Pilot Study of Deep Brain Stimulation (DBS) in Area LC for Chronic Tinnitus

This is a single institution, open-label, phase I clinical trial to estimate the treatment
effect size and to assess preliminary safety and tolerability of DBS in the caudate nucleus
(area LC) in adults with a big or very big problem (tinnitus functional index TFI>50) with
chronic tinnitus. Up to 10 subjects will be implanted. The DBS stimulation parameters are
patient-specific and will be allowed to vary over the course of the treatment periods,
calibrated by the TFI. During Period I, stimulation will be continuous. During Period II,
there will be three stimulation OFF/ON epochs, where the stimulation will be turned OFF and
then turned back ON when the tinnitus loudness returns to a certain level (based on a change
in the TFI score). During Period III, stimulation will be "on demand," i.e. controlled by the
subject and determined by subject preference. An important goal is to determine whether
tinnitus can be controlled through optimization of stimulation parameters.

Inclusion Criteria:

Men and women between the ages of 22 and 75 years. Subjective, unilateral or bilateral,
non-pulsatile tinnitus of 1 year's duration or greater.

Tinnitus Functional Index (TFI) score greater than 50. Tinnitus unresponsive acoustical and
behavioral therapies. Prospective subjects must have received at least one acoustical
(masker, hearing aid, Neuromonics®) or behavioral therapy (cognitive behavioral, directive
counseling, tinnitus retraining therapy) to be eligible for study enrollment, but partial
response to conventional therapy does not exclude a prospective subject if the individual
meets the TFI > 50 study participation threshold.

Montreal Cognitive Assessment (MoCA) ≥ 26. Subjects of child-bearing potential using an
appropriate form of birth control acceptable to the research team and with a negative urine
pregnancy test or has undergone sterilization procedure.

Capacity to give informed consent. English-speaking.

Exclusion Criteria:

Patients experiencing tinnitus related to untreated retrocochlear lesion, or other known
anatomic/structural lesions of the ear or temporal bone.

Patients with hyperacusis or misophonia (hypersensitivity to loud noises). Hearing loss of
moderately severe or greater severity in either ear. History of seizure disorder or
currently under treatment for seizure disorder. Patients with cardiac pacemakers,
intracardiac lines, implanted medication pumps, implanted electrodes in the brain, other
intracranial metal objects with the exception of dental fillings, or any other
contraindication for obtaining a MRI scan.

Patients with an acute or chronic unstable medical condition which, in the opinion of the
PI, would require stabilization prior to or preclude DBS surgery.

Patients with any active ear disease that, in the opinion of the PI, needs to be further
evaluated.

Patients with psychiatric symptoms that, in the opinion of the study team, are not
adequately treated or would interfere with study activities.

Any psychiatric co-morbidity that may complicate the interpretation of study results.

Pregnancy. Currently breast-feeding. Patients with tinnitus related to Workman's
Compensation claim or litigation-related event.

Patients taking any medication(s), in the opinion of the PI, that is (are) deemed to be
etiologically related to the development of tinnitus.

Preoperative neurophychological evaluation that indicates either of the following:

Dementia - Using DSM-IV criteria of memory impairment and at least one of the following:
aphasia, apraxia, agnosia or disturbances in executive functioning. The cognitive
impairments must be severe enough to cause impairment in social and occupational
functioning and must represent a decline from a previously higher level of functioning. The
diagnosis of dementia will not be made if the cognitive deficits occur exclusively during
the course of a delirium.

Cognitive impairment (z < -1.5) in multiple domains without dementia (i.e. patient is
functionally intact), but in the opinion of the study team would not or could not comply
with study requirements.

Beck Depression Inventory-II (BDI-II) > 29, indicating severe depression. Patients with a
history of claustrophobia that would interfere with MRI or surgery.

Active alcohol and/or drug dependence or history of alcohol and/or ETOH dependence within
the last year.

Any medical condition that, in the opinion of the investigators, confounds study results or
places the subject at greater risk.

Unable to provide informed consent.