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EEG photic driving: Right-hemisphere reactivity de!cit in childhood autism.A pilot study

Vladimir V. Lazarev !, Adailton Pontes, Leonardo C. deAzevedoLaboratory of Neurobiology and Clinical Neurophysiology, Fernandes Figueira Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

a b s t r a c ta r t i c l e i n f o

Article history:Received 13 August 2008Accepted 29 August 2008Available online 9 September 2008

Keywords:ElectroencephalogramPhotic drivingAutismChildrenRight hemisphere

In 14 autistic boys, aged 6–14 years, free of drug treatment, with relatively intact verbal functions andwithout severe or moderate mental retardation (I.Q. 91.4±22.8), intermittent photic stimulation at 11 !xedfrequencies of 3–24 Hz revealed latent de!ciency of the right hemisphere in the photic driving reactivity,predominantly at the fast alpha and beta frequencies of stimulation. The left-side prevalence was observed:1) in the total number of driving peaks evaluated for the !rst four harmonics in the EEG spectra of 14 corticalareas and 2) in the driving amplitude in the spectra of the 2 occipital areas. As compared to 21 normallydeveloping boys matched on age who did not show interhemispheric asymmetry in the driving reactivity, theautistic patients had signi!cantly lower driving characteristics only in the right hemisphere. There were nosigni!cant differences between the autistic and control groups in the spontaneous EEG spectra of theoccipital areas in the resting state.

© 2008 Elsevier B.V. All rights reserved.

Intermittent photic stimulation (IPS) inducesphotic driving responsein the electroencephalogram (EEG). This rhythmic activity is time-locked to the stimulus at a frequency identical or harmonically related tothat of the stimulus. The resonance-like mechanisms of the drivingresponse may enhance latent normal or abnormal bioelectrical oscilla-tions (Takahashi, 1987). Besides paroxysmal reaction to IPS in photo-sensitive epilepsy, non-paroxysmal driving responses were found tocorrelate with various types of cerebral pathology, not alwaysmanifested in the resting EEG (Scheuler, 1983), such as partial epilepsyand brain lesions (Beydoun et al., 1998). These responses can also beinformative in the neurophysiological study of neuropsychiatric func-tional and endogenous disorders such as headache (Gronseth andGreenberg,1995) and schizophrenia (Jin et al., 2000),which, as a rule, arenot evident in the EEG diagnostics. In these pathologies, topographicevaluation of the photic driving response in different brain areas hasshown a promising potential for revealing subtle functional distur-bances in regional reactivity (Jin et al., 2000). It was demonstrated thatIPS can emphasize the functional interhemispheric asymmetry (Hirotaet al., 2001) and can also indicate regional functional alterations throughasymmetric driving effects (Scheuler, 1983; Beydoun et al., 1998).

Our previous research has shown that detailed topographicquantitative analysis of the EEG photic driving at various stimulationfrequencies, may be a quite sensitive indicator of functional brainmaturation in children. This approach enabled us to reveal certainadditional features of the brain electrical activity development via latent

theta oscillations in the posterior brain areas not present in the restingEEG at preadolescent and adolescent stages (Lazarev et al., 2001, 2004).In normal subjects, the topographic index of the photic drivinggeneralization in the non-visual cortical areas proved to be positivelycorrelatedwith age.Moreover, this index re"ected a likely delay in brainmaturation in patients with partial epilepsy. Similarly, this indexappeared to be useful as a tool to evaluate the effects of antiepilepticdrug therapy (Lazarev et al., 2006). These promising results prompted usto test the capacity of the proposed IPS methodology to re"ectneurophysiological features of functional neuropsychiatric disordersthat do not manifest explicit alterations in the spontaneous EEG.

Childhood autism can be considered one of such disorders. Theliterature on the EEG correlates in autism is quite discrepant and usuallydescribes general and nonspeci!c changes, such as some prevalence ofslow bioelectrical activity and alpha rhythm suppression and disorga-nization (Cantor et al.,1986; Small,1987; Bashina et al.,1994; Chan et al.,2007). Some authors observed EEG signs of relatively lower activation inthe left anterior areas in comparisonwith the right ones (Dawson et al.,1983; Harrison et al., 1998). In many cases, such asymmetry couldprobably re"ect language developmental problems inherent to mostautistic patients and traditionally considered as a central feature ofautism. On the other hand, recent neuropsychological data emphasize acrucial role of right-hemisphere dysfunction in the development ofsome basic features of the autistic spectrum (Ozonoff and Miller, 1996;Siegal et al.,1996; Sabbagh,1999). These features include impairments insocial interaction, communication and imaginationwhich constitute theclassical autistic triad (Wing,1997). The right-hemisphere abnormalitiesin the high-functioning forms of autism have been observed inneuroimaging studies (McKelvey et al., 1995; Waiter et al., 2005).

International Journal of Psychophysiology 71 (2009) 177–183

! Corresponding author. Av. Rui Barbosa, 716, Flamengo, Rio de Janeiro, RJ, 22250-020, Brazil. Tel.: +55 21 9424 7741; fax: +55 21 2554 1805.

E-mail address: vlad.v@iname.com (V.V. Lazarev).

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However, to date in the electrophysiological literature, only in somespecial tasks of event-related potential paradigm such as discriminationof speech prosody (Kujala et al., 2005) or processing gaze direction inface perception (Senju et al., 2005), certain right-hemisphere alterationsin autistic patients were detected. For the spontaneous rhythmic EEGactivity, abnormal left-side prevalence in the EEG spectral power duringsustained visual attentionwas recently described for the temporal areasin young autistic children (Stroganova et al., 2007).

Since the left-hemisphere specialization for language is a decisivedeterminant of the EEG interhemispheric asymmetry (Butler andGlass, 1974; Lazarev, 1998), language disorders may probably shadesome !ner right-hemisphere manifestations. For this reason, in thepresent research, the IPS test was applied in autistic patients withoutsigni!cant language problems or mental retardation. This approachwas expected to facilitate detecting likely right-hemisphere dysfunc-tion not apparent in the resting EEG and thus testing the sensitivity ofthe proposed methodology to reveal subtle functional alterations.

1. Materials and methods

Fourteen boys aged 6–14 years (mean±standard deviation: 9.7±2.3)were diagnosed as autistic patients according to the DSM-IV criteria(Filipek et al., 1999). All of them had a classical autistic triad ofimpairments in social interaction, communication and imagination(Wing, 1997), with relatively intact verbal functions and without severeor moderate mental retardation. According to the WISC-III intelligencetest (Wechsler,1991), their I.Q. levelswere average (90–109)—7 patients,below average—4 patients or above average—3 patients. Their verbal,performance and total I.Q. levels were, on average, 91.2±27.5, 94.3±20.4and 91.4±22.8, respectively. The patients did not have epilepticsymptoms and abnormalities in the neurological examination otherthan those directly related to autism. Computerized helicoidal tomo-graphy of the brain was normal for all cases. The patients were free ofdrug treatment. The control group consisted of 21 boys, aged 6–16 years(10.1±3.3), without a history of neurological, psychiatric or drug relatedillnesses and with normal academic achievement. The patients andcontrols were right-handed according to their hand preference and thereports of their parents. The study was approved by the local EthicsCommittee.

EEG signals were recorded by a Nihon Kohdenmachine EEG-4418 at14 scalp points (International 10/20 System, see Fig. 1) with unilateralreferences to the corresponding earlobes, during 2–3 min of initialresting state before stimulation (background) and during white "ickerIPS of 11 !xed frequencies of 3, 4, 5, 6, 8,10,12,15,18, 21 and 24 Hz, 25-sduration each, with 30-s periods between stimulation runs. Each EEGfragment registered was of 25-s duration. The artifact control duringrecording was visual with simultaneous registration of EOG. Thesubjects were wakeful with eyes closed throughout the experiment.Photic stimulator was Nihon Kohden 4418 K-LS-701B—a xenon lampwhose"ashhaddurationof less than20 !s. The lampwaspositioned at adistance of 25 cm from the eyes, with dim surrounding light. Therecording characteristics were: 0.3-s time constant, 70-Hz highfrequency !lter and 15-µV/mm sensitivity. Ground electrode wasapplied in Fpz. EEG signals were digitized at the sampling frequency of256 Hz.

The duration of EEG epochs submitted to spectral analysis (FFT)was 2 s. The results were presented in the absolute form of amplitudespectra, i.e., the square root of the power spectrum, with a frequencyresolution of 0.5 Hz. For each lead, the presence of the drivingresponse at the frequency of stimulation was ascertained by in-housesoftware as an amplitude peak which was at least 20% higher than theamplitudes at adjacent frequencies (±1 Hz) (20% criterion). Incomputer simulation, this level of prevalence gave a false-positiverate of less than 5% when the spectrum of signals was white, i.e., whenthere was no response to the stimuli (Lazarev et al., 2001). Ourprevious research in normal subjects has shown that most of the

driving responses detected by this criterion proved to be signi!cant (inrelation to the previous background) according to the statisticalestimation by spectral F-test (Lazarev et al., 2004).

Two aspects of the photic driving effect were evaluatedquantitatively:

1. The photic driving presence according to the 20% criterion wasestimated for each of the !rst four harmonics, i.e. fundamental IPSfrequency and its three integral multiples (provided they fell at EEGfrequencies below 70 Hz—high frequency !lter which determinedevaluation of only three harmonics for the IPS 18 and 21 Hz and twoharmonics for 24 Hz). The total number of the driving peaks at eachharmonic and their sum for the !rst 4 harmonics were evaluated asaverage for all IPS frequencies corresponding to each standardfrequency band (i.e. for 4 IPS frequencies in the beta, 3—in the alphaand in the theta and 1—in the delta bands) separately for 6 non-visual and 1 occipital visual leads in each hemisphere. In the lattercase, only the sum of such averages for 4 harmonics was calculated.

2. Analysis of the driving magnitude was performed for the twooccipital leads traditionally considered most representatives for thestudy of this reaction due to the highest occurrence of the drivingresponse and its higher amplitude in this region (Lazarev et al., 2001,2004). In order to observe simultaneously the responses to all the IPSfrequencies, amplitude spectra measured at the stimulation fre-quency for each of the 11 EEG fragments corresponding to differentstimulation runs, were plotted on a single graph called frequency“pro!le” of the individual driving reactions (Lazarev et al., 2001). Foreach standard frequency band, mean pro!le values and meanbackground amplitude spectra were evaluated (delta—3.0 and 3.5;theta—4.0–7.0; alpha—7.5–12.5; and beta—13.0–24.0 Hz). At each IPSfrequency, an increase in amplitude spectra during stimulation(pro!le value) in relation to the spontaneous background EEG at thesame frequency was also calculated.

The interhemispheric asymmetry in the total number of drivingpeaks in each group and the difference between autistic and controlgroups in each hemisphere were evaluated for each frequency band:at each of the four harmonics in the non-visual areas and for the sumof the four harmonics in both non-visual and occipital visual areas.

The amplitude differences between the occipital driving pro!les(between groups in each hemisphere and between hemispheres ineach group) were estimated in 4 frequency bands and also at each of11 frequencies of stimulation. The same comparisons were made foran amplitude increase during stimulation in relation to the back-ground EEG. For the resting spontaneous EEG spectra in the occipitalareas, the differences between hemispheres and groups wereevaluated only for mean amplitude in each band.

The statistical signi!cance of the interhemispheric and intergroupdifferences was calculated by non-parametric Kruskal–Wallis multipletest followed byWilcoxon (for related samples) andWilcoxon–Mann–Whitney (for independent samples) post-hoc pair tests. The data atdifferent IPS frequencies or at their harmonics as well as in differentfrequency bands were not compared statistically among themselves.

The likely association between interhemispheric asymmetry and agewas estimated by one linear regression model applied to the asymmetrycharacteristics averaged for all the frequencies in each band. For the 12non-visual leads, theasymmetrywasevaluatedas thedifferencebetweenthe number of driving peaks in the left (L) and right (R) hemispheresrelated to the total number in both, i.e. (L!R)/(L+R). For the drivingpro!les in the two occipital leads, the interhemispheric amplitudedifference was related to the mean amplitude, i.e. (L!R)/(L+R)/2.

2. Results

Two examples of strong and generalized driving response to theIPS of 6 Hz in normal subject (A) and autistic patient (B)may be seen inthe spectrograms of Fig. 1. They show the driving peaks at the

178 V.V. Lazarev et al. / International Journal of Psychophysiology 71 (2009) 177–183

stimulation frequency and some harmonics not only in the occipital‘visual’ region (where the driving effects are usually studied) but alsoin the other ‘non-visual’ areas. In these areas, the reaction peakamplitudes are lower and decrease towards the frontal region. Thistrend was observed in all other subjects and patients studied (Lazarevet al., 2004). Individual topography of driving peaks' occurrence wasvery variable across both groups, however, a reduced number ofdriving responses in the right hemisphere in Fig. 1B proved to becharacteristic (usually to a lesser degree) for autistic patients.

In both groups, the highest occurrence of the driving responses wasas a rule in the occipital (visual) areas, where they could be observed atthe !rst harmonic (stimulation frequency) in 62–95% of normal subjectsat different frequencies of IPS (Fig. 2B). In autistic patients, thispercentage was more or less similar in the left lead (64–93%) while inthe right one, it was substantially lower than in the control group at theIPS frequencies of 3 and 4 Hz and particularly at the beta frequencies(Fig. 2C). This resulted in the percentage prevalence of the left occipitalarea over the right one in the autistic group at all the IPS frequencies

Fig. 1. Examples of individual spectrograms of normal subject (A) and autistic patient (B) in 14 leads (marked above each spectrum) during intermittent photic stimulation of 6 Hzwith strong generalized driving effect (A) and strong interhemispheric asymmetry (B). Vertical lines mark a frequency of stimulation and its harmonics. Ordinates: amplitude spectra,µV/"Hz. Arrows show driving peaks with amplitudes 20% greater than those of adjacent frequencies.

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(Fig. 2, A and C). Such prevalencewas also observed at higher harmonics.In the rightoccipital area, each IPS frequencyevokeddriving response at,on average, 2.39±0.36 harmonics in normal subjects and at 1.55±0.49harmonics in autistic patients, while in the left one these indices weresimilar: 2.34±0.45 and 2.57±0.47, respectively. The mean total numberof occipital driving peaks at the !rst four harmonics in the autistic groupwas substantially lower in the right hemisphere: 1.88 as against 2.74 inthe left one at the theta stimulation frequencies (pb0.01),1.81 as against3.07 at the alpha (pb0.001), and 1.11 as against 2.20 at the betafrequencies (pb0.001), respectively. There was no signi!cant asymme-try in the control group. As a result, the prevalence of the normalsubjects over autistics in the right occipital lead was observed for thetheta (pb0.05), alpha (pb0.05) and beta (pb0.001) IPS frequencieswhilein the left lead, there was no signi!cant difference in any band. For allthese differences, the Kruskal–Wallis multiple test showed p=0.108 fortheta, p=0.009 for alpha and p=0.000 for beta IPS frequencies.

In the 12 non-visual areas, where the localization of the leads withdriving peaks varied at different IPS in both groups, the general extent oftopographic generalization of the driving reaction could be evaluated bymeans of the total number of peaks in the left and right hemispheres. Thesummary scalp maps of the response percentage at the !rst harmonic inthe group of autistic patients showed the left-side reactivity prevalence atalmost all IPS frequencies, except for 4 and 5 Hz (Fig. 2A). In the controlgroup, suchprevalencewas apparent only at!ve of eleven IPS frequencies(Fig. 2B). However, a comparison of the reactivity percentage in the twogroups in each lead (by subtraction of the values of the maps for controlgroup from the corresponding values for patients) showed that in mostpairs of homologous leads (except for 4 and5Hz), the autistic patients hadrelatively higher percentage in the left hemisphere and the controls in therightone (Fig. 2C). Thismeans, forexample, that evenat 15Hz,wherebothgroups had higher percentage in the left hemisphere, a degree of suchprevalence was noticeably more pronounced in the patients.

Fig. 2. Scalp maps with the percentage of autistic patients (A) and normally developing control subjects (B) who had in each lead a driving response (according to the criterion of spectralpeak amplitude 20% greater than those of adjacent frequencies) at each of 11 frequencies of intermittent photic stimulation (IPS). Each square cell represents a lead (plotted on eachmapaccording to the head scheme in the right lower cornerof the!gure)with a percentage for the group of 14patients or21 control subjects at a frequencyof IPS givenabove the correspondingmap. C: maps of difference of the percentages between the two groups in each lead. In each pair of homologous symmetrical leads, a cell with higher percentage is grey or black.

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In the right hemisphere of autistic patients, the total number of‘non-visual’ leads with driving peaks at the !rst four harmonics wasonly 54.98% of those in the left one in the alpha band (pb0.001) and

51.25% in the beta band (pb0.01). These percentages decreased from78.63% at the !rst harmonic to 39.58% at the fourth one for the alphaIPS frequencies and from 53.27% at the !rst harmonic to 30.86% at thethird one (the fourth harmonic was not estimated) for the beta IPSfrequencies (pb0.01 for asymmetry at all harmonics of both bands). Inthe control group, no signi!cant asymmetry was observed (Table 1).Correspondingly, in the right hemisphere, the total number of drivingpeaks for the !rst four harmonics in the autistic group was 74.03% ofthose in the control group for the alpha IPS frequencies (pb0.1) and55.21% for the beta ones (pb0.01). Such ratio was signi!cant for thethird (58.11%) and fourth (47.03%) harmonics of the alpha IPSfrequencies (pb0.05) and second (60.17%, pb0.05) and third (35.71%,pb0.01) harmonics of the beta ones, with a strong tendency towardsthe lower percentage in autistics (67.05%, p=0.59) at the !rst betaharmonic. No signi!cant differences between the groups wereobserved in the left hemisphere (Table 1). The Kruskal–Wallis multipletest applied to the number of driving peaks in the non-visual areasshowed signi!cant p-values (0.05–0.01) for all three harmonics of thebeta IPS frequencies and three higher harmonics of the alpha ones.

In the occipital areas, where the driving magnitude was evaluated,themean values of the background amplitude spectra in the alpha bandin the autistic group were lower than in normal subjects. However, theKruskal–Wallis test did not show signi!cant differences for any band inthe spontaneous EEG. Only post-hoc evaluation revealed a tendency to

Fig. 3. Group average EEG photic driving pro!les (broken lines) and background spectra (curves) in the occipital areas. (A and B) Comparison between left (solid lines) and right(dashed lines) hemispheres in autistic (A) and control (B) groups. (C and D) Comparison between autistic (solid lines) and control (dashed lines) groups in right (C) and left(D) occipital areas. Arrows show signi!cant differences (pb0.05) between pro!le values at different IPS frequencies.

Table 1Topographic generalization of photic driving in non-visual cortical areas (6 leads in eachhemisphere) evaluated in number of leads with driving peaks (according to 20%criterion) averaged over all IPS frequencies in each band (4 IPS frequencies in the beta, 3in the alpha and in the theta and 1 in the delta bands)

Band Delta Theta Alpha Beta

IPS frequencies (Hz) 3 4, 5 and 6 8, 10 and 12 15,18, 21 and 24

Hemisphere Left Right Left Right Left Right Left Right

Autistics 1 harm. 0.93 0.57 1.98 2 3.79! 2.98! 4.43! 2.36!°2 harm. 1.64 1.71 2.26 2.05 3.19! 1.69! 3.57! 2.07!°3 harm. 0.71 1.14 2.31 1.74 3.17!° 1.29!° 1.62! 0.5!°4 harm. 1.14 0.86 1.55 1.17 2.40! 0.95!° 0 0#1–4 harm. 4.43 4.29 8.1 6.95 12.55! 6.90!°° 9.62! 4.93!°

Controls 1 harm. 0.81 0.57 2 1.94 2.92 2.9 4 3.52°2 harm. 1.86 1.52 2.21 2.41 2.59 2.17 3.81 3.44°3 harm. 1 1.43 1.79 1.56 2.24° 2.22° 1.62 1.4°4 harm. 0.81 0.29 1.37 1.4 2.19 2.02° 0 0#1–4 harm. 4.48 3.81 7.37 7.3 9.94 9.32°° 9.67 8.93°

#1–4 harm—sum for four harmonics; !—pb0.05 for interhemispheric differences; °—pb0.05 and °°—p=0.07 for differences between the groups.

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the prevalence of the controls in the left hemisphere (p=0.75) (Fig. 3, Cand D). In both groups, the right-side mean amplitude prevalence wasobserved in all the bands. In the control group, the post-hoc estimationshowed signi!cance of this asymmetry in the delta and beta bands andin the autistic patients in the theta band (pb0.05), with a tendency(pb0.1) in the alpha band for both groups (Fig. 3, A and B).

Pronounced difference between the two groups was observed in theinterhemispheric asymmetry of the occipital photic driving amplitudepro!les. In the autistic patients, the values in the right hemisphere, incontrast to the background pattern, proved to be lower than in the leftone (Fig. 3A). When averaged for each frequency band, the right-sidepro!le values were 82.83% (pb0.1) of the left ones in the theta, 85.50%(pb0.05) in the alpha and 59.76% (pb0.001) in the beta bands. In thecontrol group, the reactivitywas almost equal in both hemispheres in allthe bands. Correspondingly, in the right hemisphere, the pro!le valuesof the autistic group were 75.79% of those in the control group in thetheta (pb0.02), 74.52 (pb0.05) in the alpha and 59.85 (pb0.01) in thebeta bands, while there were no signi!cant differences in the lefthemisphere. Kruskal–Wallismultiple test showed for the band averagedvalues: p=0.086 for the theta, p=0.184 for the alpha and p=0.001 for thebeta bands.

For 11 separate pro!le values, this multiple test detected signi!cantdifferences at 4 Hz (p=0.031), 18 Hz (p=0.005), 21 Hz (p=0.004) and24 Hz (p=0.000), and relatively low value at 15 Hz (p=0.15). Post-hocpair comparisons speci!ed these differences showing left-side ampli-tude prevalence in the autistic group at 5 and 6 Hz (pb0.05), 12 Hz(pb0.01) and at all the beta frequencies (pb0.01, except for 15 Hz:pb0.05) (Fig. 3A). In the control group, the reactivitywas almost equal inboth hemispheres, except for the peak alpha frequency of 10Hz that hadsigni!cant right-side amplitude prevalence (pb0.01) similar to thebackground asymmetry (Fig. 3B). When directly compared, the pro!lesof the two groups did not show any signi!cant differences in the lefthemisphere (Fig. 3D), while in the right one, the pro!le voltage in thepatients was signi!cantly lower at almost all IPS frequencies utilized(pb0.05–0.001), except for 6 and 8 Hz (pb0.1 at 6 Hz) (Fig. 3C).

The amplitude increase during IPS in relation to the backgroundresting state in the autistic patients also prevailed in the left hemisphereat all the IPS frequencies (pb0.05–0.001; except for 3 and 10 Hz: pb0.1).In the control group was found no signi!cant asymmetry in this moredirect reactivity characteristic. When compared to the controls, theautistic patients showed signi!cantly lower amplitude increase only inthe right hemisphere at eight IPS frequencies (pb0.05–0.001) with sucha tendency at 6 and 10 Hz (pb0.1) and except for 8 Hz. The results ofKruskal–Wallis test were signi!cant at all beta frequencies (p=0.05 at15 Hz and pb0.01 at 18, 21 and 24 Hz), had a character of tendency at12 Hz (p=0.75) and relatively low value at 4 Hz (p=0.15).

The regression coef!cients did not show any signi!cant associationbetween age and interhemispheric asymmetry, except for the numberof driving peaks in the non-visual areas for the third harmonic of thebeta IPS frequencies in the autistic group (pb0.02; regressioncoef!cient 0.18) and for the beta pro!le amplitudes in the occipitalareas of normal subjects (pb0.02; regression coef!cient !0.013).

3. Discussion

The EEG photic driving quantitative characteristics proved to besensitive enough to detect in autistic patients functional alterations inthe right hemisphere, not reported in the EEG literature. The capacityof this methodology to uncover latent abnormalities is most obviousin the occipital areas, where the background EEG spectra did not showsigni!cant differences between autistic and control groups, while thedriving pro!les demonstrated strongly pronounced interhemisphericasymmetry only in the autistic patients. This asymmetry may beapparently treated as a right-hemisphere de!cit in the photic drivingreactivity, since in the left hemisphere, the driving pro!les in bothgroups were similar.

The right-hemisphere driving de!cit proved to be spatially general-ized and was also apparent in the non-visual brain areas through theleft-side topographic prevalence in the total numberof thedrivingpeaksand in the group percentage of the driving responses. This !ndingcon!rms the importance of the topographic approach to the photicdriving study argued in our previous publication (Lazarev et al., 2004).

The nature of the driving reactivity de!cit needs further investiga-tion. However, some latent de!ciency in the right-hemisphereactivation can be hypothesized since the observed asymmetry wasmost pronounced at the IPS frequencies of the alpha and beta bandsand at their harmonics. The latter for the greater part fell in the EEGfrequencies of the gamma band. Some authors have shown that thephotic driving prevalence at higher frequencies and particularly athigher harmonics correlates with a higher functional state of the brain(Mundy-Castle, 1953; Danilova, 1961). The photic driving reactivitycan probably re"ect some !ner aspects of the cortical activationdifferent from those related to traditional EEG signs of arousal such asalpha rhythm desynchronization etc. (Lazarev, 2006).

The results of the present research could also be considered in termsof the brain maturation due to the ability of the photic driving to revealand emphasize latentneuronal sources of synchronization characteristicfor certain stages of the brain development. In our previous research,weobserved an enhanced driving reaction in the theta band in normalpreadolescents and adolescentswhodidnot showany theta peaks in theEEG spectra of the resting state (Lazarev et al., 2001). We also observedpositive correlation of age with the number of driving peaks in the non-visual cortical areas (Lazarev et al., 2006). In this way, the right-hemisphere de!ciency in resonance synchronization at fast alpha andbeta frequencies observed in our autistic patients only in the drivingpatterns and not in the spontaneous EEG (at least in the occipital areas)may also re"ect a likely delay in the development of this hemisphere,taking into account that the increasing frequency of photic driving ispeculiar to normal brain maturation (Eeg-Olofsson,1980). However, themain results of the present research have not shown an apparentcorrelation of the interhemispheric asymmetry with age. On the otherhand, a reduced spontaneous EEG synchronization in the theta andalpha bands in the right temporal lobe was recently described for theyounger autistic boys (mean age 5.2 years) (Stroganova et al., 2007). Theauthors consider this effect in terms of a diminished capacity of theregional cortex to “generate sustained synchronous oscillations” due tolikely decrease in inter-neuronal connectivity. Such a decrease is positedto relate to a decrease of the deepwhite matter in the right hemisphereof autistics observed in neuroimaging studies (Boddaert et al., 2004;Waiter et al., 2005). This suggests that the developmental aspect of theEEG photic driving interhemispheric asymmetry in autistic patientsdeserves special investigation in larger groups of individuals.

Our !ndings are in accordance with the afore stated correlationbetween the autistic triad of symptoms (impairments in socialinteraction, communication and imagination) (Wing, 1997) and func-tional alterations in the right hemisphere (Ozonoff and Miller, 1996;Siegal et al.,1996; Sabbagh,1999). In addition, the results also show thatthis syndrome in autistic patients with relatively preserved languagefunctions and without signi!cant mental retardation may be accom-panied by a lack of apparent electrophysiological signs of left-hemi-sphere impairment. The EEG patterns of the interhemisphericasymmetry are, to a greater degree, determined normally by the signsof higher activation of the left hemisphere and particularly its verbalfronto-temporal regions, predominantly owing to the verballymediatedprocesses of voluntary attention (Butler and Glass, 1974; Lazarev, 1998).This canpartially explainwhymany EEG studies of autistic patientswithlanguage disorders describe abnormalities predominantly in theanterior and temporal areas of the left hemisphere (Dawson et al.,1983; Harrison et al., 1998). A strong in"uence of the “verbal factor” canmask subtle right-hemisphere functional manifestations (Lazarev,1998). In the present work, probably due to a relative exclusion of thisfactor, the utilization of a sensitive photic driving test enabled us to

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detect such alterations. Consequently, these !ndings lend certainelectrophysiological support to the hypothesis of right-hemispherealterations in autistic subjects proposed in the above-mentionedneuropsychological studies and con!rmed by neuroimaging (McKelveyet al.,1995;Waiter et al., 2005), EEG (Stroganova et al., 2007) and event-related potential techniques (Kujala et al., 2005; Senju et al., 2005). Theresults obtained show that quantitative topographic characteristics ofthe EEG photic driving may provide an additional instrument for theinvestigation of neurophysiological mechanisms underlying autisticsymptoms. However, further researchwouldneed special investigationsof the interhemispheric driving asymmetry in relation to other autisticsyndromes, I.Q. and character and degree of hemispheric dominanceestimated by special neuropsychological tests.

Acknowledgments

The authors are grateful to Dr. D. Morsch and her collaborators forpsychological evaluation of the patients.We thank A. Peres for technicalassistance, S.C. Gomes Junior for assistance in the data processing andProf. Dr. A.F.C. Infantosi, Dr. P.R. Galhanone and Dr. C. Hedin-Pereira forvaluable comments on this manuscript.

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