Prenatal exposure to antiepileptic drugs and early processing of emotionally relevant sounds.

INTRODUCTION: Prenatal exposure to antiepileptic drugs (AEDs) is associated with developmental compromises in verbal intelligence and social skills in childhood. Our aim was to evaluate whether a multifeature Mismatch Negativity (MMN) paradigm assessing semantic and emotional components of linguistic and emotional processing would be useful to detect possible alterations in early auditory processing of newborns with prenatal AED exposure. MATERIAL AND METHODS: Data on AED exposure, pregnancy outcome, neuropsychological evaluation of the mothers, information on maternal epilepsy type, and a structured neurological examination of the newborn were collected prospectively. Blinded to AED exposure, we compared a cohort of 36 AED-exposed with 46 control newborns at the age of two weeks by measuring MMN with a multifeature paradigm with six linguistically relevant deviant sounds and three emotionally uttered sounds. RESULTS: Frontal responses for the emotionally uttered stimulus Happy differed significantly in the exposed newborns compared with the control newborns. In addition, responses to sounds with or without emotional component differed in newborns exposed to multiple AEDs compared with control newborns or to newborns exposed to only one AED. CONCLUSIONS: These preliminary findings suggest that prenatal AED exposure may alter early processing of emotionally and linguistically relevant sound information.

Prenatal exposure to the herbicide 2,4-D is associated with deficits in auditory processing during infancy.

INTRODUCTION: Despite widespread use, many herbicides and fungicides are not well studied for neurological effects. Fetal and infant brains are rapidly developing, yet the effects of early-life exposure to these classes of pesticides on visual and auditory function are unknown. Here we examined the effects of prenatal herbicide and fungicide exposure on infant grating visual acuity (VA) and auditory brainstem response (ABR). METHODS: 9 herbicides and 13 fungicides were measured in umbilical cord blood plasma from a cohort of infants in Fuyang County, China (n = 232). Grating VA and ABR latencies for waves I, III, V were measured at 3 time points: 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and ABR central conduction time (CCT [wave V- wave I]). Pesticides were analyzed as 3-level ordinal (non-detect [ND]/medium/high), or dichotomous (ND/detect), depending on detection rates. Linear mixed models were used to evaluate relations between pesticides and VA and ABR outcomes. RESULTS: 2,4-dichloroacetic acid (2,4-D), prometryn, simazine, and tetrahydrophthalamide (THPI, a metabolite of captan) were detected in 27%, 81%, 17%, and 16% of samples, respectively. Infants prenatally exposed to 2,4-D had slower auditory response times at 6 weeks. Infants with cord levels of 2,4-D > 1.17 ng/mL had wave V latencies that were 0.12 (95% CI: 0.03, 0.22) ms slower (p = 0.01) and overall CCTs that were 0.15 (95% CI:0.05, 0.25) ms slower (p = 0.003) than infants with non-detectable 2,4-D in their cord blood. No other statistically significant findings were observed for the other herbicides and fungicides or for the grating VA outcome. CONCLUSIONS: Prenatal exposure to the herbicide 2,4-D was associated with slower auditory signal transmission in early infancy. ABR latencies reflect auditory pathway maturation and longer latencies may indicate delayed auditory development.

Mismatch negativity in tobacco-naïve cannabis users and its alteration with acute nicotine administration.

Chronic cannabis use may interact with factors, such as age of onset of cannabis use, family history, and genetic factors, to elicit schizophrenia (SZ)-like symptoms, including sensory and cognitive deficits. However, evidence of a relationship between cannabis use and cognitive impairment is confounded by concomitant use of tobacco. The objective of this study was to compare tobacco-naïve cannabis users with individuals without a history of tobacco/cannabis use on the auditory mismatch negativity (MMN) event-related potential (ERP), a neural measure of auditory deviance detection which is diminished in SZ. An exploratory arm of the study, conducted within a randomized, double-blind, placebo controlled design, examined the acute effects of nicotine gum (6mg) on MMN in cannabis users. MMN was recorded in response to 5 deviant stimuli within an optimal MMN paradigm in 44 healthy, non-tobacco smoking volunteers aged 18-26. Cannabis users (n=21) started smoking cannabis prior to age 17, at least 1 joint per month. To examine the effects of chronicity, users were grouped into relatively heavy long-term (HLT; n=11) users and light short-term (LST; n=10) users. Impaired deviance detection was shown in cannabis users vs. nonusers as reflected by a smaller MMN to duration deviants. Chronicity of use was also associated with MMN alterations, as HLTs displayed a reduced duration and gap MMN vs. LSTs. Compared with placebo, nicotine treatment enhanced select MMN deviants in cannabis user subgroups. As deficits associated with early and persistent cannabis use are similar to those seen in SZ, these dose-dependant disturbances in early sensory processing with cannabis use may be one cognitive pathway which mediates an increased risk for SZ in vulnerable youth, and be influenced by concurrent cigarette smoking behavior.

Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome.

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow-up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive-related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow-up. Thus, a multidisciplinary approach and long-term monitoring of these patients may be necessary.

Salicylate-induced auditory perceptual disorders and plastic changes in nonclassical auditory centers in rats.

Previous studies have shown that sodium salicylate (SS) activates not only central auditory structures, but also nonauditory regions associated with emotion and memory. To identify electrophysiological changes in the nonauditory regions, we recorded sound-evoked local field potentials and multiunit discharges from the striatum, amygdala, hippocampus, and cingulate cortex after SS-treatment. The SS-treatment produced behavioral evidence of tinnitus and hyperacusis. Physiologically, the treatment significantly enhanced sound-evoked neural activity in the striatum, amygdala, and hippocampus, but not in the cingulate. The enhanced sound evoked response could be linked to the hyperacusis-like behavior. Further analysis showed that the enhancement of sound-evoked activity occurred predominantly at the midfrequencies, likely reflecting shifts of neurons towards the midfrequency range after SS-treatment as observed in our previous studies in the auditory cortex and amygdala. The increased number of midfrequency neurons would lead to a relative higher number of total spontaneous discharges in the midfrequency region, even though the mean discharge rate of each neuron may not increase. The tonotopical overactivity in the midfrequency region in quiet may potentially lead to tonal sensation of midfrequency (the tinnitus). The neural changes in the amygdala and hippocampus may also contribute to the negative effect that patients associate with their tinnitus.

Alucinaciones auditivas musicales secundarias al uso de tramadol: a propósito de un caso / Musical auditive hallucinations secondary to tramadol administration: a case report

Las alucinaciones auditivas musicales son un fenómeno psicopatológico infrecuente que se da fundamentalmente en pacientes psiquiátricos, neurológicos y otológicos. Los primeros casos de alucinaciones auditivas musicales fueron descritos por Baillarger y Coleman en 1846 y 1849, respectivamente. Se muestra el caso de una mujer de 69 años, sin antecedentes psiquiátricos de psicosis, que presenta un cuadro de alucinaciones auditivas musicales de aparición aguda y que se relaciona con la administración de tramadol. Se discute la importancia de la consideración de los fármacos como factores etiopatogénicos en el paciente anciano, con la consiguiente evitación de tratamientos innecesarios y la acumulación de efectos secundarios en dicha población (AU)

Musical auditory hallucinations are a rare psychopathological phenomenon, occurring primarily in psychiatric, neurological and otological patients. The first cases of musical hallucinations were described by Baillarger and Coleman in 1846 and 1849 respectively. We describe the case of a 69 year old woman with no history of psychiatric psychosis presents a picture of musical hallucinations and acute onset is associated with tramadol. We discuss the importance of considering drugs as etiological factors in the elderly and therefore avoiding unnecessary treatment and side effects accumulation in this population (AU)

Temporal auditory processing in rural workers exposed to pesticide.

PURPOSE: The objective of this research was to assess the ordering and temporal resolution auditory abilities in rural workers exposed to pesticides and compare them with laborers exposure index. METHODS: A sectional study assessed 33 individuals of both genders, aged 18-59 years, who were exposed to pesticides during their daily routine. The procedures were: questionnaire, meatoscopy, basic audiological evaluation and Temporal Auditory Processing tests: pattern test duration and Gaps-in-Noise. In order to analyse the results, a variable called 'index of exposure' was set up through a simple sum of variables present in the questionnaire. The tests' results on Temporal Auditory Processing were categorized according to the tercis of distribution, based on the results observed - in this study, tertile 1, tertile 2, and tertile 3 - and then compared with the exposure index. RESULTS: Difference was verified in all tertiles, with a dose-response relationship, i.e. increased average exposure was associated to worse performance on pattern test duration (p=0.001) and Gaps-in-Noise (p=0.001) in all tertiles. The highest correlation was observed between tertiles 3 and 1. CONCLUSION: Workers exposed to pesticide performed bellow average on Temporal Auditory Processing tests. There was association between the index of exposure to pesticides and worse performance in Temporal Auditory Processing tests, suggesting that the pesticides may be harmful to central auditory pathways.

Deviant ERP response to spoken non-words among adolescents exposed to cocaine in utero.

Concern for the impact of prenatal cocaine exposure (PCE) on human language development is based on observations of impaired performance on assessments of language skills in these children relative to non-exposed children. We investigated the effects of PCE on speech processing ability using event-related potentials (ERPs) among a sample of adolescents followed prospectively since birth. This study presents findings regarding cortical functioning in 107 prenatally cocaine-exposed (PCE) and 46 non-drug-exposed (NDE) 13-year-old adolescents. PCE and NDE groups differed in processing of auditorily presented non-words at very early sensory/phonemic processing components (N1/P2), in somewhat higher-level phonological processing components (N2), and in late high-level linguistic/memory components (P600). These findings suggest that children with PCE have atypical neural responses to spoken language stimuli during low-level phonological processing and at a later stage of processing of spoken stimuli.

Temporal auditory processing in rural workers exposed to pesticide / Processamento auditivo temporal de trabalhadores rurais expostos a agrotóxico

PURPOSE: The objective of this research was to assess the ordering and temporal resolution auditory abilities in rural workers exposed to pesticides and compare them with laborers exposure index. METHODS: A sectional study assessed 33 individuals of both genders, aged 18-59 years, who were exposed to pesticides during their daily routine. The procedures were: questionnaire, meatoscopy, basic audiological evaluation and Temporal Auditory Processing tests: pattern test duration and Gaps-in-Noise. In order to analyse the results, a variable called 'index of exposure' was set up through a simple sum of variables present in the questionnaire. The tests' results on Temporal Auditory Processing were categorized according to the tercis of distribution, based on the results observed - in this study, tertile 1, tertile 2, and tertile 3 - and then compared with the exposure index. RESULTS: Difference was verified in all tertiles, with a dose-response relationship, i.e. increased average exposure was associated to worse performance on pattern test duration (p=0.001) and Gaps-in-Noise (p=0.001) in all tertiles. The highest correlation was observed between tertiles 3 and 1. CONCLUSION: Workers exposed to pesticide performed bellow average on Temporal Auditory Processing tests. There was association between the index of exposure to pesticides and worse performance in Temporal Auditory Processing tests, suggesting that the pesticides may be harmful to central auditory pathways.

OBJETIVO: Investigar as habilidades auditivas de ordenação e resolução temporal, em trabalhadores rurais expostos ocupacionalmente a agrotóxicos, e correlacionar estes resultados com o grau de exposição dos laboriosos a estas substâncias. MÉTODOS: Foi realizado um estudo seccional, por meio da avaliação de 33 indivíduos de ambos os gêneros, com idades entre 18 e 59 anos, expostos ocupacionalmente a agrotóxicos. Aplicou-se os seguintes procedimentos: questionário, meatoscopia, audiometria, imitanciometria e testes do Processamento Auditivo Temporal: Teste de Padrão de Duração e Gaps-in-Noise. Para análise dos resultados criou-se uma variável denominada índice de exposição, por meio de um somatório de variáveis presentes no questionário. Os resultados dos testes de Processamento Auditivo Temporal aplicados foram categorizados segundo os tercis de distribuição, de acordo com o resultado observado - sendo neste estudo denominado de Tercil 1, Tercil 2 e Tercil 3 - e então, comparado com o índice de exposição. RESULTADOS: Verificou-se diferença em todos os tercis, havendo relação dose-resposta: conforme foi aumentada a média de exposição, pior foi o desempenho no Teste de Padrão de Duração (p=0,001) e no Gaps-in-Noise (p=0,001), em todos os tercis. A maior correlação foi observada entre o Tercil 3 e o Tercil 1. CONCLUSÃO: Os trabalhadores expostos ao agrotóxico apresentaram desempenho inferior ao esperado para os padrões de normalidade nos testes de Processamento Auditivo Temporal. Houve associação entre o índice de exposição a agrotóxico e pior desempenho nos testes de Processamento Auditivo Temporal, sugerindo que o agrotóxico pode ser uma substância nociva às vias auditivas centrais.

Malformation of the superior olivary complex in an animal model of autism.

Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.

Evaluation of central auditory processing in adolescents exposed to metallic mercury.

BACKGROUND: central auditory processing and exposure to metallic mercury. AIM: to evaluate the performance on tests of central auditory processing in adolescents exposed to metallic mercury. METHOD: participants were 52 adolescents, of both genders, who presented hearing thresholds within normal limits. The study group (SG) was composed by 21 adolescents who worked on the burning of gold-mercury amalgams, on the re-burning of gold in stores that sell this metal or who lived next to gold mines or gold shops. The control group (CG) was composed by 31 adolescents who had no history of exposure to mercury. Investigation procedures included the application of a clinical, occupational and mercury exposure history questionnaire, basic audiometric assessment as well as central auditory processing tests. RESULTS: Statistical significant differences in the auditory processing tests of non-verbal sound sequence memory test (p = 0,001), frequency pattern test (p = 0,000), duration pattern test (p = 0,000) and SSW test in Portuguese (p = 0,006) were observed between SG and CG. CONCLUSION: adolescents exposed to metallic mercury presented a lower performance on most of the auditory processing tests when compared to those who had no history of exposure to mercury. The main deficit found in the study was related to difficulty in distinguishing successive brief sounds.

Avaliação do processamento auditivo central em adolescentes expostos ao mercúrio metálico / Evaluation of central auditory processing in adolescents exposed to metallic mercury

TEMA: processamento auditivo central e exposição ao mercúrio metálico. OBJETIVO: comparar o desempenho nos testes comportamentais de processamento auditivo central entre adolescentes expostos e não expostos ao mercúrio metálico. MÉTODO: foram avaliados 52 adolescentes de ambos os sexos que apresentavam limiares auditivos dentro dos padrões de normalidade. O grupo de estudo (GE) incluiu 21 adolescentes que referiram trabalhar na queima dos amálgamas de ouro-mercúrio, re-queimar ouro em lojas que comercializam este metal ou residir próximos às áreas de garimpos e às lojas que comercializam ouro. O grupo de comparação (GC) foi composto por 31 adolescentes que não apresentaram história de exposição ao mercúrio. Os procedimentos incluíram um questionário sobre a história clínica, laboral e da exposição ao mercúrio, audiometria tonal liminar e bateria de testes para avaliação do processamento auditivo central. RESULTADOS: As diferenças de desempenho na avaliação do processamento auditivo central entre o GE e o GC foram estatisticamente significantes para o teste de memória seqüencial para sons não verbais (p = 0,001), para os testes de padrão de freqüência (p = 0,000) e de duração (p = 0,000) e para o SSW em Português (p = 0,006). CONCLUSÃO: os adolescentes expostos ao mercúrio metálico apresentaram desempenho significativamente inferior aos não expostos para a maioria dos testes comportamentais do processamento auditivo central e a principal alteração encontrada nessa população foi no processamento de sons breves e sucessivos.

BACKGROUND: central auditory processing and exposure to metallic mercury. AIM: to evaluate the performance on tests of central auditory processing in adolescents exposed to metallic mercury. METHOD: participants were 52 adolescents, of both genders, who presented hearing thresholds within normal limits. The study group (SG) was composed by 21 adolescents who worked on the burning of gold-mercury amalgams, on the re-burning of gold in stores that sell this metal or who lived next to gold mines or gold shops. The control group (CG) was composed by 31 adolescents who had no history of exposure to mercury. Investigation procedures included the application of a clinical, occupational and mercury exposure history questionnaire, basic audiometric assessment as well as central auditory processing tests. RESULTS: Statistical significant differences in the auditory processing tests of non-verbal sound sequence memory test (p = 0,001), frequency pattern test (p = 0,000), duration pattern test (p = 0,000) and SSW test in Portuguese (p = 0,006) were observed between SG and CG. CONCLUSION:adolescents exposed to metallic mercury presented a lower performance on most of the auditory processing tests when compared to those who had no history of exposure to mercury. The main deficit found in the study was related to difficulty in distinguishing successive brief sounds.

Carbamazepine-induced transient auditory pitch-perception deficit.

This report presents six cases of transient auditory disturbance caused by carbamazepine, with a particular focus on pitch-perception deficit. Basic disorders in the six cases included epilepsy (cryptogenic localization-related epilepsy and benign childhood epilepsy) and glossopharyngeal neuralgia. Since 1993, in which we reported the first description of transient pitch-perception deficit associated with carbamazepine, a further 26 cases have been reported. However, this carbamazepine-induced transient pitch-perception deficit may be more frequent than previously suspected. Moreover, because auditory disturbance occurs at therapeutic serum levels of carbamazepine, patient awareness of reversible hearing impairment on initiating carbamazepine therapy is important.

[Two cases of auditory disturbance caused by carbamazepine].

Two cases of auditory disturbance caused by carbamazepine are reported. Patient 1, a 9-year-old boy with benign Rolandic epilepsy, developed impairment of pitch perception one day after administration of carbamazepine. Patient 2, a 33-year-old female with glossopharyngeal neuralgia, developed impairment of pitch perception several hours after administration of carbamazepine, complaining that the perceived sounds became lower than previously by a semitone. Her pitch perception recovered soon after the cessation of carbamazepine. The carbamazepine-induced disturbance in pitch perception may be more frequent than we guess.

Auditory and visual dysfunction following lead exposure.

The effects of lead exposure on cognitive function have been intensively studied during the past decade, but relatively little effort has been made to understand the impact on sensory function. Subtle impairments of visual and/or auditory processing, however, could have profound effects on learning. The objectives of this paper are to review what is known about the effects of lead exposure on visual and auditory function and to identify related research needs. In particular, the effects of lead exposure on sensory function in children, which have not been studied adequately, will be discussed. Evidence from human and animal studies reveal that lead exposure impairs auditory function. The cochlear nerve and more central structures appear to be preferentially sensitive in both developing and mature humans and experimental animals. Elevations in hearing thresholds and increased latencies of brainstem auditory evoked potential have been reported at low-moderate levels of lead exposure. Higher doses of lead increase the threshold of the auditory nerve action potential, produce segmental demyelination and axonal degeneration of the cochlear nerve, but appear to have no effect on cochlear microphonics or structure. Lead exposure affects both the retina and visual cortex of the developing and mature visual system. Low to moderate level developmental lead exposure produces selective rod deficits which can be detected with electrophysiological and behavioral techniques. At slightly higher levels of lead exposure the visual cortex is affected. A wide range of functional and neurochemical effects on retinal function occurring at blood lead levels below 20 micrograms/dl, the current level of concern, have been observed in rats. Structural, biophysical and photochemical similarities of rods in rats, monkeys and humans argue the relevance of this data for pediatric lead screening. To date, however, rod-mediated visual functions have not been examined in lead-exposed children. Undetected sensory deficits of these kinds may have profound impact on the motor and mental development of children as well as on the quality of life of affected adults. There is clearly a need for more extensive sensory testing in children and workers to screen for lead-induced health effects and in animal models to clarify the mechanisms of lead neurotoxicity.

Organic mental disorders associated with bupropion in three patients.

Bupropion hydrochloride is a phenylaminoketone antidepressant whose clinical pharmacology is poorly understood. Part of bupropion's action may be attributed to inhibition of dopamine reuptake that may induce organic mental disorders in certain susceptible patients. We report three cases of organic mental disorders in patients receiving bupropion hydrochloride for treatment of the depressed phase of their bipolar-type mood instability. The organic mental disorders that occurred in these patients were characterized largely by visual disturbances--visual hallucinations and visual illusions--although one patient also experienced auditory hallucinations. The patients' use of concomitant medications and potential drug interactions are carefully evaluated and the literature on bupropion's ability to induce organic mental disorders is reviewed. We suggest a number of possible mediating mechanisms for these syndromes including dose-related dopaminergic augmentation, accumulation of toxic metabolites, predisposition to psychosis, and drug interactions.

Lead exposure and the central auditory processing abilities and cognitive development of urban children: the Cincinnati Lead Study cohort at age 5 years.

This analysis examined the relationship between lead exposure as registered in whole blood (PbB) and the central auditory processing abilities and cognitive developmental status of the Cincinnati cohort (N = 259) at age 5 years. Although the effects were small, higher prenatal, neonatal, and postnatal PbB levels were associated with poorer central auditory processing abilities on the Filtered Word Subtest of the SCAN (a screening test for auditory processing disorders). Higher postnatal PbB levels were associated with poorer performance on all cognitive developmental subscales of the Kaufman Assessment Battery for Children (K-ABC). However, following adjustment for measures of the home environment and maternal intelligence, few statistically or near statistically significant associations remained. Our findings are discussed in the context of the related issues of confounding and the detection of weak associations in high risk populations.