Navigated rTMS for the treatment of tinnitus: a pilot study with assessment by fMRI and AEPs.

OBJECTIVE: Repeated transcranial magnetic stimulation (rTMS) of auditory cortex has been proposed to treat refractory chronic tinnitus, but the involved mechanisms of action remain largely unknown. The purpose of this pilot study was to evaluate the impact of rTMS on auditory cortex activity in a series of tinnitus patients, using for the first time both functional magnetic resonance imaging (fMRI) of the brain and auditory evoked potentials (AEPs). METHOD: In six patients with chronic, lateralized refractory tinnitus, we performed five sessions of neuronavigated rTMS delivered at 1Hz over the secondary auditory cortex (defined on morphological MRI), contralateral to tinnitus side. The effects of rTMS were assessed on clinical scales, fMRI, and AEPs (N1 and P2 components). RESULTS: The clinical impact of rTMS on tinnitus was good for three patients (25-50% improvement of tinnitus severity compared to baseline), moderate for two patients (15% improvement), and null for one patient who had the most severe tinnitus at baseline. The changes induced by rTMS on fMRI data varied with the baseline level of auditory cortex activation before rTMS. This baseline level of activation was itself related to the severity of tinnitus. Thus, cortical stimulation increased auditory cortex activation in patients who had less severe tinnitus and low level of activation before rTMS, whereas it decreased auditory cortex activation in patients who had more severe tinnitus and higher level of activation before rTMS. Regarding AEPs, rTMS decreased N1 amplitude in all patients, except in the patient who had the most severe tinnitus at baseline and showed no improvement after rTMS. Conversely, P2 amplitude decreased after rTMS only in patients with severe tinnitus, at least for auditory stimulation contralateral to tinnitus, but increased in patients with less severe tinnitus. CONCLUSIONS: The changes produced by rTMS in auditory cortex activity, as assessed by fMRI and AEPs, appeared to depend on a process of disease-related homeostatic cortical plasticity, regardless of the therapeutic impact of rTMS on tinnitus.

Developmental regulation of the membrane properties of central vestibular neurons by sensory vestibular information in the mouse.

The effect of the lack of vestibular input on the membrane properties of central vestibular neurons was studied by using a strain of transgenic, vestibular-deficient mutant KCNE1(-/-) mice where the hair cells of the inner ear degenerate just after birth. Despite the absence of sensory vestibular input, their central vestibular pathways are intact. Juvenile and adult homozygous mutant have a normal resting posture, but show a constant head bobbing behaviour and display the shaker/waltzer phenotype characterized by rapid bilateral circling during locomotion. In juvenile mice, the KCNE1 mutation was associated with a strong decrease in the expression of the calcium-binding proteins calbindin, calretinin and parvalbumin within the medial vestibular nucleus (MVN) and important modifications of the membrane properties of MVN neurons. In adult mice, however, there was almost no difference between the membrane properties of MVN neurons of homozygous and control or heterozygous mutant mice, which have normal inner ear hair cells and show no behavioural symptoms. The expression levels of calbindin and calretinin were lower in adult homozygous mutant animals, but the amount of calcium-binding proteins expressed in the MVN was much greater than in juvenile mice. These data demonstrate that suppression of sensory vestibular inputs during a 'sensitive period' around birth can generate the circling/waltzing behaviour, but that this behaviour is not due to persistent abnormalities of the membrane properties of central vestibular neurons. Altogether, maturation of the membrane properties of central vestibular neurons is delayed, but not impaired by the absence of sensory vestibular information.