The Neuroscience of Tinnitus: Understanding Abnormal and Normal Auditory Perception

Abstract

Tinnitus (chronic ringing of the ears in the absence of a sound source) is a major public health challenge affecting quality of life for millions of individuals around the world. Its principal cause (damage to the cochlea, which may be hidden and detected years after injury) appears to be increasing among youthful populations owing to exposure to recreational and occupational sounds for which current protective standards may be inadequate. And at present, there are no curative treatments for tinnitus. These facts alone, and the looming public health challenge they portend, are sufficient to spark its study. But research into the neural basis of tinnitus also addresses a fundamental question in neuroscience. If we can understand how the brain generates the sound of tinnitus, we may gain insight into the question of how the brain generates the sensation of other sounds. The papers published in this special issue (indicated in italics) address topics related to the neural basis of tinnitus, their implications for hearing, and the health challenge. Deafferentation of central auditory structures by cochlear injury leads to several neural changes in auditory pathways that appear to underlie the sensation of tinnitus (discussed by Brozoski et al., 2012; Diesch et al., 2012b; Langers et al., 2012; Middleton and Tzounopoulos, 2012; Schaette and Kempter, 2012; Stolzberg et al., 2012 and other papers). Included among the neural changes are tonotopic map reorganization in auditory cortical and thalamic structures, hyperactivity in these structures (but typically not in auditory nerve fibers), increased burst firing in subcortical auditory nuclei, and increased synchronous neural activity particularly in tonotopic regions affected by hearing loss where tinnitus percepts also localize (Noreña and Eggermont, 2006; Roberts et al., 2010). Reduced input from the auditory periphery appears to trigger adaptive compensatory shifts in the balance of excitation and inhibition that may preserve neuron firing rates within a prescribed range; however an unwanted side effect reviewed by Schaette and Kempter (2012) may be an increase spontaneous neural activity that when phase locked into synchronous patterns leads to the experience of tinnitus percepts. Neural changes underlying tinnitus appear to modify the expression of training-induced neural plasticity in the primary (A1) but not secondary (A2) auditory cortex of human tinnitus sufferers, reflecting diminished inhibition and enhanced neural synchrony in regions of A1 affected by hearing loss (Roberts et al., 2012). Attentional effects on the auditory steady state response in tinnitus patients were deemed unlikely (Diesch et al., 2012a). Although cortical map reorganization cannot itself generate a tinnitus sound (only the activity of the affected neurons can do this), map reorganization is widely believed to play an enabling role in the generation of tinnitus. However, Langers et al. (2012) were unable to detect macroscopic map reorganization below 8 kHz in functional imaging data in human tinnitus patients with normal audiometric thresholds. Whether map reorganization can be detected at higher frequencies in such patients is not known but may be the case. Map reorganization assessed by neuromagnetic imaging has been reported in tinnitus patients for whom hearing loss was present (Wienbruch et al., 2006). Genetic aspects of tinnitus have so far not been conclusively demonstrated and the paper by Sand et al. (2012) follows that trend. An important mechanism in the induction of neural plasticity is stress. Stress may have protective effects against noise trauma, but a combination of stress and hearing loss could enhance the likelihood of tinnitus (Mazurek et al., 2012). The involvement of stress networks in tinnitus is reviewed in Vanneste and De Ridder (2012). Other papers in the special issue describe animal models and computational approaches to understand mechanisms of tinnitus. Animal models are important, because such models permit measurements and interventions that cannot be performed on human tinnitus subjects. In one animal model the presence of tinnitus is signaled by making tinnitus a cue for a behaviorally relevant event. Brozoski et al. (2012) combined this method with magnetic resonance spectroscopy to uncover alterations in GABAergic and glutaminergic neurotransmission in specific subcortical auditory nuclei in rats showing behavioral evidence of tinnitus after traumatic noise exposure. A second and more widely used approach introduced by Turner et al. (2006), cautioned by Eggermont (2012), and evaluated by Dehmel et al. (2012) determines whether a tinnitus sound (in this case induced by noise exposure in guinea pigs) fills a silent gap in a background sound that would otherwise suppress an evoked startle response. Stolzberg et al. (2012) and Guitton (2012) discuss in depth how neural changes induced by salicylate in animal preparations are both congruent and in some respects different from those observed when tinnitus and hearing loss are induced by noise exposure. Middleton and Tzounopoulos (2012) call for detailed investigations of network neural activity in animal models of tinnitus, looking specifically at communication between thalamic nuclei and brain regions known to be active in tinnitus. Taking a different tack, Schaette and Kempter (2012) discuss how computational studies can reveal (or refute) whether neural network models of tinnitus are able to generate properties of tinnitus revealed in physiological and psychoacoustic studies. They emphasize that incorporating forms of neural plasticity in the models determines whether the models are able to simulate measured attributes of tinnitus. An important fact about tinnitus revealed by functional brain imaging studies is that the brain regions affected by tinnitus extend beyond auditory structures to include brain areas that are involved in higher level cognitive processing....