Abnormal EEG lateralization in boys with autism

Stroganova, Tatiana A.; Nygren, Gudrun; Tsetlin, Marina M.; Posikera, I. N.; Gillberg, Christopher; Elam, Mikael; Orekhova, Elena V.

doi:10.1016/j.clinph.2007.05.005

Cited by 111 publications

(98 citation statements)

References 63 publications

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“…Interestingly, abnormalities in low-frequency neuronal oscillations have been reported in ASD children (33,34). In addition, impairments in α and γ oscillations have also been described in ASDs, as α is believed to function in attention suppression of distracting stimuli and γ in feature binding (42,43).…”

Section: Discussionmentioning

confidence: 99%

“…Given that oscillatory activity in low-frequency ranges is associated with long-range neuronal circuit communication and high-frequency oscillations with local circuit communication (28,32), our data suggest that ERP deficits in Cdkl5 -/y mice may be mediated by impairments in long-range communication. Notably, EEG studies in ASD children have reported specific deficits in low-frequency δ, θ, and α oscillations (33,34), indicating that similar neuronal network defects exist in Cdkl5 -/y mice and ASD patients.…”

Section: Disruption Ofmentioning

confidence: 99%

See 1 more Smart Citation

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

Wang

Allen²,

Goffin³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

181

247

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Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKTmammalian target of rapamycin (mTOR) cascade, upon Cdkl5 loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders.C yclin-dependent kinase-like 5 (CDKL5) is an X-linked gene associated with early infantile epileptic encephalopathy 2 (EIEE2) (1), atypical Rett syndrome (RTT) (2), and autism spectrum disorders (ASDs) (3, 4). Patients with CDKL5 mutations display a heterogenous array of clinical phenotypes, the most prominent of which include early-onset seizures, intellectual disability, and autistic features (5).CDKL5 is a serine/threonine (S/T) kinase that is highly expressed in the brain (6). In vitro studies have demonstrated that CDKL5 may mediate the phosphorylation of methyl-CpG binding protein 2 (MeCP2) (7), DNA methyltransferase 1 (DNMT1) (8), and netrin-G1 ligand (NGL-1) (9). RNAi-mediated knockdown studies show that CDKL5 can regulate neuronal outgrowth and synapse stability (9, 10). Despite these proposed functions, the exact role of CDKL5 in the phosphorylation of MeCP2 (7, 11) and in dendritic outgrowth (9, 10) remains unclear, and thus requires further investigation. The limited understanding of CDKL5 function and its associated signal transduction pathways has hindered the development of therapeutics for CDKL5-related disorders. Current treatments focus on managing symptoms and reducing seizure frequency, but have limited effectiveness (12).To investigate the function of CDKL5 in a disease model and identify potential avenues of therapeutic intervention, we developed a Cdkl5 knockout mouse. We found that mice lacking CDKL5 show autistic-like behavioral abnormalities, deficits in neural circuit communication, and alterations in multiple signal transduction pathways. We establish a causal link between Cdkl5 loss-of-function and disease-related phenotypes and identify the AKT-mammalian target of rapamycin (mTOR) pathway as a unique candidate for targeted therapeutic intervention of CDKL5-related disorders. ResultsGeneration of Cdkl5 Knockout Mice. To investigate the pathophysiology underlying CDKL5-related disorders, we generated ...

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Section: Discussionmentioning

confidence: 99%

Section: Disruption Ofmentioning

confidence: 99%

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

Wang

Allen²,

Goffin³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

181

247

View full text Add to dashboard Cite

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“…Some researchers reported that delta, alpha3 and beta activity is increased in children with autism [14,15]. On the other hand, Dawson et al [16] did not find increased power (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32) in children and adolescents with autism.…”

Section: Introductionmentioning

confidence: 89%

“…The aim of this study was to extract significant differences in qEEG of children with ASD that can be used for diagnosis of this group. Studies in very young children are of particular importance for understanding the pathogenesis of ASD, but the possibility of functional neuroimaging is limited in investigations of very young children [17,18]. In contrast, qEEG can be used even in infants.…”

Section: Introductionmentioning

confidence: 96%

Detection of Abnormalities for Diagnosing of Children with Autism Disorders Using of Quantitative Electroencephalography Analysis

et al. 2010

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Quantitative electroencephalography (qEEG) has been used as a tool for neurophysiologic diagnostic. We used spectrogram and coherence values for evaluating qEEG in 17 children (13 boys and 4 girls aged between 6 and 11) with autism disorders (ASD) and 11 control children (7 boys and 4 girls with the same age range). Evaluation of qEEG with statistical analysis demonstrated that alpha frequency band (8-13 Hz) had the best distinction level of 96.4% in relaxed eye-opened condition using spectrogram criteria. The ASD group had significant lower spectrogram criteria values in left brain hemisphere, (p < 0.01) at F3 and T3 electrodes and (p < 0.05) at FP1, F7, C3, Cz and T5 electrodes. Coherence values at 171 pairs of EEG electrodes indicated that there are more abnormalities with higher values in the connectivity of temporal lobes with other lobes in gamma frequency band (36-44 Hz).

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“…Neurologically, research has demonstrated decreases in activity (Dawson et al 1995;Stroganova et al 2007) and blood flow (Chiron et al 1995) in the left hemisphere; significantly increased activity in the right frontal and temporal lobes, versus controls (Kleinhans et al 2008); a lack of expected leftward structural asymmetry in gray and white matter, versus controls (Haznedar et al 2006;Lo et al 2011;Wan et al 2012); and an abnormal enlargement of the right hemisphere (Herbert et al 2005), all perhaps suggesting hyper-activation of the right hemisphere and hypo-activation of the left hemisphere in ASD (Shamay-Tsoory et al 2010). These differences have been noted more readily in areas of the brain where white matter mylenates later in development (Herbert et al 2004(Herbert et al , 2005, and have been linked to social skills and approach in ASD (Kylliäinen et al 2012;Sutton et al 2005), suggesting a potential important impact of experience/environment on this progression of atypicality.…”

Section: Behavioral and Cortical Development In Adolescencementioning

confidence: 99%

Measuring the Plasticity of Social Approach: A Randomized Controlled Trial of the Effects of the PEERS Intervention on EEG Asymmetry in Adolescents with Autism Spectrum Disorders

Hecke

Stevens

Carson

et al. 2013

J Autism Dev Disord

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This study examined whether the Program for the Education and Enrichment of Relational Skills (PEERS: Social skills for teenagers with developmental and autism spectrum disorders: The PEERS treatment manual, Routledge, New York, 2010a) affected neural function, via EEG asymmetry, in a randomized controlled trial of adolescents with Autism spectrum disorders (ASD) and a group of typically developing adolescents. Adolescents with ASD in PEERS shifted from right-hemisphere gamma-band EEG asymmetry before PEERS to left-hemisphere EEG asymmetry after PEERS, versus a waitlist ASD group. Left-hemisphere EEG asymmetry was associated with more social contacts and knowledge, and fewer symptoms of autism. Adolescents with ASD in PEERS no longer differed from typically developing adolescents in leftdominant EEG asymmetry at post-test. These findings are discussed via the Modifier Model of Autism (Mundy et al. in Res Pract Persons Severe Disabl 32(2):124, 2007), with emphasis on remediating isolation/withdrawal in ASD.

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Abnormal EEG lateralization in boys with autism

Cited by 111 publications

References 63 publications

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

Detection of Abnormalities for Diagnosing of Children with Autism Disorders Using of Quantitative Electroencephalography Analysis

Measuring the Plasticity of Social Approach: A Randomized Controlled Trial of the Effects of the PEERS Intervention on EEG Asymmetry in Adolescents with Autism Spectrum Disorders

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