Acute high-intensity sound exposure alters responses of place cells in hippocampus.

Overstimulation is known to activate neural plasticity in the auditory nervous system causing changes in function and re-organization. It has been shown earlier that overstimulation using high-intensity noise or tones can induce signs of tinnitus. Here we show in studies in rats that overstimulation causes changes in the way place cells of the hippocampus respond as rats search for rewards in a spatial maze. In familiar environments, a subset of hippocampal pyramidal neurons, known as place cells, respond when the animal moves through specific locations but are relatively silent in others. This place-field activity (i.e. location-specific firing) is stable in a fixed environment. The present study shows that activation of neural plasticity through overstimulation by sound can alter the response of these place cells. Rats implanted with chronic drivable dorsal hippocampal tetrodes (four microelectrodes) were assessed for stable single-unit place-field responses that were extracted from multiunit responses using NeuroExplorer computer spike-sorting software. Rats then underwent either 30 min exposure to a 4 kHz tone at 104 dB SPL or a control period in the same sound chamber. The place-field activity was significantly altered after sound exposure showing that plastic changes induced by overstimulation are not limited to the auditory nervous system but extend to other parts of the CNS, in this case to the hippocampus, a brain region often studied in the context of plasticity.

Tinnitus and pain.

Tinnitus has many similarities with the symptoms of neurological disorders such as paresthesia and central neuropathic pain. There is considerable evidence that the symptoms and signs of some forms of tinnitus and central neuropathic pain are caused by functional changes in specific parts of the central nervous system and that these changes are caused by expression of neural plasticity. The changes in the auditory nervous system that cause tinnitus and the changes in the somatosensory systems that cause central neuropathic pain may have been initiated from the periphery, i.e. the ear or the auditory nerve for tinnitus and receptors and peripheral nerves in the body for pain. In the chronic condition of tinnitus and pain, abnormalities in the periphery may no longer play a role in the pathology, but the tinnitus is still referred to the ear and central neuropathic pain is still referred to the location on the body of the original pathology. In this chapter we will discuss specific similarities between tinnitus and pain, and compare tinnitus with other phantom disorders. Since much more is known about pain than about tinnitus, it is valuable to take advantage of the knowledge about pain in efforts to understand the pathophysiology of tinnitus and find treatments for tinnitus.

Symptoms and signs caused by neural plasticity.

Plastic changes in the central nervous system are associated with hyperactivity, hypersensitivity, and spread of activity including activation of brain regions that are not typically involved. Symptoms and signs such as neuropathic pain and tinnitus and hyperactive disorders such as muscle spasm and synkinesis may result from such changes in function. Plastic changes that cause symptoms of diseases can be initiated by novel stimulations, overstimulation, or deprivation of input and the induced changes in the function of central nervous system structures may persist and aggravate after these events have ceased if the condition is not reversed. Disorders that are caused by neural plasticity are potentially reversible with treatment. However, the absence of morphologic abnormalities makes diagnosis of these conditions difficult and their treatment has been hampered by lack of understanding of their pathophysiology. Here the role of neural plasticity in the pathophysiology of several disorders is reviewed.

Neurophysiologic basis for cochlear and auditory brainstem implants.

The physiologic basis for cochlear and brainstem implants is discussed. It is concluded that the success of cochlear implants may be explained by assuming that the auditory system can adequately discriminate complex sounds, such as speech sounds, on the basis of their temporal structure when that is encoded in a few separate frequency bands to offer moderate separation of spectral components. The most important roles of the cochlea seems to be to prepare complex sounds for temporal analysis and to create separate channels through which information in different frequency bands is transmitted separately to higher nervous centers for decoding of temporal information. It is then pertinent to ask how many channels are needed. Because speech discrimination is very important, it is probably sufficient to use enough channels to separate formants from each other.

Similarities between severe tinnitus and chronic pain.

The symptoms and signs of severe tinnitus and chronic pain have many similarities and similar hypotheses have been presented regarding how the symptoms are generated. Pain and tinnitus have many different forms. The severity of the symptoms of both varies within wide limits, and it is not likely that all forms have the same pathology. Some individuals with severe tinnitus perceive sounds to be unpleasant or painful. This may be similar to what is known as allodynia, which is a painful sensation of normally innocuous stimulation of the skin. Many individuals with chronic pain experience a worsening of their pain from repeated stimulation (the "wind-up" phenomenon). This is similar to the increasingly unpleasant feeling from sounds that are repeated that many individuals with severe tinnitus experience. There are also similarities in the hypotheses about the generation of pain and tinnitus. Although less severe tinnitus may be generated in the ear, it is believed that severe tinnitus in many cases is caused by changes in the nervous system that occur as a result of neural plasticity. Acute pain caused by tissue injury is generated at the site of injury but chronic pain is often generated in the central nervous system, yet another similarity between chronic pain and severe tinnitus. The changes in the nervous system consist of altered synaptic efficacy including opening of dormant synapses. For pain, this is believed to occur in the wide dynamic range neurons of the spinal cord and brain stem. Less is known about the anatomic location of the changes that cause severe tinnitus but there are indications that it may be the inferior colliculus. It is also possible that other auditory systems than the classical ascending pathways may be involved in severe tinnitus.

Vascular compression of cranial nerves: II: pathophysiology.

The pathophysiology of trigeminal neuralgia, hemifacial spasm and other disorders that can be cured by microvascular decompression of cranial nerves, is reviewed and different hypotheses about its pathophysiology are discussed. It is found that the pathophysiology of these disorders is complex and other factors than vascular compression are necessary to cause symptoms. While the efficacy of the microvascular decompression (MVD) operation is indisputable, it is questionable if the symptoms and signs of these disorders are caused by abnormal neural activity in the respective cranial nerves that result from the compression from a blood vessel. Instead, studies point to hyperactivity and hyperexcitability of the respective nuclei as a cause of the symptoms and signs of these disorders. Results of several studies indicate that irritation of the cranial nerve in question from close contact with a blood vessel may promote such development, and it seems necessary that other factors in addition to the vascular contact must be present in order that such a condition develops.

Review of the roles of temporal and place coding of frequency in speech discrimination.

Numerous studies have demonstrated that the frequency spectrum of sounds is represented in the neural code of single auditory nerve fibres both spatially and temporally, but few experiments have been designed to test which of these two representations of frequency is used in the discrimination of complex sounds such as speech and music. This paper reviews the roles of place and temporal coding of frequency in the nervous system as a basis for frequency discrimination of complex sounds such as those in speech. Animal studies based on frequency analysis in the cochlea have shown that the place code changes systematically as a function of sound intensity and therefore lacks the robustness required to explain pitch perception (in humans), which is nearly independent of sound intensity. Further indication that the place principle plays a minor role in discrimination of speech comes from observations that signs of impairment of the spectral analysis in the cochlea in some individuals are not associated with impairments in speech discrimination. The importance of temporal coding is supported by the observation that injuries to the auditory nerve, assumed to impair temporal coherence of the discharges of auditory nerve fibres, are associated with grave impairments in speech discrimination. These observations indicate that temporal coding of sounds is more important for discrimination of speech than place coding. The implications of these findings for the design of prostheses such as cochlear implants are discussed.

Vascular compression of cranial nerves. I. History of the microvascular decompression operation.

The development of the microvascular decompression (MVD) operation is reviewed. It is stressed that a few innovative neurosurgeons discovered the role of vascular compression of cranial nerves V and VII in trigeminal neuralgia (TGN) and hemifacial spasm (HFS) and developed an operation, later to be known as the MVD operation. While the understanding of the pathophysiology of these disorders has improved, the surgical procedure has undergone little change since Gardner described the operation about 1960.

Correlation between latency and amplitude of peak V in the brainstem auditory evoked potentials: intraoperative recordings in microvascular decompression operations.

Intraoperative prolongation of the latency and decrement of the amplitude of peak V of brainstem auditory evoked potentials (BAEP) were studied in 38 microvascular decompression operations in which prolongation of the latency of peak V exceeded 1.0 msec. Postoperative hearing tests of all patients were compared with their preoperative hearing tests. Postoperative hearing loss was unrelated to the maximum prolongation of latency, but the amplitude decreased to lower values in patients with postoperative hearing loss compared to patients whose postoperative hearing was unchanged (P < 0.05). Twelve (32%) of 38 patients whose latency of peak V was prolonged more than 1.0 msec and 11 (61%) of 18 patients whose amplitude of peak V decreased more than 40% during the operations had decreased hearing postoperatively. In all patients, a prolongation of the latency of peak V was always accompanied by a decrease in the amplitude of peak V. The decrement of the amplitude was greater in the patients with decreased postoperative hearing thresholds than in the patients with unchanged postoperative hearing thresholds. The results of this study indicate that it would be valuable to monitor changes in the amplitude of peak V of BAEP in addition to monitoring the latency of peak V during operations where the VIIIth cranial nerve is manipulated.

Nerve wrapping with vein grafts in a rat model: a safe technique for the treatment of recurrent chronic compressive neuropathy.

The surgical outcome in recurrent chronic nerve compression remains unsatisfactory. Clinically, it has been reported that vein grafts can be used to wrap the nerve, following nerve decompression, to improve the functional recovery of the nerve. In order to determine the safety and feasibility of the technique of vein wrapping of nerve, this study assessed the effect of vein-graft wrapping around normal nerve. In each of 30 rats, a segment of femoral vein was wrapped around the sciatic nerve. Functional, electrophysiologic, and histologic testing was performed at 9, 12 and 15 weeks postoperatively, and the results showed no significant differences between the experimental and control groups. Neither scar tissue between the nerve and the vein graft, nor demyelinization or degeneration of the nerve fibers were identified histologically. The study demonstrated that autogenous vein-graft wrapping did not result in any pathologic nerve entrapment. The technique of vein wrapping of nerve appears to be safe, feasible, and reliable. The results supported further study for the use of vein-graft wrapping in the surgical management of recurrent chronic nerve compression.

Microvascular decompression of the cochlear nerve in patients with severe tinnitus. Preoperative findings and operative outcome in 22 patients.

We evaluated the operative outcome in 22 consecutive patients who underwent microvascular decompression (MVD) of the intracranial portion of the cochlear nerve to relieve incapacitating tinnitus and related it to preoperative findings. The patients were selected for operation from the following criteria: severe tinnitus with sensorineural hearing loss and/or changes in brainstem auditory evoked potentials (BAEPs). Fifty percent had unilateral tinnitus. Before operation, 17 patients (77%) had sensorineural hearing loss in their affected ear. BAEPs were abnormal in 21 patients (95%) and acoustic middle ear reflex response was abnormal in six patients (27%). Vascular compression of the cochlear nerve was found in all patients during the operation. After the operation, 33% had relief of their tinnitus (two patients were totally free of tinnitus and five were markedly improved). Eight patients were slightly improved (38%), and the tinnitus did not change in four patients; two patients (10%) became worse. Of the patients with unilateral tinnitus, 63% had relief of their tinnitus. In one patient hearing was noticeably improved after the operation. Five patients (23%) had mild to moderate sensorineural hearing loss due to the operation. No other complications were detected.

Delayed hearing loss after microvascular decompression of the trigeminal nerve.

OBJECTIVE: The development of sudden postoperative hearing loss as a complication of microvascular decompression (MVD) operations in the cerebellopontine angle has already been reported. A sudden hearing loss of vascular origin may also occur hours or days after such operations, but even in such cases an improvement of hearing over the following weeks is possible. Here we report on a gradual deterioration of hearing over a period of two weeks after MVD which has not been described in the literature up to now. CLINICAL PRESENTATION: A MVD operation was performed twice on a 36 year old patient with trigeminal neuralgia. After the second operation the patient developed a slight hearing impairment 3 days postoperatively which increased over a period of two weeks and ended up with total deafness. The course of intra-operative brainstem auditory evoked potentials and postoperative audiograms is documented. CONCLUSION: Because of gradual development of the delayed hearing loss, we conclude that postoperative tissue scarring may be the underlying pathology.

Temporal integration of pain from electrical stimulation of the skin.

The threshold of sensation and the threshold of pain in response to electrical stimulation (impulses of 1 msec duration) of the skin on the forearm or hand in individuals without pain were compared with the thresholds of individuals with chronic pain in the range 1 to 100 pulses per second repetition rate. The threshold of sensation in patients without pain was little affected by the repetition rate of the stimulation within the range studied, and the threshold for pain decreased exponentially with increasing repetition rate. In individuals with chronic pain the threshold of sensation was similar to that of individuals without pain over the entire range of stimulus repetition rates studied, but the threshold of pain in patients with pain was lower and less affected by the stimulus rate than it was in the individuals without pain, thus closer to the threshold of sensation.

Similarities between chronic pain and tinnitus.

OBJECTIVE: The aim of this study is to review hypotheses about the mechanisms of chronic pain and to compare them with that of tinnitus. Hypotheses about the pathophysiology of severe tinnitus and chronic pain have been of mainly two kinds: one of which claims that pathology located in the periphery (the ear for tinnitus, and peripheral nerves for pain) can explain the symptoms, while the other claims that the symptoms are caused by changes in the function of nuclei of the central nervous system. DATA SOURCES: A search of the literature from the past 35 years was used. CONCLUSIONS: There is considerable evidence that both chronic pain and some forms of tinnitus are caused by changes in the central nervous system and that the anatomic location of the physiologic abnormality causing the symptoms of chronic pain and some forms of tinnitus is not the same location to which the symptoms are referred, i.e., the ear for tinnitus and the location of injury for pain. Such changes in the central nervous system may have been induced by peripheral processes such as tissue damage, but the changes can persist a long time after complete healing of a peripheral lesion. Different forms of tinnitus may respond to different treatments as is the case for chronic pain. If the different forms of tinnitus cannot be separated, then the results of studies of the efficacy of different kinds of drugs may be misleading.

Contralateral evoked brainstem auditory potentials as an indicator of intraoperative brainstem manipulation in cerebellopontine angle tumors.

Brainstem auditory evoked potentials (BAEP) were studied during operations to remove acoustic tumors using the retromastoid approach. BAEP were elicited from the side contralateral to the tumor, and changes in the latencies of peaks III and V of the BAEP were compared with changes in cardiovascular parameters throughout the operation. When the changes in the determined cardiovascular parameters were related to surgical manipulations, the related changes in the latencies of peaks III and V of the BAEP were more consistent than the changes in the cardiovascular parameters and they tended to occur earlier than the changes noted in the cardiovascular parameters.

Effects of (-)-baclofen, clonazepam, and diazepam on tone exposure-induced hyperexcitability of the inferior colliculus in the rat: possible therapeutic implications for pharmacological management of tinnitus and hyperacusis.

Recent investigations in the authors' laboratory have shown that acute tone exposure (4 kHz continuous tone, 104 dB sound pressure level (SPL), 30-min duration) induces increases in the amplitude of click-evoked potentials in the inferior colliculus (IC). These increases have been attributed to a decrease in GABAA-mediated inhibition on IC neurons. In the present study, we examined the effects of three compounds (diazepam, clonazepam, and (-)-baclofen) that are known to enhance GABAergic inhibition on these tone exposure-induced increases and on changes in temporal integration in the IC. (-)-Baclofen was the only one of the three compounds tested that reversed in a dose-dependent manner the effects of tone exposure on both the amplitude of the click-evoked potentials recorded from the IC and on measures of the changes in temporal integration based on these potentials. Diazepam and clonazepam exhibited remarkably different effects on the click-evoked potentials recorded from the surface of the IC. Diazepam caused a dose-dependent decrease in one of the components of the IC potentials that reflects postsynaptic activity in the IC, whereas clonazepam caused a dose-dependent decrease in a peak that reflects input to the IC from the superior olivary complex (SOC). At dosages up to 40 mg/kg, neither diazepam nor clonazepam reversed the changes in temporal integration in the IC that were induced by the tone exposure; diazepam caused a small, but statistically significant, enhancement of the effects of tone exposure on this function. The results of this study show that (-)-baclofen is a potent modulator of both the excitability of neurons in the ascending auditory pathway and the processing of auditory information by IC neurons. The finding of the present study that two benzodiazepines (clonazepam and diazepam) have remarkably different effects on evoked potentials, which reflects both input to the IC and postsynaptic events in the IC neurons, suggests heterogenicity of the GABAA receptor from one structure to another in the ascending auditory pathway. We suggest that (-)-baclofen may be clinically useful in treating disorders of the auditory system that are caused by plasticity in the ascending auditory pathway.