Auditory Evoked Potentials

Middle Latency Auditory Evoked Potentials in Temporal Lobe Disorders Wafaa Shehata-Dieler, MD; Hiroshi Shimizu, MD, MScD; Salah M. Soliman, MD, ScD; Ronald J. Tusa, MD, PhD The Johns Hopkins Medical Institutions, Baltimore, Maryland (H.S, R.J. T.) and Ain Shams University Hospitals, Cairo, Egypt (W.S.-D., S.M.S.)

ABSTRACT Middle latency auditory evoked potentials (MAEP) were recorded in 30 normal subjects and in 19 age-matched patients with temporal lobe lesions. MAEP appeared to be differentially affected by the specific structures involved within the temporal lobe. In the majority of patients with lesions involving the auditory area and/or auditory radiation, Na-Pa amplitude was significantly reduced over the involved hemisphere. No similar reduction in amplitude was noted in subjects with lesions not involving the auditory structures within the temporal lobe. We also observed a shift in a Pa latency over the involved hemisphere in patients with temporal lobe lesions involving the auditory structures. This latency shift was less pronounced than the amplitude reduction. The generators of MAEP in humans are discussed according to these findings and to the available literature. Normal intersubject variability of the conventional amplitude measures, and the occasional myogenic contamination of the response, limits establishing reliable criteria for abnormality that can be applied clinically for the diagnosis of patients with temporal lobe disorders. (Ear Hear 12 6:377-388).

THE MIDDLE LATENCY auditory evoked potentials (MAEP) have attracted the attention of several investigators as an adjunct to auditory brain stem response (ABR) in the diagnosis of lesions central to the brain stem. However, there is a lack of complete understanding of the extent of its underlying neural generators and of the validity of the procedure as an objective, noninvasive technique for the diagnosis of such lesions. There have been conflicting reports on the effects of temporal lobe lesions of MAEP. Graham, Greenwood, and Lecky (1 980) and Ozdamar, Kraus, and Curry ( 1982) reported absent MAEP in patients with bilateral lesions involving the temporal lobes, whereas Parving, Salomon, Elberting, Larsen, and Lassen ( 1980) showed normal Ear and Hearing, Vol. 12, No. 6, 1991

MAEP in one patient with bilateral temporal lobe lesions. Kraus, Ozdamar, Hier, and Stein (1982) found abnormal responses in patients with unilateral temporal lobe lesions, but in some patients the response remained intact in spite of the presence of substantial temporal lobe damage. Both Kileny, Paccioretti, and Wilson (1987) and Ibaiiez, Deiber, and Fischer (1989) reported Pa amplitude reduction over the involved hemisphere in patients with unilateral lesions affecting the temporal lobe or the acoustic radiation. Woods, Clayworth, Knight, Simpson, and Naeser (1987), on the other hand, reported intact MAEP in three out of five patients with bilateral lesions involving the temporal lobe. Ho, Kileny, Paccioretti, and McLean ( 1987) demonstrated severe impairment of the MAEP in a patient with bilateral temporal lobe lesions. The response showed an improvement which was consistent with the improvement seen in the computerized tomography (CT) scan of the patient. The diversity of findings in those patients can be due to several factors, the most important of which is the diversity of the generators themselves. However, other factors, such as the effects of aging or a coexisting peripheral hearing loss, were not accounted for in the majority of reports and can lead to response modifications in these patients, thus confounding the effects of the target lesion. Age-related central changes in auditory processing was reported to cause amplitude enhancement and latency prolongation of the Pa component of the MAEP (Woods & Clayworth, 1986). The presence of peripheral hearing loss can also affect the response amplitude and, to a lesser degree, lead to latency shift, especially with earlier peaks (Maurizi, Ottavian, Paludetti, Rosignoli, Almadon, & Tassoni, 1984; McFarland, Vivion, & Goldstein, 1977; Thornton, Mendel, & Anderson, 1977). Conflicting results associated with different pathological lesions at various levels of the auditory pathway require further investigation of pathophysiological correlates of MAEP in patients with temporal lobe lesions. We have measured the MAEP in a group of patients with lesions affecting various areas of the temporal lobe with different etiologies to investigate the effects of site of lesion within the temporal lobe on the response latency and amplitude, to compare the response latency and amplitude values of patients to those of age matched normal subjects, and to evaluate the diagnostic

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0196/0202/91/1206-0377$03.00/0 ' EARAND HEARING Copyright 0 1991 by Williams & Wilkins Printed in the U S A .

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value of M A E P in temporal lobe lesions. To avoid confounding effects of aging on the response, we limited our sample t o patients under 60 yr old. T h e effects of peripheral hearing loss were accounted for by performing pure-tone audiometry a n d selecting a stimulus for eliciting the M A E P (broad-I1 or narrowband stimulus) according to the patient's hearing configuration to ensure normal thresholds. MATERIALS AND METHODS

Subjects MAEP were recorded in 30 normal subjects (normal-hearing and neurologically free) and 19 patients with unilateral temporal lobe lesions. Both normal subjects and patients were in the same age range ( 16-60 yr) and were agematched (+5 yr). All subjects had conventional behavioral audiometry (pure tones and speech audiometry). Patients were excluded from the study if they showed impaired thresholds (more than 25 dB HL) within the frequency range of the stimulus which was used to elicit the MAEP (0.1 msec click or 1 .O kHz-tone burst).

Selection of Patients Evaluation of the locations of temporal lobe lesions was based on CT scan, magnetic resonance imaging (MRI), or surgical notes. Patients were classified according to the structures involved within the temporal lobe into two groups. auditory (A) and nonauditory (B). Lesions were reconstructed on templates of horizontal sections of the human brain based on CT scans made in the orbital-meatal plane. Reconstruction of lesions and classifying patients into groups were done by a neurologist who was unfamiliar with the patients' MAEP results. The temporal lobe lesions were of different etiologies, including tumors ( n = 6), vascular lesions involving the middle cerebral artery or its temporal branches ( n = l), and Sjoegren's syndrome with central nervous system (CNS) complications ( n = 1). Tables 1 and 2 describe the extent of brain lesions and their etiologies. All these patients showed normal ABR with respect to the waveform morphology and peak latency values. ABR were recorded before MAEP. Patients with temporal lobe lesions with various etiologies were selected to be in the study group. Vascular lesions are better than other types of lesions and permit clear cut anatomical correlations to physiological findings. However, to be able

~________

Table 1. Summary of data obtained from patients with temporal lobe lesions involving the auditory areas (group A)."

Case

Age

Lesion Site

Etiology

2

57 41

Temporoparietal (L) Temporoparietal (R)

Tumor Tumor

3

25

Temporal (R)

5

30

6 7

46 25

Temporoparietal(L) 8 Corpus Callosum Temporoparietal(R) Frontotemporal (R)

Hematoma (trauma) Tumor

12 16 17 18

48 60 46 44

Temporal (R) Temporal (R) Temporoparietal (R) Temporoparietal (L)

Infarct Hematoma (trauma) lschaemia Infarct Tumor Infarct

19

52

Temporoparietal (L)

Infarct

1

Hearing

Stimulus

Normal Normal (R) Mild HF HL (L) Normal

Click Click & Tone Burst

Pa Largest CElL Pa Reduced IL

MAEP

Click

Pa Reduced IL

Normal

Click

Pa, Na Reduced IL

Normal Normal

Click Click

Pa Reduced IL Pa Reduced IL

Normal Mod HF HL Mod HF HL Mild to mod HF HL Normal

Click Tone burst Tone burst Tone burst

Pa Mild Reduction IL Pa Reduced IL Pa, Na Reduced IL Myogenic

Click & Tone Burst

Myogenic

(L), left; (R), right; IL, hemisphere ipsilateral to the lesion; CL,hemisphere contralateral to the lesion; HF, high-frequency; HL, hearing loss; Mod, moderate; CE,contralateral ear (relative to the active electrode). a

Table 2. Summary of data obtained from patients with temporal lobe lesions involving the nonauditory areas (group B).'

Case

a

378

Stimulus

MAEP

4 8

Age 18 19

Temporoparietal (L) Temporal (L)

Lesion Site

Trauma Gun Shot Lobectomy

Etiology

Normal Normal

Hearing Click Click

9 10

32 50

Lobectomy Lobectomy

Normal Normal

Click 8 Tone Burst Click 8. Tone Burst

11

53

Temporal(R) Temporofrontal & Occipital (R) Temporal (L)

Normal Na Reduced Pa Reduced IL Pa, Na Larger IL Pa, Na Larger IL

Soegren's Syndrome

Click & Tone Burst

Normal

13 14 15

25 33 59

Temporal (L) Temporal & frontal (L) Fronrotemporal (L)

Epilepsy Tumor Tumor

Normal (R) Mild HF HL (L) Normal Normal Normal

Click Click Click

Normal Myogenic Normal

(L),left; (R), right. Shehata-Dieler et al

Ear and Hearing, Vol. 12, No. 6, 1991

to investigate the clinical value of MAEP as an objective mean for diagnosis and follow-up of patients, it was essential to include patients with lesions of various etiologies like trauma and tumors. Patient 4 (cf. Table 2) had a penetrating injury with well-defined localized brain laceration, and the other two trauma patients (3 and 7) (cf. Table 1) had hematomas after head traumas. In tumor patients, the deficits caused by the lesion can be the result of local structural damage and/or perifocal edema, which can both be detected on the CT scan or MRI. Distant effects of herniation in tumor patients would not allow a clear cut roentogenographic determination of the site of lesion; however, there was no evidence of herniation in any of the tumor cases. Moreover, effects of lesions of MAEP in the trzuma and tumor patients corresponded to the effects of lesions caused by strokes in this study as well as in previous reports (Kileny et al, 1987; Kraus et al, 1982; Woods et al, 1987; Ibaiiez et al, 1989). Therefore, we included data from these patients in our study. Patients with temporal lobectomies were assigned to the nonauditory group, because only the anterior and middle temporal gyri and the amygdaloid nucleus were excised and the superior temporal gyrus was left intact. To estimate the location ofauditory projections from the thalamus to the primary auditory cortex, we measured the distance between the anterior tip of the temporal lobe and the medial geniculate body from three post mortem human brains after autopsy. This was done to evaluate the possibility of injuring the thalamic projections to the auditory cortex during lobectomy. Stimuli Two types of stimuli were used to elicit the MAEP: a broadband alternating click of 0.1 msec duration and a 1.0 kHz tone burst with rise/decay time of 2 msec and no plateau (2-0-2). Real time analysis of the frequency spectrum (power spectrum) of the signal used showed that for the click stimulus, the main peak was at 3.250 kHz, with the second prominent peak at 6.0 kHz and the spectrum extending out to 6.750 kHz. For the 1.0 kHz tone burst, the peak was at 1.0 kHz and extended to 0.4 kHz on the low end and 1.350 at the high end (Fig. I). In the control group, subjects received both click and tone burst stimuli. In the patient group, the response was elicited either by click or by tone burst, according to the hearing thresholds; in patients with normal hearing up to 6.0 kHz the response was elicited by click, whereas in patients with high-frequency hearing loss beyond 1.5 kHz, the response was elicited by tone burst. This was done to ensure that patients’ hearing thresholds were normal for the frequency range of the stimulus. In six patients, for whom the general conditions allowed longer testing time, the response was elicited by both click and tone burst stimuli. Tables 1 and 2 describe the hearing profile of each patient and the stimulus/stimuli used to elicit the MAEP. All stimuli were delivered monaurally at 70 dB nHL at a repetition rate of 9/sec. MAEP Recording MAEP were recorded simultaneously at scalp locations C5 and C6 (located approximately over the superior temporal plane, midway between C3-T3 and C4-T4, respectively) as well as from the vertex location Cz. All recordings were referenced to the earlobe ipsilateral to the stimulated ear with the ground electrode on the opposite earlobe. Interelectrode impedance was maintained below 3 kohm throughout the recording session. The earlobe placement was used for the reference electrode to decrease the possibility of myogenic contamination, which is usually more common with mastoid placement. Recordings were done in a sound-treated, electrically shielded room. At least two trials of 1000 stimuli were collected for each recording condition. Ear and Hearing, Vol. 12, No. 6, 1991

When the response was not identifiable, 2048 sweeps were collected. The response recorded with the surface electrodes was amplified (X50,000), bandpass filtered (10-1000 Hz, 12 dB/octave), and averaged for 102 msec beginning with the stimulus onset. Artifact rejection was set at 43 pV. MAEP evaluation was based on waveform identifiability, Na and Pa latency, and peak to peak amplitudes measured from wave V (of ABR) to Na (ABR-Na) and from Na to Pa (Na-Pa) (Fig. 2A). Response identification as well as latency and amplitude

A

2

I

0

3

4

5

7

6

8

3.25

PWK SPECTKA :- 32.3 dBV

9

10

kHz

kHz

S P A N O.Oo0 H~-10.000kHz

0

1

2

3

4

5

7 8 9 1 0 k H z 1.00 kHz

6

PWK SPECTKA :- 30.6 dBV

SPAN: O.Oo0 Hz-10.000kHz

Figure 1. Frequency spectrum of the acoustic signals used to elicit MLR. A, click; B, 1 kHz tone burst. V

Na

o

a

24

Nb

40

56

12

aa

msec

Figure 2. Tracings showing MAEP recorded at the vertex (Cz)from a normal-hearing adult in response to click stimulus at 70 dB HL. A) Composite waveform from the summation of 2000 sweeps (represented in B). B) Two responses, each consisting of 1000 sweeps.

MAEP in Temporal Lobe Disorders

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measurements were done visually by two investigators, independently, one of whom was unfamiliar with the CT scan data or the patient’s group. The latency was measured by moving the computer cursor (with 0.4 msec analysis interval) to the highest point of the peak. In the present study, peak to peak amplitude measures were preferred to absolute (zero) amplitude measures because the latter are usually affected by baseline level. The amplitude measures from waveforms which were not identified were recorded as absent (rather than 0).Peaks Na and Pa were the only measures considered to be due to the poor identifiability of the other MAEP components. Peaks No, Po, Nb, and Pb were identifiable in less than 65% of normal subjects. Myogenic contamination of the response, mainly by postauricular muscle response (PAMR, see Fig. 3) was observed in some subjects, particularly at the beginning of the recording session. Cases in which myogenic contamination of the response persisted were excluded from the analysis. Criteria for identifying myogenic contamination of the response were: large amplitude with a sudden drop in amplitude on decreasing the stimulus intensity, sharp configuration, tendency toward earlier latency, and presence in some tracings and absence in others (same subject). The data were analyzed statistically by means of an analysis of variance (ANOVA) through a mixed model. In this model, the effect of the subject (as a random effect variable) was added to the model together with the effects of other factors. In the normal (control) group, these factors were the stimulus (click or tone burst) and the recording site (ipsilateral, contralateral to the stimulated ear, and midline Cz). In the patient groups, these factors were recording hemisphere (ipsi- or contralateral to the lesion) and the stimulated ear (ipsi- or contralateral to the recording electrode site). Testing for significant differences between individual pairs of means was done by Duncan’s Multiple Range test with a level of significance at 0.05.

RESULTS

Normal MAEP Mean values and SD of MAEP latency and amplitude for normal subjects are summarized in Table 3. Responses from one normal subject to click and 1.0 kHz tone burst are shown in Figures 2 and 4, respectively. The ANOVA results indicated that latencies for peaks Na and Pa were significantly shorter for click than for 1.O kHz tone burst stimulus ( F = 36.8; df = 1,104; p < 0.01 for Na and F = 16.44; df = 1,106; p < 0.01 for Pa). Na and Pa peak amplitudes were slightly, although not significantly, larger for tone burst than click stimuli ( p > 0.05). Na-Pa amplitude was significantly larger at the vertex (Cz) as compared to the temporal electrodes both ipsilateral (IE) and contralateral (CE) to the stimulated ear ( F = 11.58; df = 2,101; p < 0.001). Na-Pa amplitude recorded contralateral to the stimulated ear (CE) was larger than that recorded ipsilateral to the stimulated ear (IE). This difference was not statistically significant ( p > 0.05). In general, amplitude measures showed

Table 3.MAEP results in normal subjects. Means f SD.

Click IE CE

cz

19.4f 1.6 32.4f 2.8 0.62f 0.24 0.73f 0.25 19.3? 1.4 32.7f 2.9 0.75f 0.27 0.88f 0.37 19.4f 1.9 31.9 f 3.6 0.70f 0.22 0.94 ? 0.35

. 0 8

24

40

56

72

88

msec

Figure 3.Tracings showing myogenic activity from the PAMR with the characteristic short latency (approximately 14 msec), large amplitude, and sharp configuration. This response was recorded at the vertex (Cz) and obscured the identification of MAEP components.

380

Shehata-Dieler et al

Na-Pa AmDlitude

18.1 f 1.4 31.3 f 2.7 0.60f 0.19 0.69f 0.22 18.2k 1.3 31.5 ? 2.4 0.58f 0.23 0.73f0.22 17.6f 1.2 30.9 f 2.7 0.65f 0.24 0.92f 0.33

Tone burst IE CE cz

0

ABR-Na AmDlitude

Na Latencv Pa Latencv

8

24

.

.

40

. 56

.

. 12

88

msec

Figure 4. Tracings showing MAEP recorded at the vertex (Cz) from a normal-hearing adult in response to 1 kHz tone burst at 70 dB HL. A) Composite waveform from the summation of 2000 sweeps (represented in B). B) Two responses, each consisting of 1000 accepted sweeps.

Ear and Hearing, Vol. 12, No. 6,1991

considerable intersubject variability for both ABR-Na and Na-Pa amplitudes. Myogenic contaminations from PAMR (Fig. 3) were observed in two normal subjects and three patients (see Tables 1 and 2) and were excluded from the analysis. Effects of Temporal Lobe Lesions of the MAEP MAEP data from patients were classified according to the hemisphere over which the response was recorded, ipsilateral to the lesion (IL) or contralateral to the lesion (CL) and the stimulated ear ipsilateral to the active electrode (IE) or contralateral to the active electrode (CE). Thus, IEIL represents responses recorded over the hemisphere containing the lesion with stimulation of the ipsilateral ear, whereas IECL means recording from the intact hemisphere (i.e., contralateral to the lesion) with stimulation of the ipsilateral ear. MAEP latency and amplitude values from all patients for both click and tone burst showed a wide range of variability that was more pronounced with Na-Pa amplitude measures. There were no statistically significant differences in response latency or amplitude between lesion and nonlesion sides with contra- or ipsilateral ear stimulation ( p > 0.05). ABR-Na and Na-Pa peak amplitude data obtained from all patients using click stimuli are shown in Figure 5 . Patients with temporal lobe lesions were classified into those with lesions involving the primary auditory area and/or auditory radiation (auditory group, n = 9*) and those with lesions not involving these structures (nonauditory group, n = 7*). Figures 6 and 7 show samples of temporal lobe lesions for the auditory group (A) and the nonauditory (B) group. A summary of the MAEP results (pooled over different recording/stimulus conditions) for every patient is represented in Tables 1 and 2. Mean (kSD) latency and amplitude values of MAEP recorded from the auditory (A) and nonauditory (B) groups are shown in Tables 4 and 5, respectively. Auditory Group (A) There was an overall reduction in the response amplitude in the auditory group compared to normal subjects. This reduction was more pronounced for Na-Pa amplitude measures than for ABR-Na amplitude. In all subjects except patient 1 (cf. Table l), this reduction in amplitude was more pronounced over the hemisphere ipsilateral to the lesion (IL) compared to the hemisphere contralateral to the lesion (CL) both with ipsi- and contralateral ear stimulation. Statistical analysis showed that Na-Pa amplitude recorded over the involved hemisphere was significantly reduced compared to that recorded over the noninvolved hemisphere ( F = 6.1 1, df = 1,9; p < 0.05 for click-evoked response and F = 8.3, df = 1,6; p < 0.05 for tone burst-evoked response). No significant difference was detected between the ears ( p < 0.05). The statistical interaction between the stimulated ear and the recording site was not significant ( p > 0.05), indicating that for group data, the reduction in ampli-

'After excluding subjects with myogenic contamination.

Ear and Hearing, Vol. 12, No. 6,1991

h

1 0.8 a 3.-- 0.6 aE" 0.4 v

0.2

0

ABR-Na

Na-Pa

Figure 5. Bar graphs showing the mean k SD for the ABR-Na amplitude and the Na-Pa amplitude in normal subjects and in temporal lobe patients. The responses were recorded at the hemisphere ipsilateral to the lesion (IL) and the contralateral intact hemisphere (CL).Na-Pa amplitude values recorded from the side of lesion (IL) showed a considerable degree of variability.

tude was not more pronounced when stimulating the ear ipsilateral to the lesion or when stimulating the ear contralateral to the lesion. No statistically significant differences were detected among hemispheres of ears for Na, Pa latency or ABR-Na amplitude ( p > 0.05). Nonauditory Group (B) A reduction in Na-Pa amplitude was not detected over the hemisphere ipsilateral to the lesion (IL) in the nonauditory group. The overall response amplitude values were comparable to those from normal subjects. The latencies and amplitude values of MAEP were not significantly different among hemispheres or ears. No significant ear-hemisphere interaction was detected ( p > 0.05). Patient 8 (cf. Table 2) showed symmetrically reduced ABR-Na amplitude on both hemispheres and reduced Na-Pa amplitude on the hemisphere ipsilateral to the lesion (IL). There was a large variability in amplitude data, particularly NaPa amplitude in response to tone burst stimulus (Table 5). Patients 9 and 10 (cf. Table 2) showed marked enhancement in Na-Pa amplitudes recorded in the CEIL condition, which contributed to this increase in variability. Figure 8 illustrates the difference in the configuration of the response amplitude recorded from the auditory and the nonauditory group. In the auditory group there was a severe reduction in Na-Pa amplitude when recorded over the involved hemisphere, whereas in the nonauditory group a similar reduction of amplitude was not seen over the side of the lesion. Na-Pa peak amplitude values recorded over the hemisphere ipsilateral to the lesion (IL) and over the contralateral hemisphere (CL) for the auditory and the nonauditory groups, as well as data from controls, are shown in Figure 9. This figure summarizes the Na-Pa MAEP in Temporal Lobe Disorders

381

Patient # I

Group A

4

R

w

Patient #6 R

w

Patient #IS R

Figure 6. Horizontal sections at different levels of the human brain with reconstructionsof lesions from three patients of group A (auditory group). The sections correspond to CT sections made at the orbital-rneatal plane. The numbers indicate the level of the sections (4-7) which pass through the auditory structures within the temporal lobes. Labels a, b, c and d indicate the locations of the sylvian fissure (a), superior temporal gyrus (b), superior temporal gyrus (c), and Heschl's gyrus (d). In the three patients shown, the lesion involved these structures. The numbers of the patients correspond to the patient numbers in Table 1.

amplitude pattern in all conditions and all groups. Marked reduction in Na-Pa amplitude recorded from the involved hemisphere (IL) in the auditory group can be noted. No similar reduction in Na-Pa amplitude can be observed in any other condition or group. Comparison of data evoked by click and recorded over the hemisphere ipsilateral to the lesion (IL) in the auditory and nonauditory groups and data from normal subjects showed that the latency of wave Pa and the amplitude value of Na-Pa differed significantly among groups ( F = 3.93, df = 2,35; p < 0.05 for Na-Pa amplitude and F = 4.27, df = 2,35; p < 0.05 for Pa latency). Duncan's

Multiple Range test showed that for both latency and amplitude, the auditory group differed significantly from normal subjects. Values from the nonauditory group fell midway between those of the normal and the auditory group. The differences between the normal group and the nonauditory group, as well as the auditory and the nonauditory group, were not statistically significant ( p > 0.05). Na latency values were not significantly different between the three groups ( p > 0.05). ABR-Na amplitude values, although reduced in the auditory group, did not differ significantly among groups ( p > 0.05).

~

382

Shehata-Dieler et al

Ear and Hearing, Vol. 12, No. 6,1991

Patient # 3

4

c

Group B

f

7

R

Patient #14 R

Patient #I5 R

Figure 7. Horizontal sections of the human brain corresponding to the CT scan levels shown in Figure 4, with reconstruction of lesions from three patients of group B (nonauditory group). The lesions are not involving the auditory structure within the temporal lobe. The numbers of the patients correspond to the patient numbers in Table 2.

Responses evoked by tone burst also showed a marked reduction in Na-Pa amplitude and a shift in Pa latency over the involved hemisphere in the auditory group when compared to data from the nonauditory and the normal (control) group. These large differences, however, did not reach a statistically significant level because of the small sample size. No statistically significant differences were detected between the latency and amplitude values of the nonauditory group and the normal group ( p > 0.05), or between the auditory and nonauditory group ( p > 0.05). Comparison of MAEP latency and amplitude data recorded over the noninvolved hemisphere (CL) in the Ear and Hearing, Vol. 12, No. 6, 1991

auditory and the nonauditory groups and data from normal subjects did not show significant differences among groups ( p > 0.05). DISCUSSION

Normal MAEP In the present study, two stimuli were used to elicit MAEP: a broadband alternating click of 0.1 msec duration and a 1.O kHz tone burst with 2 msec rise/decay time and 0 msec duration. Clearly detectable MAEP were obtained with both types of stimuli with no differences in the general morphology of the response. The MAEP in Temporal Lobe Disorders

383

Table 4. MAEP results in the auditory group. Means k SD.

Na Latency Pa Latency Click IElL CElL IECL CECL IL CL Tone burst" IElL CElL IECL CECL IL CL

ABR-Na Amplitude

Na-Pa Amplitude

18.0f 1.5 18.2f 1.3 17.7t 1.8 18.0f 1.4 18.1 f 1.3 18.0t 1.3

34.3f 1.9 34.8f 2.8 34.0f 1.6 33.1 f 1.4 34.5 f 2.2 33.4f 1.5

0.42f 0.21 0.44f 0.20 0.49f 0.31 0.37f 0.22 0.53f 0.27 0.56f 0.19 0.37f 0.03 0.60f 0.29 0.44f 0.24 0.42f 0.20 0.42f 0.15 0.57f 0.25

20.5f 3.2 19.1 & 2.8 18.0t 1.1 18.6f 2.0 19.8f 2.8 18.3f 1.4

35.3? 4.3 32.8f 4.4 32.9 f 3.3 33.6f 3.0 34.1 f 4.1 33.3 f 2.8

0.38f 0.10 0.57f 0.35 0.40f 0.25 0.72k 0.14 0.84t 0.18 1.00f 0.08 0.35f 0.21 0.88f 0.19 0.39f 0.17 0.61 f 0.22 0.65t 0.13 0.94k 0.15

a There is an overlap between click and tone burst data from two patients (see table 7).

Table 5. MAEP results in the nonauditory group. Means f SD.

Na Latency Pa Latency Click IElL CElL IECL CECL IL CL Tone burst" IElL CElL IECL CECL IL CL

ABR-Na Amplitude

Na-Pa Amplitude

18.4f 0.6 17.9f 1.5 18.5f 2.2 19.4f 0.9 18.2f 1.1 18.9f 1.6

32.9 f 1.8 32.8f 3.3 33.5 f 3.2 32.9 f 2.3 32.9 f 2.6 33.2f 2.7

0.63f 0.32 0.61 f 0.28 0.68f 0.19 0.69 f 0.46 0.64f 0.19 0.71 f 0.19 0.56f 0.23 0.69f 0.28 0.66f 0.25 0.65f 0.37 0.60f 0.19 0.70f 0.22

18.7f 2.0 19.9f 1.9 18.0f 1.9 19.3f 2.4 19.3 f 1.9 18.7f 2.1

32.2f 1.3 32.4f 1.4 31.9 f 1.5 31.8 f 2.0 32.3f 1.2 31.8f 1.6

0.59f 0.18 0.69 f 0.58 0.88t 0.56 1.11 f 0.15 0.52 f 0.21 0.74f 0.33 0.54f 0.35 0.72f 0.21 0.74f 0.42 0.90f 0.45 0.53t 0.27 0.73f 0.26

a There is an overlap between click and tone burst data from four patients (see table 2).

shorter latency values for Na and Pa in click-evoked response, as compared to those in response to tone burst, correspond to previously published data (Maurizi et al, 1984; McFarland et al, 1977; Vivion, Hirsh, & Frye-Osier, 1980). The mean latency values of MAEP peaks obtained from control subjects elicited by both click and 1.0 kHz tone burst agreed with the MAEP data recorded from normal adults using similar stimulus and recording parameters (Kavanagh, Harker, & Tyler, 1984; Kodera, Hink, Yamada, & Suzuki, 1979; Maurizi et al, 1984; Ozdamar & Kraus, 1983; Suzuki, Kobayashi, & Hirabayash, 1984). Peak amplitude values obtained from normal subjects agreed with amplitude values from several reports (Debruyne, 1984; Goldstein, Rodman, & Karlovich, 1972; Maurizi et al, 1984; Woods et al, 1987). However, other investigators reported slightly larger peak amplitude values (Kileny et al, 1987; Lane, Kupperman, & Goldstein, 1971; 384

Shehata-Dieler et al

Ozdamar & Kraus, 1983). An explanation for this difference could be the strict criteria we used to avoid including responses with possible myogenic contamination (see methodology). Other possibilities that could have contributed to our amplitude values include restricting the upper limit of our age group to 60 yr and avoiding mastoid placement of the reference electrode. In normal subjects, the Na-Pa amplitude showed a coronal distribution similar to previously reported normal MAEP (Kdeny et al, 1987; Ozdamar & Kraus 1983). Na-Pa amplitude was significantly largest at the vertex and was enhanced slightly when recorded contralaterally. ABR-Na amplitude, Na latency, and Pa latency values did not show any significant differences among recording sites. Effects of Aging and Peripheral Hearing Loss on MAEP We have restricted the upper age limit of 60 yr to avoid peak Pa amplitude enhancement and latency shaft observed with aging (Woods & Clayworth, 1986). Some patients examined in this study had peripheral hearing loss. Patients 16, 17, and 18 had bilateral high-frequency hearing loss and Patients 2 and 11 had unilateral mild high-frequency hearing loss (cf. Tables 1, 2). It is unlikely that peripheral hearing loss had any effects on our results. The selection of the stimulus to elicit MAEP depended on the pure-tone thresholds of the patients. The patients' hearing thresholds were always within the normal limits in the frequency range of the stimulus used. Patients with peripheral hearing loss had normal hearing up to 4.0 kHz except patient 17 (cf. Table l), who suffered from bilateral sloping high-frequency hearing loss starting at 2 kHz. The latency and peak amplitude values of MAEP measured over the noninvolved hemisphere in this patient were within the normal range. It is, thus, unlikely that the decrease in Na-Pa amplitude over the involved hemisphere was due to the patients' peripheral hearing loss. Effects of Temporal Lobe Lesions on MAEP The reduction of Na-Pa amplitude over the hemisphere ipsilateral to the lesion in patients with temporal lobe disorders involving the auditory area and/or auditory radiation correspond with the results of Kraus et a1 (1982), Kileny et a1 (1987) and Ibaiiez et a1 (1989). A significant shift in Pa latency, as observed in the present study, was not reported by these authors. Nevertheless, evaluation of Kileny et a1 (1987) results (Table 4) suggests a slight shift in Pa latency for subjects with temporal lobe involvement when compared to normal subjects. Our results have also showed a tendency to increased latency values of Pa on the intact hemisphere. This corresponded to the results of Ho et a1 (1987), who reported a delay in Pa latency associated with a temporal lobe lesion. The shift in Pa latency observed here can be explained on the basis of involvement of the thalamic projections to the auditory cortex in the majority of the auditory group patients (see below). The Na-Pa amplitude asymmetry in the auditory group was observed on stimulation of the ipsi- or conEar and Hearing, Vol. 12, No. 6, 1991

Figure 8. Representative MAEP tracings recorded from patients with temporal lobe lesions with reconstructions of the lesions of horizontal sections corresponding to CT scan levels (5 and 6). Auditory group (A), patient 5; nonauditory group (B), patient 4. a) Responses recorded from the hemisphere ipsilateral to the lesion (IL); b) responses recorded from the hemisphere contralateralto the lesion (CL); c) responses recorded at the vertex (Cz).

-B-

- A1.2

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-

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-

0.8

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0.6

a

0.4

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Na-Pa Figure 9. Bar graph representing the mean k SD of the Na-Pa amplitude values recorded from normal (control) subjects, and temporal lobe patients. Data from temporal lobe patients are presented according to the group: auditory (A) and nonauditory (B). The amplitude values shown were recorded from the hemisphere ipsilateral to the lesion (IL) and the intact, contralateral hemisphere (CL). There was a significant reduction ( 8 ) in amplitude recorded from the hemisphere ipsilateral to the lesion in the auditory group (A). No similar reduction in amplitude was observed in the nonauditory group (B).

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tralateral ears with no significant differences between ears. This was also reported by Scherg and von Cannon ( I986), who also observed that the response amplitude was usually largest on stimulation of the ear contralatera1 to the intact hemisphere (i.e., ipsilateral to the lesion), indicating the dominance of the contralateral pathway in the generation of Pa. Both Ibaiiez et a1 (1989) and Kileny et a1 (1987) indicated a tendency towards larger Na-Pa asymmetry between the involved and the intact hemispheres when stimulating the ear ipsilateral to the lesion. However, the results of their statistical analysis did not support the significance of this phenomenon. The reduction of Na-Pa amplitude over the involved hemisphere was not observed in patient 1 (cf. Table 1). MAEP recorded in this patient were intact. There was an enhancement of Na-Pa amplitude in the CEIL condition in spite of the evidence, according to the CT scan, of involvement of the auditory areas within the temporal lobe. Because the lesion in this patient was caused by a tumor, compression, or penfocal edema, in addition to the actual tissue, infiltration has to be taken into consideration. MAEP recorded from the nonauditory group did not show a similar reduction in Na-Pa amplitude as that observed in the auditory group. The MAEP in general showed larger amplitudes and shorter latencies, specifically for the Pa component. Results from two lobectomy patients showed an enhancement of the response amplitude over the operated side. This has previously MAEP in Temporal Lobe Disorders

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been reported (Kileny et al, 1987) and may be due to the skull defect after surgery. MAEP recorded from the third lobectomy patient, however, showed symmetrical ABR-Na amplitude reduction on both sides, and NaPa amplitude reduction over the operated side (lesioned hemisphere). This patient had undergone left anterior temporal lobectomy with excision of 4 cm from the tip of the temporal lobe. The auditory radiation passes from the medial geniculate body through the sublenticular portion of the internal capsule to reach the auditory cortex (located on the superior surface of the superior temporal gyrus). According to our measurements in three adult human brains, the medial geniculate body is located approximately 5 cm medial to the tip of the temporal lobe. Thus, it is unlikely that the lobectomy may have impaired the thalamic projections, except if anatomical variations were present. The impaired response in this patient might be due to impairment of anatomically variant structures. MAEP Generator Sources The results of the present study support the hypothesis that Pa is bilaterally generated and that it, at least in part, reflects activity from the auditory cortex and the thalamic radiations. The coronal distribution of Na-Pa amplitude in normal subjects and the MAEP results in temporal lobe patients observed in this study give further support to the model proposed by Ozdamar and Kraus (1983). Their model suggested that the human Pa component is generated by a bilateral, vertically oriented dipole source located in the temporal lobe. The overall reduction of response amplitude noted in the auditory group is likely to be the outcome of the contribution of each generator to the response picked up on the opposite hemisphere. Kileny et a1 (1987) suggested that the posterior half or middle third of the superior temporal gyrus accounts for the generations of peak Pa. Scherg and von Carmon (1986) also suggested that the primary N19t-P30t components of the MAEP originate in a restricted and more medially located zone of Heschl’s gyri. Kraus et a1 (1982) and Ibaiiez et a1 (1989) showed that Pa was attenuated in lesions involving the primary and association cortex and adjacent white matter thalamic projections. Our finding that patients with temporal lobe lesions not involving the auditory areas did not show latency and amplitude changes as those observed in the auditory group further supports the hypothesis that the generator source of Pa, within the temporal lobe, is restricted to auditory structures. Woods et a1 (1987), however, found no direct relationship between Na-Pa amplitude and the extent of damage to the primary or association cortex in patients with bilateral temporal lobe lesions. They suggested that abnormalities of MAEP do not necessarily reflect damage to the primary auditory cortex per se, but rather to the degree of damage to adjacent areas, including subcortical structures. Our results do not support this suggestion. In the present study, most of the subjects in the auditory group had lesions involving both the auditory cortex and the distal part of the auditory radiation (thalamic projections). In patients with lesions 386

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involving only the auditory radiation, the lesions were extensive enough to cause complete interruption of the primary afferent input to the auditory cortex. Retrograde degeneration or denervation of subcortical structures (thalamic projections) is also expected to take place in extensive lesions involving the auditory cortex (Kraus et al, 1982; Woods et al, 1987). MAEP characteristics suggest that they are primarily a product of postsynaptic potential activity (Ozdamar & Kraus, 1983). Thus, it is difficult to conceive that auditory radiation is solely responsible for the response generation. It is more likely that Pa reflects the activity of several contributing sites. Although there is a large body of data showing impairment of the MAEP in unilateral temporal lobe lesions and absence of the response with bilateral lesions, several reports have been presented showing normal to severely impaired, yet detectable, responses in patients with bilateral temporal lobe lesions (Ho et al, 1987; Parving et al, 1980; Woods et al, 1987). These findings, together with the abnormal MAEP observed in patient 8 (cf. Table 2) and the results of patients 1 (cf. Table 1) in the present study, indicate that generators other than the auditory cortex contribute to the generation of the Pa component. Other candidate generator sources include widespread projections from the medial and dorsal nuclear group of the medial geniculate body to the superior temporal plane, as well as portions of the temporal lobe, parietal opercula, and inferior parietal lobules (Galaburda & Sanides, 1980; Winer & Morest, 1983). The variation of results of MAEP from patients with bilateral temporal lobe lesions may also point to the contribution of a less stable or variable generator source. Kraus, Smith, & McGee (1988) suggested that the midline component of Pa receives contributions from nontemporal lobe structures such as the reticular formation, which can dominate the response generation in absence of the more stable temporal lobe generators. Experimental data obtained from guinea pigs and cats showed that two components of MAEP with a different scalp topography exist, and that one of these components is mainly generated by the contralateral auditory cortex (Buchwald, Hirman, Norman, Huang, & Brown, 1981; Chen & Buchwald, 1986; Smith & Kraus, 1987). Indeed, Kraus et a1 (1988) gave strong evidence that in guinea pigs, the response components recorded over the temporal lobe are generated by the auditory cortex, whereas the less stable midline component seemed to be generated by subcortical areas such as the reticular formation or the polymodal thalamus. Human responses, on the other hand, have a widespread scalp topography (Picton, Hillyard, Krausz, & Galambos, 1974), which makes it difiicult to determine the extent of contribution of different generators. The possibility that the reticular formation contributes to responses other than the midline response in humans is considered, because MAEP recorded from temporal and/or suprasylvian electrodes also showed variable patterns with bilateral temporal lobe lesions (Ho et al, 1987; Woods et al, Ear and Hearing, Vol. 12, No. 6, 1991

1987). Evidence for the contribution of the reticular information to MAEP generation in children has been given (Kraus, McGee, & Comperatore, 1989). Scherg and von Carmon (1986) introduced a model describing MAEP in terms of “dipole source potentials.” Using this model, they could demonstrate that the scalp recorded responses can be decomposed into tangenital and radial source components. Based on data from patients with confirmed cortical lesions, they could relate the tangential activity to the primary auditory cortex. The radial activity was suggested to be related to other generator sources such as the secondary auditory cortex. The absence of asymmetry of ABR-Na amplitude in lesions leading to asymmetry of the Na-Pa, as observed in the present study and reported by other investigators (Kileny et al, 1987; Kraus et al, 1982), may be cautiously interpreted on the basis of separate generators for both components. Simultaneous intracranial and scalp recording of the MAEP (Hashimoto, 1982) gave evidence that the origin of peaks No and Na (sometimes fused together in a smooth rounded negativity) lies in the midbrain, probably representing postsynaptic activity within the inferior colliculus. The data presented are in favor of several hypothesis regarding the generator sources of MAEP. We are able to confirm the major contribution of the auditory structures within the temporal lobe (auditory cortex and thalamic radiation) to the generation of MAEP in humans. Our data also suggest that the response reflects activity from several contributing sites. However, no conclusive evidence can be given yet as to the extent and the exact nature of other generator sources. During the past few years the reports published on the MAEP generators in animal models have contributed to a more comprehensive understanding of the nature of the response. In humans, further studies are required to resolve this issue. Clinical Implications This study demonstrated that Na-Pa amplitude was significantly reduced on the lesioned hemisphere in the auditory group. However, amplitude data in both patients and normal subjects showed a relatively high degree of variability. In 66.6% of patients in the auditory group the response was still within the range of mean f 2 SD of the norms established. This indicates that the mean f 2 SD criteria used in evaluation of ABR abnormalities cannot be used to establish MAEP abnormalities. Controlling for factors such as aging, peripheral hearing loss, and myogenic contamination reduced, but did not eliminate, the variability in response amplitude. Amplitude measures have been reported by several investigators to be a less reliable parameter that cannot be used to establish response abnormality due to the high intersubject variability (Ibaniiez et al, 1989; Maurizi et al, 1984). This can put serious limitation on the use of these measures in the evaluation and follow-up of patients with suspected or established temporal lobe lesions. Kileny et a1 (1 987) and Kraus et a1 ( 1982) reported severe amplitude reduction or absence of the response over the Ear and Hearing, Vol. 12, No. 6, 1991

involved hemisphere. It was not clearly indicated, however, whether there was any overlap between normal and patients’ data. The difference between their results and the present data could also be due to the nature of lesions examined in these studies. In these studies (Kileny et al, 1987; Kraus et al, 1982), most of the patients had vascular lesions leading to more consistent deficits. In the present study, the majority of patients suffered from these lesions, which may or may not lead to actual destruction of tissues. Nevertheless, in a clinical setting temporal lobe lesions of all possible etiologies will need to be evaluated, and it is impossible to use the response in diagnosis of one type of lesion only. Alternatively, other means of refining the recording and/or measurement techniques would help to reduce variability in the response amplitude and to establish clear boundaries between a normal and an abnormal response. Such methods as the index of asymmetry proposed by Ibaiiez et a1 (1989) or the dipole source potential by Scherg and von Carmon ( 1986) were reported to help reduce the variability of amplitude in normal subjects and to clearly demonstrate abnormalities in patients with temporal lobe lesions. REFERENCES Buchwald JS, Hinman C, Norman R, Huang C, and Brown K. Middle and long latency auditory evoked responses recorded from the vertex of normal and chronically lesioned cats. Brain Res 198 1 ;205:9 1-109. Chen BM and Buchwald JS. Midlatency auditory evoked responses: differential effects of sleep in the cat. Electroencephalogr Clin Neurophysiol 1986;65:373-382. Debruyne F. Binaural interaction in early, middle and late auditory evoked responses. Scand Audio1 1984;13:293-296. Galaburda A and Sanides F. Cytoarchitectonic organization of the human auditory cortex. J Comp Neurol 1980;190:597-610. Goldstein R, Rodman LB, and Karlovich RS. Effects of stimulus rate and number on the early components of the averaged electroencephalic response. J Speech Hear Res 1972;15:559-566. Graham J, Greenwood R, and Lecky B. Cortical deafness: a case report and review of the literature. J Neurol Sci 1980;48:35-49. Hashimoto I. Auditory evoked potentials from the human brain: slow brainstem responses. Electroencephalogr Clin Neurophysiol 1982;53:652-657. Ho KJ, Kileny P, Paccioretti D, and McLean DR. Neurologic, audiologic and electrophysiologic sequelae of bilateral temporal lobe lesions. Arch Neurol 1987;44:982-987. lbaiiez V, Deiber MP, and Fischer C. Middle latency auditory evoked potentials in cortical lesions. Criteria of interhemispheric asymmetry. Arch Neurol 1989;46:1325-1332. Kavanagh K, Harker L, and Tyler R. Auditory brainstem and middle latency responses. I. Effects of response filtering and waveform identification. 11. Threshold responses to a 500 Hz tone pip. Ann Otol Rhino1 Laryngol 1984;Suppl 108:93, part 2. Kileny P, Paccioretti D, and Wilson AF. Effects of cortical lesions on middle latency auditory evoked responses (MLR). Electroencephalogr Clin Neurophysiol 1987;66:108- 120. Kodera K, Hink RF, Yamada 0, and Suzuki JI. Effects of rise time on simultaneously recorded auditory evoked potentials from the early, m,iddle and late ranges. Audiology 1979;I8:395-402. Kraus N, Ozdamar 0, Hier D, and Stein L. Auditory middle latency responses (MLRs) in patients with cortical lesions. Electroencephalogr Clin Neurophysiol I982;54:275-287. Kraus N, Smith DI, and McGee T. Midline and temporal lobe MLRs in the guinea pig originate from different generator systems: a conceptual framework for new and existing data. Electroencephalogr Clin Neurophysiol 1988;70:541-558.

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Kraus N, McGee T, and Comperatore C. MLRs in children are consistently present during wakefullness, stage I , and REM sleep. Ear Hear 1989;10:339-345. Lane RH, Kupperman GL, and Goldstein R. Early components of the ABR in relation to rise-decay time and duration of pure tones. J Speech Hear Res 197 I ; 14:408-4 15. Maurizi M, Ottaviani F, Paludetti G, Rosignoli M, Almadori G, and Tassoni A. Middle-latency auditory components in response to clicks and low and middle frequency tone pips (0.5-1 kHz). Audiology 1984;23:569-580. McFarland W, Vivion M, and Goldstein R. Middle component of the AER to tone-pips in normal hearing and hearing impaired subjects. J Speech Hear Res 1977;20:781-798. Ozdamar 0, Kraus N, and Curry F. Auditory brain stem and middle latency responses in a patient with cortical deafness. Electroencephalogr Clin Neurophysiol 1982;53:224-230. Ozdamar 0 and Kraus N. Auditory middle latency response in humans. Audiology 1983;22:34-39. Parving A, Salomon G, Elberling C, Larsen B, and Lassen NA. Middle component of the auditory evoked response in bilateral temporal lobe lesions. Scand Audiol 1980;9:16 1- 167. Picton T, Hillyard S, Krausz H, and Galambos R. Human auditory evoked potentials: evaluation of components. Electroencephalogr Clin Neurophysiol 1974;36:179-190. Scherg M and von Cramon D. Evoked dipole source potentials of the human auditory cortex. Electroencephalogr Clin Neurophysiol 1986;65:344-360. Smith DI and Kraus N. Effects of chloral hydrate, pentobarbital, ketamine and curare on the auditory middle latency response. Am J Otolaryngol 1987;8:241-248. Suzuki T, Kobayashi K, and Hirabayashi M. Effects of analog and digital filtering on auditory middle latency responses in adults and

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young children. Ann Otol Rhino1 Laryngol 1984;93:267-270. Thornton A, Mendel M, and Anderson C. Effects of stimulus frequency and intensity on the middle components of the averaged auditory electroencephalic response. J Speech Hear Res 1977; 2018 1-94. Vivion MC, Hirsch JE, and Frye-Osier X. Effects of stimulus rise-fall time and equivalent duration on middle component of AER. Scand Audiol I980;9:223-232. Winer JA and Morest DK. The medial division of the medial geniculate body of the cat: implications for thalamic organization. J Neurosci 1983;3:2629-265 1. Woods DL and Clayworth C. Age related changes in human middlelatency evoked potentials. Electroencephalogr Clin Neurophysiol 1986;65:297-303. Woods DL, Clayworth CC, Knight RT, Simpson GV, and Naeser MA. Generators of middle and long latency auditory evoked potentials: implications from studies of patients with bitemporal lesions. Electroencephalogr Clin Neurophysiol I987;68: 132- 148.

Acknowledgments: We thank Dr. Ralf Dieler, Center for Hearing Sciences, Johns Hopkins School of Medicine, for his help in constructing the figures and his editorial comments. We also thank Dr. Mark Chertoff, Center for Hearing Sciences, Johns Hopkins School of Medicine, for his editorial comments. Address reprint requests to Hiroshi Shimizu, M.D., Hearing & Speech Clinic, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions,600 N. Wolfe St., Baltimore, MD 21205. Received February 12, 1989; accepted August 29,1991.

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