Long-term effect of middle ear disease on temporal processing and P300 in two different populations of children.

BACKGROUND/OBJECTIVE: The effects of otitis media on the function of the central auditory nervous system in different populations is unknown. Understanding how the history of otitis media affects children from different nations will guide health professionals worldwide on the importance of adequate auditory stimulus in childhood. For this reason, the aim of the present study was to investigate the long-term auditory effects of middle ear disease on temporal processing and P300 in two different populations of children: Australian and Brazilian. METHODS: Temporal processing tests (Frequency Pattern Tests-FPT and Gaps in noise-GIN) and P300 were measured in 68 Brazilian and Australian children, aged between 8 to 14 years. The Brazilian otitis media group (BrOM) and Australian otitis media group (AusOM) consisted of 20 children each who had a documented history of otitis media. Control groups of 14 children (BrControl and AusControl) were also recruited from each country, all with no documented history of otitis media. RESULTS: The BrOM group showed significantly poorer performance (p<0.001) for FPT and the GIN compared to BrControl. The P300 response showed significantly longer mean latencies (p = 0.02) compared to BrControls. The AusOM group also showed significant delayed latency of P300 (p = 0.04) compared to the AusControl. The FPT showed significantly poorer performance (p = 0.04) compared to AusControls. The two otitis media groups showed no significant differences between each other on P300. Significant differences were seen however in temporal processing tests performance between the two cohorts for the otitis media groups. The BrOM group had significantly poorer responses (p<0.001) for FPT and GIN compared to the AusOM group. CONCLUSIONS: These findings support that although differences exist between BrOM and AusOM groups, otitis media can be demonstrated to affect the underlying mechanisms of the P300 measures and behavioral auditory responses in two different populations of children.

Administration of memantine reverses behavioral, histological, and electrophysiological abnormalities in rats subjected to early maternal deprivation.

Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder with onset occurring during adolescence or early adulthood; notwithstanding, the brain dysfunction occurs before the disease and is not clinically evident. Recently, memantine (MEM) had been postulated as an effective preventive treatment in rats. In this study, was performed the Early Maternal Deprivation (EMD) protocol in Sprague-Dawley rats, establishing four groups (control, EMD, EMD treated with MEM, and MEM treatment). Behavioral parameters such as active linking (AL) and T maze were evaluated as well as quantitative brain histological changes at 3, 7, and 10 weeks of age, to understand the longitudinal demeanor of the disease. Prefrontal evoked potentials (PFEPs) were recorded to study functional synaptic connectivity and neuronal synchronicity changes. The results showed that EMD induces a decrease of AL and poor performance of T maze, in addition to volumetric changes of cortical and subcortical brain structures and abnormalities in PFEPs. The majority of this changes were absent by neonatal MEM administration. Taking into account that all these abnormalities are associated to SCZ, we propose to MEM as a potential preventive treatment.

Auditory maturation and psychological risk in the first year of life.

PURPOSE: To assess the potential association between psychological risk and limited auditory pathway maturation. METHODS: In this longitudinal cohort study, 54 infants (31 non-risk and 23 at-risk) were assessed from age 1 to 12 months. All had normal hearing and underwent assessment of auditory maturation through cortical auditory evoked potentials testing. Psychological risk was assessed with the Child Development Risk Indicators (CDRIs) and PREAUT signs. A variety of statistical methods were used for analysis of results. RESULTS: Analysis of P1 and N1 latencies showed that responses were similar in the both groups. Statistically significant differences between-groups were observed only for the variables N1 latency and amplitude at 1 month. Significant maturation occurred in both groups (p<0.05). There was moderate correlation between P1 latency and Phase II CDRIs, which demonstrates that children with longer latencies at age 12 months were more likely to exhibit absence of these indicators in Phase II and, therefore, were at greater psychological risk. The Phase II CDRIs also correlated moderately with P1 and N1 latencies at 6 months and N1 latencies at 1 month; again, children with longer latency were at increased risk. CONCLUSION: Less auditory pathway maturation correlated with presence of psychological risk. Problems in the mother-infant relationship during the first 6 months of life are detrimental not only to cognitive development, but also to hearing. A fragile relationship may reflect decreased auditory and linguistic stimulation.

Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is one of the most common copy number variants and confers a markedly increased risk for schizophrenia. As such, 22q11.2DS is a homogeneous genetic liability model which enables studies to delineate functional abnormalities that may precede disease onset. Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that top-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia relative to healthy controls in MMN tasks. In the search for early risk-markers for schizophrenia we investigated the neural basis of change detection in a group with 22q11.2DS. We recorded high-density EEG from 19 young non-psychotic 22q11.2 deletion carriers, as well as from 27 healthy non-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater fronto-temporal N1 component in the 22q11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top-down, connection from the right inferior frontal gyrus to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison. We discuss these findings in terms of reduced adaptation and a general increased sensitivity to tones in 22q11.2DS.

Auditory maturation and psychological risk in the first year of life / Maturação auditiva e risco psíquico no primeiro ano de vida

ABSTRACT Purpose To assess the potential association between psychological risk and limited auditory pathway maturation. Methods In this longitudinal cohort study, 54 infants (31 non-risk and 23 at-risk) were assessed from age 1 to 12 months. All had normal hearing and underwent assessment of auditory maturation through cortical auditory evoked potentials testing. Psychological risk was assessed with the Child Development Risk Indicators (CDRIs) and PREAUT signs. A variety of statistical methods were used for analysis of results. Results Analysis of P1 and N1 latencies showed that responses were similar in the both groups. Statistically significant differences between-groups were observed only for the variables N1 latency and amplitude at 1 month. Significant maturation occurred in both groups (p<0.05). There was moderate correlation between P1 latency and Phase II CDRIs, which demonstrates that children with longer latencies at age 12 months were more likely to exhibit absence of these indicators in Phase II and, therefore, were at greater psychological risk. The Phase II CDRIs also correlated moderately with P1 and N1 latencies at 6 months and N1 latencies at 1 month; again, children with longer latency were at increased risk. Conclusion Less auditory pathway maturation correlated with presence of psychological risk. Problems in the mother-infant relationship during the first 6 months of life are detrimental not only to cognitive development, but also to hearing. A fragile relationship may reflect decreased auditory and linguistic stimulation.

RESUMO Objetivo Avaliar a associação entre risco psíquico e maturação da via auditiva. Método Neste estudo de coorte longitudinal, 54 crianças ouvintes (31 sem risco e 23 em risco psíquico) de 1 a 12 meses foram avaliadas. Todas foram submetidas à avaliação da maturação auditiva através dos Potenciais Evocados Auditivos Corticais. O risco psíquico foi avaliado com os Indicadores de Risco de Desenvolvimento Infantil (IRDI) e Sinais PREAUT. Uma variedade de métodos estatísticos foi utilizada para análise de resultados. Resultados A análise das latências de P1 e N1 mostraram respostas similares entre os grupos. Diferenças estatisticamente significantes entre os grupos foram observadas somente para as variáveis latência e amplitude de N1 no primeiro mês. A maturação auditiva foi significante nos dois grupos (p<0,05). Houve correlação moderada entre latência de P1 e a fase II dos IRDI, demonstrando que crianças com maior latência aos 12 meses apresentaram maior probabilidade de exibir a ausência desses indicadores na Fase II, estando em maior risco psíquico. A fase II dos IRDI também teve correlação moderada com as latências de P1 e N1 aos 6 meses e latências de N1 ao 1 mês; novamente, crianças com latência mais longa estavam em maior risco. Conclusão A menor maturação auditiva correlacionou-se com a presença de risco psíquico. Problemas na relação mãe-filho durante os primeiros 6 meses de vida são prejudiciais não apenas ao desenvolvimento cognitivo, mas também à audição. Um relacionamento frágil pode refletir diminuição da estimulação auditiva e linguística.

Auditory processing assessment suggests that Wistar audiogenic rat neural networks are prone to entrainment.

Epilepsy is a neurological disease related to the occurrence of pathological oscillatory activity, but the basic physiological mechanisms of seizure remain to be understood. Our working hypothesis is that specific sensory processing circuits may present abnormally enhanced predisposition for coordinated firing in the dysfunctional brain. Such facilitated entrainment could share a similar mechanistic process as those expediting the propagation of epileptiform activity throughout the brain. To test this hypothesis, we employed the Wistar audiogenic rat (WAR) reflex animal model, which is characterized by having seizures triggered reliably by sound. Sound stimulation was modulated in amplitude to produce an auditory steady-state-evoked response (ASSR; -53.71Hz) that covers bottom-up and top-down processing in a time scale compatible with the dynamics of the epileptic condition. Data from inferior colliculus (IC) c-Fos immunohistochemistry and electrographic recordings were gathered for both the control Wistar group and WARs. Under 85-dB SLP auditory stimulation, compared to controls, the WARs presented higher number of Fos-positive cells (at IC and auditory temporal lobe) and a significant increase in ASSR-normalized energy. Similarly, the 110-dB SLP sound stimulation also statistically increased ASSR-normalized energy during ictal and post-ictal periods. However, at the transition from the physiological to pathological state (pre-ictal period), the WAR ASSR analysis demonstrated a decline in normalized energy and a significant increase in circular variance values compared to that of controls. These results indicate an enhanced coordinated firing state for WARs, except immediately before seizure onset (suggesting pre-ictal neuronal desynchronization with external sensory drive). These results suggest a competing myriad of interferences among different networks that after seizure onset converge to a massive oscillatory circuit.

Cortical maturation in children with cochlear implants: Correlation between electrophysiological and behavioral measurement.

Central auditory pathway maturation in children depends on auditory sensory stimulation. The objective of the present study was to monitor the cortical maturation of children with cochlear implants using electrophysiological and auditory skills measurements. The study was longitudinal and consisted of 30 subjects, 15 (8 girls and 7 boys) of whom had a cochlear implant, with a mean age at activation time of 36.4 months (minimum, 17 months; maximum, 66 months), and 15 of whom were normal-hearing children who were matched based on gender and chronological age. The auditory and speech skills of the children with cochlear implants were evaluated using GASP, IT-MAIS and MUSS measures. Both groups underwent electrophysiological evaluation using long-latency auditory evoked potentials. Each child was evaluated at three and nine months after cochlear implant activation, with the same time interval adopted for the hearing children. The results showed improvements in auditory and speech skills as measured by IT-MAIS and MUSS. Similarly, the long-latency auditory evoked potential evaluation revealed a decrease in P1 component latency; however, the latency remained significantly longer than that of the hearing children, even after nine months of cochlear implant use. It was observed that a shorter P1 latency corresponded to more evident development of auditory skills. Regarding auditory behavior, it was observed that children who could master the auditory skill of discrimination showed better results in other evaluations, both behavioral and electrophysiological, than those who had mastered only the speech-detection skill. Therefore, cochlear implant auditory stimulation facilitated auditory pathway maturation, which decreased the latency of the P1 component and advanced the development of auditory and speech skills. The analysis of the long-latency auditory evoked potentials revealed that the P1 component was an important biomarker of auditory development during the rehabilitation process.

Reboxetine Improves Auditory Attention and Increases Norepinephrine Levels in the Auditory Cortex of Chronically Stressed Rats.

Chronic stress impairs auditory attention in rats and monoamines regulate neurotransmission in the primary auditory cortex (A1), a brain area that modulates auditory attention. In this context, we hypothesized that norepinephrine (NE) levels in A1 correlate with the auditory attention performance of chronically stressed rats. The first objective of this research was to evaluate whether chronic stress affects monoamines levels in A1. Male Sprague-Dawley rats were subjected to chronic stress (restraint stress) and monoamines levels were measured by high performance liquid chromatographer (HPLC)-electrochemical detection. Chronically stressed rats had lower levels of NE in A1 than did controls, while chronic stress did not affect serotonin (5-HT) and dopamine (DA) levels. The second aim was to determine the effects of reboxetine (a selective inhibitor of NE reuptake) on auditory attention and NE levels in A1. Rats were trained to discriminate between two tones of different frequencies in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance of ≥80% correct trials in the 2-ACT were randomly assigned to control and stress experimental groups. To analyze the effects of chronic stress on the auditory task, trained rats of both groups were subjected to 50 2-ACT trials 1 day before and 1 day after of the chronic stress period. A difference score (DS) was determined by subtracting the number of correct trials after the chronic stress protocol from those before. An unexpected result was that vehicle-treated control rats and vehicle-treated chronically stressed rats had similar performances in the attentional task, suggesting that repeated injections with vehicle were stressful for control animals and deteriorated their auditory attention. In this regard, both auditory attention and NE levels in A1 were higher in chronically stressed rats treated with reboxetine than in vehicle-treated animals. These results indicate that NE has a key role in A1 and attention of stressed rats during tone discrimination.

Temporal resolution in individuals with neurological disorders.

OBJECTIVE: Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion. METHOD: This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated. RESULTS: There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively. CONCLUSIONS: Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients.

Temporal resolution in individuals with neurological disorders

OBJECTIVE:Temporal processing refers to the ability of the central auditory nervous system to encode and detect subtle changes in acoustic signals. This study aims to investigate the temporal resolution ability of individuals with mesial temporal sclerosis and to determine the sensitivity and specificity of the gaps-in-noise test in identifying this type of lesion.METHOD:This prospective study investigated differences in temporal resolution between 30 individuals with normal hearing and without neurological lesions (G1) and 16 individuals with both normal hearing and mesial temporal sclerosis (G2). Test performances were compared, and the sensitivity and specificity were calculated.RESULTS:There was no difference in gap detection thresholds between the two groups, although G1 revealed better average thresholds than G2 did. The sensitivity and specificity of the gaps-in-noise test for neurological lesions were 68% and 98%, respectively.CONCLUSIONS:Temporal resolution ability is compromised in individuals with neurological lesions caused by mesial temporal sclerosis. The gaps-in-noise test was shown to be a sensitive and specific measure of central auditory dysfunction in these patients.

Desde la corteza auditiva a la cóclea: progresos en el sistema eferente auditivo / From auditory cortex to cochlea: progress in the auditory efferent system

El sistema eferente auditivo está constituido por el sistema olivococlear y por vías descendentes que provienen de la corteza auditiva y se dirigen a la cóclea. El sistema olivococlear se divide en una porción medial y una lateral, con neuronas que inervan a las células ciliadas externas y a fibras del nervio auditivo respectivamente. El principal neurotransmisor de las sinapsis olivococleares es acetilcolina, y tanto las células ciliadas externas como las fibras del nervio auditivo poseen receptores para esta molécula. El sistema eferente córtico-coclear se origina en la capa V y VI de la corteza auditiva y proyecta a los colículos inferiores y complejo olivar superior, donde a través del sistema olivococlear se conecta con el órgano receptor auditivo. En este artículo se revisan importantes hallazgos obtenidos en los últimos años que involucran (i) nuevos neurotransmisores y receptores del sistema eferente auditivo; (ii) vías descendentes de la corteza auditiva y su rol fisiológico sobre las respuestas cocleares y (iii) rol del sistema eferente auditivo en patologías audiológicas y neuropsiquiátricas.

The auditory efferent system is composed by the olivocochlear fibers and descending projections that originate in the auditory cortex and end in the cochlea. The olivocochlear system is divided into a medial and lateral division, with fibers directed to the outer hair cells and to the auditory nerve fibers respectively. It is known that acetylcholine is the main neurotransmitter of the olivocochlear synapses and that outer hair cells and auditory nerve fibers have receptors to this molecule. The cortico-cochlear efferent system originates in layers V and VI of the auditory cortex. These descending projections are directed to the inferior colliculus and superior olivary complex, a site in which the olivocochlear fibers emerge and connect the brain with the cochlear receptor. In this article recent discoveries obtained in the last years are reviewed: (i) new neurotransmitters and receptors of the olivocochlear system; (ii) anatomy and physiology of descending pathways from the auditory cortex to the cochlea and, (iii) clinical role of auditory efferents in audiological and neuropsychiatric pathologies.

Cortical activity in tinnitus patients and its modification by phonostimulation.

OBJECTIVE: The goal of this study was to observe spontaneous cortical activity and cortical activity modulated by tinnitus-matched sound in tinnitus patients and healthy subjects with no otoneurologic symptoms. METHOD: Data were prospectively collected from 50 tinnitus patients and 25 healthy subjects. Cortical activity was recorded in all subjects with eyes closed and open and during photostimulation, hyperventilation and acoustic stimulation using 19-channel quantitative electroencephalography. The sound applied in the tinnitus patients was individually matched with the ability to mask or equal the tinnitus. The maximal and mean amplitude of the delta, theta, alpha and beta waves and the type and amount of the pathologic EEG patterns were noted during each recording. Differences in cortical localization and the influence of sound stimuli on spontaneous cortical activity were evaluated between the groups. RESULTS: The tinnitus group exhibited decreased delta activity and increased alpha and beta activity. Hyperventilation increased the intensity of the differences. The tinnitus patients had more sharp-slow waves and increased slow wave amplitude. Sound stimuli modified the EEG recordings; the delta and beta wave amplitudes were increased, whereas the alpha-1 wave amplitude was decreased. Acoustic stimulation only slightly affected the temporal region. CONCLUSION: Cortical activity in the tinnitus patients clearly differed from that in healthy subjects, i.e., tinnitus is not a "phantom" sign. The changes in cortical activity included decreased delta wave amplitudes, increased alpha-1, beta-1 and beta-h wave amplitudes and pathologic patterns. Cortical activity modifications occurred predominantly in the temporal region. Acoustic stimulation affected spontaneous cortical activity only in tinnitus patients, and although the applied sound was individually matched, the pathologic changes were only slightly improved.

Cortical activity in tinnitus patients and its modification by phonostimulation

OBJECTIVE: The goal of this study was to observe spontaneous cortical activity and cortical activity modulated by tinnitus-matched sound in tinnitus patients and healthy subjects with no otoneurologic symptoms. METHOD: Data were prospectively collected from 50 tinnitus patients and 25 healthy subjects. Cortical activity was recorded in all subjects with eyes closed and open and during photostimulation, hyperventilation and acoustic stimulation using 19-channel quantitative electroencephalography. The sound applied in the tinnitus patients was individually matched with the ability to mask or equal the tinnitus. The maximal and mean amplitude of the delta, theta, alpha and beta waves and the type and amount of the pathologic EEG patterns were noted during each recording. Differences in cortical localization and the influence of sound stimuli on spontaneous cortical activity were evaluated between the groups. RESULTS: The tinnitus group exhibited decreased delta activity and increased alpha and beta activity. Hyperventilation increased the intensity of the differences. The tinnitus patients had more sharp-slow waves and increased slow wave amplitude. Sound stimuli modified the EEG recordings; the delta and beta wave amplitudes were increased, whereas the alpha-1 wave amplitude was decreased. Acoustic stimulation only slightly affected the temporal region. CONCLUSION: Cortical activity in the tinnitus patients clearly differed from that in healthy subjects, i.e., tinnitus is not a “phantom” sign. The changes in cortical activity included decreased delta wave amplitudes, increased alpha-1, beta-1 and beta-h wave amplitudes and pathologic patterns. Cortical activity modifications occurred predominantly in the temporal region. Acoustic stimulation affected spontaneous cortical activity only in tinnitus patients, and although the applied sound was individually matched, the pathologic changes were only slightly improved. .

Processamento temporal auditivo: relação com dislexia do desenvolvimento e malformação cortical / Temporal auditory processing: correlation with developmental dyslexia and cortical malformation

TEMA: processamento temporal auditivo e dislexia do desenvolvimento. OBJETIVO: caracterizar o processamento temporal auditivo em escolares com dislexia do desenvolvimento e correlacionar com malformação cortical. MÉTODO: foram avaliados 20 escolares, com idade entre 8 e 14 anos, divididos em grupo experimental (GE) composto por 11 escolares (oito do gênero masculino) com o diagnóstico de dislexia do desenvolvimento e grupo controle (GC) composto por nove escolares (seis do gênero masculino) sem alterações neuropsicolinguísticas. Após avaliações neurológica, neuropsicológica e fonoaudiológica (avaliação de linguagem e leitura e escrita) para obtenção do diagnóstico, os escolares foram submetidos à avaliação audiológica periférica e posteriormente aplicou-se o teste Random Gap Detection Test e/ou Random Gap Detection Test Expanded. RESULTADOS: observou-se diferença estatisticamente significante entre os escolares do GE e GC, com pior desempenho para o GE. A maioria dos escolares do GE apresentou polimicrogiria perisylviana. CONCLUSÃO: escolares com dislexia do desenvolvimento podem apresentar alterações no processamento temporal auditivo com prejuízo no processamento fonológico. Malformação do desenvolvimento cortical pode ser o substrato anatômico dos distúrbios.

BACKGROUND: temporal auditory processing and developmental dyslexia. AIM: to characterize the temporal auditory processing in children with developmental dyslexia and to correlate findings with cortical malformations. METHOD: twenty school-aged children, ranging in age from 8 to 14 years were evaluated. These children were divided into two groups: the experimental group (EG) was composed by 11 children (eight were male) with developmental dyslexia and the control group (CG) was composed by nine normal children (six were male). After neurological assessment and verification of the intellectual level, language, reading and writing skills in order to determine the diagnosis, children underwent a peripheral audiological evaluation and Random Gap Detection Test and/or Random Gap Detection Test Expanded. RESULTS: a statistically significant difference between children in the EG and CG were observed, with children in the EG presenting worst performances. Most of the children in the EG presented perisylvian polymicrogyria. CONCLUSION: children with developmental dyslexia may present temporal auditory processing disorders with deficits in phonological processing. Cortical malformations may be the anatomical substrate of these disorders.

Temporal auditory processing: correlation with developmental dyslexia and cortical malformation.

BACKGROUND: Temporal auditory processing and developmental dyslexia. AIM: To characterize the temporal auditory processing in children with developmental dyslexia and to correlate findings with cortical malformations. METHOD: Twenty school-aged children, ranging in age from 8 to 14 years were evaluated. These children were divided into two groups: the experimental group (EG) was composed by 11 children (eight were male) with developmental dyslexia and the control group (CG) was composed by nine normal children (six were male). After neurological assessment and verification of the intellectual level, language, reading and writing skills in order to determine the diagnosis, children underwent a peripheral audiological evaluation and Random Gap Detection Test and/or Random Gap Detection Test Expanded. RESULTS: A statistically significant difference between children in the EG and CG were observed, with children in the EG presenting worst performances. Most of the children in the EG presented perisylvian polymicrogyria. CONCLUSION: Children with developmental dyslexia may present temporal auditory processing disorders with deficits in phonological processing. Cortical malformations may be the anatomical substrate of these disorders.

Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study.

BACKGROUND AND PURPOSE: Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing. METHODS: Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS. RESULTS: After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

Functional change of the auditory cortex related to brain serotonergic neurotransmission in type 1 diabetic adolescents with and without depression.

The aim of this study was to determine whether diabetic patients who were depressed present a decrease of brain serotonergic activity compared to diabetic patients without depression or patients with depression but without diabetes. Determination was made with plasma free fraction of L-tryptophan (FFT) and intensity-dependent auditory-evoked potentials (IDAEPs). Thirty-seven adolescents were studied (20 type 1 diabetic subjects: nine with depression, 11 without depression), nine controls and eight subjects with only depression. FFT, glucose, glycated haemoglobin, free fatty acids, albumin and IDAEPs were determined. All diabetic patients showed a significant decrease of FFT. The group diabetic subjects with depression presented a steeper slope of the amplitude-intensity function of N1/P2 component, suggesting a higher reactivity of the auditory cortex in comparison to diabetic subjects without depression, subjects with only depression, and controls. This was associated with lower plasma FFT. Diabetic subjects with depression had a deficiency of metabolic control due to poor treatment adherence. These findings suggest an enhanced deterioration of brain serotonergic neurotransmission in diabetic subjects with depression with abnormal responses of the auditory cortex. The N1/P2 component of IDAEP is proposed as a non-invasive indicator of brain serotonergic tone that differentiates depressed from non-depressed diabetic patients.

Hallazgos sobre la alteración de la señal auditiva aferente cortical en la enfermedad de Méniére / Findings on the alteration of the cortical afferent auditive signal in the Méniére disease

Se presenta un trabajo retrospectivo, donde se analizaron las respuestas del sistema auditivo aferente central en 36 enfermos que presentaban vértigos y desequilibrio, hipoacusia fluctuante y tinnitus que clínicamente fueron considerados portadores de la Enfermedad de Méniére clásica. Se estudiaron con los exámenes otoneurológicos habituales, y además se estudió la vía auditiva aferente central con el mapeo cerebral auditivo promediado. Este estudio se realizó en todos estos pacientes mediante la estimulación sonora de un oído, y posteriormente se registraron las respuestas aferentes en la corteza cerebral hasta los 15 milisegundos, a través de un electroencefalógrafo computarizado de 22 canales, y promediándolas para eliminar actividad cerebral no auditiva, lo que permitió a través de la Transformada rápida de Fourier, hacer un mapeo topográfico de las respuestas eléctricas del tronco cerebral y de las zonas cerebrales que procesan la audición. Luego de las respuestas de un oído se examinó sucesivamente el otro oído. Los mapeos cerebrales así obtenidos en los 36 enfermos portadores la Enfermedad de Méniére unilateral, y repetidos en fases de hipoacusia, como de normalidad auditiva, se compararon con los que se obtienen en las personas sanas y sin patología auditiva. El hallazgo más relevante fue: en todos los enfermos de Méniére encontramos alteración de la señal aferente a nivel de la corteza cerebral auditiva primaria contra lateral y de la corteza auditiva secundaria ipsilateral. Esta respuesta de la corteza cerebral auditiva, diferente de la que encontramos en las personas normales, podría ser útil para buscar el origen de la Enfermedad de Méniére.

Tinnitus and brain activation: insights from transcranial magnetic stimulation.

The mechanisms underlying tinnitus are still not completely elucidated, but advances in neuroimaging and brain stimulation have provided us with new insights. Evidence suggests that tinnitus might actually be generated by central rather than peripheral structures. To illustrate the importance of brain activity changes in the pathology of tinnitus, we report the cases of 2 patients who experienced a recurrence/worsening of their tinnitus after they had undergone treatment for major depression with repetitive transcranial magnetic stimulation. We suggest that the tinnitus in these 2 patients was induced by changes in brain activity resulting from transcranial magnetic stimulation of the prefrontal cortex. We also review the pathophysiology and other aspects of tinnitus, focusing on associated brain reorganization.

Spontaneous musical auditory perceptions in patients who develop abrupt bilateral sensorineural hearing loss. An uninhibition syndrome?

CONCLUSIONS: Spontaneous musical auditory perceptions commonly occur in patients who develop abrupt bilateral sensorineural hearing loss. The findings in both subjects who were image tested while having these perceptions are suggestive of a biological substrate for this process and of a central locus for auditory memory seemingly located in and around area 39 of Brodmann. When an individual has abrupt bilateral sensorineural hearing loss, stored musical memory can be released and this person can have musical perceptions without an external source. It is likely that an abrupt bilateral loss of inner ear function might uninhibit neuronal groups storing auditory memory. OBJECTIVES: The objectives of this study were as follows. (1) To determine if spontaneous musical auditory perceptions occur in patients who develop abrupt bilateral severe sensorineural hearing loss (not necessarily simultaneously). (2) To determine if there is a biological substrate to the process of recalling previous auditory perceptions. (3) To compare these findings with our normal databases of unstimulated and pure tone-stimulated volunteers. (4) To establish a hypothesis for the mechanisms of these occurrences. PATIENTS AND METHODS: Thirty two patients who had had abrupt bilateral severe sensorineural hearing loss (the interval between the losses of both ears could have been years) were contacted. They were asked if they had ever had the sensation of having musical auditory perceptions without external auditory stimuli. Two of these patients were image tested with single photon computerized emission tomography (neuroSPECT) while they were having these perceptions. RESULTS: All of the 32 subjects had musical auditory perceptions following their hearing loss in the second ear or when hearing loss in both ears occurred simultaneously. The two patients who were image tested with neuroSPECT had similar findings. There was a statistically significant increase in perfusion in area 39 of Brodmann, more intense on the right side, with increased perfusion also in both frontal lobes at the middle gyrus, with bilateral hypoperfusion in area 38 of Brodmann. These findings are similar to those observed in normal volunteers stimulated with pure tones.