Blythe A. Corbett

Examining executive functioning in children with autism spectrum disorder, attention deficit hyperactivity disorder and typical development.

Executive functioning (EF) is an overarching term that refers to neuropsychological processes that enable physical, cognitive, and emotional self-control. Deficits in EF are often present in neurodevelopmental disorders, but examinations of the specificity of EF deficits and direct comparisons across disorders are rare. The current study investigated EF in 7- to 12-year-old children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and typical development using a comprehensive battery of measures assessing EF, including response inhibition, working memory, cognitive flexibility, planning, fluency and vigilance. The ADHD group exhibited deficits in vigilance, inhibition and working memory relative to the typical group; however, they did not consistently demonstrate problems on the remaining EF measures. Children with ASD showed significant deficits in vigilance compared with the typical group, and significant differences in response inhibition, cognitive flexibility/switching, and working memory compared with both groups. These results lend support for previous findings that show children with autism demonstrate generalized and profound impairment in EF. In addition, the observed deficits in vigilance and inhibitory control suggest that a significant number of children with ASD present with cognitive profiles consistent with ADHD.

The paradox of cognitive flexibility in autism

We present an overview of current literature addressing cognitive flexibility in autism spectrum disorders. Based on recent studies at multiple sites, using diverse methods and participants of different autism subtypes, ages and cognitive levels, no consistent evidence for cognitive flexibility deficits was found. Researchers and clinicians assume that inflexible everyday behaviors in autism are directly related to cognitive flexibility deficits as assessed by clinical and experimental measures. However, there is a large gap between the day-to-day behavioral flexibility and that measured with these cognitive flexibility tasks. To advance the field, experimental measures must evolve to reflect mechanistic models of flexibility deficits. Moreover, ecologically valid measures are required to be able to resolve the paradox between cognitive and behavioral inflexibility.

A functional and structural study of emotion and face processing in children with autism

Children with autism exhibit impairment in the processing of socioemotional information. The amygdala, a core structure centrally involved in socioemotional functioning, has been implicated in the neuropathology of autism. We collected structural and functional magnetic resonance images (MRI) in children 8 to 12 years of age with high-functioning autism (n=12) and typical development (n=15). The functional MRI experiment involved matching facial expressions and people. Volumetric analysis of the amygdala was also performed. The results showed that children with autism exhibited intact emotion matching, while showing diminished activation of the fusiform gyrus (FG) and the amygdala. Conversely, the autism group showed deficits in person matching amidst some FG and variable amygdala activation. No significant between-group differences in the volume of the left or right amygdala were found. There were associations between age, social anxiety and amygdala volume in the children with autism such that smaller volumes were generally associated with more anxiety and younger age. In summary, the data are consistent with abnormalities in circuits involved in emotion and face processing reported in studies of older subjects with autism showing reductions in amygdala activation related to emotion processing and reduced fusiform activation involved in face processing.

Processing Affective Stimuli in Children with Attention-Deficit Hyperactivity Disorder

Neuropsychological investigations have suggested a contribution of right hemisphere dysfunction in attention-deficit hyperactivity disorder (ADHD). Right hemisphere dysfunction has been implicated in deficits of attention, motor impersistence, and processing emotion-laden stimuli. The current study investigated the ability of ADHD children to perceive emotional stimuli in the form of facial expressions and speech intonation. The subjects consisted of 37 ADHD and 37 control children aged 7 to 12 years. ANCOVA analysis indicated that ADHD children demonstrate mild-to-moderate deficits in the perception of affect. Furthermore, deficits in attention may contribute to inaccurate or incomplete encoding of stimulus properties. The results lend tentative support for the notion that the right cerebral hemisphere may play a critical role in ADHD.

Comparing Cortisol, Stress and Sensory Sensitivity in Children with Autism

Previously we reported that children with autism show significant variability in cortisol. The current investigation was designed to extend these findings by exploring plausible relationships between cortisol and psychological measures of stress and sensory functioning. Salivary cortisol values for diurnal rhythms and response to stress in children with and without autism were compared to parent‐report measures of child stress, the Stress Survey Schedule (SSS), sensory functioning, Short Sensory Profile (SSP), and Parenting Stress Index. In autism, a negative relationship between morning cortisol and the SSS revealed that higher observed symptoms of stress were related to lower cortisol. Lower cortisol is seen in conditions of chronic stress and in social situations characterized by unstable social relationships. Sensory sensitivity painted a more complicated picture, in that some aspects of SSP were associated with higher while others were associated with lower cortisol. We propose that increased sensory sensitivity may enhance the autistic childs susceptibility to the influence of zeitgeibers reflected in variable cortisol secretion. Evening cortisol was positively associated with SSS such that the higher the level of evening cortisol, the higher the childs parent‐reported daily stress, especially to changes, such as in daily routine. Regarding the response to stress, the psychological and parent variables did not differentiate the groups; rather, discrete subgroups of cortisol responders and nonresponders were revealed in both the autism and neurotypical children. The results support a complex interplay between physiological and behavioral stress and sensory sensitivity in autism and plausible developmental factors influencing stress reactivity across the groups.

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4–6 years of age (n=69) were compared to typically developing children (n=35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size >0.99 with a P<0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

Autism and attention deficit hyperactivity disorder: assessing attention and response control with the integrated visual and auditory continuous performance test.

Symptoms of attention deficit hyperactivity disorder (ADHD) have been widely reported in children with autism spectrum disorder (ASD). The current study investigated attention and response control in children with ASD, ADHD, and typical development using the Integrated Visual and Auditory Continuous Performance Test. Results indicate that many children with ASD show significant deficits in visual and auditory attention and greater deficits in impulsivity than children with ADHD or typical development. These findings suggest that many of the children with ASD demonstrate significant ADHD-like deficits. These findings are discussed in the context of symptoms, subtypes, and comorbidity.

Functional Disconnection of Frontal Cortex and Visual Cortex in Attention-Deficit/Hyperactivity Disorder

BACKGROUNDnCurrent pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) suggest that impaired functional connectivity within brain attention networks may contribute to the disorder. In this electroencephalographic (EEG) study, we analyzed cross-frequency amplitude correlations to investigate differences in cue-induced functional connectivity in typically developing children and children with ADHD.nnnMETHODSnElectroencephalographic activity was recorded in 25 children aged 8 to 12 years (14 with ADHD) while they performed a cross-modal attention task in which cues signaled the most likely (.75 probability) modality of an upcoming target. The power spectra of the EEG in the theta (3-5 Hz) and alpha (8-12 Hz) bands were calculated for the 1-sec interval after the cue and before the target while subjects prepared to discriminate the expected target.nnnRESULTSnBoth groups showed behavioral benefits of the predictive attentional cues, being faster and more accurate for validly cued targets (e.g., visual target preceded by a cue predicting a visual target) than to invalidly cued targets (e.g., visual target preceded by a cue predicting an auditory target); in addition, independent of cue-target validity, typical children were faster to respond overall. In the typically developing children, the alpha activity was differentially modulated by the two cues and anticorrelated with midfrontal theta activity; these EEG correlates of attentional control were not observed in the children with ADHD.nnnCONCLUSIONSnOur findings provide neurophysiological evidence for a specific deficit in top-down attentional control in children with ADHD that is manifested as a functional disconnection between frontal and occipital cortex.

In Search of Cellular Immunophenotypes in the Blood of Children with Autism

Background Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism. Methods We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (nu200a=u200a70) compared with age-matched controls (nu200a=u200a35). Children with a confirmed diagnosis of autism (4–6 years of age) were further subdivided into low (IQ<68, nu200a=u200a35) or high functioning (IQ≥68, nu200a=u200a35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry. Results There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls. Conclusions These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed.

Examining cortisol rhythmicity and responsivity to stress in children with Tourette syndrome

BACKGROUNDnTourette syndrome (TS) is characterized by motor and vocal tics, which are often exacerbated by stress. The hypothalamic-pituitary-adrenocortical (HPA) axis, a major stress response system is thus of interest for understanding TS.nnnMETHODSnDiurnal cortisol rhythms were estimated in medication-free children 7-13 years with TS (N=20) and healthy age-matched controls (N=16). Salivary samples were collected on 3 consecutive days from the home. HPA responsivity was assessed by examining cortisol in response to a mock and real MRI scan.nnnRESULTSnThe results of diurnal rhythmicity revealed a trend showing marginally lower evening cortisol for the TS group. By contrast, the TS group had higher cortisol levels in response to the stressor. There were strong, negative correlations between evening cortisol and tic severity as well as diurnal cortisol and anxiety.nnnCONCLUSIONSnThe children with TS showed increased cortisol in response to the MRI environment, supporting a model of enhanced HPA responsivity. The lower evening cortisol may be the result of chronic daily stress. Alternatively, the negative associations between cortisol and reported anxiety and tics may reflect biologically based anxiolytic properties of tic expression. Taken together, the results clearly implicate involvement of the HPA axis in the neuropathology of TS.