Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. Acta Otorrinolaringol Esp. 2013;64(4):265---272 www.elsevier.es/otorrino ORIGINAL ARTICLE Evaluation of Psychoacoustic Tests and P300 Event-Related Potentials in Elderly Patients With Hyperhomocysteinemia夽 Sergio Díaz-Leines,a,∗ Yolanda R. Peñaloza-López,b Tirzo A. Serrano-Miranda,c Blanca Flores-Ávalos,d Martha T. Vidal-Ixta,e Blanca Jiménez-Herreraf a Departamento de Patología del Lenguaje y Procesamiento Central Auditivo, Instituto Nacional de Rehabilitación, Mexico City, Mexico b Departamento de Procesamiento Central Auditivo, Instituto Nacional de Rehabilitación, Mexico City, Mexico c Departamento de Epidemiología, Instituto Nacional de Rehabilitación, Mexico City, Mexico d Departamento de Neurofisiología, Instituto Nacional de Rehabilitación, Mexico City, Mexico e Departamento de Audiología, Laboratorio Starkey, Mexico City, Mexico f Departamento de Rehabilitación Geriátrica, Instituto Nacional de Rehabilitación, Mexico City, Mexico Received 8 May 2012; accepted 9 January 2013 KEYWORDS Homocysteine; Elderly; Central auditory processing disorder; Evoked brainstem auditory; P300 event-related potentials Abstract Introduction and objectives: Hyperhomocysteinemia as a risk factor for hearing impairment, neuronal damage and cognitive impairment in elderly patients is controversial and is limited by the small number of studies. The aim of this work was determine if elderly patients detected with hyperhomocysteinemia have an increased risk of developing abnormalities in the central auditory processes as compared with a group of patients with appropriate homocysteine levels, and to define the behaviour of psychoacoustic tests and long latency potentials (P300) in these patients. Methods: This was a cross-sectional, comparative and analytical study. We formed a group of patients with hyperhomocysteinemia and a control group with normal levels of homocysteine. All patients underwent audiometry, tympanometry and a selection of psychoacoustic tests (dichotic digits, low-pass filtered words, speech in noise and masking level difference), auditory evoked brainstem potentials and P300. Results: Patients with hyperhomocysteinemia had higher values in the test of masking level difference than did the control group (P=.049) and more protracted latency in P300 (P=.000). Conclusions: Hyperhomocysteinemia is a factor that alters the central auditory functions. Alterations in psychoacoustic tests and disturbances in electrophysiological tests suggest that the central portion of the auditory pathway is affected in patients with hyperhomocysteinemia. © 2012 Elsevier España, S.L. All rights reserved. 夽 Please cite this article as: Díaz-Leines S, et al. Evaluación de pruebas psicoacústicas y de potenciales relacionados a eventos P300 en adultos mayores con hiperhomocisteinemia. Acta Otorrinolaringol Esp. 2013;64:265---272. ∗ Corresponding author. E-mail addresses: serch [email protected], joss [email protected] (S. Díaz-Leines). 2173-5735/$ – see front matter © 2012 Elsevier España, S.L. All rights reserved. Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 266 PALABRAS CLAVE Homocisteína; Adulto mayor; Desorden de procesamiento auditivo central; Potenciales evocados auditivos de tallo cerebral; Potenciales relacionados a eventos P300 S. Díaz-Leines et al. Evaluación de pruebas psicoacústicas y de potenciales relacionados a eventos P300 en adultos mayores con hiperhomocisteinemia Resumen Introducción y objetivos: La hiperhomocisteinemia como un factor de riesgo para daño auditivo, daño neuronal y deterioro cognitivo en pacientes adultos mayores es controversial y se encuentra limitado por un pequeño número de estudios. El objetivo de este trabajo es determinar si los pacientes adultos mayores con hiperhomocisteinemia presentan mayor riesgo de desarrollar alteraciones en los procesos centrales de la audición contra un grupo de pacientes con niveles de homocisteína adecuados y definir el comportamiento de las pruebas psicoacústicas y de potenciales de latencia larga (P300) en estos grupos. Método: Estudio transversal, comparativo y analítico. Se formó un grupo de pacientes con hiperhomocisteinemia y un grupo control con valores normales de homocisteína. A todos los pacientes se les realizó audiometría tonal, impedanciometría y una selección de pruebas psicoacústicas (dígitos dicóticos, palabras filtradas pasa bajo, palabra en ruido y diferencia en niveles de enmascaramiento) así como potenciales provocados auditivos de tallo cerebral y P300. Resultados: Los pacientes con hiperhomocisteinemia presentaron valores en la prueba de diferencia en los niveles de enmascaramiento superiores a los del grupo control (p = 0,049), así como latencias más prologadas en los P300 (p = 0,000). Conclusiones: La hiperhomocisteinemia es un factor que altera las funciones auditivas centrales. Las pruebas psicoacústicas alteradas junto con la alteración en las pruebas electrofisiológicas sugieren que la porción central de la vía auditiva está afectada en pacientes con hiperhomocisteinemia. © 2012 Elsevier España, S.L. Todos los derechos reservados. Introduction Homocysteine (Hcy) is a sulphurated amino acid formed by the conversion of methionine to cysteine.1 Its values in plasma range from 5 to 15 mol/l in a rapid state.2 The evidence of hyperhomocysteinemia (HHcy) as a factor of risk for cognitive deterioration in patients without dementia is controversial and limited by a few studies. Sachdev3 indicated that all the transversal studies reported up to that moment showed an inverse association between HHcy presence and cognitive deficit measurements. Duthie et al.4 reported that HHcy represented approximately 7.8% of the variance in cognitive performance in the elderly. Explanations for these HHcy-related alterations have been based on the consideration of the mechanisms of Hcy neurotoxicity, such as: generation reactive species of oxygen, prothrombotic effects and promotion of oxidative stress, among others.5 The auditory pathway, as it is a set of neural structures, can be susceptible to presenting alterations from HHcy. Cohen-Salmon et al.6 published congenital hypoacusis related to connexin 30 in mice with HHcy, as well as disruption of the vascular epithelium in the vascular stria of the inner ear associated with this same cause. Kundu et al.7 showed that Hcy regulated the composition and concentration of the extracellular matrix, which forms part of the basement membranes of the inner ear. It has also been reported that HHcy can be a factor of risk for developing sudden deafness; Marcucci et al.8 found that patients with a diagnosis of idiopathic sudden deafness presented greater concentrations of Hcy when compared with a control group. The central auditory functions are defined as ‘‘the perceptual processing of auditory information in the central nervous system (CNS), the neurobiological activity this process involves and the efficiency and effectiveness with which the CNS uses the auditory information’’.9 Experimental and clinical methodologies in the study of central auditory functions are based on various techniques: psychoacoustic, electrophysiological---electroencephalographic, imaging, biochemical studies, studies based on injuries and behavioural observation studies.10 A few psychoacoustic tests are: Dichotic Digits: this has shown itself to be highly sensitive for CNS dysfunctions associated with hemispheric as well as interhemispheric injuries. The results can also be affected by dysfunctions at the level of the brain stem.11 Filtered Speech: this is a test designed to assess skill in recognising speech under conditions of degradation of the acoustic signal.12 Word in Noise: this is a method to reduce redundancy, consisting of presenting an ipsilateral masking noise that competes with the monosyllables.13 This test is capable of identifying injuries associated with the 8th cranial nerve, intra- and extraaxial brainstem lesions, affection of the temporal lobe and diffuse brain lesions.13 Masking Level Differences (MLD): the study of MLD seems to assess regions of the lower brain stem, more specifically the superior olivary complex. The test consists of presenting a continuous 1000 Hz tone dichotically and then dichotically in the presence of a continuous wide-band noise at 60 dB HL. The result is established based on the differences in the detection of the threshold between both conditions.12 Music Test: the degree to which a person can Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. Evaluation of psychoacoustic tests in elderly patients specifically identify a particular sound mostly depends on their experience; however, the cognitive associations and other ‘‘higher level’’ associations play a key role in identifying a sound.14 The long-latency auditory evoked potentials (P300) offer the possibility of studying central auditory processes in an empirical manner, making it possible to establish inference on the mental events implicit in the resolution of proposals. The P300 potential occurs between 220 and 389 ms with an approximate amplitude of 12 V15 and constitutes the component of the cortical provoked response obtained with the task of discriminating 2 stimuli.16 The clinical applications of P300 are varied; given that its latency is related to processing time, its application is very significant in the diagnosis of dementia or other illnesses in the context of the ‘‘central processes of hearing’’.17 In this study, it was of interest to pose the following research question: Is HHcy a factor that alters peripheral hearing and central auditory processing tests in older adult patients? The objectives were to determine if older adult patients detected as having HHcy presented a greater risk of developing alterations in the central auditory processes than a group of patients with appropriate levels of Hcy, and to define the behaviour of the psychoacoustic tests and of long latency potentials (P300) in these groups. Method We carried out a prospective, comparative and analytic study. The patients gave their authorisation with a signed informed consent. Criteria of Inclusion The inclusion criteria were: patients of 60 years and older, with a tonal auditory threshold at 1 kHz of 30 dB or less, with adequate understanding; if the patients had systemic arterial hypertension, diabetes mellitus or dyslipidemia, that they were under regular medical control. Criteria of Exclusion The exclusion criteria were: patients younger than 60 years, with chronic degenerative or metabolic diseases, without regular medical control, antecedents of epilepsy or seizures, antecedents of drug addiction, major depression, psychiatric disorders, antecedents of stroke or degenerative CNS diseases, kidney failure or chronic hepatitis and antecedents of severe traumatic brain injury. Relatives, friends and patients of the institution who wished to participate and fulfilled the criteria of inclusion were convoked. The case histories and a directed interrogation were prepared to identify the symptoms related to disorders in central auditory processing. All patients had determinations of Hcy, glucose, total cholesterol and triglycerides. We confirmed that the patients did not have dementia by applying the Mini-Mental State exam. In addition, the abbreviated form of the Yesavage geriatric depression scale was applied to be able to rule out depressive states. Otoscopy 267 was performed, and then tonal audiometry using the ascending method with a Madsen Orbiter 922® unit calibrated in trimester form as per ANSI regulations S3.6 and S3.26. Tympanometry was carried out with a calibrated (ANSI regulation S3.39) Zodiac 901® unit, considering normal values to be as follows: static compliance of 0.5---1.5 cm3 and middle ear pressure of +50 to −100 daPa. These results were later catalogued in agreement with the Jerger classification.18 The acoustic reflex was assessed, determining the amount of decibels needed for the presentation of the frequencies of 500, 1, 2 and 4 kHz. A group of cases with HHcy (>15 mol/l) and a group of patients with normal Hcy values (5---15 mol/l) were formed, pairing by age in the majority of the cases. The following phase consisted of applying psychoacoustic tests, beginning with dichotic digits; in this test, stimuli are presented in bilateral form 50 dB above the threshold at 1000 Hz. Thirty items were evaluated and the percentage of right, left, mixed and omissions that the patient gave were quantified. The filtered speech test was given next, at 50 dB above the threshold for the ear being assessed, while the contralateral ear was masked with white noise, 30 dB/s below the stimulus level used for the ear testing. A total of 25 items was assessed and the percentage of appropriate responses was calculated. The word in noise test was given sending stimuli to the ear being assessed, 50 dB above the threshold at 1000 Hz, as well as ipsilateral white noise 10 dB under the stimulus used to assess the words. A total of 25 items as assessed and the percentage of correct responses that the patient had was calculated. In the music test 20 series (each composed of 2 melodies) were assessed; there were 10 series for the right each and 10 for the left, 50 dB above the threshold for 1 kHz, using white noise to mask the contralateral ear. The patients were asked to identify whether the melodies presented equal or different tones and, after that, the percentage of correct responses for each ear was calculated. In the MLD test the patients were instructed to listen to 2 sounds simultaneously and bilaterally: 1 tone and 1 continuous noise. The patients then had to keep pressing a switch during the entire time that they heard the tone, letting go only when they stopped perceiving it entirely. An initial SoNo was used with an S180No stimulus, obtaining the difference in decibels between these 2 phases; and the result was obtained as a binaural test for the two groups. In the electrophysiological assessment, brainstem auditory evoked potentials (BAEP) were performed. Electrodes were applied at the vertex, to both mastoids and ground electrode in Fz. Electrode impedance was less than 5k Ohm. Stimuli were sent at 80 dB with contralateral white noise masking at 50 dB. The values for i---v, i---iii and iii---v complexes were assessed by an expert neurophysiologist. For the P300 study, the electrodes were placed in Fz, Cz and Pz to obtain referenced optimum recordings in a mastoid link. The frequent stimulus was replicated on 160 occasions with a tone of 750 Hz (approximately 80% of the time); the infrequent or oddball stimulus was a tone of 2000 Hz that occurred randomly on 20% of the occasions. Both were presented binaurally at 70 dB HL. The latency and amplitude of the P300 were then determined. Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 268 Table 1 S. Díaz-Leines et al. Demographic Characteristics and Homocysteine Values in the Populations Assessed. Group with HHcy Control group Patient No. Age, years Sex Education Hcy level, micromol/l Patient No. Age, years Sex Education Hcy level, mol/l 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 78 65 60 65 64 67 67 63 72 68 66 77 61 60 85 87 85 Female Female Female Male Male Male Male Male Male Female Female Female Female Female Female Female Male Primary High School Degree Middle School Postgraduate Postgraduate Degree Degree Degree Primary Middle School Middle School Degree Primary Primary Primary Primary 16.9 23.4 25.9 26 16.2 19.3 18.4 20 18 18 19 22.8 23 16 15.3 18.1 16.9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 78 65 62 64 64 66 76 60 73 64 60 75 81 82 61 72 Female Female Female Female Female Female Female Male Male Female Female Female Female Female Female Female Primary High School Degree Middle School Middle School Primary Degree Postgraduate Middle School Degree Degree Primary Primary Primary High School Degree 12.3 10.2 13.4 9.6 14.3 8.2 13.63 9.3 14 8.9 8.4 11.8 11.8 7.2 11.4 14 Using SPSS® version 16 software, measurement of central tendency was measured: arithmetic mean and standard deviation; and as a measurement of significance, the Mann---Whitney U (MWU). Results We assessed 38 individuals; 5 of them were excluded because their auditory threshold in 1 kHz was greater than 30 dB. The final population was 33 individuals, 24 women (73%) and 9 men (27%). The mean age was 69 years. Of the 33 patients assessed, 16 had Hcy values that fell within normal limits (<15 mol/l) and 17 were classified as within the group of patients with HHcy. The mean Hcy concentration in the case group was 19.6 mol/l with SD=2.3 and it was 11.1 mol/l with SD=3.3 for the control group (Table 1). Upon analysing the interview, it was observed that 18 patients reported tinnitus, 7 patients from the control group (21.2%) and 11 (33.3%) from the group with HHcy; the remaining patients (45.5%) denied having this symptom. The other questions asked were not statistically significant. After we analysed the audiometries performed by frequency, we observed that the mean of the responses was similar in the deep frequencies, as well as in the mean frequencies between the group with HHcy and the control group. However, the values of the group with HHcy were greater for the high-pitched frequencies. There were no statistically significant values for any frequencies (Table 2). Tympanometry was performed on all the patients assessed in the study. Of the total right ears assessed, 72.8% presented a Jerger A curve (36.4% of the control group and 36.4% of the group with HHcy). Seven ears (21.2%) presented a Jerger As curve (6.1% in the control group and 15.1% in the group with HHcy), 3% an Ad curve and 3% a C curve. Of the left ears assessed, the A curve was present in 72.7% of the cases (36.4% in the control group and 36.4% in the group with HHcy), and the As curve was present in 21.2% (12.1% in the control group and 9.1% in the group with HHcy). A total of 6.0% had an Ad curve (3% in the control group and 3% in the group with HHcy). When the acoustic reflex was analysed, it was observed that the mean response at 500 and 1000 Hz for both ears was 90 dB, in both the group with HHcy and in the control group. At the frequency of 2000 Hz, the mean response in the right ear in both groups was 90 dB; for the left ear, the mean response for the group with HHcy was 90 dB, while it was 95 dB for the control group. At 4000 Hz, we found that in the right ear the mean response for the control group was 80 dB, while it was 90 dB for the group with HHcy. For the left ear, the mean response at 4000 Hz was 90 dB for both ears. No statistically significant differences were observed in any of the frequencies. When the dichotic digits test was analysed, we found that the mean of the percentage of responses for the right ear in the control group was 62.6%, while for the group with HHcy it was 54.7%; MWU test=89 with P=.94. For the left ear, the mean of the responses for the control group was 17.2% and, for the group with HHcy, it was 16.6%; MWU test =130 500 with P=.845. For the mixed responses, the mean was 14.9% for the control group and 19.3% for the group with HHcy; MWU test =115 000 with P=.465. In the omissions, there was a mean of 3.9% in the control group, while for the group with HHcy the mean was 9.9%; MWU=94 000 with P=.136. In the filtered word test, the mean of responses in the right ear for the control group was 58.5%, while for the group with HHcy it was 52.4%; MWU test =113 000 with P=.423. For the left ear, the mean of correct responses for the control group was 61.2% and for the group with HHcy it was 56.5%; MWU test =125 000 with P=.709. Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. Evaluation of psychoacoustic tests in elderly patients Table 2 269 Analysis by Frequency of the Audiometries Performed. Variables studied Response threshold in dB Results Control HHcy 125 Hz Right ear Left ear 21.2 23.4 20 21.4 123 000 124 500 .657 .683 250 Hz Right ear Left ear 18.4 20.3 19.7 19.7 117 500 129 500 .510 .817 500 Hz Right ear Left ear 15.9 16.5 19.1 18.2 101 500 122 000 .217 .631 1000 Hz Right ear Left ear 14.3 14.3 18.5 17.0 104 500 115 000 .260 .465 2000 Hz Right ear Left ear 19.0 18.1 23.2 20.5 104 500 113 500 .260 .465 4000 Hz Right ear Left ear 33.75 33.75 38.8 39.7 99 500 107 000 .191 .309 8000 Hz Right ear Left ear 48.7 45.9 55.5 56.1 99 500 90 000 .191 .102 The word in noise test presented, for the right ear, a mean of correct responses of 74.5% for the control group, while for the group with HHcy it was 73.8%; the analysis with MWU=130 000 with P=.845. For the left ear, the mean of correct responses was 69.75% in the control group and 70.4% in the group with HHcy; MWU=119 000 with P=.557. In the music test, the mean of correct responses for the right ear in the control group was 90.6% and for the group with HHcy, 78.2%; MWU=88 500 with P=.87. For the left ear, the mean of correct answers in the control group was 90.6%, while it was 78.2% for the group with HHcy; MWU test =92 000 with P=.118. For the MLD test, the mean of responses obtained in the control group was 8.7 dB while for the group with HHcy it was 13.49 dB; MWU=81 000 with P=.049, which was statistically significant (Fig. 1 and Table 3). The BAEP study showed latency values in the i---iii complex for the right ear of the control group of 2.12 ms on average with SD=0.23, while for the group with HHcy the mean of the inter-wave latency for this same ear was 2.15 ms with SD=0.28. It should be pointed out that this complex could not be identified in 2 patients of the group with HHcy; MWU=93 000 with P=.299. For the i---iii complex in the left ear of the control group, the mean latency was 2.04 ms with SD=0.46, while for the group of patients with HHcy the mean latency was 2.21 ms with SD=0.51; MWU test=82 000 with P=.224. The iii---iv complex for the right ear in the control group showed a mean inter-round latency of 2.02 ms with SD=0.34, while for the group with HHcy it was 2.29 ms with SD=0.33; Mann Whitney U P value MWU=69 000 with P=.015. In the left ear, the mean latency for the control group was 2.11 ms with SD=0.33, while for the group with HHcy it was 2.27 ms with SD=0.25; MWU test =86 000 with P=.74. When the i---v complex was assessed, it was observed that the mean inter-round latency for the right ear in the control group was 4.14 ms with SD=0.36, while for the group with HHcy it was 4.47 ms with SD=0.25; MWU=56 500 with P=.11. For the left ear, the mean latency in the i---v complex of the left ear in the control group was 4.15 ms with SD=0.55, while for the group with HHcy it was 4.37 ms with SD=0.35; MWU=70 500 with P=.85. Finally, we analysed the P300 assessed in the patients, finding a mean latency of 303 ms for the control group with SD=28, while in the group with HHcy there was a mean latency of 353 ms with SD=44; MWU test =39.00 with P=.000. With respect to the amplitude of P300, we found a mean of 1.04 mV for the control group with SD=0.58 and of 1.46 mV with SD=1.04 for the group with HHcy; MWU=109 000 with P=.345 (Table 4). Discussion From the analysis of the clinical variables studied, tinnitus stood out with a high rate in the entire population studied; this seems to reflect the conditions of prevalence of the symptom in the older adults, who normally present auditory sensorial deficits that affect central auditory functions responsible for its persistence. Experts in the subject matter Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 270 S. Díaz-Leines et al. 35 30 Decibels 25 20 15 10 5 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 No. of patients Control Figure 1 Table 3 HHcy MLD values obtained in each of the patients. Results of the Psychoacoustic Tests. Variables studied Correct responses Results Control, % HHcy, % Mann Whitney U P value Dichotic digits Right ear Left ear Mixed Omissions 62.6 17.2 14.9 3.9 54.7 16.6 19.3 9.9 89 130 500 115 94 .94 .845 .465 .136 Filtered Word Right ear Left ear 58.5 61.2 52.4 56.5 113 125 .423 .709 Word in noise Right ear Left ear 74.5 69.7 73.8 70.4 130 119 .845 .557 Music test Right ear Left ear 90.6 90.6 78.2 78.2 88.5 92 .87 .118 13.4 dB 81 .049 8.7 dB MLD Table 4 BAEP and P300 Results. Variables studied Mean latency Results Control HHcy BAEP i---iii Right ear Left ear MWU P value 2.12 ms 2.04 ms 2.15 ms 2.21 ms 93.00 82.00 .299 .224 BAEP iii---v Right ear Left ear 2.02 ms 2.11 ms 2.29 ms 2.27 ms 69.00 86 .01 .74 BAEP i---v Right ear Left ear 4.14 ms 4.15 ms 4.47 ms 4.37 ms 56.50 70.50 .423 .85 P300 Latency Amplitude 303 ms 1.04 mV 353 ms 1.46 mV 39.00 109 .000 .345 Documento descargado de http://www.elsevier.es el 19/11/2016. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. Evaluation of psychoacoustic tests in elderly patients have commented on the association of tinnitus with vascular problems and states of depression and psychic conflict. However, in our study we found no differences between the groups, in part because they were regulated by the criteria of exclusion. The histological changes in structures identified as replacements in the auditory pathway, from effects of age, show successive changes in neuronal morphology, synapsing and white matter density,18 which can explain the variations in response observed. Added to the effect of age, we find the metabolic condition under study, the HHcy, and (in the opposite sense) the cerebral plasticity, which shows its characteristics in the elderly adult. The psychoacoustic tests did not show any notable differences with respect to the control group except in the MLD test. Nevertheless, in spite of not being statistically significant, it is noteworthy that the majority of the group with HHcy had a tendency to present lower average responses than the control group. It is useful to emphasise that the rate of alterations in the central auditory processes (evident by means of lower score in the psychoacoustic tests inherent to age) could not be distinguished easily from the control of this variable. The dichotic digits test requires the competence of the systems of attentional control19 and the integrity of the peripheral and central auditory pathways.20 The greater number of omissions presented in the group with HHcy is probably explained by functional alteration of the mechanisms of selective attention, which are related with cognitive systems and with the activation of cortical and subcortical areas that process information relevant for an individual.19 The results obtained in studies such as that of Olsen et al.21 suggest that the patients with presbycusis tend to present low MLD values (≤7---8 dB), which coincide with the values obtained by the control group. The MLD test has been used to assess injuries in the brain stem22 and the test has classically been related to the assessment of the superior olivary complex.23 The higher values of MLD in the group with HHcy make us suspect that HHcy may condition alterations in the integration, comparison and analysis of the temporality of the auditory information related to alterations at this level or in superior levels. In prior experiences in academic studies carried out by the authors, there was evidence that suggested alterations in the highest portions of the auditory pathway, especially in the cerebral cortex, which eventually modified MLD scores towards high values. It is speculated, therefore, that HHcy might be responsible for the altered values in this test. Wack et al.18 studied the function anatomy of MLD using simultaneous application of functional magnetic resonance, observing that with the improvement of the threshold registered by changing from a diotic processing to a dichotic one; there was activation of the left inferior frontal gyrus, of the left insular lobe and of other areas. Those authors mentioned, among their antecedents, cases in which the individual MLD values could be more than 20 dB,18 as we have observed in individual cases of temporal cortical lesion. The iii---v inter-wave latency is an indicator of the conduction of the rostral area of the bridge and of the section of the auditory pathway in the midbrain.24 The inter-latencies for the right ear of the group with HHcy were significantly greater; however, we have found no clear explanation for 271 the reason why conduction times were more affected unilaterally in these patients. ‘‘The latency of the P300 wave tells us the speed with which the subject discriminates the infrequent stimulus, compares the information in relation to the stimulus that is stored in memory and arrives at the appropriate decision’’.24 Classically, it has been related with cognitive perceptual processes that result from higher brain functions, so its register makes it possible to make inferences about higher competencies or central auditory competencies. In this study, the group with HHcy showed greater P300 latency (P=.000). It is known that factors such as tonal auditory level, age,17 education25 and state of wakefulness,26 among others, can affect the latency values of P300. Fortunately, our study presented the strength of having compared groups with tonal threshold close to normal and with similar age and wakefulness conditions, so our findings coincide with the statements of several authors in indicating that HHcy conditions alteration in cognitive processes in elderly adults. Conclusions The alterations in the psychoacoustic and electrophysiological tests observed in the study suggest that CNS is functionally compromised in patients with HHcy. In the clinical audiological symptoms, there are various questions with respect to the vascular and metabolic implications of neural and sensorial hypoacusis, as well as implications of disorders in the central processes of audition. These questions might be clarified through further research on HHcy. 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