Background
Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas ...oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation.
Methods
Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures.
Results
We observed decreased saccade duration (∆M = −0.50, CI −0.21, −0.78) and amplitude (∆M = −0.42, CI −0.12, −0.72), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior.
Conclusions
We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are ...neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD.
As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits.
We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders.
Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition.
Neurofeedback (NF) is a non-pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) that is targeting self-regulation, is efficacious when standard protocols are used and ...induces partly specific neurophysiological changes in the inhibitory network. However, its effects on reward processing, which is also considered an important aspect of ADHD and has been linked to neurophysiological deficits, remain unknown. Children with ADHD (
N
= 15, mean age 11.8, SD 1.52) were randomly assigned to either slow cortical potential NF (
n
= 8) or EMG biofeedback control training (
n
= 7) and received 20 sessions of training under comparable conditions. Learning was defined as the slope of successful training runs across all transfer sessions. Whole brain analysis, region-of-interest analysis of anticipatory ventral striatal (VS) activation, and analysis of behavioral data were performed. Clinically, the NF group improved more than the EMG group. Whole brain analysis indicated increased activation in the left superior frontal gyrus in the control group only, and in medial prefrontal cortex and dorsolateral prefrontal gyrus (DLPFC) after treatment across all groups. Only successful learners of self-regulation (
n
= 8) showed increased left inferior frontal gyrus and DLPFC activation after treatment. Left VS activation was increased after treatment and showed a significant time*medication-status interaction. Specific treatment effects were found in left frontal regions for the control treatment and successful learners. Also, unmedicated participants, irrespective of treatment type or successful learning, showed treatment-induced improvement in reward processing. The results suggest no prominent specific effect of NF on reward processing. However, cautious interpretation is warranted due to the small sample.
Abstract Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the ...effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6–30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior–temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing.
Abstract
Evidence suggests that maternal care constitutes a protective factor for psychopathology which may be conditional on the level of family adversity. Given that psychopathology is frequently ...linked with social deficits and the amygdala with social functioning, we investigated the impact of early maternal care on amygdala function under high vs low familial risk for psychopathology. Amygdala activity and habituation during an emotional face-matching paradigm was analyzed in participants of an epidemiological cohort study followed since birth (n = 172, 25 years). Early mother–infant interaction was assessed during a standardized nursing and play setting at the age of 3 months. Information on familial risk during the offspring’s childhood and on the participants’ lifetime psychopathology was obtained with diagnostic interviews. An interaction between maternal stimulation and familial risk was found on amygdala habituation but not on activation, with higher maternal stimulation predicting stronger amygdala habituation in the familial risk group only. Furthermore, amygdala habituation correlated inversely with Attention Deficit Hyperactivity Disorder (ADHD) diagnoses. The findings underline the long-term importance of early maternal care on the offspring’s socioemotional neurodevelopment and of interventions targeting maternal sensitivity early in life, particularly by increasing maternal interactive behavior in those with familial risk.
Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. ...However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2-19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years).CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors.
The debilitating effects of social dysfunction in many psychiatric disorders prompt the need for systems-level biomarkers of social abilities that can be applied in clinical populations and ...longitudinal studies. A promising neuroimaging approach is the animated shapes paradigm based on so-called Frith-Happé animations (FHAs) which trigger spontaneous mentalizing with minimal cognitive demands. Here, we presented FHAs during functional magnetic resonance imaging to 46 subjects and examined the specificity and sensitivity of the elicited social brain responses. Test-retest reliability was additionally assessed in 28 subjects within a two-week interval. Specific responses to spontaneous mentalizing were observed in key areas of the social brain with high sensitivity and independently from the variant low-level kinematics of the FHAs. Mentalizing-specific responses were well replicable on the group level, suggesting good-to-excellent cross-sectional reliability intraclass correlation coefficients (ICCs): 0.40-0.99; dice overlap at P
<0.001: 0.26-1.0. Longitudinal reliability on the single-subject level was more heterogeneous (ICCs of 0.40-0.79; dice overlap at P
<0.001: 0.05-0.43). Posterior temporal sulcus activation was most reliable, including a robust differentiation between subjects across sessions (72% of voxels with ICC>0.40). These findings encourage the use of FHAs in neuroimaging research across developmental stages and psychiatric conditions, including the identification of biomarkers and pharmacological interventions.
Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. ...This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G×E) on neuronal activity during reward processing.
168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview.
At reward delivery, a G×E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA.
These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G×E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention.
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