Research suggests a relationship between anorexia nervosa and autism spectrum disorder. The aim of the current study was to examine social attention in anorexia nervosa and autism spectrum disorder ...compared with age- and sex-matched typically developing groups, and to examine whether lowered social motivation could explain reductions in social attention across the two disorders. Participants’ eye movements were tracked while watching a dynamic social scene. The proportion of fixation duration to faces, bodies and non-social areas of interest were compared across groups. Participants with autism spectrum disorder looked at faces significantly less often than controls, however, there were no differences between anorexia nervosa and controls in attention to faces. Typically developing -normed z-scores indicated that attention to faces showed the greatest deviation from normative data compared with body or non-social areas of interest in both autism spectrum disorder and anorexia nervosa, however, differences were larger in autism spectrum disorder than in anorexia nervosa. Social motivation scores did not predict attention to faces in either autism spectrum disorder or anorexia nervosa. Our results do not support the hypothesis that differences in social motivation underlie reduced social attention in both anorexia nervosa and autism spectrum disorder.
Lay abstract
Research suggests a relationship between autism and anorexia nervosa. For example, rigid and inflexible behaviour, a preference for routine and social difficulties are seen in both conditions. In this study, we examined whether people with anorexia and people with autism show similarities in social attention (where they look while engaging in social interactions or watching a scene with people interacting). This could help us understand why people with anorexia and autism experience difficulties in social situations. Participants with either anorexia or autism, as well as participants with no mental health problems watched a video of a social scene while we recorded which parts of the scene they looked at with an eye-tracker. Participants also completed questionnaires to assess characteristics of autism. We found that autistic participants looked at faces less than typically developing participants. However, participants with anorexia did not show a similar reduction in attention to faces, contrary to our predictions. Autistic features were not related to attention in either group. The results suggest that autistic people may miss important social cues (like facial expressions), potentially contributing to social difficulties. However, this mechanism does not appear explain social difficulties in people with anorexia.
Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle ...study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94). Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.
Background
Uncovering the neural mechanisms that underlie symptoms of attention deficit hyperactivity disorder (ADHD) requires studying brain development prior to the emergence of behavioural ...difficulties. One new approach to this is prospective studies of infants with an elevated likelihood of developing ADHD.
Methods
We used a prospective design to examine an oscillatory electroencephalography profile that has been widely studied in both children and adults with ADHD – the balance between lower and higher frequencies operationalised as the theta–beta ratio (TBR). In the present study, we examined TBR in 136 10‐month‐old infants (72 male and 64 female) with/without an elevated likelihood of developing ADHD and/or a comparison disorder (Autism Spectrum Disorder; ASD).
Results
Infants with a first‐degree relative with ADHD demonstrated lower TBR than infants without a first‐degree relative with ADHD. Further, lower TBR at 10 months was positively associated with temperament dimensions conceptually related to ADHD at 2 years. TBR was not altered in infants with a family history of ASD.
Conclusions
This is the first demonstration that alterations in TBR are present prior to behavioural symptoms of ADHD. However, these alterations manifest differently than those sometimes observed in older children with an ADHD diagnosis. Importantly, altered TBR was not seen in infants at elevated likelihood of developing ASD, suggesting a degree of specificity to ADHD. Taken together, these findings demonstrate that there are brain changes associated with a family history of ADHD observable in the first year of life.
An ability to perceive tactile and visual stimuli in a common spatial frame of reference is a crucial ingredient in forming a representation of one's own body and the interface between bodily and ...external space. In this study, the authors investigated young infants' abilities to perceive colocation between tactile and visual stimuli presented on the hands. They examined infants' visual preferences for spatially congruent and incongruent visual-tactile events across two age groups (6 months and 10-months). They observed increased duration of looking to incongruent stimuli displays in both age groups, indicating that infants from at least 6 months of age demonstrate the ability to determine whether simultaneously presented visual-tactile perceptual events are colocated or not. These findings indicate that an ability to perceive visual and tactile stimuli within a common spatial frame of reference is available by the end of the first half year of life.
Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% of FTLD cases. Identification of genetic risk variants related to innate/adaptive immunity have ...highlighted a role for neuroinflammation and neuroimmune interactions in FTLD. Studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY-Tau22 tauopathy mice. However, this remains to be confirmed in FTLD-tau patients. We conducted a detailed post-mortem study of FTLD-tau cases including 45 progressive supranuclear palsy with clinical frontotemporal dementia, 33 Pick's disease, 12 FTLD-MAPT and 52 control brains to characterize the link between phosphorylated tau (pTau) epitopes and the innate and adaptive immunity. Tau pathology was assessed in the cerebral cortex using antibodies directed against: Tau-2 (phosphorylated and unphosphorylated tau), AT8 (pSer202/pThr205), AT100 (pThr212/pSer214), CP13 (pSer202), PHF1 (pSer396/pSer404), pThr181 and pSer356. The immunophenotypes of microglia and astrocytes were assessed with phenotypic markers (Iba1, CD68, HLA-DR, CD64, CD32a, CD16 for microglia and GFAP, EAAT2, glutamine synthetase and ALDH1L1 for astrocytes). The adaptive immune response was explored via CD4+ and CD8+ T cell quantification and the neuroinflammatory environment was investigated via the expression of 30 inflammatory-related proteins using V-Plex Meso Scale Discovery. As expected, all pTau markers were increased in FTLD-tau cases compared to controls. pSer356 expression was greatest in FTLD-MAPT cases versus controls (P < 0.0001), whereas the expression of other markers was highest in Pick's disease. Progressive supranuclear palsy with frontotemporal dementia consistently had a lower pTau protein load compared to Pick's disease across tau epitopes. The only microglial marker increased in FTLD-tau was CD16 (P = 0.0292) and specifically in FTLD-MAPT cases (P = 0.0150). However, several associations were detected between pTau epitopes and microglia, supporting an interplay between them. GFAP expression was increased in FTLD-tau (P = 0.0345) with the highest expression in Pick's disease (P = 0.0019), while ALDH1L1 was unchanged. Markers of astrocyte glutamate cycling function were reduced in FTLD-tau (P = 0.0075; Pick's disease: P < 0.0400) implying astrocyte reactivity associated with a decreased glutamate cycling activity, which was further associated with pTau expression. Of the inflammatory proteins assessed in the brain, five chemokines were upregulated in Pick's disease cases (P < 0.0400), consistent with the recruitment of CD4+ (P = 0.0109) and CD8+ (P = 0.0014) T cells. Of note, the CD8+ T cell infiltration was associated with pTau epitopes and microglial and astrocytic markers. Our results highlight that FTLD-tau is associated with astrocyte reactivity, remarkably little activation of microglia, but involvement of adaptive immunity in the form of chemokine-driven recruitment of T lymphocytes.
Alterations in the development of attention control and learning have been associated with autism and can be measured using the ‘antisaccade task’, which assesses a child’s ability to make an ...oculomotor response away from a distracting stimulus, and learn to instead anticipate a later reward. We aimed to assess these cognitive processes using portable eye-tracking in an understudied population of pre-school children with and without a diagnosis of autism spectrum disorder in community settings in New Delhi, India. The eye-tracking antisaccade task was presented to children in three groups (n = 104) (children with a clinical diagnosis of autism spectrum disorder or intellectual disability and children meeting developmental milestones). In accordance with findings from high-income, laboratory-based environments, children learnt to anticipate looks towards a reward, as well as inhibit eye-movements towards a distractor stimulus. We also provide novel evidence that while differences in inhibition responses might be applicable to multiple developmental conditions, a reduced learning to anticipate looks towards a target in this age group may be specific to autism. This eye-tracking task may, therefore, have the potential to identify and assess autism specific traits across development, and be used in longitudinal research studies such as investigating response to intervention in low-resource settings.
Lay abstract
The development of cognitive processes, such as attention control and learning, has been suggested to be altered in children with a diagnosis of autism spectrum disorder. However, nearly all of our understanding of the development of these cognitive processes comes from studies with school-aged or older children in high-income countries, and from research conducted in a controlled laboratory environment, thereby restricting the potential generalisability of results and away from the majority of the world’s population. We need to expand our research to investigate abilities beyond these limited settings. We address shortcomings in the literature by (1) studying attention control and learning in an understudied population of children in a low- and middle-income country setting in India, (2) focusing research on a critical younger age group of children and (3) using portable eye-tracking technology that can be taken into communities and healthcare settings to increase the accessibility of research in hard-to-reach populations. Our results provide novel evidence on differences in attention control and learning responses in groups of children with and without a diagnosis of autism spectrum disorder. We show that learning responses in children that we assessed through a portable eye-tracking task, called the ‘antisaccade task’, may be specific to autism. This suggests that the methods we use may have the potential to identify and assess autism-specific traits across development, and be used in research in low-resource settings.
The neural correlates of intraindividual response variability were investigated in a serial choice reaction time (CRT) task. Reaction times (RTs) from the faster and slower portions of the RT ...distribution for the task were separately aggregated and associated P300 event-related potentials computed. Independent behavioral measures of executive function and IQ were also recorded. Across frontal, fronto-central, central, centro-parietal and parietal scalp regions, P300 amplitudes were significantly greater for faster relative to slower behavioral responses. However, P300 peak amplitude latencies did not differ according to the speed of the behavioral RT. Importantly, controlling for select independent measures of executive function attenuated shared variance in P300 amplitude for faster and slower trials. The findings suggest that P300 amplitude rather than latency is associated with the speed of behavioral RTs, and the possibility that fluctuations in executive control underlie variability in speeded responding.
Background
Social attention affords learning opportunities across development and may contribute to individual differences in developmental trajectories, such as between male and female individuals, ...and in neurodevelopmental conditions, such as autism.
Methods
Using eye‐tracking, we measured social attention in a large cohort of autistic (n = 123) and nonautistic females (n = 107), and autistic (n = 330) and nonautistic males (n = 204), aged 6–30 years. Using mixed Growth Curve Analysis, we modelled sex and diagnostic effects on the temporal dynamics of proportional looking time to three types of social stimuli (lean‐static, naturalistic‐static, and naturalistic‐dynamic) and examined the link between individual differences and dimensional social and nonsocial autistic traits in autistic females and males.
Results
In the lean‐static stimulus, average face‐looking was higher in females than in males of both autistic and nonautistic groups. Differences in the dynamic pattern of face‐looking were seen in autistic vs. nonautistic females, but not males, with face‐looking peaking later in the trial in autistic females. In the naturalistic‐dynamic stimulus, average face‐looking was higher in females than in males of both groups; changes in the dynamic pattern of face looking were seen in autistic vs. nonautistic males, but not in females, with a steeper peak in nonautistic males. Lower average face‐looking was associated with higher observer‐measured autistic characteristics in autistic females, but not in males.
Conclusions
Overall, we found stronger social attention in females to a similar degree in both autistic and nonautistic groups. Nonetheless, the dynamic profiles of social attention differed in different ways in autistic females and males compared to their nonautistic peers, and autistic traits predicted trends of average face‐looking in autistic females. These findings support the role of social attention in the emergence of sex‐related differences in autistic characteristics, suggesting an avenue to phenotypic stratification.
We investigated infant’s manual motor behaviour; specifically behaviours crossing the body midline. Infants at elevated likelihood of Autism Spectrum Disorder (ASD) and/or Attention Deficit ...Hyperactivity Disorder (ADHD) produced fewer manual behaviours that cross the midline compared to infants with a typical likelihood of developing these disorders; however this effect was limited to 10-month-olds and not apparent at age 5 and 14 months. Although, midline crossing did not predict ASD traits, it was related to ADHD traits at 2 years of age. We rule out motor ability and hand dominance as possible explanations for this pattern of behaviour, positing that these results may be a consequence of multisensory integration abilities, and the neurobehavioural shift period, in the first year of life.
Background
Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes ...such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype.
Methods
Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9‐ to 24‐month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3‐year ASD outcome, polygenic liability for ASD and dimensional 3‐year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants.
Results
While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (β = −.16, 95% CI = −0.31, −0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ‘catch‐up’) between 14 and 24 months relative to those with other outcomes (typical: β = .54, 95% CI = 0.08, 0.99; other: β = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD‐related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9‐ to 14‐month amplitude was associated with higher SA (β = .08, 95% CI = 0.01, 0.14) and RRB (β = .05, 95% CI = 0.004, 0.11) traits.
Conclusions
These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
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