Evoked potential maps in learning disabled children

Electroencephalography and clinical Neurophysiology, 1986, 65:399-404 Elsevier Scientific Publishers Ireland, Ltd.

399

Short communication EVOKED

POTENTIAL

MAPS

IN LEARNING

DISABLED

CHILDREN

JEFFREY P. SUTTON 1, JOEL L. WHITTON, MICHAEL TOPA and HARVEY MOLDOFSKY Department of Psychiatry, University of Toronto, Toronto, Ont. M 5 S IA 7 (Canada)

(Accepted for publication: April 17, 1986)

Summary Some childhood learning disabilities are associated with altered synchrony patterns of brain evoked potentials. Scalp recorded electrical synchrony between selected brain regions was measured in response to visual, auditory and somatosensory stimuli and compared between a group of learning disabled children and a group of normal children. Statistically significant inter-group differences revealed stimulus dependent greater inter-regional EP synchrony in the learning disabled group. These findings support the notion that some childhood learning disabilities reflect, in part, altered connections between selected brain regions. Keywords: evoked potential maps - learning disabilities - children

The possibility that a neurophysiological alteration may underlie some learning disabilities (LD) of childhood has been considered since the turn of this century (Hinshelwood 1900). While there is still no universally accepted theory concerning the nature of this alteration, it has been suggested that a disturbance in the connections between selected brain regions may, in part, be associated with some LD (Geschwind 1965; Sevush and Heilman 1984). This notion has been supported by several scalp electroencephalogram (EEG) spectral coherence findings. In particular, some LD children have been reported to display greater intra-hernispheric and less homologous inter-hemispheric spectral EEG coherences than normal children (Sklar et al. 1973; Montagu 1975). Increased EEG alpha coherence between the left parietal and left occipital regions has also been observed in a group of dyslexic children (Leisman and Ashkenazi 1980). Evoked potential (EP)' investigations of children with LD have traditionally examined amplitude and component latency measures of the averaged EP (reviewed by John 1977; Andriola 1983) and have generally not addressed the possibility that real time synchrony measures between different scalp locations within an EP may prove informative. Recently, inter-hemispheric synchrony has been measured within verbal averaged brain evoked potentials in a group of dyslexic boys and has been found to be greater than that found in a group of normal boys (Cohen and Breslin 1984). In addition to examining averaged EP synchrony, evidence of altered inter-regional brain connectivity associated with some childhood LD may be found in examining synchrony patterns within unaveraged EPs. This technique is based on the 1 Requests for reprints should be addressed to: Dr. J.P. Sutton, Dept. of Physics, Univ. of Toronto, Toronto, Ont. M5S 1A7, Canada.

concept that during individual EPs many brain areas are functionally related and has been used to study EPs during purposive tasks in normal adults (Gevins et al. 1981, 1985). To our knowledge, however, the technique of examining synchrony patterns within unaveraged EPs has not been used in EEG studies of individuals with neurological or psychiatric conditions. In the present study, we hypothesize that an alteration in EEG activity in some childhood LD can be demonstrated by measuring synchrony patterns within unaveraged EPs.

Method Subjects

A population of 150 children in grades 1 and 2 from middle-class urban families was psychologically assessed for LD. This assessment was administered on both a group and individual basis in the natural elementary school classroom setting and consisted of the following psychological tests: the Goodenough Draw a Person Test (GDAPT) (Goodenough 1926), the Bender Visual-Motor Gestalt Test (Bender 1938), a printing task in which children were asked to reproduce the numerals 1-20 which assessed the number of correct reproductions and the number of reversals, the Raven's Colored Progressive Matrices Test (Raven 1965), the Loban Language Rating Scale (Loban 1976), the reading recognition portion of the Peabody Individual Achievement Test (PIAT) (Dunn and Markwardt 1970), and the error and latency scores from the Matching Familiar Figures Test (MFFT) (Kagen et al. 1964). A grade equivalent score derived from teacher estimates of reading achievement was also obtained. The testing was conducted late in the spring term of the academic year. The same teachers had therefore followed the progress of each student

0168-5597/86/$03.50 © 1986 Elsevier Scientific Publishers Ireland, Ltd.

400

J.P. SUTTON ET AL.

TABLE I

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Psychometric profiles of the LD and control groups giving the mean standard scores with standard deviations in parentheses.

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Psychological test

Control

LD

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Draw a person Bender Gestalt Numerals Reversals Raven's Colored Matrices

102.1 (14.0) 102.3 (10.6) 103.7 (12.4) 94.4(23.4) 101.6 (18.2)

91.7 (11.5) 92.2 (6.3) 87.4 (19.6) 87.2(18.4) 84.4 (10.0)

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Loban Language Scale P l A T Reading Achievement M F F T - errors M F F T - latency Teacher estimates - reading

110.9(11.5) 113.7 (23.1) 102.5 (13.4) 97.3 (9.8) 111.1 (26.3)

91.1(9.4) 92.7 (4.7) 87.5 (14.1) 88.5 (14.3) 90.6 (8.2)

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5 girls with a mean age of 7.4+0.6 years was diagnosed as learning disabled. All 11 children were right handed for writing. Criteria for inclusion in the LD group were: (a) normal intelligence as determined by a standard score of greater than 80 on the G D A P T , a test that has been shown to agree significantly with other estimates of children's intelligence (Harris 1963); (b) low Loban Language Rating Scale and PIAT Reading Achievement scores; and (c) a low teacher estimated grade equivalent score of reading achievement given the child's intelligence, age and previous schooling. This last measure has been shown to be reliable in distinguishing normal from learning disabled children (reviewed in Colarusso et al. 1980).

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for several months. All children screened had normal or corrected-to-normal hearing and vision and had no history of neurological or psychiatric disturbances. A group of 11 Caucasian children consisting of 6 boys and

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Fig. 1. Visual grand averaged EPs at 1)3 are shown for the LD and control groups. A typical standard error of the mean (S.E.M.) value for both curves is illustrated on the left side of the graph.

photostimulator was 1 m from the subject and produced a 10 /xsec flash peak intensity of 4.75 x 106 lumens. The click was delivered binaurally through TDH-39 headphones and consisted of a 100 ~sec 90 dB tone with spectral energy peaking at 500 and 2000 Hz. The tap was delivered by a solonoid plunger traveling 1 cm to tap a 0.5 cm 2 area overlying the left median nerve at the wrist with a force of 50-60 g / m m 2. The children were instructed to carefully attend to the stimuli throughout the testing. Amplification of the EP signals was achieved by a polygraph with half-power points of 0.3 and 35 Hz. A PDP 11/02

Scores from the other screening tests were also used to delineate the learning disabled group. Each of the children in the LD group was matched to a right handed control by sex, age to within 3 months, and standard G D A P T score to within 1 S.D. None of the children in either the LD or the control group was on any medication. Summary data on the psychometric profiles of the two groups are reported in Table I.

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Procedure

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Evoked potential testing of the 11 LD children and their matched controls was conducted with informed consent within 1 m o n t h of psychological testing. Each subject was individually familiarized with the laboratory during an EEG recording session conducted before the EP testing was performed. During the EP procedures, the subject was seated in a comfortable armchair within an electrostatistically shielded room. Ag-AgC1 electrodes were placed at the homologous scalp areas F3, F4, C3, C4, T3, T4, P3, I)4, O1 and O z according to the standard 1 0 / 2 0 system and referenced to linked earlobes. A forehead ground was used, and the electro-oculogram was monitored, EPs were elicited by 50 trials each of a binocular stroboscopic flash, binaural click, and somatosensory tap to the left wrist delivered in a random order at a random rate. The Grass PS2E

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T 1 me (ms@c) Fig. 2. Comparison of the C3-P3 averaged normalized correlation coefficient ( N C C ) c u r v e s for the visual EP. Representative standard error of the mean (S.E.M.) values are shown at the left of the graph. Points where the two curves differ at the P < 0.001 level are marked by an asterisk (*).

EP MAPS IN L E A R N I N G DISABLED C H I L D R E N was used for data acquisition and included a program that rejected EPs containing eye movement artifacts. The EP channels were digitized at 7.8125 msec and bidirectionally filtered of 60 Hz artifact by a 4-pole 0.5 dB ripple Chebyshev filter run twice end-to-end in a manner that preserved phase relationships,

Data analysis All digital analysis was performed on an IBM 370 computer located at the University of Toronto. For each subject, 500 msec averaged EPs were constructed for each electrode site and for each stimulus type. Grand averaged EPs for both the LD and control groups were determined. Inter-group comparison of grand averaged EP amplitudes was performed at each digitized sampling time using the standard normal statistic.

401 Peak amplitude latencies of several EP components including the late postive component P3 were visually determined for each averaged EP by a technician who was blind to the diagnosis of the subjects. The peak amplitude latencies for each stimulus type and subject group were averaged. Between group differences in component latencies were calculated using standard normal statistics. Synchrony within the EPs was determined by analysis of unaveraged data. For each subject and each digitized sampling time, the amplitudes of any two different unaveraged EP signals were compared wiflfin the 50 trials of any one stimulus response using the Pearson's sample correlation coefficient. If xs(t) and ys(t) denote the amplitude of a given subject's unaveraged signal recorded from electrodes x and y on the s 'h EP trial, then the Pearson's coefficient rxy(t ) is given by

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Fig. 3. Diagrams of differences between the L D and control groups in scalp recordings of EP synchrony. Each diagram schematically shows electrode placement according to the standard 10/20 system as illustrated in the bottom left diagram. Significant inter-group differences at the P < 0.001 level are mapped in space and time for each stimulus response, 0 msec corresponding to the time of stimulus onset. For simplicity, the temporal component of cach inter-group difference is restricted to ] of 6 epochs within the first 500 msec of the EP. In all cases, the L D group displays greater inter-regional synchrony than the control group.

402

J.P. S U T T O N ET AL. 5O [xs(t ) -~(t)][ys(t ) -y(t)] S=|

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[x~(t) - £(t)] 2 ~ [ys(t) - y(t)] 2 s= 1 ~= 1 , s0 f where f(t) = g0Y~s=l ~(t), f = x,y. The rxy(t ) values were normalized by the Fisher transformation r~y(t) --+ tanh 1 [rxy(t)]" The average electrode pair correlation coefficients across subjects for the two populations were compared using the standard normal statistic at each sampling time. To avoid selection of the extremes, significant differences in averaged correlation coefficients between the two groups were taken to be at the P < 0.001 level. Significant inter-population differences in EP synchrony consisted of P < 0.001 averaged correlation coefficient differences that occurred over two or more consecutive sampling times of an EP.

Results

Subject analysis The prevalence rate of learning disabilities among the 150 children was found to be 7.3%. A multivariate analysis of variance of the psychometric profiles summarized in Table I revealed that Loban Language Rating Scale scores accounted for 55% of the variance in identifying the LD population. The next highest variance measures were the P l A T Reading Achievement test and the teacher estimates of reading achievement, each accounting for approximately 30% of the psychometric variance,

Evoked potential analysis Plotted in Fig. 1 are the grand averaged visual EPs for the left parietal electrode. Analysis of these EPs as well as all other grand averaged EPs did not reveal any significant inter-pQpulation differences in EP amplitudes or peak amplitude latencies at the P < 0.001 level. In particular, no significant differences in P3 component latencies were found between the two groups in any of the stimulus type grand averaged EPs. Significant inter-population EP differences, however, were found in the synchrony analysis performed on unaveraged EPs. In Fig. 2, the averaged normalized correlation curves for left central-left parietal visual EP synchrony are plotted. From these plots, it is noted that the learning disabled group displayed significantly greater correlation values than the control group from 31 msec to 39 msec, from 54 msec to 70 msec, from 133 msec to 140 msec, from 203 msec to 257 msec and from 359 to 367 msec of the visual EP. A s u m m a r y of the significant inter-population EP synchrony differences for all stimulus types is given in Fig. 3. In a// cases where significant synchrony differences exist, the learning disabled population revealed greater inter-regional EP synchrony than the control group, Within the visual EP, the children with LD were found to have increased synchrony in the frontoparietal areas between 30 msec and 40 msec, in the centroparietal and occipitotem-

poral areas between 120 msec and 150 msec, and in the frontotemporal and frontoparietal areas after 350 msec ( P < 0.001). It was also observed that differences in the synchrony patterns between the two populations moved along an anteroposterior axis during the first 120 msec of the visual EP and that the LD population displayed greater EP synchrony in the left parietal area throughout most of the recorded visual EP. Many symmetric intra- and inter-hemispheric synchrony differences including increased synchrony between central, parietal and occipital areas in the LD group were observed between 50 msec and 80 msec of the auditory EP ( P < 0.00l). By approximately 120 msec of the auditory EP, inter-group differences had localized to bilateral frontotemporal regions ( P < 0.001). In contrast to the visual and auditory EP findings, there were relatively few inter-group somatosensory EP synchrony differences. After 350 msec of the somatosensory EP, the LD children showed greater right temporal-left frontal, parietal and occipital synchrony than the normal children ( P < 0.001). C o m m o n between-group differences for all 3 stimulus modalities occurred in the left centroparietal region between 250 msec and 260 msec of the EPs ( P < 0.001). Canonical correlations between this observation and the raw psychometric scores were found to best correlate with the Loban Language Rating Scale scores.

Discussion The results of this study reveal altered EP synchrony patterns in the LD group. EP synchrony differences were identified despite the fact that no significant inter-group differences were detected using measures of grand averaged EP amplitudes and component latencies. In general, the ability of grand averaged EPs to distinguish LD and normal children remains unclear since there are several contradictory reports concerning grand averaged EP findings in LD children (Conners 1971; Sobotka and May 1977; Dainer et al. 1981). Criteria differences for identifying LD, age and population subtype effects, and EP paradigm differences may all contribute to apparent inconsistencies in the literature. In this study, identification of LD subjects was based on findings of academic difficulty despite normal G D A P T scores and no demonstrable physical, emotional or social handicap. Academic difficulty was defined as depressed language and reading abilities given the child's intelligence, age and previous schooling. The prevalence rate for LD of 7.3% was consistent with previous reports of LD prevalence (Rutter et al. 1970; Meier 1971; Berger et al. 1975). Three different standard sensory stimuli were used to elicit the EPs. The possibility that some LD children may have an EP alteration as early as 30 or 40 msec, a time when cortical processes associated with sensory EPs have been relatively well understood (reviewed in Goff et al. 1978), was a central consideration in using sensory stimuli. A cognitive paradigm m a y have been more appropriate to use than simple stimuli if the investigation had focused on later EP components when

EP MAPS IN L E A R N I N G DISABLED C H I L D R E N levels of attention have been shown to influence EP measures (Holcomb et al. 1985). The observation that no significant inter-group differences in P3 amplitudes were detected in this study suggests that both groups of children attended similarly as the sensory stimuli were presented in random order at a random rate. All 3 stimuli elicited inter-group EP synchrony differences, most differences occurring before 150 msec of the EP. Each stimulus was characterized by separate patterns of inter-group correlation differences. From a mass action perspective, these patterns reflect complex altered interactions of neural masses within and between hemispheres in the LD children in response to simple sensory stimulation. The details of these patterns may prove informative to studies of inter- and intrahemispheric processing of simple sensory stimuli in LD children (Broman et al. 1985). A possible explanation for why synchrony analysis revealed significant inter-group EP correlation differences whereas grand averaged EP analysis did not may lie in the structural form of Pearson's coefficient. The denominator of the coefficient is a function of the inter-trial EP variances, a measure which is lost in calculating the grand averaged EP. EP variance has been considered valuable in investigations of children with behavioral problems (Callaway et al. 1983), and this may also apply to LD children. In all cases where significant inter-group differences existed, the LD group showed greater inter-regional EP synchrony than the control group. Specifically, greater inter-regional EP synchrony in the LD population was found during the visual response, consistent with findings of delayed alpha rhythm attenuation in some LD children (Fuller 1977). Within the auditory EP, dramatic inter-group synchrony differences between 50 msec and 120 msec suggest that some LD children m a y have an alteration in auditory association. The few intergroup somatosensory EP differences that were found occurred late in the EP and were likely not stimulus specific; their significance is not known, Localized inter-population synchrony differences c o m m o n to all 3 sensory modalities occurred in the left parietal area. This finding is consistent with the observation of increased left parietal area coherence in the resting EEG of some LD children (Leisman and Ashkenazi 1980) and the fact that the best correlated psychological measure was a language task (Giannitrapani 1985). The finding of a left parietal area EP alteration in the LD children also provides quantitative support for theories that regard this area as important in language and learning operations (Orton 1925; Geschwind et al. 1979; Luria 1980). In conclusion, whether a mass action or localization view of the data is adopted, both interpretations support the notion that alterations in connections between selected brain regions may, in part, underlie some childhood LD.

403 R6sum6

Cartes des potentiels booqubs chez l'enfant prbsentant des difficultbs d'acquisition Certains d6ficits d'acquisition chez l'enfant sont associ6s des perturbations de la synchronic des potentiels 6voqu6s (PE) c~r6braux. On a mesur6 sur le scalp, la synchronic 61ectrique entre r6gions c6r6brales choisies, ceci en r6ponse h des stimulus visuels, auditifs et somatosensoriels, et pour deux groupes d'enfants, r u n normal, l'autre atteints de d6ficits. Des diff6rences inter-groupe, statistiquement significatives, ont r6v61~ une synchronic PE inter-r6gions plus d6pendante du stimulus dans le groupe des enfants d6ficitaires. Ces r6sultats sont en faveur de l'hypoth~se qu'un trouble de lecture refl&e, en partie, une perturbation des connexions entre certaines r6gions c6r6brales. The authors would like to thank Professor George Owen for his help in the statistical analysis involved in this study. The authors also acknowledge Jim Mourant and Terry Jones for their technical assistance, and Jennifer Borins for her help in editing the manuscript. This research was supported by the Canadian Psychiatric Research Foundation.

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