Computational models of neurophysiological correlates of tinnitus

The understanding of tinnitus has progressed considerably in the past decade, but the details of the mechanisms that give rise to this phantom perception of sound without a corresponding acoustic stimulus have not yet been pinpointed. It is now clear that tinnitus is generated in the brain, not in the ear, and that it is correlated with pathologically altered spontaneous activity of neurons in the central auditory system. Both increased spontaneous firing rates and increased neuronal synchrony have been identified as putative neuronal correlates of phantom sounds in animal models, and both phenomena can be triggered by damage to the cochlea. Various mechanisms could underlie the generation of such aberrant activity. At the cellular level, decreased synaptic inhibition and increased neuronal excitability, which may be related to homeostatic plasticity, could lead to an over-amplification of natural spontaneous activity. At the network level, lateral inhibition could amplify differences in spontaneous activity, and structural changes such as reorganization of tonotopic maps could lead to self-sustained activity in recurrently connected neurons. However, it is difficult to disentangle the contributions of different mechanisms in experiments, especially since not all changes observed in animal models of tinnitus are necessarily related to tinnitus. Computational modeling presents an opportunity of evaluating these mechanisms and their relation to tinnitus. Here we review the computational models for the generation of neurophysiological correlates of tinnitus that have been proposed so far, and evaluate predictions and compare them to available data. We also assess the limits of their explanatory power, thus demonstrating where an understanding is still lacking and where further research may be needed. Identifying appropriate models is important for finding therapies, and we therefore, also summarize the implications of the models for approaches to treat tinnitus

Einfluss der Kräuterfutterkomponente eines kommerziellen Ergänzungsfuttermittels auf Serumparameter, Fruchtbarkeit und Langlebigkeit von Milchkühen

A randomized placebo controlled trial investigates an herbal mixture containing mainly Urtica dioica L. (herba), Trigonella foenum-greacum L. (semen), Silybum marianum (L.) Gaert. (fructus) and Achillea millefolium L. (herba). The herbal mixture was fed daily (50g per cow) about 60d from dry off to calving date. 63 dairy cows (32 in the herb-(h)- and 31 in the placebo-(p)-group) of one organic farm were included in the study. Cows were differentiated depending on their lactation number: 19 first lactating cows (L1; h: n=10, p: n=9), 23 cows of second to fourth lactation (L2-4; h: n=11, p: n=12) and 21 cows with more than four lactations (L>4; h: n=11, p: n=10). The herbal group showed the following significant differences (p4 were higher; abnormalities in at least one of 7 tested serum parameters in lactating group L1 were less; in L>4 less ovarian follicles and larger uteri could be found in early lactation; a longer intercalving period (h: 387 days; p: 344 days) but a lower overall culling rate (h: 17%; p: 50%) and culling rate for fertility reasons (h: 3%; p: 23%). The herbal mixture seemed 1. to improve the postpartal metabolic status of dairy cows, 2. to prolong the postnatal anoestrus but 3. to decrease the culling rate particularly for fertility reasons. Overall the prolonged intercalving period will have a lower economic effect than the decreased culling rate

Time course and frequency specificity of sub-cortical plasticity in adults following acute unilateral deprivation

Auditory deprivation and stimulation can change the threshold of the acoustic reflex, but the mechanisms underlying these changes remain largely unknown. In order to elucidate the mechanism, we sought to characterize the time-course as well as the frequency specificity of changes in acoustic reflex thresholds (ARTs). In addition, we compared ipsilateral and contralateral measurements because the pattern of findings may shed light on the anatomical location of the change in neural gain. Twenty-four normal-hearing adults wore an earplug continuously in one ear for six days. We measured ipsilateral and contralateral ARTs in both ears on six occasions (baseline, after 2, 4 and 6 days of earplug use, and 4 and 24 hours after earplug removal), using pure tones at 0.5, 1, 2 and 4 kHz and a broadband noise stimulus, and an experimenter-blinded design. We found that ipsi-as well as contralateral ARTs were obtained at a lower sound pressure level after earplug use, but only when the reflex was elicited by stimulating the treatment ear. Changes in contralateral ARTs were not the same as changes in ipsilateral ARTs when the stimulus was presented to the control ear. Changes in ARTs were present after 2 days of earplug use, and reached statistical significance after 4 days, when the ipsilateral and contralateral ARTs were measured in the treatment ear. The greatest changes in ARTs occurred at 2 and 4 kHz, the frequencies most attenuated by the earplug. After removal of the earplug, ARTs started to return to baseline relatively quickly, and were not significantly different from baseline by 4-24 hours. There was a trend for the recovery to occur quicker than the onset. The changes in ARTs are consistent with a frequency-specific gain control mechanism operating around the level of the ventral cochlear nucleus in the treatment ear, on a time scale of hours to days. These findings, specifically the time course of change, could be applicable to other sensory systems, which have also shown evidence of a neural gain control mechanism

Using acoustic reflex threshold, auditory brainstem response and loudness judgments to investigate changes in neural gain following acute unilateral deprivation in normal hearing adults

Unilateral auditory deprivation induces a reduction in the acoustic reflex threshold (ART) and an increase in loudness. These findings have been interpreted as a compensatory change in neural gain, governed by changes in excitatory and inhibitory neural inputs. There is also evidence to suggest that changes in neural gain can be measured using the auditory brainstem response (ABR). The present study extended Munro et al. (2014) [J. Acoust. Soc. Am. 135, 315-322] by investigating changes after 4 days of unilateral earplug use to: (i) ART, (ii) ABR and (iii) loudness. Because changes may occur during the post-deprivation test session (day 4), ART measurements were taken 1 h and 2 h post-earplug removal. There was a significant reduction in ART in the treatment ear immediately after the removal of the earplug, which is consistent with a compensatory increase in neural gain. A novel finding was the significant return of ARTs to baseline within 2 h of earplug removal. A second novel finding was a significant decrease in the mean amplitude of ABR wave V in the treatment ear, but a significant increase in the control ear, both after 4 days of deprivation. These changes in the ABR are in the opposite direction to those predicted. We were unable to replicate the change in loudness reported in previous deprivation studies; however, the short period of earplug use may have contributed to this null finding

Reversible Induction of Phantom Auditory Sensations through Simulated Unilateral Hearing Loss

Tinnitus, a phantom auditory sensation, is associated with hearing loss in most cases, but it is unclear if hearing loss causes tinnitus. Phantom auditory sensations can be induced in normal hearing listeners when they experience severe auditory deprivation such as confinement in an anechoic chamber, which can be regarded as somewhat analogous to a profound bilateral hearing loss. As this condition is relatively uncommon among tinnitus patients, induction of phantom sounds by a lesser degree of auditory deprivation could advance our understanding of the mechanisms of tinnitus. In this study, we therefore investigated the reporting of phantom sounds after continuous use of an earplug. 18 healthy volunteers with normal hearing wore a silicone earplug continuously in one ear for 7 days. The attenuation provided by the earplugs simulated a mild high-frequency hearing loss, mean attenuation increased from <10 dB at 0.25 kHz to >30 dB at 3 and 4 kHz. 14 out of 18 participants reported phantom sounds during earplug use. 11 participants presented with stable phantom sounds on day 7 and underwent tinnitus spectrum characterization with the earplug still in place. The spectra showed that the phantom sounds were perceived predominantly as high-pitched, corresponding to the frequency range most affected by the earplug. In all cases, the auditory phantom disappeared when the earplug was removed, indicating a causal relation between auditory deprivation and phantom sounds. This relation matches the predictions of our computational model of tinnitus development, which proposes a possible mechanism by which a stabilization of neuronal activity through homeostatic plasticity in the central auditory system could lead to the development of a neuronal correlate of tinnitus when auditory nerve activity is reduced due to the earplug

Earplug-induced changes in acoustic reflex thresholds suggest that increased subcortical neural gain may be necessary but not sufficient for the occurrence of tinnitus

The occurrence of tinnitus is associated with hearing loss and neuroplastic changes in the brain, but disentangling correlation and causation has remained difficult in both human and animal studies. Here we use earplugs to cause a period of monaural deprivation to induce a temporary, fully reversible tinnitus sensation, to test whether differences in subcortical changes in neural response gain, as reflected through changes in acoustic reflex thresholds (ARTs), could explain the occurrence of tinnitus. Forty-four subjects with normal hearing wore an earplug in one ear for either 4 (n = 27) or 7 days (n = 17). Thirty subjects reported tinnitus at the end of the deprivation period. ARTs were measured before the earplug period and immediately after taking the earplug out. At the end of the earplug period, ARTs in the plugged ear were decreased by 5.9 ± 1.1 dB in the tinnitus-positive group, and by 6.3 ± 1.1 dB in the tinnitus-negative group. In the control ear, ARTs were increased by 1.3 ± 0.8 dB in the tinnitus-positive group, and by 1.6 ± 2.0 dB in the tinnitus-negative group. There were no significant differences between the groups with 4 and 7 days of auditory deprivation. Our results suggest that either the subcortical neurophysiological changes underlying the ART reductions might not be related to the occurrence of tinnitus, or that they might be a necessary component of the generation of tinnitus, but with additional changes at a higher level of auditory processing required to give rise to tinnitus

The search for noise-induced cochlear synaptopathy in humans:Mission impossible?

Animal studies demonstrate that noise exposure can permanently damage the synapses between inner hair cells and auditory nerve fibers, even when outer hair cells are intact and there is no clinically relevant permanent threshold shift. Synaptopathy disrupts the afferent connection between the cochlea and the central auditory system and is predicted to impair speech understanding in noisy environments and potentially result in tinnitus and/or hyperacusis. While cochlear synaptopathy has been demonstrated in numerous experimental animal models, synaptopathy can only be confirmed through post-mortem temporal bone analysis, making it difficult to study in living humans. A variety of non-invasive measures have been used to determine whether noise-induced synaptopathy occurs in humans, but the results are conflicting. The overall objective of this article is to synthesize the existing data on the functional impact of noise-induced synaptopathy in the human auditory system. The first section of the article summarizes the studies that provide evidence for and against noise-induced synaptopathy in humans. The second section offers potential explanations for the differing results between studies. The final section outlines suggested methodologies for diagnosing synaptopathy in humans with the aim of improving consistency across studies