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Department of Neurobiology and Developmental Sciences
Jackson T. Stephens Spine & Neurosciences Institute
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Research

Dornhoffer lab DornhofferJohnL@uams

     Subjective tinnitus, the perception of sound in the absence of acoustic stimulation, is a common phenomenon, affecting approximately 17% of the general population.  About one-fourth of these individuals seek professional help due to associated mood, sleep, and attention disturbances.  The exact mechanisms of tinnitus generation and the related central nervous system dysfunction remain a mystery, making diagnosis and treatment difficult and often empirical.  While most believe that the inciting event for tinnitus generation lies in cochlear or auditory nerve dysfunction, the perception of tinnitus can be ascribed to central mechanisms in most cases.  Although many tinnitus sufferers complain of poor concentration, neuropsychological testing has revealed that the cognitive deficiency appears to be associated with the control of attention, especially regarding the inhibition of attending to task-irrelevant activity.
     In the past we used the sleep state-dependent midlatency auditory evoked P50 potential to assess the level of arousal and of habituation to repetitive stimuli in tinnitus patients and in age- and gender-matched control subjects.  No significant difference in the amplitude of the P50 potential was evident between individuals with tinnitus and age-matched controls.  This suggests that tinnitus patients have no detectable impairment in the level of arousal using the P50 potential.  There were, however, significant differences in habituation in the tinnitus group at the 250-msec and 1000-msec ISI.  This is in agreement with Hallum's theory that tinnitus represents a fundamental deficit in habituation.  Impaired habituation leading to a sensory gating deficit may explain some of the attention deficits and cognitive disturbances described in tinnitus patients.  Our findings, likewise, are in agreement with a subcortical source of habituation and suggest that a deficit in sensory gating may be present in tinnitus sufferers.
     More recently, our efforts have focused on developing an effective method for using repetitive transcranial magnetic stimulation (rTMS) as a therapy for tinnitus.  Several studies over the past two to three years, including our own, have enhanced the general understanding of tinnitus pathophysiology and the potential mechanisms by which rTMS may alleviate symptoms in tinnitus sufferers.  For example, we found that a psychomotor vigilance measure based upon simple reaction-time testing improves following rTMS treatment, further lending support to our belief that tinnitus is related to deficits in attention.  We have demonstrated that neuro-navigated rTMS delivered to the primary auditory cortex within the temporal lobe showing the most asymmetric hypermetabolism on PET-CT scan results in a reduction in tinnitus perception in about half of individuals tested.  In addition, we were the first to incorporate post-rTMS PET-CT scans into our research, which demonstrated a reduction in cortical metabolic activity within the regions treated with rTMS and a return to symmetrical auditory cortex activation in several subjects.  These findings may represent the first potentially useful objective measure of tinnitus response to rTMS therapy.  However, a reduction in tinnitus perception did not always correlate with these PET findings, suggesting that treating the auditory cortex alone may be insufficient for rTMS therapy in some individuals.
     Perhaps the most important concerns regarding rTMS therapy at present are the short duration of subjective tinnitus improvement and the less-than-ideal response rate (about 50% in most studies).  Our preliminary work has shown that maintenance rTMS sessions given at the return of tinnitus symptoms may offer a progressively longer-lasting benefit for tinnitus patients who respond well initially to rTMS therapy, and a larger study will soon be underway at UAMS to evaluate the role of maintenance therapy incorporation into rTMS treatment protocols.  Our attempts to address the 50% response rate have been met with some frustration, as this level of response has persisted regardless of which cerebral hemisphere is treated.  Our future endeavors will evaluate the effects of modulating the frequency of rTMS delivery (previously we used only low-frequency, 1-Hz stimulation) and of treating tinnitus-related cortical regions outside of the primary auditory cortices. 

Figure 1:  Three PET-CT scans from the same subject.   a) Pre-rTMS cortical hypermetabolic activity in the right superior temporal lobe (primary auditory cortex) in a subject with severe left-sided tinnitus perception.  b) Post-rTMS scan demonstrating initial reduction in temporal lobe hypermetabolic activity following one week of active treatment.  c) A later scan following several maintenance rTMS sessions demonstrating even further reduction in the temporal lobe hypermetabolic activity.