Phantom Sounds Research Articles

Central auditory processing: integration with other systems. Proceedings of a meeting, May 2002 in Ascona, Switzerland.

The present volume of Experimental Brain Research covers a substantial part of the scientific content of a scientific meeting that took place in May 2002 at the Conference Center of the Stefano Franscini Foundation at Monte Verita (Ascona), Switzerland. The aim of the invited editors and organizers of the meeting (S.E. Shore, S. Clarke and E.M. Rouiller) was to survey the current knowledge concerning processing of acoustic information in the central auditory system with emphasis on various aspects of integration of auditory and non-auditory information. Most scientific contributions thus focused on interactions between discrete auditory structures, or anatomical and functional connections with other sensory systems or with the motor system. Along the same line, the meeting addressed issues related to the role of auditory processing in animal or human behavioral models. Some contributors discussed the mechanisms by which central auditory processing is altered as a result of peripheral hearing impairment, resulting in the perception of phantom sounds, or tinnitus. This disease is a good example of pathological changes affecting several stations of the central auditory system as well as its interactions with other sensory modalities. A substantial integration of information is already apparent at the first relay structure of the auditory pathway, the cochlear nucleus. Several authors presented recent experimental or review data on the functions of distinct neuronal populations in the cochlear nucleus, and how they are altered by connections from other brainstem locations (Verhey et al., Palmer et al., Shore et al., Loquet et al., Manis et al., Babalian et al.). A relatively new concept is that a structure as peripheral as the cochlear nucleus can be directly influenced by the auditory cortex, via the corticobulbar projection, an issue addressed in the present volume in two papers (Doucet al., Jacomme et al.). The corticobulbar projection terminates principally in the so-called “granular cell domain”, a zone of the cochlear nucleus specialized for the integration of multiple auditory and non-auditory inputs, as reviewed by Ryugo et al. Finally, the cochlear nucleus is under control of diffuse systems of modulation, such as noradrenergic inputs, whose origin has been described here (Thompson). A prominent feature of the auditory system is the feedback control exerted by central auditory nuclei on more peripheral structures. For instance, the sensory cells (hair cells) of the acoustic receptor organ are influenced by efferent projections coming from the superior olivary complex, corresponding to the so-called olivocochlear system (see Brown et al., Warr and Boche) or from other sources (Kim et al.). Another important feedback system is the corticofugal projection directed to the inferior colliculus and the auditory thalamus, described here by Bledsoe et al. and He, respectively. The influence of identified inputs, state of vigilance, or learning, on responses of single neurons in the auditory midbrain and thalamus were detailed in several contributions (Malmierca et al., Hu, Lui and Mendelson, Edeline, Massaux and Edeline). Mechanisms underlying auditory perception in human subjects were addressed here in a context of age dependence (Grube et al.) or of the specialized and segregated acoustico-motor pathways involved respectively in the localization or in the recognition of sounds (Adriani et al.). More basic mechanisms of acoustico-motor integration were reported in the present volume from investigations conducted in the auditory and motor cortices of behaving subhuman primates (Durif et al., Keysers et al.). Still at a cortical level, and pertinent for polymodal interactions, the consequences of congenital deafness on reorganization (developmental plasticity) were examined in an animal S. E. Shore Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI 48109, USA

Effects of trigeminal ganglion stimulation on unit activity of ventral cochlear nucleus neurons

The trigeminal ganglion sends a projection to the granule and magnocellular regions of the ventral cochlear nucleus (VCN; [J Comp Neurol 419 (2000) 271]), as well as to the cochlea ([Neuroscience 79 (1997) 605; Neuroscience 84 (1998a) 559]). We investigated the effects of electrically stimulating the trigeminal ganglion on unit responses in the guinea-pig VCN. Responses consisted of one, two or more phases of excitation, sometimes followed by a longer inhibitory phase. The latencies to the first excitation peak ranged between 5 and 17 ms from the onset of stimulation. These responses were preceded by a slow wave potential evoked by the stimulation. Applying kainic acid, which eliminates VIIIth nerve responses, diminished the firing rates of VCN units to trigeminal stimulation, and increased their first spike latencies. Cochlear destruction had a similar effect. The responses in VCN evoked by trigeminal ganglion stimulation therefore appear to result from direct stimulation of the trigeminal ganglion—cochlear nucleus pathway, as well as modulation by the trigeminal ganglion—cochlear pathway. Alternatively, a reduction in spontaneous rate of VCN neurons by removal of VIIIth nerve input could explain the decreased response to trigeminal stimulation after cochlear manipulations. The modulation of firing rate in second order auditory neurons by first order somatosensory neurons could influence central auditory targets and may be involved in generating or modulating perceptions of phantom sounds which can be modified by manipulations of somatic regions of the head and neck (“somatic tinnitus”).

A behavioral paradigm to judge acute sodium salicylate-induced sound experience in rats: a new approach for an animal model on tinnitus

Behavioral conditioning studies on rats have been proven to be a valid animal model for the evaluation of acute and chronic phantom auditory experience (tinnitus). We developed an animal model for short-term, acute induced phantom auditory sensations in rats. Rats were trained in a conditioning chamber to actively access a liquid feeder whenever a constant white noise sound was present. During silence, no reward was given. Fulfilling the demands of animal protection laws for maximal avoidance of pain and fear, punitive paradigms were maximally reduced. After 15–17 learning sessions, all animals performed more accesses to the reward feeder during periods of sound than during periods of silence. Tinnitus was induced by the administration of sodium salicylate (350 mg/kg body weight) given 3 h before testing. The feeder access activity of a rat treated with salicylate was significantly increased during periods of silence, indicating a phantom auditory experience. The presumptive auditory experience was estimated to be comparable to a white noise sound of about 30 dB SPL rms. The activity increase was less pronounced for lower doses of sodium salicylate (150 mg/kg body weight) and was not found in animals trained on a dark–light paradigm, as expected. As the learning sessions of the operant conditioning were performed without pharmacological treatment, unintentional drug effects, for example, on learning and motivation of a rat were minimized in this behavioral paradigm. Furthermore, the behavioral changes reported here were shown to be a specific drug effect evoking a phantom auditory experience of a rat and cannot be explained by unspecific drug effects on motor activity, motivation, learning or hearing loss. The conditional paradigm is discussed in the context of its potential as a model for testing drugs that may have a therapeutic value in tinnitus research.

Bilateral activation of auditory association areas in gaze-evoked phantom auditory sensation.

Bilateral activation of auditory association areas in gaze-evoked phantom auditory sensation.

Phantom auditory sensation in rats: an animal model for tinnitus.

In order to measure tinnitus induced by sodium salicylate injections, 84 pigmented rats, distributed among 14 groups in five experiments, were used in a conditioned suppression paradigm. In Experiment 1, all groups were trained with a conditioned stimulus (CS) consisting of the offset of a continuous background noise. One group began salicylate injections before Pavlovian training, a second group started injections after training, and a control group received daily saline injections. Resistance to extinction was profound when injections started before training, but minimal when initiated after training, which suggests that salicylate-induced effects acquired differential conditioned value. In Experiment 2 we mimicked the salicylate treatments by substituting a 7 kHz tone in place of respective injections, resulting in effects equivalent to salicylate-induced behavior. In a third experiment we included a 3 kHz CS, and again replicated the salicylate findings. In Experiment 4 we decreased the motivational level, and the sequential relation between salicylate-induced effects and suppression training was retained. Finally, no salicylate effects emerged when the visual modality was used. These findings support the demonstration of phantom auditory sensations in animals.

Phantom auditory sensation in rats: An animal model for tinnitus.

Phantom auditory sensation in rats: An animal model for tinnitus.

Population control in the small bowel.

Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.

Obituary: Henry A. Magnus

Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.