Enhancement of steady-state auditory evoked magnetic ®elds in tinnitus Eugen Diesch, 1 Maren Struve, 1 Andre Rupp, 2 Steffen Ritter, 2 Manfred HuÈlse 3 and Herta Flor 1 1 Department of Neuropsychology, University of Heidelberg, Central Institute of Mental Health, Square J5, D-68159, Mannheim, Germany 2 Department of Neurology, Section of Biomagnetism, University Hospital Heidelberg, Heidelberg, Germany 3 Department of Otorhinolaryngology, University Hospital Mannheim, Mannheim, Germany Keywords: cortical plasticity, human, magnetoencephalography, tinnitus Abstract The steady-state auditory evoked magnetic ®eld and the Pbm, the magnetic counterpart of the second frontocentrally positive middle latency component of the transitory auditory evoked potential, were measured in ten tinnitus patients using a 122-channel gradiometer system. The patients had varying degrees of hearing loss. In all patients, the tinnitus frequency was located above the frequency of the audiometric edge, i.e. the location on the frequency axis above which hearing loss increases more rapidly. Stimuli were amplitude- modulated sinusoids with carrier frequencies at the tinnitus frequency, the audiometric edge, two frequencies below the audiometric edge, and two frequencies between the audiometric edge and the tinnitus frequency. Below the audiometric edge, the root-mean- square ®eld amplitude of the steady-state response computed across the whole head as well as the contralateral and the ipsilateral dipole moment decreased as a function of carrier frequency. With carrier frequency above the audiometric edge, the steady-state response increased again. The amplitudes of the transitory Pbm component were patterned in a qualitatively similar way, but without the differences being signi®cant. For the steady-state response, both whole-head root-mean-square ®eld amplitude and the dipole moment of the sources at the tinnitus frequency showed signi®cant positive correlations with subjective ratings of tinnitus intensity and intrusiveness. These correlations remained signi®cant when the in¯uence of hearing loss was partialled out. The observed steady-state response amplitude pattern likely re¯ects an enhanced state of excitability of the frequency region in primary auditory cortex above the audiometric edge. The relationship of tinnitus to auditory cortex hyperexcitability and its independence of hearing loss is discussed with reference to loss of surround inhibition in and map reorganization of primary auditory cortex. Introduction Tinnitus is an auditory sensation experienced in the absence of adequate stimulation. In industrialized countries approximately 35± 40% of adults experience episodes of tinnitus at some stage of their life, approximately 0.5±1.0% are permanently and severely affected (Feldmann, 1992). Tinnitus is found in all age groups, but tends to increase in frequency among those above 40 years of age (Jastreboff et al., 1996). Tinnitus has been related to discordant damage to inner and outer hair cells (Jastreboff, 1990), to increased correlated ®ring of cochlear nerve ®bers caused by pathological spontaneous periodic ®ring of inner hair cells (Eggermont, 1990; Zenner & Ernst, 1993) or `ephaptic' communication between hair cells and/or between cochlear nerve ®bers (Mùller, 1984), to altered motility of outer hair cells (Zenner & Ernst, 1993), to enhanced responsiveness of the nuclei of the afferent auditory pathway after cochlear damage (Gerken, 1996; Salvi et al., 2000), to reduced inhibitory input to the inferior colliculus, increased inferior colliculus activity, and increased activity of the auditory cortex (WallhaÈusser-Franke et al., 1996), to rhythmic bursting activity of thalamic units induced by a loss of excitatory input (Jeanmonod et al., 1996), to coherent low-frequency oscillatory thalamocortical activity (Llinas et al., 1999), and to maladaptive plastic changes of the functional organization of the auditory system and the auditory cortex in particular (MuÈhlnickel et al., 1998; Rauschecker, 1999). These hypotheses do not necessarily exclude one another. Peripheral damage to the cochlea or to the auditory nerve triggers a cascade of changes in the subcortical and cortical structures of the auditory central nervous system that alter the balance of excitation and inhibition. A possible consequence is the generation of a tonic pathological signal in the auditory periphery that is interpreted by and that eventually alters the function of the auditory nervous system. Another common conse- quence of mechanical lesions of the cochlea, biochemical lesions of the hair cells, and loss of hair cells by ageing or noise exposure is a reduction of activity in the auditory nerve (Kiang & Moxon, 1972; Liberman & Dodds, 1984), excitatory and inhibitory input deprivation of the nuclei of the afferent auditory pathway, and as a consequence down-regulation of inhibition and an increase of excitability in several subcortical nuclei (Gerken, 1996; Salvi et al., 2000; Zacharek et al., 2002) as well as the auditory cortex (Rajan, 1998). These changes may induce alterations of function and functional reorganization in central auditory structures that may result in the sensation of tinnitus (Syka, 2002). European Journal of Neuroscience, Vol. 19, pp. 1093±1104, 2004 ß Federation of European Neuroscience Societies doi:10.1111/j.1460-9568.2004.03191.x Correspondence: Dr Eugen Diesch, as above. E-mail: diesch@zi-mannheim.de Received 16 June 2003, revised 5 October 2003, accepted 14 November 2003