Lower glutamate and GABA levels in auditory cortex of tinnitus patients: a 2D-JPRESS MR spectroscopy study

Abstract

We performed magnetic resonance spectroscopy (MRS) on healthy individuals with tinnitus and no hearing loss (n = 16) vs. a matched control group (n = 17) to further elucidate the role of excitatory and inhibitory neurotransmitters in tinnitus. Two-dimensional J-resolved spectroscopy (2D-JPRESS) was applied to disentangle Glutamate (Glu) from Glutamine and to estimate GABA levels in two bilateral voxels in the primary auditory cortex. Results indicated a lower Glu concentration (large effect) in right auditory cortex and lower GABA concentration (medium effect) in the left auditory cortex of the tinnitus group. Within the tinnitus group, Glu levels positively correlated with tinnitus loudness measures. While the GABA difference between groups is in line with former findings and theories about a dysfunctional auditory inhibition system in tinnitus, the novel finding of reduced Glu levels came as a surprise and is discussed in the context of a putative framework of inhibitory mechanisms related to Glu throughout the auditory pathway. Longitudinal or interventional studies could shed more light on interactions and causality of Glu and GABA in tinnitus neurochemistry.

Is it up there? - an MR spectroscopy study of frontal lobes and non-primary-auditory temporal areas in subjective bilateral and unilateral tinnitus

“…Although it still remains unclear whether the reported effects are due to tinnitus per se or the accompanying hearing loss, even if non-severe (as in e.g. Isler et al 31 and Yoo et al 88 ).…”

“…Some authors opt for using large voxels for local metabolite measurements (e.g. in tinnitus MRS studies: Isler et al 31 ; Sedley et al 16 ) that, however, do not warrant high regional speci city. Others use voxels of smaller sizes, which approach nevertheless requires signal-to-noise ratio to be improved, e.g.…”

“…Correlation analysis between PTA values, Glx/tCr levels, and Chol/tCr levels Concentrations of Glu 31,78 and Cho 16 in regions of interest including the auditory cortex have been shown to correlate with hearing loss levels (and thus confounding to effect of tinnitus per se). We veri ed whether this effect exists in our data by testing for Pearson correlation between Glx and Cho levels and PTA values derived from an audiometric evaluation.…”

“…Our main aim was to expand the existing limited knowledge regarding the potential involvement of glutamate/glutamine levels (basic excitatory neurotransmitter in CNS) and other metabolites in the occurrence of subjective tinnitus. To the best of our knowledge, our work is the second one, following Isler and colleagues 31 , that measured glutamate concentration with MRS speci cally in people with tinnitus and a control group, and the rst one to investigate metabolite levels in frontal and non-primary auditory temporal brain areas in unilateral vs bilateral tinnitus subgroups. Our cohort of 52 tinnitus patients is the largest examined thus far with MRS and psychological questionnaires.…”

“…Up until now, however, its implementation has been very limited. To the best of our knowledge, there have only been three works investigating Glu or GABA levels in tinnitus, with the authors only focused on the auditory cortex, as most probably inspired by animal models 16,30,31 .…”