Download The Effects of Salicylate on Auditory Evoked Potential

The Effects of Salicylate on
Auditory Evoked Potential
Amplitudes from the Auditory
Cortex and Brainstem
Brian Sawka
AuD Project
Tinnitus
 Subjective
tinnitus is the sensation of
sound in the absence of an acoustic
stimulus.
 Tinnitus can be induced by
 noise
exposure
(Axelsson & Hamernik, 1987; Job et al. 2007)
 ototoxic
drugs
(Huang & Schacht, 1989; Day et al. 1989)
 Tinnitus
is usually associated with
cochlear damage
(Demeester et al. 2007; Job et al. 2007).
Salicylate Causes Hearing Loss
and Tinnitus

Salicylate causes temporary hearing loss
and tinnitus in humans
(Hicks & Bacon, 1999; Halla et al. 1991).

Tinnitus-like behaviors suggest that
animals experience tinnitus with treatment
of salicylate
(Bauer et al. 1999; Jastreboff et al. 1988; Lobarinas et al. 2004;
Yang et al, 2007).

Consequently, tinnitus has been
extensively used in research to study
tinnitus
Salicylate Enhances Auditory Evoked
Potential Amplitude at the Auditory Cortex
2.0
Nomalized AC Amp

Yang et. al (2007) showed enhancement of auditory
cortex (AC) response amplitude with high intensity 16
and 20 kHz tone burst stimuli post salicylate treatment
These frequencies were associated with tinnitus-like
behavior in another set of animals (Yang et al. 2007)
Amplitude in mV

Pre
SS-1h
1.5
1.0
0.5
0.0
30
50
70
dB SPL
Time in ms
Lu et al. (2008)
90
110
Cochlear/8th nerve, Cochlear Nucleus, and Inferior
Colliculus I/O Functions Pre and Post Noise
Exposure
 Salvi et al. found enhancement at the inferior
colliculus with high level 1 kHz tone bursts post
noise exposure using local implants in
chinchillas (2000)
Salvi et al. 2000
Aim of Study
 Observe if the enhancement of the AC waveform
post salicylate is also present in the ABR
waveform.
 To address this question, four implanted animals
will be tested pre and post salicylate treatment for
both:
 AC response
 ABR response
Cochlea
8th
Cochlear
Nucleus
Inferior
Colliculus
Auditory
Cortex
Methods: Subjects

Subjects: Four male Sprague Dawley rats



Implanted at 2-3 months of age
Tested at 6-7 months of age
Implants consist of:





Auditory Cortex electrode (right side)
Frontal lobe skull electrode
Screw for head restraint
Affixed to skull with dental cement and stainless steel screws
The implant procedure has been described in detail
(Yang et al, 2007; Lobarinas et al, 2006).
Methods: Animal Restraint

The rats were trained to remain still during
awake recordings:
 Small
modified plastic cage
 Head restraint using head screw and a mechanical
arm

Awake recordings:
 Required
for AC recordings
 Chosen for ABR to avoid influences of anesthesia
Methods: Auditory Stimuli



4 ms alternating polarity tone bursts of 4, 8, 12, 16 and
20 KHz
Created in Tucker Davis Technologies (TDT)
SigGen
RP 4.4 software
TDT Stimuli Hardware:




Processor
Attenuator
Headphone driver
8 ohm tweeter ~ 2 ¼ inches from ear



Left ear for AC recordings (contralateral to recording electrode)
Right ear for ABR recordings (ispilateral to recording electrode)
The auditory stimuli will be binaural as both ears will
remain unrestricted
Methods: Recording Hardware and
Parameters

TDT Recording hardware:





Recording Software: TDT BioSig RP 4.41
BioSig and electrode settings for AC recording:




Four channel head stage
Medusa Preamp
Medusa Base Station
Recording electrode placed at the auditory cortex and reference
at the frontal lobe of the skull (contralateral recording)
Band pass filter 3 Hz - 1000 Hz and 60 Hz notch
Stimulation rate 2/second and averaged 100 sweeps for each
waveform.
BioSig and electrode settings for ABR recording:



Recording electrode placed at the skull and reference at the
auditory cortex (ipsilateral recording)
Band pass 100 Hz - 3000 Hz and 60 Hz notch
Stimulation rate 19/second and averaged 512 sweeps for each
waveform.
Methods: Amplitude Measure for
AC and ABR

AC recordings
Large positive peak ~ 11-15 ms
 Amplitude recorded peak to following trough
in micro volts


ABR recordings
Positive peak ~ 4.5 - 5 ms (estimated latency
of inferior colliculus)
 Amplitude recorded peak to following trough
in micro volts

Results: Auditory cortex response enhancement
was observed for most conditions
Auditory Cortex Amplitudes in Response to
20 KHz Tone Bursts for Animal 102607
Pre Salicylate 1
140
Pre Salicylate 2
2 hours post Salicy
1 day post Salicy
3 days post Salicy
100
80
60
40
20
Tone Burst Intensity in dB SPL
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
0
AC Amplitudes in Micro Volts
120
Results: Auditory Cortex Statistical
Analysis

Paired t test comparisons of pre and post salicylate AC
amplitudes for all four animals:

4k: p = .047
8k: p = .0045
12k: p = .032
16k: p = .068
20k: p = .032




Alpha = .05
Micro Volts

Across Animal Average for 20 KHz Auditory
Cortex Amplitude at 90 dB SPL
120
100
Baseline
80
2 Hours Post Salicy
60
40
20
0
1
Results: ABR results for high intensity stimuli were
typically smaller amplitude for 2 hours post salicylate
compared to baseline
Brainstem Responce Amplitudes in Response to
20 KHz Tone Bursts for Animal 102607
Pre Salicylate 1
2
Pre Salicylate 2
2 hours post Salicy
1.6
1 day post Salicy
3 days post Salicy
1.4
1.2
1
0.8
0.6
0.4
0.2
Tone Burst Intensity in dB SPL
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
0
ABR Amplitudes in Micro Volts
1.8
Results: ABR Statistical Analysis

Paired t test comparisons of pre and post salicylate ABR
amplitudes for all four animals:

4k: Missing data
8k: Missing data
12k: p = .001
16k: p = .061
20k: Missing data




Alpha = .05
Micro Volts

Across Animal Average for 12 KHz Brainstem
Response Amplitude at 90 dB SPL
4
3.5
3
Baseline
2.5
2 Hours Post Salicy
2
1.5
1
0.5
0
1
Conclusions
The AC results confirm high intensity
tone burst enhancement post salicylate
treatment
 The ABR data suggests that the
amplitudes are overall decreased post
salicylate at the inferior colliculus

Discussion: Comparison of Results
Salvi et al. studies using noise exposure
Cochlea
8th
Cochlear
Nucleus
Inferior
Colliculus
Auditory
Cortex
Current observations for salicylate
treatment
Cochlea
8th
Cochlear
Nucleus
Inferior
Colliculus
Auditory
Cortex
Discussion
This study is useful as a small pilot study
 The results suggest that hearing damage
and tinnitus from salicylate may have a
different physiological mechanism than
noise exposure.
 A follow up study is recommended that
would use local inferior collicului implants
to verify these results.

Recognition

I would like to thank my research
committee for their advisement and
assistance for this project:
 Wei
Sun, Ph.D
 Richard Salvi, Ph.D
 Joan Sussman, Ph.D

Special thanks to:
 Lu
Jianzhong, Ph.D
References

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Axelsson, A. & Hamernik, R.P. (1987). Acute acoustic trauma. Acta
Otolaryngol, 104, 225-233.
Bauer, C.A., Brozoski, T.J., Rojas, R., Boley, J. & Wyder, M. (1999).
Behavioral model of chronic tinnitus in rats. Otolaryngol Head Neck Surg,
121, 457-462.
Day, R.O., Graham, G.G., Bjeri, D., Brown, M., Cairns, D., Harris, G.,
Hounsell, J., Platt-Hepworth, S., Reeve, R., Sambrook, P.N., et al. (1989).
Concentration-response relationships for salicylate-induced ototoxicity in
normal volunteers. Br J Clin Pharmacol, 28, 695-702.
Demeester, K., Van Wieringen, A., Hendrickx, J.J., Topsakal, V., Fransen, E.,
Van Laer, L., De Ridder, D., Van Camp, G. & Van de Heyning, P. (2007).
Prevalance of tinnitus and audiometric shape. Belgium ENT, 3(7), 37-49.
Halla, J.T., Atchinson, S.L. & Hardin, J.G. (1991). Symptomatic salicylate
ototoxicity: A useful indicator of serum salicylate concentration? Ann
Rheum Dis, 50, 682-684.
Hicks, M.L. & Bacon, S.P. (1999). Effects of aspirin on psychophysical
measures of frequency selectivity, two-tone suppression, and growth of
masking. J Acoust Soc Am, 106, 1436-1451.
Huang, M.Y. & Schacht, J. (1989). Drug-induced ototoxicity, pathogenesis
and prevention. Med Toxicol Adverse Drug Exp, 4(6), 452-67.
References
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Huang, M.Y. & Schacht, J. (1989). Drug-induced ototoxicity,
pathogenesis and prevention. Med Toxicol Adverse Drug Exp, 4(6), 45267.
Jastreboff, P.J., Brennan, J.F., Coleman, J.K. & Sasaki, C.T. (1988).
Phantom auditory sensation in rats: an animal model for tinnitus. Behav
Neurosci, 102, 811-822.
Job, A., Raynal, M. & Kosowski, M. (2007). Susceptibility to tinnitus
revealed at 2 KHz range by bilateral lower DPOAEs in normal hearing
subjects with noise exposure. Audiol Neurootol, 12(3), 137-44.
Lu, J., Laundrie, E., Stoltzburg, D., Sun, W., Salvi, R. (2008). Abstract,
Association for Research of Otolaryngology. Phoenix, AZ.
Lobarinas, E., Sun, W., Cushing, R. & Salvi, R. (2004). A novel
behavioral paradigm for assessing tinnitus using schedule-induced
polydipsia avoidance conditioning (SIP-AC). Hear Res, 190 (1-2), 109-14.
Salvi, R. J., Wang, J. & Ding, D. (2000). Auditory plasticity and
hyperactivity following cochlear damage. Hear Res, 147, 261-274.
Yang, G., Lobarinas, E., Zhang, L., Turner, J., Stolzberg, D., Salvi, R. &
Sun, W. (2007). Salicylate induced tinnitus: Behavioral measures and
neural activity in auditory cortex of awake rats. Hear Res, 226, 244-253.