Inhibition of Experimental Tinnitus With High Frequency Stimulation of the Rat Medial Geniculate Body

Abstract

Background: Neuromodulation is a promising treatment modality for tinnitus, especially in chronic and severe cases. The auditory thalamus plays a key role in the pathophysiology of tinnitus, as it integrates and processes auditory and limbic information.

Objective: The effect of high frequency stimulation and low frequency stimulation of the medial geniculate bodies on tinnitus in a noise-induced tinnitus rat model is assessed.

Materials and methods: Presence of tinnitus was verified using the gap-induced prepulse inhibition of the acoustic startle response paradigm. Hearing thresholds were determined before and after noise trauma with auditory brainstem responses. Anxiety-related side-effects were evaluated in the elevated zero maze and open field.

Results: Results show tinnitus development after noise exposure and preserved hearing thresholds of the ear that was protected from noise trauma. We found that high frequency stimulation of the medial geniculate bodies suppressed tinnitus. This effect maintained directly after stimulation when the stimulator was turned off. Low frequency stimulation did not have any effects on the gap:no-gap ratio of the acoustic startle response.

Conclusion: High frequency stimulation of the MGB has a direct and residual suppressing effect on tinnitus in this animal model. Low frequency stimulation of the MGB did not inhibit tinnitus.

Keywords: Deep brain stimulation; medial geniculate body; neuromodulation; preclinical; tinnitus.

Figure 1

Timeline of the experimental procedures. ABR, auditory brainstem response recordings; EZM, elevated zero maze; GPIAS, gap‐prepulse inhibition of the acoustic startle reflex paradigm for tinnitus assessment; HFS, high frequency stimulation; LFS, low frequency stimulation; post‐HFS, stimulation off after 30 minutes of high frequency stimulation; OF, open field. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

a. Representative example of an electrode trajectory in the medial geniculate body. b. Schematic representation of the electrode sites in the medial geniculate body. The symbol (•) indicates the locations of all electrode tips, shown schematically in one hemisphere. cp, cerebral peduncle; HC, hippocampus; MGD, dorsal part of the medial geniculate body; MGV, ventral part of the medial geniculate body; RN, red nucleus; SC, superior colliculus; SNR, reticular part of substantia nigra. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Auditory brainstem responses measured at baseline (round, solid) and after noise exposure in the traumatized ear (square, dotted) and the contralateral side (triangle, dashed). Thresholds are presented as means ± SE. * p < 0.05; ** p < 0.001.

Figure 4

a. Gap‐prepulse inhibition of the acoustic startle reflex paradigm for tinnitus assessment before and after exposure to the 16 kHz tone, during stimulation off and HFS. Notice the reduced effect of the prepulse gap at 16 kHz background sound on the startle response after noise exposure. During HFS the effect of the prepulse gap was restored at 16 kHz and increased at 20 kHz. Gap:no‐gap ratios are presented as means ± SE. Presented significances are simple effects, * p < 0.05; ** p < 0.001. b. Gap‐prepulse of the acoustic startle reflex paradigm for tinnitus assessment at 10 and 16 kHz background sound after 16 kHz exposure. Four different stimulation paradigms were tested: 1) stimulation off; 2) HFS; 3) post‐HFS; 4) LFS. Compared to stimulation off, HFS and post‐HFS significantly increased the effect of the gap prepulse on the acoustic startle response. Gap:no‐gap ratios are presented as means ± SE. * p < 0.05; ** p < 0.001. c. Individual gap:no‐gap ratios before and after exposure to the 16 kHz tone, during stimulation off and HFS. Each colored line represents one subject. d. Individual gap:no‐gap ratios at 10 and 16 kHz background sound after 16 kHz exposure during the four different stimulation paradigms. Each colored line represents one subject. BBN, broadband noise; HFS, high frequency stimulation (100 Hz, 60 μs pulse width, and 100 μA amplitude); LFS, low frequency stimulation (10 Hz, 60 μs pulse width, and 100 μA amplitude); post‐HFS, DBS off after 30 minutes of high frequency stimulation; stimulation off, attached to cable without stimulation. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

a. Number of entries in the open arm and time spent in the enclosed arms (in sec) of the elevated zero maze. b. Total distance moved (in cm) and time spent in corners and walls (in sec) in the open field. Data are presented as means ± SE. There were no significant differences between high frequency stimulation (HFS) and stimulation off.