Patterns of Visual Attention to Faces and Objects in Autism Spectrum Disorder

This study used eye-tracking to examine visual attention to faces and objects in adolescents with autism spectrum disorder (ASD) and typical peers. Point of gaze was recorded during passive viewing of images of human faces, inverted human faces, monkey faces, three-dimensional curvilinear objects, and two-dimensional geometric patterns. Individuals with ASD obtained lower scores on measures of face recognition and social-emotional functioning but exhibited similar patterns of visual attention. In individuals with ASD, face recognition performance was associated with social adaptive function. Results highlight heterogeneity in manifestation of social deficits in ASD and suggest that naturalistic assessments are important for quantifying atypicalities in visual attention

Neurophysiological correlates of holistic face processing in adolescents with and without autism spectrum disorder

Background: Face processing has been found to be impaired in autism spectrum disorders (ASD). One hypothesis is that individuals with ASD engage in piecemeal compared to holistic face processing strategies. To investigate the role of possible impairments in holistic face processing in individuals with autism, the current study investigated behavioral and electroencephalography (EEG) correlates of face processing (P1/N170 and gamma-band activity) in adolescents with ASD and sex-, age-, and IQ-matched neurotypical controls. Methods: Participants were presented with upright and inverted Mooney stimuli; black and white low information faces that are only perceived as faces when processed holistically. Participants indicated behaviorally the detection of a face. EEG was collected time-locked to the presentation of the stimuli. Results: Adolescents with ASD perceived Mooney stimuli as faces suggesting ability to use holistic processing but displayed a lower face detection rate and slower response times. ERP components suggest slowed temporal processing of Mooney stimuli in the ASD compared to control group for P1 latency but no differences between groups for P1 amplitude and at the N170. Increases in gamma-band activity was similar during the perception of the Mooney images by group, but the ASD group showed prolonged temporal elevation in activity. Conclusion: Overall, our results suggest that adolescents with ASD were able to utilize holistic processing to perceive a face within the Mooney stimuli. Delays in early processing, marked by the P1, and elongated elevation in gamma activity indicate that the neural systems supporting holistic processing are slightly altered suggesting a less automatic and less efficient facial processing system

Fear-Potentiated Startle Response Is Unrelated to Social or Emotional Functioning in Adolescents With Autism Spectrum Disorders: Startle response in adolescents with ASD

It has been suggested that atypical amygdala function contributes to the social impairments characteristic of autism spectrum disorders (ASDs). Previous research has demonstrated that adolescents and adults with ASD generate normal response during a fear-potentiated startle paradigm, suggesting this aspect of amygdala function is intact and may not account for the social dysfunction associated with the condition. The amygdala also plays a crucial role in the expression of anxiety and may contribute to high rates of reported anxiety in individuals with ASD. The present study partially replicates prior work by examining the fear-potentiated startle response in adolescents with ASD, and extends this to investigate the relationship between startle response and anxiety. Eyeblink magnitude and latency (electromyographic activity; EMG) were collected from 20 adolescents with ASD and 19 typically developing (TD) age-matched adolescents during a fear-potentiated startle paradigm. Parent report and self-report of anxiety and additional psychiatric symptoms were collected. Parental reports indicated higher rates of associated psychopathology in adolescents with ASD compared with TD adolescents. Consistent with previous results, both groups showed normal potentiated startle response, and no group differences in EMG were found. Symptoms of anxiety and level of social impairment were unrelated to startle response. These findings held for all levels of anxiety, suggesting that within the context of the fear-potentiated startle paradigm, amygdala response is not associated with degree of atypical social or emotional functioning in ASD

Disengagement of visual attention in infancy is associated with emerging autism in toddlerhood

Background: Early emerging characteristics of visual orienting have been associated with a wide range of typical and atypical developmental outcomes. In the current study, we examined the development of visual disengagement in infants at risk for autism. Methods: We measured the efficiency of disengaging from a central visual stimulus to orient to a peripheral one in a cohort of 104 infants with and without familial risk for autism by virtue of having an older sibling with autism. Results: At 7 months of age, disengagement was not robustly associated with later diagnostic outcomes. However, by 14 months, longer latencies to disengage in the subset of the risk group later diagnosed with autism was observed relative to other infants at risk and the low-risk control group. Moreover, between 7 months and 14 months, infants who were later diagnosed with autism at 36 months showed no consistent increases in the speed and flexibility of visual orienting. However, the latter developmental effect also characterized those infants who exhibited some form of developmental concerns (but not meeting criteria for autism) at 36 months. Conclusions: Infants who develop autism or other developmental concerns show atypicality in the development of visual attention skills from the first year of life

Developmental Change in the ERP Responses to Familiar Faces in Toddlers With Autism Spectrum Disorders Versus Typical Development: Developmental Change in the ERP Responses to Familiar Faces

Individuals with ASD show differences in face processing abilities from early in development. To examine whether these differences reflect an atypical versus delayed developmental trajectory, neural responses to familiar and unfamiliar faces in 24 18-to 47-month-old children with ASD were compared to responses of 32 12- to 30-month-old typically developing children. Results of two experiments revealed that neural responses to faces in children with ASD resembled those observed in younger typically developing children, suggesting delayed development. Electrophysiological responses to faces were also related to parent-report of adaptive social behaviors for both children with ASD and typical development. Slower development of the face processing system in ASD may be related to reduced self-directed ‘expected’ experience with faces in early development

EEG functional connectivity in infants at elevated familial likelihood for autism spectrum disorder

Background Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, we know relatively little about the development of these differences in infancy. Methods We used a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6 and 12 months of age in infants at typical (N = 92) or elevated likelihood for ASD (N = 90), determined by the presence of an older sibling with ASD. We computed the functional connectivity between cortical sources of EEG during video watching using the corrected imaginary part of phase-locking values. Results Our main analysis found no significant association between functional connectivity and ASD, showing only significant effects for age, sex, age-sex interaction, and site. Given these null results, we performed an exploratory analysis and observed, at 12 months, a negative correlation between functional connectivity and ADOS calibrated severity scores for restrictive and repetitive behaviors (RRB). Limitations The small sample of ASD participants inherent to sibling studies limits diagnostic group comparisons. Also, results from our secondary exploratory analysis should be considered only as potential relationships to further explore, given their increased vulnerability to false positives. Conclusions These results are inconclusive concerning an association between EEG functional connectivity and ASD in infancy. Exploratory analyses provided preliminary support for a relationship between RRB and functional connectivity specifically, but these preliminary observations need corroboration on larger samples

Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study

Background: The increased male prevalence of autism spectrum disorder (ASD) may be mirrored by the early emergence of sex differences in ASD symptoms and cognitive functioning. The female protective effect hypothesis posits that ASD recurrence and symptoms will be higher among relatives of female probands. This study examined sex differences and sex of proband differences in ASD outcome and in the development of ASD symptoms and cognitive functioning among the high-risk younger siblings of ASD probands and low-risk children. Methods: Prior to 18 months of age, 1824 infants (1241 high-risk siblings, 583 low-risk) from 15 sites were recruited. Hierarchical generalized linear model (HGLM) analyses of younger sibling and proband sex differences in ASD recurrence among high-risk siblings were followed by HGLM analyses of sex differences and group differences (high-risk ASD, high-risk non-ASD, and low-risk) on the Mullen Scales of Early Learning (MSEL) subscales (Expressive and Receptive Language, Fine Motor, and Visual Reception) at 18, 24, and 36 months and Autism Diagnostic Observation Schedule (ADOS) domain scores (social affect (SA) and restricted and repetitive behaviors (RRB)) at 24 and 36 months. Results: Of 1241 high-risk siblings, 252 had ASD outcomes. Male recurrence was 26.7 % and female recurrence 10.3 %, with a 3.18 odds ratio. The HR-ASD group had lower MSEL subscale scores and higher RRB and SA scores than the HR non-ASD group, which had lower MSEL subscale scores and higher RRB scores than the LR group. Regardless of group, males obtained lower MSEL subscale scores, and higher ADOS RRB scores, than females. There were, however, no significant interactions between sex and group on either the MSEL or ADOS. Proband sex did not affect ASD outcome, MSEL subscale, or ADOS domain scores. Conclusions: A 3.2:1 male:female odds ratio emerged among a large sample of prospectively followed high-risk siblings. Sex differences in cognitive performance and repetitive behaviors were apparent not only in high-risk children with ASD, but also in high-risk children without ASD and in low-risk children. Sex differences in young children with ASD do not appear to be ASD-specific but instead reflect typically occurring sex differences seen in children without ASD. Results did not support a female protective effect hypothesis. Electronic supplementary material The online version of this article (doi:10.1186/s13229-015-0027-y) contains supplementary material, which is available to authorized users

Resting state EEG in youth with ASD: age, sex, and relation to phenotype

Background Identification of ASD biomarkers is a key priority for understanding etiology, facilitating early diagnosis, monitoring developmental trajectories, and targeting treatment efforts. Efforts have included exploration of resting state encephalography (EEG), which has a variety of relevant neurodevelopmental correlates and can be collected with minimal burden. However, EEG biomarkers may not be equally valid across the autism spectrum, as ASD is strikingly heterogeneous and individual differences may moderate EEG-behavior associations. Biological sex is a particularly important potential moderator, as females with ASD appear to differ from males with ASD in important ways that may influence biomarker accuracy. Methods We examined effects of biological sex, age, and ASD diagnosis on resting state EEG among a large, sex-balanced sample of youth with (N = 142, 43% female) and without (N = 138, 49% female) ASD collected across four research sites. Absolute power was extracted across five frequency bands and nine brain regions, and effects of sex, age, and diagnosis were analyzed using mixed-effects linear regression models. Exploratory partial correlations were computed to examine EEG-behavior associations in ASD, with emphasis on possible sex differences in associations. Results Decreased EEG power across multiple frequencies was associated with female sex and older age. Youth with ASD displayed decreased alpha power relative to peers without ASD, suggesting increased neural activation during rest. Associations between EEG and behavior varied by sex. Whereas power across various frequencies correlated with social skills, nonverbal IQ, and repetitive behavior for males with ASD, no such associations were observed for females with ASD. Conclusions Research using EEG as a possible ASD biomarker must consider individual differences among participants, as these features influence baseline EEG measures and moderate associations between EEG and important behavioral outcomes. Failure to consider factors such as biological sex in such research risks defining biomarkers that misrepresent females with ASD, hindering understanding of the neurobiology, development, and intervention response of this important population

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in vivo in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis, by combining non-invasive neuroimaging and blood biomarkers. We performed quantitative microstructural MRI and single molecule ELISA plasma neurofilament measurement in 73 patients with newly diagnosed, immunotherapy naïve relapsing-remitting multiple sclerosis. Myelin integrity was evaluated using aggregate g-ratios, derived from magnetization transfer saturation (MTsat) and neurite orientation dispersion and density imaging (NODDI) diffusion data. We found significantly higher g-ratios within cerebral white matter lesions (suggesting myelin loss) compared with normal-appearing white matter (0.61 vs 0.57, difference 0.036, 95% CI 0.029 to 0.043, p < 0.001). Lesion volume (Spearman’s rho rs= 0.38, p < 0.001) and g-ratio (rs= 0.24 p < 0.05) correlated independently with plasma neurofilament. In patients with substantial lesion load (n = 38), those with higher g-ratio (defined as greater than median) were more likely to have abnormally elevated plasma neurofilament than those with normal g-ratio (defined as less than median) (11/23 [48%] versus 2/15 [13%] p < 0.05). These data suggest that, even at multiple sclerosis diagnosis, reduced myelin integrity is associated with axonal damage. MRI-derived g-ratio may provide useful additional information regarding lesion severity, and help to identify individuals with a high degree of axonal damage at disease onset. York, Martin et al. simultaneously measured g-ratio and plasma neurofilament in 73 relapsing-remitting multiple sclerosis patients at diagnosis using advanced MRI and single molecule ELISA. They demonstrate that g-ratio of cerebral white matter lesions varies at diagnosis, and show that high g-ratio of lesions is associated with elevated plasma neurofilament

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine