European Journal of Neuroscience, Vol. 19, pp. 2337±2344, 2004 ß Federation of European Neuroscience Societies Lateral inhibition and habituation of the human auditory cortex C. Pantev1,2, H. Okamoto2,4, B. Ross1,2, W. Stoll3, E. Ciurlia-Guy4, R. Kakigi5 and T. Kubo6 1Institute for Biomagnetism and Biosignalanalysis, MuÈnster University Hospital, Kardinal-von-Galen-Ring 10, 48129 MuÈnster, Germany 2Rotman Research Institute, Baycrest Centre for Geriatric Care, University of Toronto, Ontario, Canada 3ENT Department, MuÈnster University Hospital, Germany 4ENT-Department, Health Science Centre Sunnybrook, Toronto, Ontario, Canada 5Department of Integrative Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan 6Department of Otolaryngology and Sensory Organ Surgery, Osaka University School of Medicine, Osaka, Japan Keywords: auditory cortex, auditory system, habituation, lateral inhibition, magnetoencephalography, MEG Abstract The goal of this study was to compare the lateral inhibition and the habituation in the human auditory cortex, two important physiological effects during auditory processing that can be reliably measured by means of magnetoencephalography when recording auditory evoked ®elds. Applying 40-Hz amplitude-modulated stimuli allowed us to record simultaneously the slow transient evoked and the steady-state ®elds and thus to characterize the lateral inhibition and the habituation effect in primary and non-primary auditory cortical structures. The main ®nding of the study is that the lateral inhibition effect of non-primary auditory areas as measured on the major component of the slow transient auditory evoked ®eld (N1) is signi®cantly stronger than the corresponding habituation effect. By contrast, this effect was not observed for the 40-Hz steady-state ®elds, characterizing the activation of the primary auditory cortex in humans. The results might be interpreted as (i) evidence that the inhibition mediated by lateral connections is stronger than the habituation of excitatory neurons in the non-primary auditory cortex and (ii) the processing hierarchy in the human auditory cortex is demonstrated by the different behaviour of lateral inhibition and habituation in primary and non-primary auditory cortical structures. Introduction The N1m component of the evoked response to an auditory stimulus is mechanism of diminishing the auditory evoked response when repe- known to decrease in amplitude (and increase in latency) if the time titive stimuli are applied. Lateral inhibition spanning a number of interval to the preceding auditory stimulus becomes shorter. This tonotopic channels has been documented in the inferior colliculus and phenomenon has different names, such as habituation (Thompson higher levels (Muller & Scheich, 1988; Vater et al., 1992). The model & Spencer, 1966; Ritter et al., 1968), adaptation (Tarkka et al., of the auditory lateral inhibition is derived from the classic visual 2002), sensory gating (Boutros & Belger, 1999) and refractoriness lateral inhibition scheme by von BeÂkeÂsy (1967). A neuron in the (Budd et al., 1998). All these terms imply assumptions regarding the central auditory pathway is characterized by its tuning curve deter- origin and the mechanisms of the observed amplitude decrement, mined by a characteristic frequency (CF) and it is surrounded by other although the exact mechanisms, the neuro-anatomical basis and the neurons that tonotopically span a range of CFs. If the neuron is functional signi®cance of the N1m decrement are still not fully activated from a lower level, it projects not only to higher levels, understood. The theoretical de®nition of habituation given by but also distributes inhibition via interneuron collaterals laterally to Thompson & Spencer (1966) includes response decrement, response adjacent neurons with higher or lower CFs of their tuning curves. The recovery and dishabituation, and an increased response after the inhibition effect depends upon the ®ring rate of the neuron and the insertion of a deviant stimulus. However, to make a clear determination number of collaterals. We propose that inhibition mediated by lateral of whether the N1m response decrement is associated with habituation connections can be assumed as an active mechanism that inervates or refractoriness is very dif®cult because they may be superimposed or inhibitory neurons and causes the decrement of the auditory evoked interactive (Picton et al., 1976). In this study we have adopted the name response. By contrast, the habituation can be understood as a passive habituation for the N1m decrement caused by a preceding sound in the inhibitory mechanism that causes the decrease of the auditory evoked spectral range of the stimulus. response through reduction of the sensitivity of excitatory neurons to Lateral inhibition in the central auditory pathway (Ehret & the applied auditory stimuli. Merzenich, 1988; Burrows & Barry, 1990; Suga, 1995) is another In normal hearing subjects, spectrally notched sound (a sound from which the power in a speci®ed frequency band was completely removed) simulates the type of reversible functional deafferentation Correspondence: Dr Christo Pantev, 1Institute for Biomagnetism and Biosignalanalysis, as (Pantev et al., 1999). In a magnetoencephalographic (MEG) experi- above. ment it has been demonstrated that after prolonged exposure to E-mail: [email protected] spectrally notched music, neurons in the auditory cortex responsive Received 6 June 2003, revised 3 February 2004, accepted 5 February 2004 to frequencies within the notch were strongly inhibited. This result was doi:10.1111/j.1460-9568.2004.03296.x 2338 C. Pantev et al. interpreted as re¯ecting the lasting effect of a lateral inhibitory process, amplitude modulated with a 40-Hz sinusoid, resulting in frequency i.e. the inhibitory in¯uence of the stimulated neurons on to those spectra as shown in Fig. 2b and c. This stimulus design allowed us to neighbouring neurons with CFs of their tuning curves within the investigate simultaneously the evoked responses from the primary and notched area. Recently, a psychoacoustic study (Norena et al., the non-primary auditory cortical areas (Engelien et al., 2000). The 2000) and an EEG experiment (Kadner et al., 2002) con®rmed our onset of the stimuli evoked an N1m response (the magnetic counterpart results (Pantev et al., 1999). of the slow auditory evoked potential with a peak amplitude around The goal of this study was to compare simultaneously in a single 100 ms after stimulus onset) originating mainly from non-primary experiment the decrease in activation of the human auditory cortex auditory structures (Pantev et al., 1995), whereas the 40-Hz rhythm of induced by habituation and lateral inhibition, respectively. the amplitude modulation evoked a 40-Hz steady-state response, which has its sources mainly in the primary auditory cortex (Pantev Materialsand methods et al., 1996). Both MSs were of 3 s duration including 20 ms rise and decay Subjects times. The durations of the CS and TS were 500 ms (12.5 ms rise and Ten right-handed subjects (six females, 35.6 Æ 7.7 years) with no decay times). The silent intervals between the CS and MS and history of otological or neurological disorders participated in this between the MS and TS, respectively, were 500 ms; the silent study. Their hearing thresholds were 15 dB hearing level (HL) or interval between a TS and the succeeding CS was 2.5 s, resulting better, in the frequency range from 250 to 8000 Hz as tested by means in a total duration of 7.5 s for the stimulus sequence. Two hundred of pure tone audiometry. The subjects consented to their participation sequences of both stimulus types (PB and SB) and the same MS were after they were completely informed about the nature of the study. The presented in a random order within one session having duration of Ethics Commission of the Baycrest Centre for Geriatric Care approved about 1 h. A second session on a different day was performed for the all experimental procedures, which are in accordance with the Declara- second MS (broad band noise, white noise) and was counterbalanced tion of Helsinki. between subjects. The two stimuli and the two masker sounds were adjusted separately Experimental design and stimulation for the same intensity above normative thresholds obtained from The schema given in Fig. 1 explains the design of the auditory subjective tests on a group of ten subjects. At the beginning of each stimulation. A masking sound (MS) was preceded by a control experimental session the individual hearing threshold for one of the stimulus (CS) and succeeded by a test stimulus (TS), which was stimuli was determined. All stimuli were presented binaurally at the identical to the CS. The masker sounds were two noise signals with intensity of 45 dB sensation level (SL). different spectral properties. The amplitude spectrum of the ®rst MS The stimuli were prepared as sound-®les and presented under (Fig. 2a) contained alternating series of pass- and stop-band sections of control of STIM software (NeuroScan Inc., El Paso, USA) using the same width on the logarithmic frequency scale. The centre ER30 transducers (Etymotic Research, Elk Grove, USA), re¯ection- frequencies of the pass-band sections were spaced by half an octave less plastic tubes of 2.5 m length, and silicon ear pieces, ®tting to the between 0.5 and 2.8 kHz. The suppression in the stop-bands was subject's ears. typically 36 dB. Because of the periodical structure of the spectrum, this MS was called comb-®ltered noise (CFN). It was obtained from a Data acquisition white noise signal by Fourier ®ltering. The spectral distribution of the Auditory evoked magnetic ®elds (AEFs) were recorded with a helmet- second MS is shown in Fig. 2d. It was a broadband noise signal that shaped 151-channel whole cortex neuro-magnetometer (OMEGA, was limited only by the transfer characteristic of the sound delivery CTF Systems Inc., Vancouver, Canada) in a quiet magnetically system. The CS and TS were complex sounds composed from ®ve shielded room. The subjects were placed in a comfortable seated spectral components each, corresponding either to the pass-band position.