1Research Institute of Developmental Physiology, 119121 Pogodinskaya 8-2, Moscow, Russia; 2Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, 1005 Lausanne, Switzerland; 3Smith-Kettlewell Eye Research Institute, San Francisco, California 94115; 4Department of Neurology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; and 5Division of Neuroanatomy and Brain Development, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden
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ABSTRACT |
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Knyazeva, M. G., D. C. Kiper, V. Y. Vildavski, P. A. Despland, M. Maeder-Ingvar, and G. M. Innocenti. Visual Stimulus-Dependent Changes in Interhemispheric EEG Coherence in Humans. J. Neurophysiol. 82: 3095-3107, 1999. We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.
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INTRODUCTION |
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Over the last few years, animal studies of brain
rhythms in the gamma band (>20 Hz) revealed two correlates of alert
states during sensory stimulation or active behavior: local
synchronization of activity, reflected in a power increase, and/or
distant synchronization between remote cortical areas, shown by
cross-correlation or coherence analyses (Bressler et al.
1993; Eckhorn 1994
; Engel et al.
1991
; Kreiter and Singer 1992
). The importance
of these findings is twofold. First, the synchronization of cortical
activity might represent the neural substrate for Gestalt-type
perceptual operations (reviewed in Singer and Gray 1995
;
von der Malsburg 1995
). Second, to the extent that the
distant synchronization of fast cortical activity depends on
cortico-cortical connections (Engel et al. 1991
;
Munk et al. 1995
; for other references see Kiper
et al. 1999
), its analysis might provide a way of assessing the
functional connectivity between cortical areas. This would be
particularly desirable in human studies, for which reliable methods for
analyzing cortico-cortical connections are scarce.
In animal studies, activity changes in the gamma frequency band were
detected by intracortical recordings, an invasive technique mostly
unusable in humans. On the other hand, the mere possibility of
recording gamma activity from the human scalp recently was a debated
topic (Lutzenberger et al. 1997; Menon et al.
1996
). Thus it is important to determine whether stimulus- and
connectivity-dependent changes of fast brain rhythms can be reliably
identified by electroencephalographic (EEG) techniques in humans. This
study was designed to replicate in humans the essential features of the
animal experiments reported by Kiper et al. (1999)
. In
that paper, we showed that in ferrets, stimulus-induced distant
synchronization of cortical activity similar to that reported in cats
and monkeys could be detected using epidural EEG recording and analysis
of the interhemispheric coherence. An increased coherence in the gamma
band was obtained for visual stimuli that activate callosally connected
neuronal pools in the two hemispheres, suggesting that coherence
changes can indeed be used to assay cortico-cortical connectivity.
A few noninvasive EEG and magnetoencephalography (MEG) studies
in humans described gamma band responses to stimuli of different modalities (Desmedt and Tomberg 1994; Joliot et
al. 1994
; Kristeva-Feige et al. 1993
;
Lutzenberger et al. 1995
; Makeig 1993
;
Müller et al. 1996
; Pantev et al.
1991
; Pullvermüller et al. 1995
;
Sannita 1994
; Sannita et al. 1995
;
Tallon et al. 1995
; Tallon-Baudry et al.
1997
; Tiitinen et al. 1993
). In the visual
domain, Müller et al. (1996)
observed a gamma
power increase in occipital and parietal regions in humans viewing a
single moving bar but not two bars moving in opposite directions.
Similarly, Lutzenberger et al. (1995)
found that gamma
band power increased in the occipital region in response to coherently
moving bars. Recently, Tallon-Baudry et al. (1997)
reported a wide-spread transient power increase in the gamma band when
human subjects were able to detect a figure hidden in a background. The
results of these experiments are considered to support the hypothesis
that the binding of perceptual features is achieved by synchronization
of activity in the gamma band. However, it remains unclear which
specific neural circuits are responsible for the synchronization.
In conclusion, it remains to be proven that cortico-cortical
connections participate in synchronizing cortical activity in humans,
as it appears to be the case in animals. This motivated the present
study of stimulus induced power and coherence changes of EEG signals.
The rationale for analyzing specifically the interhemispheric coherence
dynamics induced by visual stimuli is identical to that discussed in
relation to the animal work (Kiper et al. 1999), under
the assumption that the relevant features of callosal connections between the visual areas are preserved across species, including man.
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METHODS |
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Subjects and experimental procedures
Nine adult volunteers (5 women, 4 men), 19-37 years of age and without neurological history, participated in this study. All subjects but one were right-handed and had normal or corrected to normal vision. The EEGs were recorded in the resting state (both with closed and open eyes) and during visual stimulation. The ongoing EEG tracings were constantly monitored during the experiment to keep the subject's wakefulness level and the quality of recording under steady watch. To check the within-subject reliability of our data, the EEGs of two subjects were recorded twice at the 4- to 5-mo interval. All the procedures conformed to the Declaration of Helsinki (1964) by the World Medical Association concerning human experimentation.
Visual stimulation
The stimuli were presented on a Eizo T-560 i monitor, driven by
an AT Truevision Vista graphics board, with a refresh rate of 104 Hz,
interlaced. A small white square in the center of the screen served as
fixation point and was alternated with stimulus frames. The subjects
were instructed to maintain their gaze on the fixation point. Adequate
fixation was monitored by on-line video recordings. The stimuli were
vertical rectangular patches of black-and-white sinusoidal gratings,
with a space-averaged luminance of 32 cd/m2,
presented on a uniform background of equal luminance. At the viewing
distance we used (42 cm), the screen subtended 39 by 28° of visual
angle, and the patches 13 by 24°. All the sinusoidal gratings had a
spatial frequency of 0.5 c/deg, a contrast of 50%, and drifted with a
temporal frequency of 2 Hz. The stimuli described below were presented
in individual sequences repeated for a minimum of 50 times and
randomized across subjects. Each stimulus was presented for 2 s (a
duration shown to be appropriate by our animal experiments,
Kiper et al. 1999). The interstimulus interval was variable, and averaged ~1.5 s. Longer intervals (breaks) were introduced when the subjects showed signs of fatigue or discomfort.
1) Left hemifield stimulus. A single patch of horizontally oriented, downward drifting gratings was presented to the left of the fixation point. The center of the patch was located 7° from the fixation point.
2) Right hemifield stimulus. Identical to 1), but presented to the right of the fixation point.
3) Bilateral identical stimuli. Gratings 1) and 2) were simultaneously presented. Therefore a vertical strip of visual field of 0.5° on each side of the vertical meridian (VM) was not stimulated.
4) Bilateral different stimuli. The grating to the left of the fixation point was as described above, but that on the right was vertically oriented and drifted to the right.
In addition to these four "close" conditions, we ran the same stimulations with gratings located further away from the fixation point. In that case, the patch centers were located 13° to the side of the fixation point. Therefore the gratings did not stimulate a vertical strip of 6.5° on each side of the VM. We refer to these as the "far" conditions.
5) Whole screen identical stimulus. This consisted of a single patch of downward drifting horizontal grating (27 by 24°) centered on the fixation point.
6) Whole screen different stimuli. In this case, we presented a patch equal in extent to the whole screen identical stimulus consisting of a horizontal downward drifting grating on the left, and of a vertical rightward drifting grating on the right.
7) Background. As a reference condition, we used a uniform gray screen with same space-averaged luminance as the other stimuli.
The stimulation protocol for humans was, thus similar to that of our
animal experiments (Kiper et al. 1999).
EEG recording and processing
The EEGs were recorded according to the 10-20 system
(Jasper 1958; Nuwer et al. 1994
) from
Fp1, Fp2, F3, F4, C3, C4, P3, P4, O1, O2, T3, T4, T5, and T6 referenced
to Fpz using a Neurofax encephalograph (Deltamed, France).
Electrode sites determined by conventional measurements were treated
with abrasive paste, and Ag-AgCl cup electrodes were affixed with
collodion and filled with conductive electrode paste. This procedure
allowed us to keep all electrode impedance below 5 k
for extended
periods of time. The signals were filtered by an analogue band-pass
filter (time constant of 1 s, upper cutoff at 100 Hz), a 50-Hz
notch filter, and sampled at a frequency of 256 Hz to avoid
contamination of the band under study (
46 Hz) from undersampled
higher frequency components. We used the PC-based "EEG Lab"
software package (Metrica, Moscow, Russia) for spectral processing.
Several methodological issues should be taken into account while
analyzing gamma activity by means of noninvasive EEG techniques (Jürgens et al. 1995; Lutzenberger et al.
1997
; Pulvermüller et al. 1997
). Because
coherence data depend on the derivation type (Andrew and
Pfurtscheller 1996
) and, in particular, are highly sensitive to
signal variations at the common reference (Fein et al.
1988
), we checked the reproducibility of our results under different montage schemes. Because there exists no universally accepted
reference electrode, we digitally converted our initial Fpz reference
into common average, bipolar, and ipsilateral earlobe reference
montages, which all emphasize different properties of the EEG signals.
In general, the common average reference acts like a spatial high-pass
filter removing the DC component from the recorded signal
(Lehmann 1986
). However, if relatively few electrodes
are used, the signal recorded from each active electrode can have a
significant impact on the reference level, and this can lead to the
emergence of spurious coherence changes over brain areas that are not
really reactive (Gibbs and Gibbs 1984
; Reilly 1993
). Bipolar derivation potentially gives information on
local voltage gradients but is highly dependent on the choice of
electrode pairs and on the spacing between the electrodes. Electrode
pairs located above co-active brain areas can thus fail to detect
significant voltage differences (Osselton 1966
,
1969
). Under our experimental conditions, ipsilateral
earlobe reference electrodes represent a good approximation of an ideal
remote reference point, not contaminated by visual cortex activity,
which is the focus of our study. In this case, any observed visual
stimulus-dependent changes in interhemispheric coherence cannot be
ascribed to the influence of a common reference, each hemisphere having
its own independent reference electrode.
To obtain statistically reliable spectral parameters, 36-70 artifact-free EEG epochs, each of 2-s duration, were selected and processed in each experimental condition for every subject. Subsequently, to test the stability of the changes, the first and the second halves of the 2-s epochs were extracted and processed separately.
The EEG segments containing artifacts, including those due to eye movements and excessive muscle activity, were identified on visual inspection and eliminated from further analysis.
To avoid a potential contamination of the data with muscle artifacts,
the individually averaged spectral functions were carefully inspected
within the frequency range 1-100 Hz. All subjects' responsive EEG
frequencies were lower than 50 Hz, below the range of frequencies that
is typical of muscle activity (Cacioppo et al. 1990).
Thus a significant impact of muscle activity was highly improbable.
Spectral power density (SPD) for every channel and coherence functions
for symmetrical interhemisperic pairs of leads (ICoh) were calculated
by averaging the primary spectral estimates (computed by fast Fourier
transformation) over all epochs and smoothing the averages by Parsen's
window. Coherence function (Coh) between two signals x
and y at each frequency f was then
calculated as
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Statistical analysis
Preliminary visual inspection suggested that stimulus-specific
responses were elicited within the beta-gamma band, i.e., at frequencies between the alpha range and 50 Hz. However, in some subjects, the beta1-frequencies (14-25 Hz) appeared to be contaminated by harmonics of the alpha rhythm and, therefore could not be used in
all subjects. Thus the resulting gamma band was determined as 25-46
Hz. Because alpha band also seemed to be responsive, it was quantified
for the standard range of 8-12 Hz, which well fitted all our subjects.
For group data analysis, the individual ICoh and SPD responses for the
bands defined above were computed as the differences between the band
averages in stimulus and background conditions. Then, the ICoh
responses were analyzed as a dependent variable with ANOVA (SPSS,
version 7.5). Although their distribution was not normal, we performed
ANOVA, because it is robust against deviations from normality, provided
that there is the same number of cases in all the groups under
comparison, and that their dispersions are not grossly inhomogeneous
(Kelly et al. 1997; Morrison 1990
). These
conditions being satisfied, we assessed the effects of stimulation (factor Stimulus), electrode pair location (factor Location), and EEG
frequency band (factor Band) on ICoh responses in the group of nine
subjects. The Stimulus factor included three levels (stimuli):
whole-screen, identical-close, and different-close. The Location factor
had levels corresponding to interhemispheric pairs O1/O2, P3/P4, T5/T6,
T3/T4, C3/C4, F3/F4, and Fp1/Fp2 with ipsilateral earlobe or common
average references; or to bipolar pairs O1-P3/O2-P4, O1-T5/O2-T6,
P3-C3/P4-C4, P3-T5/P4-T6, C3-F3/C4-F4, F3-Fp1/F4-Fp2. The Band factor
had two levels: the alpha (8-12 Hz) and the gamma (25-46 Hz) ranges.
Analyses of variance for different EEG montages (with ipsilateral
earlobe reference, common average, and bipolar) were performed
separately. For the analysis of SPD, where application of ANOVA was
questionable because of significant inhomogeneity of the data, we used
the Friedman test for several related samples, which does not assume a
normal distribution of the data. Multiple comparisons were performed
using the conservative Tamhane's T2 test for samples with unequal variances.
Having in mind to use EEG coherence analysis in future studies of individual cases, we gave special consideration to the reproducibility of the data both within and between subjects. To this end, we applied the nonparametric Wilcoxon's test to mean band values of the SPD and ICoh for single epochs of 2 s using built-in routines of the "EEG Lab."
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RESULTS |
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Group data analysis of ICoh changes under visual stimulation
A three-way ANOVA with the following fixed factors: Band (alpha vs. gamma), Stimulus (whole-screen, identical-close, different-close) and Location (symmetrical electrode pairs; see METHODS) was performed on the individual ICoh responses, separately for each of the three montage schemes. For ipsilateral earlobe referenced data, the Band and Stimulus factors were highly significant (F1,349 = 131.21, P < 0.0005 for Band and F2,349 = 11.74, P < 0.0005 for Stimulus). Their interaction (F2,349 = 11.48, P < 0.0005) indicates that the ICoh responses to the various stimuli were clearly different in the two frequency bands under consideration. Location failed to reach statistical significance (F6,349 = 1.99, P = 0.066) but significantly interacted with Band (F6,349 = 6.84, P < 0.0005). This suggests that the topographical variations of the ICoh responses were band-specific. Figure 1, A-C, illustrates these results.
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Indeed, responses in the alpha band consisted in a decreased ICoh in all the derivation pairs and stimulus conditions (Fig. 1A) in contrast to the gamma band location- and stimulus-specific coherence increases (Fig. 1B). Thus the next step was to analyze variance in the gamma band alone.
A two-way ANOVA with Stimulus and Location as factors and ICoh response as a dependent variable confirmed the main effects of both factors at a significance level of P < 0.0005 (F2,174 = 23.14 for Stimulus and F6,174 = 6.20 for Location). The interaction between them was also significant (F12,174 = 1.99, P = 0.029).
Multiple comparisons showed that the ICoh response to the whole screen
stimulation was higher than to any of the other two stimuli
(identical-close or different-close; P < 0.05) in
occipital, parietal, posterior temporal, and central pairs. The ICoh
responses associated with the whole screen stimulation depended on the
location of the electrode pair. Parietal and occipital responses were
similar (P = 0.927): both were larger than the frontal
(Fp1/Fp2 and F3/F4) and anterior temporal (T3/T4) pairs
(P < = 0.001), and marginally larger than central
(C3/C4) and posterior temporal (T5/T6) responses (P 0.1). No other stimulation condition resulted in such a
location-specific pattern of responses.
Similar results were obtained with common average reference (Fig. 1C), except for a significant ICoh increase during the whole screen condition in the Fp1/Fp2 pair. However, the latter was not confirmed with bipolar derivations (see following text), suggesting that this frontal response is an artifact inherent to the common average montage, and due to activity in the occipital and parietal regions.
The same two-way ANOVA applied to bipolar EEG coherence data showed that the Stimulus and Location factors were significant (F2,149 = 24.80, P < = 0.0005, and F5,149 = 2.32, P < 0.05, respectively). Multiple comparisons revealed that ICoh responses in posterior pairs of electrodes only changed as a function of stimulation condition. In summary, for posterior electrode locations all the montage schemes gave consistent results. Therefore we will restrict further descriptions to the ICoh responses computed with ipsilateral earlobe referenced EEG signals.
Individual ICoh changes under visual stimulation
The above group statistics are confined to the whole-screen, different-close, and identical-close stimulus conditions, which were presented to nearly all subjects. Systematic ICoh changes were revealed in the gamma band in the occipital and parietal regions. Analysis of the individual data (Table 1) indicated that the gamma band ICoh increase in response to the whole screen stimulation is highly reproducible between subjects.
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Indeed, compared with the background condition, it was significant in all but one of the subjects and restricted to the occipital and parietal electrode pairs (Fig. 2).
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Individually, some moderate increase was occasionally obtained for the identical-close (3 subjects) and different-close (4 subjects) stimulus conditions. A between-conditions comparison showed that ICoh levels were always greater for the whole screen gratings compared with the other stimuli (Table 2), including the whole-screen-different stimulus, which was presented in three experiments.
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In five subjects, we used unilateral stimuli close to the VM, as well as a set of far stimuli. These were analyzed by means of individual statistics only. No reproducible ICoh responses were found either for the unilateral-close stimuli (Tables 1 and 2), or for any of the far stimuli. Individual examples of spectral curves obtained during the unilateral and the far stimulation are shown in Figs. 3 and 4, respectively.
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To determine whether the ICoh changes were reproducible over long time intervals in the same individual, we recorded the EEGs of two subjects (IC and NB) twice, at a several month interval. In both cases, significantly larger responses were obtained with the whole-screen than with other stimuli (Tables 1 and 2).
Temporal stability of the gamma band coherence response
The data presented so far are based on the analysis of 2-s EEG segments. To study the temporal stability of the ICoh responses during stimulation, we performed a MANOVA with Epoch of analysis as a factor (1st vs. 2nd second), and ICoh values for the O1/O2 and P3/P4 pairs as dependent variables, for the background and whole screen conditions separately. This analysis showed no significant changes between the first and second halves of exposure to the stimuli (F1,17 = 0.580, P = 0.682 for background, and F1,17 = 0.085, P = 0.986 for the whole screen). In addition, individual statistics also revealed no significant ICoh differences between the first and last seconds in any of the stimulus conditions. The group results and a representative individual example are shown in Fig. 5.
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EEG spectral power response to visual stimulation and its relation to the ICoh response in the gamma band
To reveal possible relations between local and distant synchronization, we analyzed stimulus-induced SPD changes of the EEG signal in the alpha and gamma bands. To determine whether the spectral power was affected by the stimulation condition (whole screen, identical-close and different-close), we applied the nonparametric Friedman test (see METHODS, Statistical analysis) separately to the group data from each EEG derivation and band. Figure 6 shows that the decrease in the alpha power was similar for all the conditions in all derivations, whereas the increase in the gamma SPD was stimulus-specific in the occipital (P = 0.040 for O1 and 0.028 for O2) and parietal (P = 0.054 for P3 and 0.069 for P4) derivations.
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Pairwise comparisons of the responses confirmed that, in the gamma band, the whole-screen stimulus was accompanied by a significantly larger SPD response than any of the other stimulation conditions (P ranged from 0.006 to 0.035 for O1, O2, and P4, and increased up to 0.08 for P3, Wilcoxon test).
As mentioned above, both ICoh and SPD in the gamma band increased
specifically with whole screen stimulation. In principle, the power
spectra of two EEG signals do not determine their coherence spectrum,
which depends also on their phase relations (Nunez
1995), and one can thus expect these two measures to vary
independently. However, if the processing of a stimulus involves both
locally and distantly distributed synchronizations at the same
frequencies, an increase in both local power and in distant coherence
should be observable. The scatterplots from Fig.
7 show that the association in question
may be expected for the whole screen stimulus. Indeed, Pearson's
correlations between SPD and ICoh responses appeared to be significant
(at the P = 0.01 level; 2-tailed) for the whole screen
condition only (0.915 for O1, 0.936 for O2, 0.845 for P3, and 0.944 for
P4).
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DISCUSSION |
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This study was designed to determine whether functional aspects of
the cortico-cortical connectivity could be analyzed in humans with EEG
coherence techniques. Our results show that in humans, as in animals
(Kiper et al. 1999), the EEG ICoh responses are
location, frequency, and stimulus specific. Comparison with animal data
suggests that, in humans, callosal fibers can synchronize the activity
in the two hemispheres, and, possibly, within the hemisphere. Indeed,
we found that the gamma activity of visual areas in the two hemispheres
becomes synchronized only when a subject views a stimulus that
presumably activates callosal connectivity.
Topography and frequency characteristics of the EEG ICoh response to visual stimulation
Pronounced and reproducible ICoh responses, consistent across
montage schemes, were restricted to occipital and parietal derivations (or parieto-occipital for bipolar EEG signals). This suggests that the
responses resulted from the activity of the neural circuits underlying
the posterior scalp electrodes. In addition, the observed changes in
ICoh were visual stimulus dependent, and these changes conformed to
predictions (see Kiper et al. 1999) based on the properties of the callosal connections between the visual areas of the
two hemispheres. This points to the visual cortex as the main source of
the activity we recorded in these experiments.
The surface electrode locations can be only roughly correlated
with underlying cortical areas (Binnie et al. 1982;
Myslobodsky and Bar-Ziv 1989
). In particular, occipital
electrodes O1 and O2, which are located lateral and superior to the
occipital pole and overlapping the calcarine sulcus, might be either
over Brodmann's area 17/V1, or 18/V2 (Homan et al.
1987
). They might also record the activity of other occipital
extrastriate areas, because neuroimaging studies have shown that
regions activated by coherently moving stimuli are considerably larger
than primary visual areas (Van Essen and Drury 1997
;
Zeki 1993
), and, in humans, callosal fibers connect both
primary and secondary visual areas (Innocenti 1986
; Zilles and Clarke 1997
).
The P3 and P4 electrodes are localized over the parietal cortex, which
is known to be concerned with visual functions (for reviews see
Cavada and Goldman-Rakic 1993;
Gulyás 1997
). In particular, these
locations were shown to occupy a portion of the superior parietal
lobule (Brodmann's area 7), in the vicinity of the intraparietal sulcus (Homan et al. 1987
). In primates, portions of
area 7 are visually responsive (Johnson et al. 1993
;
Mouncastle et al. 1975
; Steinmetz et al.
1987
), and, in humans, this region may partially include the
motion-selective area V3A (Tootell et al. 1997
).
In five subjects, the response extended to posterior temporal
derivations. The posterior temporal electrode over the left hemisphere
(T5) falls on Brodmann's area 37, whereas on the right side (T6), it
may be either over areas 19, 37, or 39 (Homan et al.
1987). Because we used moving stimuli, a more consistent
response at T5 and T6 electrodes could have been expected because they are the closest to the presumptive motion associated visual area MT
(Kaas 1995
; Roland 1993
; Tootell
1995
; Van Essen and Drury 1997
). However,
considering the small size of this area, and inevitable differences in
area and electrode location between subjects, the instability of the
ICoh response in these electrodes is not surprising.
Of all the EEG rhythmic components, the alpha (8-12 Hz) and higher
frequencies are considered mainly of cortical origin (Lopes da
Silva 1991; Steriade et al. 1990
). The alpha
rhythms are viewed as a reflection of a "resting" state of the
cortical areas (for review see Niedermeyer 1993
;
Pfurtscheller et al. 1996
). Active states, such as the
perception of visual stimuli, are accompanied by a desynchronization in
the alpha-range (Lehtonen and Lehtinen 1972
;
Pfurtscheller et al. 1994
; Ray and Cole
1985
; Vanni et al. 1997
). Consistent with this
view, we observed a decreased power in the alpha band during visual
stimulation with gratings, compared with the uniformly illuminated
screen. In humans, interhemispheric synchronization in the alpha band
was shown to be dependent on the integrity of the corpus callosum (CC)
in the resting state (Koeda et al. 1995
;
Pinkofsky et al. 1997
). In our experiments, ICoh in the
alpha band tended to decrease or remained unchanged with visual
stimulation. When an occasional increase was present, it appeared to be
a component of a broadband response that involved the gamma frequencies
as well. In addition, all changes in ICoh within this band were not
stimulus specific.
Several human EEG studies revealed early-onset responses to visual
stimuli in the gamma band. Lutzenberger et al. (1995)
found an increase in the power of the 35- to 45-Hz band within the
first 500 ms of stimulation. It was obtained with horizontal bars
moving coherently in the right and left quadrants of the upper or lower hemifield. A significant increase in the power at 40-96 Hz was obtained by Müller et al. (1996)
, in response to a
single vertical moving bar in the left hemifield, but not to two
incoherently moving bars. The responses were predominantly from within
the right hemisphere (O2, P4, T6 locations) and were most pronounced between 400 and 900 ms after the motion onset. Finally, recent studies
using static visual stimuli (Tallon et al. 1995
;
Tallon-Baudry et al. 1997
) revealed a short-lived gamma
response to a real or illusory object. The gamma response was widely
distributed over the cortex, covering both postcentral and precental
areas. These studies support the notion that the gamma band dynamics is
associated with perception in humans, as it was originally suggested in
animal studies (reviewed in Pulvermüller et al.
1997
), but they cannot be interpreted in terms of cortical circuitry.
Activation of callosal connections increases interhemispheric and, possibly, intrahemispheric synchronization
Results presented in the companion paper (Kiper et al.
1999) suggested that callosal connections between areas 17, 18, and, possibly, 19 of the two hemispheres, when activated by a visual stimulus, synchronized the gamma band activity of these areas. These
conclusions were based on three aspects of the results. First, the
activation was obtained by stimuli located close to the VM of the
visual field, whose representations are selectively connected by the
CC, not for more peripheral stimuli. Second, the activation was
obtained with bilateral iso-oriented gratings, but not with gratings of
different orientation. Finally, the effects were eliminated by
transection of the CC, as is also the case for the correlated activity
of single neurons (Engel et al. 1991
).
In humans, as in other species (reviewed in Innocenti
1986; Kennedy et al. 1991
), the representations
of the VM of the visual field are selectively interconnected by
callosal axons in the primary and in some of the secondary visual areas
(Clarke and Miklossy 1990
). Therefore by comparison with
the animal work, the present results suggest that the increased
coherence in the gamma band is due to activation of callosal
connections, which probably interconnect exclusively or preferentially
iso-orientation columns (Gilbert and Wiesel 1989
;
discussed in Houzel et al. 1994
). Whether callosal axons
selectively interconnect iso-orientation columns in primates is not
known, although a columnar organization of callosal connections was
demonstrated in monkeys (Kennedy et al. 1986
). It is
tempting to assume that callosal axons do selectively interconnect
iso-orientation columns in man. This might be a general trait of
cortico-cortical connectivity implementing "collinearity," a
fundamental principle of "Gestalt" perception (Bosking et
al. 1997
; Schmidt et al. 1997
). Unlike in our
animal study, we do not know whether the transection of the CC would
eliminate the stimulus-dependent interhemispheric synchronization of
gamma activity in humans. This is likely, however, because recent
studies support a role of callosal connections in synchronizing the
activity of the two hemispheres in humans (Koeda et al.
1995
). A study in split-brain patients could help to rule out
the possibility that, in spite of our precautions, volume conduction
could contribute to the stimulus-dependent ICoh dynamics.
There is one important difference between our animal and human results.
In the animal experiments, EEG coherence increased with stimuli
separated 2.6° from the VM. In humans, instead, it increased only
with stimuli extending across the VM. One possible explanation of these
differences is that the callosal connections cover a narrower strip of
visual field representation in man than in ferret. Furthermore, a
complete activation of the region of bilateral representation in the
cortex might be required. This region was estimated to extend ~1°
on either side of the VM (Fendrich et al. 1996), and
therefore only half of it was stimulated by the bilateral identical
stimuli. Alternatively, in awake humans, ICoh might increase only when
the stimuli are perceived as a whole, rather than two separate gratings
(Kiper et al. 1998
; Knyazeva et al.
1998
).
The same explanation relates to the question of the functional
significance of the increased coherence in the gamma band. Assuming
that the synchronicity of activity serves as a "tag" for perceived
"connectedness" across cortical networks, the occurrence of
oscillations in the gamma band is currently interpreted as a way of the
temporal tag spreading (Roelfsema and Singer 1998). If
this is true, and, if the callosal connections are critical in
propagating the tag, one would predict errors in perceiving connectedness when callosal connections are interrupted. The rich literature on split-brain and acallosal subjects provides evidence in
favor of such a conclusion. Indeed, each hemisphere of a split-brain patient can erroneously complete its own version of incomplete or
chimeric figures flashed along the VM (Levy et al. 1972
;
reviewed in Trevarthen 1990
). Furthermore, a patient's
performance in judging the alignment of two lines is degraded when
these are flashed to separate hemispheres. Also, the patients cannot
perform lexical decision on letters divided between the two hemifields
and perform poorly on other tasks requiring interactions between the
two hemispheres (reviewed in Corballis 1995
). In
addition, split brain or acallosal patients are impaired in the
stereoscopic vision along the VM (Lassonde et al. 1995
;
Mitchell and Blakemore 1970
), a low level type of
cortical binding, for which the role of the CC is debated (reviewed in
Berlucchi and Antonini 1990
).
With the limitations mentioned, it appears that changes in
interhemispheric EEG coherence can probably be used to assay
electrophysiologically the functionality of callosal connections.
Therefore this method complements others such as the psychophysical
study of the interference between gratings presented near the VM
(Berardi et al. 1989), the analysis of ipsilaterally
evoked responses (Brown et al. 1994
), and transcranial
magnetic stimulation (Paus et al. 1997
).
It should be mentioned that anatomic studies in the cat and computer
simulations predicted that callosal connections would play a role not
only in the synchronization of activity between the two hemispheres,
but also on the local activity within each hemisphere (Innocenti
et al. 1994). The prediction seems to be borne out in the
present study because the whole screen condition not only increased the
distant interhemispheric synchronization, but also the EEG power in the
gamma band. It was previously shown that an increase in the EEG power
is indicative of local synchronization of the postsynaptic potentials
in the vicinity of the recording electrode (Creutzfeldt et al.
1966
). However, a comparable increase in the EEG power was not
obtained in our animals study (Kiper et al. 1999
). The
reasons for this difference are not known. It may be due to the effect
of anesthesia in the animal work, or to differences in the functional
callosal connectivity between ferrets and man.
Possible mechanisms of callosal action
How activation of callosal connections modifies the synchronous
activity in the hemispheres remains unclear. One obvious possibility is
that the activity in callosal axons can, on its own, control the
activity of the postsynaptic targets. This is consistent with observations in split-chiasm cats (Berlucchi and Rizzolatti
1968; Milleret et al. 1994
; Tardif et al.
1997
), and with the fact that callosally projecting neurons can
display oscillatory activity (Nunez et al. 1992
).
However, in our experimental conditions, the stimulation of one
hemifield, with gratings extending near the VM, and, therefore
presumably activating the callosally projecting neurons, was
insufficient to modify the interhemispheric coherence and to increase
the local power in the gamma band. This relative weakness of the
callosal input is compatible with recent morphometric observations,
stressed relative inadequacy of the callosal compared with
thalamocortical axons to drive the postsynaptic targets (Tettoni et al. 1998
). As an alternative to the direct drive
explanation, it could be suggested that the activity of the two
hemispheres synchronizes when two conditions are present: 1)
direct thalamic input to the two hemispheres and 2)
reverberating activation between the hemispheres. A neural network
embodying such features did in fact generate synchronous oscillations
in the two hemispheres, albeit in the theta rhythm (Innocenti et
al. 1995
). Gamma oscillations might be generated when callosal
input, adding to the thalamocortical input, brings the depolarization
of the callosally projecting neurons and/or their targets to a
sufficient level of depolarization to trigger their intrinsic rhythm
(Gray and McCormick 1996
; Steriade 1997
). This interpretation is compatible with the many
electrophysiological observations demonstrating that the CC increases
cortical excitability (Berlucchi 1966
; Bremer et
al. 1956
; Innocenti 1986
). In particular, Bremer (1967)
showed that evoked potentials in the cat
visual cortex increased in amplitude if preceded by stimulation of the homotopic area in the contralateral hemisphere. Creutzfeldt et al. (1969)
reported synchronous excitation of the neurons in
superficial cortical layers in the case of contralaterally evoked
callosal potential. This effect disappeared after section of the CC.
Obviously, the fact that the activity of callosal connections may be
limited to facilitatory influences in certain conditions does not imply that it is, by itself, never sufficient to drive the postsynaptic targets. One appealing possibility is that the callosal and other cortico-cortical connections can switch from a feed-forward mode to an
assembly creating mode, the latter revealed by the appearance of gamma oscillations.
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ACKNOWLEDGMENTS |
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We thank the technicians in the EEG department at the Centre Hospitalier Universitaire Vaudois for precious help during the recording sessions. We are also grateful to the Institut de Biologie Cellulaire et de Morphologie staff members who agreed to participate in this study as subjects.
This research was supported by PNR38 Grant 4038-043990 of the Swiss National Science Foundation.
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FOOTNOTES |
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Address for reprint requests: G. M. Innocenti, Division of Neuroanatomy and Brain Development, Dept. of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 14 December 1998; accepted in final form 9 August 1999.
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REFERENCES |
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