The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.

OBJECTIVE: To investigate the peripheral and central auditory pathways in mucopolysaccharidosis (MPS) individuals.
METHODS: The research sample comprised 15 individuals (one female and 14 males), aged 8 to 46 years. The following procedures were used: medical history survey, otoscopy, speech and pure-tone threshold audiometry, acoustic immittance measures, and central auditory pathway assessment with brainstem auditory evoked potentials (BAEP) and long-latency auditory evoked potentials (LLAEP).
RESULTS: The pure-tone audiometry identified hearing loss in 13 individuals, and more than 90 % of the hearing loss was sensorineural. The degree of hearing loss was between mild to moderately severe with descendent configuration. Type A tympanogram predominated, and acoustic reflexes were present according to the types and degrees of hearing loss. Among the individuals with abnormal BAEP, longer wave III and V absolute latencies were the main findings. In addition, the unilateral absence of wave I was observed in two cases. In the LLAEP, longer latencies were observed in 14 individuals, and the most impaired components were the P1 and P3 in children and adolescents and the P2, N2 and P3 in adult individuals.
CONCLUSIONS: The peripheral auditory pathway assessment revealed a predominantly sensorineural hearing loss, affecting mainly high frequencies, and in the central pathway was observed abnormal brainstem and cortical auditory processing in individuals with MPS.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) may induce micro-vascular and macro-vascular changes that can lead to neuropathic changes which may affect the auditory pathway resulting in hearing loss. The study aims to evaluate the outcome of ipsilateral and contralateral acoustic reflex (AR) parameters and reflex decay tests (RDT) in patients with T2DM, and the relationship between average AR parameters, and duration and control of T2DM.
METHODS: An analytical cross-sectional study was conducted in a tertiary care setup in 126 subjects which included 42 subjects with T2DM between 30 and 60 years of age, age-matched with 84 non-diabetic subjects. The subjects were evaluated for pure tone average (PTA), speech identification score (SIS), AR parameters [acoustic reflex threshold (ART), acoustic reflex amplitude (ARA), acoustic reflex latency (ARL)] and RDT.
RESULTS: The subjects with T2DM showed increased PTA in both ears when compared to the subjects with no disease. No significant difference was found in the SIS between both groups. There was no significant difference in the ART and ARL between the two groups. There was a significant difference in the ipsilateral and contralateral ARA at 500 Hz, 1000 Hz and broadband noise (BBN) when compared between the diabetic and non-diabetic groups. No significant difference was found between average AR parameters and duration and control of T2DM.
CONCLUSIONS: T2DM increases hearing thresholds and reduces ipsilateral and contralateral AR at lower frequencies and BBN. Duration and control of T2DM do not affect the AR parameters.

To characterize the peripheral and central auditory pathways in individuals with Acute Lymphoid Leukemia (ALL) and compare assessment results before and during chemotherapy.
The study included 17 subjects with ALL, divided into two age groups: 3 to 6 (11 individuals) and 7 to 16 years old (6 individuals). Each subject was evaluated twice (before and 3 to 6 months after chemotherapy treatment) with the following procedures: medical history survey, otoscopy, Pure-Tone Threshold (PTA) and speech audiometry, acoustic immittance measures, Brainstem Auditory Evoked Potentials (BAEP) and Long-Latency Auditory Evoked Potentials (LLAEP).
PTA was normal. Tympanometry was abnormal in the second assessment in 2 individuals aged 3 to 6 years. One subject in each age group had absent ipsilateral acoustic reflexes. In high-frequency audiometry, 1 individual had abnormal results. BAEP was abnormal in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years and 2 (first assessment) and 1 individual (second assessment) aged 7 to 16 years. As for LLAEP, P1 latency was increased in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years.
No hearing loss was identified in the behavioral audiological assessment. BAEP was more affected in the 3-to-6-year-old group, with greater impairment in the lower brainstem in the first and second assessments. In LLAEP, P1 was the most impaired component in children aged 3 to 6 years, and P2 and N2 were so for those 7 to 16 years old, especially in the second assessment.

OBJECTIVE: To investigate the functionalities of the neural pathways through the auditory evoked potentials of the brainstem and the contralateral stapedial acoustic reflexes in normal-hearing individuals with type 1 diabetes mellitus, in order to detect possible alterations in the central auditory pathways.
METHODS: This is a cross-sectional study with a comparison group and a convenience sample, consisting of 32 individuals with type 1 diabetes mellitus and 20 controls without the disease. All subjects had hearing thresholds within normal limits and type A tympanometric curves. The acoustic reflex arc and brainstem auditory potentials were investigated. Statistical analyses were performed using the SPSS 17.0. The Chi-square test, Student´s t-test, and Multiple linear regression were used.
RESULTS: The auditory thresholds of the acoustic reflex were statistically lower in the group with the disease at frequencies of 0.5 kHz and 1.0 kHz in the left ear (p=0.01 and p=0.01, respectively). The absolute latencies III and V of the auditory potentials of the brainstem in the right ear and V in the left ear were increased in subjects with type 1 diabetes mellitus (p=0.03, p=0.02 and p=0.03, respectively).
CONCLUSIONS: The findings suggest that subjects with type 1 diabetes mellitus are more likely to present alterations in the central auditory pathways, even with auditory thresholds within normal limits.

Congenital cytomegalovirus infection (cCMVi) is a leading cause of sensorineural hearing loss (SNHL) and developmental delay. Brainstem auditory evoked potentials (BAEPs) recording allows assessment of central auditory pathway maturation in neonates. We aimed to characterize the effect of cCMVi on the maturation of the brainstem auditory pathway in term neonates. We retrospectively reviewed medical records of neonates born with cCMVi in 2010-2018 and characterized their auditory pathway maturation using brainstem auditory-evoked potentials (BAEPs). We compared inter-peak latency differences (IPLDs) of the main BAEP components (I-V, I-III, and III-V) in terms of cCMVi patients and healthy controls and described their changes in cCMVi patients throughout the first year of life. Of 101 cCMVi patients, 57 (56.4%) were considered symptomatic, 6 (5.9%) were small for gestational age, 6 (5.9%) had microcephaly, 4 (4%) had thrombocytopenia, 5 (6.6%) had hepatitis, 2 (2.1%) had retinitis, 47 (49.5%) had typical abnormalities on head ultrasound, 9 (8.9%) developed SNHL, and 34 (59.6%) received antiviral therapy. No significant difference was found between IPLDs of full-term cCMVi patients compared to controls throughout the entire auditory pathway (I-III, III-V, and I-V IPLDs), for both ears (p > 0.05). On serial BAEP examinations, cCMVi patients presented decreased IPLDs throughout the first year of life (p < 0.05 of compared 1st, 2nd, and 3rd BAEPs in both ears).   Conclusions: Intrauterine cytomegalovirus infection does not affect the auditory brainstem maturation process in term neonates. Our findings support previous studies noting the normal neurodevelopmental outcome of asymptomatic cCMVi patients, suggesting antiviral treatment is not warranted in these cases. What is Known: • cCMVi is a leading cause of developmental delay and hearing loss. Treatment is recommended for patients with symptomatic diseases who are at significant risk of long-term sequelae. • It is unknown whether cCMVi affects the central nervous system maturation process. What is New: • We performed a neurophysiological evaluation of brainstem conduction by recording the BAEPs. We found that cCMVi has no significant impact on central conduction times along the auditory pathways in the brainstem at birth nor changes the neuronal maturation process during the first year of life. • Our findings suggest that cCMVi does not universally affect central nervous system maturation, supporting a highly selective approach when considering the benefits of antiviral therapy.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia associated with retinal degeneration. The disease is rare in Japan, and this is the first full description of clinicopathological findings in a Japanese autopsy case of genetically confirmed SCA7 having 49 cytosine-adenine-guanine (CAG) trinucleotide repeats in the ataxin 7 gene. A 34-year-old Japanese man with no family history of clinically apparent neurodegenerative diseases presented with gait disturbance, gradually followed by truncal instability with progressive visual loss by the age of 42 years. He became wheelchair-dependent by 51 years old, neurologically exhibiting cerebellar ataxia, slow eye movement, slurred and scanning speech, lower limb spasticity, hyperreflexia, action-related slowly torsional dystonic movements in the trunk and limbs, diminished vibratory sensation in the lower limbs, auditory impairment, and macular degeneration. Brain magnetic resonance imaging revealed atrophy of the brainstem and cerebellum. He died of pneumonia at age 60 with a 26-year clinical duration of disease. Postmortem neuropathological examination revealed pronounced atrophy of the spinal cord, brainstem, cerebellum, external globus pallidus (GP), and subthalamic nucleus, microscopically showing neuronal cell loss and fibrillary astrogliosis with polyglutamine-immunoreactive neuronal nuclei and/or neuronal nuclear inclusions (NNIs). Degeneration was also accentuated in the oculomotor system, auditory and visual pathways, upper and lower motor neurons, and somatosensory system, including the spinal dorsal root ganglia. There was a weak negative correlation between the frequency of nuclear polyglutamine-positive neurons and the extent of neuronal cell loss. Clinicopathological features in the present case suggest that neurological symptoms, such as oculomotor, auditory, visual, and sensory impairments, are attributable to degeneration in their respective projection systems affected by SCA7 pathomechanisms and that dystonic movement is related to more significant degeneration in the external than internal GP.

OBJECTIVE: To analyze age-related changes in the central auditory pathway in healthy elderly individuals.
METHODS: A prospective, quantitative cross-sectional study. The caseload comprised 18 adults (mean age, 22.78 years) and 18 elderly individuals (mean age, 66.72 years) of both sexes, who met inclusion criteria. Subjects were submitted to basic audiological evaluation and related electrophysiologic tests: brainstem auditory evoked potential with click stimulus and frequency-following response.
RESULTS: Elderly individuals had higher wave and interpeak latencies (waves I, III and V and interpeaks I-V and III-V) of brainstem auditory evoked potential. Latencies of frequency following response waves A, E, F and O were also higher in elderly individuals. Frequency following response amplitudes were better in A than in D, F and O waves in these subjects. Likewise, interpeak intervals (V-A and V-O) were larger in elderly relative to adult individuals. Lower slope values were observed in elderly individuals.
CONCLUSIONS: Brainstem auditory evoked potential and frequency-following response allowed appropriate assessment of age-related changes in the auditory pathway. Slower neural response to auditory stimuli suggests reduced synchrony between neural structures.

OBJECTIVE: To analyze the results of Long-latency Auditory Evoked Potentials (LLAEP) in children with Speech Sounds Disorder (SSD) after speech therapy.
METHODS: Longitudinal and prospective clinical study at 14 children with SSD, with ages ranging from five to seven years, of both genders. Were applied Picture Naming task and Imitation task, and from these tasks it was calculated the Percentage of Consonants Correct index. For an analysis of the LLAEP with speech stimulus and recorded the latency and amplitude values ​​of P1, N1, P2, N2 and P3 components. Each child was evaluated in two different moments: initial evaluation and after 12 sessions of speech therapy.
RESULTS: It was observed that after twelve sessions of speech therapy the value of Percentage of Consonants Correct index increased, and a greater number of components were observed in the LLAEP records of children with SSD, as well as a statistically significant increase in the amplitude of the P3 component, demonstrating that anatomical and physiological changes occurred in the central auditory nervous system after intervention, resulting in improved of the LLAEP results.
CONCLUSIONS: After speech therapy, improvement in the children\'s phonology was observed, and there was an increase in the number of components present in the LLAEP, as well as an increase in the amplitude of the P3 component, demonstrating that plasticity occurred in the auditory pathway during these three months of therapeutic intervention.
UNASSIGNED: Avaliar os achados dos Potenciais Evocados Auditivos de Longa Latência (PEALL) em crianças com Transtorno dos Sons na Fala (TSF) após terapia fonoaudiológica.
UNASSIGNED: Estudo clínico longitudinal e prospectivo em um grupo de 14 crianças com TSF, de cinco a sete anos de idade, de ambos os sexos. Foram aplicadas as provas de Nomeação de Figuras e Imitação de palavras, para as quais foi calculado o índice de gravidade Porcentagem de Consoantes Corretas. Foram registrados os PEALL com estímulo de fala e foram analisados os valores de latência e amplitude dos componentes P1, N1, P2, N2 e P3. Cada criança foi avaliada em dois diferentes momentos: avaliação inicial e após 12 sessões de terapia fonoaudiológica.
UNASSIGNED: Os resultados mostraram que após terapia fonoaudiológica, o valor do índice de gravidade Porcentagem de Consoantes Corretas aumentou e um maior número de componentes foi observado nos registros dos PEALL nas crianças com TSF. Também foi observado um aumento estatisticamente significativo na amplitude do componente P3, demostrando que modificações anatomofisiológicas ocorreram no sistema nervoso auditivo central após intervenção, proporcionando melhora nos resultados dos PEALL.
UNASSIGNED: Após terapia fonoaudiológica, foi observada melhora no desempenho fonológico das crianças, aumento no número de componentes presentes nos PEALL, bem como aumento na amplitude do componente P3, demonstrando que ocorreu plasticidade na via auditiva após um curto período de intervenção fonoaudiológica.

The frequency-following response (FFR) to periodic complex sounds has gained recent interest in auditory cognitive neuroscience as it captures with great fidelity the tracking accuracy of the periodic sound features in the ascending auditory system. Seminal studies suggested the FFR as a correlate of subcortical sound encoding, yet recent studies aiming to locate its sources challenged this assumption, demonstrating that FFR receives some contribution from the auditory cortex. Based on frequency-specific phase-locking capabilities along the auditory hierarchy, we hypothesized that FFRs to higher frequencies would receive less cortical contribution than those to lower frequencies, hence supporting a major subcortical involvement for these high frequency sounds. Here, we used a magnetoencephalographic (MEG) approach to trace the neural sources of the FFR elicited in healthy adults (N = 19) to low (89 Hz) and high (333 Hz) frequency sounds. FFRs elicited to the high and low frequency sounds were clearly observable on MEG and comparable to those obtained in simultaneous electroencephalographic recordings. Distributed source modeling analyses revealed midbrain, thalamic, and cortical contributions to FFR, arranged in frequency-specific configurations. Our results showed that the main contribution to the high-frequency sound FFR originated in the inferior colliculus and the medial geniculate body of the thalamus, with no significant cortical contribution. In contrast, the low-frequency sound FFR had a major contribution located in the auditory cortices, and also received contributions originating in the midbrain and thalamic structures. These findings support the multiple generator hypothesis of the FFR and are relevant for our understanding of the neural encoding of sounds along the auditory hierarchy, suggesting a hierarchical organization of periodicity encoding.