Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus

Abstract

Tinnitus, a phantom auditory percept, is strongly associated with cochlear trauma. The latter leads to central changes in auditory pathways such as increased spontaneous activity and this may be involved in tinnitus generation. As not all people with cochlear trauma develop tinnitus, recent studies argue that non-auditory structures, such as prefrontal cortex (PFC), play an important role in tinnitus development. As part of sensory gating circuitry, PFC may modify activity in auditory thalamus and consequently in auditory cortex. Human studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive tool for neurostimulation, can alter tinnitus perception. This study used a guinea pig model of hearing loss and tinnitus to investigate effects of low-intensity rTMS (LI-rTMS) over PFC on tinnitus and spontaneous activity in auditory thalamus. In addition, immunohistochemistry for calbindin and parvalbumin in PFC was used to investigate the possible mechanism of action of LI-rTMS. Three treatment groups were compared: sham treatment, LI, low frequency (1 Hz) or LI, high frequency (10 Hz) rTMS (10 min/day, 2 weeks, weekdays only). None of the treatments affected the behavioural measures of tinnitus but spontaneous activity was significantly increased in auditory thalamus after 1 Hz and 10 Hz treatment. Immunostaining showed significant effects of rTMS on the density of calcium-binding protein expressing neurons in the dorsal regions of the PFC suggesting that rTMS treatment evoked plasticity in cortex. In addition, calbindin-positive neuron density in the superficial region of PFC was negatively correlated with spontaneous activity in auditory thalamus suggesting a possible mechanism for change in activity observed.

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Abbreviations

CAP:

Compound action potential

ECG:

Electrocardiogram

GPIAS:

Gap prepulse inhibition of acoustic startle

i.p.:

Intraperitoneal

i.m.:

Intramuscular

LI:

Low intensity

MGN:

Medial geniculate nucleus

PB:

Phosphate buffer

PFC:

Prefrontal cortex

PPI:

Prepulse inhibition

rTMS:

Repetitive transcranial magnetic stimulation

s.c.:

Subcutaneous

SPL:

Sound pressure level

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Acknowledgements

This work was supported by grants from the Medical Health and Research Infrastructure Fund and funds provided by the School of Human Sciences UWA. JR is funded by a fellowship from MSWA (Multiple Sclerosis Western Australia) and the Perron Institute for Neurological and Translational Science. The authors would like to thank Ms. Marissa Penrose-Menz for her help in creating Fig. 1.

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Mulders, W.H.A.M., Leggett, K., Mendis, V. et al. Low-intensity repetitive transcranial magnetic stimulation over prefrontal cortex in an animal model alters activity in the auditory thalamus but does not affect behavioural measures of tinnitus. Exp Brain Res 237, 883–896 (2019). https://doi.org/10.1007/s00221-018-05468-w

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Keywords

  • Tinnitus
  • Compound action potential
  • Gap prepulse inhibition
  • Guinea pig
  • Audiogram