A neuromagnetic analysis of the mechanism for generating auditory evoked fields

International Journal of Psychophysiology 56 (2005) 93 – 104 www.elsevier.com/locate/ijpsycho

A neuromagnetic analysis of the mechanism for generating auditory evoked fields Takashi Hamada* National Institute of Advanced Industrial Science and Technology (AIST)-Kansai, 1-8-31, Midoriga-oka, Ikeda, Osaka 563-8577, Japan Received 8 June 2004; received in revised form 14 October 2004; accepted 21 October 2004 Available online 26 November 2004

Abstract Averaged and non-averaged neuromagnetic responses to repetitive transients of sound were analyzed in the frequency and time domains. It was found that ongoing oscillations between 3 and 16 Hz are relevant to the generation of auditory evoked fields (AEF). First, phases of the oscillation were locked at around the timings of N100m, but randomly distributed from trial to trial at the other timings. Secondly, amplitudes of the oscillation were larger on average at around the timings of N100m than at the other timings, although the amplitudes fluctuated from trial to trial with almost the same standard deviations throughout the periods of observation. Thirdly, spatial distributions of the oscillatory activities were often reduced to an equivalent current dipole in the auditory cortex at around the timings of N100m, but seldom reduced at the other timings. An explanation of these results would be to suppose several oscillators within the cortex whose phases are locked at around the timings of N100m, but fluctuated randomly at the other timings. D 2004 Elsevier B.V. All rights reserved. Keywords: Evoked field; Audition; Phase-locking; Ongoing oscillation; Single trial analysis; MEG

1. Introduction If electroencephalogram (EEG) or magnetoencephalogram (MEG) in response to repetitive auditory stimuli are averaged with respect to the stimuli, auditory evoked responses (AER, e.g. Picton et al., 1974) or fields (AEF, e.g. Pantev et al., 1995) emerge. AER and AEF are composed of several peaks with

* Tel.: +81 727 51 8794; fax: +81 727 51 8416. E-mail address: [email protected]. 0167-8760/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpsycho.2004.10.004

different latency and polarities, such as P50(m) and N100(m). Methods of MEG (e.g. Pantev et al., 1995; Herdman et al., 2003) and intracerebral EEG (Gody et al., 2001) localized each of the peaks as a source or sources in the auditory cortex. Besides, the cortex spontaneously yields ongoing oscillations at around the alpha range (Tiihonen et al., 1991). These evidence provide bases for the traditional view as to the mechanism for generating AER and AEF (Rugg and Coles, 1995; Penny et al., 2002). Namely, it has been assumed that raw data of EEG or MEG within each trial of stimulation is a sum of transient signals

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from the sources and ongoing oscillations irrelevant to the stimuli, i.e. noises. Thus, averaging with respect to the stimuli was thought to eliminate the oscillations, while the signals with the shape of AER or AEF are left. We name this view the bsignal plus noise modelQ as to the generation of AEP or AEF. However, recent evidence suggests that the ongoing oscillations are no more irrelevant to the stimuli. First, Barry et al. (2003) showed that amplitudes of the P50 and the N100 depend on the phases of ongoing oscillations within delta and alpha ranges at the timings of stimulation. Secondly, Beagley and Henshall (1974) showed that phases of the oscillations are locked during the period of AER and suggested that this phase-locking is at least a part of the mechanism for producing AER. Recent studies confirmed this view (Jervis et al., 1983; Kolev and Yordanova, 1997; Kolev et al., 2001; Jansen et al., 2003), which is named here the bphase-locking modelQ. Makeig et al. (2002) showed that visual evoked potentials are also generated, at least partly, by the phase-locking of alpha oscillations. The model is revolutionary, because it asserts that phase, rather than amplitude, is the main parameter to be modulated for producing evoked potentials (Penny et al., 2002). Similar words, such as oscillatory synchrony and phase synchrony, are used for representing phaselocking among oscillations, in beta or gamma range during cognitive tasks, observed by electrodes positioned at long distances on the scalp (Rodriguez et al., 1999; Tallon-Baudry, 2003). However, the word bphase-lockingQ is used here for describing generations of evoked potentials or fields, i.e. it refers to locking between phases of oscillations and timings of stimulation. Although the bphase-locking modelQ is recently preferred as the mechanism for generating AER, its details such as the frequency range of the relevant oscillations and the temporal evolution of the phaselocking are not yet fully elucidated. Moreover, the model has been evaluated with respect to the oscillatory signals observed on the scalp. I thereby studied the mechanism not only more quantitatively, but also from the point of oscillator(s) in the brain by applying MEG. Some kinds of signal processing, such as analyses in the frequency or time–frequency domain and estimating a dipole, were applied both to averaged data and to data within each trial.

Considering results of these processing together, I will conclude that both phase-locking and amplitude enhancement of oscillations take place during the periods when the AEF emerges. A hypothesis will be presented for explaining the results.

2. Materials and methods 2.1. Auditory stimuli We used two types of repetitive auditory stimuli. One of the types was composed of tone-bursts. Their duration was short and constant at 100 ms and their frequencies and inter-stimulus intervals (ISI, periods during which no sounds were applied) were randomly changed from trial to trial between 0.5 and 4 kHz and between 1.1 and 2.2 s, respectively. The frequencies were varied, because N100 responses to repetitive tones are known to be larger when frequencies of the tones were varied than when kept to be constant (Butler, 1968; Na¨a¨ta¨nen et al., 1988). In one of the subjects, tone-bursts at a constant frequency of 1 kHz, but with the other parameters same as above, were also used. Onsets of the tones were marked with triggers for later signal processing. The other type of stimuli was composed of pure tones with longer duration: The duration was randomly varied from trial to trial between 1.4 and 2 s, while their frequencies and inter-stimulus intervals (ISI) were varied in the same way as for the tone-bursts. Onsets of the tones were marked with triggers. We used this type of stimuli, because onsets of the longer tones are simple in the sense that they are not immediately followed by offsets, differently from onsets of the tone-bursts. However, the results were the same irrespective of the types of the stimuli (see Results). The tones were generated by a small speaker and delivered to either the right ear or the left of the subjects through a plastic tube of 80 cm long. The sound intensity (around 65 dB SPL) was adjusted to be comfortable to the subjects. 2.2. Experimental procedure Eight subjects participated in this study. They were aged between 22 and 50 years without any histories of neural pathology. Informed consents had been

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obtained from them before experiments. Three small coils were attached on the scalp and their positions relative to the two preauricular points and the nasion were measured with a 3-D digitizer (Polhemus, USA). They then seated with a helmet of MEG (NeuroMag122, Ha¨ma¨la¨inen et al., 1993) on their heads. The head was attached on the back wall of the helmet for minimizing any head motions. Position of the head relative to the sensor array within the helmet was measured by feeding currents to the coils. Then an experiment for measuring MEG signals started. The experiment was composed of four sessions, during each of which a subject repeatedly listened to either

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type of the stimuli through either the right ear or the left. Each session was composed of more than 50 trials and lasted about 2 min. The MEG signals were sampled at 400 Hz and stored in MO disks for later signal processing. 2.3. Signal processing Raw (non-averaged) data of MEG (r) is composed of temporal signals in 122 channels (Fig. 1). The r was averaged (ave) with respect to the triggers, as usual, for yielding AEF. The results are named r-ave for convenience. During averaging, epochs containing

Fig. 1. Procedures of signal processing. Raw data (r) was averaged (ave) with respect to triggers for yielding the evoked field (r-ave or AEF). By positioning the center of a Hanning window either at
244 ms or at 106 ms with respect to the triggers in r-ave, we calculated the magnitude spectrum (magnitude or square root of power vs. frequency, spct(mag)) of r-ave before and during AEF, respectively (r-ave-spct(mag)). As an complementary processing, spct(mag) of r within each trial was first calculated by positioning the Hanning window either before or during AEF, and the spct(mag) of all the trials within a session were averaged for yielding r-spct(mag)-ave of either before or during AEF. If spct(mag) in the above processing was replaced by spct(phase), the averaged spectrum of phases (defined between Fp) either during or before AEF is obtained (r-spct(phase)-ave). If the raw data is band-pass filtered between 3 and 16 Hz (bpf), rectified (abs) and then averaged (ave), the result (r-bpf-abs-ave) reflects both the phase-locked and -unlocked components. If the rectification was omitted, the result (r-bpf-ave) reflects only the phase-locked components. Standard deviations (SD) of amplitude in r-bpf were also calculated (r-bpf-SD). The above sets of processing were carried out in each of 122 channels. Sources in the brain was estimated (x-fit) from r-ave as usual (r-ave-fit) and also from rbpf within each trial (r-bpf-fit). Two boxes with the same numbers in the figure represent results of processing complementary each other.

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large-amplitude (N3000 fT/cm) artifacts were automatically rejected; The number of averaging was more than 50. Fig. 2a shows 122 traces of r-ave above the whole cortex when a subject (S1) heard the tonebursts through his left ear. Traces in the two channels that yielded the largest N100m peaks within each hemisphere are surrounded by circles, and the right trace is enlarged with a continuous line in Fig. 2b. Sources in the brain were estimated (x-fit) from r-ave at the timings of N100m (r-ave-fit). Namely, selecting 24 channels above the left temporal cortex or the right (shown by trapezoids in Fig. 2a), we searched an equivalent current dipole (ECD) with goodness of fit (Ha¨ma¨la¨inen et al., 1993) more than 80% at around 100 ms after the triggers. The origin of the conductor model of the head used in the fitting was determined from MR images of the subjects. Since the MR images were available only in three of the subjects, only their r-ave-fit will be described. The r-ave was also used for calculating its magnitude spectrum (magnitude or square root of power vs. frequency, spct(mag), fft size=256 points). Namely, positioning the center of a Hanning window (640 ms in length) at either
244 ms or at 106 ms with respect to the triggers, we calculated the magnitude spectrum of r-ave before or during the

period of AEF (r-ave-spct(mag)). Note the processing was carried out in each of the 122 channels. Continuous and broken lines in each of the subfigures in Fig. 3a represent examples of r-ave-spct(mag) in one of the channels during and before AEF, respectively (for details, in Results). R-ave-spct(mag) before AEF was served just as a control. Thus it was subtracted from r-ave-spct(mag) during AEF for yielding r-ave-spct(mag) due to AEF by itself (continuous lines in Fig. 3c). For a comprehensive grasp, reminders after the subtractions were averaged among the 24 channels above either the left temporal cortex or the right (surrounded by trapezoids in Fig. 2a) in each of the subjects, and then further averaged across the subjects for yielding grand averages of differences in r-ave-spct(mag) of either the left temporal cortex or the right (upper two traces in each of the four subfigures in Fig. 4). The raw data (r) was also processed as follows. First, by placing the center of the Hanning window at either
244 or 106 ms with respect to each of the triggers in r, we calculated spct(mag) before or during AEF within each of the trials in a session. Then the spct(mag)’s of all the trials were averaged for yielding r-spct(mag)-ave before and during AEF of the session (broken and continuous lines in Fig.

Fig. 2. (a) Evoked responses (r-ave) in 122 channels above the whole cortex. Stimulus: tone-bursts to the left ear. Small circles surround traces with the maximum N100m peaks within each of the left and right hemispheres. Ranges of the channels for source estimations and for calculating grand-averages are surrounded by trapezoids, one above the left hemisphere and the other above the right. Vertical bar: onset of the stimulus and 100 fT/cm. Horizontal bar: 100 ms. Subject: S1. (b) AEF or r-ave (continuous line) and r-bpf-ave (broken line) in a channel surround by the right circle in (a). Others are the same as in (a).

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Fig. 3. (a) Magnitude spectrum of the evoked response (r-ave-spct(mag)) before (broken pffilines) and during (continuous lines) AEF in two (left and right) channels, which were surrounded by circles in Fig. 2a. Vertical bar: 10 fT/cmd Hz. Horizontal thick bar: 10 Hz. Others are the same as in Fig. 2. (b) Magnitude spectrum of the raw data (r) before (broken lines) and during (continuous lines) AEF, averaged across trials in a session (r-spct(mag)-ave). Others are the same as in (a). (c) Differences between the two traces in (a) (continuous lines) and in (b) (broken lines). Others are the same as in (a).

3b). Then, r-spct(mag)-ave before AEF was subtracted from that during AEF. The reminders, shown by broken lines in Fig. 3c, were then averaged among the 24 channels above either the left temporal corex or the right in each of the subjects, and further grandaveraged across the subjects (lower two traces in each of the subfigures of Fig. 4), in the same way as for the grand-averages in r-ave-spct(mag). As another processing, phase spectrum (phase angle defined between Fp vs. frequency, spct(phase), fft size=256 points) was calculated by applying the Hanning window before or during AEF within each trial, and then averaged across trials within a session for yielding r-spct(phase)-ave of before and during AEF. If phases at different frequencies fluctuated uniformly between Fp from trial to trial before AEF, r-spct(phase)-ave at each of the frequencies would be close to zero. In contrast, if phases at certain frequencies were locked during AEF, r-spct(phase)-

ave during AEF should yield some nonzero values between Fp at the frequencies. For a comprehensibe grasp, the r-spct(phase)-ave was grand-averaged in the same way as above: R-spct(phase)-ave before AEF was subtracted from that during AEF, and the reminders were averaged within the several channels and then grand-averaged across the subjects (Fig. 7). The raw data (r) was processed in the time– frequency domain as follows. Namely, r was passed through a band-pass filter between 3 and 16 Hz and 640 ms in length (bpf). Then, the results were averaged with respect to the triggers for yielding temporal evolutions of the means in r-bpf (r-bpf-ave, the broken line in Fig. 2b and the lower continuous lines in each of the subfigures of Fig. 5). Note that rbpf-ave is the same as r-ave-bpf, where r-ave is first calculated and then applied by bpf, because both ave and bpf are linear operations. The r-bpf-ave reflects only the phase-locked components in r-bpf, because

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Fig. 4. Grand averages of the differences between before and during AEF in r-ave-spct (mag) (upper two traces in each of the four subfigures) and in r-spct(mag)-ave (lower two traces in each subfigure). The left and right subfigures are for the left and right hemispheres, respectively. Stimulated ear was either left (a) pffior right (b). Auditory stimuli were either tone-bursts (continuous lines) or onsets of the longer tones (broken lines). Vertical bar: 2.5 fT/cmd Hz. Horizontal thick bar: 10 Hz.

the phase-unlocked components are cancelled out after sufficient number of averaging. As a measure how much the amplitudes of r-bpf fluctuate across the trials, we calculated standard deviations (S.D.) with respect to the means in r-bpf (r-bpf-SD, mostly flat lines above the baselines in each of the subfigures of Fig. 6). As a processing complementary to r-bpf-ave, the signal after bpf within each trial was first rectified (abs) and then averaged (r-bpf-abs-ave, upper continuous lines in each of the subfigures in Fig. 5). The r-bpf-abs-ave is the same processing as the btemporal spectral evolutionQ (TSE; Salmelin and Hari, 1994), except that baselines before triggers were not set to be zero in this study. In contrast to rbpf-ave, this r-bpf-abs-ave reflects both the phaselocked and -unlocked components, because abs prevents the phase-unlocked components to be cancelled out by the averaging, similarly as the processing of event-related synchronization/desynchronization (ERS/ERS, Pfurtscheller and Lopes da Silva, 1999) where rectifing is replaced by squaring.

For being compared with r-bpf-abs-ave, r-bpf-ave was further rectified (abs) for yielding r-bpf-ave-abs (Fig. 5, broken lines). Finally, an equivalent current dipole was searched (x-fit) from the band-passed data within each trial (r-bpf-fit, Fig. 8), with exactly the same procedures as r-ave-fit.

3. Results The broken and continuous lines in the left of Fig. 3a are r-ave-spct(mag)’s in one of the channels above the left temporal cortex of a subject before and during AEF, respectively. The difference between the two traces (the continuous line minus the broken line) was plotted with the continuous line in the left of Fig. 3c. The continuous line in the right of Fig. 3c was similarly calculated from the two traces in the right of Fig. 3a. Both the continuous traces in Fig. 3c were peaked at around 6 Hz. As already described in the section of signal processing, if the bsignal plus noise modelQ holds, each of the continuous traces in Fig. 3c

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Fig. 5. r-bpf-abs-ave (the upper continuous line in each of the four subfigures), r-bpf-ave (the lower continuous lines in each subfigure) and rbpf-ave-abs (the broken line in each subfigure). The left and right subfigures are for a left and a right channel, respectively. Vertical bar: onset of stimulus and 100 fT/cm. Horizontal bar: 100 ms. (a): S1, (b): S2. Others are the same as in Fig. 2b.

should represent the magnitude spectrum of the signal component above the left temporal cortex or the right, respectively. The traces in Fig. 3b are r-spct(mag)-ave’s before (broken line) and during (continuous line) AEF. Note spct(mag) and ave were applied to r here in the order opposite to the above processing. If the bsignal plus noise modelQ holds, r-spct(mag)-ave during AEF should be spct(mag) of the signal plus that of the noises (oscillations), while r-spct(mag)-ave before AEF should be composed of only the latter. Then, their differences shown by broken lines in Fig. 3c should again correspond to spct(mag) of the signals. Thus, the continuous and broken traces in each subfigure of Fig. 3c should coincide. However, the broken line was lower than the continuous line in each of the subfigures at around their peaks. Fig. 4 shows grand-averages of the differences between during and before AEF in r-ave-spct(mag) (upper two traces in each of the four subfigures) and

in r-spct(mag)-ave (lower traces in each subfigure). The left and right subfigures are for the left and right hemispheres, (a) to the stimulation of the left ear and (b) to the right, and the stimuli were the tone-bursts (continuous lines) or onsets of the longer tones (broken lines), respectively. In spite of these differences, the results were essentially the same and also close to those in Fig. 3c (the peaks were lower in Fig. 4 than in Fig. 3c, because the formers reflect signals in several channels with non-maximum values). Four points should be mentioned. First, the traces in each subfigure peaked at around 6 Hz. Secondly, traces for r-ave-spct(mag) were higher than the corresponding traces for r-spct(mag)-ave: The range of frequency where the differences between the two were commonly significant was between 3 and 16 Hz (onetailed paired t-test, pb0.05). The third point is a generalization of the argument that was already made on Fig. 3c. Namely, if the bsignal plus noise modelQ holds, the differences in r-ave-spct(mag) and those in

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Fig. 6. (a) Superimpose of r-bpf within consecutive 20 trials. The continuous line above the baseline shows +S.D. of the amplitudes in r-bpf across the trials. The stimuli were tone-bursts whose frequencies were varied from trial to trial. Vertical bar: onset and 10 fT/cm. Horizontal bar: 100 ms. S1. (b) Same as in (a), but the frequency of the tones was kept at 1 kHz. S1. (c): S2. Others are the same as in (a).

r-spct(mag)-ave should both represent spct(mag) of the signals and thereby should coincide, but these were not the case. This means that the bcomponents plus noise modelQ does not hold, irrespectively of the hemispheres, stimulated ears and types of the tones. The fourth point is related to the bphase-locking modelQ. If the model implies changes only in phase, but no changes on average in amplitude of the oscillations, then r-spct(mag)-ave should be the same between before and during AEF, i.e. broken and continuous lines in Fig. 3b should coincide; In other words, the differences between the two, which are plotted by the broken lines in Fig. 3c and also by the lower two traces in each of the subfigures in Fig. 4, should be zero. However, these were evidently not the case, which means that the bphase-locking modelQ in the above strict sense does not hold.

Results by analyses in the time–frequency domain further confirmed and extended the above results. First, shapes of r-bpf-ave (broken line in Fig. 2b) mostly coincided with that of r-ave (continuous line in Fig. 2b). This means that r-ave (evoked field) was mostly made of frequency components between 3 and 16 Hz defined by bpf. Now, the upper continuous lines in Fig. 5 show r-bpf-abs-ave. First, the traces before the triggers were shifted upward mostly in parallel with the baselines, which means that there constantly exist oscillations between 3 and 16 Hz even before the stimulation. The lower continuous lines in the figure are r-bpf-ave and the broken lines their rectification (r-bpf-ave-abs). Interestingly, timings and amplitudes of the main peaks in r-bpf-abs-ave and r-bpf-ave-abs coincided: The peaks that coincided always included N100m, but one or both of the adjacent peaks, P50m and P200m, were often additionally included. Since r-bpf-absave reflects both phase-locked and -unlocked components while r-bpf-ave-abs reflects only the former, the above results mean that the N100m peaks and often their adjacent peak(s) were composed of only phase-locked activities. In other words, phaseunlocked components did not exist at around the timings of N100m. It should also be noted that the amplitudes of the peaks in r-bpf-abs-ave were higher than the levels of the traces before the triggers. This again shows that the bphase-locking modelQ in the above strict sense, i.e. phase-locking without any changes in amplitude, does not hold. In summary, the oscillations were not only phaselocked, but also increased in amplitude at around the timings of N100m. These properties were held irrespectively of hemispheres, stimulated ears and types of the tones in all of the subjects. The results described so far are after averaging. If we look at r-bpf’s within each of the trails, amplitudes of the oscillations were found to fluctuate from trial to trial to the same extent irrespective of before, during and after AEF (Fig. 6a for a subject and c for another subject). Namely, temporal evolutions of S.D. of the amplitudes (continuous lines above the baselines) were mostly kept to be constant before, during and after AEF. The stimuli used in these experiments were the tone-bursts whose frequencies were varied from trial to trial. However, the above variability in amplitude cannot

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Fig. 7. Grand averages of differences between before and during AEF in r-spct(phase)-ave. Left part of the figure is for the left hemisphere, the right for the right hemisphere. Continuous lines (—): Tone-bursts to the left ear. Finest broken lines (- - -): Tone-bursts to the right ear. Moderately broken lines (– –): Onsets of longer tones to the left ear. Coarsest broken lines (— —): Onsets of longer tones to the right ear.

be attributed to the variability in frequency of the tones, because the amplitudes still fluctuated throughout observations including during the period

of AEF even if the stimuli were the tone-bursts whose frequencies were kept to be constant from trial to trial (Fig. 6b).

Fig. 8. (a, b) r-bpf in one of the channels. The vertical broken lines are the timings (t 1) for r-bpf-fit. Vertical bar: onset of the tones and 100 fT/ cm. Horizontal bar: 100 ms. (a): S1, (b): S2. (c, d) Contour maps of the magnetic field at t=t 1 for the bpf shown in (a) and (b). Continuous and broken lines are upward and downward flux of the field, respectively. Contour step is 20 fT. The arrow represents the dipole. (c): above the right cortex of S1. (d): above the left cortex of S2. (e, f) Magnitudes of the dipoles (upper traces) and goodness of fit (gof, lower traces) of the dipoles in (c, d) vs. time. (e) corresponds to the upper subfigures in (a) and (c), similarly for (f). Vertical scale: 10 nAm and 10%. Horizontal scale: 20 ms. gof at t=t 1 is N90% in (e) and N80% in (f).

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Phases of the oscillations within each of the trials behaved differently, however. As Fig. 6 shows, the phases fluctuated before and after AEF, but mostly locked (the phases were aligned) during AEF. Fig. 7 shows grand averages of differences between before and during AEF in r-spct(phase)-ave within the left or the right hemisphere. Although the traces before AEF were close to zero (not shown), the differences had non-zero values at around 6 Hz, irrespectively of stimulated ears, hemispheres and types of the tones. This again suggests that the phases at around 6 Hz were locked during the period of AEF. As is already known (e.g. Pantev et al., 1995), N100m peaks in r-ave (Fig. 2) yielded the so-called dipole patterns, from which a dipole was estimated in the auditory cortex (r-ave-fit, the small rectangle with an arrow in Fig. 9). Interestingly, peaks at the timings of N100m in r-bpf (Fig. 8a for a subject, b for another subject) often yielded similar dipole patterns (Fig. 8c,d), from each of which a dipole could be estimated (r-bpf-fit) with goodness of fit more than 80% (Fig. 8e,f, lower traces). The position and orientation of the dipole (the small circle with an arrow in Fig. 9) mostly coincided with those estimated from r-ave. Now, suppose that the bphase-locking modelQ implies only one oscillator within each of the temporal

Fig. 9. Positions (small square and circle) and orientations (arrows) of the dipoles in the coronal section of MR image of S1. The square is for the dipole estimated from r-ave-fit, the circle for the dipole from r-bpf-fit.

cortices, whose phases are locked during AEF. Then, r-bpf-fit should yield the same dipole at the other peaks even before and after AEF. However, as a matter of fact, r-bpf seldom showed the dipole patterns before and after AEF, thus a dipole could not be estimated by r-bpf-fit with goodness of fit more than 80% (Fig. 8a). Thus, the bphase-locking modelQ does not imply only one oscillator within each of the temporal cortices.

4. Discussion We tested whether generations of the auditory evoked field can be explained by the bsignal plus noise modelQ, where bsignalQ refers to sequential activities of several sources in the auditory cortex and bnoiseQ refers to ongoing oscillations irrelevant to stimulation. For testing this issue, we calculated the magnitude spectrum (square root of power vs. frequency, spct(mag)) in two ways. On one hand, we averaged the raw data (r) with respect to triggers, for yielding the auditory evoked field (AEF or r-ave) and then its spct(mag) was calculated by positioning a Hanning window either before and during the periods when AEF emerged (r-ave-spct(mag)). If the model holds, r-ave-spct(mag) during AEF minus that before AEF should correspond to spct(mag) of the signal. On the other hand, we calculated spct(mag) of r either before or during AEF within each trial and then averaged these spectrums across trials (rspct(mag)-ave). If the model holds, r-spct(mag)ave during AEF should be spct(mag) of both the signal and the noise, while r-spct(mag)-ave before AEF should reflect only spct(mag) of the noise. Then, r-spct(mag)-ave during AEF minus that before AEF should again represent spct(mag) of the signal and be the same as the difference in r-ave-spct(mag). However, the difference in r-ave-spct(mag) was always larger than that in r-spct(mag)-ave at the frequencies between 3 and 16 Hz. Thus, the bsignal plus noise modelQ did not hold. The alternative bphase-locking modelQ (Beagley and Henshall, 1974; Jervis et al., 1983; Kolev and Yordanova, 1997; Jansen et al., 2003) supposes that phases of the ongoing oscillation are locked during the periods of AER. For testing this model, we calculated r-spct(phase)-ave, which suggested the

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phase-locking during AEF at around 6 Hz. For elucidating how the phase-locking temporally evolves, we calculated r-bpf-abs-ave and r-bpf-aveabs. First, as the prerequisite of the model, r-bpf-absave showed that there exist constant oscillations at frequencies between 3 and 16 Hz. Secondly, N100m and often its adjacent peak(s) in r-bpf-abs-ave coincided with those in r-bpf-ave-abs both with respect to their timings and to their amplitudes. This means that the peaks derive from phase-locking of the oscillation and any phase-unlocked components do not exist at around the timings of N100m. Moreover, r-bpf’s in several trials directly showed phase-lockings of the ongoing oscillations. Thus, the results described so far were consistent with the bphaselocking modelQ. However, if the model is strictly defined as if the amplitudes of the oscillations do not change at least on average, then the following results were not compatible with the model. First, if the model defined as above holds, r-spct(mag)-ave should be the same between before and during AEF. However, in fact, rspct(mag)-ave was always larger during AEF than before. Another analysis more directly showed that the peaks in r-bpf-abs-ave and r-bpf-ave-abs were higher than the levels in r-bpf-abs-ave before AEF. Cacase et al. (2003) also described similar increase of amplitude at less than 10 Hz during the period of AER. In summary, the present results confirmed that not only the phases are locked, but also their amplitudes are increased during AEF. Our final analysis of r-bpf-fit resolves the above complexity as to the bphase-locking modelQ. Before describing this issue, it should be mentioned that some studies have already succeeded in estimating sources in the brain from band-passed data within each trial (Liu et al., 1998; Ishii et al., 2000). These studies used similar pass-bands (Liu et al.: 3–20 Hz; Ishii et al.: 6–8 Hz), but the former analyzed only during the period of AER and the latter in an abnormal situation of the auditory hallucination in schizophrenia. We also could estimate a dipole at the timings of N100m within each trial (r-bpf-fit, Fig. 8), but importantly the estimation was seldom successful before or after AEF. Thus, it is not plausible to suppose only one oscillator within each hemisphere. One possible explanation would be to suppose multiple oscillators within each of the auditory cortices,

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whose phases would be locked at around the timings of N100m, but unlocked at the other timings. The locking of the phases could explain not only why the activities were reduced to a dipole during the period of AEF, but also why the amplitude was increased during AEF than before and after AEF. The unlocking could explain spatial complexities of the magnetic field before and after AEF. Recordings of local field potentials at multiple sites or optical image recording could settle the above predictions.

Acknowledgement The author thanks Dr. S. Iwaki of AIST and Dr. H. Yoshida at Kitami Institute of Technology for their critical readings of this manuscript.

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