Variable changes in PET activity before and after rTMS treatment for tinnitus

Abstract

Objective/Hypothesis Determine whether low-frequency rTMS improves tinnitus by decreasing neural activity in auditory processing regions of the temporal cortex and the utility of PET for targeting treatment. Study Design Randomized, sham-controlled crossover. Methods Patients received a 5-day course of active and sham 1-Hz rTMS (1800 pulses at 110% of motor threshold) to the temporal cortex, with a week separating active and sham treatment. Visual analogue ratings of tinnitus loudness (VARL) were assessed at baseline and the end of each treatment week; regional brain blood flow (rBBF) and glucose metabolism (via PET) were measured before and after treatment in regions of interest (ROI) beneath the stimulating coil and control sites. Results The VARL for both ears significantly decreased after active but not sham treatment. Responders comprised 43% of patients, experiencing at least a 33% drop in tinnitus loudness. The site most consistently associated with a positive response was the secondary auditory cortex (Brodmann Area 22) in either hemisphere. PET asymmetries were variable across patients and not always accessible to rTMS. Whereas PET activity decreased significantly beneath the stimulating coil following active treatment, similar changes occurred at control sites and after sham stimulation. Change in tinnitus perception did not correlate significantly with change in PET activity at the treatment site ROI. Conclusions Active TMS led to a significant reduction in tinnitus loudness, but PET scans failed to support the hypothesis that low-frequency rTMS improves tinnitus by reducing cortical activation at the stimulation site, questioning the utility of PET for targeting rTMS.

Effectiveness of Theta-Burst Repetitive Transcranial Magnetic Stimulation for Treating Chronic Tinnitus

“…Thus, in some cases, the coverage of rTMS may include the auditory cortex. Even where there are no direct interactions, propagation of brain activity from the stimulant foci can result in widespread changes [Mennemeier et al, 2011]. It seemed that targeting on the auditory cortex was not more mainstreamed into the tinnitus treatment.…”

“…This can be accomplished using a combination of positron emission tomography and computed tomography (PET-CT), which indicates the areas that experience the highest levels of cortical activation [Mennemeier et al, 2011]. However, this is an invasive procedure and requires that researchers first convince patients to submit to injection of radioactive isotopes.…”

“…First, burst rTMS may neuromodulate the lemniscal and extralemniscal auditory systems differently through connecting neural pathways between superficial and deeper brain structures; second, there is a 'neglect-like' effect subsequent to theta-burst stimulation [Fox et al, 1997;Nyffeler et al, 2009]. Mennemeier et al [2011] used 1-Hz rTMS to target temporal lobe PET asymmetry and reported that there were significantly changes in PET following active treatment, including in the inferior lateral parietal temporal cortex, primary visual cortex, sensory motor cortex, and superior lateral temporal cortex. A subsequent nervous propagation to other brain structures might lead to changes in tinnitus perception.…”

“…Several rTMS protocols that reduce the abnormal hyperactive auditory cortex have been proposed, the most common of which is a daily application of 1 Hz rTMS to produce long-lasting inhibitory effects on the auditory cortex. However, late studies have suggested that it may be effective to direct rTMS towards temporoparietal area in general, rather than just the auditory cortex specifically [Frank et al, 2010;Langguth et al, 2010;Mennemeier et al, 2011]. Only recently has clinical research begun to focus on theta-burst stimulation (TBS), a novel form of rTMS that also creates inhibitory effects [Huang et al, 2005].…”

Neuromodulation for the Treatment of Tinnitus

“…Progress in functional imaging has helped explain the pathophysiology and identified brain lesions related to tinnitus [32]. Several studies have reported that positron emission tomography (PET) can be used to identify the region of unbalanced cortical activity where rTMS could be applied [33,34]; however, controversy remains regarding the usefulness of PET for rTMS targeting [35] and the function of PET and other neuroimaging modalities in determining the stimulation site is debatable. Rossi [36] reported that stimulation (5 days, 1-Hz rTMS) in the left temporoparietal area was effec- tive and not related to tinnitus laterality.…”