Tinnitus is a phantom perception occurring very frequently in individuals with hearing loss. At Karolinska Institutet, and the Karolinska Hospital Hörsel och Balans, we strive to better understand the fundamental mechanisms of tinnitus and its objective diagnosis in animal and humans.
We use an animal model of auditory synaptopathy that display normal hearing but show a reduction of 50% of the synaptic connections between inner hair cells and spiral ganglion neurons. These animals have a greater susceptibility of developing tinnitus and thus establish a robust pre-clinical model to further understand how tinnitus develops and persists.
a) Example of startle responses during gap detection. A gap (2) presented before a startling noise stimulus (3) represses the startling response (4) in control individuals when compared to responses in absence of pre-stimulus (1, 4). Tinnitus interferes with the inhibition caused by the gap, and the startle response is less suppressed (5). (b) Gap-detection deficits at different background intensities correlating with tinnitus severity at a 32 kHz frequency in GLAST KO mice in comparison to WT mice. (c) Normal hearing thresholds in GLAST WT and KO mice (n=23-25). (d) 50% decreased wave 1 amplitude of the ABR in GLAST KO mice when compared to WT mice (n=10-13). (e) Normal pre-synaptic ribbon abundance in GLAST WT and KO mice (n=4-13), although severely impacted synaptic pairing in GLAST KO mice (f). (g) Confocal images showing coupled synapses in GLAST WT mice (left) but not in GLAST KO mice (right). From Yu et al., Front. Behav. Neurosci., 2016 and Tserga et al., in press.
In humans, our research group has been involved in large EU consortiums (TINNET, ESIT, UNITI, and TIGER) that investigate the heterogeneity of tinnitus to better design clinical trials and improve the efficacy of outcome testing.
We investigate risk factors in cross-sectional and longitudinal datasets from Sweden, but also developed our own cohort of highly characterized tinnitus participants – STOP. In the latter, we have shown strong relationships between tinnitus and temporo-mandibular joint complaints, headaches and hyperacusis. Our work was pioneering in establishing a heritability of tinnitus depending on its subtype, in twins, adoptees and familial aggregation studies. This led us to conduct genetic and plasma biomarker studies in order to improve diagnosis and patient stratification.
Our research group is also currently developing new methods for the objective diagnosis of tinnitus using magnetoencephalography.
Role of glutamate transporters in noise and drug-induced hearing loss and tinnitus
Circadian vulnerability of cisplatin-induced ototoxicity in the cochlea.
Tserga E, Moreno-Paublete R, Sarlus H, Björn E, Guimaraes E, Göritz C, et al
FASEB J 2020 Aug;():
GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus. Yu H, Vikhe Patil K, Han C, Fabella B, Canlon B, Someya S, et al Front Behav Neurosci 2016 ;10():158
STOP: Swedish Tinnitus Outreach Project
Impact of Temporomandibular Joint Complaints on Tinnitus-Related Distress. Edvall NK, Gunan E, Genitsaridi E, Lazar A, Mehraei G, Billing M, et al Front Neurosci 2019 ;13():879
Relationship between headaches and tinnitus in a Swedish study. Lugo A, Edvall NK, Lazar A, Mehraei G, Lopez-Escamez JA, Bulla J, et al Sci Rep 2020 05;10(1):8494
Association between Hyperacusis and Tinnitus. Cederroth CR, Lugo A, Edvall NK, Lazar A, Lopez-Escamez JA, Bulla J, et al J Clin Med 2020 Jul;9(8):
The genetic basis of hearing loss and tinnitus
Association of Genetic vs Environmental Factors in Swedish Adoptees With Clinically Significant Tinnitus. Cederroth CR, PirouziFard M, Trpchevska N, Idrizbegovic E, Canlon B, Sundquist J, et al JAMA Otolaryngol Head Neck Surg 2019 Mar;145(3):222-229
Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort. Maas IL, Brüggemann P, Requena T, Bulla J, Edvall NK, Hjelmborg JVB, et al Genet. Med. 2017 09;19(9):1007-1012
The epidemiology of hearing loss and tinnitus
Gender-Specific Risk Factors and Comorbidities of Bothersome Tinnitus. Basso L, Boecking B, Brueggemann P, Pedersen NL, Canlon B, Cederroth CR, et al Front Neurosci 2020 ;14():706
Sex-Specific Association of Tinnitus With Suicide Attempts. Lugo A, Trpchevska N, Liu X, Biswas R, Magnusson C, Gallus S, et al JAMA Otolaryngol Head Neck Surg 2019 Jul;145(7):685-687
TODD: Tinnitus Objective Diagnostic Device
Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice. Moreno-Paublete R, Canlon B, Cederroth CR Front Cell Neurosci 2017 ;11():19