J Am Acad Audiol 25:62-75 (2014)

Review Sound Therapy for Tinnitus Management: Practicable Options DOI: 10.3766/jaaa.25.1.5 Derek J. Hoare*t Grant D. Searchfield$ Amr El Refaie§ James A. Henry**tt

Abstract Background: The authors reviewed practicable options of sound therapy for tinnitus, the evidence base for each option, and the implications of each option for the patient and for clinical practice. Purpose: To provide a general guide to selecting sound therapy options in clinical practice. Intervention: Practicable sound therapy options. Data Collection and Analysis: Where available, peer-reviewed empirical studies, conference proceedings, and review studies were examined. Material relevant to the purpose was summarized in a narrative. Results: The number of peer-reviewed publications pertaining to each sound therapy option reviewed varied significantly (from none to over 10). Overall there is currently insufficient evidence to support or refute the routine use of individual sound therapy options. It is likely, however, that sound therapy combined with education and counseling is generally helpful to patients. Conclusions: Clinicians need to be guided by the patient's point of care, patient motivation and expectations of sound therapy, and the acceptability of the intervention both in terms of the sound stimuli they are to use and whether they are willing to use sound extensively or intermittently. Clinicians should also clarify to patients the role sound therapy is expected to play in the management plan. Key Words: Habituation, masking, neuromodulation, progressive management, residual inhibition Abbreviations: EEG = electroencephalography; MEG = magnetoencephalography; PTM = Progressive Tinnitus Management; RCT = randomized controlled trial; Rl = residual inhibition; THI = Tinnitus Handicap Inventory; TRT = Tinnitus Retraining Therapy

he observation that sounds can effect changes in the nature or intrusiveness of tinnitus has a long history. Indeed, the earliest recording of this practice in the medico-scientific literature comes from

T

Jean-Marie Itard, a French writer who in 1821 noted in his medical textbook that running water or wood crackling on the fire can help those suffering with tinnitus (Stephens, 2000). Fast-forward to 1976, and

'National Institute for Health Research (NIHR), Nottingham Hearing Biomédical Research Unit, University of Nottingham, Nottingham, United Kingdom' tOtology and Hearing Group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, United Kingdom; tSection of Audiology and Centre for Brain Research, University of Auckland, New Zealand; §Human Communication Sciences, La Trobe University, Melbourne, Australia; **\/A RR&D National Center for Rehabilitative Auditory Research (NCRAR), VA Medical Center, Portland, OR; ttDepartment of Otolaryngology/Head and Neck Surgery, Oregon Health and Science University, Portland, OR Dr. Derek Hoare, NIHR Nottingham Hearing Biomédical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham, UK, NG5 1DU; E-mail; [email protected] Author D.J.H. is funded by the National Institute for Health Research (NiHR) Biomédical Research Unit Program. The views expressed are those of the authors and not necessarily those of the ÜK National Health Service, the NIHR, or the UK Department of Health. Author D.J.H. is PI on the current clinical trial of CR Neuromodulation, referred to in this manuscript.

Tinnitus Sound Therapy/Hoare et al

sound therapy devices were introduced on essentially the same principal of distraction, turning total masking with white noise into a clinical management technique (Vernon, 1976). The founder of the "masking" method (J. Vernon) described its purpose as rendering the tinnitus inaudible with a more acceptable sound (Vernon, 1976, 1977). Soon thereafter, combination instruments (combination hearing aid and masking device) became avañable, and "partial masking" became an objective of treatment. Vernon (1981) stated "masking that is incomplete can be nevertheless acceptable" (p. 17). He later noted that combination instruments sometimes resulted in "only a partial reduction in the tinnitus: it is still perceivable but in a suppressed form" (Vernon, 1988) (p. 101). Vernon (1988) reported that combination instruments were recommended to 67% of his patients, while tinnitus maskers were recommended to 21%. Thus, in the early years of sound therapy using ear-level devices, combination instruments were the preferred device, and partial masking was most often the objective of treatment. Further developments in the 1990s led to the concept that, to promote "habituation" to the tinnitus, therapeutic sound should be used "below the mixing point," that is, at a level low enough to maintain the usual perception of the tinnitus (Jastreboffand Jastreboff, 2000). The term sound generator emerged to distinguish devices used for partial masking/sound enrichment as opposed to maskers used for total masking. Unfortunately, the terms masker and masking continue to be used to refer to sound therapy in general. Currently, sound therapy may refer to a specific treatment approach or be used as a catch-all phrase for the clinical use of sound. Even the term sound therapy can lead to confusion. One recent review of sound therapy (McKenna and Irwin, 2008) excluded masking therapy, while another (Hobson et al, 2010) included masking (citing Mehlum et al, 1984; Hazell et al, 1985; Vernon and Meikle, 2000; Henry et al, 2006) and sound used to attempt tinnitus habituation (citing Jastreboff and Hazell, 1993; Bauer and Brozoski, 2011). Sound therapy is defined in the present review as any use of sound where the intention is to alter the tinnitus perception and/or the reactions to tinnitus in a clinically meaningful way. Traditional approaches to tinnitus management typically constitute a complex intervention involving education and counseling, stress reduction and relaxation, and use of therapeutic sound, as in Tinnitus Retraining Therapy (TRT; Jastreboff and Jastreboff, 2000) or other less protocol-driven habituation therapies. The use of sound or sound enrichment is now core to many tinnitus management programs, whether the intention is to make tinnitus less noticeable, provide immediate relief, promote control, promote habituation, provide a distraction of attention, or promote plastic

change in the central auditory system (Newman and Sandridge, 2012). But there is a great deal of debate as to its usefulness and modes of effect of different approaches (McKenna and Irwin, 2008; Hobson et al, 2010). The purpose of this review is to provide clinicians with a general guide to using sound in tinnitus management and so to inform decision making for effective individualized patient care. Appreciating that hearing aids (with or without a sound generator component) are a current mainstay of the audiological management of tinnitus and indicated for the management of hearing loss in any case, this review has more focus on recently developed device technologies and all published reports relating to these devices. The evidence base for different sound-based interventions, factors that may influence success or failure, and potential neurophysiological bases are discussed. PUTATIVE MECHANISMS OF TINNITUS AMENABLE TO SOUND THERAPY

C

urrent consensus is that damage to the afferent input to the auditory pathway initiates events that result in plastic changes at the central level giving rise to the percept of tinnitus (Noreña, 2011). Models of these plastic changes describe changes in specificity or functional organization of the auditory nerve fibers and central auditory neurons, or hyperactivity with increases in cortical neural synchrony, or increases in central gain. These models account for the percept of tinnitus (hearing the tinnitus sound) but do not account for the reactions to tinnitus, which can include psychological effects including anxiety, depression, and insomnia, which impair quality of life (Langguth, 2011). Cortical and Tonotopic Reorganization The reorganizational model of tinnitus generation proposes that as peripheral hearing loss deprives central auditory neurons of their normal input, the deprived neurons begin to show responsiveness to the characteristic frequency of neighboring neurons that have retained their original place in the tonotopic map (for a review see Eggermont and Roberts, 2004). This process may involve either neuronal rewiring or be the result of unmasking or disinhibition of latent cochlear inputs to those regions newly deprived of direct inputs. The resulting overrepresentation of certain characteristic frequencies, all of which will show spontaneous activity, is proposed as a mechanism of tinnitus generation. Inducing reorganization is therefore a potential mechanism for reducing overrepresentation and interrupting tinnitus. Long-term exposure to a spectrally enhanced acoustic environment was observed to induce tonotopic map reorganization in juvenile cat auditory cortex, without inducing hearing loss (Noreña

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Journal of the American Academy of AudiologyA^olume 25, Number 1, 2014

et al, 2006), and compensatory sound enrichment can interrupt the tonotopic cortical changes normally associated with noise-induced hearing loss (Noreña and Eggermont, 2005). Extensive tonotopic reorganization as a result of auditory perceptual learning for pure tones has also been reported in the animal literature (Recanzone et al, 1993). There are currently no commercial sound therapy devices that explicitly target this mechanism of tinnitus, although behavioral data from Moffat et al (2009) show a change in the low-frequency components of tinnitus after hearing-aid fitting, suggestive of some level of reorganization at the cortical level. Hyperactivity, Neural Synchrony, Increased Central Gain As well as functional reorganization, hearing loss has been shown to significantly increase spontaneous neuronal activity at various points in the auditory pathway, to increase evoked responses in the hearing brain, and to increase synchrony in auditory cortex (Noreña, 2011). Overall hyperactivity could result from increases in central gain where the central system is tr3dng to stabilize mean firing in response to reduced afferent input (Noreña, 2011). Tinnitus has been linked to decreased oscillatory brain rhythm activity in the alpha band (8-13 Hz) and increased activity in the delta band (1.5-4 Hz) and the gamma band (e.g., 25-80 Hz) (Weisz et al, 2007; Adjamian et al, 2012). Gamma activity in particular has been associated with synchronization of neuralfiringboth within and between neural ensembles (Gray et al, 1989, Singer, 1999), and from a clinical perspective, enhanced neuronal activity in the gamma frequency range in the resting state has been linked to symptoms in tinnitus and other neuropsychiatrie disorders (Lünás et al, 1999). Sound therapy devices that reputedly target the breakdown of neural hyperactivity or pathological synchronous activity are reviewed further below. Emotional Disturbance The mechanisms of emotional disturbance associated with tinnitus define the "reaction" to hearing the tinnitus sound, as opposed to the "perception" of the sound. Recent models propose a role for the emotional centers of the brain in tinnitus maintenance. The presence of a salient signal out of context creates focus and commands attentional resources feeding into nonsensory cognitive processes that are strongly associated with tinnitus distress (De Ridder et al, 2011). This process should be infiuenced by sound therapy if it trains attention and the new auditory activity introduced by the sound therapy becomes the focal stimulus forcing tinnitus to become a backgroimd soimd (Searchfield et al, 2012). Electroencephalography (EEG) measures of restingstate oscillatory electrical activity in the tinnitus brain

suggest that there is enhanced activity in the amygdala (Vanneste et al, 2010). However, there is mixed anatomical evidence to suggest a difference in the brain of those with and without tinnitus. While some studies report differences in gray matter in the emotional centers (subcallosal area) between those with tinnitus and those without it (e.g.. Mühlau et al, 2006), Melcher et al (2013) demonstrated that this effect could be due to differences in hearing thresholds between subjects, irrespective of the presence or absence of tinnitus. Emotional disturbance generally refers to the "stress response," which is a constellation of physiological events that occurs in response to some stress-inducing stimulus (Iversen et al, 2000). The use of music has been shown in numerous studies to reduce the stress of patients in clinical settings (Salamon et al, 2003). Relaxing music lowers blood pressure, reduces heart rate, and creates a sense of well-being (Steelman, 1990; Krumhansl, 1997). The mechanisms underlying these effects have been extensively studied (Chrousos and Gold, 1992). Physiological and behavioral reactions to tinnitus can be mitigated through the use of music. More generally, any sound that is perceived as relaxing can reduce stress; thus, sound therapy targeting the relaxation response can be an important component of any tinnitus management program (Henry, Zaugg, Myers, Schechter, 2008). PUTATIVE EFFECTS OF SOUND ON TINNITUS PERCEPTION AND REACTION any types of sound (generation of noise, environmental sounds, music, or the amplification of naturally occurring sounds by hearing aids) have been applied to the task of tinnitus treatment (Jastreboff, 2007a; Henry, Zaugg, Myers, Schechter, 2008). Sound therapy has been proposed to exert its benefits through tinnitus masking by reducing audibility (Vernon, 1977) or by inducing a sense of relief (Vernon and Meikle, 2000), through habituation (Jastreboff and Hazell, 1993), by reversing abnormal cortical reorganization or acti^vity thought to contribute to tinnitus (Noreña and Eggermont, 2005; Tass et al, 2012), or through the promotion of relaxation (Sweetow and Sabes, 2010).

M

Masking In psychoacoustic terms, masking can be categorized as either "energetic" or "informational" (Bennett et al, 2012). With energetic masking, interference of auditory signals takes place within the cochlea, resulting in suppression of the resultant neural activity. Whereas energetic masking can be thought of as a "bottom-up" peripheral process, informational masking is more of a "top-down" central process. Specific psychoacoustic protocols have been developed to test informational

Tinnitus Sound Therapy/Hoare et al

masking (e.g., Kidd et al, 1994; Durlach et al, 2003, Richards and Neff, 2004), hut for our purposes we can consider it to he a process of neural interference that occurs at more central levels. A great deal has heen written ahout the speculated mechanisms of tinnitus masking, starting 'with the seminal paper hy Feldmann (1971), who descrihed data supporting a retrocochlear origin of the tinnitus signal. Indeed, the prevailing view has heen that tinnitus has a central origin. This view has heen challenged, however, by alternative explanations that tinnitus can he generated in the cochlea or auditory nerve (Penner and Bilger, 1995; Nouvian et al, 2012). Until the physiological origin(s) of tinnitus are confirmed, we must rely on phenomenological data to generate reasonahle hypotheses upon which to hase rational therapies involving sound. In practical terms, "total" tinnitus masking involves the use of sufficient external sound to make tinnitus inaudible. "Partial" masking is the interference of the perception of tinnitus through sound where hoth the tinnitus and masker sound are audible at the same time. Masking for any given individual or clinician may range across a signal (tinnitus) to noise (sound therapy) continuum from the minimum effective level to total masking (Tyler, 2006). Masking is sometimes thought of as a relief therapy (Henry et al, 2006), providing a sense of relief from stress or anxiety caused hy tinnitus. It should he emphasized that the primary purpose of Vernon's method of "tinnitus masking" is to induce a sense of relief (Vernon and Meikle, 2000), with the actual effect on the perception of tinnitus usually being partial masking. In a Cochrane review, Hohson et al (2010) evaluated the effectiveness of sound-generating devices for managing tinnitus. These authors used the terms sound therapy and masking interchangeahly, thus any reference to masking did not imply total masking. The review identified six randomized controlled trials (RCTs) that met their inclusion criteria, three of which (Mehlum et al, 1984; Hazell et al, 1985; Henry et al, 2006) included sound in a masking manner (the other studies used a TRT-like approach or the Neuromonics treatment, hoth discussed later). Only one study (Hazell et al, 1985) compared the effect of masking to a nosound control, finding that a reduction in the effects of tinnitus on sleep and overall quality of life was greater for those who used maskers (ear-level sound generators). It was concluded that masking/sound therapy was a useful approach, but it was acknowledged that counseling was important to overall therapy success (Hazell et al, 1985). One potential outcome of high-intensity masking is residual inhihition (RI), a partial or total suppression of tinnitus typically lasting seconds to minutes following the presentation of relatively intense sound (Roherts et al, 2006). RI has heen used clinically as an aid for

counseling and to demonstrate that broadband noise can impart a beneficial effect (Vernon and Meikle, 2000). The finding that RI occurs with most patients who receive the appropriate type of auditory stimulation (Vernon, 1981, 1988; Tyler et al, 1983; Meikle and Walsh, 1984) makes it surprising that this phenomenon has received little investigation with regard to specific parameters of acoustic stimuli that are responsible for its occurrence. At least one company (Tipa Tinnitus Corporation) is marketing a device that is claimed to produce prolonged RI (reviewed further below). Recent magnetoencephalography (MEG) data from Adjamian et al (2012) further suggests that there is a physiological effect of tinnitus masking: they reported a reduction in delta hand activity when participants experienced tinnitus masking, demonstrating a possible neuronal marker for the effect of masking. Habituation A decline in the reactions to and the perception of tinnitus over time is often descrihed as heing the result of hahituation (McKenna, 2004). Habituation is the basis of common tinnitus treatment methods used in psychology (Hallam et al, 1984) and audiology (Jastreboff and Hazell, 1993). The original habituation model of tinnitus was based on the hypothesis that most people naturally habituate to tinnitus, that is, they come to classify tinnitus as a meaningless sound, and their negative reactions to tinnitus consequently decline with time (Hallam et al, 1984). According to this model, people with chronic intrusive tinnitus are those who fail to habituate. The most established and protocol-driven tinnitus management strategy to promote hahituation is TRT (Jastreboff and Hazell, 1993). TRT aims to facilitate habituation of reaction to tinnitus, primarily through counseling, and habituation of perception through use of sound. All TRT patients are advised to continuously "enrich their sound environment" with low-level, relatively henign soimd, thus creating a constant "passive listening" environment that promotes habituation (Jastreboff and Hazell, 2004). Patients with more severe tinnitus are advised to wear ear-level sound generators during all waking hours to optimize the sound therapy protocol. An important concept relevant to sound therapy with TRT is that the external sound should always he perceived "below the mixing point." The rationale for this requirement is that hahituation is stimulus specific (Thompson and Donegan, 1987). Sound therapy helow the mixing point means that the external sound does not alter the tinnitus percept; that is, the spectral characteristics of the tinnitus percept should not be altered so that hahituation can take place to the "usual tinnitus" (Jastrehoff and Hazell, 2004).

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Journal of the American Academy of AudiologyA^olume 25, Number 1, 2014

Trials of TRT suggest benefits but have been criticized for the difficulties disassociating sound stimulation effects from counseling effects (McKenna and Ir'win, 2008). A controlled study comparing TRT and "tinnitus masking" showed that both methods could provide significant benefit to a large majority of individuals with severely bothersome tinnitus (Henry et al, 2006). TRT, however, achieved greater benefit in the long term, and patients with more severe tinnitus improved more with TRT. A more recent RCT compared classical TRT to counseling with a reduced sound component (Bauer and Brozoski, 2011). Although tinnitus handicap progressively improved for both the placebo and sound therapy groups over the 18 mo trial, at 18 mo the clinical effect size was greater for the group recei'ving the full sound component of TRT. Psychoacoustic loudness did not change in this trial suggesting no effect of the interventions on the neural activity responsible for the tinnitus signal (Bauer and Brozoski, 2011). Questions remain as to the effectiveness of different components of TRT. For example, the developers of TRT stated that "If tinnitus is suppressed ("masked") habituation will never occur" (Jastreboff and Hazell, 2004). This claim was tested by Tyler et al (2012), who randomized subjects into three groups: total masking, TRT, and counseling only. All three groups showed improvement on a tinnitus outcome questionnaire, and there was no significant difference between groups. The results of this study call into question the premise that total masking precludes habituation but do not definitively answer the question due to limitations of the study (e.g., small group design, hearing aid users excluded, no intent-to-treat analysis) and the need to replicate these results. It is imperative that well-designed, well-controlled studies be conducted to answer basic questions about the optimal use of sound as therapy for tinnitus. Sound to Target Both Tinnitus Percept and Reaction There are confiicting accounts for the putative action of many practicable sound therapy options as to whether they target the tinnitus reaction to promote relaxation and reduce stress or whether they are actually targeting neuromodulation through plastic change. The correlation between habituation of reaction and habituation of perception, and if achieving the first will lead to the latter, was also an important concept arising from Jastreboffs (1990) neurophysiological model. Complex tones or music have certainly been demonstrated to modulate attention, emotion, cognition, behavior, and communication and are consequently believed to have benefits for health (Koelsch, 2009; Attanasio et al, 2012). And, as a tinnitus therapy, music has been used both singularly (Argstatter et al, 2012) or as part of a multifaceted intervention (Davis, 2006).

6B

Music has been manipulated in an attempt to enhance treatment by accounting for the frequency spectrum of music relative to auditory threshold and tinnitus, or to promote lateral inhibition between tinnitus and nontinnitus areas of the auditory cortex (Davis, 2006; Okamoto et al, 2010). Okamoto et al (2010) modified music with a one-octave notch at the individual's tinnitus pitch. Music was used because of its emotional and motivational benefit and was notched at the putative tinnitus frequency in an attempt to achieve lateral inhibition and reverse maladaptive activity. In this study, after 12 mo of daily listening, participants' tinnitus annoyance and handicap were reduced relative to a placebo music (notch distant from tinnitus pitch) control group. MEG further indicated significantly reduced auditory steady state and Nlm responses in the notched music group but not controls (Okamoto et al, 2010), possibly due to a reduced neural population and/or less synchrony in response to tinnitus matched tones (Stracke et al, 2010). More recently, Vanneste et al (2013) examined the relative efficacy of listening to music that either compensated for hearing loss, overcompensated for hearing loss, or unmodified music, for 3 hr per day over 1 mo. In this shorter study, there was no change in visual analog scale scores for tinnitus annoyance across the three groups. There was, however, an increase in gamma band activity in the auditory cortex after music exposure for the group receiving the overcompensated stimulus, suggesting that this form of modulated music could actually worsen tinnitus-related brain activity.

CURRENT PRACTICABLE OPTIONS FOR SOUND THERAPY summary of the options renewed here and the highest level of research evidence identified for each option are given in Table 1.

A

Acoustic Coordinated Reset (CR) Neuromodulation This method was developed by Adaptive Neuromodulation GmbH (ANM) (www.anm-medical.com/) and explicitly targets pathological neural synchrony that may be responsible for tinnitus generation. Sound stimuli are individualized to span a frequency range centered on the dominant tinnitus pitch. Patients are required to listen to sequences of tones presented at a low volume over open-fit headphones for up to 8 hr daily. The pattern of sound stimuli is predicted to force asynchronous firing of neurons from 'within a pathologically firing population through a reduction of mean S3maptic weight (Hauptmann and Tass, 2007), an effect measurable using EEG. Indeed, in their exploratory trial, Tass et al (2012) measured EEG activity at baseline and again after 12 weeks of Acoustic CR Neuromodulation

Tinnitus Sound Therapy/Hoare et al Table 1. Practicable Sound Options Sound Device Acoustic CR Neuromodulation

Putative Mechanism of Action

Serenade

Neuromodulation—disruption of pathological neurai synchrony Relaxation, neuromodulation

Oasis Hearing Aids

Relaxation Masking, neuromodulation

Wearable White Noise Generators

Masking, habituation

Combi-Devices: Hearing Aid with White Noise Generator

Masking, relaxation

Phase-Out/Phase-Shift

Noise cancellation

Tipa Tinnitus Device

Extended residual inhibition

Table-Top Devices

Relaxation

1

Indications/Requirements

Highest Supporting Evidence

4+ hr daily over several months

Safety of the device demonstrated in an exploratory study

^ 1 hr per day for short-term relief. e.g., to support sleep 2+ hr per day for 6 mo Aid a hearing loss, functional hearing difficulties; to be worn maximally during waking hours Used variably to provide acute relief or maximally during waking hours as per therapy plan Hearing loss and tinnitus; devices to be worn maximally throughout waking hours

No clinical trials or other evidence identified Clinical trials but of limited quality Number of open trials and cohort studies: inconclusive

30 min sessions for short-lasting relief repeated as required 10 min sessions for short-term relief repeated as required Intermittent use for immediate relief such as at night

treatment, most notably finding there to be an increase in alpha band power (strongest in temporal and prefrontal cortex), a reduction in delta (strongest in auditory cortices), and a general reduction in gamma power after treatment. Tass et al (2012) also reported clinically significant improvements in tinnitus handicap (reduction on the Goebel Hiller Tinnitus Questionnaire, GHTQ score; Goebel and Hiller, 1994) after treatment. This trial was exploratory, however, and so the efficacy of the device has yet to be demonstrated. An independent Phase 2 clinical trial is currently underway in the UK (clinicaltrials.gov identifier: NCT01541969). SoundCure The Serenade device was developed in the United States by SoundCure Inc. (www.soundcure.com). The device delivers programs of sounds, recently described by the provider in an industry magazine as "cortically interesting," that are designed to effect highly synchronous cortical responses (Strom, 2012). This approach stems from the work of Zeng et al (2011), who reported a single-case study of electrical stimulation delivered by a unilateral cochlear implant to relieve tinnitus. Zeng et al (2011) found that whereas high-rate (2-5 kHz) electrical stimulation had no effect on tinnitus, a 100 Hz electrical stimulation pulse delivered to an apical electrode provided total tinnitus suppression and led to an increase in alpha band (7-9 Hz) power. More recently, the same group examined tinnitus suppression

Cochrane review of clinical trials: inconclusive of effect of masking independent of counseling Low-level evidence of improvement in tinnitus handicap for some patients from one small-scale cohort study Randomized double-blind crossover study showed no specific effect No clinical triais identified No clinical trials identified

during and after exposure to a series of modulated sounds at different modulation rates and carrier frequencies, and unmodulated sounds at different carrier frequencies (Reavis et al, 2012). A 40 Hz amplitudemodulated tone with carrier frequencies near the tinnitus pitch generated the best tinnitus suppression (up to total suppression during stimulation, with residual inhibition lasting up to 90 sec after stimulation ended). The Serenade device delivers two tracks of temporally patterned sounds ("S tones") that are determined according to the span of hearing loss and the dominant tinnitus pitch. It also delivers a customized narrowband sound and a broadband sound. The manufacturer recommends its use on an "as needed" basis to gain relief, for example, before going to bed. But whereas the sound element of the intervention is considered to target the neural activity associated with tinnitus, it is stressed that the treatment process relies on counseling to address the psychological reaction to tinnitus. The clinical effectiveness and neurophysiological effects of Serenade have yet to be demonstrated. Neuromonics Neuromonics uses modified music that compensates for hearing loss and provides less low-frequency bias than unmodified music (www.neuromonics.com). Music is delivered using a lightweight Oasis device with headphones in a two-stage process starting with high tinnitus interaction (total masking) for about 2 hr per day (stage

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1), followed by a lower level of music in which the tinnitus is intermittently masked through the natural d5mamics (peaks and troughs) of the music (stage 2). Considered from the perspective of an acoustic desensitization theory (Yulis et al, 1975), tinnitus creates a negative "phobic-like" reaction in patients. The gradual exposure of patients to their tinnitus in a controlled and supportive manner (through counseling and relaxing music) is claimed to lead to a decrease in reaction (Davis et al, 2008), which is, in essence, a systematic desensitization approach (Yulis et al, 1975). Neuromonics has been the subject of a number of clinical investigation papers and re'views (Davis et al, 2007; Davis et al, 2008; Hanley and Davis, 2008; Hanley et al, 2008; Henry, Zaugg, Myers, Schechter, 2008; Goddard et al, 2009; Henry and Istvan, 2010; Jang et al, 2010; Seidman et al, 2010; Távora-Vieira et al, 2011; Wazen et al, 2011). Most studies show there to be significant improvements in tinnitus questionnaire scores occurring across 6 to 24 mo of therapy, particularly if patients meet the majority of the developer's clinical selection criteria (Davis et al, 2008). However, few studies used a controlled comparison. Davis et al (2008) compared (a) 2 hr daily use of Neuromonics with (b) 2 hr daily use of the de'vice plasdng broadband noise at the mixing point and (c) a no sound control. All groups received counseling. In the Neuromonics group, 86% reported a clinically significant improvement (40% reduction in Tinnitus Reaction Questionnaire), and 47% met the same criteria in the broadband noise group, while 23% in the no sound control group reported significantly reduced tinnitus handicap (Davis et al, 2008). This result suggests that the provision of the de'vice and the type of sound used influenced treatment outcome. In a more recent retrospective between-subjects clinical study, Newman and Sandridge (2012) compared the cost-effectiveness and cost utility of Neuromonics versus ear-level sound generators. While both interventions resulted in reduced tinnitus handicap score, there was no difference in improvement between groups. Sound generators, therefore, as the less expensive option, emerged as the preferred choice in tenns of cost-effectiveness and utility. General reviews of Neuromonics trials also cast doubt on our confidence in the published data. Henry and Istvan (2010) were critical of the lack of methodological rigor in the three controlled studies published at the point of their review. Potential physiological mechanisms affected by the interventions have not been defined. However, one aspect of auditory processing that may count against the intermittent masking (stage 2) used by Neuromonics is the ability of the auditory system tofillgaps, so-called continuity or auditory restoration (Petkov and Sutter, 2011). Tinnitus may appear continuous even if at certain points in time the tinnitus is obscured. This continuity

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effect may contribute to the need to maintain a higher level of masking and limit or delay intermittent masking. Such effects require further study. Hearing Aids Hearing aids amplify external sounds, which reduces the contrast between tinnitus perception and the external sounds, thereby reducing the relative salience of tinnitus (McNeill et al, 2012). Alternatively, amplification by hearing aids may simply help to refocus attention on sounds that are different from the tinnitus sound. Hearing aids also improve communication (Surr et al, 1985; Carmen and Uram, 2002), which alone may indirectly lead to improved tinnitus self-report. It can also be hypothesized that hearing aids act as a form of sound enrichment, decreasing the possibility of sensory deprivation and thus decreasing neuroplastic changes within the central auditory system that contribute to tinnitus generation. Despite being recommended as a potentially useful intervention for tinnitus since the 1940s, hearing aids have been the subject of many open trials and cohort studies (beyond our scope but recently re'viewed by Shekhawat et al, 2013) but trials of hearing aids for tinnitus have only recently been systematically reviewed (Hoare et al, 2014). It is uncertain what benefit fi:-om hearing aids results from a change in reactions to tinnitus as opposed to improvement in hearing fimction. Wearable White Noise Generators A number of studies have explored the efficacy or relative efficacy of ear-level white noise generators (also referred to as sound generators and maskers). In their systematic review of masking for tinnitus, Hobson et al (2010) reported that there was little current evidence to indicate the effectiveness of maskers. Indeed, sound therapy using masking appeared to be no more effective than education or relaxation training (Dineen et al, 1999), the provision of hearing aids (Mehlum et al, 1984; Hazell et al, 1985), or a waiting list control (Groebel et al, 1999). Where recorded, masking did not effect changes in tinnitus quality (Dineen et al, 1999), suggesting that the changes to occur during tinnitus masking are likely habituations rather than modulation of the tinnitus generating activity. Hobson et al (2010) concluded "the absence of conclusive evidence should not be interpreted as evidence of lack of effectiveness," and "optimal management may involve multiple strategies" (p. 2). Combination Instruments—Examples Widex Zen The Widex Zen combines a hearing aid and sound generator using an altemative to conventionally composed

Tinnitus Sound Therapy/Hoare et al

and performed music in the form of fractal "music" or tones (www.widex.co.uk/en/products/thewidexsound/zen/). A fractal is a mathematical algorithm that generates a series of sounds, and, like music, fractal tones have been proposed to promote relaxation, which might in turn have some benefits for persons with tinnitus. In an industry magazine article Kuk et al (2010) reported a survey of patients who had been fitted with the device by clinicians with some training in tinnitus management. Forty-three patients participated, but only 26 completed a tinnitus quality of life measure (the Tinnitus Reaction Questionnaire—TRQ; Wilson et al, 1991) both pre- and post-fitting. Of the 26 patients, 18 (69%) had TRQ improvements of greater than 20 points. At the same time, a research study from Sweetow and Sabes (2010) monitored changes in Tinnitus Handicap Inventory (THI; Newman et al 1996) questionnaire score and TRQ score over a 6 mo period following the fitting of the fractal combination aids to 14 participants. Five participants (36%) had a 20-point THI improvement, and four (29%) had a 40% or greater TRQ improvement at the 6 mo follow-up. The most widely preferred fractal sounds in both studies were those with slow-medium tempos and restricted dynamic range, which were also found to be the most relaxing (Sweetow and Sabes, 2010). It is difficult to ascertain from these studies whether the fractal tones were beneficial because of their relaxation effect or masking or the extent of benefit from concurrent background amplification relative to the fractal sounds. No physiological measures have been undertaken toward identifying the effect of fractals on putative tinnitus mechanisms.

I

Danalogic iFIT Tinnitus

The Danalogic iFIT Tinnitus is another example of a combination instrument. This device offers sound generator options of broadband signals, a narrowband signal focused on the frequency of the tinnitus, and the option of using amplitude modulation (AM; fiuctuation in the level of noise signal while all other spectral components remain uniform). The stated purpose from the company is to provide options to personalize the sounds to those preferred or most acceptable to the individual (www.danalogic-ifit.com). ReSound Live TS ReSound Live TS is another combination instrument providing options for the use of broadband or narrowband noise, with additional options for amplitude modulation and environmental steering (www.gnresound. com). The suggested mechanism of action is the diversion of attention away from tinnitus, thereby promoting habituation. AM and the speed at which AM fluctuations occur are used as "comfort settings." The Environ-

mental Steering option allows automatic volume control and has seven different environmental settings, negating the need to manually adjust the device when moving between different noise and listening environments. Piskosz and Kulkarni (2010) provided an industry magazine report on two studies using the Live TS in combination with counseling over a 6 mo period. Study A was a cohort study that found significant improvement in tinnitus handicap (mean reduction in THI score of 20 points) at the end of the 6 mo. Study B looked at the preferences for broadband or narrowband sound, the environmental steering feature versus volume control, and AM versus continuous noise. In their sample of 24 patients, 82% preferred the broadband noise option, 68% preferred the volume control feature over Environmental Steering, and 73% preferred unmodulated soimd to AM sounds. Summary of Combination Instruments Combination instruments have been available since the 1980s. Until fairly recently, however, these devices tended to provide limited hearing aid options and/or quality. Within the past few years, most major hearing aid companies have developed combination instruments that offer full-featured hearing aids. Some of these are described above. Other combination instruments currently available include devices produced by Starkey (Xino Tinnitus) and Siemens (Life and Pure Carat). Although data are not definitive, the addition of noise or other sounds to hearing aids seems to benefit many patients with tinnitus. Provided there is no sacrifice to the amplification needs of the patient, fitting combination instruments rather than hearing aids may be the preferred option when reactions to tinnitus are a concern. These instruments, without amplification, can also be employed in the management of tinnitus for people with normal hearing. Pbase-Sbift and Phase-Out Phase-Out therapy is based on the principle of noisecancellation; Choy et al (2010) hypothesized that if a sound was pitch and volume matched to tinnitus, and then phase shifted sequentially by 6° at intervals of 30 sec (i.e., 360° over a 30 min intervention), the neuronal complex in the auditory cortex responsible for that tinnitus tone would be cancelled at least temporarily. However, in a large population study, Choy et al (2010) found that only 1% of patients had what was defined as a long-term total resolution of their tinnitus. Various lesser reductions were reported, but with the lack of appropriate control data, spontaneous improvements in tinnitus or placebo effects are not accounted for. In an earlier open prospective clinical trial of PhaseOut, Vermeire et al (2007) reported a mean improvement

Journal of the American Academy of AudiologyA^^olume 25, Number 1, 2014

of 5.5 points on the Tinnitus Questionnaire (TQ; Hallam, 1996; minimum clinically important difference is 5 points). Although clinically significant, a shift of 5 points has been reported elsewhere as a test-retest effect in tinnitus studies (Dohrmann et al, 2007), so we can have little confidence in the estimate of the effect. Phase-shift is another device hased on the same principle of noise cancellation. Produced by Tinnitus Care (London), this device delivers a stimulus that is of the same amplitude and frequency as the tinnitus sound but with an inverted phase. The stimulus is delivered over a 30 min session. Lipman and Lipman (2007) reported the results of 61 participants who underwent 2 wk of phase-shift treatment. One infivereported a clinically significant reduction in THI score (20 points or more). Most participants reported a reduction in tinnitus loudness induced by the stimulus (41% had complete residual inhihition for some period). Tinnitus loudness increased for 22% of participants. While this result looks more promising than that for Phase-Out, when the use of the inverted phase tone was compared to noninverted phase tone in a randomized douhle-blind crossover study, there was no difference in effect hetween groups in terms of change in handicap questionnaire score, tinnitus quality, or loudness or annoyance ratings (Heijneman et al, 2012). So the effect of the phaseinverted signal was no greater than its hest control. The concept of noise cancellation with tinnitus warrants some comment. Noise cancellation headphones available commercially are designed to detect a continuous signal and to add the same signal but phase shifted hy 180°. Combining these two signals cancels the original signal. This effect is limited to low-frequency sounds such as the constant roar from inside an airplane. It is tempting to think that the same approach could be used with tinnitus, which is also a continuous signal. Tinnitus, however, is not an acoustic signal and therefore does not have an acoustic phase. It is theoretically impossible to cancel tinnitus through noise cancellation procedures. Any henefit from such devices may be attributed to sound therapy effects in general or to nonspecific effects. Tipa Tinnitus Device The Tipa Tinnitus Device reputedly works through the induction of extended periods of residual inhibition "probably through inhihitory pathways using digital non sinusoidal low frequency sounds" (http://tipatinnitus. com/). The system uses three different complex tones each presented for 3 min and played in the order 1,2,1,3 (12 min stimulus in total per day). Case studies presented at conference by Winkler (2009) claim that the signal can induce RI lasting many hours. Although some anecdotal evidence of the effects are presented on

the Tipa Web site, the effect has yet to he tested in controlled and peer-reviewed studies. Non-Ear-Level Sound Options Alternatives to ear-level devices in sound therapy include sound therapy Web sites (e.g., heyondtinnitus. com), the use of music from a speaker system, or the use of hedside or table-top sound generators. Bedside or table-top sound generators typically deliver a variety of simple or natural sounds to choose from. Indeed, Handscomb (2006) found that the choice of sound selected for use with hedside sound generators was infiuenced more hy emotional than sensory factors. Therapeutic sounds delivered in this way may elicit positive responses due to positive memory associations (Henry et al, 2004). RECOMMENDATIONS FOR THE CLINICAL MANAGEMENT OF TINNITUS USING SOUND AS PART OF INDIVIDUALIZED, MULTIDISCIPLINARY CARE here are many different models of tinnitus management in use and under investigation worldwide (Henry, Zaugg, Myers, Kendall, 2008; Department of Health, 2009; Biesinger et al, 2010; Cima et al, 2012). All of these models advocate a multidisciplinary approach (Daugherty and Wazen, 2010). The introduction of sound therapy to care therefore needs to foUow a pragmatic line.

T

Is the Patient at the Right Stage of Care to Introduce Sound Therapy? For successful engagement with sound therapy, it is essential that the patient is sufficiently informed of their sound therapy options, motivated to try sound therapy, and has expressed realistic expectations of the effects of the proposed therapy. Henry, Zaugg, Myers, and Kendall (2008) descrihe a Progressive Tinnitus Management (PTM) approach using a hierarchical (stepped-care) program of triage, audiological evaluation, skills education, interdisciplinary evaluation, and individual patient management. Within this program it is envisaged that the patient reaches autonomous decisions on their choice of sound therapy, for example, whether soothing (to calm anxiety or nervousness), hackground (for contrast reduction), or interesting (to shift attention) sounds are going to he of henefit to them in different situations. With PTM, the goal is for patients to achieve self-efficacy in managing their reactions to tinnitus. The skills education level of PTM is designed to pro'vide patients with coping and sound therapy skills. The philosophy with PTM is to provide these skills at the earliest level of intervention so as to empower patients with the ability to self-manage their

Tinnitus Sound Therapy/Hoare et al tinnitus and to make informed choices regarding specific forms of treatment that might be available. Tinnitus and reactions to tinnitus may be altered by the specific sound chosen, which can have effects involving different levels of processing: encoding (tinnitus and sound interact such that tinnitus is totally suppressed, i.e., energetic masking), central analysis (where tinnitus and sound—distractor—are similar but distinguishable, i.e., informational masking), mood and arousal (e.g., music), and psychosocial (e.g., hearing aids). These stages in processing involve both bottom-up and topdown auditory modulation of activity. It has been hypothesized that bottom-up adaptation processes are major contributors to determining the signal strength of tinnitus (Searchfield et al, 2012); a significant top-down contribution is an individual's detection thresholds (Welch and Dawes, 2008). For the full benefits of any sound therapy, an effective intervention may initially require management of residual and psychological factors, such as arousal, through effective counseling and pro'viding relief through higher levels of sound; once the individual has some level of control (i.e., they have adjusted to tinnitus), a second stage of lower soimd might facilitate adaptation. This is coimtered by an argument fi-om Pineda et al (2008), however, who propose that combining customized sound therapy (designed to draw attention away from the tinnitus sound) with directive counseling (which ultimately draws attention to tinnitus) could be counterproductive. Such an effect, if actual, might be acute but recurring in the case of a therapy where sound is used continuously and directive counseling is delivered in a limited series of educational interactions. The choice of an individualized patient counseling or psychoeducation approach that is complementary to the sound therapy intended (and vice versa) is consequently an important consideration.

What Is the Patient's Hearing Like? As hearing loss is a high risk factor for tinnitus (Sindhusake et al, 2004) it should be addressed with all tinnitus patients. In most circumstances hearing loss will require hearing aids or, occasionally, cochlear implants. The use of hearing aids may have strong psychosocial benefits as well as infiuencing most of the processes postulated in the model to drive tinnitus, that is, sound enrichment. Combination instruments pro'vide a further option for those with an aidable hearing loss, with further technology options of environmental steering and modulated masking sounds available with some devices. This provides a range of options to explore and individualize the device to particular preferences. What Sound Therapy Options Are Acceptable? When assessing the suitability of sound therapy for a particular patient, there is a need to understand from

the outset what sort of tinnitus exacerbating factors there are and whether the patient has identified any factors that reduce the tinnitus (perception or reactions) such as particular sound situations. In terms of selfmanagement, patients could be ad'vised on the potential benefit of using sound-producing devices at their disposal such as personal music players or radios, electric fans, table fountains, and so on. Assessment for the presence of hyperacusis, which is not an uncommon association with tinnitus, might be an important first step if the patient expresses abnormal reactions to everyday sounds. Acceptability of the sound to be used is essential. For example, if sound level needs to be raised to an uncomfortable level to mask tinnitus, then the patient is not a good candidate for that intervention. Henry, Zaugg, Myers, and Kendall (2008) examined the relative acceptance of dynamic reproduced environmental sound as masking sounds finding that the more dynamic (water, nature) sounds reduced tinnitus annoyance more than the less dynamic (air) sounds, although only 11 of their 21 participants reported any relief from tinnitus, and for four participants the sounds increased tinnitus annoyance. Mental imagery techniques may be used to enhance the effect of positive sounds on tinnitus (e.g., imagining sitting on a beach). Once learned, associated relaxation may persist on cessation of therapeutic sound. The Cleveland Clinic Sound Therapy Option Profile (STOP) tool contains a number of questions on issues that are likely to influence a patient's preference or aversion to particular sound therapies (available at audiologyonline.com). The questionnaire probes the issues of patient motivation to use sound therapy, the amount of intervention they are willing to accept (hours per day, months of continued therapy), expectations and confidence in sound therapy, acceptability of different sounds, and willingness to pay. This tool may be useful in particular when a number of sound therapy options are available to the patient. RESEARCH THAT IS NEEDED

M

ost sound therapy interventions focus on a single putative mechanism. The complex nature of tinnitus however (Roberts et al, 2010; De Ridder et al, 2011), suggests that we should either use sound therapy that targets a broad range of potential tinnitus mechanisms or identify subgroups of tinnitus patients that, based on their symptom profile would be predicted to benefit from a specific therapy. It is also important to understand those subgroups for which sound therapy is wholly ineffective or indeed exacerbates tinnitus. The current body of research available on sound therapy is insufficient for us to do that. Many research reports also fail to distinguish between individuals who do not seek help for tinnitus and those who do. It is possible that those two groups might have different

Journal of the American Academy of AudiologyA'^olume 25, Number 1, 2014

underlying mechanisms and hence would respond differently to the same intervention. Although sound therapy is commonly used, we still know very few details about its specific benefits and modes of effect. Consequently, any model of sound therapy needs to be open for critique and modification as evidence becomes available. The absence of RCTs for sound therapy has been bemoaned (McKenna and Irwin, 2008; Hoare et al, 2011); however, to support the design of large-scale trials there is also a need for small-scale heuristic or well-designed single-subject studies to examine the components of sound therapy that likely contribute to treatment success. As we report here, while some sound therapies have been the subject of a number of chnical trials (e.g., masking, TRT, Neuromonics), most have received little investigation. Proponents of sound therapy need to systematically evaluate both behavioral effects in a more rigorous manner and exploit the developments in auditory electrophysiology and neuroimaging to elucidate mechanisms that contribute to any improvement in tinnitus (perception and/or reactions) that is reliably demonstrated. The inclusion of objective measures in an attempt to understand contributing mechanisms is highly desirable (e.g., MEG studies undertaken alongside behavioral measures of notched music effects by Okamoto et al, 2010).

patients with and without hearing loss. JAssoc Res Otolaryngol 13(5):715-731.

CONCLUSIONS

Cima RFE, Maes IH, Joore MA, et al. (2012) Specialised treatment based on cognitive behaviour therapy versus usual care for tinnitus: a randomised controlled trial. Lancet 379(9830): 1951-1959.

ound therapy on its own is of unproven benefit; equally, there is little to suggest it is of potential harm to patients. In particular there is limited evidence of the benefit of sound therapy independent from other concomitant treatment factors such as counseling (McKenna and Irwin, 2008). Our understanding of the neuroscience of tinnitus has made great strides Eind gathered momentum particularly with the use of advanced imaging techniques (Lanting et al, 2009; Adjamian et al, 2012; Melcher et al, 2013), and while sound therapy research has been rooted largely in the behavioral domain, studies of the neurophysiological consequences of sound therapies are beginning to emerge (Tass et al, 2012). There are few large-scale controlled studies to support or refute many of the sound therapy options currently in use, amounting to considerable gaps in our evidence base, and therefore opportunities to design and run exciting explanatory trials. Despite the current lack of explanatory evidence, sound therapy should be considered an essential component of any clinical program of tinnitus management.

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Argstatter H, Grapp M, Hutter E, Plinkert P, Bolay HV. (2012) Long-term effects of the "Heidelberg Model of Music Therapy" in patients with chronic tinnitus. Int J Clin Exp Med 5(4): 273-288. Attanasio G, Gartocci G, Covelli E, et al. (2012) The Mozart effect in patients suffering from tinnitus. Acta Otolaryngol 132(11): 1172-1177. Bauer CA, Brozoski TJ. (2011) Effect of tinnitus retraining therapy on the loudness and annoyance of tinnitus: a controlled trial. Ear Hear 32(2): 145-155. Bennett KO, Billings CJ, Molis MR, Leek MR. (2012) Neural encoding and perception of speech signals in informational masking. Ear Hear 33(2):231-238. Biesinger E, Del Bo L, De Ridder D, et al. (2010) Algorithm for the Diagnostic and Therapeutic Management of Tinnitus, www. tinnitusresearch.org/eny'documents/downloads/TRI_Tinnitus_ Flowchart.pdf. Carmen R, Uram S. (2002) Hearing loss and anxiety in adults. Hear J 55:48-54. Choy DS, Lipman RA, Tassi GP. (2010) Worldwide experience with sequential phase-shift sound cancellation treatment of predominant tone tinnitus. J Laryngol Otol 124(4):366-369. Chrousos GP, Gold PW. (1992) The concepts of stress and stress system disorders. Gverview of physical and behavioral homeostasis. JAMA 267(9):1244-1252.

Daugherty J, Wazen J. (2010) A new model for tinnitus treatment. Hear Rev 17:26-30. Davis P. (2006) Music and the acoustic desensitization protocol for tinnitus. In: Tyler RS, ed. Tinnitus Treatment. New York: Thieme, 146-160. Davis PB, Paki B, Hanley PJ. (2007) Neuromonics Tinnitus Treatment: third clinical trial. Ear Hear 28(2):242-259. Davis PB, Wilde RA, Steed LG, Hanley PJ. (2008) Treatment of tinnitus with a customized acoustic neural stimulus: a controlled clinical study. Ear Nose Throat J 87(6):330-339. Department of Health. i2009)Provisionof Services for Adults with Tinnitus. A Good Practice Guide. London: Central Office of Information. De Ridder D, Elgoyhen AB, Romo R, Langguth B. (2011) Phantom percepts: tinnitus and pain as persisting aversive memory networks. Proc Nati Acad Sei USA 108(20):8075-8080. Dineen R, Doyle J, Bench J, Perry A. (1999) The influence of training on tinnitus perception: an evaluation 12 months after tinnitus management training. Br J Audiol 33(1):29-51.

REFERENCES

Dohrmann K, Elbert T, Schlee W, Weisz N. (2007) Tuning the tinnitus percept by modification of synchronous brain activity. Restor Neurol Neurosa 25(3-4):371-378.

Adjamian P, Sereda M, Zobay O, Hall DA, Palmer AR. (2012) Neuromagnetic indicators of tinnitus and tinnitus masking in

Durlach NI, Mason CR, Shinn-Cunningham BG, Arbogast TL, Colbum HS, Kidd G, Jr. (2003) Informational masking: counteracting

7S

Tinnitus Sound Therapy/Hoare et al the effects of stimulus uncertainty by decreasing target-masker simUarity. J Acoust Soc Am 114(l):368-379. Eggermont JJ, Roberts LE. (2004) The neuroscience of tinnitus. Trends Neurosd 27(ll):676-682.

Henry JA, Zaugg TL, Myers PJ, Schechter MA. (;2008) Using therapeutic sound with progressive audiologic tinnitus management. Trends Amplif 12(3): 188-209.

Feldmann H. (1971) Homolateral and contralateral masking of tinnitus by noise-bands and by pure tones. Audiology 10(3):138-144.

Hoare DJ, Edmondson-Jones M, Sereda M, Akeroyd MA, Hall D. (2014) Amplification with hearing aids for patients with tinnitus and co-existing hearing loss. Cochrane Database Syst Rev (1)CD010151.

Goddard JC, Berliner K, Luxford WM. (2009) Recent experience with the neuromonics tinnitus treatment. Int Tinnitus J 15(2): 168-173.

Hoare DJ, Kowalkowski VL, Kang S, Hall DA. (2011) Systematic review and meta-analyses of randomized controlled trials examining tinnitus management. Laryngoscope 121(7):1555-1564.

Goebel G, Hiller W. (1994) The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire. [In German.] HNO 42(3):166-172.

Hobson J, Chisholm E, El Refaie A. (2010) Sound therapy (masking) in the management of tinnitus in adults. Cochrane Database Syst Rev (12):CD006371.

Goebel G, Rübler D, Stepputat F, Hiller 'W, Heuser J, Fichter MM. (1999) Controlled prospective study of tinnitus retraining therapy compared to tinnitus coping therapy and broad-hand noise generator therapy. In: Hazell J, ed. Proceedings of the Sixth International Tinnitus Seminar. 302-306. Gray CM, König P, Engel AK, Singer W. (1989) Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. Nature 338(6213): 334-337. Handscomb L. (2006) Use of bedside sound generators by patients with tinnitus-related sleeping difficulty: which sounds are preferred and why? Acta Otolaryngol Suppl 126(556):59-63. Hallam RS. (1996) Manual of the Tinnitus Questionnaire (TQ). London: Psychological Corporation. Hallam RS, Rachman S, Hinchcliffe R. (1984) Psychological aspects of tinnitus. In: Rachman S, ed. Contributions to Medical Psychology. 1st ed. New York: Pergamon Press, 31-53. Hanley PJ, Davis PB. (2008) Treatment of tinnitus with a customized, dynamic acoustic neural stimulus: underlying principles and chnical efficacy. Trends Amplif 12(3):210-222. Hanley PJ, Davis PB, Paki B, Quinn SA, Bellekom SR. (2008) Treatment of tinnitus with a customized, dynamic acoustic neural stimulus: chnical outcomes in general private practice. Ann Otol Rhinol Laryngol 117(ll):791-799.

Iversen S, Kupfermann I, Kandel ER. (2000) Emotional states and feelings. In: Kandel ER, Schwartz JH, Jessell TM, eds. Principles of Neural Science. New York: McGraw-Hill, 982-997. Jang D'W, Johnson E, Chandrasekhar SS. (2010) Neuromonics^" Tinnitus Treatment: prehminary experience in a private practice setting. Laryngoscope 120(Suppl. 4):S208. Jastreboff PJ. (1990) Phantom auditory perception (tinnitus): mechanisms of generation and perception. Neurosd Res (4):221-254. Jastreboff PJ, Hazell JW. (1993) A neurophysiological approach to tinnitus: clinical imphcations. Br J Audiol 27(1):7-17. Jastreboff PJ, Hazell JWP. (2004) Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. New York: Cambridge University Press. Jastreboff PJ, Jastreboff MM. (2000) Tinnitus Retraining Therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients. J Am Acad Audiol 11(3):162-177. Kidd G, Jr, Mason CR, Deliwala PS, Woods WS, Colburn HS. (1994) Reducing informational masking by sound segregation. J Acoust Soc Am 95(6):3475-3480. Koelsch S. (2009) A neuroscientific perspective on music therapy. Ann N Y Acad Sei 1169:374-384. Krumhansl CL. (1997) An exploratory study of musical emotions and psychophysiology. Can J Exp Psychol 51(4):336-353.

Hauptmann C, Tass PA. (2007) Therapeutic rewiring by means of desynchronizing brain stimulation. Biosystems 89(1-3):173-181.

Kuk F, Peeters H, Lau C. (2010) The efficacy offractalmusic employed in hearing aids for tinnitus management. Hear Rev 17:32-42.

Hazell JW, Wood SM, Cooper HR, et al. (1985) A clinical study of tinnitus maskers. Br J Audiol 19(2):65-146.

Langguth B. (2011) A review of tinnitus symptoms beyond 'ringing in the ears': a call to action. Curr Med Res Opin 27(8):1635-1643.

Heijneman KM, de Kleine E, van Dijk P. (2012) A randomized double-blind crossover study of phase-shift sound therapy for tinnitus. Otolaryngol Head Neck Surg 147(2):308-315.

Lanting CP, de Kleine E, van Dijk P. (2009) Neural activity underlying tinnitus generation: results from PET and fMRI. Hear Res 255(1-2):1-13.

Henry JA, Istvan J. (2010) An independent review of Neuromonics Tinnitus Treatment controlled chnical trials. Aust N Z J Audiol 32:41-55. ,

Lipman RI, Lipman SP. (2007) Phase-shift treatment for predominant tone tinnitus. Otolaryngol Head Neck Surg 136(5):763-768.

Henry JA, Rheinsburg B, Zaugg T. (2004) Comparison of custom sounds for achieving tinnitus rehef. J Am Acad Audiol 15(8):585-598.

Llinás RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP. (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatrie syndrome characterized by magnetoencephalography. Proc Nati Acad SciUSA 96:15222-15227.

Henry JA, Schechter MA, Zaugg TL, et al. (2006) Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy. J Am Acad Audiol 17(2): 104-132.

McKenna L. (2004) Models of tinnitus suffering and treatment compared and contrasted. Audiol Med 2:41-53.

Henry JA, Zaugg TL, Myers PJ, Kendall CJ. (2008) Progressive Tinnitus Management: Clinical Handbook for Audiologists. San Diego: Plural Publishing.

McKenna L, Irwin R. (2008) Sound therapy for tinnitus—sacred cow or idol worship?: An investigation of the evidence. Audiol Med 6:16-24.

Journal of the American Academy of AudiologyA^'olume 25, Number 1, 2014

McNeill C, Távora-Vieira D, Alnafian F, Searchfield GD, Welch D. (2012) Tinnitus pitch, masking, and the effectiveness of hearing aids for tinnitus therapy. Int J Audiol 51(12):914-919. Mehlum D, Grasel G, Fankhauser C. (1984) Prospective crossover evaluation of four methods of clinical management of tinnitus. Otolaryngol Head Neck Surg 92(4):448-453. Meikle M, Walsh ET. (1984) Characteristics of tinnitus and related observations in over 1800 tinnitus patients. J Laryngol Otol Suppl 9:17-21. Melcher JR, Knudson IM, Levine RA. (2013) Subcallosal brain structure: correlation with hearing threshold at supra-clinical frequencies (>8 kHz), but not with tinnitus. Hear Res 295:79-86 10.1016/j.heares.2009.04.016,

discrimination training in adult owl monkeys. J Neurosci 13(1): 87-103. Richards VM, Neff DL. (2004) Cuing effects for informational masking. J Acoust Soc Am 115(l):289-300. Roberts LE, Eggermont JJ, Caspary DM, Shore SE, Melcher JR, Kaltenbach JA. (2010) Ringing ears: the neuroscience of tinnitus. J Neurosci 30(45): 14972-14979. Roberts LE, Moffat G, Bosnyak DJ. (2006) Residual inhibition functions in relation to tinnitus spectra and auditory threshold shift. Acta Otolaryngol Suppl 126(556):27-33. Salamon E, Kim M, Beaulieu J, Stefano GB. (2003) Sound therapy induced relaxation: down regulating stress processes and pathologies. Med Sei Monit 9(5):RA96-RA101.

Moffat G, Adjout K, Gallego S, Thai-Van H, Collet L, Noreña AJ. (2009) Effects of hearing aid fitting on the perceptual characteristics of tinnitus. Hear Res 254(l-2):82-91.

Searchfield GD, Kobayashi K, Sanders M. (2012) An adaptation level theory of tinnitus audibility. Front Syst Neurosci 6:46.

Mühlau M, Rauschecker JP, Oestreicher E, et al. (2006) Structural brain changes in tinnitus. Cereb Cortex 16(9):1283-1288.

Seidman MD, Standring RT, Dornhoffer JL. (2010) Tinnitus: current understanding and contemporary management. Curr Opin Otolaryngol Head Neck Surg 18(5):363-368.

Newman CW, Jacobson GP, Spitzer JB. (1996) Development of the Tinnitus Handicap Inventory. Arch Otolaryngol Head Neck Surg 122(2): 143-148. Newman CW, Sandridge SA. (2012) A comparison of benefit and economic value between two sound therapy tinnitus management options. J Am Acad Audiol 23(2):126-138. Noreña AJ. (2011) An integrative model of tinnitus based on a central gain controlling neural sensitivity. Neurosci Biobehav Rev 35 (5): 1089-1109. Noreña AJ, Eggermont JJ. (2005) Enriched acoustic environment after noise trauma reduces hearing loss and prevents cortical map reorganization. J Neurosci 25(3):699—705. Noreña AJ, Gourévitch B, Aizawa N, Eggermont JJ. (2006) Spectrally enhanced acoustic environment disrupts frequency representation in cat auditory cortex. Nat Neurosci 9(7):932-939. Nouvian R, Eybalin M, Puel JL. (2012) The cochlea and the auditory nerve as a primary source of tinnitus. In: Eggermont JJ, Zeng FG, Popper AN, Fay RN, eds. Tinnitus. New York: Springer, 83-95.

Shekhawat G, Searchfield G, Stinear C. (2013) Role of hearing aids in tinnitus intervention: a scoping review. J Am Acad Audiol 24(8):747-762. Sindhusake D, Golding M, Wigney D, Newall P, Jakobsen K, Mitchell P. (2004) Factors predicting severity of tinnitus: a population-based assessment. J Am Acad Audiol 15(4):269-280. Singer W. (1999) Neuronal synchrony: a versatile code for the definition of relations? iVeurora 24(l):49-65, 111-125. Steelman VM. (1990) Intraoperative music therapy. Effects on anxiety, blood pressure. AOnATJ" 52(5): 1026-1034. Stephens D. (2000) A History of Tinnitus. In: Tyler R, ed. Tinnitus Handbook. San Diego: Singular Thomson Learning. Stracke H, Okamoto H, Pantev C. (2010) Customized notched music training reduces tinnitus loudness. Commun Integr Bid 3(3):274-277. Strom KE. (2012) Novel sound therapy: SoundCure harnesses research on brain science in fighting tinnitus. Hear Rev 19:52—54.

Okamoto H, Stracke H, Stoll W, Pantev C. (2010) Listening to tailor-made notched music reduces tinnitus loudness and tinnitusrelated auditory cortex activity. Proc Nati Acad Sei USA 107 (3):1207-1210.

Surr RK, Montgomery AA, Mueller HG. (1985) Effect of amplification on tinnitus among new hearing aid users. Ear Hear 6(2): 71-75.

Penner MJ, Bilger RC. (1995) Psychophysical observations and the origin of tinnitus. In: Vernon JA, M0ller AR, eds. Mechanisms of Tinnitus. Needham Heights, MA: Allyn and Bacon, 219-230.

Sweetow RW, Sabes JH. (2010) Effects of acoustical stimuli delivered through hearing aids on tinnitus. J Am Acad Audiol 21(7): 461-473.

Petkov CI, Sutter ML. (2011) Evolutionary conservation and neuronal mechanisms of auditory perceptual restoration. Hear Res 271(l-2):54-65.

Tass PA, Adamchic I, Freund H-J, von Stackelberg T, Hauptmann C. (2012) Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restor Neurol Neurosci 30(2):137-159.

Pineda JA, Moore FR, Viirre E. (2008) Tinnitus treatment with customized sounds. Int Tinnitus J 14(l):17-25. Piskosz M, Kulkarni S. (2010) An innovative combination device to assist in tinnitus management. Hear Rev 17:26-30. Reavis KM, Rothboltz VS, Tang Q, Carroll JA, Djalilian H, Zeng F-G. (2012) Temporary suppression of tinnitus hy modulated sounds. J Assoc Res Otolaryngol 13(4):561-571. Recanzone GH, Schreiner CE, Merzenich MM. (1993) Plasticity in the frequency representation of primary auditory cortex following

Távora-Vieira D, Eikelboom RH, Miller S. (2011) Neuromonics tinnitus treatment for patients with significant level of hearing loss: an adaptation of the protocol. Int J Audiol 50(12):881-886. Thompson RF, Donegan NH. (1987) Learning and memory. In: Adelman G, ed. Vol. 1 of Encyclopedia ofNeuroscience. Boston: Birkhauser, 571-574. Tyler RS. (2006) Neuropbysiological models, psychological models, and treatments for tinnitus. In: Tyler R, ed. Tinnitus Treatment. New York: Thieme Medical Publishers, 1-22.

Tinnitus Sound Therapy/Hoare et al Tyler RS, Babin RW, Neibuhr DP. (1983) Some observations on the masking anci post-masking effects of tinnitus. J Laryngol Otol Suppl 9:150-156.

Vernon JA. (1988) Current use of masking for the relief of tinnitus. In: Kitahara M, ed. Tinnitus. Pathophysiology and Management. Tokyo: Igaku-Shoin, 96-106.

Tyler RS, Noble W, Coelho CB, Ji H. (2012) Tinnitus retraining therapy: mixing point and total masking are equally effective. Ear Hear 33(5):588-594.

Vernon J, Meikle MB. (2000) Tinnitus masking. In: Tyler R, ed. Tinnitus Handbook. San Diego: Singular Publishing Group, 313-355.

Vanneste S, Plazier M, van der Loo E, Van de Heyning P, De Ridder D. (2010) The differences in brain activity between narrow band noise and pure tone tinnitus. PLoS One 5(10): el3618.

Wazen JJ, Daugherty J, Pinsky K, et al. (2011) Evaluation of a customized acoustical stimulus system in the treatment of chronic tinnitus. Otol Neurotol 32(4):710-716. Weisz N, Müller S, Schlee W, Dohrmann K, Hartmann T, Elbert T. (2007) The neural code of auditory phantom perception. J Neurosci 27(6): 1479-1484.

Vanneste S, van Dongen M, De Vree B, et al. (2013) Does enriched acoustic en'vironment in humans abolish chronic tinnitus clinically and electrophysiologically? A double blind placebo controlled study. Hear Res 296:141-148.

Welch D, Dawes PJ. (2008) Personality and perception of tinnitus. Ear Hear 29(5):684-692.

Vermeire K, Heyndrickx K, De Ridder D, Van de Heyning P. (2007) Phase-shift tinnitus treatment: an open prospective clinical trial. B-ENT 3(Suppl. 7):65-69.

Wilson PH, Henry J, Bowen M, Haralambous G. (1991) Tinnitus reaction questionnaire: psychometric properties of a measure of distress associated with tinnitus. J Speech Hear Res 34(l):197-201.

Vernon J. (1976) The use of masking for relief of tinnitus. In: Silverstein H, Norrell H, eds. Neurological Surgery of the Ear Vol. II. Birmingham: Aesculapius Publishing Co., 104-118.

Winkler P. (2009) Early patient experience with the TIPA tinnitus device. Proceedings of the 3"^ International TRI Tinnitus Conference. Stresa, Italy.

Vernon J. (1977) Attempts to relieve tinnitus. J Am Audiol Soc 2(4):124-131.

Yulis S, Brahm G, Chames G, Jacard LM, Picota E, Rutman F. (1975) The extinction of phobic behavior as a function of attention shifts. Behav Res Ther 13(2-3): 173-176.

Vernon JA. (1981) Some observations on residual inhibition. In: Paparella MM, Meyerhoff WL, eds. Sensorineural Hearing Loss, Vertigo and Tinnitus. Ear Clinics International Vol. 1. Baltimore: Williams and Wilkins, 138-144.

Zeng FG, Tang Q, Dimitrijevic A, Starr A, Larky J, Blevins NH. (2011) Tinnitus suppression by low-rate electric stimulation and its electrophysiological mechanisms. Hear Res 277(l-2):61-66.

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