin causes a small fiber neuropathy and is associated with a delay in healing of shallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.

Protective effect of oryzanol isolated from crude rice bran oil in experimental model of diabetic neuropathy

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Somsuvra B. Ghatak

2012-09-01

Full Text Available Several studies have implicated the involvement of poor glycemic control and oxidative/nitrosative stress in the development of diabetic neuropathic pain, an important microvascular complication affecting more than 50% of diabetic patients. However, lack of understanding of the underlying etiology, development of tolerance, inadequate relief and possible toxicity associated with classical analgesics warrant the investigation of the novel agents. Therefore, the present study was carried out to investigate the effect of oryzanol (OZ, a commercially-important potent antioxidant component isolated from from crude rice bran oil (cRBO, in streptozotocin (STZ-induced diabetic neuropathy in rats. After eight weeks, diabetic rats developed neuropathy which was evident from decreased tail-flick latency (thermal hyperalgesia and increased nociceptive behavior during the formalin test. This was accompanied by decreased motor coordination based on the evaluation of neuromuscular strength. Na+ K+ ATPase, a biochemical marker associated with the development of diabetic neuropathy, was significantly inhibited in the sciatic nerve of diabetic animals. The activities of antioxidant enzymes and lipid peroxidation levels were significantly elevated in diabetic rats, indicating the involvement of oxidative stress in diabetic neuropathy. Chronic treatment with oryzanol (OZ (50 and 100 mg/kg per oral (p.o. and standard drug glibenclamide (Gl (10 mg/kg, p.o. significantly attenuated the behavioral as well as biochemical changes associated with diabetic neuropathy. The findings provide experimental evidence to the protective effects of OZ on hyperglycemia-induced thermal hyperalgesia and oxidative stress which might be responsible for diabetes induced nerve damage.

Resource allocation models of auditory working memory.

Science.gov (United States)

Joseph, Sabine; Teki, Sundeep; Kumar, Sukhbinder; Husain, Masud; Griffiths, Timothy D

2016-06-01

Auditory working memory (WM) is the cognitive faculty that allows us to actively hold and manipulate sounds in mind over short periods of time. We develop here a particular perspective on WM for non-verbal, auditory objects as well as for time based on the consideration of possible parallels to visual WM. In vision, there has been a vigorous debate on whether WM capacity is limited to a fixed number of items or whether it represents a limited resource that can be allocated flexibly across items. Resource allocation models predict that the precision with which an item is represented decreases as a function of total number of items maintained in WM because a limited resource is shared among stored objects. We consider here auditory work on sequentially presented objects of different pitch as well as time intervals from the perspective of dynamic resource allocation. We consider whether the working memory resource might be determined by perceptual features such as pitch or timbre, or bound objects comprising multiple features, and we speculate on brain substrates for these behavioural models. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2016 Elsevier B.V. All rights reserved.

Animal model of neuropathic tachycardia syndrome

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Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Neural circuits in auditory and audiovisual memory.

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Plakke, B; Romanski, L M

2016-06-01

Working memory is the ability to employ recently seen or heard stimuli and apply them to changing cognitive context. Although much is known about language processing and visual working memory, the neurobiological basis of auditory working memory is less clear. Historically, part of the problem has been the difficulty in obtaining a robust animal model to study auditory short-term memory. In recent years there has been neurophysiological and lesion studies indicating a cortical network involving both temporal and frontal cortices. Studies specifically targeting the role of the prefrontal cortex (PFC) in auditory working memory have suggested that dorsal and ventral prefrontal regions perform different roles during the processing of auditory mnemonic information, with the dorsolateral PFC performing similar functions for both auditory and visual working memory. In contrast, the ventrolateral PFC (VLPFC), which contains cells that respond robustly to auditory stimuli and that process both face and vocal stimuli may be an essential locus for both auditory and audiovisual working memory. These findings suggest a critical role for the VLPFC in the processing, integrating, and retaining of communication information. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies

DEFF Research Database (Denmark)

Ba-Ali, Shakoor; Lund-Andersen, Henrik

2017-01-01

of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among...... the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we...... will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies....

Role of sigma 1 receptor in high fat diet-induced peripheral neuropathy.

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Song, Tieying; Zhao, Jianhui; Ma, Xiaojing; Zhang, Zaiwang; Jiang, Bo; Yang, Yunliang

2017-09-26

The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy. Wild-type mice developed tactile allodynia and thermal hypoalgesia after 24-week HFD treatment. HFD-induced peripheral neuropathy correlated with increased expression of GluN2A and GluN2B subunits of NMDARs, PDS-95, and Sig-1R, as well as increased Sig-1R-NMDAR interaction in the spinal cord. In contrast, Sig-1R-/- mice did not develop thermal hypoalgesia or tactile allodynia after 24-week HFD treatment, and the levels of GluN2A, GluN2B, and PSD-95 were not altered in the spinal cord of HFD-fed Sig-1R-/- mice. Finally, repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice attenuated peripheral neuropathy. Our results suggest that obesity-associated peripheral neuropathy may involve Sig-1R-mediated enhancement of NMDAR expression in the spinal cord.

Paraneoplastic neuropathies.

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Antoine, Jean-Christophe; Camdessanché, Jean-Philippe

2017-10-01

To review recent advances in paraneoplastic neuropathies with emphasis on their definition, different forms and therapeutic development. A strict definition of definite paraneoplastic neuropathies is necessary to avoid confusion. With carcinoma, seronegative sensory neuronopathies and neuronopathies and anti-Hu and anti-CV2/Contactin Response Mediator Protein 5 antibodies are the most frequent. With lymphomas, most neuropathies occur with monoclonal gammopathy including AL amyloidosis, Polyneuropathy-Organomegaly-Endocrinopathy-M component-Skin changes (POEMS) syndrome, type I cryoglobulinemia and antimyelin-associated glycoprotein (MAG) neuropathies and Waldenström's disease. Neuropathies improving with tumor treatment are occasional, occur with a variety of cancer and include motor neuron disease, chronic inflammatory demyelinating neuropathy and nerve vasculitis. If antibodies toward intracellular antigens are well characterized, it is not the case for antibodies toward cell membrane proteins. Contactin-associated protein-2 antibodies occur with neuromyotonia and thymoma with the Morvan's syndrome in addition to Netrin 1 receptor antibodies but may not be responsible for peripheral nerve hyperexcitability. The treatment of AL amyloidosis, POEMS syndrome, anti-MAG neuropathy and cryoglobulinemia is now relatively well established. It is not the case with onconeural antibodies for which the rarity of the disorders and a short therapeutic window are limiting factors for the development of clinical trials. A strict definition of paraneoplastic neuropathies helps their identification and is necessary to allow an early diagnosis of the underlying tumor.

Vasculitic Neuropathies.

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Naddaf, Elie; Dyck, P James Bonham

2015-10-01

From pathological standpoint, we divide vasculitic neuropathies in two categories: nerve large arteriole vasculitides and nerve microvasculitis. It is also important to determine whether a large arteriole vasculitis has an infectious etiology as it entails different treatment approach. Treatment of non-infectious large arteriole vasculitides consists initially of induction therapy with corticosteroids. Adding an immunosuppressant, mainly cyclophosphamide, is often needed. Treatment of infectious large arteriole vasculitides needs a multidisciplinary approach to target both the underlying infection and the vasculitis. Corticosteroids are the first-line therapy for classic non-systemic vasculitic neuropathy. Stable or improving patients without biopsy evidence of active vasculitis can be either observed or treated. Currently, adding an immunosuppressant is only indicated for patients who continue to progress on corticosteroids alone or patients with a rapidly progressive course. The treatment of the radiculoplexus neuropathies such as diabetic lumbosacral radiculoplexus neuropathy, lumbosacral radiculoplexus neuropathy (in non-diabetic patients), and diabetic cervical radiculoplexus neuropathy, as well as painless diabetic motor neuropathy, is not well established yet. We treat patients, if they present early on in the disease course or if they have severe disabling symptoms, with IV methylprednisolone 1 g once a week for 12 weeks.

Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

Institute of Scientific and Technical Information of China (English)

Runsheng Wang; Xiaodi Wang; Peilin Lü; Jianwei Bai; Jianzhou Wang; Xiaoqin Lei; Xiaoliang Zhou; Hongfen Sun; Aizhu Pan

2006-01-01

BACKGROUND: Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy (AION).OBJECTIVE: To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography (FFA), optical coherence tomography (OCT), flash visual evoked potential (F-VEP), and histopathologically confirm its reliability.DESIGN: A randomized control trial.SETTINGS: Department of Ophthalmology, Xi'an Fourth Hospital; Xi'an Institute of Ocular Fundus Diseases.MATERIALS: The experiments were carried out in the research room of Xi'an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g,were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK (Military)2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed.The rats were randomly divided into blank control group (n =5), laser group (n =5), hematoporphyrin derivative (HPD) group and AION group (n =15), each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one.METHODS: In the AION group, the rats were injected with HPD (10 mg/kg) via caudal vein, and then the optic discs were exposed to krypton red (647 nm, 80 mV) for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red (647 nm, 80 mV) for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only

Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

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Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

2016-03-01

Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Modelling the Emergence and Dynamics of Perceptual Organisation in Auditory Streaming

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Mill, Robert W.; Bőhm, Tamás M.; Bendixen, Alexandra; Winkler, István; Denham, Susan L.

2013-01-01

Many sound sources can only be recognised from the pattern of sounds they emit, and not from the individual sound events that make up their emission sequences. Auditory scene analysis addresses the difficult task of interpreting the sound world in terms of an unknown number of discrete sound sources (causes) with possibly overlapping signals, and therefore of associating each event with the appropriate source. There are potentially many different ways in which incoming events can be assigned to different causes, which means that the auditory system has to choose between them. This problem has been studied for many years using the auditory streaming paradigm, and recently it has become apparent that instead of making one fixed perceptual decision, given sufficient time, auditory perception switches back and forth between the alternatives—a phenomenon known as perceptual bi- or multi-stability. We propose a new model of auditory scene analysis at the core of which is a process that seeks to discover predictable patterns in the ongoing sound sequence. Representations of predictable fragments are created on the fly, and are maintained, strengthened or weakened on the basis of their predictive success, and conflict with other representations. Auditory perceptual organisation emerges spontaneously from the nature of the competition between these representations. We present detailed comparisons between the model simulations and data from an auditory streaming experiment, and show that the model accounts for many important findings, including: the emergence of, and switching between, alternative organisations; the influence of stimulus parameters on perceptual dominance, switching rate and perceptual phase durations; and the build-up of auditory streaming. The principal contribution of the model is to show that a two-stage process of pattern discovery and competition between incompatible patterns can account for both the contents (perceptual organisations) and the

Interconnected growing self-organizing maps for auditory and semantic acquisition modeling

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Mengxue eCao

2014-03-01

Full Text Available Based on the incremental nature of knowledge acquisition, in this study we propose a growing self-organizing neural network approach for modeling the acquisition of auditory and semantic categories. We introduce an Interconnected Growing Self-Organizing Maps (I-GSOM algorithm, which takes associations between auditory information and semantic information into consideration, in this paper. Direct phonetic--semantic association is simulated in order to model the language acquisition in early phases, such as the babbling and imitation stages, in which no phonological representations exist. Based on the I-GSOM algorithm, we conducted experiments using paired acoustic and semantic training data. We use a cyclical reinforcing and reviewing training procedure to model the teaching and learning process between children and their communication partners; a reinforcing-by-link training procedure and a link-forgetting procedure are introduced to model the acquisition of associative relations between auditory and semantic information. Experimental results indicate that (1 I-GSOM has good ability to learn auditory and semantic categories presented within the training data; (2 clear auditory and semantic boundaries can be found in the network representation; (3 cyclical reinforcing and reviewing training leads to a detailed categorization as well as to a detailed clustering, while keeping the clusters that have already been learned and the network structure that has already been developed stable; and (4 reinforcing-by-link training leads to well-perceived auditory--semantic associations. Our I-GSOM model suggests that it is important to associate auditory information with semantic information during language acquisition. Despite its high level of abstraction, our I-GSOM approach can be interpreted as a biologically-inspired neurocomputational model.

The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

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Chowdhury, Subir K Roy; Smith, Darrell R; Fernyhough, Paul

2013-03-01

Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). This article attempts to relate these findings to the development of critical neuropathological hallmarks of the disease. Recent work reveals that hyperglycemia in diabetes triggers nutrient excess in neurons that, in turn, mediates a phenotypic change in mitochondrial biology through alteration of the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling axis. This vital energy sensing metabolic pathway modulates mitochondrial function, biogenesis and regeneration. The bioenergetic phenotype of mitochondria in diabetic neurons is aberrant due to deleterious alterations in expression and activity of respiratory chain components as a direct consequence of abnormal AMPK/PGC-1α signaling. Utilization of innovative respirometry equipment to analyze mitochondrial function of cultured adult sensory neurons from diabetic rodents shows that the outcome for cellular bioenergetics is a reduced adaptability to fluctuations in ATP demand. The diabetes-induced maladaptive process is hypothesized to result in exhaustion of the ATP supply in the distal nerve compartment and induction of nerve fiber dissolution. The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich

Auditory thalamic circuits and GABAA receptor function: Putative mechanisms in tinnitus pathology.

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Caspary, Donald M; Llano, Daniel A

2017-06-01

Tinnitus is defined as a phantom sound (ringing in the ears), and can significantly reduce the quality of life for those who suffer its effects. Ten to fifteen percent of the general adult population report symptoms of tinnitus with 1-2% reporting that tinnitus negatively impacts their quality of life. Noise exposure is the most common cause of tinnitus and the military environment presents many challenging high-noise situations. Military noise levels can be so intense that standard hearing protection is not adequate. Recent studies suggest a role for inhibitory neurotransmitter dysfunction in response to noise-induced peripheral deafferentation as a key element in the pathology of tinnitus. The auditory thalamus, or medial geniculate body (MGB), is an obligate auditory brain center in a unique position to gate the percept of sound as it projects to auditory cortex and to limbic structures. Both areas are thought to be involved in those individuals most impacted by tinnitus. For MGB, opposing hypotheses have posited either a tinnitus-related pathologic decrease or pathologic increase in GABAergic inhibition. In sensory thalamus, GABA mediates fast synaptic inhibition via synaptic GABA A receptors (GABA A Rs) as well as a persistent tonic inhibition via high-affinity extrasynaptic GABA A Rs and slow synaptic inhibition via GABA B Rs. Down-regulation of inhibitory neurotransmission, related to partial peripheral deafferentation, is consistently presented as partially underpinning neuronal hyperactivity seen in animal models of tinnitus. This maladaptive plasticity/Gain Control Theory of tinnitus pathology (see Auerbach et al., 2014; Richardson et al., 2012) is characterized by reduced inhibition associated with increased spontaneous and abnormal neuronal activity, including bursting and increased synchrony throughout much of the central auditory pathway. A competing hypothesis suggests that maladaptive oscillations between the MGB and auditory cortex

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice.

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Moon, Eunjung; Lee, Sung Ok; Kang, Tong Ho; Kim, Hye Ju; Choi, Sang Zin; Son, Mi-Won; Kim, Sun Yeou

2014-09-01

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

Unipedal stance testing in the assessment of peripheral neuropathy.

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Hurvitz, E A; Richardson, J K; Werner, R A

2001-02-01

To define further the relation between unipedal stance testing and peripheral neuropathy. Prospective cohort. Electroneuromyography laboratory of a Veterans Affairs medical center and a university hospital. Ninety-two patients referred for lower extremity electrodiagnostic studies. A standardized history and physical examination designed to detect peripheral neuropathy, 3 trials of unipedal stance, and electrodiagnostic studies. Peripheral neuropathy was identified by electrodiagnostic testing in 32%. These subjects had a significantly shorter (p unipedal stance time (15.7s, longest of 3 trials) than the patients without peripheral neuropathy (37.1s). Abnormal unipedal stance time (unipedal stance time had a negative predictive value of 90%. Abnormal unipedal stance time was associated with an increased risk of having peripheral neuropathy on univariate analysis (odds ratio = 8.8, 95% confidence interval = 2.5--31), and was the only significant predictor of peripheral neuropathy in the regression model. Aspects of the neurologic examination did not add to the regression model compared with abnormal unipedal stance time. Unipedal stance testing is useful in the clinical setting both to identify and to exclude the presence of peripheral neuropathy.

Auditory analysis for speech recognition based on physiological models

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Jeon, Woojay; Juang, Biing-Hwang

2004-05-01

To address the limitations of traditional cepstrum or LPC based front-end processing methods for automatic speech recognition, more elaborate methods based on physiological models of the human auditory system may be used to achieve more robust speech recognition in adverse environments. For this purpose, a modified version of a model of the primary auditory cortex featuring a three dimensional mapping of auditory spectra [Wang and Shamma, IEEE Trans. Speech Audio Process. 3, 382-395 (1995)] is adopted and investigated for its use as an improved front-end processing method. The study is conducted in two ways: first, by relating the model's redundant representation to traditional spectral representations and showing that the former not only encompasses information provided by the latter, but also reveals more relevant information that makes it superior in describing the identifying features of speech signals; and second, by observing the statistical features of the representation for various classes of sound to show how different identifying features manifest themselves as specific patterns on the cortical map, thereby becoming a place-coded data set on which detection theory could be applied to simulate auditory perception and cognition.

Abnormal Auditory Gain in Hyperacusis: Investigation with a Computational Model

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Peter U. Diehl

2015-07-01

Full Text Available Hyperacusis is a frequent auditory disorder that is characterized by abnormal loudness perception where sounds of relatively normal volume are perceived as too loud or even painfully loud. As Hyperacusis patients show decreased loudness discomfort levels (LDLs and steeper loudness growth functions, it has been hypothesized that hyperacusis might be caused by an increase in neuronal response gain in the auditory system. Moreover, since about 85% of hyperacusis patients also experience tinnitus, the conditions might be caused by a common mechanism. However, the mechanisms that give rise to hyperacusis have remained unclear.Here we have used a computational model of the auditory system to investigate candidate mechanisms for hyperacusis. Assuming that perceived loudness is proportional to the summed activity of all auditory nerve fibers, the model was tuned to reproduce normal loudness perception. We then evaluated a variety of potential hyperacusis gain mechanisms by determining their effects on model equal-loudness contours and comparing the results to the LDLs of hyperacusis patients with normal hearing thresholds. Hyperacusis was best accounted for by an increase in nonlinear gain in the central auditory system. Good fits to the average patient LDLs were obtained for a general increase in gain that affected all frequency channels to the same degree, and also for a frequency-specific gain increase in the high-frequency range. Moreover, the gain needed to be applied after subtraction of spontaneous activity of the auditory nerve, which is in contrast to current theories of tinnitus generation based on amplification of spontaneous activity. Hyperacusis and tinnitus might therefore be caused by different changes in neuronal processing in the central auditory system.

Hearing after congenital deafness: central auditory plasticity and sensory deprivation.

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Kral, A; Hartmann, R; Tillein, J; Heid, S; Klinke, R

2002-08-01

The congenitally deaf cat suffers from a degeneration of the inner ear. The organ of Corti bears no hair cells, yet the auditory afferents are preserved. Since these animals have no auditory experience, they were used as a model for congenital deafness. Kittens were equipped with a cochlear implant at different ages and electro-stimulated over a period of 2.0-5.5 months using a monopolar single-channel compressed analogue stimulation strategy (VIENNA-type signal processor). Following a period of auditory experience, we investigated cortical field potentials in response to electrical biphasic pulses applied by means of the cochlear implant. In comparison to naive unstimulated deaf cats and normal hearing cats, the chronically stimulated animals showed larger cortical regions producing middle-latency responses at or above 300 microV amplitude at the contralateral as well as the ipsilateral auditory cortex. The cortex ipsilateral to the chronically stimulated ear did not show any signs of reduced responsiveness when stimulating the 'untrained' ear through a second cochlear implant inserted in the final experiment. With comparable duration of auditory training, the activated cortical area was substantially smaller if implantation had been performed at an older age of 5-6 months. The data emphasize that young sensory systems in cats have a higher capacity for plasticity than older ones and that there is a sensitive period for the cat's auditory system.

A human model of small fiber neuropathy to study wound healing.

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Illigens, Ben M W; Gibbons, Christopher H

2013-01-01

The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter) and deep (>3 millimeter) punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (PDeep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (Pshallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.

Modeling auditory processing and speech perception in hearing-impaired listeners

DEFF Research Database (Denmark)

Jepsen, Morten Løve

in a diagnostic rhyme test. The framework was constructed such that discrimination errors originating from the front-end and the back-end were separated. The front-end was fitted to individual listeners with cochlear hearing loss according to non-speech data, and speech data were obtained in the same listeners......A better understanding of how the human auditory system represents and analyzes sounds and how hearing impairment affects such processing is of great interest for researchers in the fields of auditory neuroscience, audiology, and speech communication as well as for applications in hearing......-instrument and speech technology. In this thesis, the primary focus was on the development and evaluation of a computational model of human auditory signal-processing and perception. The model was initially designed to simulate the normal-hearing auditory system with particular focus on the nonlinear processing...

Decision criterion dynamics in animals performing an auditory detection task.

Directory of Open Access Journals (Sweden)

Robert W Mill

Full Text Available Classical signal detection theory attributes bias in perceptual decisions to a threshold criterion, against which sensory excitation is compared. The optimal criterion setting depends on the signal level, which may vary over time, and about which the subject is naïve. Consequently, the subject must optimise its threshold by responding appropriately to feedback. Here a series of experiments was conducted, and a computational model applied, to determine how the decision bias of the ferret in an auditory signal detection task tracks changes in the stimulus level. The time scales of criterion dynamics were investigated by means of a yes-no signal-in-noise detection task, in which trials were grouped into blocks that alternately contained easy- and hard-to-detect signals. The responses of the ferrets implied both long- and short-term criterion dynamics. The animals exhibited a bias in favour of responding "yes" during blocks of harder trials, and vice versa. Moreover, the outcome of each single trial had a strong influence on the decision at the next trial. We demonstrate that the single-trial and block-level changes in bias are a manifestation of the same criterion update policy by fitting a model, in which the criterion is shifted by fixed amounts according to the outcome of the previous trial and decays strongly towards a resting value. The apparent block-level stabilisation of bias arises as the probabilities of outcomes and shifts on single trials mutually interact to establish equilibrium. To gain an intuition into how stable criterion distributions arise from specific parameter sets we develop a Markov model which accounts for the dynamic effects of criterion shifts. Our approach provides a framework for investigating the dynamics of decisions at different timescales in other species (e.g., humans and in other psychological domains (e.g., vision, memory.

Autonomic Neuropathy

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... risk of autonomic neuropathy. Other diseases. Amyloidosis, porphyria, hypothyroidism and cancer (usually due to side effects from treatment) may also increase the risk of autonomic neuropathy. ...

Adapting the Theory of Visual Attention (TVA) to model auditory attention

DEFF Research Database (Denmark)

Roberts, Katherine L.; Andersen, Tobias; Kyllingsbæk, Søren

Mathematical and computational models have provided useful insights into normal and impaired visual attention, but less progress has been made in modelling auditory attention. We are developing a Theory of Auditory Attention (TAA), based on an influential visual model, the Theory of Visual...... Attention (TVA). We report that TVA provides a good fit to auditory data when the stimuli are closely matched to those used in visual studies. In the basic visual TVA task, participants view a brief display of letters and are asked to report either all of the letters (whole report) or a subset of letters (e...... the auditory data, producing good estimates of the rate at which information is encoded (C), the minimum exposure duration required for processing to begin (t0), and the relative attentional weight to targets versus distractors (α). Future work will address the issue of target-distractor confusion, and extend...

[Communication and auditory behavior obtained by auditory evoked potentials in mammals, birds, amphibians, and reptiles].

Science.gov (United States)

Arch-Tirado, Emilio; Collado-Corona, Miguel Angel; Morales-Martínez, José de Jesús

2004-01-01

amphibians, Frog catesbiana (frog bull, 30 animals); reptiles, Sceloporus torcuatus (common small lizard, 22 animals); birds: Columba livia (common dove, 20 animals), and mammals, Cavia porcellus, (guinea pig, 20 animals). With regard to lodging, all animals were maintained at the Institute of Human Communication Disorders, were fed with special food for each species, and had water available ad libitum. Regarding procedure, for carrying out analysis of auditory evoked potentials of brain stem SPL amphibians, birds, and mammals were anesthetized with ketamine 20, 25, and 50 mg/kg, by injection. Reptiles were anesthetized by freezing (6 degrees C). Study subjects had needle electrodes placed in an imaginary line on the half sagittal line between both ears and eyes, behind right ear, and behind left ear. Stimulation was carried out inside a no noise site by means of a horn in free field. The sign was filtered at between 100 and 3,000 Hz and analyzed in a computer for provoked potentials (Racia APE 78). In data shown by amphibians, wave-evoked responses showed greater latency than those of the other species. In reptiles, latency was observed as reduced in comparison with amphibians. In the case of birds, lesser latency values were observed, while in the case of guinea pigs latencies were greater than those of doves but they were stimulated by 10 dB, which demonstrated best auditory threshold in the four studied species. Last, it was corroborated that as the auditory threshold of each species it descends conforms to it advances in the phylogenetic scale. Beginning with these registrations, we care able to say that response for evoked brain stem potential showed to be more complex and lesser values of absolute latency as we advance along the phylogenetic scale; thus, the opposing auditory threshold is better agreement with regard to the phylogenetic scale among studied species. These data indicated to us that seeking of auditory information is more complex in more

Peripheral neuropathy

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... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

A hardware model of the auditory periphery to transduce acoustic signals into neural activity

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Takashi eTateno

2013-11-01

Full Text Available To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.

Comparison of peripheral nerve blockade characteristics between non-diabetic patients and patients suffering from diabetic neuropathy: a prospective cohort study.

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Baeriswyl, M; Taffé, P; Kirkham, K R; Bathory, I; Rancati, V; Crevoisier, X; Cherix, S; Albrecht, E

2018-06-02

Animal data have demonstrated increased block duration after local anaesthetic injections in diabetic rat models. Whether the same is true in humans is currently undefined. We, therefore, undertook this prospective cohort study to test the hypothesis that type-2 diabetic patients suffering from diabetic peripheral neuropathy would have increased block duration after ultrasound-guided popliteal sciatic nerve block when compared with patients without neuropathy. Thirty-three type-2 diabetic patients with neuropathy and 23 non-diabetic control patients, scheduled for fore-foot surgery, were included prospectively. All patients received an ultrasound-guided popliteal sciatic nerve block with a 30 ml 1:1 mixture of lidocaine 1% and bupivacaine 0.5%. The primary outcome was time to first opioid request after block procedure. Secondary outcomes included the time to onset of sensory blockade, and pain score at rest on postoperative day 1 (numeric rating scale 0-10). These outcomes were analysed using an accelerated failure time regression model. Patients in the diabetic peripheral neuropathy group had significantly prolonged median (IQR [range]) time to first opioid request (diabetic peripheral neuropathy group 1440 (IQR 1140-1440 [180-1440]) min vs. control group 710 (IQR 420-1200 [150-1440] min, p = 0.0004). Diabetic peripheral neuropathy patients had a time ratio of 1.57 (95%CI 1.10-2.23, p peripheral neuropathy group 0 (IQR 0-1 [0-5]) vs. control group 3 (IQR 0-5 [0-9]), p = 0.001). In conclusion, after an ultrasound-guided popliteal sciatic nerve block, patients with diabetic peripheral neuropathy demonstrated reduced time to onset of sensory blockade, with increased time to first opioid request when compared with patients without neuropathy. © 2018 The Association of Anaesthetists.

Can animal models contribute to understanding tinnitus heterogeneity in humans?

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Jos J Eggermont

2016-11-01

Full Text Available The brain activity of humans with tinnitus of various etiologies is typically studied with EEG/MEG and fMRI-based imaging techniques. Consequently, they measure population responses and mostly from the neocortex. The latter also underlies changes in neural networks that may be attributed to tinnitus. However, factors not strictly related to tinnitus such as hearing loss and hyperacusis, as well as other co-occurring disorders play a prominent role in these changes. Different types of tinnitus can often not be resolved with these brain-imaging techniques. In animal models of putative behavioral signs of tinnitus, neural activity ranging from auditory nerve to auditory cortex, is studied largely by single unit recordings, augmented by local field potentials (LFPs, and the neural correlates of tinnitus are mainly based on spontaneous neural activity, such as spontaneous firing rates (SFR and pair-wise spontaneous spike-firing correlations. Neural correlates of hyperacusis rely on measurement of stimulus-evoked activity and are measured as increased driven firing rates and LFP amplitudes. Connectivity studies would rely on correlated neural activity between pairs of neurons or LFP amplitudes, but are only recently explored. In animal models of tinnitus only two etiologies are extensively studied; tinnitus evoked by salicylate application and by noise exposure. It appears that they have quite different neural biomarkers. The unanswered question then is: does this different etiology also result in different tinnitus?

Computational spectrotemporal auditory model with applications to acoustical information processing

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Chi, Tai-Shih

A computational spectrotemporal auditory model based on neurophysiological findings in early auditory and cortical stages is described. The model provides a unified multiresolution representation of the spectral and temporal features of sound likely critical in the perception of timbre. Several types of complex stimuli are used to demonstrate the spectrotemporal information preserved by the model. Shown by these examples, this two stage model reflects the apparent progressive loss of temporal dynamics along the auditory pathway from the rapid phase-locking (several kHz in auditory nerve), to moderate rates of synchrony (several hundred Hz in midbrain), to much lower rates of modulations in the cortex (around 30 Hz). To complete this model, several projection-based reconstruction algorithms are implemented to resynthesize the sound from the representations with reduced dynamics. One particular application of this model is to assess speech intelligibility. The spectro-temporal Modulation Transfer Functions (MTF) of this model is investigated and shown to be consistent with the salient trends in the human MTFs (derived from human detection thresholds) which exhibit a lowpass function with respect to both spectral and temporal dimensions, with 50% bandwidths of about 16 Hz and 2 cycles/octave. Therefore, the model is used to demonstrate the potential relevance of these MTFs to the assessment of speech intelligibility in noise and reverberant conditions. Another useful feature is the phase singularity emerged in the scale space generated by this multiscale auditory model. The singularity is shown to have certain robust properties and carry the crucial information about the spectral profile. Such claim is justified by perceptually tolerable resynthesized sounds from the nonconvex singularity set. In addition, the singularity set is demonstrated to encode the pitch and formants at different scales. These properties make the singularity set very suitable for traditional

Susceptibility of various areas of the nervous system of hens to TOCP-induced delayed neuropathy.

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Classen, W; Gretener, P; Rauch, M; Weber, E; Krinke, G J

1996-01-01

Sensitivity of in-life parameters, biochemical endpoints, and susceptibility of various areas of the chicken nervous system to delayed neuropathy induced by tri-orthocresyl phosphate (TOCP) was assessed. Groups of hens were exposed to a single oral dose of TOCP of 0, 50, 200 or 500 mg/kg and the animals observed for 21 days. Perfusion fixed, paraffin embedded tissue sections were stained with Bodian's silver and Luxol blue and semi-thin epoxy sections with toluidine blue. Sciatic and tibial nerves, lumbosacral, midthoracic, and upper cervical spinal cord, medulla oblongata and cerebellum were examined using a semiquantitative scoring system. In pair-dosed hens inhibition of brain and spinal cord neurotoxic esterase (NTE) and cholinesterase and of plasma and erythrocyte cholinesterases was determined 24 hr and 48 hr after administration. At all dose levels NTE in brain and spinal cord and plasma cholinesterase was inhibited markedly. Quantitative inhibition of NTE was seen also in absence of neuropathy. Ataxia and body weight loss occurred in high-dose animals only, while dose-related neuropathy was seen in the distal tibial nerve, medulla oblongata and cerebellum. Ataxia was correlated best with neuropathy in peripheral nerves while degeneration of nerve fibers in the cerebellum, seen best in mid-longitudinal sections, was the most sensitive histological indicator of TOCP-induced delayed neuropathy. The particular susceptibility of spinocerebellar neurons was recognized long ago, but often has been neglected in delayed neurotoxicity studies and respective guidelines. Optimal sensitivity of toxicity tests is a prerequisite for risk assessment, can be cost efficient, and nowadays should be a main interest of animal welfare in order to reduce animals' suffering. Based on these data, determination of NTE inhibition together with histopathological examination of longitudinal sections of distal tibial nerves, mid-longitudinal sections of rostral cerebellum and cross

Acquired neuropathies.

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Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

2013-09-01

Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

Beneficial auditory and cognitive effects of auditory brainstem implantation in children.

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Colletti, Liliana

2007-09-01

with a CI, had auditory neuropathy; one child showed total cochlear ossification bilaterally due to meningitis; and one child had profound hearing loss with cochlear fractures after a head injury. Twelve of these children had multiple associated psychomotor handicaps. The retrosigmoid approach was used in all children. Intraoperative electrical auditory brainstem responses (EABRs) and postoperative EABRs and electrical middle latency responses (EMLRs) were performed. Perceptual auditory abilities were evaluated with the Evaluation of Auditory Responses to Speech (EARS) battery - the Listening Progress Profile (LIP), the Meaningful Auditory Integration Scale (MAIS), the Meaningful Use of Speech Scale (MUSS) - and the Category of Auditory Performance (CAP). Cognitive evaluation was performed on seven children using the Leiter International Performance Scale - Revised (LIPS-R) test with the following subtests: Figure ground, Form completion, Sequential order and Repeated pattern. No postoperative complications were observed. All children consistently used their devices for >75% of waking hours and had environmental sound awareness and utterance of words and simple sentences. Their CAP scores ranged from 1 to 7 (average =4); with MAIS they scored 2-97.5% (average =38%); MUSS scores ranged from 5 to 100% (average =49%) and LIP scores from 5 to 100% (average =45%). Owing to associated disabilities, 12 children were given other therapies (e.g. physical therapy and counselling) in addition to speech and aural rehabilitation therapy. Scores for two of the four subtests of LIPS-R in this study increased significantly during the first year of auditory brainstem implant use in all seven children selected for cognitive evaluation.

Is there treatment for nonarteritic anterior ischemic optic neuropathy.

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Katz, David M; Trobe, Jonathan D

2015-11-01

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of an acute optic neuropathy over the age 50 with an annual incidence of 2-10/100 000. Most patients are left with a permanent decrease in visual acuity and visual field loss. No approved treatment has conclusively reversed the process or prevented a second event that typically involves the previously unaffected eye. Many medical and surgical treatments have been proposed with conflicting results. The goal of this review is to present current data in order to permit clinicians and patients to make an educated decision about treatment. Recently, there has been a flurry of case reports, small clinical trials and testing in animal models of NAION for various treatments for NAION and this review attempts to present the data concisely with the authors' opinions about the reliability of the data. To date, there is no class I evidence of benefit for the treatment of NAION; however, the aphorism attributed to Carl Sagan, PhD aptly applies: 'Absence of evidence is not evidence of absence'.

Delayed neurotoxicity - do trichlorphon and/or dichlorvos cause delayed neuropathy in man or in test animals?

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Johnson, M K

1981-01-01

Many, but not all, reports of delayed neuropathy associated with acute poisoning by trichlorphon refer to cases in U.S.S.R. Adulteration of technical trichlorphon with the ethyl analogue would greatly increase the neurotoxic hazard but analysis of a few samples has not revealed such impurities. Simultaneous ingestion of alcohol does not appear to increase neuropathic hazard. In hens double doses of trichlorphon each exceeding unprotected LD50 can produce moderate neuropathy associated with appropriately high inhibitions of neurotoxic esterase. Similar results are obtained with 2 doses of 10 x LD50 of dichlorvos. In vitro the inhibitory power of dichlorvos against neurotoxic esterase of hen brain is 0.02 x the power against acetylcholinesterase. This ratio correlates reasonably with the ratio of LD50/neuropathic dose. The factor for human brain enzymes is 0.06 suggesting that man is more susceptible to neuropathic effects of near-lethal doses of circulating dichlorvos. It is concluded that the only neuropathic hazard to man from good quality trichlorphon arises from rapid ingestion of massive doses. To obtain critical levels of inhibition of neurotoxic esterase and to cause neuropathy in man by repeated doses would require each dose to be severely toxic. Dichlorvos ingested in large doses is likely to kill rather than to cause neuropathy.

Auditory cortex involvement in emotional learning and memory.

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Grosso, A; Cambiaghi, M; Concina, G; Sacco, T; Sacchetti, B

2015-07-23

Emotional memories represent the core of human and animal life and drive future choices and behaviors. Early research involving brain lesion studies in animals lead to the idea that the auditory cortex participates in emotional learning by processing the sensory features of auditory stimuli paired with emotional consequences and by transmitting this information to the amygdala. Nevertheless, electrophysiological and imaging studies revealed that, following emotional experiences, the auditory cortex undergoes learning-induced changes that are highly specific, associative and long lasting. These studies suggested that the role played by the auditory cortex goes beyond stimulus elaboration and transmission. Here, we discuss three major perspectives created by these data. In particular, we analyze the possible roles of the auditory cortex in emotional learning, we examine the recruitment of the auditory cortex during early and late memory trace encoding, and finally we consider the functional interplay between the auditory cortex and subcortical nuclei, such as the amygdala, that process affective information. We conclude that, starting from the early phase of memory encoding, the auditory cortex has a more prominent role in emotional learning, through its connections with subcortical nuclei, than is typically acknowledged. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

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Gyula Varadi

2015-01-01

Full Text Available We designed a transdermal system to serve as a delivery platform for benfotiamine utilizing the attributes of passive penetration enhancing molecules to penetrate through the outer layers of skin combined with the advance of incorporating various peripherally-acting vasodilators to enhance drug uptake.  Benfotiamine, incorporated into this transdermal formulation, was applied to skin in an animal model in order to determine the ability to deliver this thiamine pro-drug effectively to the sub-epithelial layers.  In this proof of concept study in guinea pigs, we found that a single topical application of either a solubilized form of benfotiamine (15 mg or a microcrystalline suspension form (25 mg resulted in considerable increases of the dephosphorylated benfotiamine (S-benzoylthiamine in the skin tissue as well as in significant increases in the thiamine and thiamine phosphate pools compared to control animals.  The presence of a ~8000x increase in thiamine and increases in its phosphorylated derivatives in the epidermis and dermis tissue of the test animals gives a strong indication that the topical treatment with benfotiamine works very well for the desired outcome of producing an intracellular increase of the activating cofactor pool for transketolase enzyme, which is implicated in the pathophysiology of diabetic neuropathy.

Subcortical pathways: Towards a better understanding of auditory disorders.

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Felix, Richard A; Gourévitch, Boris; Portfors, Christine V

2018-05-01

Hearing loss is a significant problem that affects at least 15% of the population. This percentage, however, is likely significantly higher because of a variety of auditory disorders that are not identifiable through traditional tests of peripheral hearing ability. In these disorders, individuals have difficulty understanding speech, particularly in noisy environments, even though the sounds are loud enough to hear. The underlying mechanisms leading to such deficits are not well understood. To enable the development of suitable treatments to alleviate or prevent such disorders, the affected processing pathways must be identified. Historically, mechanisms underlying speech processing have been thought to be a property of the auditory cortex and thus the study of auditory disorders has largely focused on cortical impairments and/or cognitive processes. As we review here, however, there is strong evidence to suggest that, in fact, deficits in subcortical pathways play a significant role in auditory disorders. In this review, we highlight the role of the auditory brainstem and midbrain in processing complex sounds and discuss how deficits in these regions may contribute to auditory dysfunction. We discuss current research with animal models of human hearing and then consider human studies that implicate impairments in subcortical processing that may contribute to auditory disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of Fyn-mediated NMDA receptor function in prediabetic neuropathy in mice

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Suo, Meng; Wang, Ping

2016-01-01

Diabetic neuropathy is a common complication of diabetes. This study evaluated the role of Fyn kinase and N-methyl-d-aspartate receptors (NMDARs) in the spinal cord in diabetic neuropathy using an animal model of high-fat diet-induced prediabetes. We found that prediabetic wild-type mice exhibited tactile allodynia and thermal hypoalgesia after a 16-wk high-fat diet, relative to normal diet-fed wild-type mice. Furthermore, prediabetic wild-type mice exhibited increased tactile allodynia and thermal hypoalgesia at 24 wk relative to 16 wk. Such phenomena were correlated with increased expression and activation of NR2B subunit of NMDARs, as well as Fyn-NR2B interaction in the spinal cord. Fyn−/− mice developed prediabetes after 16-wk high-fat diet treatment and exhibited thermal hypoalgesia, without showing tactile allodynia or altered expression and activation of NR2B subunit, relative to normal diet-fed Fyn−/− mice. Finally, intrathecal administrations of Ro 25-6981 (selective NR2B subunit-containing NMDAR antagonist) dose-dependently alleviated tactile allodynia, but not thermal hypoalgesia, at 16 and 24 wk in prediabetic wild-type mice. Our results suggested that Fyn-mediated NR2B signaling plays a critical role in regulation of prediabetic neuropathy and that the increased expression/function of NR2B subunit-containing NMDARs may contribute to the progression of neuropathy in type 2 diabetes. PMID:27146985

Neuromechanistic Model of Auditory Bistability.

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James Rankin

2015-11-01

Full Text Available Sequences of higher frequency A and lower frequency B tones repeating in an ABA- triplet pattern are widely used to study auditory streaming. One may experience either an integrated percept, a single ABA-ABA- stream, or a segregated percept, separate but simultaneous streams A-A-A-A- and -B---B--. During minutes-long presentations, subjects may report irregular alternations between these interpretations. We combine neuromechanistic modeling and psychoacoustic experiments to study these persistent alternations and to characterize the effects of manipulating stimulus parameters. Unlike many phenomenological models with abstract, percept-specific competition and fixed inputs, our network model comprises neuronal units with sensory feature dependent inputs that mimic the pulsatile-like A1 responses to tones in the ABA- triplets. It embodies a neuronal computation for percept competition thought to occur beyond primary auditory cortex (A1. Mutual inhibition, adaptation and noise are implemented. We include slow NDMA recurrent excitation for local temporal memory that enables linkage across sound gaps from one triplet to the next. Percepts in our model are identified in the firing patterns of the neuronal units. We predict with the model that manipulations of the frequency difference between tones A and B should affect the dominance durations of the stronger percept, the one dominant a larger fraction of time, more than those of the weaker percept-a property that has been previously established and generalized across several visual bistable paradigms. We confirm the qualitative prediction with our psychoacoustic experiments and use the behavioral data to further constrain and improve the model, achieving quantitative agreement between experimental and modeling results. Our work and model provide a platform that can be extended to consider other stimulus conditions, including the effects of context and volition.

Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline

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2016-11-28

Title: Hidden Hearing Loss and Computational Models of the Auditory Pathway: Predicting Speech Intelligibility Decline Christopher J. Smalt...representation of speech intelligibility in noise. The auditory-periphery model of Zilany et al. (JASA 2009,2014) is used to make predictions of...auditory nerve (AN) responses to speech stimuli under a variety of difficult listening conditions. The resulting cochlear neurogram, a spectrogram

Seeing the sound after visual loss: functional MRI in acquired auditory-visual synesthesia.

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Yong, Zixin; Hsieh, Po-Jang; Milea, Dan

2017-02-01

Acquired auditory-visual synesthesia (AVS) is a rare neurological sign, in which specific auditory stimulation triggers visual experience. In this study, we used event-related fMRI to explore the brain regions correlated with acquired monocular sound-induced phosphenes, which occurred 2 months after unilateral visual loss due to an ischemic optic neuropathy. During the fMRI session, 1-s pure tones at various pitches were presented to the patient, who was asked to report occurrence of sound-induced phosphenes by pressing one of the two buttons (yes/no). The brain activation during phosphene-experienced trials was contrasted with non-phosphene trials and compared to results obtained in one healthy control subject who underwent the same fMRI protocol. Our results suggest, for the first time, that acquired AVS occurring after visual impairment is associated with bilateral activation of primary and secondary visual cortex, possibly due to cross-wiring between auditory and visual sensory modalities.

Investigation of auditory brainstem function in elderly diabetic patients with presbycusis.

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Kovacií, Jelena; Lajtman, Zoran; Ozegović, Ivan; Knezević, Predrag; Carić, Tomislav; Vlasić, Ana

2009-01-01

We performed brainstem auditory evoked potential (BAEP) examinations in 100 patients older than 60 years and having type I diabetes mellitus and presbycusis. The aim of our investigation was to compare the BAEP results of this group with those of healthy controls with presbycusis and to look for possible correlations between alteration of the auditory brainstem function and the aging of elderly diabetic patients. Absolute and interpeak latencies of all waves were prolonged significantly in the study group of diabetic patients. The amplitudes of all waves I through V were diminished in the study group as compared to those in the control group, with statistical significance present for all waves. Analysis of the latencies (waves I, II, I, and V), interpeak latencies (I-V), and amplitudes (I, II, III, and V) of BAEP revealed a significant difference between those of diabetics and those of healthy elderly controls with presbycusis. These data support a hypothesis that there is a brainstem neuropathy in diabetes mellitus that can be assessed with auditory brainstem response testing even in the group of elderly patients with sensorineural hearing loss.

Transient Abnormalities in Masking Tuning Curve in Early Progressive Hearing Loss Mouse Model

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Marion Souchal

2018-01-01

Full Text Available Damage to cochlear outer hair cells (OHCs usually affects frequency selectivity in proportion to hearing threshold increase. However, the current clinical heuristics that attributes poor hearing performance despite near-normal auditory sensitivity to auditory neuropathy or “hidden” synaptopathy overlooks possible underlying OHC impairment. Here, we document the part played by OHCs in influencing suprathreshold auditory performance in the presence of noise in a mouse model of progressive hair cell degeneration, the CD1 strain, at postnatal day 18–30 stages when high-frequency auditory thresholds remained near-normal. Nonetheless, total loss of high-frequency distortion product otoacoustic emissions pointed to nonfunctioning basal OHCs. This “discordant profile” came with a huge low-frequency shift of masking tuning curves that plot the level of interfering sound necessary to mask the response to a probe tone, against interfering frequency. Histology revealed intense OHC hair bundle abnormalities in the basal cochlea uncharacteristically associated with OHC survival and preserved coupling with the tectorial membrane. This pattern dismisses the superficial diagnosis of “hidden” neuropathy while underpinning a disorganization of cochlear frequency mapping with optimistic high-frequency auditory thresholds perhaps because responses to high frequencies are apically shifted. The audiometric advantage of frequency transposition is offset by enhanced masking by low-frequency sounds, a finding essential for guiding rehabilitation.

The vasculitic neuropathies: an update.

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Collins, Michael P

2012-10-01

Vasculitic neuropathy is a heterogeneous disorder that usually occurs in systemic diseases, but less commonly appears as nonsystemic vasculitic neuropathy (NSVN). This review is intended to highlight recent developments in the field of vasculitic neuropathies. A Peripheral Nerve Society guideline provides data-driven consensus recommendation on classification of vasculitic neuropathies and diagnosis/treatment of NSVN. NSVN is sometimes accompanied by subclinical inflammation of adjacent skin. Amyotrophic lateral sclerosis with sensory involvement can mimic NSVN. Systemic vasculitides with neuropathy include polyarteritis nodosa, microscopic polyangiitis (MPA), rheumatoid vasculitis, Churg-Strauss syndrome (CSS), and hepatitis C-related mixed cryoglobulinemic vasculitis (MCV). At autopsy, MPA affects limb nerves diffusely, with maximal damage in proximal/middle segments. CSS can be accompanied by antineutrophil cytoplasmic antibodies (ANCAs), but most patients with neuropathy lack ANCAs. Cryoglobulinemic neuropathies are usually caused by vasculitis, irrespective of phenotype. Two randomized trials revealed rituximab to be noninferior to cyclophosphamide for inducing remission in ANCA-associated vasculitis. Many reports also document efficacy of rituximab in MCV. Consensus guidelines on NSVN should be evaluated prospectively. MPA-associated vasculitic neuropathy results from vasculitic lesions distributed diffusely throughout peripheral extremity nerves. Rituximab is effective for ANCA-associated and cryoglobulinemic vasculitis with neuropathy.

Modeling of Auditory Neuron Response Thresholds with Cochlear Implants

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Frederic Venail

2015-01-01

Full Text Available The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement, electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device. The electrical response, measured using auto-NRT (neural responses telemetry algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, P<0.01, the scalar placement of the electrodes (β = −8.50 ± 1.97, P<0.01, and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF. Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas.

Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

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Molina, S J; Capani, F; Guelman, L R

2016-04-01

It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

No auditory experience, no tinnitus: Lessons from subjects with congenital- and acquired single-sided deafness.

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Lee, Sang-Yeon; Nam, Dong Woo; Koo, Ja-Won; De Ridder, Dirk; Vanneste, Sven; Song, Jae-Jin

2017-10-01

Recent studies have adopted the Bayesian brain model to explain the generation of tinnitus in subjects with auditory deafferentation. That is, as the human brain works in a Bayesian manner to reduce environmental uncertainty, missing auditory information due to hearing loss may cause auditory phantom percepts, i.e., tinnitus. This type of deafferentation-induced auditory phantom percept should be preceded by auditory experience because the fill-in phenomenon, namely tinnitus, is based upon auditory prediction and the resultant prediction error. For example, a recent animal study observed the absence of tinnitus in cats with congenital single-sided deafness (SSD; Eggermont and Kral, Hear Res 2016). However, no human studies have investigated the presence and characteristics of tinnitus in subjects with congenital SSD. Thus, the present study sought to reveal differences in the generation of tinnitus between subjects with congenital SSD and those with acquired SSD to evaluate the replicability of previous animal studies. This study enrolled 20 subjects with congenital SSD and 44 subjects with acquired SSD and examined the presence and characteristics of tinnitus in the groups. None of the 20 subjects with congenital SSD perceived tinnitus on the affected side, whereas 30 of 44 subjects with acquired SSD experienced tinnitus on the affected side. Additionally, there were significant positive correlations between tinnitus characteristics and the audiometric characteristics of the SSD. In accordance with the findings of the recent animal study, tinnitus was absent in subjects with congenital SSD, but relatively frequent in subjects with acquired SSD, which suggests that the development of tinnitus should be preceded by auditory experience. In other words, subjects with profound congenital peripheral deafferentation do not develop auditory phantom percepts because no auditory predictions are available from the Bayesian brain. Copyright © 2017 Elsevier B.V. All rights

Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS).

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San Juan, Juan; Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

2017-01-01

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom

Tinnitus alters resting state functional connectivity (RSFC in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS.

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Juan San Juan

Full Text Available Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex and non-region of interest (adjacent non-auditory cortices and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz, broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to

Social interaction with a tutor modulates responsiveness of specific auditory neurons in juvenile zebra finches.

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Yanagihara, Shin; Yazaki-Sugiyama, Yoko

2018-04-12

Behavioral states of animals, such as observing the behavior of a conspecific, modify signal perception and/or sensations that influence state-dependent higher cognitive behavior, such as learning. Recent studies have shown that neuronal responsiveness to sensory signals is modified when animals are engaged in social interactions with others or in locomotor activities. However, how these changes produce state-dependent differences in higher cognitive function is still largely unknown. Zebra finches, which have served as the premier songbird model, learn to sing from early auditory experiences with tutors. They also learn from playback of recorded songs however, learning can be greatly improved when song models are provided through social communication with tutors (Eales, 1989; Chen et al., 2016). Recently we found a subset of neurons in the higher-level auditory cortex of juvenile zebra finches that exhibit highly selective auditory responses to the tutor song after song learning, suggesting an auditory memory trace of the tutor song (Yanagihara and Yazaki-Sugiyama, 2016). Here we show that auditory responses of these selective neurons became greater when juveniles were paired with their tutors, while responses of non-selective neurons did not change. These results suggest that social interaction modulates cortical activity and might function in state-dependent song learning. Copyright © 2018 Elsevier B.V. All rights reserved.

Drug-induced peripheral neuropathy

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Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

2014-01-01

Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

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Topakian, Raffi; Wimmer, Sibylle; Pischinger, Barbara; Pichler, Robert

2014-10-17

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing. 2014 BMJ Publishing Group Ltd.

Towards an auditory account of speech rhythm: application of a model of the auditory 'primal sketch' to two multi-language corpora.

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Lee, Christopher S; Todd, Neil P McAngus

2004-10-01

The world's languages display important differences in their rhythmic organization; most particularly, different languages seem to privilege different phonological units (mora, syllable, or stress foot) as their basic rhythmic unit. There is now considerable evidence that such differences have important consequences for crucial aspects of language acquisition and processing. Several questions remain, however, as to what exactly characterizes the rhythmic differences, how they are manifested at an auditory/acoustic level and how listeners, whether adult native speakers or young infants, process rhythmic information. In this paper it is proposed that the crucial determinant of rhythmic organization is the variability in the auditory prominence of phonetic events. In order to test this auditory prominence hypothesis, an auditory model is run on two multi-language data-sets, the first consisting of matched pairs of English and French sentences, and the second consisting of French, Italian, English and Dutch sentences. The model is based on a theory of the auditory primal sketch, and generates a primitive representation of an acoustic signal (the rhythmogram) which yields a crude segmentation of the speech signal and assigns prominence values to the obtained sequence of events. Its performance is compared with that of several recently proposed phonetic measures of vocalic and consonantal variability.

Neural Correlates of Auditory Processing, Learning and Memory Formation in Songbirds

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Pinaud, R.; Terleph, T. A.; Wynne, R. D.; Tremere, L. A.

Songbirds have emerged as powerful experimental models for the study of auditory processing of complex natural communication signals. Intact hearing is necessary for several behaviors in developing and adult animals including vocal learning, territorial defense, mate selection and individual recognition. These behaviors are thought to require the processing, discrimination and memorization of songs. Although much is known about the brain circuits that participate in sensorimotor (auditory-vocal) integration, especially the ``song-control" system, less is known about the anatomical and functional organization of central auditory pathways. Here we discuss findings associated with a telencephalic auditory area known as the caudomedial nidopallium (NCM). NCM has attracted significant interest as it exhibits functional properties that may support higher order auditory functions such as stimulus discrimination and the formation of auditory memories. NCM neurons are vigorously dr iven by auditory stimuli. Interestingly, these responses are selective to conspecific, relative to heterospecific songs and artificial stimuli. In addition, forms of experience-dependent plasticity occur in NCM and are song-specific. Finally, recent experiments employing high-throughput quantitative proteomics suggest that complex protein regulatory pathways are engaged in NCM as a result of auditory experience. These molecular cascades are likely central to experience-associated plasticity of NCM circuitry and may be part of a network of calcium-driven molecular events that support the formation of auditory memory traces.

Tinnitus. I: Auditory mechanisms: a model for tinnitus and hearing impairment.

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Hazell, J W; Jastreboff, P J

1990-02-01

A model is proposed for tinnitus and sensorineural hearing loss involving cochlear pathology. As tinnitus is defined as a cortical perception of sound in the absence of an appropriate external stimulus it must result from a generator in the auditory system which undergoes extensive auditory processing before it is perceived. The concept of spatial nonlinearity in the cochlea is presented as a cause of tinnitus generation controlled by the efferents. Various clinical presentations of tinnitus and the way in which they respond to changes in the environment are discussed with respect to this control mechanism. The concept of auditory retraining as part of the habituation process, and interaction with the prefrontal cortex and limbic system is presented as a central model which emphasizes the importance of the emotional significance and meaning of tinnitus.

Functional mapping of the primate auditory system.

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Poremba, Amy; Saunders, Richard C; Crane, Alison M; Cook, Michelle; Sokoloff, Louis; Mishkin, Mortimer

2003-01-24

Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

Impairment of retrograde neuronal transport in oxaliplatin-induced neuropathy demonstrated by molecular imaging.

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Dawid Schellingerhout

Full Text Available BACKGROUND AND PURPOSE: The purpose of our study was to utilize a molecular imaging technology based on the retrograde axonal transport mechanism (neurography, to determine if oxaliplatin-induced neurotoxicity affects retrograde axonal transport in an animal model. MATERIALS AND METHODS: Mice (n = 8/group were injected with a cumulative dose of 30 mg/kg oxaliplatin (sufficient to induce neurotoxicity or dextrose control injections. Intramuscular injections of Tetanus Toxin C-fragment (TTc labeled with Alexa 790 fluorescent dye were done (15 ug/20 uL in the left calf muscles, and in vivo fluorescent imaging performed (0-60 min at baseline, and then weekly for 5 weeks, followed by 2-weekly imaging out to 9 weeks. Tissues were harvested for immunohistochemical analysis. RESULTS: With sham treatment, TTc transport causes fluorescent signal intensity over the thoracic spine to increase from 0 to 60 minutes after injection. On average, fluorescence signal increased 722%+/-117% (Mean+/-SD from 0 to 60 minutes. Oxaliplatin treated animals had comparable transport at baseline (787%+/-140%, but transport rapidly decreased through the course of the study, falling to 363%+/-88%, 269%+/-96%, 191%+/-58%, 121%+/-39%, 75%+/-21% with each successive week and stabilizing around 57% (+/-15% at 7 weeks. Statistically significant divergence occurred at approximately 3 weeks (p≤0.05, linear mixed-effects regression model. Quantitative immuno-fluorescence histology with a constant cutoff threshold showed reduced TTc in the spinal cord at 7 weeks for treated animals versus controls (5.2 Arbitrary Units +/-0.52 vs 7.1 AU +/-1.38, p0.56, T-test. CONCLUSION: We show-for the first time to our knowledge-that neurographic in vivo molecular imaging can demonstrate imaging changes in a model of oxaliplatin-induced neuropathy. Impaired retrograde neural transport is suggested to be an important part of the pathophysiology of oxaliplatin-induced neuropathy.

Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures.

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Choo, Daniel I; Tawfik, Kareem O; Martin, Donna M; Raphael, Yehoash

2017-12-01

The inner ear contains the sensory organs for hearing and balance. Both hearing and balance are commonly affected in individuals with CHARGE syndrome (CS), an autosomal dominant condition caused by heterozygous pathogenic variants in the CHD7 gene. Semicircular canal dysplasia or aplasia is the single most prevalent feature in individuals with CHARGE leading to deficient gross motor skills and ambulation. Identification of CHD7 as the major gene affected in CHARGE has enabled acceleration of research in this field. Great progress has been made in understanding the role of CHD7 in the development and function of the inner ear, as well as in related organs such as the middle ear and auditory and vestibular neural pathways. The goals of current research on CHD7 and CS are to (a) improve our understanding of the pathology caused by CHD7 pathogenic variants and (b) to provide better tools for prognosis and treatment. Current studies utilize cells and whole animals, from flies to mammals. The mouse is an excellent model for exploring mechanisms of Chd7 function in the ear, given the evolutionary conservation of ear structure, function, Chd7 expression, and similarity of mutant phenotypes between mice and humans. Newly recognized developmental functions for mouse Chd7 are shedding light on how abnormalities in CHD7 might lead to CS symptoms in humans. Here we review known human inner ear phenotypes associated with CHD7 pathogenic variants and CS, summarize progress toward diagnosis and treatment of inner ear-related pathologies, and explore new avenues for treatment based on basic science discoveries. © 2017 Wiley Periodicals, Inc.

Effect of flavonol and its dimethoxy derivatives on paclitaxel-induced peripheral neuropathy in mice.

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Sayeli, Vijaykumar; Nadipelly, Jagan; Kadhirvelu, Parimala; Cheriyan, Binoy Varghese; Shanmugasundaram, Jaikumar; Subramanian, Viswanathan

2018-04-13

Peripheral neuropathy is the dose limiting side effect of many anticancer drugs. Flavonoids exhibit good antinociceptive effect in animal models. Their efficacy against different types of nociception has been documented. The present study investigated the effect of flavonol (3-hydroxy flavone), 3',4'-dimethoxy flavonol, 6,3'-dimethoxy flavonol, 7,2'-dimethoxy flavonol and 7,3'-dimethoxy flavonol against paclitaxel-induced peripheral neuropathy in mice. A single dose of paclitaxel (10 mg/kg, i.p.) was administered to induce peripheral neuropathy in mice and the manifestations of peripheral neuropathy such as tactile allodynia, cold allodynia and thermal hyperalgesia were assessed 24 h later by employing Von Frey hair aesthesiometer test, acetone bubble test and hot water tail immersion test, respectively. The test compounds were prepared as a suspension in 0.5% carboxymethyl cellulose and were administered s.c. in various doses (25, 50, 100 and 200 mg/kg). The above behavioral responses were assessed prior to and 30 min after drug treatment. In addition, the effect of test compounds on proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and free radicals was investigated by using suitable in vitro assays. A dose-dependent attenuation of tactile allodynia, cold allodynia and thermal hyperalgesia was evidenced in mice treated with flavonol derivatives. The test compounds inhibited TNF-α, IL-1β and free radicals in a concentration-dependent manner. These results revealed that flavonol and its dimethoxy derivatives ameliorated the manifestations of paclitaxel-induced peripheral neuropathy in mice. The inhibition of proinflammatory cytokines and free radicals could contribute to this beneficial effect.

Evaluation and Prevention of Diabetic Neuropathy

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Pajouhi M

2007-07-01

Full Text Available Background: Diabetic neuropathy is an incapacitating disease that afflicts almost 50 percent of patients with diabetes. A late finding in type 1 diabetes, diabetic neuropathy can be an early finding in non insulin-dependent diabetes. Diabetic neuropathies are divided primarily into two groups, sensorimotor and autonomic. Patients may acquire only one type of diabetic neuropathy or may present with combinations of neuropathies, such as autonomic neuropathy or distal symmetric polyneuropathy, the latter of which the most common form. Motor deficits, orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis, bladder dysfunction, and sexual dysfunction can also result from diabetic neuropathy. Strict control of blood sugar, combined with proper daily foot care, is essential to avoid the complications of this disorder. With the potential to afflict any part of the nervous system, diabetic neuropathy should be suspected in all patients with type 2 diabetes as well as patients who have had type 1 diabetes for over five years. Although some patients with diabetic neuropathy notice few symptoms, upon physical examination mild to moderately severe sensory loss may be noted by the physician. Idiopathic neuropathy has been known to precede the onset of type 2 diabetes.

Mathematical model for space perception to explain auditory horopter curves; Chokaku horopter wo setsumeisuru kukan ichi chikaku model

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Okura, M. [Dynax Co., Tokyo (Japan); Maeda, T.; Tachi, S. [The University of Tokyo, Tokyo (Japan). Faculty of Engineering

1998-10-31

For binocular visual space, the horizontal line seen as a straight line on the subjective frontoparallel plane does not always agree with the physically straight line, and the shape thereof depends on distance from the observer. This phenomenon is known as a Helmhotz`s horopter. The same phenomenon may occur also in binaural space, which depends on distance to an acoustic source. This paper formulates a scaler addition model that explains auditory horopter by using two items of information: sound pressure and interaural time difference. Furthermore, this model was used to perform simulations on different learning domains, and the following results were obtained. It was verified that the distance dependence of the auditory horopter can be explained by using the above scaler addition model; and difference in horopter shapes among the subjects may be explained by individual difference in learning domains of spatial position recognition. In addition, such an auditory model was shown not to include as short distance as in the learning domain in the auditory horopter model. 21 refs., 6 figs.

Peripheral Neuropathy and Agent Orange

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... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

MODELING SPECTRAL AND TEMPORAL MASKING IN THE HUMAN AUDITORY SYSTEM

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Dau, Torsten; Jepsen, Morten Løve; Ewert, Stephan D.

2007-01-01

An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997)] but inclu......An auditory signal processing model is presented that simulates psychoacoustical data from a large variety of experimental conditions related to spectral and temporal masking. The model is based on the modulation filterbank model by Dau et al. [J. Acoust. Soc. Am. 102, 2892-2905 (1997...... was tested in conditions of tone-in-noise masking, intensity discrimination, spectral masking with tones and narrowband noises, forward masking with (on- and off-frequency) noise- and pure-tone maskers, and amplitude modulation detection using different noise carrier bandwidths. One of the key properties...

Peripheral Neuropathy: Symptoms and Signs

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... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

Imaging of neuropathies about the hip

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Martinoli, Carlo, E-mail: carlo.martinoli@unige.it [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Miguel-Perez, Maribel [Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapy, Faculty of Medicine (C Bellvitge), University of Barcelona, Barcelona (Spain); Padua, Luca [Fondazione Don Gnocchi Onlus and Department of Neurology, Policlinico “A. Gemelli”, Università Cattolica del Sacro Cuore, Rome (Italy); Gandolfo, Nicola [IM2S – Institut Monégasque de Médecine and Chirurgie Sportive, Montecarlo (Monaco); Zicca, Anna [Radiologia – DISC, Università di Genova, Largo Rosanna Benzi 8, I-16132 Genoa (Italy); Tagliafico, Alberto [Radiologia – National Institute for Cancer Research, Genoa (Italy)

2013-01-15

Neuropathies about the hip may be cause of chronic pain and disability. In most cases, these conditions derive from mechanical or dynamic compression of a segment of a nerve within a narrow osteofibrous tunnel, an opening in a fibrous structure, or a passageway close to a ligament or a muscle. Although the evaluation of nerve disorders primarily relies on neurological examination and electrophysiology, diagnostic imaging is currently used as a complement to help define the site and aetiology of nerve compression and exclude other disease possibly underlying the patient’ symptoms. Diagnosis of entrapment neuropathies about the hip with US and MR imaging requires an in-depth knowledge of the normal imaging anatomy and awareness of the anatomic and pathologic factors that may predispose or cause a nerve injury. Accordingly, the aim of this article is to provide a comprehensive review of hip neuropathies with an emphasis on the relevant anatomy, aetiology, clinical presentation, and their imaging appearance. The lateral femoral cutaneous neuropathy (meiralgia paresthetica), femoral neuropathy, sciatic neuropathy, obturator neuropathy, superior and inferior gluteal neuropathies and pudendal neuropathy will be discussed.

Plasticity in the Primary Auditory Cortex, Not What You Think it is: Implications for Basic and Clinical Auditory Neuroscience

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Weinberger, Norman M.

2013-01-01

Standard beliefs that the function of the primary auditory cortex (A1) is the analysis of sound have proven to be incorrect. Its involvement in learning, memory and other complex processes in both animals and humans is now well-established, although often not appreciated. Auditory coding is strongly modifed by associative learning, evident as associative representational plasticity (ARP) in which the representation of an acoustic dimension, like frequency, is re-organized to emphasize a sound that has become behaviorally important. For example, the frequency tuning of a cortical neuron can be shifted to match that of a significant sound and the representational area of sounds that acquire behavioral importance can be increased. ARP depends on the learning strategy used to solve an auditory problem and the increased cortical area confers greater strength of auditory memory. Thus, primary auditory cortex is involved in cognitive processes, transcending its assumed function of auditory stimulus analysis. The implications for basic neuroscience and clinical auditory neuroscience are presented and suggestions for remediation of auditory processing disorders are introduced. PMID:25356375

Catecholamines and diabetic autonomic neuropathy

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Hilsted, J

1995-01-01

In diabetic patients with autonomic neuropathy plasma noradrenaline concentration, used as an index of sympathetic nervous activity, is low. This decrease is, however, only found in patients with a long duration of diabetes with clinically severe autonomic neuropathy. This apparent insensitivity...... of plasma catecholamine measurements is not due to changes in the clearance of catecholamines in diabetic autonomic neuropathy. The physiological responses to infused adrenaline and to noradrenaline are enhanced, for noradrenaline mainly cardiovascular responses. Adrenoceptors (alpha and beta adrenoceptors......) are not altered in circulating blood cells in diabetic autonomic neuropathy. Thus, a generalized up-regulation of adrenoceptors does not occur in diabetic autonomic neuropathy....

Animal models

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Gøtze, Jens Peter; Krentz, Andrew

2014-01-01

In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

Psychoacoustic and cognitive aspects of auditory roughness: definitions, models, and applications

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Vassilakis, Pantelis N.; Kendall, Roger A.

2010-02-01

The term "auditory roughness" was first introduced in the 19th century to describe the buzzing, rattling auditory sensation accompanying narrow harmonic intervals (i.e. two tones with frequency difference in the range of ~15-150Hz, presented simultaneously). A broader definition and an overview of the psychoacoustic correlates of the auditory roughness sensation, also referred to as sensory dissonance, is followed by an examination of efforts to quantify it over the past one hundred and fifty years and leads to the introduction of a new roughness calculation model and an application that automates spectral and roughness analysis of sound signals. Implementation of spectral and roughness analysis is briefly discussed in the context of two pilot perceptual experiments, designed to assess the relationship among cultural background, music performance practice, and aesthetic attitudes towards the auditory roughness sensation.

Auditory-Motor Interactions in Pediatric Motor Speech Disorders: Neurocomputational Modeling of Disordered Development

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Terband, H.; Maassen, B.; Guenther, F.H.; Brumberg, J.

2014-01-01

Background/Purpose Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. Method In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Results Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. Conclusions These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. PMID:24491630

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy.

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Callaghan, Brian C; Gao, LeiLi; Li, Yufeng; Zhou, Xianghai; Reynolds, Evan; Banerjee, Mousumi; Pop-Busui, Rodica; Feldman, Eva L; Ji, Linong

2018-04-01

To determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large population-based cohort from Pinggu, China. A cross-sectional, randomly selected, population-based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Tree-based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components. The mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy. Similar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.

Gasoline sniffing multifocal neuropathy.

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Burns, T M; Shneker, B F; Juel, V C

2001-11-01

The polyneuropathy caused by chronic gasoline inhalation is reported to be a gradually progressive, symmetric, sensorimotor polyneuropathy. We report unleaded gasoline sniffing by a female 14 years of age that precipitated peripheral neuropathy. In contrast with the previously reported presentation of peripheral neuropathy in gasoline inhalation, our patient developed multiple mononeuropathies superimposed on a background of sensorimotor polyneuropathy. The patient illustrates that gasoline sniffing neuropathy may present with acute multiple mononeuropathies resembling mononeuritis multiplex, possibly related to increased peripheral nerve susceptibility to pressure in the setting of neurotoxic components of gasoline. The presence of tetraethyl lead, which is no longer present in modern gasoline mixtures, is apparently not a necessary factor in the development of gasoline sniffer's neuropathy.

Auditory preferences of young children with and without hearing loss for meaningful auditory-visual compound stimuli.

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Zupan, Barbra; Sussman, Joan E

2009-01-01

Experiment 1 examined modality preferences in children and adults with normal hearing to combined auditory-visual stimuli. Experiment 2 compared modality preferences in children using cochlear implants participating in an auditory emphasized therapy approach to the children with normal hearing from Experiment 1. A second objective in both experiments was to evaluate the role of familiarity in these preferences. Participants were exposed to randomized blocks of photographs and sounds of ten familiar and ten unfamiliar animals in auditory-only, visual-only and auditory-visual trials. Results indicated an overall auditory preference in children, regardless of hearing status, and a visual preference in adults. Familiarity only affected modality preferences in adults who showed a strong visual preference to unfamiliar stimuli only. The similar degree of auditory responses in children with hearing loss to those from children with normal hearing is an original finding and lends support to an auditory emphasis for habilitation. Readers will be able to (1) Describe the pattern of modality preferences reported in young children without hearing loss; (2) Recognize that differences in communication mode may affect modality preferences in young children with hearing loss; and (3) Understand the role of familiarity in modality preferences in children with and without hearing loss.

Learning-dependent plasticity in human auditory cortex during appetitive operant conditioning.

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Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

2013-11-01

Animal experiments provide evidence that learning to associate an auditory stimulus with a reward causes representational changes in auditory cortex. However, most studies did not investigate the temporal formation of learning-dependent plasticity during the task but rather compared auditory cortex receptive fields before and after conditioning. We here present a functional magnetic resonance imaging study on learning-related plasticity in the human auditory cortex during operant appetitive conditioning. Participants had to learn to associate a specific category of frequency-modulated tones with a reward. Only participants who learned this association developed learning-dependent plasticity in left auditory cortex over the course of the experiment. No differential responses to reward predicting and nonreward predicting tones were found in auditory cortex in nonlearners. In addition, learners showed similar learning-induced differential responses to reward-predicting and nonreward-predicting tones in the ventral tegmental area and the nucleus accumbens, two core regions of the dopaminergic neurotransmitter system. This may indicate a dopaminergic influence on the formation of learning-dependent plasticity in auditory cortex, as it has been suggested by previous animal studies. Copyright © 2012 Wiley Periodicals, Inc.

Auditory Deprivation and Early Conductive Hearing Loss from Otitis Media.

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Gunnarson, Adele D.; And Others

1990-01-01

This article reviews auditory deprivation effects on anatomy, physiology, and behavior in animals and discusses the sequelae of otitis media with effusion (OME) in children. Focused on are central auditory processing disorders associated with early fluctuating hearing loss from OME. (DB)

EFEKTIVITAS MODEL PEMBELAJARAN AUDITORY INTELLECTUALLY REPETITION (AIR TERHADAP PEMAHAMAN SISWA PADA KONSEP ENERGI DALAM

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S. Linuwih

2014-07-01

Full Text Available Telah dilakukan pembelajaran fisika melalui penerapan model pembelajaran Auditory Intellectually Repetition (AIR pada pokok bahasan konsep energi dalam. Tujuan penelitian ini untuk mengetahui peningkatan pemahaman konsep siswa dan efektivitas model pembelajaran Auditory Intellectually Repetition (AIR terhadap pemahaman siswa pada konsep energi dalam. Penelitian ini menggunakan metode penelitian eksperimen kependidikan (educational experiment research, dengan rancangan pre test-post test control group design. Subjek penelitian adalah dua kelompok belajar yang terdiri atas 32 siswa (eksperimen dan 32 siswa (kontrol kelas XI IPA di SMA N 2 Ungaran tahun ajaran 2013/2014. Data dianalisis menggunakan uji gain dan uji t. Hasil penelitian menunjukkan adanya peningkatan pemahaman konsep siswa dan hasil belajar kognitif siswa. Berdasarkan hasil analisis dapat disimpulkan bahwa penerapan model pembelajaran Auditory Intellectually Repetition (AIR dalam pembelajaran fisika SMA efektif untuk meningkatkan pemahaman konsep siswa.ABSTRACTThe physics learning on concept of the internal energy was carried out through application of Auditory Intellectually Repetition (AIR learning model. This study aimed to determining the improvement of students’ concept understanding and the effectiveness of Auditory Intellectually Repetition (AIR learning model on students’ understanding of the internal energy concept. The research used educational experiment research with pre test-post test control group design. The subject of research consisted of 32 students in eksperimental group and 32 students in control group of XI IPA SMA N 2 Ungaran, academic year 2013/2014. The data were analyzed by using gain test and t test. The result showed that there was an increase of students’ concept understanding and the outcome of students’ cognitive learning. Based on the result, it can be concluded that the application of Auditory Intellectually Repetition (AIR learning model in

Selective increase of auditory cortico-striatal coherence during auditory-cued Go/NoGo discrimination learning.

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Andreas L. Schulz

2016-01-01

Full Text Available Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcementmodels, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functionalcoupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed.

HIV Associated Sensory Neuropathy.

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G, Amruth; S, Praveen-Kumar; B, Nataraju; Bs, Nagaraja

2014-07-01

In the era of highly active antiretroviral therapy, sensory neuropathies have increased in prevalence. We have documented the frequency and profile of the two most common forms of sensory neuropathies associated with Human Immunodeficiency Virus (HIV) infection and looked into clinicoelectrophysiological correlates to differentiate the two entities. The study population comprised of all consecutive patients detected to be HIV positive and attending the Neurology outpatient department (from March 2011 to March 2012) who were aged ≥ 18 years and were able to give informed consent. The data were collected from the patient records (including CD4 counts and treatment details) and questionnaire based interview with each patient. All patients underwent detailed clinical examination and nerve conduction studies (NCSs). Among the total study population of 50 patients, there were 31 men and 19 women. Thirty two patients were in age range of 21 - 40 years and rest were above 40 years. 25 were on antiretroviral therapy (18 on regimen containing zidovudine; seven on regimen containing stavudine). The mean duration of antiretroviral therapy was 16.6±8.4 months. Low CD4 counts ( 40 years. Subclinical neuropathy was common in those on antiretroviral therapy. Axonal neuropathy was the commonest pattern noted in patients who were receiving antiretroviral therapy and demyelinating neuropathy in patients not on antiretroviral therapy. Surprisingly no significant correlation was found between low CD4 counts and symptomatic neuropathy.

Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

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Suat Kamışlı

2013-03-01

Full Text Available Objective: Diabetic neuropathy (DN is a common complication in Diabetes Mellitus. The streptozotocin-induced diabetic rodent is the most commonly used animal model of diabetes and increased sodium channel expression and activity were revealed in this model. At this study, we evaluated the effect of three different nafimidone derivatives which have possible anticonvulsant activity on disorders of thermal pain sensation in diabetic mice. Study Design: Randomized animal experiment. Material and Methods: Mice were divided randomly into five groups (5 mice per group: Control, Diabetes, Dibetes+C1, Diabetes+C2, Diabetes+C3. We used hot and cold plate, and tail-immersion tests for assessment of thermal nociceptive responses. Results: Compared with the control group, the hot-plate response time and the number of paw liftings on cold plate as important indicators of loss of sensation increased, but no significant difference (p>0.05 was found in tail-immersion response time test in diabetes group. C3 compound moved it back to control group levels in the all of three tests. C1 and C2 compounds were effective only in cold-plate test. Conclusion: Nafimidone derivatives may be effective in the cases where epilepsy and diabetes occur together since it has shown efficacy against “loss of sensation” which evolves in diabetic neuropathy over time as well as its antiepileptic effect.

Burn-related peripheral neuropathy: A systematic review.

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Tu, Yiji; Lineaweaver, William C; Zheng, Xianyou; Chen, Zenggan; Mullins, Fred; Zhang, Feng

2017-06-01

Peripheral neuropathy is the most frequent disabling neuromuscular complication of burns. However, the insidious and progressive onset of burn neuropathy makes it often undiagnosed or overlooked. In our study, we reviewed the current studies on the burn-related peripheral neuropathy to summarize the morbidity, mechanism, detecting method and management of peripheral neuropathy in burn patients. Of the 1533 burn patients included in our study, 98 cases (6.39%) were presented with peripheral neuropathy. Thermal and electrical burns were the most common etiologies. Surgical procedures, especially nerve decompression, showed good effect on functional recovery of both acute and delayed peripheral neuropathy in burn patients. It is noteworthy that, for early detection and prevention of peripheral neuropathy, electrodiagnostic examinations should be performed on burn patients independent of symptoms. Still, the underlying mechanisms of burn-related peripheral neuropathy remain to be clarified. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Oligodendrocyte death, neuroinflammation, and the effects of minocycline in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

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Mehrabian, Zara; Guo, Yan; Weinreich, Daniel; Bernstein, Steven L

2017-01-01

Optic nerve (ON) damage following nonarteritic anterior ischemic optic neuropathy (NAION) and its models is associated with neurodegenerative inflammation. Minocycline is a tetracycline derivative antibiotic believed to exert a neuroprotective effect by selective alteration and activation of the neuroinflammatory response. We evaluated minocycline's post-induction ability to modify early and late post-ischemic inflammatory responses and its retinal ganglion cell (RGC)-neuroprotective ability. We used the rodent NAION (rNAION) model in male Sprague-Dawley rats. Animals received either vehicle or minocycline (33 mg/kg) daily intraperitoneally for 28 days. Early (3 days) ON-cytokine responses were evaluated, and oligodendrocyte death was temporally evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis. Cellular inflammation was evaluated with immunohistochemistry, and RGC preservation was compared with stereology of Brn3a-positive cells in flat mounted retinas. Post-rNAION, oligodendrocytes exhibit a delayed pattern of apoptosis extending over a month, with extrinsic monocyte infiltration occurring only in the primary rNAION lesion and progressive distal microglial activation. Post-induction minocycline failed to improve retinal ganglion cell survival compared with the vehicle treated (893.14 vs. 920.72; p>0.9). Cytokine analysis of the rNAION lesion 3 days post-induction revealed that minocycline exert general inflammatory suppression without selective upregulation of cytokines associated with the proposed alternative or neuroprotective M2 inflammatory pathway. The pattern of cytokine release, extended temporal window of oligodendrocyte death, and progressive microglial activation suggests that selective neuroimmunomodulation, rather than general inflammatory suppression, may be required for effective repair strategies in ischemic optic neuropathies.

Witnessing traumatic events and post-traumatic stress disorder: Insights from an animal model.

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Patki, Gaurav; Salvi, Ankita; Liu, Hesong; Salim, Samina

2015-07-23

It is becoming increasingly recognized that post-traumatic stress disorder (PTSD) can be acquired vicariously from witnessing traumatic events. Recently, we published an animal model called the "Trauma witness model" (TWM) which mimics PTSD-like symptoms in rats from witnessing daily traumatic events (social defeat of cage mate) [14]. Our TWM does not result in any physical injury. This is a major procedural advantage over the typical intruder paradigm in which it is difficult to delineate the inflammatory response of tissue injury and the response elicited from emotional distress. Using TWM paradigm, we examined behavioral and cognitive effects in rats [14] however, the long-term persistence of PTSD-like symptoms or a time-course of these events (anxiety and depression-like behaviors and cognitive deficits) and the contribution of olfactory and auditory stress vs visual reinforcement were not examined. This study demonstrates that some of the features of PTSD-like symptoms in rats are reversible after a significant time lapse of the witnessing of traumatic events. We also have established that witnessing is critical to the PTSD-like phenotype and cannot be acquired solely due to auditory or olfactory stresses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bilateral Alternating Auditory Stimulations Facilitate Fear Extinction and Retrieval

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Boukezzi, Sarah; Silva, Catarina; Nazarian, Bruno; Rousseau, Pierre-François; Guedj, Eric; Valenzuela-Moguillansky, Camila; Khalfa, Stéphanie

2017-01-01

Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD). Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS) during eye movement desensitization and reprocessing (EMDR) therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to ...

Diminished auditory sensory gating during active auditory verbal hallucinations.

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Thoma, Robert J; Meier, Andrew; Houck, Jon; Clark, Vincent P; Lewine, Jeffrey D; Turner, Jessica; Calhoun, Vince; Stephen, Julia

2017-10-01

Auditory sensory gating, assessed in a paired-click paradigm, indicates the extent to which incoming stimuli are filtered, or "gated", in auditory cortex. Gating is typically computed as the ratio of the peak amplitude of the event related potential (ERP) to a second click (S2) divided by the peak amplitude of the ERP to a first click (S1). Higher gating ratios are purportedly indicative of incomplete suppression of S2 and considered to represent sensory processing dysfunction. In schizophrenia, hallucination severity is positively correlated with gating ratios, and it was hypothesized that a failure of sensory control processes early in auditory sensation (gating) may represent a larger system failure within the auditory data stream; resulting in auditory verbal hallucinations (AVH). EEG data were collected while patients (N=12) with treatment-resistant AVH pressed a button to indicate the beginning (AVH-on) and end (AVH-off) of each AVH during a paired click protocol. For each participant, separate gating ratios were computed for the P50, N100, and P200 components for each of the AVH-off and AVH-on states. AVH trait severity was assessed using the Psychotic Symptoms Rating Scales AVH Total score (PSYRATS). The results of a mixed model ANOVA revealed an overall effect for AVH state, such that gating ratios were significantly higher during the AVH-on state than during AVH-off for all three components. PSYRATS score was significantly and negatively correlated with N100 gating ratio only in the AVH-off state. These findings link onset of AVH with a failure of an empirically-defined auditory inhibition system, auditory sensory gating, and pave the way for a sensory gating model of AVH. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral neuropathy associated with mitochondrial disease in children.

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Menezes, Manoj P; Ouvrier, Robert A

2012-05-01

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

A neural network model of normal and abnormal auditory information processing.

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Du, X; Jansen, B H

2011-08-01

The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. Copyright © 2011 Elsevier Ltd. All rights reserved.

Treatment options in painful diabetic neuropathy.

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Nash, T P

1999-01-01

Diabetic neuropathy is common in patients with diabetes mellitus, and 7.5% of diabetics experience pain from diabetic neuropathy. Complications of diabetes mellitus are more common where control of the disease is not optimal. By improving the control of the disease, both the neuropathy and the pain it can produce may be improved. The pain of diabetic neuropathy can frequently be controlled using analgesics, antidepressants, anticonvulsants, topical capsaicin, and neuromodulation, either alone or in any combination.

Animal Model of Sensorineural Hearing Loss Associated with Lassa Virus Infection.

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Yun, Nadezhda E; Ronca, Shannon; Tamura, Atsushi; Koma, Takaaki; Seregin, Alexey V; Dineley, Kelly T; Miller, Milagros; Cook, Rebecca; Shimizu, Naoki; Walker, Aida G; Smith, Jeanon N; Fair, Joseph N; Wauquier, Nadia; Bockarie, Bayon; Khan, Sheik Humarr; Makishima, Tomoko; Paessler, Slobodan

2015-12-30

Approximately one-third of Lassa virus (LASV)-infected patients develop sensorineural hearing loss (SNHL) in the late stages of acute disease or in early convalescence. With 500,000 annual cases of Lassa fever (LF), LASV is a major cause of hearing loss in regions of West Africa where LF is endemic. To date, no animal models exist that depict the human pathology of LF with associated hearing loss. Here, we aimed to develop an animal model to study LASV-induced hearing loss using human isolates from a 2012 Sierra Leone outbreak. We have recently established a murine model for LF that closely mimics many features of human disease. In this model, LASV isolated from a lethal human case was highly virulent, while the virus isolated from a nonlethal case elicited mostly mild disease with moderate mortality. More importantly, both viruses were able to induce SNHL in surviving animals. However, utilization of the nonlethal, human LASV isolate allowed us to consistently produce large numbers of survivors with hearing loss. Surviving mice developed permanent hearing loss associated with mild damage to the cochlear hair cells and, strikingly, significant degeneration of the spiral ganglion cells of the auditory nerve. Therefore, the pathological changes in the inner ear of the mice with SNHL supported the phenotypic loss of hearing and provided further insights into the mechanistic cause of LF-associated hearing loss. Sensorineural hearing loss is a major complication for LF survivors. The development of a small-animal model of LASV infection that replicates hearing loss and the clinical and pathological features of LF will significantly increase knowledge of pathogenesis and vaccine studies. In addition, such a model will permit detailed characterization of the hearing loss mechanism and allow for the development of appropriate diagnostic approaches and medical care for LF patients with hearing impairment. Copyright © 2016, American Society for Microbiology. All Rights

Auditory-motor interactions in pediatric motor speech disorders: neurocomputational modeling of disordered development.

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Terband, H; Maassen, B; Guenther, F H; Brumberg, J

2014-01-01

Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of auditory evoked potentials for intra-operative awareness in anesthesia: a consciousness-based conceptual model.

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Dong, Xuebao; Suo, Puxia; Yuan, Xin; Yao, Xuefeng

2015-01-01

Auditory evoked potentials (AEPs) have been used as a measure of the depth of anesthesia during the intra-operative process. AEPs are classically divided, on the basis of their latency, into first, fast, middle, slow, and late components. The use of auditory evoked potential has been advocated for the assessment of Intra-operative awareness (IOA), but has not been considered seriously enough to universalize it. It is because we have not explored enough the impact of auditory perception and auditory processing on the IOA phenomena as well as on the subsequent psychological impact of IOA on the patient. More importantly, we have seldom tried to look at the phenomena of IOP from the perspective of consciousness itself. This perspective is especially important because many of IOA phenomena exist in the subconscious domain than they do in the conscious domain of explicit recall. Two important forms of these subconscious manifestations of IOA are the implicit recall phenomena and post-operative dreams related to the operation. Here, we present an integrated auditory consciousness-based model of IOA. We start with a brief description of auditory awareness and the factors affecting it. Further, we proceed to the evaluation of conscious and subconscious information processing by auditory modality and how they interact during and after intra-operative period. Further, we show that both conscious and subconscious auditory processing affect the IOA experience and both have serious psychological implications on the patient subsequently. These effects could be prevented by using auditory evoked potential during monitoring of anesthesia, especially the mid-latency auditory evoked potentials (MLAERs). To conclude our model with present hypothesis, we propose that the use of auditory evoked potential should be universal with general anesthesia use in order to prevent the occurrences of distressing outcomes resulting from both conscious and subconscious auditory processing during

Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

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Abdel-Wahhab, Khaled G; Daoud, Eitedal M; El Gendy, Aliaa; Mourad, Hagar H; Mannaa, Fathia A; Saber, Maha M

2018-03-12

Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine

Auditory orientation in crickets: Pattern recognition controls reactive steering

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Poulet, James F. A.; Hedwig, Berthold

2005-10-01

Many groups of insects are specialists in exploiting sensory cues to locate food resources or conspecifics. To achieve orientation, bees and ants analyze the polarization pattern of the sky, male moths orient along the females' odor plume, and cicadas, grasshoppers, and crickets use acoustic signals to locate singing conspecifics. In comparison with olfactory and visual orientation, where learning is involved, auditory processing underlying orientation in insects appears to be more hardwired and genetically determined. In each of these examples, however, orientation requires a recognition process identifying the crucial sensory pattern to interact with a localization process directing the animal's locomotor activity. Here, we characterize this interaction. Using a sensitive trackball system, we show that, during cricket auditory behavior, the recognition process that is tuned toward the species-specific song pattern controls the amplitude of auditory evoked steering responses. Females perform small reactive steering movements toward any sound patterns. Hearing the male's calling song increases the gain of auditory steering within 2-5 s, and the animals even steer toward nonattractive sound patterns inserted into the speciesspecific pattern. This gain control mechanism in the auditory-to-motor pathway allows crickets to pursue species-specific sound patterns temporarily corrupted by environmental factors and may reflect the organization of recognition and localization networks in insects. localization | phonotaxis

Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

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Ayumu Matsuoka

Full Text Available Bevacizumab (BEV, a humanized anti-vascular endothelial growth factor (VEGF monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83 were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095; at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016. At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017. In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012.The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast

Modeling Auditory-Haptic Interface Cues from an Analog Multi-line Telephone

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Begault, Durand R.; Anderson, Mark R.; Bittner, Rachael M.

2012-01-01

The Western Electric Company produced a multi-line telephone during the 1940s-1970s using a six-button interface design that provided robust tactile, haptic and auditory cues regarding the "state" of the communication system. This multi-line telephone was used as a model for a trade study comparison of two interfaces: a touchscreen interface (iPad)) versus a pressure-sensitive strain gauge button interface (Phidget USB interface controllers). The experiment and its results are detailed in the authors' AES 133rd convention paper " Multimodal Information Management: Evaluation of Auditory and Haptic Cues for NextGen Communication Dispays". This Engineering Brief describes how the interface logic, visual indications, and auditory cues of the original telephone were synthesized using MAX/MSP, including the logic for line selection, line hold, and priority line activation.

Auditory Sketches: Very Sparse Representations of Sounds Are Still Recognizable.

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Vincent Isnard

Full Text Available Sounds in our environment like voices, animal calls or musical instruments are easily recognized by human listeners. Understanding the key features underlying this robust sound recognition is an important question in auditory science. Here, we studied the recognition by human listeners of new classes of sounds: acoustic and auditory sketches, sounds that are severely impoverished but still recognizable. Starting from a time-frequency representation, a sketch is obtained by keeping only sparse elements of the original signal, here, by means of a simple peak-picking algorithm. Two time-frequency representations were compared: a biologically grounded one, the auditory spectrogram, which simulates peripheral auditory filtering, and a simple acoustic spectrogram, based on a Fourier transform. Three degrees of sparsity were also investigated. Listeners were asked to recognize the category to which a sketch sound belongs: singing voices, bird calls, musical instruments, and vehicle engine noises. Results showed that, with the exception of voice sounds, very sparse representations of sounds (10 features, or energy peaks, per second could be recognized above chance. No clear differences could be observed between the acoustic and the auditory sketches. For the voice sounds, however, a completely different pattern of results emerged, with at-chance or even below-chance recognition performances, suggesting that the important features of the voice, whatever they are, were removed by the sketch process. Overall, these perceptual results were well correlated with a model of auditory distances, based on spectro-temporal excitation patterns (STEPs. This study confirms the potential of these new classes of sounds, acoustic and auditory sketches, to study sound recognition.

Rapid-rate transcranial magnetic stimulation of animal auditory cortex impairs short-term but not long-term memory formation.

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Wang, Hong; Wang, Xu; Wetzel, Wolfram; Scheich, Henning

2006-04-01

Bilateral rapid-rate transcranial magnetic stimulation (rTMS) of gerbil auditory cortex with a miniature coil device was used to study short-term and long-term effects on discrimination learning of frequency-modulated tones. We found previously that directional discrimination of frequency modulation (rising vs. falling) relies on auditory cortex processing and that formation of its memory depends on local protein synthesis. Here we show that, during training over 5 days, certain rTMS regimes contingent on training had differential effects on the time course of learning. When rTMS was applied several times per day, i.e. four blocks of 5 min rTMS each followed 5 min later by a 3-min training block and 15-min intervals between these blocks (experiment A), animals reached a high discrimination performance more slowly over 5 days than did controls. When rTMS preceded only the first two of four training blocks (experiment B), or when prolonged rTMS (20 min) preceded only the first block, or when blocks of experiment A had longer intervals (experiments C and D), no significant day-to-day effects were found. However, in experiment A, and to some extent in experiment B, rTMS reduced the within-session discrimination performance. Nevertheless the animals learned, as demonstrated by a higher performance the next day. Thus, our results indicate that rTMS treatments accumulate over a day but not strongly over successive days. We suggest that rTMS of sensory cortex, as used in our study, affects short-term memory but not long-term memory formation.

The effect of Ginkgo extract EGb761 in cisplatin-induced peripheral neuropathy in mice

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Oeztuerk, Guerkan; Anlar, Oemer; Erdogan, Ender; Koesem, Mustafa; Oezbek, Hanefi; Tuerker, Aybars

2004-01-01

Neuroprotective effect of Ginkgo biloba extract EGb761 in cisplatin (cis-diamminedi-chloroplatinum, or CDDP)-induced peripheral neuropathy was investigated. Swiss albino mice were treated with CDDP, 2 mg/kg ip twice a week for nine times. One group of the animals also received EGb761 in the drinking water at an estimated dosage of 100 mg/kg per day. Two other groups received vehicle (control) or EGb761 only. Development of neuropathy was evaluated with changes in sensory nerve conduction velocity (NCV). Following the treatments, dorsal root ganglia (DRGs) were microscopically examined and some were cultured for 3 days. EGb761 proved effective in preventing the reduction in NCV (P < 0.0001) caused by CDDP. CDDP caused a decrease in the number of migrating cells (P < 0.01) and in the length of outgrowing axons (P < 0.01) while EGb761 treatment prevented the latter. CDDP led to smaller nuclear and somatic sizes in neurons (P < 0.01), while with EGb761 co-administration, both were close to control values. Animals having EGb761 only had similar results with controls. In conclusion, EGb761 was found to be effective in preventing some functional and morphological deteriorations in CDDP-induced peripheral neuropathy

Word Recognition in Auditory Cortex

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DeWitt, Iain D. J.

2013-01-01

Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

Stereotactically-guided Ablation of the Rat Auditory Cortex, and Localization of the Lesion in the Brain.

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Lamas, Verónica; Estévez, Sheila; Pernía, Marianni; Plaza, Ignacio; Merchán, Miguel A

2017-10-11

The rat auditory cortex (AC) is becoming popular among auditory neuroscience investigators who are interested in experience-dependence plasticity, auditory perceptual processes, and cortical control of sound processing in the subcortical auditory nuclei. To address new challenges, a procedure to accurately locate and surgically expose the auditory cortex would expedite this research effort. Stereotactic neurosurgery is routinely used in pre-clinical research in animal models to engraft a needle or electrode at a pre-defined location within the auditory cortex. In the following protocol, we use stereotactic methods in a novel way. We identify four coordinate points over the surface of the temporal bone of the rat to define a window that, once opened, accurately exposes both the primary (A1) and secondary (Dorsal and Ventral) cortices of the AC. Using this method, we then perform a surgical ablation of the AC. After such a manipulation is performed, it is necessary to assess the localization, size, and extension of the lesions made in the cortex. Thus, we also describe a method to easily locate the AC ablation postmortem using a coordinate map constructed by transferring the cytoarchitectural limits of the AC to the surface of the brain.The combination of the stereotactically-guided location and ablation of the AC with the localization of the injured area in a coordinate map postmortem facilitates the validation of information obtained from the animal, and leads to a better analysis and comprehension of the data.

Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

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Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

2015-01-01

Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

Diagnostic approach to peripheral neuropathy

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Misra Usha

2008-01-01

Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

Effect of Urtica dioica on memory dysfunction and hypoalgesia in an experimental model of diabetic neuropathy.

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Patel, Sita Sharan; Udayabanu, M

2013-09-27

Diabetic neuropathy is considered as a disease of the peripheral nervous system, but recent evidences suggest the involvement of central nervous system as well. In this study we evaluated the effect of Urtica dioica (UD) extract against memory dysfunction and hypoalgesia on a mouse model of streptozotocin (STZ) induced diabetic neuropathy. STZ (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes, followed by treatment with the UD extract (50 mg/kg, oral) and rosiglitazone (5 mg/kg, oral) for 8 weeks. Cognitive functions were evaluated using Morris water maze and passive avoidance step through task. Pain thresholds were measured using thermal, mechanical and chemical induced hyperalgesia. We observed that chronic diabetes resulted in a decline in circulating insulin level, elevated blood glucose, reduced body weight, increased water intake, cognitive impairment and hypoalgesia. UD significantly reduced the blood glucose and polydypsia, as well as improved the body weight, insulin level, cognition and insensate neuropathy. In conclusion, UD showed results comparable to rosiglitazone in reversing the long standing diabetes induced complications such as central and peripheral neuronal dysfunction. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Hyperacute peripheral neuropathy is a predictor of oxaliplatin-induced persistent peripheral neuropathy.

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Tanishima, Hiroyuki; Tominaga, Toshiji; Kimura, Masamichi; Maeda, Tsunehiro; Shirai, Yasutsugu; Horiuchi, Tetsuya

2017-05-01

Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN). Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation. The average total dose of oxaliplatin was 625.8 mg/m 2 , and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068). HAPN was found to be a predictor of oxaliplatin-induced PPN.

From sounds to words: a neurocomputational model of adaptation, inhibition and memory processes in auditory change detection.

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Garagnani, Max; Pulvermüller, Friedemann

2011-01-01

Most animals detect sudden changes in trains of repeated stimuli but only some can learn a wide range of sensory patterns and recognise them later, a skill crucial for the evolutionary success of higher mammals. Here we use a neural model mimicking the cortical anatomy of sensory and motor areas and their connections to explain brain activity indexing auditory change and memory access. Our simulations indicate that while neuronal adaptation and local inhibition of cortical activity can explain aspects of change detection as observed when a repeated unfamiliar sound changes in frequency, the brain dynamics elicited by auditory stimulation with well-known patterns (such as meaningful words) cannot be accounted for on the basis of adaptation and inhibition alone. Specifically, we show that the stronger brain responses observed to familiar stimuli in passive oddball tasks are best explained in terms of activation of memory circuits that emerged in the cortex during the learning of these stimuli. Such memory circuits, and the activation enhancement they entail, are absent for unfamiliar stimuli. The model illustrates how basic neurobiological mechanisms, including neuronal adaptation, lateral inhibition, and Hebbian learning, underlie neuronal assembly formation and dynamics, and differentially contribute to the brain's major change detection response, the mismatch negativity. Copyright © 2010 Elsevier Inc. All rights reserved.

Diabetic peripheral neuropathy, is it an autoimmune disease?

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Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

2015-11-01

Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Extensive cochleotopic mapping of human auditory cortical fields obtained with phase-encoding FMRI.

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Ella Striem-Amit

Full Text Available The primary sensory cortices are characterized by a topographical mapping of basic sensory features which is considered to deteriorate in higher-order areas in favor of complex sensory features. Recently, however, retinotopic maps were also discovered in the higher-order visual, parietal and prefrontal cortices. The discovery of these maps enabled the distinction between visual regions, clarified their function and hierarchical processing. Could such extension of topographical mapping to high-order processing regions apply to the auditory modality as well? This question has been studied previously in animal models but only sporadically in humans, whose anatomical and functional organization may differ from that of animals (e.g. unique verbal functions and Heschl's gyrus curvature. Here we applied fMRI spectral analysis to investigate the cochleotopic organization of the human cerebral cortex. We found multiple mirror-symmetric novel cochleotopic maps covering most of the core and high-order human auditory cortex, including regions considered non-cochleotopic, stretching all the way to the superior temporal sulcus. These maps suggest that topographical mapping persists well beyond the auditory core and belt, and that the mirror-symmetry of topographical preferences may be a fundamental principle across sensory modalities.

Great Expectations: Is there Evidence for Predictive Coding in Auditory Cortex?

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Heilbron, Micha; Chait, Maria

2017-08-04

Predictive coding is possibly one of the most influential, comprehensive, and controversial theories of neural function. While proponents praise its explanatory potential, critics object that key tenets of the theory are untested or even untestable. The present article critically examines existing evidence for predictive coding in the auditory modality. Specifically, we identify five key assumptions of the theory and evaluate each in the light of animal, human and modeling studies of auditory pattern processing. For the first two assumptions - that neural responses are shaped by expectations and that these expectations are hierarchically organized - animal and human studies provide compelling evidence. The anticipatory, predictive nature of these expectations also enjoys empirical support, especially from studies on unexpected stimulus omission. However, for the existence of separate error and prediction neurons, a key assumption of the theory, evidence is lacking. More work exists on the proposed oscillatory signatures of predictive coding, and on the relation between attention and precision. However, results on these latter two assumptions are mixed or contradictory. Looking to the future, more collaboration between human and animal studies, aided by model-based analyses will be needed to test specific assumptions and implementations of predictive coding - and, as such, help determine whether this popular grand theory can fulfill its expectations. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Current concepts in the diagnosis, pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy.

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Miller, N R; Arnold, A C

2015-01-01

Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15-19% risk of developing a similar event in the opposite eye over the subsequent 5 years.

Modelling auditory attention: Insights from the Theory of Visual Attention (TVA)

DEFF Research Database (Denmark)

Roberts, K. L.; Andersen, Tobias; Kyllingsbæk, Søren

modelled using a log-logistic function than an exponential function. A more challenging difference is that in the partial report task, there is more target-distractor confusion for auditory than visual stimuli. This failure of object-formation (prior to attentional object-selection) is not yet effectively......We report initial progress towards creating an auditory analogue of a mathematical model of visual attention: the ‘Theory of Visual Attention’ (TVA; Bundesen, 1990). TVA is one of the best established models of visual attention. It assumes that visual stimuli are initially processed in parallel......, and that there is a ‘race’ for selection and representation in visual short term memory (VSTM). In the basic TVA task, participants view a brief display of letters and are asked to report either all of the letters (whole report) or a subset of the letters (e.g., the red letters; partial report). Fitting the model...

Genetically determined optic neuropathies

DEFF Research Database (Denmark)

Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

2010-01-01

The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

Three-dimensional sound localisation with a lizard peripheral auditory model

DEFF Research Database (Denmark)

Kjær Schmidt, Michael; Shaikh, Danish

the networks learned a transfer function that translated the three-dimensional non-linear mapping into estimated azimuth and elevation values for the acoustic target. The neural network with two hidden layers as expected performed better than that with only one hidden layer. Our approach assumes that for any...... location of an acoustic target in three dimensions. Our approach utilises a model of the peripheral auditory system of lizards [Christensen-Dalsgaard and Manley 2005] coupled with a multi-layer perceptron neural network. The peripheral auditory model’s response to sound input encodes sound direction...... information in a single plane which by itself is insufficient to localise the acoustic target in three dimensions. A multi-layer perceptron neural network is used to combine two independent responses of the model, corresponding to two rotational movements, into an estimate of the sound direction in terms...

Auditory-motor learning influences auditory memory for music.

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Brown, Rachel M; Palmer, Caroline

2012-05-01

In two experiments, we investigated how auditory-motor learning influences performers' memory for music. Skilled pianists learned novel melodies in four conditions: auditory only (listening), motor only (performing without sound), strongly coupled auditory-motor (normal performance), and weakly coupled auditory-motor (performing along with auditory recordings). Pianists' recognition of the learned melodies was better following auditory-only or auditory-motor (weakly coupled and strongly coupled) learning than following motor-only learning, and better following strongly coupled auditory-motor learning than following auditory-only learning. Auditory and motor imagery abilities modulated the learning effects: Pianists with high auditory imagery scores had better recognition following motor-only learning, suggesting that auditory imagery compensated for missing auditory feedback at the learning stage. Experiment 2 replicated the findings of Experiment 1 with melodies that contained greater variation in acoustic features. Melodies that were slower and less variable in tempo and intensity were remembered better following weakly coupled auditory-motor learning. These findings suggest that motor learning can aid performers' auditory recognition of music beyond auditory learning alone, and that motor learning is influenced by individual abilities in mental imagery and by variation in acoustic features.

Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

International Nuclear Information System (INIS)

Johnstone, Peter A. S.; DeLuca, Anne Marie; Bacher, John D.; Hampshire, Victoria A.; Terrill, Richard E.; Anderson, William J.; Kinsella, Timothy J.; Sindelar, William F.

1995-01-01

Purpose: The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Methods and Materials: Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. Results: All animals treated with ≥ 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED 50 ) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Conclusions: Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED 50 determined here is in keeping with data from other animal trials, and from clinical trials in humans

Therapeutic potential of stem cells in auditory hair cell repair

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Ryuji Hata

2009-01-01

Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

An animal model of tinnitus: a decade of development.

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Jastreboff, P J; Sasaki, C T

1994-01-01

Although tinnitus affects approximately 9 million people in the United States, a cure remains elusive and the mechanisms of its origin are speculative. The crucial obstacle in tinnitus research has been the lack of an animal model. Over the last decade we have been creating such a model by combining a variety of methodologies, including a behavioral component, to allow for the detection of tinnitus perception. Initially, 2-deoxyglucose had been used to map changes in the metabolic activity after unilateral destruction of the cochlea. It has been found that the initial decrease of the metabolic rate in the auditory nuclei recovered to preoperative values, which could be attributable to the development of tinnitus. The spontaneous activity of single units recorded from the inferior colliculus before and after salicylate administration revealed an increase of discharges, which might reflect the presence of salicylate-induced tinnitus. Recent data have confirmed, and further elaborated this observation, including the discovery of abnormal, epileptic-like, neuronal activity. Finally, the authors have developed a behavioral model of tinnitus, tested it extensively, and used it to measure tinnitus pitch and loudness. The model is presently used for investigating the hypotheses for the mechanisms of tinnitus.

ANTIOXIDANT STATUS IN DIABETIC NEUROPATHY

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Giriraja Vrushabaiah Kanakapura

2017-09-01

Full Text Available BACKGROUND Diabetic neuropathy, retinopathy and nephropathy are the chronic complications of diabetes mellitus. Neuropathy, retinopathy and nephropathy are microvascular complication of diabetes mellitus. Antioxidant status is reduced in DM-induced retinopathy and nephropathy. Present study is undertaken to evaluate the degree of oxidative stress in diabetic neuropathy patients. The aim of the study is to study on oxidative stress as measured by lipid peroxidation marker, malondialdehyde and antienzyme status in type II DM patients with neuropathy and compared them with a controlled nondiabetic group. MATERIALS AND METHODS The study included 100 subjects from Sapthagiri Medical College, Bangalore, from January 1, 2015, to December 31, 2015, of age group 50 to 70 yrs. out of which 50 patients were non-insulin-dependent DM with neuropathy and rest 50 age and sex matched apparently healthy individuals (control group. Antioxidant status was assessed by measuring superoxide dismutase (SOD, glutathione peroxidase (GPx, glutathione reductase (GR, Catalase and Reduced Glutathione (GSH. RESULTS It showed a significant increase p<0.001 in FBS, PPBS, TC, TG, LDL, VLDL, CAT, MDA, while HDL, GSH, GPX, GR and SOD were found to be decreased significantly (p 0.001. CONCLUSION MDA was significantly elevated in diabetic group, whereas antioxidant enzymes superoxide dismutase, glutathione peroxidase, glutathione reductase and reduced glutathione were significantly decreased, which might be helpful in risk assessment of various complications of DM. The data suggests that alteration in antioxidant status and MDA may help to predict the risk of diabetic neuropathy.

In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory Impairment

Science.gov (United States)

2015-06-01

of JP-8 and a Fischer- Tropsch synthetic jet fuel following subacute inhalation exposure in rats. Toxicol Sci 116(1): 239-248. Gallinat, J...AFRL-RH-WP-TR-2015-0084 IN VITRO STUDIES AND PRELIMINARY MATHEMATICAL MODEL FOR JET FUEL AND NOISE INDUCED AUDITORY IMPAIRMENT...April 2014 – September 2014 4. TITLE AND SUBTITLE In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

The effects of auditory enrichment on gorillas.

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Robbins, Lindsey; Margulis, Susan W

2014-01-01

Several studies have demonstrated that auditory enrichment can reduce stereotypic behaviors in captive animals. The purpose of this study was to determine the relative effectiveness of three different types of auditory enrichment-naturalistic sounds, classical music, and rock music-in reducing stereotypic behavior displayed by Western lowland gorillas (Gorilla gorilla gorilla). Three gorillas (one adult male, two adult females) were observed at the Buffalo Zoo for a total of 24 hr per music trial. A control observation period, during which no sounds were presented, was also included. Each music trial consisted of a total of three weeks with a 1-week control period in between each music type. The results reveal a decrease in stereotypic behaviors from the control period to naturalistic sounds. The naturalistic sounds also affected patterns of several other behaviors including locomotion. In contrast, stereotypy increased in the presence of classical and rock music. These results suggest that auditory enrichment, which is not commonly used in zoos in a systematic way, can be easily utilized by keepers to help decrease stereotypic behavior, but the nature of the stimulus, as well as the differential responses of individual animals, need to be considered. © 2014 Wiley Periodicals, Inc.

Peripheral neuropathy in HIV: prevalence and risk factors

Science.gov (United States)

Evans, Scott R.; Ellis, Ronald J.; Chen, Huichao; Yeh, Tzu-min; Lee, Anthony J.; Schifitto, Giovanni; Wu, Kunling; Bosch, Ronald J.; McArthur, Justin C.; Simpson, David M.; Clifford, David B.

2011-01-01

Objectives To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART. Design AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally. Methods Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations. Results Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/µl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use. Conclusion Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for

What determines auditory distraction? On the roles of local auditory changes and expectation violations.

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Jan P Röer

Full Text Available Both the acoustic variability of a distractor sequence and the degree to which it violates expectations are important determinants of auditory distraction. In four experiments we examined the relative contribution of local auditory changes on the one hand and expectation violations on the other hand in the disruption of serial recall by irrelevant sound. We present evidence for a greater disruption by auditory sequences ending in unexpected steady state distractor repetitions compared to auditory sequences with expected changing state endings even though the former contained fewer local changes. This effect was demonstrated with piano melodies (Experiment 1 and speech distractors (Experiment 2. Furthermore, it was replicated when the expectation violation occurred after the encoding of the target items (Experiment 3, indicating that the items' maintenance in short-term memory was disrupted by attentional capture and not their encoding. This seems to be primarily due to the violation of a model of the specific auditory distractor sequences because the effect vanishes and even reverses when the experiment provides no opportunity to build up a specific neural model about the distractor sequence (Experiment 4. Nevertheless, the violation of abstract long-term knowledge about auditory regularities seems to cause a small and transient capture effect: Disruption decreased markedly over the course of the experiments indicating that participants habituated to the unexpected distractor repetitions across trials. The overall pattern of results adds to the growing literature that the degree to which auditory distractors violate situation-specific expectations is a more important determinant of auditory distraction than the degree to which a distractor sequence contains local auditory changes.

An update on electrophysiological studies in neuropathy

DEFF Research Database (Denmark)

Krarup, Christian

2003-01-01

The review concentrates on the use of clinical neurophysiology in peripheral nerve disorders covered in the present issue. It is pertinent to distinguish different types of involvement of fibers in diabetic neuropathy, including the involvement of small and large fibers, to outline the diagnostic...... criteria of inflammatory neuropathies, and to describe the spectrum of peripheral nerve pathophysiology in inherited neuropathies. Painful neuropathies represent a particular challenge to clinical neurophysiology since it is mainly small fibers, which are difficult to study, that are affected....

Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores

NARCIS (Netherlands)

Meijer, J.W.; Lefrandt, J.D.; Links, T.P.; Smit, J.A.; Stewart, R.E.; van der Hoeven, J.H.; Hoogenberg, K.

OBJECTIVE - To evaluate the discriminative power of the Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores for diagnosing diabetic polyneuropathy (PNP), as well as their relation with cardiovascular autonomic function testing (cAFT) and electro-diagnostic studies

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

Science.gov (United States)

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

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Valentina A Carozzi

Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

Children with Auditory Neuropathy Spectrum Disorder Fitted with Hearing Aids Applying the American Academy of Audiology Pediatric Amplification Guideline: Current Practice and Outcomes.

Science.gov (United States)

Walker, Elizabeth; McCreery, Ryan; Spratford, Meredith; Roush, Patricia

2016-03-01

Up to 15% of children with permanent hearing loss (HL) have auditory neuropathy spectrum disorder (ANSD), which involves normal outer hair cell function and disordered afferent neural activity in the auditory nerve or brainstem. Given the varying presentations of ANSD in children, there is a need for more evidence-based research on appropriate clinical interventions for this population. This study compared the speech production, speech perception, and language outcomes of children with ANSD, who are hard of hearing, to children with similar degrees of mild-to-moderately severe sensorineural hearing loss (SNHL), all of whom were fitted with bilateral hearing aids (HAs) based on the American Academy of Audiology pediatric amplification guidelines. Speech perception and communication outcomes data were gathered in a prospective accelerated longitudinal design, with entry into the study between six mo and seven yr of age. Three sites were involved in participant recruitment: Boys Town National Research Hospital, the University of North Carolina at Chapel Hill, and the University of Iowa. The sample consisted of 12 children with ANSD and 22 children with SNHL. The groups were matched based on better-ear pure-tone average, better-ear aided speech intelligibility index, gender, maternal education level, and newborn hearing screening result (i.e., pass or refer). Children and their families participated in an initial baseline visit, followed by visits twice a year for children 2 yr of age. Paired-sample t-tests were used to compare children with ANSD to children with SNHL. Paired t-tests indicated no significant differences between the ANSD and SNHL groups on language and articulation measures. Children with ANSD displayed functional speech perception skills in quiet. Although the number of participants was too small to conduct statistical analyses for speech perception testing, there appeared to be a trend in which the ANSD group performed more poorly in background noise

Olesoxime (cholest-4-en-3-one, oxime): Analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel

OpenAIRE

Xiao, Wen Hua; Zheng, Felix Y.; Bennett, Gary J.; Bordet, Thierry; Pruss, Rebecca M.

2009-01-01

Olesoxime is a small cholesterol-like molecule that was discovered in a screening program aimed at finding treatment for amyotrophic lateral sclerosis and other diseases where motor neurons degenerate. In addition to its neuroprotective and pro-regenerative effects on motor neurons in vitro and in vivo, it has been shown to have analgesic effects in rat models of painful peripheral neuropathy due to vincristine and diabetes. We used a rat model of painful peripheral neuropathy produced by the...

Cutaneous manifestations of diabetic peripheral neuropathy.

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Dogiparthi, S N; Muralidhar, K; Seshadri, K G; Rangarajan, S

2017-01-01

There is a rise in number of people diagnosed with Diabetes Mellitus. The incidence is rising in modern Indian society because of Industrial development and drastically changing lifestyles. Diabetic neuropathies are microvascular disorders that are usually associated with the duration of Diabetes. Among the various forms, the most common is Diabetic Peripheral Neuropathy. The disease if neglected leads to chronic ulcer formation leading to amputations frequently. Hence the aim of this study is to document the early cutaneous changes and create an early awareness in the importance of controlling Diabetes. The study consisted of 205 patients with Type 2 DM. Participant's neuropathy status was determined based on Neuropathy Disability Score and Diabetic Neuropathy Symptom Score. Among the Skin changes documented, the common changes seen were: Peripheral hair loss in 185 (90.2%), Xerosis in 168 (82%), Anhydrosis in 162 (79%), Plantar Fissures in 136 (66.3%), Plantar Ulcer in 80 (39%), common nail changes documented were Onychomycosis in 165 (80.5%) and Onychauxis in 53 (25.8%) patients in relation to the occupation and duration of Diabetes mellitus. In conclusion, it is important to control glycemic levels in the all stages of Diabetes and institute foot care measures to prevent the complications of neuropathy.

Treatment of painful diabetic peripheral neuropathy.

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Rosenberg, Casandra J; Watson, James C

2015-02-01

Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

Herpes Zoster Optic Neuropathy.

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Kaufman, Aaron R; Myers, Eileen M; Moster, Mark L; Stanley, Jordan; Kline, Lanning B; Golnik, Karl C

2018-06-01

Herpes zoster optic neuropathy (HZON) is a rare manifestation of herpes zoster ophthalmicus (HZO). The aim of our study was to better characterize the clinical features, therapeutic choices, and visual outcomes in HZON. A retrospective chart review was performed at multiple academic eye centers with the inclusion criteria of all eyes presenting with optic neuropathy within 1 month of cutaneous zoster of the ipsilateral trigeminal dermatome. Data were collected regarding presenting features, treatment regimen, and visual acuity outcomes. Six patients meeting the HZON inclusion criteria were identified. Mean follow-up was 2.75 months (range 0.5-4 months). Herpes zoster optic neuropathy developed at a mean of 14.1 days after initial rash (range 6-30 days). Optic neuropathy was anterior in 2 eyes and retrobulbar in 4 eyes. Other manifestations of HZO included keratoconjunctivitis (3 eyes) and iritis (4 eyes). All patients were treated with systemic antiviral therapy in addition to topical and/or systemic corticosteroids. At the last follow-up, visual acuity in 3 eyes had improved relative to presentation, 2 eyes had worsened, and 1 eye remained the same. The 2 eyes that did not receive systemic corticosteroids had the best observed final visual acuity. Herpes zoster optic neuropathy is an unusual but distinctive complication of HZO. Visual recovery after HZON is variable. Identification of an optimal treatment regiment for HZON could not be identified from our patient cohort. Systemic antiviral agents are a component of HZON treatment regimens. Efficacy of systemic corticosteroids for HZON remains unclear and should be considered on a case-by-case basis.

Performance-based Physical Functioning and Peripheral Neuropathy in a Population-based Cohort of Women at Midlife

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Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D.

2013-01-01

Peripheral neuropathy is underappreciated as a potential cause of functional limitations. In the present article, we assessed the cross-sectional association between peripheral neuropathy and physical functioning and how the longitudinal association between age and functioning differed by neuropathy status. Physical functioning was measured in 1996–2008 using timed performances on stair-climb, walking, sit-to-stand, and balance tests at the Michigan site of the Study of Women's Health Across the Nation, a population-based cohort study of women at midlife (n = 396). Peripheral neuropathy was measured in 2008 and defined as having an abnormal monofilament test result or 4 or more symptoms. We used linear mixed models to determine whether trajectories of physical functioning differed by prevalent neuropathy status. Overall, 27.8% of the women had neuropathy. Stair-climb time differed by neuropathy status (P = 0.04), and for every 1-year increase in age, women with neuropathy had a 1.82% (95% confidence interval: 1.42, 2.21) increase compared with a 0.95% (95% confidence interval: 0.71, 1.20) increase for women without neuropathy. Sit-to-stand time differed by neuropathy status (P = 0.01), but the rate of change did not differ. No differences between neuropathy groups were observed for the walk test. For some performance-based tasks, poor functioning was maintained or exacerbated for women who had prevalent neuropathy. Peripheral neuropathy may play a role in physical functioning limitations and future disability. PMID:23524038

Abnormalities in auditory efferent activities in children with selective mutism.

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Muchnik, Chava; Ari-Even Roth, Daphne; Hildesheimer, Minka; Arie, Miri; Bar-Haim, Yair; Henkin, Yael

2013-01-01

Two efferent feedback pathways to the auditory periphery may play a role in monitoring self-vocalization: the middle-ear acoustic reflex (MEAR) and the medial olivocochlear bundle (MOCB) reflex. Since most studies regarding the role of auditory efferent activity during self-vocalization were conducted in animals, human data are scarce. The working premise of the current study was that selective mutism (SM), a rare psychiatric disorder characterized by consistent failure to speak in specific social situations despite the ability to speak normally in other situations, may serve as a human model for studying the potential involvement of auditory efferent activity during self-vocalization. For this purpose, auditory efferent function was assessed in a group of 31 children with SM and compared to that of a group of 31 normally developing control children (mean age 8.9 and 8.8 years, respectively). All children exhibited normal hearing thresholds and type A tympanograms. MEAR and MOCB functions were evaluated by means of acoustic reflex thresholds and decay functions and the suppression of transient-evoked otoacoustic emissions, respectively. Auditory afferent function was tested by means of auditory brainstem responses (ABR). Results indicated a significantly higher proportion of children with abnormal MEAR and MOCB function in the SM group (58.6 and 38%, respectively) compared to controls (9.7 and 8%, respectively). The prevalence of abnormal MEAR and/or MOCB function was significantly higher in the SM group (71%) compared to controls (16%). Intact afferent function manifested in normal absolute and interpeak latencies of ABR components in all children. The finding of aberrant efferent auditory function in a large proportion of children with SM provides further support for the notion that MEAR and MOCB may play a significant role in the process of self-vocalization. © 2013 S. Karger AG, Basel.

Propylthiouracil and peripheral neuropathy

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Valentina Van Boekel

1992-06-01

Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

Diagnosis and therapeutic options for peripheral vasculitic neuropathy

Science.gov (United States)

2015-01-01

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

Genetics Home Reference: hereditary sensory neuropathy type IA

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... sensory neuropathy type IA Hereditary sensory neuropathy type IA Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Hereditary sensory neuropathy type IA is a condition characterized by nerve abnormalities in ...

Attending to auditory memory.

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Zimmermann, Jacqueline F; Moscovitch, Morris; Alain, Claude

2016-06-01

Attention to memory describes the process of attending to memory traces when the object is no longer present. It has been studied primarily for representations of visual stimuli with only few studies examining attention to sound object representations in short-term memory. Here, we review the interplay of attention and auditory memory with an emphasis on 1) attending to auditory memory in the absence of related external stimuli (i.e., reflective attention) and 2) effects of existing memory on guiding attention. Attention to auditory memory is discussed in the context of change deafness, and we argue that failures to detect changes in our auditory environments are most likely the result of a faulty comparison system of incoming and stored information. Also, objects are the primary building blocks of auditory attention, but attention can also be directed to individual features (e.g., pitch). We review short-term and long-term memory guided modulation of attention based on characteristic features, location, and/or semantic properties of auditory objects, and propose that auditory attention to memory pathways emerge after sensory memory. A neural model for auditory attention to memory is developed, which comprises two separate pathways in the parietal cortex, one involved in attention to higher-order features and the other involved in attention to sensory information. This article is part of a Special Issue entitled SI: Auditory working memory. Copyright © 2015 Elsevier B.V. All rights reserved.

PENGARUH MODEL PEMBELAJARAN AUDITORY, INTELLECTUALLY, AND REPETITION TERHADAP KEMAMPUAN PEMAHAMAN KONSEP DI SMP PUSTEK SERPONG

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Selviani Fitri

2016-09-01

Full Text Available This research aims to know the effect of learning model of Auditory, Intellectually, and Repetition (AIR about cube concept comprehension to students' VIII grade at SMP Pustek Serpong. Kind of the research is experiment quasi research. The research instrument that used is analysis question pretest and postest. The data analyze by using normality test, homogenity test, and t-test. The result of the research show that there is the different ability of cube concept comprehension among students' who gave air learning model with convensional learning model. Keywords: Model Pembelajaran Auditory Intellectually and Repetition (AIR, concept comprehension

Clinical spectrum of Castleman disease-associated neuropathy.

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Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay; Mauermann, Michelle L

2016-12-06

To define the peripheral neuropathy phenotypes associated with Castleman disease. We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. © 2016 American Academy of Neurology.

Clinical spectrum of Castleman disease–associated neuropathy

Science.gov (United States)

Naddaf, Elie; Dispenzieri, Angela; Mandrekar, Jay

2016-01-01

Objective: To define the peripheral neuropathy phenotypes associated with Castleman disease. Methods: We conducted a retrospective chart review for patients with biopsy-proven Castleman disease evaluated between January 2003 and December 2014. Patients with associated peripheral neuropathy were identified and divided into 2 groups: those with Castleman disease without POEMS syndrome (CD-PN) and those with Castleman disease with POEMS syndrome (CD-POEMS). We used a cohort of patients with POEMS as controls. Clinical, electrodiagnostic, and laboratory characteristics were collected and compared among patient subgroups. Results: There were 7 patients with CD-PN, 20 with CD-POEMS, and 122 with POEMS. Patients with CD-PN had the mildest neuropathy characterized by predominant sensory symptoms with no pain and mild distal sensory deficits (median Neuropathy Impairment Score of 7 points). Although both patients with CD-POEMS and patients with POEMS had a severe sensory and motor neuropathy, patients with CD-POEMS were less affected (median Neuropathy Impairment Score of 33 and 66 points, respectively). The degree of severity was also reflected on electrodiagnostic testing in which patients with CD-PN demonstrated a mild degree of axonal loss, followed by patients with CD-POEMS and then those with POEMS. Demyelinating features, defined by European Federation of Neurologic Societies/Peripheral Nerve Society criteria, were present in 43% of the CD-PN, 78% of the CD-POEMS, and 86% of the POEMS group. Conclusion: There is a spectrum of demyelinating peripheral neuropathies associated with Castleman disease. CD-PN is sensory predominant and is the mildest phenotype, whereas CD-POEMS is a more severe sensory and motor neuropathy. Compared to the POEMS cohort, those with CD-POEMS neuropathy have a similar but less severe phenotype. Whether these patients respond differently to treatment deserves further study. PMID:27807187

Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy

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Jayaraman, Manju; Gandhi, Rashmin Anilkumar; Ravi, Priya; Sen, Parveen

2014-01-01

Purpose: To investigate the effect of optic neuritis (ON), ischemic optic neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT). Results: Median of mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73 (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect. PMID:24088641

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

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Harry Liu

2017-02-01

Full Text Available Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A “gain of toxicity” model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s causes a “loss of function”, resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons of CMT2B are needed to precisely define the disease mechanisms.

Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

Science.gov (United States)

Liu, Harry; Wu, Chengbiao

2017-02-04

Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

Neuropathy in a petrol sniffer.

Science.gov (United States)

Hall, D M; Ramsey, J; Schwartz, M S; Dookun, D

1986-09-01

A 4 year old boy developed a profound motor neuropathy after repeated deliberate inhalation of petroleum vapour. The condition was characterised by extreme slowing of the nerve conduction velocity. He made a gradual recovery over six months. The neuropathy was attributed to the N-hexane component of petroleum.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

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Hana Starobova

2017-05-01

Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

Science.gov (United States)

Sun, Hai-Ying; Hu, Yu-Juan; Zhao, Xue-Yan; Zhong, Yi; Zeng, Ling-Ling; Chen, Xu-Bo; Yuan, Jie; Wu, Jing; Sun, Yu; Kong, Wen; Kong, Wei-Jia

2015-07-01

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long-term exposure to d-galactose (d-Gal). We also explored changes in thioredoxin-interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p-ASK1) expression, as well as the Trx2-TXNIP/Trx2-ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2-ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p-ASK1 expression, and Trx2-TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP-Trx2-ASK1 signal pathway may participate in the pathogenesis of central presbycusis. © 2015 FEBS.

Hypothyroidism: Can It Cause Peripheral Neuropathy?

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Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

Diabetic cachectic neuropathy: An uncommon neurological ...

African Journals Online (AJOL)

Diabetic cachectic neuropathy, also called diabetic neuropathic cachexia, is a very rare ... type 1 and type 2 diabetics and occurs irrespective of the duration of diabetes. .... distal symmetrical peripheral neuropathy in pregnancy. However,.

An improved experimental model for peripheral neuropathy in rats

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Q.M. Dias

2013-03-01

Full Text Available A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively, but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively. The modified method required less surgical skill than the spinal nerve ligation model.

An improved experimental model for peripheral neuropathy in rats

International Nuclear Information System (INIS)

Dias, Q.M.; Rossaneis, A.C.; Fais, R.S.; Prado, W.A.

2013-01-01

A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model

An improved experimental model for peripheral neuropathy in rats

Directory of Open Access Journals (Sweden)

Q.M. Dias

Full Text Available A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively, but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively. The modified method required less surgical skill than the spinal nerve ligation model.

An improved experimental model for peripheral neuropathy in rats

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Dias, Q.M.; Rossaneis, A.C.; Fais, R.S.; Prado, W.A. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2013-03-15

A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

OpenAIRE

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

Animal model of cochlear third window in the scala vestibuli or scala tympani.

Science.gov (United States)

Attias, Joseph; Preis, Michal; Shemesh, Rafi; Hadar, Tuvia; Nageris, Ben I

2010-08-01

The auditory impact of a cochlear third window differs by its location in the scala vestibuli or scala tympani. Pathologic third window has been investigated primarily in the vestibular apparatus of animals and humans. Dehiscence of the superior semicircular canal is the clinical model. Fat sand rats (n = 11) have a unique inner-ear anatomy that allows easy surgical access. A window was drilled in the bony labyrinth over the scala vestibuli in 1 group (12 ears) and over the scala tympani in another (7 ears) while preserving the membranous labyrinth. Auditory brain stem responses to high- and low-frequency stimuli delivered by air and bone conduction were recorded before and after the procedure. Scala vestibuli group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.3 and 9.6 dB, respectively, and bone-conduction thresholds, 4.6 and 3.3 dB, respectively; after fenestration, air-conduction thresholds averaged 40.4 and 41.8 dB, respectively, and bone-conduction thresholds, -1 and 5.6 dB, respectively. Scala tympani group: preoperative air-conduction thresholds to clicks and tone-bursts averaged 8.6 dB each, and bone-conduction thresholds, 7.9 dB and 7.1 dB, respectively; after fenestration, air-conduction thresholds averaged 11.4 and 9.3 dB, respectively, and bone-conduction thresholds, 9.3 and 4.2 dB, respectively. The changes in air- (p = 0.0001) and bone-conduction (p = 0.04) thresholds were statistically significant only in the scala vestibuli group. The presence of a cochlear third window over the scala vestibuli, but not over the scala tympani, causes a significant increase in air-conduction auditory thresholds. These results agree with the theoretic model and clinical findings and contribute to our understanding of vestibular dehiscence.

Animal models of dementia

DEFF Research Database (Denmark)

Olsson, I. Anna S.; Sandøe, Peter

2011-01-01

This chapter aims to encourage scientists and others interested in the use of animal models of disease – specifically, in the study of dementia – to engage in ethical reflection. It opens with a general discussion of the moral acceptability of animal use in research. Three ethical approaches...... are here distinguished. These serve as points of orientation in the following discussion of four more specific ethical questions: Does animal species matter? How effective is disease modelling in delivering the benefits claimed for it? What can be done to minimize potential harm to animals in research? Who...... bears responsibility for the use of animals in disease models?...

The role of temporal coherence in auditory stream segregation

DEFF Research Database (Denmark)

Christiansen, Simon Krogholt

The ability to perceptually segregate concurrent sound sources and focus one’s attention on a single source at a time is essential for the ability to use acoustic information. While perceptual experiments have determined a range of acoustic cues that help facilitate auditory stream segregation......, it is not clear how the auditory system realizes the task. This thesis presents a study of the mechanisms involved in auditory stream segregation. Through a combination of psychoacoustic experiments, designed to characterize the influence of acoustic cues on auditory stream formation, and computational models...... of auditory processing, the role of auditory preprocessing and temporal coherence in auditory stream formation was evaluated. The computational model presented in this study assumes that auditory stream segregation occurs when sounds stimulate non-overlapping neural populations in a temporally incoherent...

Modelling Farm Animal Welfare

Science.gov (United States)

Collins, Lisa M.; Part, Chérie E.

2013-01-01

Simple Summary In this review paper we discuss the different modeling techniques that have been used in animal welfare research to date. We look at what questions they have been used to answer, the advantages and pitfalls of the methods, and how future research can best use these approaches to answer some of the most important upcoming questions in farm animal welfare. Abstract The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively) based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested. PMID:26487411

New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.

Science.gov (United States)

Foroozan, Rod

2017-02-01

Despite increasing knowledge about the risk factors and clinical findings of nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this optic neuropathy has remained limited and without clear evidence-based benefit. Historical treatments of NAION are reviewed, beginning with the Ischemic Optic Neuropathy Decompression Trial. More recent treatments are placed within the historical context and illustrate the need for evidence-based therapy for ischemic optic neuropathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-sensory integration in brainstem and auditory cortex.

Science.gov (United States)

Basura, Gregory J; Koehler, Seth D; Shore, Susan E

2012-11-16

Tinnitus is the perception of sound in the absence of a physical sound stimulus. It is thought to arise from aberrant neural activity within central auditory pathways that may be influenced by multiple brain centers, including the somatosensory system. Auditory-somatosensory (bimodal) integration occurs in the dorsal cochlear nucleus (DCN), where electrical activation of somatosensory regions alters pyramidal cell spike timing and rates of sound stimuli. Moreover, in conditions of tinnitus, bimodal integration in DCN is enhanced, producing greater spontaneous and sound-driven neural activity, which are neural correlates of tinnitus. In primary auditory cortex (A1), a similar auditory-somatosensory integration has been described in the normal system (Lakatos et al., 2007), where sub-threshold multisensory modulation may be a direct reflection of subcortical multisensory responses (Tyll et al., 2011). The present work utilized simultaneous recordings from both DCN and A1 to directly compare bimodal integration across these separate brain stations of the intact auditory pathway. Four-shank, 32-channel electrodes were placed in DCN and A1 to simultaneously record tone-evoked unit activity in the presence and absence of spinal trigeminal nucleus (Sp5) electrical activation. Bimodal stimulation led to long-lasting facilitation or suppression of single and multi-unit responses to subsequent sound in both DCN and A1. Immediate (bimodal response) and long-lasting (bimodal plasticity) effects of Sp5-tone stimulation were facilitation or suppression of tone-evoked firing rates in DCN and A1 at all Sp5-tone pairing intervals (10, 20, and 40 ms), and greater suppression at 20 ms pairing-intervals for single unit responses. Understanding the complex relationships between DCN and A1 bimodal processing in the normal animal provides the basis for studying its disruption in hearing loss and tinnitus models. This article is part of a Special Issue entitled: Tinnitus Neuroscience

Docetaxel-induced neuropathy

DEFF Research Database (Denmark)

Eckhoff, Lise; Feddersen, Søren; Knoop, Ann

2015-01-01

Background. Docetaxel is a highly effective treatment of a wide range of malignancies but is often associated with peripheral neuropathy. The genetic variability of genes involved in the transportation or metabolism of docetaxel may be responsible for the variation in docetaxel-induced peripheral...... neuropathy (DIPN). The main purpose of this study was to investigate the impact of genetic variants in GSTP1 and ABCB1 on DIPN. Material and methods. DNA was extracted from whole blood from 150 patients with early-stage breast cancer who had received adjuvant docetaxel from February 2011 to May 2012. Two...

Biomedical Simulation Models of Human Auditory Processes

Science.gov (United States)

Bicak, Mehmet M. A.

2012-01-01

Detailed acoustic engineering models that explore noise propagation mechanisms associated with noise attenuation and transmission paths created when using hearing protectors such as earplugs and headsets in high noise environments. Biomedical finite element (FE) models are developed based on volume Computed Tomography scan data which provides explicit external ear, ear canal, middle ear ossicular bones and cochlea geometry. Results from these studies have enabled a greater understanding of hearing protector to flesh dynamics as well as prioritizing noise propagation mechanisms. Prioritization of noise mechanisms can form an essential framework for exploration of new design principles and methods in both earplug and earcup applications. These models are currently being used in development of a novel hearing protection evaluation system that can provide experimentally correlated psychoacoustic noise attenuation. Moreover, these FE models can be used to simulate the effects of blast related impulse noise on human auditory mechanisms and brain tissue.

Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

LENUS (Irish Health Repository)

Saidha, Shiv

2010-04-19

Abstract Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15\\/30) developed following relatively short procedures. In 27% of cases (8\\/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7\\/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12\\/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.

Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.

Science.gov (United States)

Moustafa, Passant E; Abdelkader, Noha F; El Awdan, Sally A; El-Shabrawy, Osama A; Zaki, Hala F

2018-04-27

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored

DNA testing in hereditary neuropathies.

LENUS (Irish Health Repository)

Murphy, Sinéad M

2013-01-01

The inherited neuropathies are a clinically and genetically heterogeneous group of disorders in which there have been rapid advances in the last two decades. Molecular genetic testing is now an integral part of the evaluation of patients with inherited neuropathies. In this chapter we describe the genes responsible for the primary inherited neuropathies. We briefly discuss the clinical phenotype of each of the known inherited neuropathy subgroups, describe algorithms for molecular genetic testing of affected patients and discuss genetic counseling. The basic principles of careful phenotyping, documenting an accurate family history, and testing the available genes in an appropriate manner should identify the vast majority of individuals with CMT1 and many of those with CMT2. In this chapter we also describe the current methods of genetic testing. As advances are made in molecular genetic technologies and improvements are made in bioinformatics, it is likely that the current time-consuming methods of DNA sequencing will give way to quicker and more efficient high-throughput methods, which are briefly discussed here.

Corneal markers of diabetic neuropathy.

Science.gov (United States)

Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2011-01-01

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Peripheral neuropathy in prediabetes and the metabolic syndrome.

Science.gov (United States)

Stino, Amro M; Smith, Albert G

2017-09-01

Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. Most patients with non-diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle-based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Across frequency processes involved in auditory detection of coloration

DEFF Research Database (Denmark)

Buchholz, Jörg; Kerketsos, P

2008-01-01

filterbank was designed to approximate auditory filter-shapes measured by Oxenham and Shera [JARO, 2003, 541-554], derived from forward masking data. The results of the present study demonstrate that a “purely” spectrum-based model approach can successfully describe auditory coloration detection even at high......When an early wall reflection is added to a direct sound, a spectral modulation is introduced to the signal's power spectrum. This spectral modulation typically produces an auditory sensation of coloration or pitch. Throughout this study, auditory spectral-integration effects involved in coloration...... detection are investigated. Coloration detection thresholds were therefore measured as a function of reflection delay and stimulus bandwidth. In order to investigate the involved auditory mechanisms, an auditory model was employed that was conceptually similar to the peripheral weighting model [Yost, JASA...

Shaping the aging brain: Role of auditory input patterns in the emergence of auditory cortical impairments

Directory of Open Access Journals (Sweden)

Brishna Soraya Kamal

2013-09-01

Full Text Available Age-related impairments in the primary auditory cortex (A1 include poor tuning selectivity, neural desynchronization and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function.

Hereditary sensory neuropathy type I

Directory of Open Access Journals (Sweden)

Auer-Grumbach Michaela

2008-03-01

Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

Hereditary sensory neuropathy type I.

Science.gov (United States)

Auer-Grumbach, Michaela

2008-03-18

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

Peripheral Neuropathy

Science.gov (United States)

... wasting. Various dietary strategies can improve gastrointestinal symptoms. Timely treatment of injuries can help prevent permanent damage. ... diabetic neuropathy is more limited. Transcutaneous electrical nerve stimulation (TENS) is a non-invasive intervention used for ...

Animal welfare and use of silkworm as a model animal.

Science.gov (United States)

Sekimizu, N; Paudel, A; Hamamoto, H

2012-08-01

Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

Auditory sensory processing deficits in sensory gating and mismatch negativity-like responses in the social isolation rat model of schizophrenia

DEFF Research Database (Denmark)

Witten, Louise; Oranje, Bob; Mørk, Arne

2014-01-01

Patients with schizophrenia exhibit disturbances in information processing. These disturbances can be investigated with different paradigms of auditory event related potentials (ERP), such as sensory gating in a double click paradigm (P50 suppression) and the mismatch negativity (MMN) component...... in an auditory oddball paradigm. The aim of the current study was to test if rats subjected to social isolation, which is believed to induce some changes that mimic features of schizophrenia, displays alterations in sensory gating and MMN-like response. Male Lister-Hooded rats were separated into two groups; one...... group socially isolated (SI) for 8 weeks and one group housed (GH). Both groups were then tested in a double click sensory gating paradigm and an auditory oddball paradigm (MMN-like) paradigm. It was observed that the SI animals showed reduced sensory gating of the cortical N1 amplitude. Furthermore...

Auditory Modeling for Noisy Speech Recognition

National Research Council Canada - National Science Library

2000-01-01

... digital filtering for noise cancellation which interfaces to speech recognition software. It uses auditory features in speech recognition training, and provides applications to multilingual spoken language translation...

The Central Role of Recognition in Auditory Perception: A Neurobiological Model

Science.gov (United States)

McLachlan, Neil; Wilson, Sarah

2010-01-01

The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior…

Penicillamin-induced neuropathy in rheumatoid arthritis

DEFF Research Database (Denmark)

Pedersen, P B; Hogenhaven, H

1990-01-01

A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse...

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

Science.gov (United States)

Sinclair, D.; Oranje, B.; Razak, K.A.; Siegel, S.J.; Schmid, S.

2017-01-01

Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and in relevant rodent models. This includes electroencephalographic measurement of event related potentials, neural oscillations and mismatch negativity, as well as habituation and pre-pulse inhibition of startle. We outline robust evidence of disrupted sensory processing in individuals with ASD and FXS, and in respective animal models, focusing on the auditory sensory domain. Animal models provide an excellent opportunity to examine common mechanisms of sensory pathophysiology in order to develop therapeutics. PMID:27235081

Genetic heterogeneity of motor neuropathies.

Science.gov (United States)

Bansagi, Boglarka; Griffin, Helen; Whittaker, Roger G; Antoniadi, Thalia; Evangelista, Teresinha; Miller, James; Greenslade, Mark; Forester, Natalie; Duff, Jennifer; Bradshaw, Anna; Kleinle, Stephanie; Boczonadi, Veronika; Steele, Hannah; Ramesh, Venkateswaran; Franko, Edit; Pyle, Angela; Lochmüller, Hanns; Chinnery, Patrick F; Horvath, Rita

2017-03-28

To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62-2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy.

Science.gov (United States)

Magnowska, Magdalena; Iżycka, Natalia; Kapoła-Czyż, Joanna; Romała, Anna; Lorek, Jakub; Spaczyński, Marek; Nowak-Markwitz, Ewa

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p peripheral neuropathy.

Peripheral neuropathy in HIV: an analysis of evidence-based approaches.

Science.gov (United States)

Nicholas, Patrice K; Corless, Inge B; Evans, Linda A

2014-01-01

Peripheral neuropathy is a common and vexing symptom for people living with HIV infection (PLWH). Neuropathy occurs in several different syndromes and is identified in the literature as distal sensory polyneuropathy or distal sensory peripheral neuropathy. More recently, the HIV literature has focused on the syndrome as painful HIV-associated sensory neuropathy, addressing the symptom rather than the underlying pathophysiology. Assessment of neuropathy in PLWH is critical and must be incorporated into nursing practice for each visit. Neuropathy has been attributed to the direct effects of HIV, exposure to antiretroviral medications (particularly the nucleoside reverse transcriptase inhibitors), advanced immune suppression, and comorbid tuberculosis infection and exposure to antituberculosis medications. Evidence supports the importance of addressing neuropathy in PLWH with pharmacologic treatment regimens and complementary/alternative approaches. This paper examines the pathophysiology, evidence, and approaches to managing peripheral neuropathy. A case study has been included to illustrate a patient's experience with neuropathy symptoms. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Modelling Farm Animal Welfare

Directory of Open Access Journals (Sweden)

Chérie E. Part

2013-05-01

Full Text Available The use of models in the life sciences has greatly expanded in scope and advanced in technique in recent decades. However, the range, type and complexity of models used in farm animal welfare is comparatively poor, despite the great scope for use of modeling in this field of research. In this paper, we review the different modeling approaches used in farm animal welfare science to date, discussing the types of questions they have been used to answer, the merits and problems associated with the method, and possible future applications of each technique. We find that the most frequently published types of model used in farm animal welfare are conceptual and assessment models; two types of model that are frequently (though not exclusively based on expert opinion. Simulation, optimization, scenario, and systems modeling approaches are rarer in animal welfare, despite being commonly used in other related fields. Finally, common issues such as a lack of quantitative data to parameterize models, and model selection and validation are discussed throughout the review, with possible solutions and alternative approaches suggested.

Association between nasopharyngeal carcinoma and risk of optic neuropathy: A population-based cohort study.

Science.gov (United States)

Fan, Chao-Yueh; Jen, Yee-Min; Su, Yuan-Chih; Chao, Hsing-Lung; Lin, Chun-Shu; Huang, Wen-Yen; Lin, Miao-Jung; Kao, Chia-Hung

2018-04-16

The purpose of this study was to assess the predictive factors of optic neuropathy among patients with nasopharyngeal carcinoma (NPC). The analysis included 16 297 patients with NPC and 65 187 controls. Each patient with NPC was randomly frequency-matched with 4 individuals without NPC by age, sex, and index year. Cox proportional hazard models were applied to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) of optic neuropathy development associated with NPC. The risk of optic neuropathy was significantly higher in the NPC cohort (adjusted HR [aHR] 3.42; 95% CI 2.85-4.09; P optic neuropathy among patients with NPC included stroke (aHR 1.7; 95% CI 1.07-2.7; P = .03) and receipt of chemotherapy (aHR 1.55; 95% CI 1.17-2.06; P = .002). The risk of optic neuropathy was significantly higher in patients with NPC than in the general population. © 2018 Wiley Periodicals, Inc.

Chronic obstructive pulmonary disease and peripheral neuropathy

Directory of Open Access Journals (Sweden)

Gupta Prem

2006-01-01

Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

Perfil pragmático longitudinal de uma criança no espectro da neuropatia auditiva Longitudinal pragmatic profile of a child with auditory neuropathy spectrum disorder

Directory of Open Access Journals (Sweden)

Andreza Carolina Bretanha

2011-06-01

Full Text Available A maior parte da comunicação humana depende da conversão de ideias em linguagem, envolvendo a interação de todos os seus componentes - fonológico, semântico, sintático e pragmático. A pragmática estuda a relação entre o significado social da linguagem e seu conteúdo semântico, manifestado pelo ato comunicativo em si. O espectro da neuropatia auditiva gera uma dessincronia na condução nervosa, contribuindo para o prejuízo na percepção da fala. Na criança deficiente auditiva, o processo de aquisição e desenvolvimento da linguagem pode ser estimulado com a intervenção. O objetivo dessa pesquisa foi realizar acompanhamento longitudinal do uso das habilidades pragmáticas de comunicação por uma criança com espectro da neuropatia auditiva. A criança realizou intervenção fonoaudiológica por três anos na área de Audiologia Educacional. Foram gravadas conversações espontâneas, ao início de cada ano, transcritas e analisadas segundo protocolo de habilidades comunicativas verbais. Na gravação inicial, a criança apresentou maior número de habilidade de respostas diretas; porém, estas foram ampliadas com o fornecimento de respostas mais complexas ao longo da intervenção. Na última gravação, já propõe novos tópicos de discurso, realiza narrativas e argumentações. O surgimento de habilidades comunicativas refinadas é explicado pelo desenvolvimento da linguagem, que é potencializado pela terapia com deficientes auditivos. Pode-se concluir que para o caso apresentado a intervenção fonoaudiológica proporcionou melhora nas habilidades pragmáticas de comunicação.Human communication depends mostly on the conversion of ideas into language, involving the interaction among all its components - phonological, semantic, syntactic and pragmatic. Pragmatics studies the relationship between the social meaning of language and its semantic content, expressed by the communicative act itself. Auditory neuropathy

A Brief Period of Postnatal Visual Deprivation Alters the Balance between Auditory and Visual Attention.

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de Heering, Adélaïde; Dormal, Giulia; Pelland, Maxime; Lewis, Terri; Maurer, Daphne; Collignon, Olivier

2016-11-21

Is a short and transient period of visual deprivation early in life sufficient to induce lifelong changes in how we attend to, and integrate, simple visual and auditory information [1, 2]? This question is of crucial importance given the recent demonstration in both animals and humans that a period of blindness early in life permanently affects the brain networks dedicated to visual, auditory, and multisensory processing [1-16]. To address this issue, we compared a group of adults who had been treated for congenital bilateral cataracts during early infancy with a group of normally sighted controls on a task requiring simple detection of lateralized visual and auditory targets, presented alone or in combination. Redundancy gains obtained from the audiovisual conditions were similar between groups and surpassed the reaction time distribution predicted by Miller's race model. However, in comparison to controls, cataract-reversal patients were faster at processing simple auditory targets and showed differences in how they shifted attention across modalities. Specifically, they were faster at switching attention from visual to auditory inputs than in the reverse situation, while an opposite pattern was observed for controls. Overall, these results reveal that the absence of visual input during the first months of life does not prevent the development of audiovisual integration but enhances the salience of simple auditory inputs, leading to a different crossmodal distribution of attentional resources between auditory and visual stimuli. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

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Watson, James C; Dyck, P James B

2015-07-01

Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Ethambutol/Linezolid Toxic Optic Neuropathy.

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Libershteyn, Yevgeniya

2016-02-01

To report a rare toxic optic neuropathy after long-term use of two medications: ethambutol and linezolid. A 65-year-old man presented to the Miami Veterans Affairs Medical Center in December 2014 for evaluation of progressive vision decrease in both eyes. The patient presented with best-corrected visual acuities of 20/400 in the right eye and counting fingers at 5 feet in the left eye. Color vision was significantly reduced in both eyes. Visual fields revealed a cecocentral defect in both eyes. His fundus and optic nerve examination was unremarkable. Because vision continued to decline after discontinuation of ethambutol, linezolid was also discontinued, after which vision, color vision, and visual fields improved. Because of these findings, the final diagnosis was toxic optic neuropathy. Final visual outcome was 20/30 in the right eye and 20/40 in the left eye. Drug-associated toxic optic neuropathy is a rare but vision-threatening condition. Diagnosis is made based on an extensive case history and careful clinical examination. The examination findings include varying decrease in vision, normal pupils and extraocular muscles, and unremarkable fundoscopy, with the possibility of swollen optic discs in the acute stage of the optic neuropathy. Other important findings descriptive of toxic optic neuropathy include decreased color vision and cecocentral visual field defects. This case illustrates the importance of knowledge of all medications and/or substances a patient consumes that may cause a toxic reaction and discontinuing them immediately if the visual functions are worsening or not improving.

[Nonarteritic ischemic optic neuropathy animal model and its treatment applications].

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Chuman, Hideki

2014-04-01

Nonarteritic ischemic optic neuropathy (NAION) is one of the most common acute unilaterally onset optic nerve diseases. One management problem in terms of NAION is the difficulty of differential diagnosis between NAION and anterior optic neuritis (ON). A second problem is that there is no established treatment for the acute stage of NAION. A third problem is that there is no preventive treatment for a subsequent attack on the fellow eye, estimated to occur in 15 to 25% of patients with NAION. For differentiation of acute NAION from anterior optic neuritis, we investigated the usefulness of laser speckle flowgraphy (LSFG). In the normal control group, the tissue blood flow did not significantly differ between the right and left eyes. In the NAION group, all 6 patients had 29.5% decreased mean blur rate (MBR), which correlates to optic disc blood flow, of the NAION eye compared with the unaffected eye. In the anterior ON group, all 6 cases had 15.9% increased MBR of the anterior ON eye compared with the unaffected eye. Thus, LSFG showed a difference of the underlying pathophysiology between NAION and anterior ON despite showing disc swelling in both groups and could be useful for differentiating both groups. For the treatment of acute stage of NAION, we tried to reproduce the rodent model of NAION (rNAION) developed by Bernstein and colleagues. To induce rNAION, after the administration of rose bengal(RB) (2.5 mM) into the tail vein of SD rats, the small vessels of the left optic nerve were photoactivated using a 514 nm argon green laser (RB-laser-induction). In the RB-laser-induction eyes, the capillaries within the optic disc were reduced markedly, the optic disc became swollen, and fluorescein angiography showed filling defect in the choroid and the optic disc at an early stage, followed by hyperfluorescence at a late stage. Electrophysiological evaluation revealed that visual evoked potential (VEP) amplitude was significantly decreased but an electroretinogram

Auditory agnosia.

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Slevc, L Robert; Shell, Alison R

2015-01-01

Auditory agnosia refers to impairments in sound perception and identification despite intact hearing, cognitive functioning, and language abilities (reading, writing, and speaking). Auditory agnosia can be general, affecting all types of sound perception, or can be (relatively) specific to a particular domain. Verbal auditory agnosia (also known as (pure) word deafness) refers to deficits specific to speech processing, environmental sound agnosia refers to difficulties confined to non-speech environmental sounds, and amusia refers to deficits confined to music. These deficits can be apperceptive, affecting basic perceptual processes, or associative, affecting the relation of a perceived auditory object to its meaning. This chapter discusses what is known about the behavioral symptoms and lesion correlates of these different types of auditory agnosia (focusing especially on verbal auditory agnosia), evidence for the role of a rapid temporal processing deficit in some aspects of auditory agnosia, and the few attempts to treat the perceptual deficits associated with auditory agnosia. A clear picture of auditory agnosia has been slow to emerge, hampered by the considerable heterogeneity in behavioral deficits, associated brain damage, and variable assessments across cases. Despite this lack of clarity, these striking deficits in complex sound processing continue to inform our understanding of auditory perception and cognition. © 2015 Elsevier B.V. All rights reserved.

Peripheral neuropathy in HIV-infected and uninfected patients in Rakai, Uganda.

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Saylor, Deanna; Nakigozi, Gertrude; Nakasujja, Noeline; Robertson, Kevin; Gray, Ronald H; Wawer, Maria J; Sacktor, Ned

2017-08-01

To determine the prevalence, risk factors, and functional impairment associated with peripheral neuropathy in a prospective cohort of adults in rural Uganda. Eight hundred participants (400 HIV- and 400 antiretroviral-naive HIV+) in the Rakai Community Cohort Study underwent detailed neurologic evaluations including assessment of neuropathy symptoms, functional measures (Patient Assessment of Own Functioning Inventory and Karnofsky Performance Status scores), and neurologic evaluation by a trained medical officer. Neuropathy was defined as ≥1 subjective symptom and ≥1 sign of neuropathy on examination. Neuropathy risk factors were assessed using log binomial regression. Fifty-three percent of participants were men, with a mean (SD) age of 35 (8) years. Neuropathy was present in 13% of the cohort and was more common in HIV+ vs HIV- participants (19% vs 7%, p neuropathy in the overall cohort. Only older age was associated with neuropathy risk in the HIV+ (RR 1.03, 95% CI 1.01-1.05) and HIV- (RR 1.06, 95% CI 1.02-1.10) cohorts. Neuropathy was associated with impaired functional status on multiple measures across all participant groups. Peripheral neuropathy is relatively common and associated with impaired functional status among adults in rural Uganda. Older age, female sex, and HIV infection significantly increase the risk of neuropathy. Neuropathy may be an underrecognized but important condition in rural Uganda and warrants further study. © 2017 American Academy of Neurology.

Diagnostic capability of retinal thickness measures in diabetic peripheral neuropathy

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Sangeetha Srinivasan

2017-10-01

Conclusions: The GCC FLV can differentiate individuals with diabetic neuropathy from healthy controls, while the inferior RNFL thickness is able to differentiate those with greater degrees of neuropathy from those with mild or no neuropathy, both with an acceptable level of accuracy. Optical coherence tomography represents a non-invasive technology that aids in detection of retinal structural changes in patients with established diabetic neuropathy. Further refinement of the technique and the analytical approaches may be required to identify patients with minimal neuropathy.

Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

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Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

2015-01-01

Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

Auditory-visual integration of emotional signals in a virtual environment for cynophobia.

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Taffou, Marine; Chapoulie, Emmanuelle; David, Adrien; Guerchouche, Rachid; Drettakis, George; Viaud-Delmon, Isabelle

2012-01-01

Cynophobia (dog phobia) has both visual and auditory relevant components. In order to investigate the efficacy of virtual reality (VR) exposure-based treatment for cynophobia, we studied the efficiency of auditory-visual environments in generating presence and emotion. We conducted an evaluation test with healthy participants sensitive to cynophobia in order to assess the capacity of auditory-visual virtual environments (VE) to generate fear reactions. Our application involves both high fidelity visual stimulation displayed in an immersive space and 3D sound. This specificity enables us to present and spatially manipulate fearful stimuli in the auditory modality, the visual modality and both. Our specific presentation of animated dog stimuli creates an environment that is highly arousing, suggesting that VR is a promising tool for cynophobia treatment and that manipulating auditory-visual integration might provide a way to modulate affect.

Neuropathies optiques héréditaires

DEFF Research Database (Denmark)

Milea, D; Verny, C

2012-01-01

Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy...... and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated...

Testing for autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1984-01-01

Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course of the di......Autonomic neuropathy is a common complication in long-term diabetes, about 30% of the patients showing measurable signs of autonomic dysfunction after 10 years duration of disease. The diagnosis is often difficult to establish because clinical symptoms generally occur late in the course...

Modeling auditory perception of individual hearing-impaired listeners

DEFF Research Database (Denmark)

Jepsen, Morten Løve; Dau, Torsten

showed that, in most cases, the reduced or absent cochlear compression, associated with outer hair-cell loss, quantitatively accounts for broadened auditory filters, while a combination of reduced compression and reduced inner hair-cell function accounts for decreased sensitivity and slower recovery from...... selectivity. Three groups of listeners were considered: (a) normal hearing listeners; (b) listeners with a mild-to-moderate sensorineural hearing loss; and (c) listeners with a severe sensorineural hearing loss. A fixed set of model parameters were derived for each hearing-impaired listener. The simulations...

Duloxetine for the treatment of painful diabetic peripheral neuropathy in Venezuela: economic evaluation.

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Carlos, Fernando; Espejel, Luis; Novick, Diego; López, Rubén; Flores, Daniel

2015-09-25

Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy. We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses. Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisition’s cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations. This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.

Righting elicited by novel or familiar auditory or vestibular stimulation in the haloperidol-treated rat: rat posturography as a model to study anticipatory motor control.

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Clark, Callie A M; Sacrey, Lori-Ann R; Whishaw, Ian Q

2009-09-15

External cues, including familiar music, can release Parkinson's disease patients from catalepsy but the neural basis of the effect is not well understood. In the present study, posturography, the study of posture and its allied reflexes, was used to develop an animal model that could be used to investigate the underlying neural mechanisms of this sound-induced behavioral activation. In the rat, akinetic catalepsy induced by a dopamine D2 receptor antagonist (haloperidol 5mg/kg) can model human catalepsy. Using this model, two experiments examined whether novel versus familiar sound stimuli could interrupt haloperidol-induced catalepsy in the rat. Rats were placed on a variably inclined grid and novel or familiar auditory cues (single key jingle or multiple key jingles) were presented. The dependent variable was movement by the rats to regain equilibrium as assessed with a movement notation score. The sound cues enhanced movements used to regain postural stability and familiar sound stimuli were more effective than unfamiliar sound stimuli. The results are discussed in relation to the idea that nonlemniscal and lemniscal auditory pathways differentially contribute to behavioral activation versus tonotopic processing of sound.

Immune mediated neuropathy following checkpoint immunotherapy.

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Gu, Yufan; Menzies, Alexander M; Long, Georgina V; Fernando, S L; Herkes, G

2017-11-01

Checkpoint immunotherapy has revolutionised cancer therapy and is now standard treatment for many malignancies including metastatic melanoma. Acute inflammatory neuropathies, often labelled as Guillain-Barre syndrome, are an uncommon but potentially severe complication of checkpoint immunotherapy with individual cases described but never characterised as a group. We describe a case of acute sensorimotor and autonomic neuropathy following a single dose of combination ipilimumab and nivolumab for metastatic melanoma. A literature search was performed, identifying 14 other cases of acute neuropathy following checkpoint immunotherapy, with the clinical, electrophysiological and laboratory features summarised. Most cases described an acute sensorimotor neuropathy (92%) with hyporeflexia (92%) that could occur from induction up till many weeks after the final dose of therapy. In contrast to Guillain-Barre syndrome, the cerebrospinal fluid (CSF) analysis often shows a lymphocytic picture (50%) and the electrophysiology showed an axonal pattern (55%). Treatment was variable and often in combination. 11 cases received steroid therapy with only 1 death within this group, whereas of the 4 patients who did not receive steroid therapy there were 3 deaths. In conclusion checkpoint immunotherapy - induced acute neuropathies are distinct from and progress differently to Guillain-Barre syndrome. As with other immunotherapy related adverse events corticosteroid therapy should be initiated in addition to usual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune-mediated neuropathies our experience over 3 years

Directory of Open Access Journals (Sweden)

Sadanandavalli Retnaswami Chandra

2018-01-01

Full Text Available Introduction: Immune-mediated peripheral neuropathy is the term applied to a spectrum of peripheral nerve disorders where immune dysregulation plays a role. Therefore, they are treatable. We analyzed the cases seen in the past 3 years by us and evaluated the clinical, laboratory, and outcome parameters in these patients. Patients and Methods: Consecutive patients seen by the authors and diagnosed as immune-mediated neuropathy were analyzed for etiology, pathology, and outcome assessed. Results: A total of sixty patients, 31 acute and 29 chronic neuropathies, were identified. Their subtypes treatment and outcome assessed. Males were significantly more in both acute and chronic cases. Miller Fisher 4, AMAN 1, paraplegic type 1, motor dominant type 19, Sensory-motor 1, MADSAM 3, Bifacial 2. Nonsystemic vasculitis was seen in 16 out of 29 chronic neuropathy and HIV, POEMS, and diabetes mellitus one each. Discussion: There is a spectrum of immune-mediated neuropathy which varies in clinical course, response to treatment, etc., Small percentage of uncommon cases are seen. In this group, mortality was nil and morbidity was minimal. Conclusion: Immune-mediated neuropathies are treatable and hence should be diagnosed early for good quality outcome.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

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Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

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Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Penicillamin-induced neuropathy in rheumatoid arthritis

DEFF Research Database (Denmark)

Pedersen, P B; Hogenhaven, H

1990-01-01

A case of penicillamin-induced severe polyradiculopathy in rheumatoid arthritis is presented. The neuropathy was of demyelinating type, purely motor, proximal and clinically fully reversible when the drug ceased. In case of a progressive neuropathy, during penicillamin treatment, this adverse eff...... effect should be born in mind, and discontinuation of the drug considered....

Approach to Peripheral Neuropathy for the Primary Care Clinician.

Science.gov (United States)

Doughty, Christopher T; Seyedsadjadi, Reza

2018-02-02

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

Carcinomatous versus radiation-induced brachial plexus neuropathy in breast cancer

International Nuclear Information System (INIS)

Bagley, F.H.; Walsh, J.W.; Cady, B.; Salzman, F.A.; Oberfield, R.A.; Pazianos, A.G.

1978-01-01

A retrospective study was performed of 18 women in whom ipsilateral brachial plexus neuropathy developed after treatment for carcinoma of the breast. In the absence of metastatic tumor elsewhere, the only distinguishing feature between carcinomatous neuropathy and radiation-induced neuropathy was the symptom-free interval after mastectomy and radiation therapy. Women with an interval of less than a year have radiation-induced neuropathy. Brachial plexus exploration in difficult diagnostic situations will permit early treatment and avoid debilitating loss of function. Brachial plexus exploration for biopsy is safe and free of complications if performed carefully. Treatment of carcinomatous neuropathy is most likely to succeed if the tumor is hormonally sensitive, but radiotherapy may also be effective. Treatment of radiation-induced neuropathy remains largely ineffective

Peripheral neuropathy in thalassemia

International Nuclear Information System (INIS)

Sawaya, Raja A.; Tahir, A.; Zahad, L.

2006-01-01

Patients with thalassemia may complain of numbness and weakness of lower extremities. The aim of the study was to determine whether these patients suffer from a polyneuropathy and to determine any contributing factors for the development of neuropathy. We examined 30 patients with thalasemia major and intermedia, clinically and electrophysiologically. We correlated these findings with demographics, blood status and treatment and compared electrophysiologic data with 30 age and sex matched normal subjects or historical controls. We found that 78% of thalassemia patients suffer from a mild sensory polyneuropathy. The neuropathy seemed to be worse in the intermedia type. Thalassemia patients who received blood transfusions and deferoaximine had better nerve faction than those who did not, irrespective of the dose of the deferoxamine. The neuropathy was worse for the older patients, irrespective of the sex. The hemoglobin level, and the fact that some patients underwent spleenctomy, did not affect the status of the patient's nerves. Patients with thalassemia may suffer from a sensor polyneuropathy especially as they grow older and they are not optimally treated. (author)

Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

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Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

2017-01-01

To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

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Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

A computational model of human auditory signal processing and perception

DEFF Research Database (Denmark)

Jepsen, Morten Løve; Ewert, Stephan D.; Dau, Torsten

2008-01-01

A model of computational auditory signal-processing and perception that accounts for various aspects of simultaneous and nonsimultaneous masking in human listeners is presented. The model is based on the modulation filterbank model described by Dau et al. [J. Acoust. Soc. Am. 102, 2892 (1997...... discrimination with pure tones and broadband noise, tone-in-noise detection, spectral masking with narrow-band signals and maskers, forward masking with tone signals and tone or noise maskers, and amplitude-modulation detection with narrow- and wideband noise carriers. The model can account for most of the key...... properties of the data and is more powerful than the original model. The model might be useful as a front end in technical applications....

An analysis of nonlinear dynamics underlying neural activity related to auditory induction in the rat auditory cortex.

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Noto, M; Nishikawa, J; Tateno, T

2016-03-24

A sound interrupted by silence is perceived as discontinuous. However, when high-intensity noise is inserted during the silence, the missing sound may be perceptually restored and be heard as uninterrupted. This illusory phenomenon is called auditory induction. Recent electrophysiological studies have revealed that auditory induction is associated with the primary auditory cortex (A1). Although experimental evidence has been accumulating, the neural mechanisms underlying auditory induction in A1 neurons are poorly understood. To elucidate this, we used both experimental and computational approaches. First, using an optical imaging method, we characterized population responses across auditory cortical fields to sound and identified five subfields in rats. Next, we examined neural population activity related to auditory induction with high temporal and spatial resolution in the rat auditory cortex (AC), including the A1 and several other AC subfields. Our imaging results showed that tone-burst stimuli interrupted by a silent gap elicited early phasic responses to the first tone and similar or smaller responses to the second tone following the gap. In contrast, tone stimuli interrupted by broadband noise (BN), considered to cause auditory induction, considerably suppressed or eliminated responses to the tone following the noise. Additionally, tone-burst stimuli that were interrupted by notched noise centered at the tone frequency, which is considered to decrease the strength of auditory induction, partially restored the second responses from the suppression caused by BN. To phenomenologically mimic the neural population activity in the A1 and thus investigate the mechanisms underlying auditory induction, we constructed a computational model from the periphery through the AC, including a nonlinear dynamical system. The computational model successively reproduced some of the above-mentioned experimental results. Therefore, our results suggest that a nonlinear, self

Autonomic Neuropathy in Diabetes Mellitus

OpenAIRE

Verrotti, Alberto; Prezioso, Giovanni; Scattoni, Raffaella; Chiarelli, Francesco

2014-01-01

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes, often overlooked and misdiagnosed. It is a systemic-wide disorder that may be asymptomatic in the early stages. The most studied and clinically important form of DAN is cardiovascular autonomic neuropathy defined as the impairment of autonomic control of the cardiovascular system in patients with diabetes after exclusion of other causes. The reported prevalence of DAN varies widely depending on inconsistent ...

Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in mouse cochlea.

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Zhang, Zhi-Jian; Guan, Hong-Xia; Yang, Kun; Xiao, Bo-Kui; Liao, Hua; Jiang, Yang; Zhou, Tao; Hua, Qing-Quan

2017-10-01

This study aimed in fully investigating the toxicities of ouabain to mouse cochlea and the related cellular environment, and providing an optimal animal model system for cell transplantation in the treatment of auditory neuropathy (AN) and sensorineural hearing loss (SNHL). Different dosages of ouabain were applied to mouse round window. The auditory brainstem responses and distortion product otoacoustic emissions were used to evaluate the cochlear function. The immunohistochemical staining and cochlea surface preparation were performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair cells. Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and permanently destroyed SGNs and their functions, while leaving the hair cells relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and induced significant loss of Schwann cells started as early as 7 days and with further damages at 14 and 30 days after ouabain exposure. The application of ouabain to mouse round window induces damages of SGNs and Schwann cells in a dose- and time-dependent manner, this study established a reliable and accurate animal model system of AN and SNHL.

System identification of perilymphatic fistula in an animal model

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Wall, C. 3rd; Casselbrant, M. L.

1992-01-01

An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans.

Animal models of sarcoidosis.

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Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

2017-03-01

Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

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Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

Auditory and audio-visual processing in patients with cochlear, auditory brainstem, and auditory midbrain implants: An EEG study.

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Schierholz, Irina; Finke, Mareike; Kral, Andrej; Büchner, Andreas; Rach, Stefan; Lenarz, Thomas; Dengler, Reinhard; Sandmann, Pascale

2017-04-01

There is substantial variability in speech recognition ability across patients with cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs). To better understand how this variability is related to central processing differences, the current electroencephalography (EEG) study compared hearing abilities and auditory-cortex activation in patients with electrical stimulation at different sites of the auditory pathway. Three different groups of patients with auditory implants (Hannover Medical School; ABI: n = 6, CI: n = 6; AMI: n = 2) performed a speeded response task and a speech recognition test with auditory, visual, and audio-visual stimuli. Behavioral performance and cortical processing of auditory and audio-visual stimuli were compared between groups. ABI and AMI patients showed prolonged response times on auditory and audio-visual stimuli compared with NH listeners and CI patients. This was confirmed by prolonged N1 latencies and reduced N1 amplitudes in ABI and AMI patients. However, patients with central auditory implants showed a remarkable gain in performance when visual and auditory input was combined, in both speech and non-speech conditions, which was reflected by a strong visual modulation of auditory-cortex activation in these individuals. In sum, the results suggest that the behavioral improvement for audio-visual conditions in central auditory implant patients is based on enhanced audio-visual interactions in the auditory cortex. Their findings may provide important implications for the optimization of electrical stimulation and rehabilitation strategies in patients with central auditory prostheses. Hum Brain Mapp 38:2206-2225, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evaluation of peripheral compression and auditory nerve fiber intensity coding using auditory steady-state responses

DEFF Research Database (Denmark)

Encina Llamas, Gerard; M. Harte, James; Epp, Bastian

2015-01-01

. Evaluation of these properties provides information about the health state of the system. It has been shown that a loss of outer hair cells leads to a reduction in peripheral compression. It has also recently been shown in animal studies that noise over-exposure, producing temporary threshold shifts, can....... The results indicate that the slope of the ASSR level growth function can be used to estimate peripheral compression simultaneously at four frequencies below 60 dB SPL, while the slope above 60 dB SPL may provide information about the integrity of intensity coding of low-SR fibers.......The compressive nonlinearity of the auditory system is assumed to be an epiphenomenon of a healthy cochlea and, particularly, of outer-hair cell function. Another ability of the healthy auditory system is to enable communication in acoustical environments with high-level background noises...

Infectious optic neuropathies: a clinical update

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Kahloun, Rim; Abroug, Nesrine; Ksiaa, Imen; Mahmoud, Anis; Zeghidi, Hatem; Zaouali, Sonia; Khairallah, Moncef

2015-01-01

Different forms of optic neuropathy causing visual impairment of varying severity have been reported in association with a wide variety of infectious agents. Proper clinical diagnosis of any of these infectious conditions is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular findings. Diagnosis is confirmed by serologic testing and polymerase chain reaction in selected cases. Treatment of infectious optic neuropathies involves the use of specific anti-infectious drugs and corticosteroids to suppress the associated inflammatory reaction. The visual prognosis is generally good, but persistent severe vision loss with optic atrophy can occur. This review presents optic neuropathies caused by specific viral, bacterial, parasitic, and fungal diseases. PMID:28539795

Incidence and risk of peripheral neuropathy with nab-paclitaxel in patients with cancer: a meta-analysis.

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Peng, L; Bu, Z; Ye, X; Zhou, Y; Zhao, Q

2017-09-01

Nab-paclitaxel, a Cremophor EL-free formulation of paclitaxel, is used to treat various malignancies. Peripheral neuropathy is one of its major toxicities, although the overall incidence remains unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy in cancer patients treated with nab-paclitaxel and to compare the relative risk (RR) with conventional taxanes. The electronic databases were searched for relevant clinical trials. Eligible studies included phase II and III prospective clinical trials of cancer patients treated with nab-paclitaxel with toxicity profile on peripheral neuropathy. Statistical analyses were done to calculate summary incidences, RRs and 95% confidence intervals (CI), using fixed-effects or random-effects models based on the heterogeneity of the included studies. Nineteen trials were selected for the meta-analysis, yielding a total of 2878 cancer patients. The overall incidences of peripheral neuropathy (all-grade) was 51.0% (95% CI: 45.1-57.6%), and that of high-grade peripheral neuropathy was 12.4% (9.8-15.7%). The RRs of peripheral neuropathy of nab-paclitaxel compared to taxanes were not increased for all-grade and high-grade peripheral neuropathy. Nab-paclitaxel is associated with an increased risk of developing peripheral neuropathy. Future clinical studies are still needed to investigate the risk reduction and possible use of nab-paclitaxel. © 2015 John Wiley & Sons Ltd.

Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

Science.gov (United States)

Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

2018-01-01

Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly

Vasculitic peripheral neuropathy

Directory of Open Access Journals (Sweden)

Mona Amini

2014-02-01

Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

HSPB1 mutations causing hereditary neuropathy in humans disrupt non-cell autonomous protection of motor neurons.

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Heilman, Patrick L; Song, SungWon; Miranda, Carlos J; Meyer, Kathrin; Srivastava, Amit K; Knapp, Amy; Wier, Christopher G; Kaspar, Brian K; Kolb, Stephen J

2017-11-01

Heat shock protein beta-1 (HSPB1), is a ubiquitously expressed, multifunctional protein chaperone. Mutations in HSPB1 result in the development of a late-onset, distal hereditary motor neuropathy type II (dHMN) and axonal Charcot-Marie Tooth disease with sensory involvement (CMT2F). The functional consequences of HSPB1 mutations associated with hereditary neuropathy are unknown. HSPB1 also displays neuroprotective properties in many neuronal disease models, including the motor neuron disease amyotrophic lateral sclerosis (ALS). HSPB1 is upregulated in SOD1-ALS animal models during disease progression, predominately in glial cells. Glial cells are known to contribute to motor neuron loss in ALS through a non-cell autonomous mechanism. In this study, we examined the non-cell autonomous role of wild type and mutant HSPB1 in an astrocyte-motor neuron co-culture model system of ALS. Astrocyte-specific overexpression of wild type HSPB1 was sufficient to attenuate SOD1(G93A) astrocyte-mediated toxicity in motor neurons, whereas, overexpression of mutHSPB1 failed to ameliorate motor neuron toxicity. Expression of a phosphomimetic HSPB1 mutant in SOD1(G93A) astrocytes also reduced toxicity to motor neurons, suggesting that phosphorylation may contribute to HSPB1 mediated-neuroprotection. These data provide evidence that astrocytic HSPB1 expression may play a central role in motor neuron health and maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

Science.gov (United States)

Binns-Hall, O; Selvarajah, D; Sanger, D; Walker, J; Scott, A; Tesfaye, S

2018-04-02

To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (Peye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point-of-care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy. © 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Comparison of Efficiencies of Michigan Neuropathy Screening Instrument, Neurothesiometer, and Electromyography for Diagnosis of Diabetic Neuropathy

Directory of Open Access Journals (Sweden)

Turkan Mete

2013-01-01

Full Text Available Aim. This study compares the effectiveness of Michigan Neuropathy Screening Instrument (MNSI, neurothesiometer, and electromyography (EMG in detecting diabetic peripheral neuropathy in patients with diabetes type 2. Materials and Methods. 106 patients with diabetes type 2 treated at the outpatient clinic of Ankara Numune Education and Research Hospital Department of Endocrinology between September 2008 and May 2009 were included in this study. Patients were evaluated by glycemic regulation tests, MNSI (questionnaire and physical examination, EMG (for detecting sensorial and motor defects in right median, ulnar, posterior tibial, and bilateral sural nerves, and neurothesiometer (for detecting alterations in cold and warm sensations as well as vibratory sensations. Results. According to the MNSI score, there was diabetic peripheral neuropathy in 34 (32.1% patients (score ≥2.5. However, when the patients were evaluated by EMG and neurothesiometer, neurological impairments were detected in 49 (46.2% and 79 (74.5% patients, respectively. Conclusion. According to our findings, questionnaires and physical examination often present lower diabetic peripheral neuropathy prevalence. Hence, we recommend that in the evaluation of diabetic patients neurological tests should be used for more accurate results and thus early treatment options to prevent neuropathic complications.

Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography

International Nuclear Information System (INIS)

Keen, Nayela N.; Chin, Cynthia T.; Saloner, David; Steinbach, Lynne S.; Engstrom, John W.

2012-01-01

Early diagnosis of ulnar neuropathy at the elbow is important. Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. The MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively. MRN was performed prospectively on 10 normal volunteers. The MR neurograms included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The sensitivity and specificity of MRN in detecting ulnar neuropathy were determined. The mean ulnar nerve size in the symptomatic and normal groups was 0.12 and 0.06 cm 2 (P 2 , sensitivity was 95% and specificity was 80%. Ulnar nerve size and signal intensity were greater in patients with ulnar neuropathy. MRN is a useful test in evaluating ulnar neuropathy at the elbow. (orig.)

Auditory Reserve and the Legacy of Auditory Experience

Directory of Open Access Journals (Sweden)

Erika Skoe

2014-11-01

Full Text Available Musical training during childhood has been linked to more robust encoding of sound later in life. We take this as evidence for an auditory reserve: a mechanism by which individuals capitalize on earlier life experiences to promote auditory processing. We assert that early auditory experiences guide how the reserve develops and is maintained over the lifetime. Experiences that occur after childhood, or which are limited in nature, are theorized to affect the reserve, although their influence on sensory processing may be less long-lasting and may potentially fade over time if not repeated. This auditory reserve may help to explain individual differences in how individuals cope with auditory impoverishment or loss of sensorineural function.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy

DEFF Research Database (Denmark)

Hansen, C.S.; Jensen, T.M.; Jensen, J.S.

2015-01-01

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy...... and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen......-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy...

Animal Models in Burn Research

Science.gov (United States)

Abdullahi, A.; Amini-Nik, S.; Jeschke, M.G

2014-01-01

Burn injury is a severe form of trauma affecting more than two million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury; to elucidate the pathophysiology and explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review paper aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research. PMID:24714880

Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management

Directory of Open Access Journals (Sweden)

Berry S

2017-09-01

Full Text Available Shauna Berry,1 Weijie V Lin,2 Ama Sadaka,1 Andrew G Lee1–7 1Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA; 2Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA; 3Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch (UTMB, Galveston, TX, USA; 4Department of Ophthalmology, 5Department of Neurology, 6Department of Neurosurgery, Weill Cornell Medicine, Houston, TX, USA; 7Department of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Nonarteritic anterior ischemic optic neuropathy (NAION is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea. The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION. Keywords: anterior ischemic optic neuropathy, nonarteritic anterior ischemic optic neuropathy, ischemic optic neuropathy

Quality assessment of online patient education resources for peripheral neuropathy.

Science.gov (United States)

Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M

2013-03-01

Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. © 2013 Peripheral Nerve Society.

Further evidence for a fluid pathway during bone conduction auditory stimulation.

Science.gov (United States)

Sohmer, Haim; Freeman, Sharon

2004-07-01

This study was designed to evaluate the suggestion that during bone vibrator stimulation on skull bone (bone conduction auditory stimulation), a major connection between the site of the bone vibrator and the inner ear is a fluid pathway. A series of experiments were conducted on pairs of animals (rats or guinea pigs). The cranial cavities of each pair of animals were coupled by means of a saline filled plastic tube sealed into a craniotomy in the skull of each animal. In response to bone conduction click stimulation to the skull bone of animal I, auditory nerve-brainstem evoked responses could be recorded in animal II. Various procedures showed that these responses were initiated in animal II in response to audio-frequency sound pressures generated within the cranial cavity of animal I by the bone conduction stimulation and transferred to the cranial cavity of animal II through the fluid in the plastic tube: they were not responses to air conducted sounds generated by the bone vibrator, were not induced in animal II by vibrations conveyed to it by the plastic tube and were not electrically conducted activity from animal I. Exposing the fluid in the tube to air was not accompanied by any change in threshold. These experiments confirm that during bone conduction stimulation on the skull, audio-frequency sound pressures (alternating condensations and rarefactions) can be conveyed by a fluid pathway to the cochlea and stimulate it.

Mosaic evolution of the mammalian auditory periphery.

Science.gov (United States)

Manley, Geoffrey A

2013-01-01

The classical mammalian auditory periphery, i.e., the type of middle ear and coiled cochlea seen in modern therian mammals, did not arise as one unit and did not arise in all mammals. It is also not the only kind of auditory periphery seen in modern mammals. This short review discusses the fact that the constituents of modern mammalian auditory peripheries arose at different times over an extremely long period of evolution (230 million years; Ma). It also attempts to answer questions as to the selective pressures that led to three-ossicle middle ears and the coiled cochlea. Mammalian middle ears arose de novo, without an intermediate, single-ossicle stage. This event was the result of changes in eating habits of ancestral animals, habits that were unrelated to hearing. The coiled cochlea arose only after 60 Ma of mammalian evolution, driven at least partly by a change in cochlear bone structure that improved impedance matching with the middle ear of that time. This change only occurred in the ancestors of therian mammals and not in other mammalian lineages. There is no single constellation of structural features of the auditory periphery that characterizes all mammals and not even all modern mammals.

Modeling auditory-nerve responses to electrical stimulation

DEFF Research Database (Denmark)

Joshi, Suyash Narendra; Dau, Torsten; Epp, Bastian

2014-01-01

μs, which is large enough to affect the temporal coding of sounds and hence, potentially, the communication abilities of the CI listener. In the present study, two recently proposed models of electric stimulation of the AN [1,2] were considered in terms of their efficacy to predict the spike timing...... for anodic and cathodic stimulation of the AN of cat [3]. The models’ responses to the electrical pulses of various shapes [4,5,6] were also analyzed. It was found that, while the models can account for the firing rates in response to various biphasic pulse shapes, they fail to correctly describe the timing......Cochlear implants (CI) directly stimulate the auditory nerve (AN), bypassing the mechano-electrical transduction in the inner ear. Trains of biphasic, charge balanced pulses (anodic and cathodic) are used as stimuli to avoid damage of the tissue. The pulses of either polarity are capable...

Subretinal fluid is common in experimental non-arteritic anterior ischemic optic neuropathy

Science.gov (United States)

Yu, C; Ho, J K; Liao, Y J

2014-01-01

Purpose Anterior ischemic optic neuropathy (AION) is an important cause of acute vision loss for which several animal models exist. It has been associated with subretinal fluid in a previous study on patients but not yet so in animal models. Patients and Methods A patient presented with acute non-arteritic AION (NAION) and underwent ophthalmic evaluation and testing including fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT). On the basis of the patient's findings, we used SD-OCT circular and volume scans to analyze retinal changes in a murine model of NAION. Results One week after left eye vision loss, the patient had clinical and imaging findings consistent with NAION. On SD-OCT, there was prominent peripapillary retinal thickening consistent with intra-retinal edema and sub-foveolar fluid. Inspired by the findings in human AION, we looked for similar changes in murine NAION using SD-OCT. The circular scan did not adequately detect the presence of subretinal fluid. Using the 25-line scan, which covered a larger part of the posterior pole, we found that 100% of murine AION resulted in subretinal fluid at day 1. The subretinal fluid resolved by week 1. Conclusion This study detailed a case of clinical NAION associated with intra-retinal and subretinal fluid. We also found that subretinal fluid was common in murine photochemical thrombosis model of AION and could be found far away from the optic disc. PMID:25257770

Peripheral Auditory Mechanisms

CERN Document Server

Hall, J; Hubbard, A; Neely, S; Tubis, A

1986-01-01

How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

[A rare cause of optic neuropathy: Cassava].

Science.gov (United States)

Zeboulon, P; Vignal-Clermont, C; Baudouin, C; Labbé, A

2016-06-01

Cassava root is a staple food for almost 500 million people worldwide. Excessive consumption of it is a rare cause of optic neuropathy. Ten patients diagnosed with cassava root related optic neuropathy were included in this retrospective study. Diagnostic criteria were a bilateral optic neuropathy preceded by significant cassava root consumption. Differential diagnoses were excluded through a neuro-ophthalmic examination, blood tests and a brain MRI. All patients had visual field examination and OCT retinal nerve fiber layer (RNFL) analysis as well as an evaluation of their cassava consumption. All patients had a bilateral optic nerve head atrophy or pallor predominantly located into the temporal sector. Visual field defects consisted of a central or cecocentral scotoma for all patients. RNFL showed lower values only in the temporal sector. Mean duration of cassava consumption prior to the appearance of visual symptoms was 22.7±11.2 years with a mean of 2.57±0.53 cassava-based meals per week. Cassava related optic neuropathy is possibly due to its high cyanide content and enabled by a specific amino-acid deficiency. Cassava root chronic consumption is a rare, underappreciated cause of optic neuropathy and its exact mechanism is still uncertain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Familial Idiopathic Cranial Neuropathy in a Chinese Family.

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Zhang, Li; Liang, Jianfeng; Yu, Yanbing

Cranial neuropathy is usually idiopathic and familial cases are uncommon. We describe a family with 5 members with cranial neuropathy over 3 generations. All affected patients were women, indicating an X-linked dominant or an autosomal dominant mode of inheritance. Our cases and a review of the literature suggest that familial idiopathic cranial neuropathy is a rare condition which may be related to autosomal dominant vascular disorders (e.g. vascular tortuosity, sclerosis, elongation or extension), small posterior cranial fossas, anatomical variations of the posterior circulation, hypersensitivity of cranial nerves and other abnormalities. Moreover, microvascular decompression is the treatment of choice because vascular compression is the main factor in the pathogenesis. To the best of our knowledge, this is the first report of familial cranial neuropathy in China.

Hearing loss patterns after cochlear implantation via the round window in an animal model.

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Attias, Joseph; Hod, Roy; Raveh, Eyal; Mizrachi, Aviram; Avraham, Karen B; Lenz, Danielle R; Nageris, Ben I

2016-01-01

The mechanism and the type of hearing loss induced by cochlear implants are mostly unknown. Therefore, this study evaluated the impact and type of hearing loss induced by each stage of cochlear implantation surgery in an animal model. Original basic research animal study. The study was conducted in a tertiary, university-affiliated medical center in accordance with the guidelines of the Institutional Animal Care and Use Committee. Cochlear implant electrode array was inserted via the round window membrane in 17 ears of 9 adult-size fat sand rats. In 7 ears of 5 additional animals round window incision only was performed, followed by patching with a small piece of periosteum (control). Hearing thresholds to air (AC) and bone conduction (BC), clicks, 1 kHz and 6 kHz tone bursts were measured by auditory brainstem evoked potential, before, during each stage of surgery and one week post-operatively. In addition, inner ear histology was performed. The degree of hearing loss increased significantly from baseline throughout the stages of cochlear implantation surgery and up to one week after (plosses were found for 1-kHz and 6-kHz frequencies. The hearing loss was not associated with significant changes in inner ear histology. Hearing loss following cochlear implantation in normal hearing animals is progressive and of mixed type, but mainly conductive. Changes in the inner-ear mechanism are most likely responsible for the conductive hearing loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Posttraining handling facilitates memory for auditory-cue fear conditioning in rats.

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Hui, Isabel R; Hui, Gabriel K; Roozendaal, Benno; McGaugh, James L; Weinberger, Norman M

2006-09-01

A large number of studies have indicated that stress exposure or the administration of stress hormones and other neuroactive drugs immediately after a learning experience modulates the consolidation of long-term memory. However, there has been little investigation into how arousal induced by handling of the animals in order to administer these drugs affects memory. Therefore, the present study examined whether the posttraining injection or handling procedure per se affects memory of auditory-cue classical fear conditioning. Male Sprague-Dawley rats, which had been pre-handled on three days for 1 min each prior to conditioning, received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by either a subcutaneous injection of a vehicle solution or brief handling without injection. A control group was placed back into their home cages without receiving any posttraining treatment. Retention was tested 24 h later in a novel chamber and suppression of ongoing motor behavior during a 10-s presentation of the auditory-cue served as the measure of conditioned fear. Animals that received posttraining injection or handling did not differ from each other but showed significantly less stimulus-induced movement compared to the non-handled control group. These findings thus indicate that the posttraining injection or handling procedure is sufficiently arousing or stressful to facilitate memory consolidation of auditory-cue classical fear conditioning.

Animal models of cerebral ischemia

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Khodanovich, M. Yu.; Kisel, A. A.

2015-11-01

Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

Auditory-somatosensory bimodal stimulation desynchronizes brain circuitry to reduce tinnitus in guinea pigs and humans.

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Marks, Kendra L; Martel, David T; Wu, Calvin; Basura, Gregory J; Roberts, Larry E; Schvartz-Leyzac, Kara C; Shore, Susan E

2018-01-03

The dorsal cochlear nucleus is the first site of multisensory convergence in mammalian auditory pathways. Principal output neurons, the fusiform cells, integrate auditory nerve inputs from the cochlea with somatosensory inputs from the head and neck. In previous work, we developed a guinea pig model of tinnitus induced by noise exposure and showed that the fusiform cells in these animals exhibited increased spontaneous activity and cross-unit synchrony, which are physiological correlates of tinnitus. We delivered repeated bimodal auditory-somatosensory stimulation to the dorsal cochlear nucleus of guinea pigs with tinnitus, choosing a stimulus interval known to induce long-term depression (LTD). Twenty minutes per day of LTD-inducing bimodal (but not unimodal) stimulation reduced physiological and behavioral evidence of tinnitus in the guinea pigs after 25 days. Next, we applied the same bimodal treatment to 20 human subjects with tinnitus using a double-blinded, sham-controlled, crossover study. Twenty-eight days of LTD-inducing bimodal stimulation reduced tinnitus loudness and intrusiveness. Unimodal auditory stimulation did not deliver either benefit. Bimodal auditory-somatosensory stimulation that induces LTD in the dorsal cochlear nucleus may hold promise for suppressing chronic tinnitus, which reduces quality of life for millions of tinnitus sufferers worldwide. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Pediatric sciatic neuropathies due to unusual vascular causes

NARCIS (Netherlands)

Srinivasan, Jayashri; Escolar, Diane; Ryan, Monique; Darras, Basil; Jones, H. Royden

Four cases of pediatric sciatic neuropathies due to unusual vascular mechanisms are reported. Pediatric sciatic neuropathies were seen after umbilical artery catheterization, embolization of arteriovenous malformation, meningococcemia, and hypereosinophilic vasculitis. Electrophysiologic studies

Vitamin B supplementation for diabetic peripheral neuropathy.

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Jayabalan, Bhavani; Low, Lian Leng

2016-02-01

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. Copyright © Singapore Medical Association.

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy.

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Gao, Fei; Wang, Guangbin; Ma, Wen; Ren, Fuxin; Li, Muwei; Dong, Yuling; Liu, Cheng; Liu, Bo; Bai, Xue; Zhao, Bin; Edden, Richard A E

2015-02-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central auditory system. Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis. Edited magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, is the most widely used technique for detecting GABA in the human brain. However, to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis. In this study, sixteen patients with presbycusis (5 males/11 females, mean age 63.1 ± 2.6 years) and twenty healthy controls (6 males/14 females, mean age 62.5 ± 2.3 years) underwent audiological and MRS examinations. Pure tone audiometry from 0.125 to 8 kHz and tympanometry were used to assess the hearing abilities of all subjects. The pure tone average (PTA; the average of hearing thresholds at 0.5, 1, 2 and 4 kHz) was calculated. The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 × 3 × 3 cm(3) volumes centered on the left and right Heschl's gyri. GABA+ concentrations were significantly lower in the presbycusis group compared to the control group (left auditory regions: p = 0.002, right auditory regions: p = 0.008). Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group (r = -0.57, p = 0.02), while a similar trend was found in the control group (r = -0.40, p = 0.08). These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis and suggest a potential treatment target for presbycusis. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnostic imaging of compression neuropathy

International Nuclear Information System (INIS)

Weishaupt, D.; Andreisek, G.

2007-01-01

Compression-induced neuropathy of peripheral nerves can cause severe pain of the foot and ankle. Early diagnosis is important to institute prompt treatment and to minimize potential injury. Although clinical examination combined with electrophysiological studies remain the cornerstone of the diagnostic work-up, in certain cases, imaging may provide key information with regard to the exact anatomic location of the lesion or aid in narrowing the differential diagnosis. In other patients with peripheral neuropathies of the foot and ankle, imaging may establish the etiology of the condition and provide information crucial for management and/or surgical planning. MR imaging and ultrasound provide direct visualization of the nerve and surrounding abnormalities. Bony abnormalities contributing to nerve compression are best assessed by radiographs and CT. Knowledge of the anatomy, the etiology, typical clinical findings, and imaging features of peripheral neuropathies affecting the peripheral nerves of the foot and ankle will allow for a more confident diagnosis. (orig.) [de

Acute optic neuropathy associated with a novel MFN2 mutation.

Science.gov (United States)

Leonardi, Luca; Marcotulli, Christian; Storti, Eugenia; Tessa, Alessandra; Serrao, Mariano; Parisi, Vincenzo; Santorelli, F M; Pierelli, Francesco; Casali, Carlo

2015-07-01

Mutations in the mitofusin 2 (MFN2) gene cause CMT2A the most common form of autosomal dominant axonal Charcot-Marie-Tooth (CMT). In addition, mutations in MFN2 have been shown to be responsible for Hereditary Motor Sensory Neuropathy type VI (HSMN VI), a rare early-onset axonal CMT associated with optic neuropathy. Most reports of HMSN VI presented with a sub-acute form of optic neuropathy. Herein, we report a CMT2A patient, who developed very rapidly progressing severe optic neuropathy. A 40-year-old Caucasian man was evaluated for gait disturbance and lower limbs weakness, slowly progressed over the last 2 years. Due to clinical data and family history, a diagnosis of CMT2 was made. The novel heterozygous c.775C > T (p.Arg259Cys) mutation in MFN2 was detected in the patient and his clinical affected mother. Interestingly, the patient developed a severe sudden bilateral visual deterioration few years early, with clinical and instrumental picture suggestive of acute bilateral optic neuropathy. Our report expands the spectrum of MFN2-related manifestation because it indicates that visual symptoms of HMSN VI may enter in the differential with acquired or hereditary acute optic neuropathies, and that severe optic neuropathy is not invariably an early manifestation of the disease but may occur as disease progressed. This report could have an impact on clinicians who evaluate patients with otherwise unexplainable bilateral acute-onset optic neuropathy, especially if associated with a motor and sensory axonal neuropathy.

Weak responses to auditory feedback perturbation during articulation in persons who stutter: evidence for abnormal auditory-motor transformation.

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Shanqing Cai

Full Text Available Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking functions abnormally in the speech motor systems of persons who stutter (PWS. Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants' compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls' and had close-to-normal latencies (∼150 ms, but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05. Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands.

Modeling auditory processing of amplitude modulation I. Detection and masking with narrow-band carriers

NARCIS (Netherlands)

Dau, T.; Kollmeier, B.; Kohlrausch, A.G.

1997-01-01

This paper presents a quantitative model for describing data from modulation-detection and modulation-masking experiments, which extends the model of the "effective" signal processing of the auditory system described in Dau et al. [J. Acoust. Soc. Am. 99, 3615–3622 (1996)]. The new element in the

Sensory neuropathy in two Border collie puppies.

Science.gov (United States)

Vermeersch, K; Van Ham, L; Braund, K G; Bhatti, S; Tshamala, M; Chiers, K; Schrauwen, E

2005-06-01

A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

Brainstem auditory evoked potentials in horses

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Juliana Almeida Nogueira da Gama

2016-04-01

Full Text Available ABSTRACT: The brainstem auditory evoked potential (BAEP evaluates the integrity of the auditory pathways to the brainstem. The aim of this study was to evoke BAEPs in 21 clinically normal horses. The animals were sedated with detomidine hydrochloride (0.013mg.kg-1 BW. Earphones were inserted and rarefaction clicks at 90 dB and noise masking at 40 dB were used. After performing the test, the latencies of waves (I, II, III, IV, and V and interpeaks(I-III, III-V, and I-V were identified. The mean latencies of the waves were as follows: wave I, 2.4 ms; wave II, 2.24 ms; wave III, 3.61ms; wave IV, 4.61ms; and wave V, 5.49ms. The mean latencies of the interpeaks were as follows: I-III, 1.37ms; III-V, 1.88ms; and I-V, 3.26ms. This is the first study using BAEPs in horses in Brazil, and the observed latencies will be used as normative data for the interpretation of tests performed on horses with changes related to auditory system or neurologic abnormalities.

Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

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Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

2017-10-01

Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy.

Science.gov (United States)

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Steven L

2015-12-01

Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION.

Does Peripheral Neuropathy Associate with Cranial Nerves Neuropathy in Type 2 diabetes Patients?

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Walaa Fadhil Jalal

2017-02-01

Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.

Tinnitus intensity dependent gamma oscillations of the contralateral auditory cortex.

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Elsa van der Loo

Full Text Available BACKGROUND: Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. METHODS AND FINDINGS: In unilateral tinnitus patients (N = 15; 10 right, 5 left source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05. CONCLUSION: Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.

The Central Auditory Processing Kit[TM]. Book 1: Auditory Memory [and] Book 2: Auditory Discrimination, Auditory Closure, and Auditory Synthesis [and] Book 3: Auditory Figure-Ground, Auditory Cohesion, Auditory Binaural Integration, and Compensatory Strategies.

Science.gov (United States)

Mokhemar, Mary Ann

This kit for assessing central auditory processing disorders (CAPD), in children in grades 1 through 8 includes 3 books, 14 full-color cards with picture scenes, and a card depicting a phone key pad, all contained in a sturdy carrying case. The units in each of the three books correspond with auditory skill areas most commonly addressed in…

Auditory and Visual Sensations

CERN Document Server

Ando, Yoichi

2010-01-01

Professor Yoichi Ando, acoustic architectural designer of the Kirishima International Concert Hall in Japan, presents a comprehensive rational-scientific approach to designing performance spaces. His theory is based on systematic psychoacoustical observations of spatial hearing and listener preferences, whose neuronal correlates are observed in the neurophysiology of the human brain. A correlation-based model of neuronal signal processing in the central auditory system is proposed in which temporal sensations (pitch, timbre, loudness, duration) are represented by an internal autocorrelation representation, and spatial sensations (sound location, size, diffuseness related to envelopment) are represented by an internal interaural crosscorrelation function. Together these two internal central auditory representations account for the basic auditory qualities that are relevant for listening to music and speech in indoor performance spaces. Observed psychological and neurophysiological commonalities between auditor...

Diagnosing ulnar neuropathy at the elbow using magnetic resonance neurography

Energy Technology Data Exchange (ETDEWEB)

Keen, Nayela N.; Chin, Cynthia T.; Saloner, David; Steinbach, Lynne S. [University of California San Francisco, Dept of Radiology and Biomedical Imaging, San Francisco, CA (United States); Engstrom, John W. [University of California San Francisco, Department of Neurology, San Francisco, CA (United States)

2012-04-15

Early diagnosis of ulnar neuropathy at the elbow is important. Magnetic resonance neurography (MRN) images peripheral nerves. We evaluated the usefulness of elbow MRN in diagnosing ulnar neuropathy at the elbow. The MR neurograms of 21 patients with ulnar neuropathy were reviewed retrospectively. MRN was performed prospectively on 10 normal volunteers. The MR neurograms included axial T1 and axial T2 fat-saturated and/or axial STIR sequences. The sensitivity and specificity of MRN in detecting ulnar neuropathy were determined. The mean ulnar nerve size in the symptomatic and normal groups was 0.12 and 0.06 cm{sup 2} (P < 0.001). The mean relative signal intensity in the symptomatic and normal groups was 2.7 and 1.4 (P < 0.01). When using a size of 0.08 cm{sup 2}, sensitivity was 95% and specificity was 80%. Ulnar nerve size and signal intensity were greater in patients with ulnar neuropathy. MRN is a useful test in evaluating ulnar neuropathy at the elbow. (orig.)

Analysis of youtube as a source of information for peripheral neuropathy.

Science.gov (United States)

Gupta, Harsh V; Lee, Ricky W; Raina, Sunil K; Behrle, Brian L; Hinduja, Archana; Mittal, Manoj K

2016-01-01

YouTube is an important resource for patients. No study has evaluated the information on peripheral neuropathy disseminated by YouTube videos. In this study, our aim was to perform a systematic review of information on YouTube regarding peripheral neuropathy. The Web site (www.youtube.com) was searched between September 19 and 21, 2014, for the terms "neuropathy," "peripheral neuropathy," "diabetic neuropathy," "neuropathy causes," and "neuropathy treatment." Two hundred videos met the inclusion criteria. Healthcare professionals accounted for almost half of the treatment videos (41 of 92; 44.6%), and most came from chiropractors (18 of 41; 43.9%). Alternative medicine was cited most frequently among the treatment discussions (54 of 145, 37.2%), followed by devices (38 of 145, 26.2%), and pharmacological treatments (23 of 145, 15.9%). Approximately half of the treatment options discussed in the videos were not evidence-based. Caution should be exercised when YouTube videos are used as a patient resource. © 2015 Wiley Periodicals, Inc.

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

NARCIS (Netherlands)

van Paassen, Barbara W.; van der Kooi, Anneke J.; van Spaendonck-Zwarts, Karin Y.; Verhamme, Camiel; Baas, Frank; de Visser, Marianne

2014-01-01

PMP22 related neuropathies comprise (1) PMP22 duplications leading to Charcot-Marie-Tooth disease type 1A (CMT1A), (2) PMP22 deletions, leading to Hereditary Neuropathy with liability to Pressure Palsies (HNPP), and (3) PMP22 point mutations, causing both phenotypes. Overall prevalence of CMT is

Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

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Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2009-10-15

Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

International Nuclear Information System (INIS)

Small, Juan E.; Gonzalez, Guido E.; Nagao, Karina E.; Walton, David S.; Caruso, Paul A.

2009-01-01

Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences

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Stanislava Knyazeva

2018-01-01

Full Text Available This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman’s population separation model of auditory streaming.

Neuronal Correlates of Auditory Streaming in Monkey Auditory Cortex for Tone Sequences without Spectral Differences.

Science.gov (United States)

Knyazeva, Stanislava; Selezneva, Elena; Gorkin, Alexander; Aggelopoulos, Nikolaos C; Brosch, Michael

2018-01-01

This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman's population separation model of auditory streaming.

Auditory Perceptual Abilities Are Associated with Specific Auditory Experience

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Yael Zaltz

2017-11-01

Full Text Available The extent to which auditory experience can shape general auditory perceptual abilities is still under constant debate. Some studies show that specific auditory expertise may have a general effect on auditory perceptual abilities, while others show a more limited influence, exhibited only in a relatively narrow range associated with the area of expertise. The current study addresses this issue by examining experience-dependent enhancement in perceptual abilities in the auditory domain. Three experiments were performed. In the first experiment, 12 pop and rock musicians and 15 non-musicians were tested in frequency discrimination (DLF, intensity discrimination, spectrum discrimination (DLS, and time discrimination (DLT. Results showed significant superiority of the musician group only for the DLF and DLT tasks, illuminating enhanced perceptual skills in the key features of pop music, in which miniscule changes in amplitude and spectrum are not critical to performance. The next two experiments attempted to differentiate between generalization and specificity in the influence of auditory experience, by comparing subgroups of specialists. First, seven guitar players and eight percussionists were tested in the DLF and DLT tasks that were found superior for musicians. Results showed superior abilities on the DLF task for guitar players, though no difference between the groups in DLT, demonstrating some dependency of auditory learning on the specific area of expertise. Subsequently, a third experiment was conducted, testing a possible influence of vowel density in native language on auditory perceptual abilities. Ten native speakers of German (a language characterized by a dense vowel system of 14 vowels, and 10 native speakers of Hebrew (characterized by a sparse vowel system of five vowels, were tested in a formant discrimination task. This is the linguistic equivalent of a DLS task. Results showed that German speakers had superior formant

The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review.

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Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L

2015-12-01

Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important

Genetics Home Reference: neuropathy, ataxia, and retinitis pigmentosa

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... Twitter Home Health Conditions NARP Neuropathy, ataxia, and retinitis pigmentosa Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that causes a variety ...

The metabolomic signature of Leber's hereditary optic neuropathy reveals endoplasmic reticulum stress.

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Chao de la Barca, Juan Manuel; Simard, Gilles; Amati-Bonneau, Patrizia; Safiedeen, Zainab; Prunier-Mirebeau, Delphine; Chupin, Stéphanie; Gadras, Cédric; Tessier, Lydie; Gueguen, Naïg; Chevrollier, Arnaud; Desquiret-Dumas, Valérie; Ferré, Marc; Bris, Céline; Kouassi Nzoughet, Judith; Bocca, Cinzia; Leruez, Stéphanie; Verny, Christophe; Miléa, Dan; Bonneau, Dominique; Lenaers, Guy; Martinez, M Carmen; Procaccio, Vincent; Reynier, Pascal

2016-11-01

Leber's hereditary optic neuropathy (MIM#535000), the commonest mitochondrial DNA-related disease, is caused by mutations affecting mitochondrial complex I. The clinical expression of the disorder, usually occurring in young adults, is typically characterized by subacute, usually sequential, bilateral visual loss, resulting from the degeneration of retinal ganglion cells. As the precise action of mitochondrial DNA mutations on the overall cell metabolism in Leber's hereditary optic neuropathy is unknown, we investigated the metabolomic profile of the disease. High performance liquid chromatography coupled with tandem mass spectrometry was used to quantify 188 metabolites in fibroblasts from 16 patients with Leber's hereditary optic neuropathy and eight healthy control subjects. Latent variable-based statistical methods were used to identify discriminating metabolites. One hundred and twenty-four of the metabolites were considered to be accurately quantified. A supervised orthogonal partial least squares discriminant analysis model separating patients with Leber's hereditary optic neuropathy from control subjects showed good predictive capability (Q 2cumulated = 0.57). Thirty-eight metabolites appeared to be the most significant variables, defining a Leber's hereditary optic neuropathy metabolic signature that revealed decreased concentrations of all proteinogenic amino acids, spermidine, putrescine, isovaleryl-carnitine, propionyl-carnitine and five sphingomyelin species, together with increased concentrations of 10 phosphatidylcholine species. This signature was not reproduced by the inhibition of complex I with rotenone or piericidin A in control fibroblasts. The importance of sphingomyelins and phosphatidylcholines in the Leber's hereditary optic neuropathy signature, together with the decreased amino acid pool, suggested an involvement of the endoplasmic reticulum. This was confirmed by the significantly increased phosphorylation of PERK and eIF2α, as well as

Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

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Gao, Patrick P; Zhang, Jevin W; Fan, Shu-Juan; Sanes, Dan H; Wu, Ed X

2015-12-01

The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical

Neuroprotective effect of erythropoietin against pressure ulcer in a mouse model of small fiber neuropathy.

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Aurore Danigo

Full Text Available An increased risk of skin pressure ulcers (PUs is common in patients with sensory neuropathies, including those caused by diabetes mellitus. Recombinant human erythropoietin (rhEPO has been shown to protect the skin against PUs developed in animal models of long-term diabetes. The aim of this work was to determine whether rhEPO could prevent PU formation in a mouse model of drug-induced SFN. Functional SFN was induced by systemic injection of resiniferatoxin (RTX, 50 µg/kg, i.p.. RhEPO (3000 UI/kg, i.p. was given the day before RTX injection and then every other day. Seven days after RTX administration, PUs were induced by applying two magnetic plates on the dorsal skin. RTX-treated mice expressed thermal and mechanical hypoalgesia and showed calcitonin gene-related peptide (CGRP and substance P (SP depletion without nerve degeneration or vascular dysfunction. RTX mice developed significantly larger stage 2 PUs than Vehicle mice. RhEPO prevented thermal and mechanical hypoalgesia and neuropeptide depletion in small nerve fibers. RhEPO increased hematocrit and altered endothelium-dependent vasodilatation without any effect on PU formation in Vehicle mice. The characteristics of PUs in RTX mice treated with rhEPO and Vehicle mice were found similar. In conclusion, RTX appeared to increased PU development through depletion of CGRP and SP in small nerve fibers, whereas systemic rhEPO treatment had beneficial effect on peptidergic nerve fibers and restored skin protective capacities against ischemic pressure. Our findings support the evaluation of rhEPO and/or its non-hematopoietic analogs in preventing to prevent PUs in patients with SFN.

Ophthalmople gic cranial neuropathy: clinical case

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N. S. Dozorova; A. S. Kotov; E. V. Mukhina

2018-01-01

Ophthalmoplegic cranial neuropathy (OCN) is a disease with unknown etiology, which manifests itself by episodes of intense headache, accompanied by completely or partially reversible dysfunction of the oculomotor nerve: ptosis, mydriasis and ophthalmoplegia. It is assumed that the pathology is demyelinating in nature, therefore in the International classification of headaches OCN excluded from rubric migraine and related to the painful cranial neuropathies. The question of the prevention and ...

Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model

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Troy A Hackett

2014-04-01

Full Text Available Our working model of the primate auditory cortex recognizes three major regions (core, belt, parabelt, subdivided into thirteen areas. The connections between areas are topographically ordered in a manner consistent with information flow along two major anatomical axes: core-belt-parabelt and caudal-rostral. Remarkably, most of the connections supporting this model were revealed using retrograde tracing techniques. Little is known about laminar circuitry, as anterograde tracing of axon terminations has rarely been used. The purpose of the present study was to examine the laminar projections of three areas of auditory cortex, pursuant to analysis of all areas. The selected areas were: middle lateral belt (ML; caudomedial belt (CM; and caudal parabelt (CPB. Injections of anterograde tracers yielded data consistent with major features of our model, and also new findings that compel modifications. Results supporting the model were: 1 feedforward projection from ML and CM terminated in CPB; 2 feedforward projections from ML and CPB terminated in rostral areas of the belt and parabelt; and 3 feedback projections typified inputs to the core region from belt and parabelt. At odds with the model was the convergence of feedforward inputs into rostral medial belt from ML and CPB. This was unexpected since CPB is at a higher stage of the processing hierarchy, with mainly feedback projections to all other belt areas. Lastly, extending the model, feedforward projections from CM, ML, and CPB overlapped in the temporal parietal occipital area (TPO in the superior temporal sulcus, indicating significant auditory influence on sensory processing in this region. The combined results refine our working model and highlight the need to complete studies of the laminar inputs to all areas of auditory cortex. Their documentation is essential for developing informed hypotheses about the neurophysiological influences of inputs to each layer and area.

The morphological difference between glaucoma and other optic neuropathies

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Burgoyne, Claude

2016-01-01

The clinical phenomenon of cupping has two principal pathophysiologic components in all optic neuropathies: prelaminar thinning and laminar deformation. We define prelaminar thinning to be the portion of cup enlargement that results from thinning of the prelaminar tissues due to physical compression and/or loss of Retinal Ganglion Cell axons. We define laminar deformation or laminar cupping to be the portion of cup enlargement that results from permanent, intraocular pressure-(IOP) induced deformation of the lamina cribrosa and peripapillary scleral connective tissues following damage and/or remodeling. We propose that the defining phenomenon of glaucomatous cupping is deformation and/or remodeling of the neural and connective tissues of the optic nerve head (ONH), which is governed by the distribution of IOP-related connective tissue stress and strain, regardless of the mechanism of insult or the level of IOP at which that deformation and/or remodeling occurs. Said in another way, “glaucomatous cupping” is the term clinicians use to describe the clinical appearance and behavior the ONH assumes as its neural and connective tissues deform, remodel or mechanically fail: 1) in a pattern and 2) by the several pathophysiologic processes governed by IOP-related connective tissue stress and strain. ONH Biomechanics explains why a given optic nerve head will demonstrate a certain form of “cupping” and at what level of IOP that might happen. Animal models are allowing us to tease apart the important components of cupping in IOP-related and non-IOP-related forms of optic neuropathy. A paradigm change in spectral domain optical coherence tomography ONH, retinal nerve fiber layer and Macular imaging should improve our ability to phenotype all forms of damage to the visual system including glaucoma. PMID:26274837

Sympathetic neuropathy in diabetes mellitus patients does not elicit Charcot osteoarthropathy

DEFF Research Database (Denmark)

Christensen, Tomas M; Simonsen, Lene; Holstein, Per E

2011-01-01

AIM: The aim of the study was to determine the degree of neuropathy (autonomic and somatic) in patients with diabetes mellitus with or without Charcot osteoarthropathy (CA). METHODS: Forty-nine patients with diabetes mellitus type 1 or 2 were investigated. The patient population of interest...... with first toe amputation (n=5), a high-risk group for development of CA, and two control groups consisting of diabetes patients with (n=9) or without somatic neuropathy (n=11) were investigated. Regional blood flow in the feet was measured by venous occlusion plethysmography. Quantitation of somatic...... neuropathy was done by the Neuropathy Disability Score and modified Neuropathy Symptom Score. Quantitation of autonomic neuropathy was done by measurements of local venoarteriolar sympathetic axon reflex in the feet and of heart rate variability during deep breathing and orthostatic challenge. RESULTS...

Bilateral Alternating Auditory Stimulations Facilitate Fear Extinction and Retrieval

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Sarah Boukezzi

2017-06-01

Full Text Available Disruption of fear conditioning, its extinction and its retrieval are at the core of posttraumatic stress disorder (PTSD. Such deficits, especially fear extinction delay, disappear after alternating bilateral stimulations (BLS during eye movement desensitization and reprocessing (EMDR therapy. An animal model of fear recovery, based on auditory cued fear conditioning and extinction learning, recently showed that BLS facilitate fear extinction and fear extinction retrieval. Our goal was to determine if these previous results found in animals can be reproduced in humans. Twenty-two healthy participants took part in a classical fear conditioning, extinction, and extinction recall paradigm. Behavioral responses (fear expectations as well as psychophysiological measures (skin conductance responses, SCRs were recorded. The results showed a significant fear expectation decrease during fear extinction with BLS. Additionally, SCR for fear extinction retrieval were significantly lower with BLS. Our results demonstrate the importance of BLS to reduce negative emotions, and provide a successful model to further explore the neural mechanisms underlying the sole BLS effect in the EMDR.

Investigation of depression in Greek patients with diabetic peripheral neuropathy.

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Rekleiti, Maria; Sarafis, Pavlos; Saridi, Maria; Toska, Aikaterini; Melos, Chrysovaladis; Souliotis, Kyriakos; Tsironi, Maria

2013-06-16

Considerable studies directly connect the complications in diabetic patients, and especially peripheral neuropathy, with the emergence of depression. Neuropathetic pain may deteriorate the general health status of the diabetic patient and glycaemic regulation. The purpose of this study was to investigate the appearance and degree of diabetic peripheral neuropathy and its correlation with depression, with other parameters of the disease and also duration. 57 diabetic patients participated with diagnosed diabetic peripheral neuropathy (male n=27, female n= 30, mean of age 72.7±6.35 years). The first part of Michigan Neuropathy Screening Instrument and the Zung Depression Rating Scale were used as tools for our study. Data was analysed with the SPSS 18.0 statistic program. 57.9% of the patients were overweight, 35.1% were obese and only 7% were within normal weight range. The BMI findings between the two genders indicate that male participants are more often obese than females. Women surpassed men in the category of overweight patients (p depression, it derives that a high degree of diabetic neuropathy is related with high score of depression [F(3.160)=9.821, p=0.001]. Moderate and severe neuropathy was found with almost the same levels of depression. The correlation between diabetic neuropathy and depression is confirmed, while a very high depression rate was found in patients with severe neuropathy. The issue needs further study by using common instruments to obtain comparative results from the scientific community.

NRP-1 Receptor Expression Mismatch in Skin of Subjects with Experimental and Diabetic Small Fiber Neuropathy.

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Nathalie Van Acker

Full Text Available The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN. Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1/semaphorin pathway. This led us to the evaluation of NRP-1 receptor expression in epidermis and dermis of subjects presenting experimentally induced small fiber neuropathy, diabetic polyneuropathy and of diabetic subjects without clinical signs of small fiber neuropathy. The NRP-1 receptor was co-stained with CD31 vessel-marker using immunofluorescence and analyzed with Definiens® technology. This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. Capsaicin induced a decrease in dermal non-vascular NRP-1 receptor expression which did not appear in diabetic polyneuropathy. We can conclude that the capsaicin model does not mimic diabetic neuropathy related changes for cutaneous NRP-1 receptor expression. In addition, our data suggest that NRP-1 might play an important role in epidermal nerve fiber loss and/or defective regeneration and that NRP-1 receptor could change the epidermal environment to a nerve fiber repellant bed possibly through Sem3A in diabetes.

Inherited focal, episodic neuropathies: hereditary neuropathy with liability to pressure palsies and hereditary neuralgic amyotrophy.

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Chance, Phillip F

2006-01-01

Hereditary neuropathy with liability to pressure palsies (HNPP; also called tomaculous neuropathy) is an autosomal-dominant disorder that produces a painless episodic, recurrent, focal demyelinating neuropathy. HNPP generally develops during adolescence, and may cause attacks of numbness, muscular weakness, and atrophy. Peroneal palsies, carpal tunnel syndrome, and other entrapment neuropathies may be frequent manifestations of HNPP. Motor and sensory nerve conduction velocities may be reduced in clinically affected patients, as well as in asymptomatic gene carriers. The histopathological changes observed in peripheral nerves of HNPP patients include segmental demyelination and tomaculous or "sausage-like" formations. Mild overlap of clinical features with Charcot-Marie-Tooth (CMT) disease type 1 (CMT1) may lead patients with HNPP to be misdiagnosed as having CMT1. HNPP and CMT1 are both demyelinating neuropathies, however, their clinical, pathological, and electrophysiological features are quite distinct. HNPP is most frequently associated with a 1.4-Mb pair deletion on chromosome 17p12. A duplication of the identical region leads to CMT1A. Both HNPP and CMT1A result from a dosage effect of the PMP22 gene, which is contained within the deleted/duplicated region. This is reflected in reduced mRNA and protein levels in sural nerve biopsy samples from HNPP patients. Treatment for HNPP consists of preventative and symptom-easing measures. Hereditary neuralgic amyotrophy (HNA; also called familial brachial plexus neuropathy) is an autosomal-dominant disorder causing episodes of paralysis and muscle weakness initiated by severe pain. Individuals with HNA may suffer repeated episodes of intense pain, paralysis, and sensory disturbances in an affected limb. The onset of HNA is at birth or later in childhood with prognosis for recovery usually favorable; however, persons with HNA may have permanent residual neurological dysfunction following attack(s). Episodes are often

The clinical identification of peripheral neuropathy among older persons.

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Richardson, James K

2002-11-01

To identify simple clinical rules for the detection of a diffuse peripheral neuropathy among older outpatients. Observational, blinded, controlled study. A tertiary-care electrodiagnostic laboratory and biomechanics laboratory. One hundred research subjects, 68 with electrodiagnostic evidence of peripheral neuropathy, between the ages of 50 and 80 years. Not applicable. One examiner, unaware of the results of electrodiagnostic testing, evaluated Achilles' and patellar reflexes, Romberg testing, semiquantified vibration, and position sense at the toe and ankle in all subjects, and unipedal stance time and the Michigan Diabetes Neuropathy Score in a subset of subjects. Significant group differences were present in all clinical measures tested. Three signs, Achilles' reflex (absent despite facilitation), vibration (128Hz tuning fork perceived for <10s), and position sense (<8/10 1-cm trials) at the toe, were the best predictors of peripheral neuropathy on both univariate and logistic regression (pseudo R(2)=.744) analyses. The presence of 2 or 3 signs versus 0 or 1 sign identified peripheral neuropathy with sensitivity, specificity, and positive and negative predictive values of 94.1%, 84.4%, 92.8%, and 87.1%, respectively. Values were similar among subgroups of subjects with and without diabetes mellitus. When other clinicians applied the technique to 12 more subjects, excellent interrater reliability regarding the presence of peripheral neuropathy (kappa=.833) and good to excellent interrater reliability for each sign (kappa range,.667-1.00) were shown. Among older persons, the presence of 2 or 3 of the 3 clinical signs strongly suggested electrodiagnostic evidence of a peripheral neuropathy, regardless of etiology. Age-related decline in peripheral nerve function need not be a barrier to the clinical recognition of a diffuse peripheral neuropathy among older persons. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of

Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

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Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

2016-03-01

Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS).

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Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory J

2016-01-01

Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex) and non-ROI (adjacent nonauditory cortices) during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS). Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

Overview of Animal Models of Obesity

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Lutz, Thomas A.; Woods, Stephen C.

2012-01-01

This is a review of animal models of obesity currently used in research. We have focused upon more commonly utilized models since there are far too many newly created models to consider, especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further, we will not discuss the generation and use of inducible transgenic animals (induced knock-out or knock-in) even though they often bear significant advantages compared to traditional transgenic animals; influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this chapter. PMID:22948848

Perceptual Plasticity for Auditory Object Recognition

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Heald, Shannon L. M.; Van Hedger, Stephen C.; Nusbaum, Howard C.

2017-01-01

In our auditory environment, we rarely experience the exact acoustic waveform twice. This is especially true for communicative signals that have meaning for listeners. In speech and music, the acoustic signal changes as a function of the talker (or instrument), speaking (or playing) rate, and room acoustics, to name a few factors. Yet, despite this acoustic variability, we are able to recognize a sentence or melody as the same across various kinds of acoustic inputs and determine meaning based on listening goals, expectations, context, and experience. The recognition process relates acoustic signals to prior experience despite variability in signal-relevant and signal-irrelevant acoustic properties, some of which could be considered as “noise” in service of a recognition goal. However, some acoustic variability, if systematic, is lawful and can be exploited by listeners to aid in recognition. Perceivable changes in systematic variability can herald a need for listeners to reorganize perception and reorient their attention to more immediately signal-relevant cues. This view is not incorporated currently in many extant theories of auditory perception, which traditionally reduce psychological or neural representations of perceptual objects and the processes that act on them to static entities. While this reduction is likely done for the sake of empirical tractability, such a reduction may seriously distort the perceptual process to be modeled. We argue that perceptual representations, as well as the processes underlying perception, are dynamically determined by an interaction between the uncertainty of the auditory signal and constraints of context. This suggests that the process of auditory recognition is highly context-dependent in that the identity of a given auditory object may be intrinsically tied to its preceding context. To argue for the flexible neural and psychological updating of sound-to-meaning mappings across speech and music, we draw upon examples

Educational Testing of an Auditory Display of Mars Gamma Ray Spectrometer Data

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Keller, J. M.; Pompea, S. M.; Prather, E. E.; Slater, T. F.; Boynton, W. V.; Enos, H. L.; Quinn, M.

2003-12-01

A unique, alternative educational and public outreach product was created to investigate the use and effectiveness of auditory displays in science education. The product, which allows students to both visualize and hear seasonal variations in data detected by the Gamma Ray Spectrometer (GRS) aboard the Mars Odyssey spacecraft, consists of an animation of false-color maps of hydrogen concentrations on Mars along with a musical presentation, or sonification, of the same data. Learners can access this data using the visual false-color animation, the auditory false-pitch sonification, or both. Central to the development of this product is the question of its educational effectiveness and implementation. During the spring 2003 semester, three sections of an introductory astronomy course, each with ˜100 non-science undergraduates, were presented with one of three different exposures to GRS hydrogen data: one auditory, one visual, and one both auditory and visual. Student achievement data was collected through use of multiple-choice and open-ended surveys administered before, immediately following, and three and six weeks following the experiment. It was found that the three student groups performed equally well in their ability to perceive and interpret the data presented. Additionally, student groups exposed to the auditory display reported a higher interest and engagement level than the student group exposed to the visual data alone. Based upon this preliminary testing,we have made improvements to both the educational product and our evaluation protocol. This fall, we will conduct further testing with ˜100 additional students, half receiving auditory data and half receiving visual data, and we will conduct interviews with individual students as they interface with the auditory display. Through this process, we hope to further assess both learning and engagement gains associated with alternative and multi-modal representations of scientific data that extend beyond

Physical Training and Activity in People With Diabetic Peripheral Neuropathy: Paradigm Shift.

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Kluding, Patricia M; Bareiss, Sonja K; Hastings, Mary; Marcus, Robin L; Sinacore, David R; Mueller, Michael J

2017-01-01

Diabetic peripheral neuropathy (DPN) occurs in more than 50% of people with diabetes and is an important risk factor for skin breakdown, amputation, and reduced physical mobility (ie, walking and stair climbing). Although many beneficial effects of exercise for people with diabetes have been well established, few studies have examined whether exercise provides comparable benefits to people with DPN. Until recently, DPN was considered to be a contraindication for walking or any weight-bearing exercise because of concerns about injuring a person's insensitive feet. These guidelines were recently adjusted, however, after research demonstrated that weight-bearing activities do not increase the risk of foot ulcers in people who have DPN but do not have severe foot deformity. Emerging research has revealed positive adaptations in response to overload stress in these people, including evidence for peripheral neuroplasticity in animal models and early clinical trials. This perspective article reviews the evidence for peripheral neuroplasticity in animal models and early clinical trials, as well as adaptations of the integumentary system and the musculoskeletal system in response to overload stress. These positive adaptations are proposed to promote improved function in people with DPN and to foster the paradigm shift to including weight-bearing exercise for people with DPN. This perspective article also provides specific assessment and treatment recommendations for this important, high-risk group. © 2017 American Physical Therapy Association.

Anterior ischemic optic neuropathy in patients undergoing hemodialysis

NARCIS (Netherlands)

DoorenbosBot, ACC; Geerlings, W; Houtman, IA

Four patients are discussed who underwent hemodialysis and developed anterior ischemic optic neuropathy (AION). Three patients had been treated by hemodialysis for several years. One patient developed bilateral optic neuropathy after the first hemodialysis session, So far, only four hemodialysis

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

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Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

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Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

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Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

Blood pressure regulation in diabetic autonomic neuropathy

DEFF Research Database (Denmark)

Hilsted, J

1985-01-01

Defective blood pressure responses to standing, exercise and epinephrine infusions have been demonstrated in diabetic patients with autonomic neuropathy. The circulatory mechanisms underlying blood pressure responses to exercise and standing up in these patients are well characterized: In both...... which may contribute to exercise hypotension in these patients. During hypoglycemia, blood pressure regulation seems intact in patients with autonomic neuropathy. This is probably due to release of substantial amounts of catecholamines during these experiments. During epinephrine infusions a substantial...... blood pressure fall ensues in patients with autonomic neuropathy, probably due to excessive muscular vasodilation. It is unresolved why blood pressure regulation is intact during hypoglycemia and severely impaired--at similar catecholamine concentrations--during epinephrine infusions....

Perception of stochastically undersampled sound waveforms: A model of auditory deafferentation

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Enrique A Lopez-Poveda

2013-07-01

Full Text Available Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects.

Perception of stochastically undersampled sound waveforms: a model of auditory deafferentation

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Lopez-Poveda, Enrique A.; Barrios, Pablo

2013-01-01

Auditory deafferentation, or permanent loss of auditory nerve afferent terminals, occurs after noise overexposure and aging and may accompany many forms of hearing loss. It could cause significant auditory impairment but is undetected by regular clinical tests and so its effects on perception are poorly understood. Here, we hypothesize and test a neural mechanism by which deafferentation could deteriorate perception. The basic idea is that the spike train produced by each auditory afferent resembles a stochastically digitized version of the sound waveform and that the quality of the waveform representation in the whole nerve depends on the number of aggregated spike trains or auditory afferents. We reason that because spikes occur stochastically in time with a higher probability for high- than for low-intensity sounds, more afferents would be required for the nerve to faithfully encode high-frequency or low-intensity waveform features than low-frequency or high-intensity features. Deafferentation would thus degrade the encoding of these features. We further reason that due to the stochastic nature of nerve firing, the degradation would be greater in noise than in quiet. This hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent frequency bands. For the signal in each band, multiple stochastically subsampled copies were obtained to roughly mimic different stochastic representations of that signal conveyed by different auditory afferents innervating a given cochlear region. These copies were then aggregated to obtain an acoustic stimulus. Tone detection and speech identification tests were performed by young, normal-hearing listeners using different numbers of stochastic samplers per frequency band in the vocoder. Results support the hypothesis that stochastic undersampling of the sound waveform, inspired by deafferentation, impairs speech perception in noise more than in quiet, consistent with auditory aging effects. PMID:23882176

A microelectromechanical system artificial basilar membrane based on a piezoelectric cantilever array and its characterization using an animal model

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Jang, Jongmoon; Lee, Jangwoo; Woo, Seongyong; Sly, David J.; Campbell, Luke J.; Cho, Jin-Ho; O'Leary, Stephen J.; Park, Min-Hyun; Han, Sungmin; Choi, Ji-Wong; Hun Jang, Jeong; Choi, Hongsoo

2015-07-01

We proposed a piezoelectric artificial basilar membrane (ABM) composed of a microelectromechanical system cantilever array. The ABM mimics the tonotopy of the cochlea: frequency selectivity and mechanoelectric transduction. The fabricated ABM exhibits a clear tonotopy in an audible frequency range (2.92-12.6 kHz). Also, an animal model was used to verify the characteristics of the ABM as a front end for potential cochlear implant applications. For this, a signal processor was used to convert the piezoelectric output from the ABM to an electrical stimulus for auditory neurons. The electrical stimulus for auditory neurons was delivered through an implanted intra-cochlear electrode array. The amplitude of the electrical stimulus was modulated in the range of 0.15 to 3.5 V with incoming sound pressure levels (SPL) of 70.1 to 94.8 dB SPL. The electrical stimulus was used to elicit an electrically evoked auditory brainstem response (EABR) from deafened guinea pigs. EABRs were successfully measured and their magnitude increased upon application of acoustic stimuli from 75 to 95 dB SPL. The frequency selectivity of the ABM was estimated by measuring the magnitude of EABRs while applying sound pressure at the resonance and off-resonance frequencies of the corresponding cantilever of the selected channel. In this study, we demonstrated a novel piezoelectric ABM and verified its characteristics by measuring EABRs.

[Acrodystrophic neuropathy in an alcoholic].

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Yamamura, Y; Hironaka, M; Shimoyama, M; Toyota, Y; Kurokawa, M; Kohriyama, T; Nakamura, S

1993-01-01

The patient was a 48-year-old alcoholic man with no contributory family history. At age 36 he had developed sensory dominant polyneuropathy with highly impaired temperature sensation and deep sensation in the lower extremities, recurrent ulcers of the toes, and sexual impotence. A sural nerve biopsy at this time revealed marked loss of myelinated fibers with relative preservation of the population of unmyelinated fibers. Subsequently, he developed muscle atrophy of the lower thighs, urinary incontinence, and Wernicke's encephalopathy, and became non-ambulatory at age 44. The peripheral nerve conduction findings suggested predominantly axonal degeneration. The entire course was characterized by alternative progression and partial recovery influenced by his alcohol intake and nutritional state. Alcoholic neuropathy is a major cause of solitary acrodystrophic neuropathy (ADN). Manifestations of autonomic and motor neuropathy are more marked in alcoholic ADN than in HSAN-I, and central nervous system involvement is the hallmark of alcoholic ADN. In the treatment of patients with alcoholic ADN, attention should be paid to diabetes mellitus, malnutritional state, and vitamin deficiency, which frequently complicate alcoholism.

Nonarteritic anterior ischemic optic neuropathy: cause, effect, and management.

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Berry, Shauna; Lin, Weijie V; Sadaka, Ama; Lee, Andrew G

2017-01-01

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common form of ischemic optic neuropathy and the second most common optic neuropathy. Patients are generally over the age of 50 years with vasculopathic risk factors (eg, diabetes mellitus, hypertension, and obstructive sleep apnea). The exact mechanism of NAION is not fully understood. In addition, several treatment options have been proposed. This article summarizes the current literature on the diagnosis, treatment, and management of NAION.

How do auditory cortex neurons represent communication sounds?

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Gaucher, Quentin; Huetz, Chloé; Gourévitch, Boris; Laudanski, Jonathan; Occelli, Florian; Edeline, Jean-Marc

2013-11-01

A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives". Copyright © 2013 Elsevier B.V. All rights reserved.

Parvalbumin immunoreactivity in the auditory cortex of a mouse model of presbycusis.

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Martin del Campo, H N; Measor, K R; Razak, K A

2012-12-01

Age-related hearing loss (presbycusis) affects ∼35% of humans older than sixty-five years. Symptoms of presbycusis include impaired discrimination of sounds with fast temporal features, such as those present in speech. Such symptoms likely arise because of central auditory system plasticity, but the underlying components are incompletely characterized. The rapid spiking inhibitory interneurons that co-express the calcium binding protein Parvalbumin (PV) are involved in shaping neural responses to fast spectrotemporal modulations. Here, we examined cortical PV expression in the C57bl/6 (C57) mouse, a strain commonly studied as a presbycusis model. We examined if PV expression showed auditory cortical field- and layer-specific susceptibilities with age. The percentage of PV-expressing cells relative to Nissl-stained cells was counted in the anterior auditory field (AAF) and primary auditory cortex (A1) in three age groups: young (1-2 months), middle-aged (6-8 months) and old (14-20 months). There were significant declines in the percentage of cells expressing PV at a detectable level in layers I-IV of both A1 and AAF in the old mice compared to young mice. In layers V-VI, there was an increase in the percentage of PV-expressing cells in the AAF of the old group. There were no changes in percentage of PV-expressing cells in layers V-VI of A1. These data suggest cortical layer(s)- and field-specific susceptibility of PV+ cells with presbycusis. The results are consistent with the hypothesis that a decline in inhibitory neurotransmission, particularly in the superficial cortical layers, occurs with presbycusis. Copyright © 2012 Elsevier B.V. All rights reserved.

Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

NARCIS (Netherlands)

de Jager, AEJ; van der Hoeven, JH

Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments

DEFF Research Database (Denmark)

Tesfaye, Solomon; Boulton, Andrew J M; Dyck, Peter J

2010-01-01

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates on cla...... on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.......Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13-18 October 2009, expert panels were convened to provide updates...

Erythropoietin in Treatment of Methanol Optic Neuropathy.

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Pakdel, Farzad; Sanjari, Mostafa S; Naderi, Asieh; Pirmarzdashti, Niloofar; Haghighi, Anousheh; Kashkouli, Mohsen B

2018-06-01

Methanol poisoning can cause an optic neuropathy that is usually severe and irreversible and often occurs after ingestion of illicit or homemade alcoholic beverages. In this study, we evaluated the potential neuroprotective effect of erythropoietin (EPO) on visual acuity (VA) in patients with methanol optic neuropathy. In a prospective, noncomparative interventional case series, consecutive patients with methanol optic neuropathy after alcoholic beverage ingestion were included. All patients initially received systemic therapy including metabolic stabilization and detoxification. Treatment with intravenous recombinant human EPO consisted of 20,000 units/day for 3 successive days. Depending on clinical response, some patients received a second course of EPO. VA, funduscopy, and spectral domain optical coherence tomography were assessed during the study. Main outcome measure was VA. Thirty-two eyes of 16 patients with methanol optic neuropathy were included. Mean age was 34.2 years (±13.3 years). The mean time interval between methanol ingestion and treatment with intravenous EPO was 9.1 days (±5.56 days). Mean follow-up after treatment was 7.5 months (±5.88 months). Median VA in the better eye of each patient before treatment was light perception (range: 3.90-0.60 logMAR). Median last acuity after treatment in the best eye was 1.00 logMAR (range: 3.90-0.00 logMAR). VA significantly increased in the last follow-up examination (P optic neuropathy and may represent a promising treatment for this disorder.

Two cases of bilateral amiodarone-associated optic neuropathy.

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Chassang, B; Bonnin, N; Moisset, X; Citron, B; Clavelou, P; Chiambaretta, F

2014-03-01

The widespread use of amiodarone is limited by its toxicity, notably to the optic nerve. We report two cases of bilateral optic nerve neuropathy due to amiodarone, and provide a detailed description of the disease. The first case was a 59-year-old man complaining from insidious monocular loss of vision within ten months of initiating amiodarone. Funduscopy and optical coherence tomography showed bilateral optic disc edema. The second case was a 72-year-old man presenting with a decrease in visual acuity in his left eye for a month. Funduscopy showed a left optic nerve edema, and fluorescein angiography showed bilateral papillitis. In both cases, the clinical presentation was not suggestive of ischemic neuropathy, because of the preservation of visual acuity and the insidious onset. In addition, both cardiovascular and inflammatory work-up were normal. An amiodarone-associated neuropathy was suspected, and amiodarone was discontinued with the approval of the cardiologist, with complete regression of the papilledema and a stabilization of visual symptoms. Differentiating between amiodarone-associated optic neuropathy and anterior ischemic optic neuropathy may be complicated by the cardiovascular background of such patients. The major criterion is the absence of a severe decrease in visual acuity; other criteria are the normality of cardiovascular and inflammatory work-up, and the improvement or the absence of worsening of symptoms after discontinuation of amiodarone. Amiodarone-associated neuropathy remains a diagnosis of exclusion, and requires amiodarone discontinuation, which can only be done with the approval of a cardiologist, and sometimes requires replacement therapy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Frequency-specific attentional modulation in human primary auditory cortex and midbrain

NARCIS (Netherlands)

Riecke, Lars; Peters, Judith C; Valente, Giancarlo; Poser, Benedikt A; Kemper, Valentin G; Formisano, Elia; Sorger, Bettina

2018-01-01

Paying selective attention to an audio frequency selectively enhances activity within primary auditory cortex (PAC) at the tonotopic site (frequency channel) representing that frequency. Animal PAC neurons achieve this 'frequency-specific attentional spotlight' by adapting their frequency tuning,

Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's syndrome.

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Feeling Y Chen

Full Text Available Sjögren's syndrome (SS is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.

Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's syndrome.

Science.gov (United States)

Chen, Feeling Y; Lee, Albert; Ge, Shaokui; Nathan, Sara; Knox, Sarah M; McNamara, Nancy A

2017-01-01

Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire) gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

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Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

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Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

1993-07-01

Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

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Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

2015-11-01

Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

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Anna R. Chambers

2016-08-01

Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

Peripheral Neuropathy – Clinical and Electrophysiological Considerations

Science.gov (United States)

Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

2013-01-01

This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

Peripheral neuropathy in patients with HIV infection: consider dual pathology.

Science.gov (United States)

Miller, R F; Bunting, S; Sadiq, S T; Manji, H

2002-12-01

Two HIV infected patients presented with peripheral neuropathy, in one patient this was originally ascribed to HIV associated mononeuritis multiplex and in the other to stavudine. Investigations confirmed these diagnoses and in both cases genetic analysis identified a second hereditary aetiology: in the first patient hereditary neuropathy with liability to pressure palsies and in the second hereditary motor and sensory neuropathy.

Chronic Pain and Neuropathy Following Adjuvant Chemotherapy

DEFF Research Database (Denmark)

Ventzel, Lise; Madsen, Caspar S; Karlsson, Páll

2017-01-01

Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning. Design: A retrospective cross-sectional study. Setting: A chro...... mechanisms useful for future studies in the tailored treatment of prevention of chemotherapy-induced peripheral neuropathy and pain.......Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning. Design: A retrospective cross-sectional study. Setting......: A chronic pain research center. Subjects: Thirty-eight patients with chronic peripheral pain and/or dysesthesia following chemotherapy. Methods:  Sensory profiles, psychological functioning, and quality of life were assessed using standardized questionnaires. In addition, standardized quantitative sensory...

Increased BOLD Signals Elicited by High Gamma Auditory Stimulation of the Left Auditory Cortex in Acute State Schizophrenia

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Hironori Kuga, M.D.

2016-10-01

We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ, 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ, and 24 healthy controls (HC, assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy

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Heung Yong Jin

2015-12-01

Full Text Available Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN. Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

Science.gov (United States)

Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

1990-01-01

Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

Animal Models for Periodontal Disease

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Helieh S. Oz

2011-01-01

Full Text Available Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed.

Animal Models for Periodontal Disease

Science.gov (United States)

Oz, Helieh S.; Puleo, David A.

2011-01-01

Animal models and cell cultures have contributed new knowledge in biological sciences, including periodontology. Although cultured cells can be used to study physiological processes that occur during the pathogenesis of periodontitis, the complex host response fundamentally responsible for this disease cannot be reproduced in vitro. Among the animal kingdom, rodents, rabbits, pigs, dogs, and nonhuman primates have been used to model human periodontitis, each with advantages and disadvantages. Periodontitis commonly has been induced by placing a bacterial plaque retentive ligature in the gingival sulcus around the molar teeth. In addition, alveolar bone loss has been induced by inoculation or injection of human oral bacteria (e.g., Porphyromonas gingivalis) in different animal models. While animal models have provided a wide range of important data, it is sometimes difficult to determine whether the findings are applicable to humans. In addition, variability in host responses to bacterial infection among individuals contributes significantly to the expression of periodontal diseases. A practical and highly reproducible model that truly mimics the natural pathogenesis of human periodontal disease has yet to be developed. PMID:21331345

Detection of asymptomatic cranial neuropathies in patients with systemic lupus erythematosus and their relation to antiribosomal P antibody levels and disease activity.

Science.gov (United States)

Gaber, Wafaa; Ezzat, Yasser; El Fayoumy, Neveen M; Helmy, Hanan; Mohey, Abeer M

2014-01-01

The objectives of this study are to assess the risk of asymptomatic cranial neuropathy among patients with systemic lupus erythematosus (SLE) and find any association with disease activity and antiribosomal P antibodies. This study is a case-control study including 60 female patients and 30 healthy female controls. Disease activity was measured with the SLE disease activity index (SLEDAI). All patients were evaluated using evoked potentials, blink reflex, and levels of antiribosomal P antibodies. Patients with abnormal electrophysiological parameters had significantly higher levels of antiribosomal P antibodies (P = 0.034) and secondary antiphospholipid syndrome (P = 0.044). Antiribosomal P antibodies (odds ratio 5.4, 95 % confidence interval 1.002-1.03, P = 0.002) and presence of anti-DNA antibodies (odds ratio 1.01, 95 % confidence interval 1.2-24.8, P = 0.032) were independent risk factors for the presence of the abnormal electrophysiological parameters. Disease duration was positively correlated with wave 1 of the auditory brain reflex (P < 0.001) and a latency of the evoked blink reflex (component R1, P = 0.013). SLEDAI scores were positively correlated with latencies of the visually evoked potential (P100, P = 0.02), wave 1 of the auditory brain reflex (P < 0.001), and a latency of the evoked blink reflex (R2c, P = 0.005). Steroid dosage was negatively correlated with P100 latencies (P = 0.042) and components of the evoked blink reflex (R1, P = 0.042; R2i, P = 0.041; R2c, P < 0.001). Because abnormalities in the visually evoked potential and blink reflex were associated with antiribosomal P antibodies, they can be useful for detecting asymptomatic cranial neuropathy. Further studies on large number of patients should be done to determine any association.

Auditory hallucinations.

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Blom, Jan Dirk

2015-01-01

Auditory hallucinations constitute a phenomenologically rich group of endogenously mediated percepts which are associated with psychiatric, neurologic, otologic, and other medical conditions, but which are also experienced by 10-15% of all healthy individuals in the general population. The group of phenomena is probably best known for its verbal auditory subtype, but it also includes musical hallucinations, echo of reading, exploding-head syndrome, and many other types. The subgroup of verbal auditory hallucinations has been studied extensively with the aid of neuroimaging techniques, and from those studies emerges an outline of a functional as well as a structural network of widely distributed brain areas involved in their mediation. The present chapter provides an overview of the various types of auditory hallucination described in the literature, summarizes our current knowledge of the auditory networks involved in their mediation, and draws on ideas from the philosophy of science and network science to reconceptualize the auditory hallucinatory experience, and point out directions for future research into its neurobiologic substrates. In addition, it provides an overview of known associations with various clinical conditions and of the existing evidence for pharmacologic and non-pharmacologic treatments. © 2015 Elsevier B.V. All rights reserved.

Evaluation of animal models of neurobehavioral disorders

Directory of Open Access Journals (Sweden)

Nordquist Rebecca E

2009-02-01

Full Text Available Abstract Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to

[Diabetic neuropathy: therapeutic nihilism is no longer acceptable].

Science.gov (United States)

Haslbeck, Manfred

2007-05-21

The repeatedly expressed doubts about the value of an effective therapy for diabetic neuropathies are no longer acceptable. Today a number of excellent longitudinal and cross-sectional studies, i.e. DCCT, Steno 2, DCCT/EDIC, European Diabetes Prospective Complications Study, are available. The attending physician should make every effort to diagnose diabetic neuropathies as soon as possible with all their multivarious manifestations. Treatment must be promptly, aggressively and multifactorially as described in evidence-based guidelines. In principle, the same risk factors apply to neuropathy in type 1 and type 2 diabetes as for macro-angiopathy and microangiopathy. Therapy focuses on establishing near-normal diabetes and blood pressure control, lipid management, intensive patient education, avoidance of exogenous noxae such as alcohol and nicotine and if necessary, an effective therapy of neuropathic pain. The objective of all diagnostic and preventive efforts must be always to avoid the development of the diabetic neuropathic foot syndrome, which is the most important end stage of somatic and autonomic diabetic neuropathy.

Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

International Nuclear Information System (INIS)

Kannan, Anusha; Srinivasan, Sivasubramanian

2012-01-01

We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

Diffusion MR Imaging of Postoperative Bilateral Acute Ischemic Optic Neuropathy

Energy Technology Data Exchange (ETDEWEB)

Kannan, Anusha; Srinivasan, Sivasubramanian [Khoo Teck Puat Hospital, Singapore (Singapore)

2012-09-15

We read with great interest, the case report on ischemic optic neuropathy (1). We would like to add a few points concerning the blood supply of the optic nerve and the correlation with the development of post-operative ischemic neuropathy. Actually, the perioperative or post-operative vision loss (postoperative ischemic neuropathy) is most likely due to ischemic optic neuropathy. Ischemic optic neuropathy (2) is classified as an anterior ischemic optic neuropathy (AION) and posterior ischemic optic neuropathy (PION). This classification is based on the fact that blood supply (2) to the anterior segment of the optic nerve (part of the optic nerve in the scleral canal and the optic disc) is supplied by short posterior ciliary vessels or anastamotic ring branches around the optic nerve. The posterior part of the optic canal is relatively less perfused, and is supplied by ophthalmic artery and central fibres are perfused by a central retinal artery. So, in the post-operative period, the posterior part of the optic nerve is more vulnerable for ischemia, especially, after major surgeries (3), one of the theories being hypotension or anaemia (2) and resultant decreased perfusion. The onset of PION is slower than the anterior ischemic optic neuropathy. AION on the other hand, is usually spontaneous (idiopathic) or due to arteritis, and is usually sudden in its onset. The reported case is most likely a case of PION. The role of imaging, especially the diffusion weighted magnetic resonance imaging, is very important because the ophthalmoscopic findings in early stages of PION is normal, and it may delay the diagnosis. On the other hand, edema of the disc is usually seen in the early stages of AION.

Animal models.

Science.gov (United States)

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Superior ophthalmic vein enlargement and increased muscle index in dysthyroid optic neuropathy.

Science.gov (United States)

Lima, Breno da Rocha; Perry, Julian D

2013-01-01

To compare superior ophthalmic vein diameter and extraocular muscle index in patients with thyroid eye disease with or without optic neuropathy. High-resolution CT scan images of 40 orbits of 20 patients with history of thyroid eye disease (with or without optic neuropathy), who underwent orbital decompression surgery from January 2007 to November 2009, were retrospectively reviewed. Superior ophthalmic vein diameter was measured in coronal and axial planes. Extraocular muscle index was calculated according to the method proposed by Barrett et al. The clinical diagnosis of optic neuropathy was based on characteristic signs that included afferent pupillary defect, decreased visual acuity, visual field defects, and dyschromatopsia. Orbits were divided in 2 groups based on presence or absence of optic neuropathy. Superior ophthalmic vein diameter was significantly higher in orbits with concomitant optic neuropathy (mean 2.4 ± 0.4mm, p optic neuropathy (mean 57.9% ± 5.7%, p = 0.0002). Muscle index greater than 50% was present in all patients with dysthyroid optic neuropathy. This study suggests that patients with thyroid eye disease with enlarged superior ophthalmic vein and increased extraocular muscle index are more likely to have concomitant optic neuropathy.

Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

Science.gov (United States)

Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

2013-12-01

The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

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Hrycushko, B; Medin, P [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

International Nuclear Information System (INIS)

Hrycushko, B; Medin, P

2016-01-01

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 of 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work

F wave index: A diagnostic tool for peripheral neuropathy

Directory of Open Access Journals (Sweden)

G R Sathya

2017-01-01

Interpretation & conclusions: Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.

Science.gov (United States)

Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent

2018-01-01

Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces

Potency of Animal Models in KANSEI Engineering

Science.gov (United States)

Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy

DEFF Research Database (Denmark)

Vestergaard, Nanna; Rosenberg, Thomas; Torp-Pedersen, Christian

2017-01-01

Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients. Methods...... patients (RR: 4.26, 95% CI: 1.91-9.48; P neuropathy, and alcohol-related disorders. Conclusions: The manifestation of LHON was associated...

Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway.

Science.gov (United States)

Zhang, Qing; Kaga, Kimitaka; Hayashi, Akimasa

2011-07-01

A 27-year-old female showed auditory agnosia after long-term severe hydrocephalus due to congenital spina bifida. After years of hydrocephalus, she gradually suffered from hearing loss in her right ear at 19 years of age, followed by her left ear. During the time when she retained some ability to hear, she experienced severe difficulty in distinguishing verbal, environmental, and musical instrumental sounds. However, her auditory brainstem response and distortion product otoacoustic emissions were largely intact in the left ear. Her bilateral auditory cortices were preserved, as shown by neuroimaging, whereas her auditory radiations were severely damaged owing to progressive hydrocephalus. Although she had a complete bilateral hearing loss, she felt great pleasure when exposed to music. After years of self-training to read lips, she regained fluent ability to communicate. Clinical manifestations of this patient indicate that auditory agnosia can occur after long-term hydrocephalus due to spina bifida; the secondary auditory pathway may play a role in both auditory perception and hearing rehabilitation.

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

NARCIS (Netherlands)

Lirk, P.; Verhamme, C.; Boeckh, R.; Stevens, M. F.; ten Hoope, W.; Gerner, P.; Blumenthal, S.; de Girolami, U.; van Schaik, I. N.; Hollmann, M. W.; Picardi, S.

2015-01-01

The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control

XX. Animal models of pneumocystosis

DEFF Research Database (Denmark)

Dei-Cas, E.; Brun-Pascaud, M.; Bille-Hansen, Vivi

1998-01-01

As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were...... a source of parasites taxonomically related to P. carinii sp. f hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown......, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis...

Auditory short-term memory in the primate auditory cortex.

Science.gov (United States)

Scott, Brian H; Mishkin, Mortimer

2016-06-01

Sounds are fleeting, and assembling the sequence of inputs at the ear into a coherent percept requires auditory memory across various time scales. Auditory short-term memory comprises at least two components: an active ׳working memory' bolstered by rehearsal, and a sensory trace that may be passively retained. Working memory relies on representations recalled from long-term memory, and their rehearsal may require phonological mechanisms unique to humans. The sensory component, passive short-term memory (pSTM), is tractable to study in nonhuman primates, whose brain architecture and behavioral repertoire are comparable to our own. This review discusses recent advances in the behavioral and neurophysiological study of auditory memory with a focus on single-unit recordings from macaque monkeys performing delayed-match-to-sample (DMS) tasks. Monkeys appear to employ pSTM to solve these tasks, as evidenced by the impact of interfering stimuli on memory performance. In several regards, pSTM in monkeys resembles pitch memory in humans, and may engage similar neural mechanisms. Neural correlates of DMS performance have been observed throughout the auditory and prefrontal cortex, defining a network of areas supporting auditory STM with parallels to that supporting visual STM. These correlates include persistent neural firing, or a suppression of firing, during the delay period of the memory task, as well as suppression or (less commonly) enhancement of sensory responses when a sound is repeated as a ׳match' stimulus. Auditory STM is supported by a distributed temporo-frontal network in which sensitivity to stimulus history is an intrinsic feature of auditory processing. This article is part of a Special Issue entitled SI: Auditory working memory. Published by Elsevier B.V.

Early auditory processing in area V5/MT+ of the congenitally blind brain.

Science.gov (United States)

Watkins, Kate E; Shakespeare, Timothy J; O'Donoghue, M Clare; Alexander, Iona; Ragge, Nicola; Cowey, Alan; Bridge, Holly

2013-11-13

Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

Change of Rin1 and Stathmin in the Animal Model of Traumatic Stresses

Directory of Open Access Journals (Sweden)

Yuxiu Shi

2017-04-01

Full Text Available The molecular mechanism of fear memory is poorly understood. Therefore, the pathogenesis of post-traumatic stress disorder (PTSD, whose symptom presentation can enhance fear memory, remains largely unclear. Recent studies with knockout animals have reported that Rin1 and stathmin regulate fear memory. Rin1 inhibits acquisition and promotes memory extinction, whereas stathmin regulates innate and basal fear. The aim of our study was to examine changes in the expression of Rin1 and stathmin in different animal models of stress, particluarly traumatic stress. We used three animal traumatic stresses: single prolonged stress (SPS, which is a rodent model of PTSD, an immobilization-stress (IM and a Loud sound stress (LSS, to examine the change and uniqueness in Rin1/stathmin expression. Behavioral tests of SPS rats demonstrated increased anxiety and contextual fear-conditioning. They showed decreased long-term potentiation (LTP, as well as decreased stathmin and increased Rin1 expression in the hippocampus and the amygdala. Expression of the stathmin effector, tubulin, and downstream molecules Rin1, Rab5, and Abl, appeared to increase. Rin1 and EphA4 were endogenously coexpressed in primary neurons after SPS stimulation. IM rats exhibited increased anxiety behavior and enhanced fear-conditioning to contextual and auditory stimuli. Similar changes in expression of Rin1/stathmin were observed in IM rats whereas no changes were observed in rats exposed to a loud sound. These data suggest that changes in expression of the Rin1 and stathmin genes may be involved in rodents with SPS and IM stresses, which provide valuable insight into fear memories under abnormal conditions, particularly in PTSD.

Neuropathy of nitroimidazole radiosensitizers: clinical and pathological description

International Nuclear Information System (INIS)

Wasserman, T.H.; Nelson, J.S.; VonGerichten, D.

1984-01-01

The dose limiting toxicity of the nitroimidazole radiosensitizers is peripherial neuropathy. Improved pharmacology of newer drugs has eliminated the encephalopathy. Peripheral neuropathies are predominently mild to moderate paresthesias of both hands and feet. Subjective changes occur with or without minimal objective changes on neurologic exam. All of the neuropathies occurred within 30 days of the last drug dose and are of varible duration. Sural nerve biopsies from patients indicate progressive axonal degeneration affecting both large and small caliber myelinated fibers. Axonal damage appears to be more severe in the distal portion of the nerves. More data are needed for correlation of clinical and pathological changes

Sciatic neuropathy as first sign of metastasising prostate cancer

DEFF Research Database (Denmark)

Hansen, Jakob Møller; Rastiemadabadi, Zoreh; Smith, Torben Aagaard

2010-01-01

idiopathic neuropathy. Here we describe a patient who was initially diagnosed with idiopathic sciatic neuropathy but who was eventually diagnosed with prostate cancer. This is an uncommon manifestation of prostate cancer, and the diagnostic was difficult because prostate-specific antigen (PSA) was normal...... and the positron emission tomography scan negative. Changes in PSA should always raise the suspicion of prostate cancer, just as idiopathic progressive neuropathy should always raise the suspicion of an underlying malignancy, even when standard diagnostics fail to explain the patient's symptoms....

Comparing Intrinsic Connectivity Models for the Primary Auditory Cortices

Science.gov (United States)

Hamid, Khairiah Abdul; Yusoff, Ahmad Nazlim; Mohamad, Mazlyfarina; Hamid, Aini Ismafairus Abd; Manan, Hanani Abd

2010-07-01

This fMRI study is about modeling the intrinsic connectivity between Heschl' gyrus (HG) and superior temporal gyrus (STG) in human primary auditory cortices. Ten healthy male subjects participated and required to listen to white noise stimulus during the fMRI scans. Two intrinsic connectivity models comprising bilateral HG and STG were constructed using statistical parametric mapping (SPM) and dynamic causal modeling (DCM). Group Bayes factor (GBF), positive evidence ratio (PER) and Bayesian model selection (BMS) for group studies were used in model comparison. Group results indicated significant bilateral asymmetrical activation (puncorr < 0.001) in HG and STG. Comparison results showed strong evidence of Model 2 as the preferred model (STG as the input center) with GBF value of 5.77 × 1073 The model is preferred by 6 out of 10 subjects. The results were supported by BMS results for group studies. One-sample t-test on connection values obtained from Model 2 indicates unidirectional parallel connections from STG to bilateral HG (p<0.05). Model 2 was determined to be the most probable intrinsic connectivity model between bilateral HG and STG when listening to white noise.

Nonarteritic anterior ischemic optic neuropathy (NAION) and its experimental models

Science.gov (United States)

Bernstein, Steven L.; Johnson, Mary A.; Miller, Neil R.

2011-01-01

Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, and the power of a `vertically integrated' multi-species approach can help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may

Peripheral neuropathy in genetically characterized patients with mitochondrial disorders: A study from south India.

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Bindu, Parayil Sankaran; Govindaraju, Chikanna; Sonam, Kothari; Nagappa, Madhu; Chiplunkar, Shwetha; Kumar, Rakesh; Gayathri, Narayanappa; Bharath, M M Srinivas; Arvinda, Hanumanthapura R; Sinha, Sanjib; Khan, Nahid Akthar; Govindaraj, Periyasamy; Nunia, Vandana; Paramasivam, Arumugam; Thangaraj, Kumarasamy; Taly, Arun B

2016-03-01

There are relatively few studies, which focus on peripheral neuropathy in large cohorts of genetically characterized patients with mitochondrial disorders. This study sought to analyze the pattern of peripheral neuropathy in a cohort of patients with mitochondrial disorders. The study subjects were derived from a cohort of 52 patients with a genetic diagnosis of mitochondrial disorders seen over a period of 8 years (2006-2013). All patients underwent nerve conduction studies and those patients with abnormalities suggestive of peripheral neuropathy were included in the study. Their phenotypic features, genotype, pattern of peripheral neuropathy and nerve conduction abnormalities were analyzed retrospectively. The study cohort included 18 patients (age range: 18 months-50 years, M:F- 1.2:1).The genotype included mitochondrial DNA point mutations (n=11), SURF1 mutations (n=4) and POLG1(n=3). Axonal neuropathy was noted in 12 patients (sensori-motor:n=4; sensory:n=4; motor:n=4) and demyelinating neuropathy in 6. Phenotype-genotype correlations revealed predominant axonal neuropathy in mtDNA point mutations and demyelinating neuropathy in SURF1. Patients with POLG related disorders had both sensory ataxic neuropathy and axonal neuropathy. A careful analysis of the family history, clinical presentation, biochemical, histochemical and structural analysis may help to bring out the mitochondrial etiology in patients with peripheral neuropathy and may facilitate targeted gene testing. Presence of demyelinating neuropathy in Leigh's syndrome may suggest underlying SURF1 mutations. Sensory ataxic neuropathy with other mitochondrial signatures should raise the possibility of POLG related disorder. Copyright © 2015. Published by Elsevier B.V.

Fundamental deficits of auditory perception in Wernicke's aphasia.

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Robson, Holly; Grube, Manon; Lambon Ralph, Matthew A; Griffiths, Timothy D; Sage, Karen

2013-01-01

This work investigates the nature of the comprehension impairment in Wernicke's aphasia (WA), by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. WA, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional-imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. We examined analysis of basic acoustic stimuli in WA participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure-tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in "moving ripple" stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. Participants with WA showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both FM and DM detection correlated significantly with auditory comprehension abilities in the WA participants. These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectro-temporal non-verbal stimuli in WA, which may have a causal contribution to the auditory language comprehension impairment. Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing. Copyright © 2012 Elsevier Ltd. All rights reserved.

Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS

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Mohamad Issa

2016-01-01

Full Text Available Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex and non-ROI (adjacent nonauditory cortices during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS. Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

Age-related auditory pathology in the CBA/J mouse

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Sha, Su-Hua; Kanicki, Ariane; Dootz, Gary; Talaska, Andra E.; Halsey, Karin; Dolan, David; Altschuler, Richard; Schacht, Jochen

2008-01-01

Commercially obtained aged male CBA/J mice presented a complex pattern of hearing loss and morphological changes. A significant threshold shift in auditory brainstem responses (ABR) occurred at 3 months of age at 4 kHz without apparent loss of hair cells, rising slowly at later ages accompanied by loss of apical hair cells. A delayed high-frequency deficit started at 24 kHz around the age of 12 months. At 20 to 26 months, threshold shifts at 12 and 24 kHz and the accompanying hair cell loss at the base of the cochlea were highly variable with some animals appearing almost normal and others showing large deficits. Spiral ganglion cells degenerated by 18 months in all regions of the cochlea, with cell density reduced by approximately 25%. There was no degeneration of the stria vascularis and the endocochlear potential remained stable from 3 to 25 months of age regardless of whether the animals had normal or highly elevated ABR thresholds. The slow high frequency hearing loss combined with a modest reduction of ganglion cell density and an unchanged endocochlear potential suggest sensorineural presbycusis. The superimposed early hearing loss at low frequencies, which is not seen in animals bred in-house, may complicate the use of these animals as a presbycusis model. PMID:18573325

Delayed radiation neuropathy

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Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

1981-07-01

A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

Delayed radiation neuropathy

International Nuclear Information System (INIS)

Nagashima, Toshiko; Miyamoto, Kazuto; Beppu, Hirokuni; Hirose, Kazuhiko; Yamada, Katsuhiro

1981-01-01

A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author)

Hereditary neuropathies: systematization and diagnostics (clinical case of hereditary motor and sensor neuropathy of the IA type