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1.	Falck-Ytter, Terje, et al. (författare) Reduced Orienting to Audiovisual Synchrony in Infancy Predicts Autism Diagnosis at 3 Years of Age 2018 Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 59:8, s. 872-880 Tidskriftsartikel (refereegranskat)abstract Background: Effective multisensory processing develops in infancy and is thought to be important for the perception of uniﬁed and multimodal objects and events. Previous research suggests impaired multisensory processing in autism, but its role in the early development of the disorder is yet uncertain. Here, using a prospective longitudinal design, we tested whether reduced visual attention to audiovisual synchrony is an infant marker of later-emerging autism diagnosis.Methods: We studied 10-month-old siblings of children with autism using an eye tracking task previously used in studies of preschoolers. The task assessed the effect of manipulations of audiovisual synchrony on viewing patterns while the infants were observing point light displays of biological motion. We analyzed the gaze data recorded in infancy according to diagnostic status at 3 years of age (DSM-5).Results: Ten-month-old infants who later received an autism diagnosis did not orient to audiovisual synchrony expressed within biological motion. In contrast, both infants at low-risk and high-risk siblings without autism at follow-up had a strong preference for this type of information. No group differences were observed in terms of orienting to upright biological motion.Conclusions: This study suggests that reduced orienting to audiovisual synchrony within biological motion is an early sign of autism. The ﬁndings support the view that poor multisensory processing could be an important antecedent marker of this neurodevelopmental condition.
2.	Hendry, Alexandra, et al. (författare) Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits 2020 Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105 Tidskriftsartikel (refereegranskat)abstract Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
3.	Konke, Linn Andersson, et al. (författare) How Does Temperament in Toddlers at Elevated Likelihood for Autism Relate to Symptoms of Autism and ADHD at Three Years of Age? 2022 Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 52, s. 995-1006 Tidskriftsartikel (refereegranskat)abstract The current study investigated longitudinal associations between parent-rated temperament, observed exuberance and accelerometer activity level at 18-months and symptoms of ASD and ADHD at 36-months in a sample of 54 children at elevated likelihood for ASD. For the specific parent-rated temperament scales, most observed significant associations appeared to be specific for either ASD or ADHD symptoms. Indeed, by controlling for overlapping symptoms a different pattern of associations emerged. These results illustrate how temperamental measures may signal risk for later ASD versus ADHD symptomatology in infants at elevated likelihood for ASD. In addition, they indicate the potential of adopting a broader view on neurodevelopmental disorders by investigating not only ASD traits, but also co-occurring disorders such as ADHD in samples of elevated likelihood for ASD.
4.	Achermann, Sheila, et al. (författare) Motor atypicalities in infancy are associated with general developmental level at 2 years, but not autistic symptoms 2020 Ingår i: Autism. - : SAGE Publications Ltd. - 1362-3613 .- 1461-7005. ; 24:7, s. 1650-1663 Tidskriftsartikel (refereegranskat)abstract Atypical motor development has frequently been reported in infants at elevated likelihood for autism spectrum disorder. However, no previous study has used detailed motion capture technology to compare infant siblings of children with autism spectrum disorder and infant siblings with no familial history of autism spectrum disorder. We investigated reaching movements during an interceptive action task in 10-month-old infants using kinematic data with high spatiotemporal resolution. The results indicated that several measures were different in infants at elevated likelihood. However, longitudinal analyses revealed that while specific infant motor measures (e.g. number of movement units) were related to broad measures of general developmental level in toddlerhood, the associations with later autism spectrum disorder symptomatology were not significant. These findings confirm that some aspects of motor functioning are atypical in infants at elevated likelihood for autism spectrum disorder, but provide no support for the view that these issues are specifically linked to autism spectrum disorder symptoms, but may rather reflect neurodevelopment more generally.Lay abstractAtypicalities in motor functioning are often observed in later born infant siblings of children with autism spectrum disorder. The goal of our study was to investigate motor functioning in infants with and without familial history of autism spectrum disorder. Specifically, we investigated how infants catch a ball that is rolling toward them following a non-straight path, a task that requires both efficient planning and execution. Their performance was measured using detailed three-dimensional motion capture technology. We found that several early motor functioning measures were different in infants with an older autistic sibling compared to controls. However, these early motor measures were not related to autistic symptoms at the age of 2 years. Instead, we found that some of the early motor measures were related to their subsequent non-social, general development. The findings of our study help us understand motor functioning early in life and how motor functioning is related to other aspects of development.
5.	Achermann, Sheila (författare) Prediction in Typical and Atypical Development 2020 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Forming predictions about what is going to happen next is a crucial ability that develops early in life. Theory and some empirical evidence suggest that predictive abilities may be impaired in Autism Spectrum Disorder (ASD). The overarching aim of this thesis is to investigate early measures of prediction in relation to concurrent and later outcomes in typical and atypical development, with a particular focus on ASD and related behavioral problems.In Study I, we used motion capture technology to examine prospective motor control and its relationship to executive functions in typically developing 18-month-olds. Our findings showed that motor control is associated with executive functioning in infancy.Study II investigated motor control in infants at low and elevated likelihood for ASD and examined how these measures relate to later development. We found group differences as well as similarities in motor control in 10-months-olds with and without a familial history of ASD. Early motor measures were related to general developmental level, but not ASD symptomatology in toddlerhood.Using eye tracking, Study III examined how infants with later ASD and neurotypical infants form predictions about visual object motion. Our findings indicated that infants with later ASD were able to form predictions about object motion and adapt to simple changes in motion patterns, and that their performance did not differ from the performance of neurotypical infants.In Study IV, we surveyed parents about their experiences during participation in an infant sibling study of ASD as a first step to understanding the benefits and risks associated with this type of research. Parents were generally positive about their experiences both from their own perspective as well as, the child’s perspective.This thesis illustrates the potential of using advanced technology, such as motion tracking and eye tracking, to study and compare prediction in typical and atypical development. It points to the important role of prediction and motor control for child development, but fails to find a specific link to ASD.
6.	Achermann, Sheila, et al. (författare) Updating Expectations about Unexpected Object Motion in Infants Later Diagnosed with Autism Spectrum Disorder 2021 Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 51:11, s. 4186-4198 Tidskriftsartikel (refereegranskat)abstract In typical development, infants form predictions about future events based on incoming sensory information, which is essential for perception and goal-directed action. It has been suggested that individuals with autism spectrum disorder (ASD) make predictions differently compared to neurotypical individuals. We investigated how infants who later received an ASD diagnosis and neurotypical infants react to temporarily occluded moving objects that violate initial expectations about object motion. Our results indicate that infants regardless of clinical outcome react similarly to unexpected object motion patterns, both in terms of gaze shift latencies and pupillary responses. These findings indicate that the ability to update representations about such regularities in light of new information may not differ between typically developing infants and those with later ASD.
7.	Borgmästars, Emmy, et al. (författare) Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples 2021 Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21 Tidskriftsartikel (refereegranskat)abstract Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
8.	Darki, Fahimeh, et al. (författare) T1-Weighted/T2-Weighted Ratio Mapping at 5 Months Captures Individual Differences in Behavioral Development and Differentiates Infants at Familial Risk for Autism from Controls 2021 Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:9, s. 4068-4077 Tidskriftsartikel (refereegranskat)abstract Identifying structural measures that capture early brain development and are sensitive to individual differences in behavior is a priority in developmental neuroscience, with potential implications for our understanding of both typical and atypical populations. T1-weighted/T2-weighted (T1w/T2w) ratio mapping, which previously has been linked to myelination, represents an interesting candidate measure in this respect, as an accessible measure from standard magnetic resonance imaging (MRI) sequences. Yet, its value as an early infancy measure remains largely unexplored. Here, we compared T1w/T2w ratio in 5-month-old infants at familial risk (n = 27) for autism spectrum disorder (ASD) to those without elevated autism risk (n =16). We found lower T1w/T2w ratio in infants at high risk for ASD within widely distributed regions, spanning both white and gray matter. In regions differing between groups, higher T1w/T2w ratio was robustly associated with higher age at scan (range: similar to 4-6.5 months), implying sensitivity to maturation at short developmental timescales. Further, higher T1w/T2w ratio within these regions was associated with higher scores on measures of concurrent developmental level. These findings suggest that T1w/T2w ratio is a developmentally sensitive measure that should be explored further in future studies of both typical and atypical infant populations.
9.	de Vries, Lyssa, et al. (författare) Investigating the development of the autonomic nervous system in infancy through pupillometry 2023 Ingår i: Journal of neural transmission. - : Springer. - 0300-9564 .- 1435-1463. ; 130, s. 723-734 Tidskriftsartikel (refereegranskat)abstract We aim to investigate early developmental trajectories of the autonomic nervous system (ANS) as indexed by the pupillary light reflex (PLR) in infants with (i.e. preterm birth, feeding difficulties, or siblings of children with autism spectrum disorder) and without (controls) increased likelihood for atypical ANS development. We used eye-tracking to capture the PLR in 216 infants in a longitudinal follow-up study spanning 5 to 24 months of age, and linear mixed models to investigate effects of age and group on three PLR parameters: baseline pupil diameter, latency to constriction and relative constriction amplitude. An increase with age was found in baseline pupil diameter (F(3,273.21) = 13.15, p < 0.001, eta(2)(p) = 0.13), latency to constriction (F(3,326.41) =3.84, p = 0.010,eta(2)(p) = 0.03) and relative constriction amplitude(F(3,282.53) =3.70, p = 0.012,eta(2)(p)= 0.04). Group differences were found for baseline pupil diameter (F(3,235.91) = 9.40, p < 0.001,eta(2)(p) = 0.11), with larger diameter in preterms and siblings than in controls, and for latency to constriction (F(3,237.10) = 3.48, p = 0.017, eta(2)(p) = 0.04), with preterms having a longer latency than controls. The results align with previous evidence, with development over time that could be explained by ANS maturation. To better understand the cause of the group differences, further research in a larger sample is necessary, combining pupillometry with other measures to further validate its value.
10.	Fish, Laurel A., et al. (författare) Development of the pupillary light reflex from 9 to 24 months : association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis 2021 Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 62:11, s. 1308-1319 Tidskriftsartikel (refereegranskat)abstract 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 (? = ?.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: ? = .54, 95% CI = 0.08, 0.99; other: ? = .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 (? = .08, 95% CI = 0.01, 0.14) and RRB (? = .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.
11.	Gredebäck, Gustaf, et al. (författare) Context dependent cognitive development in Bhutanese children 2023 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13 Tidskriftsartikel (refereegranskat)abstract We assessed risk/protective factors for cognitive development of Bhutanese children (504 3-5 year-olds, 49% girls, major ethnicities Ngalop 26%, Tshangla 30%, Lhotsampa 34%) using a non-verbal test of cognitive capacity (SON-R) and primary caregiver interviews. Cognitive capacity was related to the family's SES and whether the family belonged to the primary Buddhist majority ethnic groups (Ngalop or Tshangla) or primarily Hindu minorities (Lhotsampa). In majority families more engagement in Buddhist practices was associated with higher cognitive capacity in children. Minority children were more impacted by parents autonomous-relatedness values. Results demonstrate that cognitive development is dependent on the financial and educational context of the family, societal events, and culture specific risk/protective factors that differ across sub-groups (majority/minority, culture/religion).
12.	Hardiansyah, Irzam, et al. (författare) Global motion processing in infants’ visual cortex and the emergence of autism 2023 Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 6:1 Tidskriftsartikel (refereegranskat)abstract Autism is a heritable and common neurodevelopmental condition, with behavioural symptoms typically emerging around age 2 to 3 years. Differences in basic perceptual processes have been documented in autistic children and adults. Specifically, data from many experiments suggest links between autism and alterations in global visual motion processing (i.e., when individual motion information is integrated to perceive an overall coherent pattern). Yet, no study has investigated whether a distinctive organization of global motion processing precede the emergence of autistic symptoms in early childhood. Here, using a validated infant electroencephalography (EEG) experimental paradigm, we first establish the normative activation profiles for global form, global motion, local form, and local motion in the visual cortex based on data from two samples of 5-month-old infants (total n = 473). Further, in a sample of 5-month-olds at elevated likelihood of autism (n = 52), we show that a different topographical organization of global motion processing is associated with autistic symptoms in toddlerhood. These findings advance the understanding of neural organization of infants’ basic visual processing, and its role in the development of autism.
13.	Hellmer, Kahl, et al. (författare) Infant acetylcholine, dopamine, and melatonin dysregulation : Neonatal biomarkers and causal factors for ASD and ADHD phenotypes 2017 Ingår i: Medical Hypotheses. - : CHURCHILL LIVINGSTONE. - 0306-9877 .- 1532-2777. ; 100, s. 64-66 Tidskriftsartikel (refereegranskat)abstract Autism spectrum disorders (ASD) and ADHD are common neurodevelopmental disorders that benefit from early intervention but currently suffer from late detection and diagnosis: neurochemical dysregulations are extant already at birth but clinical phenotypes are not distinguishable until preschool age or later. The vast heterogeneity between subjects' phenotypes relates to interaction between multiple unknown factors, making research on factor causality insurmountable. To unlock this situation we pose the hypothesis that atypical pupillary light responses from rods, cones, and the recently discovered ipRGC system reflect early acetylcholine, melatonin, and dopamine dysregulation that are sufficient but not necessary factors for developing ASD and/or ADHD disorders. Current technology allows non-invasive cost-efficient assessment already from the first postnatal month. The benefits of the current proposal are: identification of clinical subgroups based on cause rather than phenotypes; facilitation of research on other causal factors; neonatal prediction of later diagnoses; and guidance for targeted therapeutical intervention.
14.	Hellmer, Kahl, et al. (författare) Spädbarns dysreglering av acetylkolin, dopamin och melatonin – nya verktyg för orsakssambandsforskning på ASD och ADHD 2017 Ingår i: Best Practice. - 1329-1874. Tidskriftsartikel (populärvet., debatt m.m.)
15.	Juvrud, Joshua, et al. (författare) People overlook subtractive changes differently depending on age, culture, and task 2024 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14 Tidskriftsartikel (refereegranskat)abstract Previous work has explored transformative strategies that adds or removes components to change an original structure or state, and showed that adults tend to search for additive solutions far more often than subtractive ones. In the current study, we replicated a Lego building task and a grid-based symmetry task from a previous study, and also introduced a novel digital puzzle task. We investigated limitations in the previous study as well as extended the investigation of the subtraction neglect in a sample of children and across two cultures. Results partially confirm previous results, and extends the literature by showing that 9-10 year old children were more likely to ignore subtractive transformations than adults. However, we found both task-based and cultural variations in strategy use in adults from Sweden and the USA. We conclude that a subtraction neglect involves complex cognitive processes that are dependent on the task, culture, and age.
16.	Juvrud, Joshua, et al. (författare) The Immersive Virtual Reality Lab : Possibilities for Remote Experimental Manipulations of Autonomic Activity on a Large Scale 2018 Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 12 Tidskriftsartikel (refereegranskat)abstract There is a need for large-scale remote data collection in a controlled environment, and the in-home availability of virtual reality (VR) and the commercial availability of eye tracking for VR present unique and exciting opportunities for researchers. We propose and provide a proof-of-concept assessment of a robust system for large-scale in-home testing using consumer products that combines psychophysiological measures and VR, here referred to as a Virtual Lab. For the first time, this method is validated by correlating autonomic responses, skin conductance response (SCR), and pupillary dilation, in response to a spider, a beetle, and a ball using commercially available VR. Participants demonstrated greater SCR and pupillary responses to the spider, and the effect was dependent on the proximity of the stimuli to the participant, with a stronger response when the spider was close to the virtual self. We replicated these effects across two experiments and in separate physical room contexts to mimic variability in home environment. Together, these findings demonstrate the utility of pupil dilation as a marker of autonomic arousal and the feasibility to assess this in commercially available VR hardware and support a robust Virtual Lab tool for massive remote testing.
17.	Lindskog, Marcus, 1980-, et al. (författare) Can the Brain Build Probability Distributions? 2021 Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 12 Tidskriftsartikel (refereegranskat)abstract How humans efficiently operate in a world with massive amounts of data that need to be processed, stored, and recalled has long been an unsettled question. Our physical and social environment needs to be represented in a structured way, which could be achieved by reducing input to latent variables in the form of probability distributions, as proposed by influential, probabilistic accounts of cognition and perception. However, few studies have investigated the neural processes underlying the brain's potential ability to represent a probability distribution's complex, global features. Here, we presented participants with a sequence of tones that formed a normal or a bimodal distribution. Using a novel, single-trial EEG analysis, we demonstrate a neural response that indexes the likelihood of an item, given previously presented items, and corresponds to the experienced tones' distribution. Our results indicate that the adult human brain can build a representation of the complex, global pattern of a probability distribution and offer a novel tool for an in-depth understanding of related neural mechanics.
18.	Lundin Kleberg, Johan, et al. (författare) Sex Differences in Social Attention in Infants at Risk for Autism 2019 Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 49:4, s. 1342-1351 Tidskriftsartikel (refereegranskat)abstract We studied visual attention to emotional faces in 10-month-old infant siblings of children with ASD (ASD-sibs; N = 70) and a siblings of typically developing children (N = 29) using static stimuli. Contrary to our predictions, we found no evidence for atypical gaze behavior in ASD-sibs when boys and girls were analyzed together. However, a sex difference was found in ASD-sibs' visual attention to the mouth. Male ASD-sibs looked more at the mouth across emotions compared to male controls and female ASD-sibs. In contrast, female ASD-sibs looked less at the mouth compared to female controls. These findings suggest that some aspects of early emerging atypical social attention in ASD-sibs may be sex specific.
19.	Mason, James E., et al. (författare) A cross-sectional and longitudinal analysis of pre-diagnostic blood plasma biomarkers for early detection of pancreatic cancer 2022 Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 23:21 Tidskriftsartikel (refereegranskat)abstract Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death that typically presents at an advanced stage. No reliable markers for early detection presently exist. The prominent tumor stroma represents a source of circulating biomarkers for use together with cancer cell-derived biomarkers for earlier PDAC diagnosis. CA19-9 and CEA (cancer cell-derived biomarkers), together with endostatin and collagen IV (stroma-derived) were examined alone, or together, by multivariable modelling, using pre-diagnostic plasma samples (n = 259 samples) from the Northern Sweden Health and Disease Study biobank. Serial samples were available for a subgroup of future patients. Marker efficacy for future PDAC case prediction (n = 154 future cases) was examined by both cross-sectional (ROC analysis) and longitudinal analyses. CA19-9 performed well at, and within, six months to diagnosis and multivariable modelling was not superior to CA19-9 alone in cross-sectional analysis. Within six months to diagnosis, CA19-9 (AUC = 0.92) outperformed the multivariable model (AUC = 0.81) at a cross-sectional level. At diagnosis, CA19-9 (AUC = 0.995) and the model (AUC = 0.977) performed similarly. Longitudinal analysis revealed increases in CA19-9 up to two years to diagnosis which indicates a window of opportunity for early detection of PDAC.
20.	Nyström, Pär, 1975-, et al. (författare) Atypical Topographical Organization of Global Form and Motion Processing in 5-Month-Old Infants at Risk for Autism 2021 Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 51:1, s. 364-370 Tidskriftsartikel (refereegranskat)abstract Research indicates that individuals with autism spectrum disorder (ASD) are superior at local processing while the integration of local features to global percepts is reduced. Here, we compared infants at familiar risk for ASD to typically developing infants in terms of global coherence processing at 5 months of age, using steady state visually evoked potentials (SSVEP). We found a different topographical organization for global form and motion processing in infants at risk (n = 50) than in controls (n = 23). In contrast, activation patterns for local visual change were strikingly similar between groups. Although preliminary, the results represent the first neurophysiological evidence supporting the view that basic atypicalities in perception may play a role in the developmental pathways leading to ASD.
21.	Nyström, Pär, 1975-, et al. (författare) Enhanced pupillary light reflex in infancy is associated with autism diagnosis in toddlerhood 2018 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9 Tidskriftsartikel (refereegranskat)abstract Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting around 1% of the population. We previously discovered that infant siblings of children with ASD had stronger pupillary light reflexes compared to low-risk infants, a result which contrasts sharply with the weak pupillary light reflex typically seen in both children and adults with ASD. Here, we show that on average the relative constriction of the pupillary light reflex is larger in 9–10-month-old high risk infant siblings who receive an ASD diagnosis at 36 months, compared both to those who do not and to low-risk controls. We also found that the magnitude of the pupillary light reflex in infancy is associated with symptom severity at follow-up. This study indicates an important role of sensory atypicalities in the etiology of ASD, and suggests that pupillometry, if further developed and refined, could facilitate risk assessment in infants.
22.	Nyström, Pär, 1975- (författare) From Motion to Movements : Revelations by the Infant EEG 2008 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The introduction of high density EEG (hd-EEG) nets for easy application on subjects of all ages has improved the possibilities to investigate the development of the infant neurophysiology. This dissertation consists of three studies (I – III) that investigate the visual motion system and mirror neuron system of the infant, and methodological sections that outline the bioelectrical background and the characteristics of the methods used. Study I covers the maturation of cortical areas involved in motion perception in adults and infants using an ERP paradigm. Over three age groups (2, 3 and 5 month olds) the cortical activation increased dramatically. All infant groups showed significant activation when moving displays was contrasted to static displays on a video screen. The study shows that 5-month-old infants and older can be expected to process motion in a similar fashion as adults.Study II covers the infant mirror neuron system (MNS). In adults the mu rhythm perturbations is considered a reliable measure of activation of the MNS. This study presented both a mu rhythm analysis and a ERP analysis to detect MNS activity in 6-month-olds and in adults. This study concludes that the infant MNS can be measured using ERPs and that the development of mu rhythm perturbations requires further study.Study III focused on exploring the mu rhythm suppressions. 8-month-olds observed a live actor that performed goal directed reaches and non-goal directed hand movements. The results show robust mu rhythm perturbations time-locked to the grasping moment. The study concluded that the MNS activity is possible to evaluate by analysis of mu rhythm perturbations and that the MNS show mature characteristics at the age of 8 months.In summary, Study 2 and 3 present new methods to investigate the infant mirror neuron system and shows that the infant MNS is active at 6 months of age. At 8 months of age the infant MNS show mature EEG responses to simple actions such as reaching. How the MNS development relates to the infants’ motor development, and how the MNS interacts with the development of social skills requires further studies that could benefit from the methods presented here.
23.	Nyström, Pär, 1975-, et al. (författare) Joint attention in infancy and the emergence of autism 2019 Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 86:8, s. 631-638 Tidskriftsartikel (refereegranskat)abstract BackgroundIn typical infant development, parents and their children jointly contribute to establishing frequent episodes of joint attention that boost language acquisition and shape social cognition. Here we used novel live eye-tracking technology to evaluate the degree to which autism spectrum disorder (ASD) is related to reduced responding to others’ joint attention bids in infancy (RJA) and to a reduced tendency to initiate joint attention episodes (IJA). Because young infants use their gaze for both RJA and IJA, this approach allowed us to quantify these elusive processes early in life.MethodsThe final sample consisted of 112 infants (54 boys and 58 girls), of whom 81 were at familial risk for ASD and 31 were typically developing low-risk infants. At follow-up (36 months of age), 22 children in the high-risk group were diagnosed with ASD.ResultsAt 10 months of age, rates of IJA were lower in infants later diagnosed with ASD than in the comparison groups (effect sizes d = 0.78–0.95) and followed an atypical developmental trajectory from 10 to 18 months (p < .002). RJA distinguished infants based on familial ASD risk, albeit not ASD diagnosis. The differences in IJA could not be explained by overall looking time, social preference, eye movement latencies, or number of fixations.ConclusionsThis live eye-tracking study suggests that during an important period for the development of social cognition (10–18 months of age), infants later diagnosed with ASD show marked atypicalities in IJA but not in RJA. The results indicate that IJA is an important target for future prodromal intervention trials.
24.	Nyström, Pär, 1975-, et al. (författare) Responding to Other People's Direct Gaze : Alterations in Gaze Behavior in Infants at Risk for Autism Occur on Very Short Timescales 2017 Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 47:11, s. 3498-3509 Tidskriftsartikel (refereegranskat)abstract Atypical gaze processing has been reported in children with autism spectrum disorders (ASD). Here we explored how infants at risk for ASD respond behaviorally to others' direct gaze. We assessed 10-month-olds with a sibling with ASD (high risk group; n = 61) and a control group (n = 18) during interaction with an adult. Eye-tracking revealed less looking at the adult in the high risk group during 300-1000 ms after the adult initiated direct gaze: a short alteration that is likely to go unnoticed by the naked eye. Data aggregated over longer segments (the traditional eye-tracking approach) showed no group differences. Although findings are limited by lack of outcome data, they are in line with theories linking atypical eye processing to the emergence of ASD.
25.	Pokorny, Florian B., et al. (författare) Earlier Identification of Children with Autism Spectrum Disorder : An Automatic Vocalisation-based Approach 2017 Ingår i: 18Th Annual Conference Of The International Speech Communication Association (INTERSPEECH 2017), Vols 1-6. - 9781510848764 ; , s. 309-313 Konferensbidrag (refereegranskat)abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder usually diagnosed in or beyond toddlerhood. ASD is defined by repetitive and restricted behaviours, and deficits in social communication. The early speech-language development of individuals with ASD has been characterised as delayed. However, little is known about ASD-related characteristics of pre-linguistic vocalisations at the feature level. In this study. we examined pre-linguistic vocalisations of 10-month-old individuals later diagnosed with ASD and a matched control group of typically developing individuals (N = 20). We segmented 684 vocalisations from parent-child interaction recordings. All vocalisations were annotated and signal-analytically decomposed. We analysed ASD-related vocalisation specificities on the basis of a standardised set (eGeMAPS) of 88 acoustic features selected for clinical speech analysis applications. 54 features showed evidence for a differentiation between vocalisations of individuals later diagnosed with ASD and controls. In addition, we evaluated the feasibility of automated, vocalisation-based identification of individuals later diagnosed with ASD. We compared linear kernel support vector machines and a 1-layer bidirectional long short-term memory neural network. Both classification approaches achieved an accuracy of 75% for subject-wise identification in a subject-independent 3-fold cross-validation scheme. Our promising results may be an important contribution en-route to facilitate earlier identification of ASD.
26.	Portugal, Ana Maria, et al. (författare) Pupil size and pupillary light reflex in early infancy : heritability and link to genetic liability to schizophrenia 2022 Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 63:9, s. 1068-1077 Tidskriftsartikel (refereegranskat)abstract Background Measures based on pupillometry, such as the pupillary light reflex (PLR) and baseline pupil size, reflect physiological responses linked to specific neural circuits that have been implicated as atypical in some psychiatric and neurodevelopmental conditions.MethodsWe investigated the contribution of genetic and environmental factors to the baseline pupil size and the PLR in 510 infant twins assessed at 5?months of age (281 monozygotic and 229 dizygotic pairs), and its associations with common genetic variants associated with neurodevelopmental (autism spectrum disorder and attention deficit hyperactivity disorder) and mental health (bipolar disorder, major depressive disorder and schizophrenia) conditions using genome-wide polygenic scores (GPSs).ResultsUnivariate twin modelling showed high heritability at 5?months for both pupil size (h2?=?.64) and constriction in response to light (h2?=?.62), and bivariate twin modeling indicated substantial independence between the genetic factors influencing each (rG?=?.38). A statistically significant positive association between infant tonic pupil size and the GPS for schizophrenia was found (??=?.15, p?=?.024), while there was no significant association with the GPS for autism or any other GPSs.ConclusionsThis study shows that some pupil measures are highly heritable in early infancy, although substantially independent in their genetic etiologies, and associated with common genetic variants linked to schizophrenia. It illustrates how genetically informed studies of infants may help us understand early physiological responses associated with psychiatric disorders which emerge much later in life.
27.	Rudling, Maja, et al. (författare) Infant responses to direct gaze and associations to autism : A live eye-tracking study 2023 Ingår i: Autism. - : Sage Publications. - 1362-3613 .- 1461-7005. Tidskriftsartikel (refereegranskat)abstract Being looked at is an important communicative signal, and attenuated responses to such direct gaze have been suggested as an early sign of autism. Using live eye tracking, we examined whether direct gaze elicits different gaze responses in infants at ages 10, 14 and 18 months with and without later autism in real-life interaction. The sample consisted of 169 infants: 35 with elevated likelihood of autism and subsequent diagnosis, 94 without subsequent diagnosis and 40 with typical likelihood of autism. Infants in all groups tended to look more towards the adult’s face shortly after the direct gaze occurred. Neither how much nor how quickly the infants responded to the direct gaze differentiated the without elevated likelihood of autism and subsequent diagnosis and with elevated likelihood of autism and subsequent diagnosis groups. Infants in the typical likelihood group looked more at the face after the direct-gaze event than infants in the two elevated likelihood groups, but this result is tentative. In an exploratory analysis, infants in the elevated likelihood of autism and subsequent diagnosis group looked away quicker from faces with direct gaze than infants in the typical likelihood group, but this measure did not correlate with dimensional autism or differentiate between the two elevated likelihood groups. The current results suggest that attenuated behavioural responses to direct gaze in infancy are neither strong nor specific early markers of autism.Lay abstractWhen other people look directly towards us, we often respond by looking back at them, and such direct-gaze responses are important for establishing eye contact. Atypical eye contact is common in autism, but how and when this aspect of autism develops is not well understood. Here, we studied whether how much and how quickly infants respond to others’ direct gaze is associated with autism in toddlerhood. We did this by measuring direct-gaze responses in a playful social interaction using live eye tracking. The study included 169 infants, of whom 129 had an elevated likelihood of developing autism due to having a first-degree family member with the condition, and 40 with typical likelihood of autism. In the elevated likelihood group, 35 were diagnosed with autism spectrum disorder at 3 years of age, and 94 were not. The results showed that infants in all three groups tended to increase their looking towards the adult’s face after the adult looked directly at them. However, neither how much nor how quickly the infants responded to direct gaze by looking back at the adult reliably differentiated the infants with or without subsequent autism. While infants in the elevated likelihood of autism and subsequent diagnosis group tended to look away quicker from faces with direct gaze than infants in the typical likelihood group, this measure did not differentiate between the two elevated likelihood groups. We interpret the results as supporting the view that atypical direct-gaze responses are not early markers of autism.
28.	Rudling, Maja, et al. (författare) Larger pupil dilation to nonsocial sounds in infants with subsequent autism diagnosis 2022 Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 63:7, s. 793-801 Tidskriftsartikel (refereegranskat)abstract Background Studies of infants with an elevated likelihood of autism spectrum disorder can identify basic developmental processes that are associated with subsequently emerging clinical symptoms. Atypical responsiveness to sounds in infancy is such a potential early marker of autism. Here, we used pupillometry to quantify reactivity to social and nonsocial sounds in infants with a subsequent diagnosis. Previous research suggest that pupil dilation reflects attentional alerting, and link it to the locus coeruleus norepinephrine system. Methods We measured pupil dilation responses to child-directed speech and the sound of running water; sounds infants often hear in their everyday life. The final sample consisted of 99 ten-month-old infants (52 girls), of whom 68 had an elevated likelihood of autism and 31 were typically developing low-likelihood infants. At follow-up (36 months of age), 18 children in the elevated-likelihood group were diagnosed with autism. Results Compared to infants without diagnosis, the infants who were subsequently diagnosed with autism had larger pupil dilation when listening to nonsocial sounds, while reactivity to speech was strikingly similar between groups. In the total sample, more pupil dilation to the nonsocial sound was associated with higher levels of autistic symptoms. We also found that on a trial-by-trial basis, across all conditions and groups, more pupil dilation was associated with making fewer gaze shifts. Conclusions This study did not find evidence of atypical pupillary reactivity to child-directed speech early in life in autism. Instead, the results suggest that certain nonsocial sounds elicit atypically strong alerting responses in infants with a subsequent autism diagnosis. These findings may have important theoretical and clinical implications.
29.	Shic, Frederick, et al. (författare) Remote, tablet-based assessment of gaze following : a nationwide infant twin study 2023 Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 14 Tidskriftsartikel (refereegranskat)abstract Introduction: Much of our understanding of infant psychological development relies on an in-person, laboratory-based assessment. This limits research generalizability, scalability, and equity in access. One solution is the development of new, remotely deployed assessment tools that do not require real-time experimenter supervision.Methods: The current nationwide (Sweden) infant twin study assessed participants remotely via their caregiver's tablets (N = 104, ages 3 to 17 months). To anchor our findings in previous research, we used a gaze-following task where experimental and age effects are well established.Results: Closely mimicking results from conventional eye tracking, we found that a full head movement elicited more gaze following than isolated eye movements. Furthermore, predictably, we found that older infants followed gaze more frequently than younger infants. Finally, while we found no indication of genetic contributions to gaze-following accuracy, the latency to disengage from the gaze cue and orient toward a target was significantly more similar in monozygotic twins than in dizygotic twins, an indicative of heritability.Discussion: Together, these results highlight the potential of remote assessment of infants' psychological development, which can improve generalizability, inclusion, and scalability in developmental research.
30.	Silfwerbrand, Lykke, et al. (författare) Directed causal effect with PCMCI in hyperscanning EEG time series 2024 Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 18 Tidskriftsartikel (refereegranskat)abstract Social activities are likely to cause effects or reactivity in the brains of the people involved in collaborative social situations. This study assesses a new method, Tigramite, for time domain analysis of directed causality between the prefrontal cortex (PFC) of persons in such situations. An experimental situation using hyperscanning EEG was applied while individuals led and followed each other in finger-tapping rhythms. This structured task has a long duration and a high likelihood of inter-brain causal reactions in the prefrontal cortices. Tigramite is a graph-based causal discovery method to identify directed causal relationships in observational time series. Tigramite was used to analyze directed causal connections within and between the PFC. Significantly directed causality within and between brains could be detected during the social interactions. This is the first empirical evidence the Tigramite can reveal inter- and intra-brain-directed causal effects in hyperscanning EEG time series. The findings are promising for further studies of causality in neural networks during social activities using Tigramite on EEG in the time domain.
31.	Thorup, Emilia, et al. (författare) Reduced alternating gaze during social interaction in infancy is associated with elevated symptoms of autism in toddlerhood 2018 Ingår i: Journal of Abnormal Child Psychology. - : Springer Science and Business Media LLC. - 0091-0627 .- 1573-2835. ; 46:7, s. 1547-1561 Tidskriftsartikel (refereegranskat)abstract In typical development, infants often alternate their gaze between their interaction partners and interesting stimuli, increasing the probability of joint attention toward surrounding objects and creating opportunities for communication and learning. Children with Autism Spectrum Disorder (ASD) have been found to engage less in behaviors that can initiate joint attention compared to typically developing children, but the role of such atypicalities in the development of ASD during infancy is not fully understood. Here, using eye tracking technology in a live setting, we show that 10-month-olds at high familial risk for ASD engage less in alternating gaze during interaction with an adult compared to low risk infants. These differences could not be explained by low general social preference or slow visual disengagement, as the groups performed similarly in these respects. We also found that less alternating gaze at 10 months was associated with more ASD symptoms and less showing and pointing at 18 months. These relations were similar in both the high risk and the low risk groups, and remained when controlling for general social preference and disengagement latencies. This study shows that atypicalities in alternating gaze in infants at high risk for ASD emerge already during the first 10 months of life - a finding with theoretical as well as potential practical implications.
32.	Thorup, Emilia, et al. (författare) What are you looking at? : Gaze following with and without target objects in ASD and typical development 2022 Ingår i: Autism. - : Sage Publications. - 1362-3613 .- 1461-7005. ; 26:7, s. 1668-1680 Tidskriftsartikel (refereegranskat)abstract Children with autism spectrum disorder (ASD) display difficulties with response to joint attention in natural settings but often perform comparably to typically developing (TD) children in experimental studies of gaze following. Previous work comparing infants at elevated likelihood for ASD versus TD infants has manipulated aspects of the gaze cueing stimulus (e.g. eyes only versus head and eyes together), but the role the peripheral object being attended to is not known. In this study of infants at elevated likelihood of ASD (N?=?97) and TD infants (N?=?29), we manipulated whether or not a target object was present in the cued area. Performance was assessed at 10, 14, and 18?months, and diagnostic assessment was conducted at age 3 years. The results showed that although infants with later ASD followed gaze to the same extent as TD infants in all conditions, they displayed faster latencies back to the model?s face when (and only when) a peripheral object was absent. These subtle atypicalities in the gaze behaviors directly after gaze following may implicate a different appreciation of the communicative situation in infants with later ASD, despite their ostensively typical gaze following ability.Lay abstractDuring the first year of life, infants start to align their attention with that of other people. This ability is called joint attention and facilitates social learning and language development. Although children with autism spectrum disorder (ASD) are known to engage less in joint attention compared to other children, several experimental studies have shown that they follow other?s gaze (a requirement for visual joint attention) to the same extent as other children. In this study, infants? eye movements were measured at age 10, 14, and 18?months while watching another person look in a certain direction. A target object was either present or absent in the direction of the other person?s gaze. Some of the infants were at elevated likelihood of ASD, due to having an older autistic sibling. At age 3?years, infants were assessed for a diagnosis of ASD. Results showed that infants who met diagnostic criteria at 3?years followed gaze to the same extent as other infants. However, they then looked back at the model faster than typically developing infants when no target object was present. When a target object was present, there was no difference between groups. These results may be in line with the view that directly after gaze following, infants with later ASD are less influenced by other people?s gaze when processing the common attentional focus. The study adds to our understanding of both the similarities and differences in looking behaviors between infants who later receive an ASD diagnosis and other infants.
33.	Valtakari, Niilo V., et al. (författare) A field test of computer-vision-based gaze estimation in psychology 2024 Ingår i: Behavior Research Methods. - : Springer. - 1554-351X .- 1554-3528. ; 56:3, s. 1900-1915 Tidskriftsartikel (refereegranskat)abstract Computer-vision-based gaze estimation refers to techniques that estimate gaze direction directly from video recordings of the eyes or face without the need for an eye tracker. Although many such methods exist, their validation is often found in the technical literature (e.g., computer science conference papers). We aimed to (1) identify which computer-vision-based gaze estimation methods are usable by the average researcher in fields such as psychology or education, and (2) evaluate these methods. We searched for methods that do not require calibration and have clear documentation. Two toolkits, OpenFace and OpenGaze, were found to fulfill these criteria. First, we present an experiment where adult participants fixated on nine stimulus points on a computer screen. We filmed their face with a camera and processed the recorded videos with OpenFace and OpenGaze. We conclude that OpenGaze is accurate and precise enough to be used in screen-based experiments with stimuli separated by at least 11 degrees of gaze angle. OpenFace was not sufficiently accurate for such situations but can potentially be used in sparser environments. We then examined whether OpenFace could be used with horizontally separated stimuli in a sparse environment with infant participants. We compared dwell measures based on OpenFace estimates to the same measures based on manual coding. We conclude that OpenFace gaze estimates may potentially be used with measures such as relative total dwell time to sparse, horizontally separated areas of interest, but should not be used to draw conclusions about measures such as dwell duration.
34.	Valtakari, Niilo V., et al. (författare) Eye tracking in human interaction : Possibilities and limitations 2021 Ingår i: Behavior Research Methods. - : Springer Nature. - 1554-351X .- 1554-3528. ; 53:4, s. 1592-1608 Tidskriftsartikel (refereegranskat)abstract There is a long history of interest in looking behavior during human interaction. With the advance of (wearable) video-based eye trackers, it has become possible to measure gaze during many different interactions. We outline the different types of eye-tracking setups that currently exist to investigate gaze during interaction. The setups differ mainly with regard to the nature of the eye-tracking signal (head- or world-centered) and the freedom of movement allowed for the participants. These features place constraints on the research questions that can be answered about human interaction. We end with a decision tree to help researchers judge the appropriateness of specific setups.
35.	Valtakari, Niilo V., et al. (författare) Eye Tracking in Human Interaction : Possibilities and Limitations 2020 Ingår i: Companion Publicaton of the 2020 International Conference on Multimodal Interaction (ICMI '20 Companion). - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450380027 ; , s. 508-508 Konferensbidrag (refereegranskat)
36.	van den Berg, Linda, et al. (författare) A Pre-registered Sticky Mittens Study : Active Training does not Increase Reaching and Grasping in a Swedish Context 2022 Ingår i: Child Development. - : John Wiley & Sons. - 0009-3920 .- 1467-8624. ; 93:6 Tidskriftsartikel (refereegranskat)abstract Several studies have previously investigated the effects of sticky mittens training on reaching and grasping development. However, recent critique casted doubts on the robustness of the motor effect of this training. The current study presents a pre-registered report that aimed to generalize these effects to Swedish infants. Three-month-old infants N = 96, 51 females, mostly White middle class in Uppsala, received daily, parent-led sticky mittens or observational training for 2 weeks or no training in 2019. Reaching and grasping abilities were assessed before and after training, using motion tracking and a 4-step reaching task. Sticky mittens training did not facilitate successful reaching. These results indicate that beneficial motor effects of sticky mittens training did not generalize to this sample.
37.	Wattam-Bell, John, et al. (författare) Form and Motion VERPs in Adults and Infants 2010 Ingår i: Current Biology. ; 20:5, s. 411-415 Tidskriftsartikel (refereegranskat)

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