Evaluation of Psychoacoustic Tests and P300 Event

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 dl@hotmail.com, joss 81@yahoo.com (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.
Conflict of Interests
The authors have no conflict of interest to declare.
References
1. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A,
Allen RH. Total homocysteine in plasma or serum: methods and
clinical applications. Clin Chem. 1993;39:1764---79.
2. Jacobsen DW, Gatautis VJ, Green R, Robinson K, Savon SR,
Secic M, et al. Rapid HPLC determination of total homocysteine
and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy
subjects. Clin Chem. 1994;40:873.
3. Sachdev P. Homocysteine and neuropsychiatric disorders. Rev
Bras Psiquiat. 2004;26:49---55.
4. Duthie SJ, Whalley LJ, Collins AR, Leaper S, Berger K, Deary IJ,
et al. Homocysteine, B vitamin status, and cognitive function
in the elderly. Am J Clin Nutr. 2002;75:908---13.
5. Sánchez M, Jiménez S, Morgado J. La Homocisteína: un aminoácido neurotóxico. Reb. 2009;28:3---8.
6. Cohen-Salmon M, Regnault B, Cayet N, Caille D, Demuth K, Hardelin JP, et al. Connexin 30 deficiency causes instrastrial fluid
blood barrier disruption within the cochlear stria vascularis.
Proc Natl Acad Sci USA. 2007;104:6229---34.
7. Kundu S, Tyagi N, Sen U, Tyagi SC. Matrix imbalance by inducing expression of metalloproteinase and oxidative stress in
cochlea of hyperhomocysteinemic mice. Mol Cell Biochem.
2009;332:215---24.
8. Marcucci R, Liotta A, Cellai A, Rogolino A, Berloco P, Leprini E, et al. Cardiovascular and thrombophilic risk factors for
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.
272
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
S. Díaz-Leines et al.
idipathic sudden sensorineural hearing loss. J Thromb Haemost.
2005;3:929---34.
Working group on auditory processing disorders. (Central) Auditory Porcessing Disorders. Technical Report: 2. USA: American
Speech-Language-Hearing Association; 2005.
Ruiz I, Castro J. Desórdenes del procesamiento auditivo.
Latreia. 2006;19:368---76.
Romero-Díaz A, Peñaloza-López Y, García-Pedroza F, Pérez Santiago J, Castro Camacho W. Evaluación de procesos centrales de
la audición con pruebas psicoacústicas en niños normales. Acta
Otorrinolaringol Esp. 2011;62:418---24.
Zenker K, Barajas J. Las funciones auditivas centrales. Audit
Rev Electrón Audiol. 2003;3:31---42.
Muellar H, Bright K. Monosyllabic procedures in central testing.
In: Katz J, editor. Handbook of clinical audiology. Baltimore:
Williams & Wilkins; 1994. p. 222---38.
Lewis J, Brefczynski J, Phinney R, Janik J, DeYoe E. Distinct
cortical pathways for processing tool versus animal sounds.
J Neurosci. 2005;25:5148---58.
McPherson D. Late potencials of the auditory system. San Diego:
Singular Publishing Group; 1996.
Descals-Moll C, Burcet J. Potenciales evocados y su aplicación
en epilepsia. Rev Neurol. 2003;34:272---7.
Baron Herrera R, Peñaloza López Y, Flores Rodríguez T, Flores
Ávalos B, García Pedroza F, Herrera Rangel A. Potenciales auditivos de latencia larga: potencial de disparidad y P300 en dos
grupos de adultos mayores. Rev Mex Neuroci. 2011;12:242---9.
Wack D, Cox J, Schirda C, Magnano C, Sussman J, Henderson D,
et al. Functional anatomy of the masking level difference, an
fMRI study. PLoS One. 2012;7:e41263.
19. Pugh K, Shaywitz B, Shaywitz S, Fulbright R, Byrd D, Skudlarski
P, et al. Auditory selective attention: an fMRI investigation.
Neuroimage. 1996;4:159---73.
20. Chermak G, Musiek F. Considerations in the assessment of central auditory processing disorders. In: Chermak G, Musiek F,
editors. Central auditory processing disorders new perspectives. Albany, NY: Thomson Learning; 1997. p. 91---107.
21. Olsen W, Noffsinger D, Cahart R. Masking level differences encounteres in clinical populations. Audiology.
1976;15:287---301.
22. Wilson R, Moncrieff D, Townsend E, Pillion A. Development of
a 500-Hz masking-level difference protocol for clinic use. J Am
Acad Audiol. 2003;14:1---8.
23. Cañete O, Certanec B, Solís F. Resultados de prueba tonal
de fusión interaural (MLD) en adultos audiológicamente normales. Rev Otorrinolaringol Cir Cabeza Cuello. 2005;65:
117---22.
24. Elías Y. Potenciales provocados auditivos del tallo cerebral en
el diagnóstico del daño auditivo y neurológico del adulto. In:
Hernández-Orozco F, Flores T, Peñaloza Y, editors. Registros
electrofisiológicos para el diagnóstico de la patología de la
comunicación humana. Distrito Federal: Instituto Nacional de
la Comunicación Humana; 1997. p. 157---72.
25. Muñoz J, Peñaloza Y, Flores B, Flores T, García F, Herrera A.
Respuestas auditivas tardías: PD y P300, diferencias por edad
y género en dos grupos de adultos mayores con alto grado
académico y actividad intelectual persistente. Rev Mex Neuroci.
2011;12:174---80.
26. Hall JP. 300 Response. In: Hall J, editor. New handbook of auditory evoked responses. Boston: Pearson; 2007. p. 518---47.