European Child & Adolescent Psychiatry 12:36–42 (2003) DOI 10.1007/s00787-003-0307-5

L. Baving M. Laucht M. H. Schmidt

Accepted: 18 November 2002

L. Baving · M. Laucht · M. H. Schmidt Department of Child and Adolescent Psychiatry and Psychotherapy Central Institute of Mental Health Mannheim, Germany Lioba Baving, M. D., Ph. D. () University of Magdeburg Department of Child & Adolescent Psychiatry E.-Larisch-Weg 17–19 39112 Magdeburg, Germany Tel.:+49-3 91/67 17-2 15 Fax:+49-3 91/67 17-2 45 E-Mail: [email protected]

ORIGINAL CONTRIBUTION

Frontal EEG correlates of externalizing spectrum behaviors

■ Abstract An atypical EEG pattern of frontal brain activation, which has been related to compromised emotional regulation in children and adults, is hypothesized to be also present in children with externalizing behavior problems. Seventy-eight children at 11 years of age were examined to answer the following questions: 1) do children with externalizing behaviors exhibit an atypical pattern of frontal brain activation which can be linked to the severity of their problem behaviors? and 2) are there gender differences in these frontal activation patterns? Spontaneous EEG activity was subjected to power spectral analysis. In externalizing girls, the well-known pattern of a significantly greater right

ECAP 307

Introduction Externalizing behavior problems represent the most common impairment to mental health in boys as well as in girls, causing considerable costs for the individual and the society. A relatively unexplored aspect of externalizing pathology is the difficulty to regulate emotions. Externalizers show more intense and frequent negative emotions, especially anger, frustration, and irritability, as well as dysregulated emotion regulation behaviors [5, 14, 15, 23]. Even within a group of children with externalizing symptomatology, parameters of emotion regulation could differentiate children with regard to behavioral symptom load: highly aggressive ADHD boys used significantly less constructive strategies of emotional

than left frontal brain activation emerged that has been found previously in emotionally disordered children, whereas healthy girls showed a significantly greater left than right frontal activation. In contrast, healthy boys demonstrated a significantly greater right than left frontal activation, whereas externalizing boys did not display a frontal brain asymmetry. Thus, the pattern of frontal brain activation was gender specific. The atypical activation pattern in externalizing children is hypothesized to be a biological correlate of difficulties in regulating emotion. ■ Key words frontal brain asymmetry – EEG – externalizing symptoms – child – gender

coping than those ADHD boys who were not more aggressive than healthy boys. Likewise, subjects’ non-compliance exhibited in a summer camp was predicted by their ability to regulate emotion [33]. Early in their life, children display stable interindividual differences in positive and negative emotional reactivity which are central to determining either vulnerability or resilience to psychopathology [8]. Activation in the left frontal brain region has been associated with the expression of positive emotions; activation in the right frontal brain corresponds to negative emotions [9, 11, 18]. Frontal brain asymmetry in the EEG, determined as the difference between right and left frontal alpha power, is used as a measure of the balance between left and right frontal brain activation. The pattern of frontal brain activation was found to indicate whether or not a

L. Baving et al. Frontal EEG correlates

certain temperamental disposition was associated with maladaptive behavior [19]. A higher occurrence of maladaptive behavior emerged in preschool children with a greater right than left frontal brain activation pattern. The type of problem behavior was determined by temperamental disposition: shy children suffered from internalizing problems when displaying a right frontal brain asymmetry, whereas in highly sociable children with this frontal activation pattern externalizing problems were found. In the same vein, children concerned by disruptive behavior disorders showed an atypical pattern of frontal brain activation compared to healthy controls [1, 2]. An important aim is to establish correlations between behavioral dysfunctions and biological markers in non-clinical samples. Therefore, a dimensional approach to externalizing symptomatology was chosen for the present investigation. Children with a heightened level of emotional symptoms were excluded for theoretical reasons, since an atypical EEG activation pattern might be attributable to emotional psychopathology. A further question concerns the existence of genderspecific differences in brain activation patterns related to gender differences in emotion regulation. Girls are more emotionally responsive than boys, as reflected by subjective and objective measures [32], a gender difference which can be found within hours after delivery [34]. On the biological level, healthy boys but not healthy girls showed attenuation of amygdalar fMRI activity in response to fearful faces with repeated presentation [39]. In a PET study, healthy women displayed extended bilateral orbitofrontal and inferior frontal activation during transient self-induced sadness whereas in men predominantly left-sided activation in these areas emerged [35]. EEG studies of frontal brain asymmetry usually did not analyze gender differences or examined predominantly or even exclusively females (e. g., 3, 12, 21, 40, 43, 44). In a recent fMRI-study, age- and genderrelated differences in amygdalar and prefrontal activation during emotional processing were demonstrated in children and adolescents [25]. In the present study, we examined frontal EEG activation patterns of children with externalizing spectrum symptoms as well as gender-related differences.

Method ■ Subjects The reported data are from the Mannheim Study of Risk Children [30], a longitudinal study of infants born at risk for later psychopathology. Three hundred and sixty two firstborn children of German parents, all of Caucasian ethnicity, especially from psychosocially disadvantaged backgrounds, had been recruited from two obstetric

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hospitals and six children’s hospitals. The proportion of approached subjects who agreed to participate was 64.5 %. Children were seen at the ages of 3 months, 2, 41/2, 8 and 11 years. For the current investigation, 11-year-old children displaying externalizing behavior problems were compared to healthy subjects from the overall sample. All subjects received the same diagnostic assessment. Psychopathological symptoms were examined by a structured interview, the Mannheim Parent Interview [16]. The Mannheim Parent Interview was administered to the child’s mother by experienced clinical psychologists who had been extensively trained in the administration of the interview. A broad range of symptoms were assessed in a standardized manner including symptom frequency, duration, intensity, and phenomenology. Symptoms were coded to reflect oppositional behavior, temper tantrums, aggressive behavior, conduct problems such as lying, stealing, and destructive behavior, attention problems, hyperactivity, dysphoric mood, shyness, overanxiety, separation anxiety, special phobias, eating and sleeping problems, etc. Symptoms were rated on a three-point severity scale (not present, moderate, severe). Additionally, several symptoms (e. g., oppositional behavior, destructive behavior) were rated by a clinical expert during the child’s examination. Symptoms were summed, leading to composite scores, among others for externalizing symptoms (such as hyperactivity, aggressive and oppositional behavior) with a maximum score of 10. A systematic investigation of interrater reliability had been carried out with the Mannheim Parent Interview conducted in children at eight years. On single behavior problems, mean inter-rater reliability was kappa = 0.77, indicating a high level of agreement. Kappas for externalizing symptoms ranged from 0.79 to 1.00 (mean kappa 0.88). Reliability was not specifically analyzed for children at eleven years of age but the same interview was used as at the age of eight years, with slight adjustment to the different age group. The interviewer training was also carried out in the same manner. Thus, it can be safely assumed that the reliability is comparable in both age groups. The Mannheim Parent Interview has been further shown to be a sensitive measure of child disturbance, as agreement with an independent child-psychiatric evaluation ranged between 71 % and 100 % of patients [17]. Children at 11 years of age with at least two externalizing symptoms were compared to healthy controls without present or previous externalizing symptoms. In both groups, only children who displayed not more than one emotional symptom (e. g., phobic anxiety, shyness, overanxiety, depression) were included. Children with a neurological disorder, motor skills disorder, communication disorder or learning disorder were excluded after a thorough assessment that included standard measures

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of neurological dysfunction, fine and gross motor skills, expressive and receptive language disorder, reading disorder, disorder of written expression, and mathematics disorder. Psychosocial risk was determined according to an “enriched” family adversity index as proposed by Rutter and Quinton [36] covering characteristics of the parents, the partnership, and the family environment [31].All children had an IQ > 80 as measured by the Culture Fair Intelligence Test (CFT 20) [42]. To control for hemispheric specialization, only right-handed children were included. Handedness was examined by inquiring the child about the dominant hand in several daily activities. Thirty-nine externalizers (28 male) and 39 healthy control children (14 male) from the total population-based sample were included in the analysis. Subjects did not take any psychotropic medication.

■ EEG recording During EEG recording, children sat in a dimly illuminated, sound attenuated and partially electrically shielded chamber in a reclining chair.We made sure that the child felt comfortable during the recording session. While the child was being prepared for EEG testing, he/she was entertained with cartoons and offered beverages and sweets. A lycra stretch cap was placed on the child’s head. The 19 electrodes in the cap were arranged according to the 10–20 system. Abralyt light® was used to gently abrade the scalp, and as an electrolyte. Impedances less than 5 kOhm were accepted. Before and after the EEG recording the child was asked if he/she felt comfortable. A three-minute period of baseline EEG activity with eyes open was recorded with a Schwarzer amplifier while the child watched a film clip with a slightly positive emotional content. Active EEG leads were referenced to averaged mastoids and, after recording, off-line re-referenced to the average reference. Vertical and horizontal EOG were recorded with electrodes placed above and below the left eye and in the outer canthi. Bandwidth ranged from 0.5 to 70 Hz. Data were digitized at a rate of 256 Hz.

■ EEG analysis and measures For off-line EEG analysis, the SCAN program (Vers. 3.0, NEUROSCAN) was used. Following digital filtering (1–30 Hz, slope 24 dB/octave), the continuously recorded EEG data were divided into 90 2-second epochs.After automatic artifact rejection of epochs with voltages exceeding ± 100 µV, all epochs were visually inspected and those contaminated by artifacts were rejected.A minimum of 15 artifact-free epochs per subject were required for the inclusion in the analysis. The average number of 2-second epochs per subject was higher,

and no significant group differences were found (externalizing boys: 24.9 ± 10.5, healthy boys: 18.9 ± 6.3, externalizing girls: 26.3 ± 13.3, healthy girls: 26.6 ± 11.5; all p > 0.05). To obtain stable estimates of spectral power, a minimum of about 10 to 15 seconds of EEG activity is needed [7].After computing the average reference a Fast Fourier Transform (FFT) was performed (cosine window, 10 % overlap). The power density was calculated for the lower alpha band (8–10 Hz) which is the relevant alpha frequency range for children in this age group. For reasons of compatibility with the existing body of literature, two homologous frontal (F3, F4) and parietal (P3, P4) electrode sites were included in the analysis. EEG power for each site was natural log (ln) transformed in order to normalize distributions. These logtransformed absolute power values were entered into the further analyses. Additionally, laterality difference scores were computed that reflect the relative power of homologous right- and left-hemisphere regions. These scores are favorable in order to control for individual differences in the general level of EEG power. This is important because a major part of individuals’ variance in absolute power is due to differences in skull thickness and volume conduction from the homologous site [43]. Positive scores indicate that the alpha power is higher at the right than at the left electrode site. Since alpha activity is assumed to be inversely related to brain activity [29, 38], positive scores indicate a greater left-sided than right-sided hemispheric brain activity.

■ Statistical analysis The psychosocial risk index, derived from summing up the number of psychosocial risk items rated as present, as well as externalizing and emotional symptom scores, were subjected to two-way analyses of variance with the factors Group and Sex. Where the analysis of variance yielded significant effects, successive single comparisons were calculated. The EEG variables were analyzed by repeated measurements analyses of variance (SPSS, Vers. 10.0). Absolute power values were used to test whether any electrical brain asymmetry existed. For absolute power values, between-subject factors were Group and Sex, within-subject factors were Region and Hemisphere. Laterality scores were used to examine group and gender differences in the balance of left and right hemisphere activation. For the analysis of laterality scores, only the factors Group, Sex and Region were of relevance since laterality scores already contain the information on hemisphere differences. Overall interaction effects were decomposed by analyses of variance performed for frontal and parietal electrode sites separately in order to prevent error cumulation, followed by single comparisons for significant effects. Pearson correlations be-

L. Baving et al. Frontal EEG correlates

tween laterality scores and externalizing symptom scores were calculated to analyze brain-behavior associations.

Results ■ Sample characteristics Externalizing children were concerned by a significantly higher level of family adversity than healthy children (Group F1,74 = 14.5, p < 0.001; Sex, Group x Sex p > 0.20; see Table 1). No intelligence differences emerged between externalizing and healthy children (externalizing girls: 103.0 ± 7.4, healthy girls: 107.1 ± 11.1, externalizing boys: 106.0 ± 11.5, healthy boys: 110.6 ± 12.5; all p > 0.10). For externalizing symptoms, significant gender effects were found (Sex and Group x Sex F1,74 = 4.25, p < 0.05). Externalizing boys displayed significantly more symptoms than girls (t37 = 2.0, p < 0.05), whereas controls did not show such behaviors. As intended, groups did not differ in the number of emotional symptoms.

■ Absolute EEG power values Means and standard deviations of log-transformed power values for single electrode sites by group and

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gender are displayed in Table 2. The interaction Group x Sex x Region x Hemisphere (F1,74 = 10.14, p < 0.01) was significant, indicating that there was a differential group and sex effect for the power values of the left and right hemisphere at a particular site. Furthermore, a main effect of Sex (F1,74 = 5.90, p < 0.05) emerged, with girls displaying higher amplitudes than boys (girls: 0.74 ± 0.57 µV2/Hz; boys: 0.44 ± 0.58 µV2/Hz). A separate analysis for the frontal and parietal electrodes showed the differential group and sex effect only for frontal electrode sites (Group x Sex x Hemisphere F1,74 = 14.72, p < 0.001), whereas no interaction effects were found at parietal electrodes. Single comparisons revealed that externalizing girls displayed a significantly greater right than left frontal brain activation (F1,10 = 5.11, p < 0.05), whereas in healthy girls a significantly greater left than right frontal activation was found (F1,24 = 4.48, p < 0.05). Healthy boys showed a significantly greater right than left frontal brain activation (F1,13 = 6.00, p < 0.05), while externalizing boys did not display a frontal asymmetry (F1,27 = 1.80, p > 0.15).

■ Laterality scores The interaction Group x Sex x Region (F1,74 = 10.14, p < 0.01; no other significant main effect or interaction effect) with the significant frontal (Group x Sex F1,74 = 14.72, p < 0.001) but not parietal interaction effect

Table 1 Sample characteristics (means ± standard deviations)

Psychosocial risk index Intelligence quotient Externalizing symptoms (Mannheim Parent Interview) Emotional symptoms (Mannheim Parent Interview)

Externalizing Healthy girls girls (n = 11) (n = 25)

Externalizing Healthy boys boys (n = 28) (n = 14)

GROUP (F values)

3.2±2.7 103.0±7.4 2.9±1.2

1.0±1.2 107.1±11.1 0.0±0.0

2.5±1.7 106.0±11.5 4.3±2.6

1.3±1.9 110.6±12.5 0.0±0.0

14.50*** n. s. 81.8***

0.4±0.5

0.6±0.5

0.5±0.5

0.5±0.5

n. s.

* p < 0.05; ** p < 0.01; *** p < 0.001

Table 2 Absolute power values and laterality scores (means ± standard deviations)

Externalizing girls (n = 11) Alpha powera Frontal left Frontal right Parietal left Parietal right Laterality scoresb Frontal Parietal a Alpha power

Externalizing boys (n = 28)

Healthy boys (n = 14)

0.87±0.50 0.73±0.52 0.86±0.73 0.91±0.72

0.61±0.52 0.69±0.49 0.79±0.76 0.70±0.64

0.46±0.51 0.52±0.57 0.47±0.80 0.48±0.75

0.42±0.44 0.35±0.43 0.30±0.64 0.40±0.56

–0.15±0.21 0.04±0.31

0.07±0.17 –0.09±0.33

0.05±0.21 0.02±0.31

–0.07±0.11 0.10±0.24

= ln [8–10 Hz] power (µV2/Hz) = ln power right – ln power left

b Laterality scores

Healthy girls (n = 25)

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as described above, was decomposed by single comparisons. The frontal activation pattern in externalizing girls differed significantly from the one found in healthy girls (F1,34 = 10.65, p < 0.01), as well as in externalizing boys compared to healthy boys (F1,40 = 4.32, p < 0.05). Healthy girls differed significantly from healthy boys (F1,37 = 7.87, p < 0.01), as did externalizing girls and boys (F1,37 = 7.19, p < 0.05). Frontal laterality scores for groups and individual subjects are displayed in Figs. 1 and 2, respectively. Externalizing symptom scores correlated significantly with frontal laterality scores for girls (r = –0.51, p < 0.01) and boys (r = 0.38, p < 0.05), while no significant correlations with parietal laterality scores emerged (girls: r = 0.13, boys: r = –0.23). More severely externalizing girls showed stronger relative right-frontal brain activation. In contrast, a higher load of externalizing behavior problems was linked to lower relative right-frontal activation in boys.

Discussion In the present study, eleven-year-old girls with externalizing behavior problems showed a significantly greater relative right-frontal activation than did healthy girls. By contrast, in externalizing boys a significantly lower relative right-frontal activation was found, as compared to healthy boys. These differences emerged only at the frontal electrode sites. The level of externalizing-spec-

Fig. 1 Means and standard deviations of frontal laterality scores (8–10 Hz) (ln right – ln left = ln power right minus ln power left; these laterality difference scores reflect relative activation of homologous right- and left-hemisphere regions)

Fig. 2 Individual frontal laterality scores (8–10 Hz) (ln right – ln left = ln power right minus ln power left; these laterality difference scores reflect relative activation of homologous right- and left-hemisphere regions)

trum symptoms was found to correlate with the extent of EEG frontal lateralization with negative correlations in boys and positive correlations in girls. Our results confirm those of Fox et al. [19] who found an atypical pattern of frontal brain activation not only in internalizers, but also in externalizers. Although children with externalizing pathology suffer also from higher rates of depressive symptomatology [41], the present findings cannot be attributed to concurrent emotional symptoms as children displaying more than one emotional symptom had been excluded. Moreover, no group or gender differences for emotional symptoms were found. Likewise, no differences for intelligence level emerged. In accordance with previous studies [4, 24], children with externalizing behavior problems were concerned by a higher level of chronic family adversity. Activation of the orbitofrontal and anterior cingulate cortex is assumed to play an important role in a regulatory circuit to control the intensity of negative emotions, especially of anger [10]. A PET study comparing angerinduced with anxiety-induced rCBF changes in the same subjects found increased activity in the left medial prefrontal cortex in both emotional states, indicating that the asymmetry in frontal brain activation was not specific of the experienced emotion [26]; no gender-specific analysis was performed. In healthy men, the experience of anger in response to an insult was associated with greater relative left-frontal activation in the EEG compared to subjects who experienced neutral feedback [22]. In females, by contrast, left-frontally applied slow

L. Baving et al. Frontal EEG correlates

repetitive transcranial magnetic stimulation (rTMS), which is assumed to decrease regional neuronal activity, enhanced selective attention to angry faces, whereas right frontal rTMS resulted in reduced processing of angry faces [6]. Our results for externalizing children are in accordance with the findings of different anger-related frontal activation patterns in men and women. Moreover, the gender differences found in the current study for healthy children are similar to the EEG findings in healthy adults [27, 28]. A positive correlation between defensiveness – a cognitive style that is associated with reduced negative affect – and left frontal activation emerged in women. Men, however, exhibited the opposite pattern, with highly defensive men showing right frontal brain activation. Externalizing symptoms in males were found to be predominantly linked to right-frontal deficits. The only parameter which differentiated ADHD children, mostly boys, with normal from those with abnormal regional cerebral blood flow (rCBF) in SPECT was behavior symptom load which correlated inversely with rCBF in the right-frontal region [20]. In male ADHD subjects compared to healthy controls, a reduction of rightfrontal volume related to an impairment of sustained attention was found [37]. Our finding that boys’ externalizing symptom load was positively linked to their degree

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of relative left-frontal activation fits nicely in this line of evidence. As emotion regulation comprises attentional control – orienting to stimuli, sustained attention, and shift of attention in order to divert from potentially aversive stimuli [13] – and inhibition of negative emotions, impairments in these prefrontal executive functions may play an important role in externalizing pathology.

Conclusions An atypical pattern of frontal brain activation was found in children with externalizing behavior problems. The level of externalizing spectrum symptoms was related to relative right-frontal activation in girls and relative leftfrontal activation in boys. The frontal brain activation pattern in EEG is discussed as a neurobiological parameter of emotion regulation in externalizing children. Distinct gender differences stress the importance of gender-specific analyses. ■ Acknowledgment This project was supported by a grant of the Deutsche Forschungsgemeinschaft as part of the Sonderforschungsbereich 258 “Indicators and risk models of the genesis and course of mental disorders” at the University of Heidelberg. We thank Drs. Hösch and Stock for performing the examinations.

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