Ultra-high field fMRI of subcortical auditory structures in patients with tinnitus

Tinnitus is a symptom characterized by the perception of sound or noise in the
absence of any objective external physical source. This disorder affects 600
million people worldwide and it has yet remained refractory to current medical
treatment.

Two neuromodulary modalities recently gained interest in the treatment of
tinnitus. One is tinnitus suppression with intracochlear electrical stimulation
(cochlear implants). The second is Deep Brain Stimulation, which has been shown
to suppress tinnitus in patients that were treated with Deep Brain Stimulation
for Parkinson*s disease. The current hypothesis of the underlying
pathophysiology is that tinnitus is triggered by injury of inner and/or outer
hair cells of the cochlea. A decrease in auditory nerve activity leads to
increased activity in the central nervous system.

Auditory structures possess a tonotopic organization: auditory neurons refer a
specific frequency, and neurons referring similar frequencies cluster together
creating smooth gradients of preferred frequency. In humans, using 7 T
functional MRI this tonotopic organization has recently been mapped in the
inferior colliculus. The majority of researches agreed that the increase in
synchrony and spontaneous activity in patients with tinnitus is the result of
tonotopic reorganization. We hypothesize that patients with tinnitus show a
modified tonotopic map in subcortical auditory areas at the location
corresponding to the tinnitus pitch. Such modification has been shown in
subcortical auditory structures in animals, but data from humans is lacking.
The optimal target for DBS might be found with ultra-high field fMRI data. The
area that shows increased activity in patients with tinnitus can be influenced
by DBS and thereby attenuates the pathological electrical activity for
treatment of tinnitus. Beneficial objective fMRI data, including the tonotopic
organization in the brain, also unravels the pathologic site inside the
cochlea, as the tonotopic organization in the cochlea is directly related to
the tonotopic organization in the brain. Therefore, tinnitus might be treated
more effectively (*customized treatment*) with intracochlear electrical
stimulation when objective fMRI data is available compared with the current
subjective diagnosis.

The primary goal of our study is to map and characterize anatomically and
functionally the subcortical structures of the auditory pathway in patients
with tinnitus and compare them to controls. To this end, we will use 7 T MRI
scanner and measure functional responses in the cochlear nucleus and inferior
colliculus. We will assess the overall activation level, the tonotopic
organization and BOLD fluctuations in each of these structures.

The proposed observational study is a pilot study which will form, after
promising results, the basis for a larger study for which funding should be
obtained.

The study will be an observational case-control pilot study. For the proposed
study 28 subjects will be included; 14 subjects will be unilateral tinnitus
sufferers and 14 healthy control volunteer.

The patients will be scanned in two separate sessions, one of 60 minutes and
one of 45 minutes. When attention is paid to the contra-indication of an MRI
scanner, the 7T MRI is harmless. An audiogram will be performed and a
questionnaire will be filled out before scanning, which also is harmless and
takes approximately 60 minutes.

Although 7T MRI is harmless if contra-indications are taken heed of and if
operated by certified users, a small amount of people (5%) may experience
vertigo or nausea while entering the scanner. However, these symptoms will be
minimised by slowing the subject*s entry and exit time into the magnetic
field. Also slight muscle contractions may be observed. The risk for muscle
contractions is low and it is not harmful. The risk of hearing loss is
minimized by the use of hearing protection during scanning.