Tinnitus and tinnitus disorder: Theoretical and operational definitions (an international multidisciplinary proposal).

As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder.

Sensorineural Tinnitus: Its Pathology and Probable Therapies.

Tinnitus is not a single disease but a group of different diseases with different pathologies and therefore different treatments. Regarding tinnitus as a single disease is hampering progress in understanding of the pathophysiology of tinnitus and perhaps, more importantly, it is a serious obstacle in development of effective treatments for tinnitus. Subjective tinnitus is a phantom sound that takes many different forms and has similarities with chronic neuropathic pain. The pathology may be in the cochlea, in the auditory nerve, or, most commonly, in the brain. Like chronic neuropathic pain tinnitus is not life threatening but influences many normal functions such as sleep and the ability to concentrate on work. Some forms of chronic tinnitus have two components, a (phantom) sound and a component that may best be described as suffering or distress. The pathology of these two components may be different and the treatment that is most effective may be different for these two components. The most common form of treatment of tinnitus is pharmacological agents and behavioral treatment combined with sound therapy. Less common treatments are hypnosis and acupuncture. Various forms of neuromodulation are becoming in use in an attempt to reverse maladaptive plastic changes in the brain.

Directing neural plasticity to understand and treat tinnitus.

The functional organization of cortical and subcortical networks can be altered by sensory experience. Sensory deprivation destabilizes neural networks resulting in increased excitability, greater neural synchronization and increased spontaneous firing in cortical and subcortical neurons. This pathological activity is thought to generate the phantom percept of chronic tinnitus. While sound masking, pharmacotherapy and cortical stimulation can temporarily suppress tinnitus for some patients, these interventions do not eliminate the pathological activity that is responsible for tinnitus. A treatment that could reverse the underlying pathology would be expected to be effective in alleviating the symptoms, if not curative. Targeted neural plasticity can provide the specificity required to restore normal neural activity in dysfunctional neural circuits that are assumed to underlie many forms of tinnitus. The forebrain cholinergic system and the noradrenergic system play a significant role in modulating cortical plasticity. Stimulation of the vagus nerve is known to activate these neuromodulatory pathways. Our earlier studies have demonstrated that pairing sounds with either nucleus basalis of Meynert (NB) stimulation or vagus nerve stimulation (VNS) generates highly specific and long-lasting plasticity in auditory cortex neurons. Repeatedly pairing tones with brief pulses of VNS reversed the physiological and behavioral correlates of tinnitus in noise exposed rats. We also recently demonstrated that VNS modulates synchrony and excitability in the auditory cortex at least in part by activation of muscarinic acetylcholine receptors, suggesting that acetylcholine is involved in the mechanism of action of VNS. These results suggest that pairing sounds with VNS provides a new avenue of treatment for some forms of tinnitus. This paper discusses neuromodulation as treatment for tinnitus with a focus on the potential value of pairing VNS with sound stimulation as a treatment of chronic tinnitus.

Techniques of intraoperative monitoring for spinal cord function: their past, present, and future directions.

PURPOSE: The authors discuss the use of intraoperative monitoring of spinal cord function as an essential part of operations in which the spinal cord is at risk. Although early documented cases of intraoperative monitoring were during operations to correct spinal deformities such as scoliosis, intraoperative monitoring has also increased safety during other operations, such as tumor resection and arteriovenous malformation ablation. METHODS: The authors highlight details involved in monitoring spinal cord function intraoperatively and discuss historical, current, and future perspectives on the use of these monitoring techniques as an essential part of operations in which the spinal cord is at risk. RESULTS: Intraoperative monitoring techniques mitigate the risk of post-operative deficits to the spinal cord by detecting injuries before they become permanent and while they can be reversed. CONCLUSIONS: Intraoperative spinal cord monitoring is safe, cost-effective, and valuable in reducing post-operative sensory and motor deficit. This technique should continue to be refined and its use consistently applied in any procedure where injury to the spinal cord is possible.

Hemilingual spasm: defining a new entity, its electrophysiological correlates and surgical treatment through microvascular decompression.

OBJECTIVE: We report on vascular compression syndrome of the 12th cranial nerve (hypoglossal), an occurrence not previously reported, and demonstrate, through corresponding objective electrophysiological evidence, that microvascular decompression of the hypoglossal nerve root can cure hemilingual spasm. CLINICAL PRESENTATION: A 52-year-old man had lower face muscle twitching and tongue spasms, which worsened with talking, chewing, or emotional stress. Carbamazepine offered only temporary relief, and relief from injections of botulinum toxin was insignificant. He was referred for surgical treatment. High-resolution magnetic resonance imaging of his posterior fossa contents revealed no obvious evidence of any compressive vessel along the facial nerve, but a compressive vessel along the hypoglossal nerve was apparent. INTERVENTION: The presence of preoperative tongue spasms encouraged interoperative monitoring of tongue motor responses. The facial nerve exit zone was explored, but microsurgical inspection of the seventh/eighth cranial nerve complex did not reveal any compressive vessel. However, at the anterolateral aspect of the medulla oblongata, the hypoglossal nerve was clearly compressed and distorted laterally by a large tortuous vertebral artery. When the artery was mobilized away from the nerve, the abnormal late electromyographic response to transcranial electrical stimulation disappeared; immediately after shredded Teflon was interpositioned between the artery and the nerve, the abnormal spontaneous tongue fasciculation also disappeared. The patient has remained spasm free 6 months after surgery. CONCLUSION: Hemilingual spasm may be caused by vascular contact/compression along cranial nerve XII at the lower brainstem and belong to the same family of cranial nerve hyperactivity disorders as hemifacial spasm.

Plasticity diseases.

OBJECTIVE: The aim of this paper is to review the effects of activation of neural plasticity and present hypotheses using a systems approach about how activation of neural plasticity can cause symptoms and signs of disease (plasticity diseases). METHODS: Literature review. RESULTS: It is hypothesized that a program that is initiated by internal or external events controls plastic changes in specific structures of the CNS. Not all structures that have abnormal activity are pathologic but some behave pathological because they receive abnormal input from pathologic structures. The changes in function may remain after the events that elicited the expression of neural plasticity no longer exist. CONCLUSION: Activation of neural plasticity can have beneficial effects and it can cause symptoms and signs of disease. Activation of neural plasticity can help to adapt to changing demands and it is necessary for normal childhood development of the central nervous system. Plastic changes can cause signs and symptoms of disease by abnormal neural activity in pathologic structures and in structures that receive input from pathologic structures. It is hypothesized that a program controls the plastic changes and that failure in activation of neural plasticity can cause developmental disorders such as autism.

Hemilingual spasm: pathophysiology.

In the present offering, the authors provide evidence for the role of the hypoglossal motonucleus in causing a cranial nerve hyperactivity syndrome, namely hemilingual spasm. During a microvascular decompression operation to treat hemilingual spasm, transcranial stimulation elicited a delayed electromyographic (EMG) response from the tongue. This late volley of EMG activity occurred with a latency of approximately 40 ms, lasted approximately 50 ms, and disappeared when the offending vessel was displaced away from the exit zone of the hypoglossal nerve root along medulla oblongata. This late tongue EMG response resembles those found in facial muscles of the patients with hemifacial spasm (HFS). In HFS, electrical stimulation of a branch of facial nerve may elicit an EMG response with a latency of approximately 10 ms in muscles innervated by another branch of the nerve, followed by a variable volley of EMG activity that may last 100 ms or longer. This abnormal response, known as the lateral spread response, is a characteristic sign for hemifacial spasm that disappears after the offending vessel is moved off the facial nerve root. The results of the present study indicate that the EMG signs of hemilingual spasm are similar to those of HFS and that the tongue spasms are most likely caused by hyperactivity of the hypoglossal motonucleus. Based on the authors' knowledge, the above detailed electrophysiological findings related to hemilingual spasm have not been previously reported in the literature.

Controversy: Does repetitive transcranial magnetic stimulation/ transcranial direct current stimulation show efficacy in treating tinnitus patients?

BACKGROUND: Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Functional imaging has demonstrated a relationship between the intensity of tinnitus and the degree of reorganization in the auditory cortex. Experimental studies have further shown that tinnitus is associated with synchronized hyperactivity in the auditory cortex. Therefore, targeted modulation of auditory cortex has been proposed as a new therapeutic approach for chronic tinnitus. METHODS: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive methods that can modulate cortical activity. These techniques have been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been successful in reducing the intensity of tinnitus during the time of stimulation and could be predictive for treatment outcome of chronic epidural stimulation using implanted electrodes. RESULTS: Another approach that uses rTMS as a treatment for tinnitus is application of low-frequency rTMS in repeated sessions, to induce a lasting change of neuronal activity in the auditory cortex beyond the duration of stimulation. Beneficial effects of this treatment have been consistently demonstrated in several small controlled studies. However, results are characterized by high interindividual variability and only a moderate decrease of the tinnitus. The role of patient-related (for example, hearing loss, tinnitus duration, age) and stimulation-related (for example, stimulation site, stimulation protocols) factors still remains to be elucidated. CONCLUSIONS: Even in this early stage of investigation, there is a convincing body of evidence that rTMS represents a promising tool for pathophysiological assessment and therapeutic management of tinnitus. Further development of this technique will depend on a more detailed understanding of the neurobiological effects mediating the benefit of TMS on tinnitus perception. Moreover clinical studies with larger sample sizes and longer follow-up periods are needed.

Tinnitus: presence and future.

Tinnitus has many forms; it can be caused by sounds generated in the body (objective tinnitus) that reaches the ear through conduction in body tissue, but much more common is the tinnitus that occurs without any physical sound reaching the ear. Such tinnitus (subjective tinnitus) is a phantom sensation, where abnormal neural activity is generated in the ear, the auditory nerve, or the central nervous system. There are many forms of subjective tinnitus and it can occur with different severity. Subjective tinnitus often occurs in connection with hearing loss such as may occur after exposure to loud sounds (noise), or after administration of drugs such as certain antibiotics, but often no cause can be found. Tinnitus often occurs together with presbycusis and it can occur in deafness. Tinnitus is a part of the symptoms of Ménière's disease and individuals with vestibular Schwannoma almost always have tinnitus. Some individuals who have severe tinnitus hear sounds as distorted and some have hyperacusis (reduced tolerance to sounds) or phonophobia (fear of sounds). Tinnitus can be referred to one ear, or both ears, or to a location inside the head. The anatomical location of the physiological abnormality of chronic subjective tinnitus, however, is rarely in the ear but more often in the auditory nervous system. There are indications that the pathophysiology of unilateral and bilateral tinnitus is different. There is considerable evidence that expression of neural plasticity plays a central role in the development of the abnormalities that cause many forms of chronic subjective tinnitus. Expression of neural plasticity can change the balance between excitation and inhibition in the nervous system, promote hyperactivity, and it can cause reorganization of specific parts of the nervous system or redirection of information to parts of the nervous system not normally involved in processing of sounds (non-classical or extralemniscal pathways). Since there are many kinds of subjective tinnitus, search for a (single) cure for tinnitus is futile. Testing of new treatments is hampered by the fact that it is not possible to distinguish between different forms of tinnitus for which different treatments may be effective.

The role of neural plasticity in tinnitus.

There is considerable evidence that expression of neural plasticity plays a central role in the development of the abnormalities that cause many forms of tinnitus. Expression of neural plasticity can change the balance between excitation and inhibition, promote hyperactivity, and cause re-organization of specific parts of the nervous system or redirection of information to parts of the nervous system not normally involved in processing of sounds (such as the non-classical, or extralemniscal pathways). The strongest promoter of expression of neural plasticity is deprivation of input, which explains why tinnitus often occurs together with hearing loss or injury to the auditory nerve.

Microvascular decompression operations.

Moving a blood vessel off the intracranial portion of the auditory nerve can successfully cure some individuals with specific forms of subjective tinnitus. This operation, known as microvascular decompression (MVD) is in general use to treat other hyperactive disorders such as hemifacial spasm (HFS) and trigeminal neuralgia (TGN) where the operation has a success rate of approximately 85%. MVD for tinnitus has lower success rate. MVD operations have also been used to treat some forms of vestibular disorders, disabling positional vertigo (DPV). In a study of treatment of a selected group of 72 patients with severe tinnitus and signs of change in the conduction properties of the auditory nerve 13 (18.2%) had total relief from tinnitus after MVD, 16 (22.2%) had marked improvement, 8 slight improvement and 33 (45.8%) no improvement. Two patients became worse (2.8%). There were 40 men and 32 women in the study group and there was considerable difference in the success rate for men and women. Fifty-five percent of the women and 29% of men showed relief or improvement. The success of the operation depended on the length of time the participants in the study had had their tinnitus and it was best for those who had had tinnitus for less than 3 years. The success rate for bilateral tinnitus was much lower than for unilateral tinnitus.

Neural plasticity in tinnitus.

Two distinctly different kinds of tinnitus occur: objective and subjective tinnitus. Objective tinnitus is caused by sounds generated in the body while subjective tinnitus is caused by abnormal neural activity that is not evoked by sound. This chapter discusses subjective tinnitus. Subjective tinnitus has many forms. In most forms of tinnitus the anatomical location of the physiological abnormality is in the central nervous system, although the sensation is often referred to one ear or both ears. The cause of most forms of subjective tinnitus is the changes that have occurred as a result of expression of neural plasticity, thus a form of reprogramming of the brain that is not to the benefit of the individual person. Tinnitus often occurs together with hearing loss, indicating that the expression of neural plasticity has been evoked by deprivation of input. Tinnitus is often accompanied by hyperacusis, and sometimes phonophobia and depression, indicating altered processing of auditory information or rerouting of information. Several studies have brought evidence that some forms of tinnitus are associated with an abnormal involvement of the nonclassical (extralemniscal, diffuse, or polysensory) auditory pathways that bypass the primary auditory cerebral cortex and provide subcortical connections to limbic structures among others. There is no general treatment for tinnitus, but there are several treatments that can alleviate or reduce the tinnitus in some patients.

History of cochlear implants and auditory brainstem implants.

Cochlear implants have evolved during the past 30 years from the single-electrode device introduced by Dr. William House, to the multi-electrode devices with complex digital signal processing that are in use now. This paper describes the history of the development of cochlear implants and auditory brainstem implants (ABIs). The designs of modern cochlear and auditory brainstem implants are described, and the different strategies of signal processing that are in use in these devices are discussed. The primary purpose of cochlear implants was to provide sound awareness in deaf individuals. Modern cochlear implants provide much more, including good speech comprehension, and even allow conversing on the telephone. ABIs that stimulate the cochlear nucleus were originally used only in patients with neurofibromatosis type 2 who had lost hearing due to removal of bilateral vestibular schwannoma. In such patients, ABIs provided sound awareness and some discrimination of speech. Recently, similar degrees of speech discrimination as achieved with cochlear implants have been obtained when ABIs were used in patients who had lost function of their auditory nerve on both sides for other reasons such as trauma and atresia of the internal auditory meatus.

Physiological basis for cochlear and auditory brainstem implants.

Cochlear implants bypass functions of the cochlea that have been regarded to be fundamental for discrimination of the frequency (or spectrum). Frequency discrimination is essential for discrimination of sounds, including speech sounds, and the normal auditory system is assumed to make use of both (power) spectral and temporal information for frequency discrimination. Spectral information is represented by the place on the basilar membrane that generates the largest amplitude of vibration on the basilar membrane. Evidence has been presented that the temporal representation of frequency is more robust than the place representation and thus regarded more important for speech discrimination. The fact that some cochlear implants provide good speech discrimination using only information about the energy in a few spectral bands seems to contradict these studies. In that way, frequency discrimination may be similar to trichromatic color vision, which is based on the energy in only three different spectral bands of light, accomplished by different color-sensitive pigments in the cones of the retina. Cochlear nucleus implants (ABIs) also bypass the auditory nerve, which does not perform any processing. Therefore, it may be expected that ABIs are equally efficient as cochlear implants. However, experience from the use of ABIs in patients with bilateral vestibular schwannoma has not been encouraging, but recent studies of the use of ABIs in patients with other causes of injuries to the auditory nerve have shown similar speech discrimination as achieved with modern cochlear implants. Cochlear implants and ABIs are successful in providing speech discrimination because of redundancy in the processing in the ear, redundancy of the speech signal and because the auditory nervous system has a high degree of plasticity. Expression of neural plasticity makes the auditory nervous system adapt to the change in demands of processing of the information provided by cochlear implants.

Primary and secondary auditory cortex stimulation for intractable tinnitus.

INTRODUCTION: Recent research suggests tinnitus is a phantom phenomenon based on hyperactivity of the auditory system, which can be visualized by functional neuroimaging, and transiently modulated by transcranial magnetic stimulation (TMS). We present the results of the first implanted electrodes on the primary and secondary auditory cortex after a successful TMS suppression. METHODS AND MATERIALS: Twelve patients underwent an auditory cortex implantation, 10 for unilateral and 2 for bilateral tinnitus, based on >50% suppression applying TMS. Results were analyzed for pure tone tinnitus and white noise tinnitus. RESULTS: TMS results in 77% pure tone tinnitus and 67% white noise reduction. Electrical stimulation via an implanted electrode results in a mean of 97% pure tone tinnitus and 24% white noise suppression. Mean Visual Analogue Scale score decreases from 9.5 to 1.5 for pure tone and from 8.8 to 6.8 for white noise postoperatively. DISCUSSION: Pure tone tinnitus might be the conscious percept of focal neuronal hyperactivity of the auditory cortex. Once visualized, this hyperactivity can be modulated by neurostimulation. CONCLUSION: The preliminary results of the first implantations suggest that patients with unilateral pure tone tinnitus are good surgical candidates for electrode implantation and permanent electrical stimulation of the auditory cortex, provided that the tinnitus is of recent origin and can be suppressed by TMS.

Are the non-classical auditory pathways involved in autism and PDD?

OBJECTIVE: To test the hypothesis that some of the abnormal sensory perceptions that characterize autism may be explained by an abnormal activation of non-classical (extra-lemniscal) sensory pathways. METHODS: Twenty-one individuals, 18--45 years of age who were diagnosed with autism participated in the study. Sounds (clicks presented at a rate of 40 per second and 65 dB above the normal threshold) were applied through earphones. Electrical stimulation (100 microS rectangular impulses at a rate of 4 per second) was applied through electrodes placed on the skin over the median nerve at the wrist. The participants were asked to match the loudness of the sound with and without the electrical stimulation applied to the median nerve. RESULTS: Electrical stimulation of the median nerve at the wrist in individuals with autism could change the perception of loudness of sounds presented to one ear through an earphone showing a statistically significant abnormal sensory cross-modal interaction. DISCUSSION: We interpreted our results to support the hypothesis that some individuals with autism have an abnormal cross-modal interaction between the auditory and the somatosensory systems. Cross-modal interaction between senses such as hearing and the somatosensory system does not occur normally in adults. As only the non-classical (extralemniscal) ascending auditory pathways receive somatosensory input, the presence of cross-modal interaction in autistic individuals is a sign that autism is associated with abnormal involvement of the non-classical auditory pathways, implying that sensory information is processed by different populations of neurons than in non-autistic individuals.

Functional anatomy of the human cochlear nerve and its role in microvascular decompressions for tinnitus.

OBJECTIVE: The functional anatomy (i.e., tonotopy) of the human cochlear nerve is unknown. A better understanding of the tonotopy of the central nervous system segment of the cochlear nerve and of the pathophysiology of tinnitus might help to ameliorate the disappointing results obtained with microvascular decompressions in patients with tinnitus. METHODS: We assume that vascular compression of the cochlear nerve can induce a frequency-specific form of hearing loss and that when the nerve is successfully decompressed, this hearing loss can recuperate. Thirty-one patients underwent a microvascular decompression of the vestibulocochlear nerve for vertigo or tinnitus. Preoperative audiograms were subtracted from postoperative audiograms, regardless of the surgical result with regard to the tinnitus and vertigo, because the hearing improvement could be the only sign of the vascular compression. The frequency of maximal improvement was then correlated to the site of vascular compression. A tonotopy of the cochlear nerve was thus obtained. RESULTS: A total of 18 correlations can be made between the site of compression and postoperative maximal hearing improvement frequency when 5-dB hearing improvement is used as threshold, 13 when 10-dB improvement is used as threshold. A clear distribution can be seen, with clustering of low frequencies at the posterior and inferior side of the cochlear nerve, close to the brainstem, and close to the root exit zone of the facial nerve. High frequencies are distributed closer to the internal acoustic meatus and more superiorly along the posterior aspect of the cochlear nerve. CONCLUSION: The tonotopic organization of the cisternal segment of the cochlear nerve has an oblique rotatory structure as a result of the rotatory course of the cochlear nerve in the posterior fossa. Knowledge of this tonotopic organization of the auditory nerve in its cisternal course might benefit surgeons who perform microvascular decompression operations for the vestibulocochlear compression syndrome, especially in the treatment of unilateral severe tinnitus.

Pathophysiology of tinnitus.

Tinnitus is not a single entity but a rather diverse group of disorders. Despite symptoms that indicate the ear is the site of the pathology, there is strong evidence that most forms of severe tinnitus are caused by functional changes in the central nervous system. The changes are induced through expression of neural plasticity, some of which may have been caused initially by abnormalities in the ear or the auditory nerve. The involvement of the nonclassical ascending auditory pathway with its subcortical connections to limbic structures (the amygdala) may explain some of the symptoms of some forms of tinnitus including hyperacusis and affective disorders, such as phonophobia and depression, which often accompany severe tinnitus.