Key Words
adults - auditory evoked potentials - AutoNRT - children - cochlear implants - deafness
INTRODUCTION
Recordings of the electrically evoked compound action potential (ECAP) from the auditory
nerve are one of the measurements that have gained widespread use as an objective
tool to estimate the appropriate cochlear implant (CI) settings for patients who are
not able to participate actively in the programming process, for example, small children
receiving implants. An advantage of ECAP is that it is a near-field measurement of
the action potential in the auditory nerve; the implanted electrode records the response
close to its source in the auditory nerve. Thus, the implanted electrode is used both
to electrically stimulate the nerve and to record the response. The measurement can
be performed during surgery and also postoperatively at any programing revisit when
the patient is awake. Measurement of the ECAP threshold has been of great interest
as a tool to assist researchers and clinicians in the programming of the threshold
(T) and comfort (C) levels of the sound processors, that is, the lowest and highest
levels of electrical stimulation assigned for each individual electrode, respectively.
The T- and C-levels control the dynamic range of the stimulation and define the absolute
levels of the stimulation. These levels should be set carefully because too low T-levels
could deprive the CI user of auditory information and too high C-levels could lead
to discomfort. The ECAP measurement also provides important information for surgeons
during implantation in the form of instant verification of electrode function and
placement as well as the responsiveness of the auditory nerve.
Since the introduction of the Nucleus Freedom system with the CI24RE implant in 2004,
a completely automatic ECAP threshold measurement called AutoNRT has been available
for CIs developed by Cochlear Ltd. Before the introduction of AutoNRT, the ECAP threshold
could only be determined by visual interpretation of the ECAP response waveform or
by extrapolation of the amplitude growth function using the slope of a series of suprathreshold
responses to calculate at which stimulation level, the first zero amplitude response
is likely to occur. Both processes can be time-consuming and require expertise to
perform correctly ([Gärtner et al, 2010]). The AutoNRT algorithm imitates the visual identification of the ECAP threshold
and also takes advantage of the much lower noise floor associated with the ECAP recordings
performed with the Freedom system compared with the earlier CI24M/R implants. The
recording process is also faster, as less averaging is needed. AutoNRT provides results
that are equally reliable to those of an experienced observer who visually determines
the thresholds. The high reliability of the AutoNRT procedure is beneficial when results
must be compared between clinics, as it eliminates the subjective differences in the
threshold definition that have been noted between untrained and expert observers ([Van Dijk et al, 2007]; [Gärtner et al, 2010]).
Although ECAP measurements are often used to predict the T- and C-levels for infants
and young children, research has shown that ECAP thresholds do not correspond directly
to the psychophysical thresholds; rather, they often represent the upper half of the
dynamic range between the T- and C-levels ([Brown et al, 2000]; [Smoorenburg et al, 2002]; [Cafarelli Dees et al, 2005]; [McKay et al, 2005]). Studies of relationship between ECAP thresholds and T- and C-levels for individual
electrodes have generally revealed results ranging from moderate to strong correlation
([Brown et al, 2000]; [Smoorenburg et al, 2002]; [Cafarelli Dees et al, 2005]; [Lai et al, 2009]). Alternative methods to use ECAP thresholds have consequently been proposed to
compensate for these differences; [Brown et al (2000)] suggested the use of ECAP in combination with a behavioral T-level measurement of
a single electrode, and more recently, [Botros and Psarros (2010)], in a study, successfully used the scaled ECAP threshold to set the T- and C-levels.
To use the ECAP threshold, it is important to know the variation of the neural thresholds
over time, and if there is a point in time after implantation where the thresholds
can be considered stable. If the ECAP thresholds used for programming vary after the
programming, it likely will affect the outcome for the patient.
A previous study by [Spivak et al (2011)] examined the longitudinal change of AutoNRT thresholds measured with the CI24RE
implant for children and adults. It compared the intraoperative measurements of five
electrodes spread across the array until 3 months of use. The study showed that thresholds
recorded intraoperatively are likely to be higher than those recorded at the initial
activation and at the 3-month follow-up. However, it stressed that the results suggested
that electrodes 11 and 16 had lower within-subject variability between the intraoperative
and postoperative measurements compared with other electrodes examined and, therefore,
most accurately would predict the postoperative result. Variation between the intraoperative
and postoperative measurements of the manual recording procedures of the CI24RE implants
have also been reported ([Gordin et al, 2009]). [Lai et al (2009)] showed stable results for the CI24RE from initial activation until 12 weeks after;
this was, however, based only on group mean values which does not necessarily would
yield the same results if individual differences were taken into account. For the
older CI24M implant, stabilization was reported to occur between 3 and 8 months ([Hughes et al, 2001]). In addition, studies with the CI24M/R implants, conducted over both 4 and 8 years,
have shown that once the ECAP thresholds become stable, they remain so for a substantial
time ([Lai et al, 2004]; [Brown et al, 2010]).
AutoNRT has gained widespread clinical use, but there is still no study that has included
results from all 22 electrodes over a sufficient period of time to determine when
stable results can be expected and examine the possibility that certain electrodes
stabilize more rapidly than others. The need for stable AutoNRT thresholds is most
evident when they are used to program the T- and C-levels in CI’s, and the use of
AutoNRT thresholds for programming is most necessary for the youngest children receiving
implants and other individuals who cannot participate in behavioral measurements.
The primary aim of this study was to verify when the AutoNRT thresholds of young children
and adults are stable and when they can be used to program the stimulation levels
of the patient’s CI.
MATERIALS AND METHODS
Participants
Data in this study were collected at 13 centers located in Israel, Italy, Spain, and
Sweden as part of a multicenter clinical investigation. The investigation was performed
according to the guidelines established by the Declaration of Helsinki; the ethics
committee approved this protocol before data collection began. Informed consent was
obtained from all participants and/or their guardians.
The study included 53 children (mean age at implantation, 1.8 years; range, 0–3 years)
and 80 adults (mean age, 56.9 years; range, 20–83 years). All participants had bilateral
severe to profound sensorineural hearing loss during a period of time that did not
exceed 15 years. The hearing loss etiologies are shown in [Table 1]. Medical examinations, including magnetic resonance imaging, were conducted to ensure
there was no cochlear abnormality or ossification that could prevent successful electrode
array insertion. Subjects with signs of retrocochlear or central hearing impairment
were not included in this study.
Table 1
Causes of Deafness
|
Etiology
|
Children (n)
|
Adults (n)
|
|
Familial
|
19
|
12
|
|
Meniere’s Disease
|
0
|
9
|
|
Meningitis
|
1
|
0
|
|
Noise exposure
|
0
|
1
|
|
Otosclerosis
|
0
|
2
|
|
Ototoxic drug
|
1
|
3
|
|
Trauma
|
0
|
1
|
|
Unknown
|
31
|
42
|
|
Viral
|
1
|
0
|
|
Total
|
53
|
80
|
All participants received the Nucleus Freedom cochlear implant CI24RE Contour Advance
with 22 electrodes and the Freedom sound processor.
AutoNRT
The AutoNRT measurements were conducted using Custom Sound software. The same ECAP
analysis algorithm was used for all versions of the software in this study. The software
uses two protocols to measure ECAP thresholds, one for intraoperative and one for
postoperative measurements. The intraoperative measurement protocol uses a 250-Hz
stimulation rate and begins the stimulation at a current level (CL) of 170; it also
uses conditioning pulses at 230 CL to reduce intraoperative artifacts associated with
the high impedance present immediately after electrode insertion. The intraoperative
protocol is primarily designed to minimize the test time and is not used if the patient
is not under general anesthesia. The postoperative protocol uses an 80-Hz stimulation
rate that starts at 100 CL and does not use conditioning pulses. The postoperative
protocol is intended for use in awake patients and was devised to avoid stimulations
that may cause patient discomfort. As a result, it requires more time than the intraoperative
protocol because of the slower stimulation rate and the lower starting point of the
stimulation. In-depth descriptions of the decision tree analysis and AutoNRT algorithm
have been previously described [Botros et al (2007)]. The stimulation rates used by the two protocols were determined to not significantly
affect the threshold response ([Spivak et al, 2011]).
AutoNRT was performed to record the ECAP thresholds from all intracochlear electrodes
of both children and adult subjects. Data were collected at six time points for children:
intraoperatively, at the initial activation, and at 1, 3, 6, and 12 months after the
initial activation. For adults, measurements were performed at four time points: intraoperatively,
at the initial activation, and at 6 and 12 months after activation.
Statistical Analysis
To compare AutoNRT thresholds between time points, the Pearson correlation coefficient
and the absolute mean difference was calculated by comparing a single electrode threshold
from one time point to the subsequent measurement. This was carried out by comparing
the thresholds for each individual electrode. All statistical analyses were performed
with IBM SPSS Statistics for Windows, version 23.0 (IBM Corp., Armonk, NY).
RESULTS
Mean Variation in AutoNRT Thresholds over Time
The mean of the AutoNRT thresholds demonstrated, on group level, that for both children
and adults, the intraoperative measurement deviated compared with the postoperative
measurements, whereas the postoperative mean results showed consistency over time
([Figure 1]). The children’s intraoperative measurements seemed to be closer to their postoperative
results than the measurements of the adults, for some electrodes. However, the AutoNRT
threshold profile was not consistent between the intra- and the postoperative measurements.
The intraoperative thresholds showed a general gradual increase in CL toward the electrode
1, whereas the postoperative measurements showed a different profile (see [Figure 1A]). Worth pointing out is that a mean result overlap is not necessarily caused by
good individual consistency over time between measurements.
Figure 1 Mean AutoNRT thresholds of (A) 53 children aged 0–3 years and (B) 80 adults aged
20–83 years, recorded at different time points from surgical insertion of the CI electrode
until 12 months after the initial activation. The standard error was 1.9–4.3 for children
and 1.3–3.7 for adults.
In contrast to the children, the adults’ results showed similar threshold profiles
at all time points. However, the intraoperative result revealed higher AutoNRT thresholds
than the postoperative ones.
Correlation of AutoNRT Thresholds When Subsequent Measurements Were Compared
Subsequent measurements were compared on an electrode-per-electrode basis for each
measurement to make the individual variation visible. The scatter plots in [Figures 2] and [3] show the variation in the individual thresholds for each electrode between subsequent
measurements. The results revealed considerable variation between the intraoperative
and initial activation measurements, and the difference between the following measurements
gradually decreased. The correlation in the children increased during the first 3
months after implantation, and remained high (r = 0.91) from 3 months onward. There was a higher correlation between the intraoperative
and initial activation measurements of the adults (r = 0.72) than those of the children (r = 0.58) ([Figures 3] and [2], respectively). There was also a high correlation (r = 0.93) between the last two measurements (6 and 12 months) of the adult subjects.
Figure 2 Scatter plot comparing the AutoNRT measurements of all 22 electrodes from the intraoperative
time point until 12 months after the initial activation of CIs in children. The Pearson
correlation coefficient r was calculated for each comparison.
Figure 3 Scatter plot comparing the AutoNRT measurements of all 22 electrodes from the intraoperative
time point until 12 months after the initial activation of CIs in adults. The Pearson
correlation coefficient r was calculated for each comparison.
The results showed that there was a higher variation between postoperative measurements
than could be seen using the mean values in [Figure 1]. The children’s results showed consistently high correlation (r = 0.89) beginning 1 month after activation. The adults were not measured at 1 and
3 months. However, the measurements taken at 6 and 12 months after activation had
a high correlation (r = 0.93).
Comparison of Each Electrode
The previously described mean AutoNRT threshold of the children indicated that electrodes
in the middle of the array are more stable over time than those near the apical and
basal ends of the array. To examine this phenomenon, we calculated the mean of the
absolute difference between the subsequent measurements of each electrode and the
correlation between each electrode and its subsequent measurement.
The mean absolute difference in the children ([Supplemental Table S1], available with the online version of this article) showed that the intraoperative
and the initial activation measurements of all electrodes varied considerably; the
mean ranged from 13 to 24 CL. However, between the two final measurements, the mean
absolute difference ranged from 3 to 9 CL. The correlation when the intraoperative
and initial activation were compared varied between r = 0.19 and r = 0.76. At 6 and 12 months after activation, r was between 0.77 and 0.97, respectively. Electrode 1 was distinguished in all comparisons
regarding the children, as it had both a high absolute mean value (9–24 CL) and a
low correlation (r = 0.57–0.88) compared with the other electrodes.
The results of the adult subjects ([Supplemental Table S2], available with the online version of this article) showed a mean absolute difference
of the intraoperative and initial activation for each electrode of 16–21 CL, which
decreased to 3–6 CL when the 6- and 12-month measurements were compared. The correlation
in the adults varied between r = 0.54 and r = 0.83 when the intraoperative and initial activation measurements were compared,
and between 6 and 12 months, it increased to between 0.81 and 0.96, respectively.
The results of the adult measurements did not indicate any single electrode to be
less stable than the others.
The variation between measurements decreased over time in both children and adults.
The results did not reveal any electrode/s or region of the electrode array that was
more stable over time for either group.
DISCUSSION
Correlation of AutoNRT Thresholds When Subsequent Measurements Are Compared
We investigated the changes in the AutoNRT thresholds during the first year after
CI in adults (20–83 years) and young children (0–3 years) on all 22 electrodes. Our
results showed that the postoperatively recorded AutoNRT thresholds clearly deviated
from those intraoperatively recorded and that no specific electrode’s threshold was
more stable over time. Stable threshold results were seen in children at 1 month after
activation and later. Our results showed that the thresholds in adults were stable
at 6 months.
The thresholds of the adults in this study were measured at fewer time points, which
made it difficult to compare the results between the two groups. Based on the comparisons
of the same time points between groups, the correlations observed in the adult subjects
were similar or even slightly better than those of the children. Therefore, it could
be that the adults also would have shown stable results at 1 month, if it would have
been measured.
The results presented here indicate that AutoNRT is a reliable and stable measurement
when performed at the correct time. Compared with the results by [Tavartkiladze et al (2015)], this study show only slightly lower correlation for a long-term follow-up period
(3 and 6 months).
The difference between the intraoperative and postoperative measurements agrees with
the AutoNRT results by [Spivak et al (2011)]. They also correspond to other studies that examined the manually recorded ECAP
thresholds ([Hughes et al, 2001]; [Gordin et al, 2009]). The variation between intraoperative and postoperative measurements may be due
to several contributing factors. The insertion of the electrode array affects the
composition of the cochlear fluids, and may cause damage to the cochlear walls, causing
the need of higher stimulation levels intraoperatively before returning to a normal
state. In addition, [Hughes et al (2001)] suggest that the fibrous tissue, which encapsulates the array over time, affects
the electrical transmission from the electrodes to the auditory nerve.
[Spivak et al (2011)] stated that the intraoperative measurements for electrodes 11 and 16 were closer
to the postoperative measurements. However, careful examination of the results of
all 22 electrodes revealed that the thresholds of adjacent electrodes can vary substantially.
A comparison of the results of all electrodes showed that the intraoperative results
were more random than the postoperative results. If only a subset of the electrodes
in each part of the array is examined, this randomness could remain undetected. Therefore,
when considering all electrodes, we cannot state that electrodes in certain regions
are generally more stable over time. This seems to be true for all electrodes, with
the exception of electrode 1 in children. Considering the variability and relatively
high mean results of electrode 1, it is advisable to take additional caution when
using the AutoNRT results of this electrode to program the implant. The higher and
more fluctuating results of electrode 1 is likely reflecting the electrode’s basal
placement in the cochlea and close proximity to the insertion point of the electrode
array. Based on our clinical experience, it may in many cases be better to deactivate
this electrode from the map.
The present results showed large variations between the AutoNRT thresholds measured
intraoperatively and at initial activation. The AutoNRT thresholds should therefore
be remeasured postoperatively to ensure they are stable enough to be used as a basis
for setting the T- and C-level profiles.
Mean Result of AutoNRT Thresholds over Time
There appeared to be a robust AutoNRT threshold profile visible in all postoperative
measurements for both children and adults; they all show a very similar relative difference
between electrodes across the array. There was an increase in the CL from the apical
end, with a well-defined decrease from approximately electrode 7 to electrode 4, which
increased again near electrode 1 at the basal end of the array. Similar threshold
profiles have been presented in other studies ([Botros and Psarros, 2010]; [Tavartkiladze et al, 2015]). This result indicates that there is a greater need to record the thresholds of
neighboring electrodes in the basal section of the array than in the middle or apical
sections because these thresholds more accurately can be interpolated.
Limitations and Future Directions
The implant CI24RE was used in this study; however, the results should also be valid
for the newer precurved implant type, CI512, which has an updated housing, but still
uses the same electrode array as the CI24RE. In addition, newer implants from Cochlear
Ltd., use similar amplifiers for the ECAP recording as the CI24RE. However, this does
not ensure that the results presented here are applicable to other types of implants.
The development of thinner electrode arrays could lead to different results, especially
regarding the intraoperative result, if it has a decreased effect on the internal
physical structure of the cochlea during insertion. Studies on other electrode types
are, therefore, required.
Although, our results have shown that AutoNRT thresholds are stable from 1 month for
children, further validation of AutoNRT as the main basis for setting the T- and C-levels
on children is needed.
CONCLUSIONS
We have demonstrated that there are large differences between the AutoNRT thresholds
recorded intraoperatively and those recorded postoperatively, that the thresholds
in children are stable from 1 month after initial activation, and that the thresholds
in adults are stable from at least 6 months after initial activation. We have also
shown that AutoNRT thresholds obtained after this stabilization period are reliable
and that there is no specific electrode that generates more reliable results than
others. For clinicians, who program CIs, we have shown the importance of repeating
the AutoNRT measurements postoperatively, at least at about 1 month after activation,
to obtain reliable and stable results to serve as a basis for setting the T- and C-level
profiles. However, the accuracy of AutoNRT-based map profiles requires further validation.
Abbreviations
CI:
cochlear implant
C-level:
comfort level
CL:
current level
ECAP:
electrically evoked compound action potential
T-level:
threshold level
