Comparative EEG study in normal and autistic children

The work represents the results of a comparative study of spectral power as well as averaged coherence in alpha, beta and gamma EEG bands in 5-to-7-year-old autistic and healthy boys in the state of rest and under cognitive load (mental calculation). The mean age of the examined children was 6 years 4 months. In both healthy and autistic children, there was a clear-cut baseline frontal-occipital gradient of the alpha activity. Performance of the cognitive task led to enhancement of spectral power in the alpha1 band and shifting its maximum to the left hemisphere, did not change the activity in the alpha2 band, and considerably increased the spectral power in the alpha3 band. In healthy children, the spectral power and average coherence of the fast rhythms increased in the central and frontal areas of the left hemisphere. The right-side dominance of the spectral power of the alpha band was revealed in autistic children both in the baseline and during cognitive task. The spectral power of the gamma band was higher in autistic children than in healthy children in the baseline. The cognitive task did not change this fast activity in autistic children.     

Interhemispheric differences in the spectral power and coherence of EEG rhythms in children with autism spectrum disorders

Electroencephalographic examination of boys aged 4–9 years with autism spectrum disorders (ASDs) showed spectral power values and coherence in high-frequency bands (20–60 Hz) in various brain areas were higher than normal. Differences in spectral power were greater in the anterior areas of the left hemisphere; differences in coherence, in the right anterior and posterior areas. Interhemispheric differences typical of healthy subjects were absent in the children with ASDs. The spectral power of the θ rhythm was lower in autism, especially in the left hemisphere. The spectral power of the α rhythm in the autistic children was lower than normal, especially in the posterior areas of the left hemisphere. The μ rhythm was higher than normal in spectral power and was localized in the right, rather than left, anterior areas. The children were examined again after corrective procedures. The α-rhythm spectral power increased (became closer to the norm) in the left posterior areas, while the γ-rhythm spectral power decreased (became closer to the norm) in the right anterior areas in some of the autistic children. The electrophysiological changes were associated with improved psychological testing results, especially in nonverbal measures.     

Increased excretion of a lipid peroxidation biomarker in autism

It is thought that autism could result from an interaction between genetic and environmental factors with oxidative stress as a potential mechanism linking the two. One genetic factor may be altered oxidative-reductive capacity. This study tested the hypothesis that children with autism have increased oxidative stress. We evaluated children with autism for the presence of two oxidative stress biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with autism and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher in children with autism. The isoprostane levels in autistic subjects were variable with a bimodal distribution. The majority of autistic subjects showed a moderate increase in isoprostane levels while a smaller group of autistic children showed dramatic increases in their isoprostane levels. There was a trend of an increase in 8-OHdG levels in children with autism but it did not reach statistical significance. There was no significant correlation between the levels of the biomarkers and vitamin intake, dietary supplements, medicine, medical disorders, or history of regression. These results suggest that the lipid peroxidation biomarker is increased in this cohort of autistic children, especially in the subgroup of autistic children.     

Level of Trace Elements (Copper,Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism

Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.     

Peak alpha frequency and psychopathological symptoms in schizophrenia

Spectral characteristic of the alpha activity (frequency of the maximum spectral peak) were comparatively studied in schizophrenic patients with predominance of positive or negative symptoms and healthy subjects in the resting state and during cognitive task performance. In patients with negative symptoms, the spectral peak frequency of the alpha activity (8-13 Hz) was decreased at rest as compared to healthy subjects in all cortical areas. In patients with positive symptoms, the peak frequency of the alpha rhythm in the occipital cortical areas was higher than in healthy subjects. The performance-induced increase in the alpha-rhythm peak frequency during cognitive tasks was less expressed in schizophrenics than in healthy subjects. A correlation of these characteristics with psychopathological symptoms was revealed. The results suggest a difference in neurophysiological mechanisms underlying positive and negative symptoms in schizophrenia.     

Urinary oxidative stress markers in children with autism

Abstract

Oxidative stress caused by increased production of free radicals and impaired functions of antioxidants remains as the major factor associated with the pathophysiology of many neuropsychiatric diseases.

Objective

The objective of the present study was to analyze the oxidative stress markers in urine sample since the collection of blood from these children is highly meticulous and also to evaluate whether these urinary markers can be correlated with the severity of autism.

Methods

The subjects of the study were 45 autistic children with different grades of severity (low functioning autism (LFA), medium functioning autism (MFA), and high functioning autism (HFA) according to Childhood Autism Rating Scale (CARS), n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were of age 4–12 years. We determined the urinary levels of oxidative stress markers like thiobarbituric acid-reacting substances, lipid hydroperoxides, 4-hydroxy nonenal, protein carbonyls, sulfhydryl groups, total antioxidant capacity, total peroxide content, oxidative stress index, and also UA/Cr ratio in autistic children.

Results

The study observed a significant elevation in the level of oxidative stress markers in autistic children when compared with normal children. The level of antioxidants excreted in urine was found to be significantly low in autistic children. These findings when correlated with the degrees of severity, oxidative stress markers showed positive correlation with increasing order of severity (LFA > MFA > HFA), whereas antioxidants showed negative correlation.

Discussion

The study reveals that the urinary levels of oxidative stress markers can be considered as the measure of oxidative stress index in autistic children. The significant correlation between the severity of autism with urinary lipid peroxidation products also support the use of oxidative stress markers and antioxidants as biomarkers of autism.     

Psychophysiologic parameters of reproducing emotions in healthy subjects and patients during the first episode of depression

We analyzed the spectral power of EEG rhythms and some psychological features in patients with depression (first episode) and in healthy subjects. In the control group, the distributions of the spectral power of the alpha3 and gamma rhythms was symmetrical. In reproducing joy, the power of the alpha3 rhythm increased in the occipital and that of the gamma rhythm increased in the temporal areas of the left hemisphere. In depressive patients, predominant activation of the left posterior cortical quadrant in the alpha3 band was observed both in the baseline activity and during reproducing emotions of both valences. In these patients, the gamma rhythm predominated in the anterior regions of the right hemisphere during rest. The mental reproduction of joy and grief in depressive patients shifted the maximal gamma rhythm spectral power to the occipital cortical regions. Thus, in depressive patients, any emotional load, regardless of its valence, results in a decrease in the pathologic gamma activity and makes the distribution of cortical electric activity more close to that of healthy subjects.     

Alpha power voluntary increasing training for cognition enhancement study

With the aim simultaneous alpha EEG stimulating and EMG decreasing biofeedback training impact on the alpha-activity and cognitive functions 27 healthy male subjects (18-34 years) were investigated in pre- and post 10 training sessions of the voluntary increasing alpha power in individual upper alpha range. The accuracy of conceptual span task, fluency and flexibility in alternatives use task performance and alpha-activity indices were compared in real (14 participants) and sham (13 participants) biofeedback groups for the discrimination of the feedback role in training. The follow up effect oftrainings was studied through month over the training sessions. Results showed that alpha biofeedback training enhanced the fluency and accuracy in cognitive performance, increased resting frequency, width and power in individual upper alpha range only in participants with low baseline alpha frequency. While mock biofeedback increased resting alpha power only in participants with high baseline resting alpha frequency and did not change the cognitive performance. Biofeedback training eliminated the alpha power decrease in response to arithmetic task in both with high and low alpha frequency participants and this effect was followed up over the month. Mock biofeedback training has no such effect. It could be concluded that alpha-EEG-EMG biofeedback has application not only for cognition enhancement, but also in prognostic aims in clinical practice and brain-computer interface technology.     

Context-dependent EEG spectral characteristics during performance of tasks

Spatial and frequency EEG characteristics of two groups of healthy adult subjects were examined in two series of experiments, which differed in conditions of the second cognitive task in a trial. The first task was the same in the two series: subjects had to evaluate size relationship between two closely spaced circles. The second task successively presented in trials of the first series consisted in the recognition of words/pseudowords, and in the second series, subjects had to localize a target letter in a matrix. It was assumed that the cognitive performance in the first series predominantly involved the ventral visual system, whereas during task performance in the second series, predominant involvement of the ventral and dorsal visual systems alternated. Multichannel EEG fragments recorded prior to the presentation of the task pairs were analyzed. Analysis of variance of the EEG spectral power revealed the generalized significant effect of the factor of the second task in the pair for delta band and lower beta subband, the power being higher in the first series. Factor brain hemisphere had a significant effect for the alpha band in the occipital area, the spectral power being lower in the left hemisphere for both experimental series. The task x hemisphere interaction was significant in the temporal cortical areas for the EEG power in alpha2 band, i.e., the predominant involvement of the ventral visual system was associated with stronger asymmetry of alpha2 rhythm and lower spectral power in this band in the left temporal area. Thus, the character of the forthcoming cognitive activity was shown to be reflected in spatio-frequency characteristics of the preceding EEG.     

Spectral power and cortical interactions in the beta2 rhythm in normal subjects and schizophrenic patients

Spectral and coherence characteristics of the beta 2 rhythm (20-40 Hz) were compared in patients with acute schizophrenia (the first episode), patients with chronic schizophrenia (disease duration more than two years), and healthy subjects (control group) during cognitive task performance. Examination showed the "excessive" spectral power of this rhythm in the prefrontal cortical areas in patients with acute schizophrenia and its "insufficient" spectral power in all derivations of the right hemisphere in patients with the chronic form as compared to the controls. The similarity of the beta 2 spectral power distribution in different cortical areas measured by covariance method decreased with increase in psychopathologic manifestations. Coherent analysis revealed a substantially lower number of cortico-cortical functional connections in schizophrenic patients than in healthy subjects, absence of interhemispheric connections in patients with acute schizophrenia, and a slight increase in their number if patients with the chronic disease. However, as distinct from the controls revealing many inter- and intrahemispheric connections in all cortical areas, in schizophrenics the interhemispheric connections were observed only in the posterior cortical regions. The results point to a disorder of interhemispheric interaction in schizophrenia.     

Iodine in autism spectrum disorders

ObjectiveThe aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology.Subjects and methodsTests were performed in 40 boys with ASD and 40 healthy boys, aged 2–17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated.Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves.Results19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician’s general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS.ConclusionThe severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required.     

Atypicalities in Perceptual Adaptation in Autism Do Not Extend to Perceptual Causality

A recent study showed that adaptation to causal events (collisions) in adults caused subsequent events to be less likely perceived as causal. In this study, we examined if a similar negative adaptation effect for perceptual causality occurs in children, both typically developing and with autism. Previous studies have reported diminished adaptation for face identity, facial configuration and gaze direction in children with autism. To test whether diminished adaptive coding extends beyond high-level social stimuli (such as faces) and could be a general property of autistic perception, we developed a child-friendly paradigm for adaptation of perceptual causality. We compared the performance of 22 children with autism with 22 typically developing children, individually matched on age and ability (IQ scores). We found significant and equally robust adaptation aftereffects for perceptual causality in both groups. There were also no differences between the two groups in their attention, as revealed by reaction times and accuracy in a change-detection task. These findings suggest that adaptation to perceptual causality in autism is largely similar to typical development and, further, that diminished adaptive coding might not be a general characteristic of autism at low levels of the perceptual hierarchy, constraining existing theories of adaptation in autism.     

Topographic characteristics of cortex activity in delta-, alpha2-, and gamma2- frequency bands related to social creativity

Social creativity-related topographic changes of the delta, alpha2, and gamma2 power were studied using 19-channel EEG. Originality and fluency indices of social thinking were evaluated on basis of specially developed 'divergent' task solution that stimulated different interpretations of social scenes; complex visual stimuli (architectural building) were used as control task. 'Divergent' task performing was characterized by both the greater power of the delta and alpha2 rhythms mostly in the right hemisphere and widespread increase in the gamma2 power as compared with the control task. Positive correlations between delta and gamma2 rhythms in baseline condition were revealed in the fronto-parietal cortex, and this relationship between low- and high-frequency oscillations while 'divergent' task performing was found in the right posterior cortex. Special topographic patterns of delta and gamma2 activity as predictors of social creativity were obtained using multiple regression analysis. These patterns can be interpreted as EEG correlates of a summation of endogenous and exogenous components of social thinking.     

The maternal effect in infantile autism: Elevated DNA damage degree in patients and their mothers

Infantile autism is a common disorder of mental development; besides hereditary predisposition, various environmental factors, including the condition of the mother’s body during pregnancy (“maternal effect”), have a significant impact on its appearance. Oxidative stress is suggested to play a key role in the pathogenesis of infantile autism. It causes a prominent genotoxic effect, which is realized through appearance of single and double strand breaks of the nuclear DNA. In patients with infantile autism and their mothers we evaluated the degree of DNA damage by using the DNA comet assay and determining the comet tail moment and DNA percent ratio in the tail. These two parameters demonstrated strong correlation (r = 0.90). Mean and median values of both parameters were significantly higher in samples from autistic children, than in agematching healthy controls. Interestingly, these parameters were also higher in healthy mothers of autistic children and they did not differ from the values in the group of autistic children. In the control group of healthy women of reproductive age, who had no children with autism, the mean value of the DNA comet tail moment significantly differed from the group of mothers of autistic children, but not from the control group of healthy children. The results suggest that mentally healthy mothers of autistic children have some genotoxic factors, which can determine development of the pathological process in the fetus via the environmental “maternal effect” during gestation.     

Phase-locked alpha oscillations evoked by illusory contour perception in normal and autistic preschool boys

We examined temporal dynamics of EEG phase-locked alpha oscillations during perception of illusory (Kanizsa square) and non-illusory images in boys with autism and age-matched typically developing boys. In typically developing boys the illusory contour (IC) as compared to the control stimulus provoked an increased alpha response at the parietal scalp areas. This IC effect demonstrated continuity within the time window of 133-267 ms after the stimulus onset. Although boys with autism did not display this effect at the group level, part of the sample showed an atypical two-stage pattern of illusory contour effect. The first early stage of IC effect (50-133 ms) was pronounced at the midline occipital electrode localized in the vicinity of the primary visual cortex. The localization and the early onset time suggest that this early IC effect is related to abnormally enhanced "low-level" locally-oriented processes of contour completion in autism. The second stage of IC effect (267-400 ms) was observed at the left parietal region only, and was delayed comparatively to that in healthy boys, suggesting the deficit of "intermediate" processes of perceptual grouping linked to the higher-order visual areas.     

Comparative study of the gamma-rhythm in the norm, pre-examination stress and patients with the first depressive episode

The work gives the results of comparative analysis of gamma-rhythm (30-40 Hz) spectral power and synchronization indices in the healthy subjects both in normal situation and before the examination with that of depressive patients with the first episode, in the rest condition and during cognitive tests performance. It is demonstrated that gamma-rhythm spectral power in frontal and temporal areas of depressive patients was significantly higher than that in the norm. In stressful situation the number of differences of healthy subjects from depressive patients decreased in the rest condition and in Kraepelin test. Spatial imagination revealed more significant differences between depressive patients and healthy subjects both in normal and in stressful situations. Gamma-rhythm synchronization level was the same in healthy subjects both in the rest condition and during the tests performance, but in stressful situation it increased in the latter situation as well as in depressive patients. Thus, in the most cases stressful situation decreases the differences of EEG indices between healthy subjects and depressive patients both in the rest condition (by spectral power) and during the tests performance (by both indices). This may point out stress as the "trigger" of depression.     

Assessment of EEG frequency dynamics using complex demodulation.

The complex demodulation (CD) approach was applied to human EEG recorded during a cognitive task performance, including voluntary goal-directed movements. The standard CD algorithm was extended by a simple procedure using frequency histograms and power spectra to select the characteristic frequencies of EEG segments around the task performance. In the majority of records, amplitude modulation was found, which decreased or disappeared in the period prior to and at the very beginning of the task performance. It was found that the decrease of modulation in fast beta and gamma components begins approximately one second before that of the alpha components. Frequency modulation appeared in some records at the end of the task in beta and gamma components. The results showed that a cognitive task performance is accompanied by non-linear processes in the frequency components of EEG. These dynamic changes could extend the findings of event-related desynchronization obtained by linear methods.     

Neural Activations during Visual Sequence Learning Leave a Trace in Post-Training Spontaneous EEG

Recent EEG studies have shown that implicit learning involving specific cortical circuits results in an enduring local trace manifested as local changes in spectral power. Here we used a well characterized visual sequence learning task and high density-(hd-)EEG recording to determine whether also declarative learning leaves a post-task, local change in the resting state oscillatory activity in the areas involved in the learning process. Thus, we recorded hd-EEG in normal subjects before, during and after the acquisition of the order of a fixed spatial target sequence (VSEQ) and during the presentation of targets in random order (VRAN). We first determined the temporal evolution of spectral changes during VSEQ and compared it to VRAN. We found significant differences in the alpha and theta bands in three main scalp regions, a right occipito-parietal (ROP), an anterior-frontal (AFr), and a right frontal (RFr) area. The changes in frontal theta power during VSEQ were positively correlated with the learning rate. Further, post-learning EEG recordings during resting state revealed a significant increase in alpha power in ROP relative to a pre-learning baseline. We conclude that declarative learning is associated with alpha and theta changes in frontal and posterior regions that occur during the task, and with an increase of alpha power in the occipito-parietal region after the task. These post-task changes may represent a trace of learning and a hallmark of use-dependent plasticity.     

Electrographic correlates of real and imaginary movements: spectral analysis

The research carried out with eight virtually healthy volunteers showed that movements were associated with the increased level of activation, primarily, in the central areas of the brain cortex, which was expressed in a reduction of the spectral power of alpha end beta frequencies and increase in the power of the gamma oscillations more expressed in the parietooccipital derivations of the left hemisphere. Mental reproduction of similar movements was accompanied by additional activation in the frontal, temporal, parietal, and occipitals regions and more pronounced increase in the power of the gamma oscillations. A number of electrographic phenomena associated with specific features of the movements were revealed.     

In vitro platelet function in infantile autism

It has previously been demonstrated that patients with infantile autism demonstrate impaired in vivo platelet behaviour. Therefore, in 14 children (13 boys and 1 girl) with infantile autism (aged 2-14, mean 6 years) and 12 healthy control boys (aged 6-15, mean 11 years) we studied in vitro platelet reactivity using ADP- and collagen-induced platelet aggregation. In each child a total of 7 different final concentrations of ADP and 4 different concentrations of collagen were employed. At all concentrations of ADP and collagen used the autistic children consistently exhibited diminished platelet aggregability; the differences, however, did not reach statistical significance. Therefore a wider panel of in vitro tests is apparently required and a larger group of patients be studied to help elucidate the functional/metabolic platelet defect met in infantile autism.