A genetic study of the human low-voltage electroencephalogram.

The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given.

Localization of a gene for the human low-voltage EEG on 20q and genetic heterogeneity.

The localization of a gene responsible for a normal variant of the human electroencephalogram to the distal part of chromosome 20q is reported. A linkage analysis, including 17 families with 191 individuals, tested with 73 RFLPs and 22 blood and serological markers, was performed for the low-voltage electroencephalogram. This is a normal variant of the human electroencephalogram with an autosomal dominant mode of inheritance. The results present strong evidence for close linkage with the highly polymorphic marker CMM6 (D20S19) and for genetic heterogeneity.

No consistent relationships between oscillations and latencies of visually and auditory evoked EEG potentials and measures of mental performance.

In this study, the hypothesis was tested whether there is any relationship between measures of intelligence and working speed on the one hand, and characteristics of visually or auditory evoked EEG potentials, on the other. The study was performed on two samples: 1. In 236 University students selected for presence of four different, inherited EEG variants, product-moment correlations were computed between test scores for various aspects of mental performance on the one hand, and two measures of averaged visual and auditory evoked EEG potentials (VEPs and AEPs), on the other. The two EP measures were the average latency of all identifiable peaks between 70 and 600 ms after stimulation; and the "oscillation", a combined measure of amplitudes, comparable to Hendrickson's "string measure". Moreover, correlations were computed between two selected test scores (IQ and Raven) on the one sides, and the amplitudes and latencies of the components named P1, N1, and P2 by Buchsbaum on the other. 2. Twenty-four adults with mental retardation of unknown origin, inmates of an institution for the mentally retarded, were compared with 19 normal controls matched for age and sex - there were no consistent positive correlations between the characteristics of VEPs and AEPs and any of the performance measures studied. Hence, the hypothesis that there are consistent correlations between oscillation and latency of EPs and measures of mental performance was not confirmed. There is no convincing overall explanation for the discrepancies between various results reported in the literature but some of them may be explained either by individual differences in EEG maturation among children, or by additional sensoric input in some series, or by admixture of subjects with organic brain damage in some of the series, or by the individual characteristics of the resting EEG - a parameter that had been neglected in all previous studies.

The 4-5 cycles per second rhythm--changes in time.

The 4-5 cycles per second (c/s) rhythm is a relatively rare, individual EEG variant. Age distribution of subjects carrying this variant and longitudinal studies over many years have indicated that it may sometimes disappear during middle age. Observations on female monozygotic twins at 15, 23 and 45 years of age suggest that disappearance of this trait might also be under genetic control.

Visually and auditory evoked EEG potentials in carriers of four hereditary EEG variants.

Visually and auditory evoked EEG potentials were studied in 248 healthy university students, who were carriers of one of the following hereditary EEG variants: Monomorphic alpha-waves; low-voltage-EEG; EEG in which the alpha-rhythm was mixed diffusely with beta-waves; and EEG with fronto-precentral beta-groups. The study uncovered consistent and statistically significant group differences between the EEG-countertypes, monomorphic alpha-waves and the low-voltage EEG: subjects with monomorphic alpha-waves showed higher amplitudes and longer latencies of most peaks of the visually evoked potential (VEP), and higher amplitudes for most peaks of the auditory evoked potentials (AEP). Similar differences between EEG types were shown for two measures--overall amplitude (oscillation) and average latency--of all peaks for VEPs and AEPs. The results are consistent with a hypothesis discussed in an earlier paper in which differences between these two EEG types in processing of information in the CNS were assumed on the basis of psychological test results and neurophysiological theory. The two EEG types with beta-waves in addition to alpha-waves showed latencies of evoked potentials in-between those found in the EEG types with monomorphic alpha-waves, on the one hand, and the low-voltage EEG on the other. There was no significant difference in the frequency of VEP augmenters and reducers between EEG types.

Relationship between behavioral maturation measured by the "Baum" test and EEG frequency. A pilot study on monozygotic and dizygotic twins.

In a pilot study, the possible influence of the inherited electroencephalogram (EEG) pattern on aspects of psychologic maturation was investigated. The twin sample consisted of 208 pairs, 110 monozygotic (MZ) and 98 dizygotic (DZ), mostly children and adolescents. The study showed a greater similarity between MZ compared with DZ twins in an immaturity score constructed from the Baum test (Koch 1976) and in a teacher's maturity scoring of essays. For both parameters, a correlation between occipital alpha-frequency and the test criterium could be demonstrated. This correlation was in the direction expected, and it was significant statistically. This result suggests an influence of genetically determined variation of brain maturation on interindividual variability of psychologic variation. Due to shortcomings of the methods used in the study, more specific conclusions cannot be drawn; the problem needs further elucidation using modern methods.

[Characterization of genetic EEG-variations with the amplitude-interval-analysis. III. Assignment of new obtained EEGs to well-known types of bioelectric activities on the basis of data of amplitude-interval-analysis (author's transl)]. / Charakterisierung erblicher EEG-Varianten mit Hilfe der Amplituden-Intervall-Analyse. III. Das Klassifizierungsproblem: Zuordnung eines neu abgeleiteten EEG zu einem de bekannten EEG-Typen aufgrund der Parameterwerte der Amplituden-Intervall-Analyse.

Quantitative description of some EEG-variants by amplitude-interval (time-domain) analysis revealed significant differences of parameter means but failed to give one single, sufficiently reliable criterion for classification. Therefore, we tried to solve the problem of classification through quantitative criteria by discriminant analysis. For each EEG, 128 different measurements were taken, but only 104 were included in the analysis; the rest failed to contribute any measurable information. For 243 of th 298 probands, the data were sufficient for inclusion in the study. Only 15 (6.2%) were classified falsely; this number was reduced to 3 (1.7%) when the calculation was performed leaving out the (64) controls. A control analysis by a Monte-Carlo-Method in which the classification criterium was calculated using 80% of all cases only, and the remaining 20% were then attributed tentatively to the variant groups, gave much less convincing results. It follows that more and better criteria for separation of these variants have to be developed before classification of EEGs exclusively on the basis of measurements will become possible.

[Characterization of genetic EEG variables with the amplitude-interval-analysis. II. Variations of the beta-activity and controls (author's transl)]. / Charakterisierung erblicher EEG-Variaten mit Hilfe der Amplituden-Intervall-Analyse. II Varianten der beta-Tätigkeit und Kontrollen.

In 165 adult male probands with different variants of beta-Activity (fronto-percentral beta-wave-groups; diffuse beta-waves) including 76 controls from the same proband population but with inconspicuous EEG patterns, a quantitative description of unipolar leads was carried out using a program for amplitude-interval (time-domain) analysis. Statistically significant differences between some means of the examined parameters were found between the various EEG variants. No single parameter, however, separates these variants reliably. For such a separation, methods of multivariate statistics will have to be used. Significant differences between left and right hemispheres (especially lower average alpha-activity together with higher beta-activity on the left-hand side) were found in all examined EEG types including the controls. Hence, the lack of a significant side difference in the variant with monotonous alpha-waves as described in the first report of this series remains unique.

[Characterization of genetic EEG-variations with the amplitude-interval-analysis. I. Variations of alpha-activity; flat-EEG; borderline flat EEG, occipital slow beta-waves; monotonous alpha-rhythm (author's transl)]. / Charakterisierung erblicher EEG-Varianten mit Hilfe der Amplituden-Intervall-Analyse. I. Varianten der alpha-Tätigkeit: Niederspannungs-EEG; Grenzfälle des Niederspannungs-EEG; okzipitale langsame beta-Wellen; EEG mit monotonen alpha-Wellen.

In 121 healthy adult male probands with different variants of alpha-activity (monotonous alpha-waves; low voltage EEG, borderline low voltage EEG; occipital slow beta-waves) a quantitative description of unipolar leads was carried out using a program for amplitude-interval (time-domain) analysis. Statistically significant differences between means of the examined parameters were discovered between the various EEG variants. No single parameter, however, separates these variants reliably. For such a separation, methods of multivariate statistics will have to be used. Significant differences between right and left hemispheres (primarily lower alpha-activity together with higher beta-activity on the left hemisphere) were found in all EEG types examined except the variant with monotonous alpha-waves.

EEG differences in neurotic as compared with normal twin pairs.

The resting EEGs of 17 twin pairs originally traced through one neurotic co-twin (10 monozygotic and 7 dizygotic pairs aged between 18 and 63 years) have been described and compared with the neuroticism scores (Schepank, 1974) of these twins. EEG comparison according to the customary visual criteria failed to show any consistent EEG differences between monozygotic co-twins, whereas dizygotic pairs often showed EEG discordance. Computerized time-domain (interval-amplitude) analysis failed to show a higher degree of EEG discordance between neurotic MZ co-twins than between co-twins in 25 adult nonneurotic male MZ pairs (age range 18--33; mean age 22.9 years). There were no significant correlations between EEG differences and differences in the neuroticism score among ten MZ pairs traced through a neurotic co-twin. It is concluded that the individual and genetically determined EEG pattern is manifest even in the face of the long-lasting psychological alterations observed in neurotics.

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. I. Rationale of the study. Material. Methods. Heritability of test parameters.

In the first section of this paper, various research designs in human behavior genetics are compared. In this context, the commonly used concept of biometric genetics is critically evaluated from the point of view of science theory. It is contrasted with the Mendelian gene concept, which, in principle, leads to a much deeper theoretical understanding by offering clues for basic mechanisms. To explore this advantage fully, a research strategy is needed that first looks for genetic variability in a physiological parameter of possible importance for human behavior and then tries to explore the influence of this parameter on the function of the human brain and on behavior. If possible, this genetic parameter should be selected in a way that inferences as to the mechanism of its influence on behavior become feasible. Such genetic variability is provided by the hereditary variants of the normal EEG discovered by earlier work (cf. Vogel, 1970). In the following section, a research program on 298 adult healthy males, most of them soldiers, with various inherited EEG variants is described. Apart from controls with inconspicuous EEGs, this material comprises probands with the following EEG variants: low-voltage (N); low-voltage borderline (NG); monotonous alpha-waves (R); occipital fast alpha-variants (BO); fronto-precentral beta-groups (BG), and diffuse beta-waves (BD). In addition to an EEG examination, the probands were examined with various test methods measuring intelligence (IST; LPS; Raven); working speed and concentration (d-2; KLT); personal attitudes (MMPI; 16PF; RKS); and sensory and motor abilities (flicker fusion; tachistoscopy; reaction time to optic, acoustic and combined stimuli; two-hand dexterity; pursuit rotor; tapping). In a supplementary twin study on 52 male adult twin pairs (26 MZ, 26 DZ), heritabilities were determined for the test scores included in the main study. For most test scores, heritabilities are relatively low; the data are compared with those from the literature. We conclude that the test methods utilized in the main study (on EEG variants) are expected to demonstrate at the most a small to moderate correlation of the EEGs with psychological phenotypes as defined by test examinations, even if a major part of the genetic variability underlying these phenotypes would be due to differences in brain physiology that could be revealed by EEG variation.

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. II. Results.

The results of psychological examinations on 298 adult male probands with various inherited EEG variants are described. They may be summarized as follows: 1) The low-voltage (N) group scored high in intelligence tests, especially in spatial orientation. Personality scores revealed this group as 'normal', extravert, group-dependent, and not very energetic. 2) The borderline low-voltage (NG) group showed slight weakness in abstract thinking, short-time memory, and motor skills and a relatively strong tendency to have 'neurotic' complaints. Reaction time and motor skills were poor. 3) The occipital fast alpha-variants (BO) group performed very well in tests of abstract thinking and motor skills. 4) The monotonous alpha (R) group showed average performance in most intelligence scores but above-average in short-time memory and in precision under stress conditions. Personality scores indicated high spontaneous activity and toughmindedness. 5) The BG (fronto-precentral beta-group) category showed very low MMPI scores, indicating little neurotic tendency. Intelligence could be above average. 6) The diffuse beta (BD) group scored low in intelligence tests, especially in spatial orientation, and had a high error rate in tests measuring concentration and precision. Most differences were relatively small; the whole range of test scores could be found in all EEG groups.

The electroencephalogram (EEG) as a research tool in human behavior genetics: psychological examinations in healthy males with various inherited EEG variants. III. Interpretation of the results.

Interpretation of the results from psychological examinations of 298 probands with inherited EEG variants requires (1) critical evaluation of previous literature on psychological EEG correlates, (2) knowledge of the main concepts and experimental approaches for elucidating the basic mechanisms of EEG rhythms, (3) discussion of previous attempts to link psychological variation in human populations with corresponding variation in brain function, and (4) interpretation of results from considerations at these three levels with the data from our own study. At the first level (previous psychological studies), comparison with Schmettau's study proved to be especially revealing: Her conclusions about personality correlates with high alpha-index and with "flat" EEGs were very similar to ours with the monotonous alpha- (R) and low-voltage (N) EEGs, respectively. Her EEG type with high beta-index overlaps with our beta-diffuse (BD) type; a tendency to psychasthenia and low resistance to stress is less obvious in our group, but is expressed indirectly by reduced speed and accuracy in tests requiring attentiveness and persistence. The correlation between alpha-frequency and intelligence found in other studies was confirmed by the especially high intelligence scores of our group with occipital fast alpha-variants (BO). At the second and third levels of the discussion (EEG mechanisms; neurophysiological theories), the cooperation of cerebral cortex (EEG battery), thalamus (pacemaker), and ARAS (tonic arousal) is discussed, and the personality typologies of Eysenck and Claridge are mentioned. From this and other evidence, the following hypotheses are discussed: 1) The personality profiles of the R group are influenced by high activity and efficiency of the thalamic alpha-pacemaker(s), which leads to a high degree of modulation, selection, and amplification of afferent stimuli. 2) In the countertype of this EEG variant, the N EEG, a low modulation and amplification by the thalamic alpha-pacemaker is assumed. This leads to relatively low intensity of feeling and to low spontaneous activity, but to faster information processing. Combined with an increased level of tonic arousal in the ARAS, it may cause certain 'neurotic' complaints (our low-voltage borderline (NG) group). 3) The EEG with diffuse beta-waves (BD) is caused by a high level of tonic arousal in the ARAS, which tends to distrub the thalamocortical circuit. This leads to reduced stress resistance and to impairment of intellectual functions, especially space perception. Due to limited evidence, the next two hypotheses are advanced only tentatively: 4) alpha-rhythm with very high frequency 16--19 c/s) leads to improvement of information processing and, hence, to high intellectual performance and motor dexterity. 5) Probands with frontoprecentral beta-groups (BG) show no psychological signs of increased tonic arousal; therefore, these beta-groups are caused not by increased tonic arousal of the ARAS, but by a genetic variant of a thalamic subsystem.