Download Acoustic Program

“Prescriptive Tinnitus Treatment”
Components:

Evaluation - Tinnitus Evaluation Program (TEP™)
*Full description is described in another document

Acoustic Program - Tinnitus Modulation Program (TMP™)
*Description of concepts are described in this document
 Cognitive/Behavioral Program - Tinnitus Adaptation Program (TAP™)
*Full description is described in another document
David W. Holmes, Ph.D.
Board Certified in Audiology
CEO & Senior Scientist
Melmedtronics Holdings, LLC
Dallas, Texas
USA
[email protected]
Viber #: 1-817-201-6791
Introduction
Prevalence of Tinnitus
Tinnitus is a disorder that affects 15% (1/6) of the general population. Severity ratings appear to follow a bellshaped curve with some individuals reporting very mild tinnitus and some (~20%) who find it devastating.
Approximately 20% of those with tinnitus report their tinnitus to be severe to profound. Nearly 90% of patients
with tinnitus also have a concomitant hearing loss. Unfortunately there is no cure for benign tinnitus (not
related to an active medical condition). However, there are some treatments that do provide partial relief for
certain individuals. This means that 97% of those with tinnitus are faced with a disorder that is not curable. To
put this into perspective, there are 50 million individuals with tinnitus in the U.S. and 135 million in Europe.
Tinnitus location
Tinnitus is described as a sound that is not externally generated. Until recently, it was perceived as an “ear”
problem. However, in 1998 (Lockwood & Salvi) discovered areas of the brain that represented activity in
individuals with tinnitus and absent in individuals without tinnitus.
This seminal paper literally transformed our attention from the ear to the brain as the locus of tinnitus. Since
1998, there have been numerous studies that have confirmed their findings. There is now great interest among
many disciplines (pharmacology, radiology, neurotology, audiology, neurophysiology and bioengineering) to
develop new methods of treatment and perhaps an ultimate cure.
The limbic system is a system of the brain that has connections to various areas of the cortex that may be
affected by tinnitus. It is hypothosized that this system of the brain may control how patients perceive thir
tinnitus.
Figure 1. Anatomy of the cortex and EEG activity of tinnitus activity (Langguth, B., 2011).
Figure 2. It has been found that there is stronger connectivity between the auditory and non-auditory regions in tinnitus
patients when compared to controls. (Schlee et al. BMC, Neuroscience, 2009).
A study conducted by Holmes (2007), utilized Quantitave EEG to record the pre and post effects of ultrasound,
and found similar changes, in not only the limbic area, but also other areas of the cortex.
Figure 3. EEG power spectrum changes before and after treatment using ultrsound
(Holmes, 2007).
Acoustic Signals Used in Tinnitus Treatments
Frequency Modulation
There is evidence that low frequencies (40-100 Hz) may “modulate” the information that is sent to the brain.
“CR treatment was safe, well-tolerated and caused a significant decrease of tinnitus loudness and
symptoms. Placebo treatment did not lead to any significant changes. Effects gained in 12 weeks of
treatment persisted through a preplanned 4-week therapy pause and showed sustained long-term effects
after 10 months of therapy: Response, i.e. a reduction of at least 6 TQ points, was obtained in 75% of
patients with a mean TQ reduction of 50% among responders. CR therapy significantly lowered tinnitus
frequency and reversed the tinnitus related EEG alterations.” (Tass, et a, 2012)
Some of the current tinnitus treatment devices (Sound Cure’s Seranade, Neuromonics’ Oasis, Widex’s
Zen2Go, Phonak’s Audeo Q, Starkey’s Xino, GN ReSound’s Altera TC, Siemens’ Life, and General Hearing ’s
Tranquil ) appear to offer some relief for some patients. These approaches have provided varying relief to
tinnitus patients that is administered over a period of months.
Zwicker Effect
“The 'Zwicker tone' (ZT) is an auditory after-image that can be evoked most effectively when a bandsuppressed noise (relative width of gap 1/3 octave) presented for a certain period of time has been
switched off. The sensation of this purely monaural phenomenon is that of a pure tone with a frequency
corresponding to the center frequency of the gap and an equivalent level of 10-15 dB above auditory
threshold. The sensation decays gradually; it may last as long as 10 s depending on how long the
evoking noise was presented. The search for a physiological correlate has been futile so far, probably
because the search was confined to more peripheral levels of the auditory system (inferior colliculus). A
neuromagnetic study was performed in normal-hearing subjects in order to look for a
neurophysiological correlate of the ZT in the auditory cortex. With a stimulation paradigm especially
designed for this study, we have been able to isolate poststimulus activity which appears to be related to
the ZT and which originates in the supratemporal auditory cortex. It is a sustained neuromagnetic
activity that shows a clear-cut dipolar field distribution, and it appears that this activity has certain
similarities with the tone-evoked auditory sustained response. The hypothesis is put forward that during
the sensation of the ZT a process takes place in the auditory cortex which is similar to that underlying
the sustained response, and which gives rise to the sensation of the ZT. In contrast to the sustained
response, however, which is due to neural activity evoked by an external acoustic stimulus, the sustained
activity associated with the ZT is due to a temporary absolute or relative reduction of neural activity
originating from those regions in which the ZT exciting stimulus caused an adaptation. These
differences in neural activity cannot be distinguished by the auditory system from a corresponding
external acoustic signal. Preliminary studies in patients suffering from tonal tinnitus yielded results
which exhibit a certain similarity with those obtained in the ZT experiment.” (Hoke, Hoke and Ross,
1996).
Figure 5. Mean variation of tinnitus loudness over time in the three sound therapy groups. Decibel units on the yaxis are mean values (+1 SE) of ∆dBt computed for three subsequent temporal classes using dBt measurements in
subsequent control visits of the same patient. See Methods for details. (WN = broadband noise; WWN = notched
broadband noise Marco Lugli1; Romano Romani1; Stefano Ponzi2; Salvatore Bacciu2; Stefano Parmigiani1Wa = water
noise.) Marco Lugli1; Romano Romani1; Stefano Ponzi2; Salvatore Bacciu2; Stefano Parmigiani1 (2009)
Music
“Chronic tinnitus, one of the most common disorders in ENT medicine, requires comprehensive and
interdisciplinary treatment.
An innovative music therapy approach, developed at the German Center for Music Therapy Research in
cooperation with the ENT clinic of the University of Heidelberg ("Heidelberg Model"), strives to integrate the
tinnitus sound into a musically controllable acoustic process. The aim of the present study is to evaluate the
effectiveness of this current treatment.
We carried out a prospective, two-armed (music therapy group vs control group) study with 20 patients (10
males, 10 females; mean age 51+/-7 years), suffering from decompensated chronic tinnitus (mean score in the
Tinnitus Questionnaire TQ=46.8+/-9.6). The target variables involved TQ values, pre- and post-measurements,
and follow-up after 3 and 6 months.
Group comparison yields a highly statistically and clinically significant decrease in mean TQ-scores pre- and
post in the music therapy group by 25 points or 52% on average as compared to 2 points (4%) in the control
group [univariate ANOVA: (F(1,31)=14.19, P=0.001), effect size d=1.73]. Logarithmic regression analysis
reveals a fast onset and long lasting effect of music therapy (B=-8.9; F(1,125)=32.11, P=0.000).
The effectiveness of this highly economic approach was proven as the innovative music therapy concept yields
statistically and clinically significant results which remain stable throughout follow-up. Further investigations
with larger sample sizes and using brain imaging should strengthen these findings.” (Argstatter H, Plinkert
P, Bolay HV., 2007).
Fractals
According to Sweetow (2013):
“The potential application of fractal tones delivered via high-fidelity hearing aids was explored in an
experiment to determine if the presence of various acoustic stimuli, including fractal tones, would (1) be
perceived as relaxing to tinnitus patients, (2) reduce short term tinnitus annoyance, and (3) lower
subjective tinnitus handicap and reaction scores in a 6 month field trial. [45] The experimental protocol
allowed for a comparison of fractal tones alone, fractal tones combined with amplification, broadband
(white) noise alone, white noise mixed with amplification, and fractal tones along with amplification and
white noise.
Results indicated that fractal tones were effective in promoting relaxation and reducing annoyance from
tinnitus. Similar results were also reported by others. [46],[47] Both fractal tones and white noise reduced
tinnitus annoyance (white noise to a greater degree than the fractal tones, likely due to greater masking
effects), but the fractal tones were preferred by subjects for longer term use for reasons discussed below.
In addition, while the majority of subjects selected slower tempos for relaxation and long-term wear,
this choice was not unanimous. This underscores the benefit of providing the individual listener with
choices. [48] Individual preferences for certain types of acoustic stimuli were also emphasized in the
Henry et al., [49] study in which they reported most, but not all, of their participants clearly preferred
certain stimuli over others.
The Sweetow and Sabes results [45] agreed with the Henry et al., [49] data in that their subjects showed a
preference for stimuli that were modulated in both the spectral and temporal domains. In the latter
study, subjects were presented with a variety of noises and environmental sounds that were filtered and
modulated. They found that most, but not all, of their subjects had clear preferences for certain stimuli
over others, and most preferred were those that were modulated or temporally varying as opposed to
steady state (i.e., pure tones, or filtered or broad band-noise) signals. Modulated signals are
characteristic of fractal and other musical stimuli. Reavis, et al., [50] indicated that electrical and
acoustic suppression was achieved most effectively using dynamically modulated signals. Their results
confirmed the conclusions of others. [51],[52] that temporally patterned sounds such as amplitude and
frequency modulated signals may produce highly synchronized and robust cortical responses as
opposed to steady state sounds, which produce mostly onset and offset responses in the cortex, and thus
may be a more attractive stimulus for this cortical effect. Zeng et al. [53] also suggested that the temporal
characteristics of an electrically generated signal are critical to suppression. Sounds that are too slow
produce bursts of activity and those that are too fast show no synchronization, but within a specific
range the neurons fire synchronously to the sound stimulus and can produce synchronized, robust
neural activity in the auditory cortex.
It is possible that there are also optimal properties for an acoustical signal designed for tinnitus relief,
though this has yet to be verified.” (Sweetow, 2013).
Adaptation/Habituation Therapy
Jastreboff is known for Tinnitus Retraining Therapy, Henry for Progressive Tinnitus Management and Holmes
& Cozort for Tinnitus Adaptation Therapy. These approaches have yielded effective results in the
maanagement of tinnitus, but results vary from one clinical setting to another for a variety of reasons (skill of
clinician, concomitant use of a variety of devices, psycho/social variables of patients and a host of other
variables). These methods are enhaced when used in conjunction with some form of accoustic device.
Figure 4.
Results of cognitive therapy used in conjunction with broad-band noise. (Holmes Cozort, 1999).
Issues
One of the problems faced with all current treatment approaches is, that the patients’ tinnitus may change and
fluctuate over time. If the treatment is partially effective, it may change the perception of the frequency and/or
the intensity of the patient’s tinnitus for a variety of reasons (additional insults, age, body physiology,
medications and treatment effects). If a tinnitus treatment program is effective for a portion of the tinnitus
spectrum and those characteristics change, then it is possible that the treatment is no longer suitable for the
residual tinnitus components. The solution should then be, to either apply an alternative method of treatment, or
modify the existing treatment in a manner that will focus on the remaining components of the tinnitus spectrum.
A second problem, effecting positive patient outcomes, is that of compliance. Patients expect quick results and
if they are not obtained, then they abandon the treatment and look for a replacement therapy, in hopes of finding
the “silver-bullet”.
Solution
The solution would be to develop a “modifiable” treatment program, that would respond to changes in the
patient’s tinnitus. The use of “intelligent” algorithms could then be used to predict which program had the
highest probability of success, based on variables that had been identifed through ongoing diagnostic
information.
Variables
Clinicians who see patients with tinnitus share a common axiom,
“If you’ve seen one tinnitus patient, you’ve seen one tinnitus patient.”
Patients with tinnitus are very complex for more reasons than can possibly be listed, but here are a few
examples:
Causes
1.
2.
3.
4.
600+ prescription drugs have a tinnitus side effect
Tinnitus effects of interactions among multiple drugs are unknown
200+ known medical conditions
Variety of frequency and intensity parameters of noise induced tinnitus
Effects
1. Personality Type Reactions
a. Sensing-Judging
b. Sensing-Perceiving
c. Intuitive-Feelers
d. Intuitive-Thinkers
2. Anxiety
3. Depression
4. Hyperacusus
5. Misophonia
6. Phonophobia
Assessments
1. Patient Information
a. Demographics
b. History (detailed)
c. Description of tinnitus
i. Type
i. Tonal
a. Frequency
b. Minimum masking level
c. Residual inhibition
ii. Noise
a. intensity
b. Minimum masking level
c. Residual inhibition
ii. Etiology
iii. Date of onset
iv. Location
i. L, R, C
d. Psycho/Social measures
i. Tinnitus Handicap inventory
ii. Tinnitus Reaction Quotient
iii. Tinnitus Severity Scale
iv. Depression scale
v. Anxiety scale
vi. Personality Index
vii.
Acoustic Parameters
There are several methods that can be used to create/modify an acoustic signal:

Frequency
o Sinusoidal
o Noise
o Modulate
 FM
 AM
o Filter
o Notch
These are the possible modifications that could be applied to a patient’s matched tinnitus:
2. Acoustic Treatment Options
a. (tones, NB noise, Zwicker, music and fractals)
Tonal
i.
ii.
iii.
iv.
v.
vi.
Non-modulated frequency
Frequency Modulated (40 Hz)
Frequency Modulated (Sweep 40-100 Hz)
Amplitude Modulated (+/- 5 dB)
Combined Modulated (AM & 40 Hz)
Combined Modulated (AM & sweep 40-100 Hz)
Noise
vii.
viii.
ix.
x.
xi.
xii.
Non-modulated Notched band
Modulated notched band (40 Hz)
Modulated notched band (sweep 40-100 Hz)
Notched band (AM +/- 5 dB)
Combined notched band (AM and 40 Hz)
Combined notched band (AM and sweep 40-100 Hz)
NB Zwicker
xiii.
xiv.
xv.
xvi.
xvii.
xviii.
Non-modulated notched Zwicker band
Modulated notched Zwicker band (40 Hz)
Modulated notched Zwicker band (sweep 40-100 Hz)
Notched band (AM +/- 5 dB)
Combined notched band Zwicker (AM and 40 Hz)
Combined notched band Zwicker (AM and sweep 40-100 Hz)
xix.
xx.
xxi.
xxii.
xxiii.
xxiv.
Non-modulated Notched band
Modulated notched band (40 Hz)
Modulated notched band (sweep 40-100 Hz)
Notched band (AM +/- 5 dB)
Combined notched band (AM and 40 Hz)
Combined notched band (AM and sweep 40-100 Hz)
Music
Fractals
xxv.
xxvi.
xxvii.
xxviii.
xxix.
xxx.
Non-modulated Notched band
Modulated notched band (40 Hz)
Modulated notched band (sweep 40-100 Hz)
Notched band (AM +/- 5 dB)
Combined notched band (AM and 40 Hz)
Combined notched band (AM and sweep 40-100 Hz)
Common Tasks
Registration
1.
2.
3.
4.
5.
6.
7.
Name
Date of birth
Sex
Social Security (last four digits)
Unique I.D.
Login (email address)
Password
Data
1. Data logging
a. Login/logout date and time
b. Treatment assigned
2. Data collection
3. Analyses
Task Sequences for Matching Tinnitus and Treatment Stimuli
1. Develop code to:
a. Match tone frequencies
b. Match narrowband noise
c. Modulate frequency
d. Modulate amplitude
e. Filter out notched frequencies
2. Selected Treatments
a. Amplitude modulation +/- 5 dB of threshold
b. Frequency modulation 40 Hz – 100 Hz
c. Zwicker
Development Stages
1. Intellectual Property
a. Identify all possible combinations of treatment options
b. Search patents for prior art
i. Widex patents that exist
ii. Widex patents that could be enhanced
iii. New applications that could be filed
2. Identify
a. All possible treatment conditions
b. Rank order development stages
c. Determine platforms
d. Identify delivery systems
3. Program Variables
a. Frequency modulation
b. Amplitude modulation
c. Notched filters
d. Combinations of the above
4. Clinical Trials
a. List variables for analyses
b. Identify existing cohorts for potential subjects
c. Develop inclusion/exclusion criteria for all conditions
d. Recruit subjects
e. Collect data
f. Analyze data with multivariate analysis
g. Identify factors that have the highest predictability of success
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Appendix B
Project Management Plan
To be completed by:
Deadline:
Team Leaders
As indicated
Phase 1 Q4 and Q1-Q4, 2013-14
% done
Items
Status
Notes
100%
100%
50%
25%
5%
Federal Supply Schedule
GSA
Identify Potential Funding Sources
Secure Round 1 funding
Program beta version of software
Contract Awarded 11-15-2011
Uploaded to GSA and GSA Advantage
75%
75%
10%
25%
Identify clinical trial sites
Identify Multivatiate loadings
Phase 2 clinical trials
Identify treatment delivery options
15-Nov-11
21-Nov-11
23-Nov-13
23-Dec-14
12-Feb-14
15-Mar14
30-Jun-14
15-Jul-14
15-Sep-14
75%
75%
Begin discussions with potential Distributors
Hire Sales Reps
15-Nov-14
1-Dec-14
Widex, Oticon, Phonak, GN ReSound, Starkey and Seim
Phase
Due By
Notes
25%
50%
75%
25%
Complete ISO:13485 and CE Mark
File FDA 510(k)
File U.S. and International Patents
Schedule Demonstrations
15-Jan-15
15-Feb-15
15-Mar-15
ongoing
Embargo and BSI
25%
50%
Trade Journal Advertising
Trade Show
monthly
8-Mar-15
Hearing Review and The Hearing Journal (print and eB
JDVAC
50%
25%
25%
Trade Shows
Develop CEU courses
R&D
ongoing
ongoing
ongoing
US, Europe, Middle East and India
Develop CEU courses
Ongoing data analyses
Meet with researchers (US, India and Germany)
Phase 2 Q1 - Q4, 20115
% done
Phase 3 Q1 - 4, 2016
% done
Phase
Due By
0%
50%
Expand Marketing and Advertising
Trade Shows
Ongoing
Ongoing
0%
Begin discussions with possible Acquisition
sources
Ongoing
New Sales Reps begin demonstrations in VA clinics