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Lozano I, Campos R, Belinchón M. Sensitivity to temporal synchrony in audiovisual speech and language development in infants with an elevated likelihood of autism: A developmental review. Infant Behav Dev 2025; 78:102026. [PMID: 39874896 DOI: 10.1016/j.infbeh.2024.102026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/06/2024] [Accepted: 12/26/2024] [Indexed: 01/30/2025]
Abstract
Detecting temporal synchrony in audiovisual speech in infancy is fundamental for socio-communicative development, especially for language acquisition. Autism is an early-onset and highly heritable neurodevelopmental condition often associated with language difficulties that usually extend to infants with an elevated likelihood of autism. Early susceptibilities in still unclear basic mechanisms may underlie these difficulties. Here, we discuss why sensitivity to temporal synchrony in audiovisual speech should be investigated in infants with an elevated likelihood of autism as a candidate mechanism underlying language difficulties. We then review direct and indirect eye-tracking evidence. Although scarce, some studies suggest that detection of temporal synchrony in audiovisual speech may be reduced in infant siblings (but evidence is mixed); however, this does not seem to account for language difficulties. Instead, a lack of relationship between selective attention to the articulating mouth and language development may be a plausible candidate mechanism. However, longitudinal studies tracking both sensitivity to temporal synchrony and selective attention to talking faces in the first year are needed for further clarification. Our discussion highlights gaps in the literature, future research directions and implications for domain-general approaches to the emergence of autism.
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Affiliation(s)
- Itziar Lozano
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, Iván Pavlov, 6, Madrid 28049, Spain; Neurocognitive Development Lab, Institute of Psychology, Polish Academy of Sciences, Jaracza, 1, Warsaw 00-378, Poland.
| | - Ruth Campos
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, Iván Pavlov, 6, Madrid 28049, Spain.
| | - Mercedes Belinchón
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Ciudad Universitaria de Cantoblanco, Iván Pavlov, 6, Madrid 28049, Spain.
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2
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Lozano I, Viktorsson C, Capelli E, Gliga T, Riva V, Tomalski P. Early selective attention to the articulating mouth as a potential female-specific marker of better language development in autism: a review. Front Psychol 2025; 16:1501688. [PMID: 39981392 PMCID: PMC11840506 DOI: 10.3389/fpsyg.2025.1501688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 01/17/2025] [Indexed: 02/22/2025] Open
Abstract
Autism is a neurodevelopmental condition with early onset, usually entailing language differences compared to neurotypical peers. Females are four times less likely than males to be diagnosed with autism, and the language features associated with this condition are less frequent in females than in males. However, the developmental mechanisms underlying these sex differences remain unclear. In neurotypical populations, sex differences in language development are also observable from early on, with females outperforming males. One mechanism underlying these sex differences may be early differences in selective attention to talking faces. During the first year, more mouth-looking generally predicts better language development, but sex differences exist. Female infants look at the mouth of a talking face more than males without penalizing looking to the eyes, and reduced mouth-looking in early infancy relates to better vocabulary in toddlerhood only in females. In this hypothesis and theory article, we propose that unique female gaze patterns to the mouth may constitute an early female-specific candidate marker that acts as a protective marker for language development also in autism. Since autism is highly heritable, investigating infants at elevated likelihood for autism offers the opportunity to search for sex-specific markers operating early in life before autistic features and language differences emerge. We argue that, as in neurotypical female infants, mouth-looking may also protect female infants-at-elevated-likelihood-for-autism population from potential later differences in language skills. If so, then sex-specific early behavioral markers, potentially acting as protective markers of language, may compensate for some genetic risk markers affecting this population. Here we gather evidence from neurotypical infants and those with elevated likelihood of autism to uncover why biological sex, the development of selective attention to the mouth, and language acquisition could be intimately related in both populations. We also propose hypotheses regarding potential sex-differentiated neurodevelopmental pathways. We end discussing future research challenges: how generalizable mouth-looking could be as a potential female-specific early language marker across contexts (experimental vs. real life), countries, and developmental time. Ultimately, we aim to target a novel protective candidate of language acquisition, informing tailored interventions that consider sex as an important source of individual variability.
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Affiliation(s)
- Itziar Lozano
- Neurocognitive Development Lab, Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland
| | - Charlotte Viktorsson
- Development and Neurodiversity Lab, Department of Psychology, Uppsala University, Uppsala, Sweden
| | - Elena Capelli
- Scientific Institute IRCCS E. Medea, Child Psychopathology Unit, Lecco, Italy
| | - Teodora Gliga
- School of Psychology, University of East Anglia, Norwich, United Kingdom
| | - Valentina Riva
- Scientific Institute IRCCS E. Medea, Child Psychopathology Unit, Lecco, Italy
| | - Przemysław Tomalski
- Neurocognitive Development Lab, Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland
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Kulke L. Coregistration of EEG and eye-tracking in infants and developing populations. Atten Percept Psychophys 2025; 87:228-237. [PMID: 38388851 PMCID: PMC11845560 DOI: 10.3758/s13414-024-02857-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2024] [Indexed: 02/24/2024]
Abstract
Infants cannot be instructed where to look; therefore, infant researchers rely on observation of their participant's gaze to make inferences about their cognitive processes. They therefore started studying infant attention in the real world from early on. Developmental researchers were early adopters of methods combining observations of gaze and behaviour with electroencephalography (EEG) to study attention and other cognitive functions. However, the direct combination of eye-tracking methods and EEG to test infants is still rare, as it includes specific challenges. The current article reviews the development of co-registration research in infancy. It points out specific challenges of co-registration in infant research and suggests ways to overcome them. It ends with recommendations for implementing the co-registration of EEG and eye-tracking in infant research to maximise the benefits of the two measures and their combination and to orient on Open Science principles while doing so. In summary, this work shows that the co-registration of EEG and eye-tracking in infant research can be beneficial to studying natural and real-world behaviour despite its challenges.
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Affiliation(s)
- Louisa Kulke
- Department of Developmental Psychology with Educational Psychology, University of Bremen, Hochschulring 18, 28359, Bremen, Germany.
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Dickinson A, McDonald N, Dapretto M, Campos E, Senturk D, Jeste S. Accelerated Infant Brain Rhythm Maturation in Autism. Dev Sci 2025; 28:e13593. [PMID: 39704490 DOI: 10.1111/desc.13593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/07/2024] [Accepted: 11/08/2024] [Indexed: 12/21/2024]
Abstract
Electroencephalography (EEG) captures characteristic oscillatory shifts in infant brain rhythms over the first year of life, offering unique insights into early functional brain development and potential markers for detecting neural differences associated with autism. This study used functional principal component analysis (FPCA) to derive dynamic markers of spectral maturation from task-free EEG recordings collected at 3, 6, 9, and 12 months from 87 infants, 51 of whom were at higher likelihood of developing autism due to an older sibling diagnosed with the condition. FPCA revealed three principal components explaining over 96% of the variance in infant power spectra, with power increases between 6 and 9 Hz (FPC1) representing the most significant age-related trend, accounting for more than 71% of the variance. Notably, this oscillatory change occurred at a faster rate in infants later diagnosed with autism, indicated by a steeper trajectory of FPC1 scores between 3 and 12 months (p < 0.001). Age-related spectral changes were consistent regardless of familial likelihood status, suggesting that differences in oscillatory timing are associated with autism outcomes rather than genetic predisposition. These findings indicate that while the typical sequence of oscillatory maturation is preserved in autism, the timing of these changes is altered, underscoring the critical role of timing in autism pathophysiology and the development of potential screening tools.
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Affiliation(s)
- Abigail Dickinson
- Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Nicole McDonald
- Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Mirella Dapretto
- Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, California, USA
| | - Emilie Campos
- UCLA Department of Biostatistics, Center for Health Sciences, University of California, Los Angeles, California, USA
| | - Damla Senturk
- UCLA Department of Biostatistics, Center for Health Sciences, University of California, Los Angeles, California, USA
| | - Shafali Jeste
- Division of Neurology and Neurological Institute, The Children's Hospital of Los Angeles, Los Angeles, California, USA
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Hou X, Zhang P, Mo L, Peng C, Zhang D. Sensitivity to vocal emotions emerges in newborns at 37 weeks gestational age. eLife 2024; 13:RP95393. [PMID: 39302291 DOI: 10.7554/elife.95393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024] Open
Abstract
Emotional responsiveness in neonates, particularly their ability to discern vocal emotions, plays an evolutionarily adaptive role in human communication and adaptive behaviors. The developmental trajectory of emotional sensitivity in neonates is crucial for understanding the foundations of early social-emotional functioning. However, the precise onset of this sensitivity and its relationship with gestational age (GA) remain subjects of investigation. In a study involving 120 healthy neonates categorized into six groups based on their GA (ranging from 35 and 40 weeks), we explored their emotional responses to vocal stimuli. These stimuli encompassed disyllables with happy and neutral prosodies, alongside acoustically matched nonvocal control sounds. The assessments occurred during natural sleep states using the odd-ball paradigm and event-related potentials. The results reveal a distinct developmental change at 37 weeks GA, marking the point at which neonates exhibit heightened perceptual acuity for emotional vocal expressions. This newfound ability is substantiated by the presence of the mismatch response, akin to an initial form of adult mismatch negativity, elicited in response to positive emotional vocal prosody. Notably, this perceptual shift's specificity becomes evident when no such discrimination is observed in acoustically matched control sounds. Neonates born before 37 weeks GA do not display this level of discrimination ability. This developmental change has important implications for our understanding of early social-emotional development, highlighting the role of gestational age in shaping early perceptual abilities. Moreover, while these findings introduce the potential for a valuable screening tool for conditions like autism, characterized by atypical social-emotional functions, it is important to note that the current data are not yet robust enough to fully support this application. This study makes a substantial contribution to the broader field of developmental neuroscience and holds promise for future research on early intervention in neurodevelopmental disorders.
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Affiliation(s)
- Xinlin Hou
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Peng Zhang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
- Department of Pediatrics, Miyun Country Maternal and Child Health Hospital, Beijing, China
| | - Licheng Mo
- Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, China
| | - Cheng Peng
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Dandan Zhang
- Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, China
- Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, China
- China Center for Behavioral Economics and Finance, Southwestern University of Finance and Economics, Chengdu, China
- School of Psychology, Chengdu Medical College, Chengdu, China
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Lozano I, Belinchón M, Campos R. Sensitivity to temporal synchrony and selective attention in audiovisual speech in infants at elevated likelihood for autism: A preliminary longitudinal study. Infant Behav Dev 2024; 76:101973. [PMID: 38941721 DOI: 10.1016/j.infbeh.2024.101973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/13/2024] [Accepted: 06/14/2024] [Indexed: 06/30/2024]
Abstract
Autism Spectrum Disorder is a highly heritable condition characterized by sociocommunicative difficulties, frequently entailing language atypicalities that extend to infants with a familial history of autism. The developmental mechanisms underlying these difficulties remain unknown. Detecting temporal synchrony between the lip movements and the auditory speech of a talking face and selectively attending to the mouth support typical early language acquisition. This preliminary eye-tracking study investigated whether these two fundamental mechanisms atypically function in infant siblings. We longitudinally tracked the trajectories of infants at elevated and low-likelihood for autism in these two abilities at 4, 8, and 12 months (n = 29). We presented two talking faces (synchronous and asynchronous) while recording infants' gaze to the talker's eyes and mouth. We found that infants detected temporal asynchronies in talking faces at 12 months regardless of group. However, compared to their typically developing peers, infants with an elevated likelihood of autism showed reduced attention to the mouth at the end of the first year and no variations in their interest to this area across time. Our findings provide preliminary evidence on a potentially atypical trajectory of reduced mouth-looking in audiovisual speech during the first year in infant siblings, with potential cascading consequences for language development, thus contributing to domain-general accounts of emerging autism.
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Affiliation(s)
- Itziar Lozano
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Madrid, Spain; Neurocognitive Development Lab, Institute of Psychology, Polish Academy of Sciences, Warsaw, Poland.
| | - Mercedes Belinchón
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Madrid, Spain.
| | - Ruth Campos
- Department of Basic Psychology, Faculty of Psychology, Universidad Autónoma de Madrid, Madrid, Spain.
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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Metabolomic changes in children with autism. World J Clin Pediatr 2024; 13:92737. [PMID: 38947988 PMCID: PMC11212761 DOI: 10.5409/wjcp.v13.i2.92737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/23/2024] [Accepted: 05/06/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD. AIM To comprehensively explore metabolomic changes in children with ASD, integrating findings from various research articles, reviews, systematic reviews, meta-analyses, case reports, editorials, and a book chapter. METHODS A systematic search was conducted in electronic databases, including PubMed, PubMed Central, Cochrane Library, Embase, Web of Science, CINAHL, Scopus, LISA, and NLM catalog up until January 2024. Inclusion criteria encompassed research articles (83), review articles (145), meta-analyses (6), systematic reviews (6), case reports (2), editorials (2), and a book chapter (1) related to metabolomic changes in children with ASD. Exclusion criteria were applied to ensure the relevance and quality of included studies. RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals. These metabolic biomarkers may serve as objective measures to support clinical assessments, improve diagnostic accuracy, and inform personalized treatment approaches. Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD. CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy, guiding personalized treatment approaches, monitoring treatment response, and improving outcomes. Further research is needed to validate findings, establish standardized protocols, and overcome technical challenges in metabolomic analysis. By advancing our understanding of metabolic dysregulations in ASD, clinicians can improve the lives of affected individuals and their families.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatric, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatric, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Pediatric, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama, Bahrain, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Chest Disease, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
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Nie W, Zhou B, Wang Z, Chen B, Wang X, Hu C, Li H, Xu Q, Xu X, Liu H. Computational Interpersonal Communication Model for Screening Autistic Toddlers: A Case Study of Response-to-Name. IEEE J Biomed Health Inform 2024; 28:3683-3694. [PMID: 38625762 DOI: 10.1109/jbhi.2024.3388836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2024]
Abstract
Interpersonal communication facilitates symptom measures of autistic sociability to enhance clinical decision-making in identifying children with autism spectrum disorder (ASD). Traditional methods are carried out by clinical practitioners with assessment scales, which are subjective to quantify. Recent studies employ engineering technologies to analyze children's behaviors with quantitative indicators, but these methods only generate specific rule-driven indicators that are not adaptable to diverse interaction scenarios. To tackle this issue, we propose a Computational Interpersonal Communication Model (CICM) based on psychological theory to represent dyadic interpersonal communication as a stochastic process, providing a scenario-independent theoretical framework for evaluating autistic sociability. We apply CICM to the response-to-name (RTN) with 48 subjects, including 30 toddlers with ASD and 18 typically developing (TD), and design a joint state transition matrix as quantitative indicators. Paired with machine learning, our proposed CICM-driven indicators achieve consistencies of 98.44% and 83.33% with RTN expert ratings and ASD diagnosis, respectively. Beyond outstanding screening results, we also reveal the interpretability between CICM-driven indicators and expert ratings based on statistical analysis.
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Pino MC, Donne IL, Vagnetti R, Tiberti S, Valenti M, Mazza M. Using the Griffiths Mental Development Scales to Evaluate a Developmental Profile of Children with Autism Spectrum Disorder and Their Symptomatologic Severity. Child Psychiatry Hum Dev 2024; 55:117-126. [PMID: 35763176 PMCID: PMC10796491 DOI: 10.1007/s10578-022-01390-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/05/2022] [Indexed: 11/03/2022]
Abstract
Early diagnosis is crucial for Autism spectrum disorder (ASD) and is achieved through a screening of developmental indicators to recognise children who are at risk of autism. One of the most widely used instruments in clinical practice for assessing child development is the Griffiths Mental Development Scale (GMDS). We sought (a) to assess longitudinally whether children diagnosed with ASD, with a mean age of 33.50 months (SD 7.69 months), show a developmental delay of abilities measured by the GMDS over time and (b) to analyse which skills of the GMDS could be associate to the symptomatologic severity of ASD. Our results showed lower scores of General Quotient and all sub-quotients of GMDS from first (T0) to second assessment (T1), except for the Performance sub-quotient. Three sub-quotients (Personal-Social, Hearing and Language and Practical Reasoning) also associate symptom severity at the time when the diagnosis of ASD is made.
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Affiliation(s)
- Maria Chiara Pino
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy.
| | - Ilenia Le Donne
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy
- Abruzzo Region Health System, Reference Regional Centre for Autism, L'Aquila, Italy
| | - Roberto Vagnetti
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy
| | - Sergio Tiberti
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy
| | - Marco Valenti
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy
- Abruzzo Region Health System, Reference Regional Centre for Autism, L'Aquila, Italy
| | - Monica Mazza
- Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, Via Vetoio, Località Coppito, 67100, L'Aquila, Italy
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Deng L, He WZ, Zhang QL, Wei L, Dai Y, Liu YQ, Chen ZL, Ren T, Zhang LL, Gong JB, Li F. Caregiver-child interaction as an effective tool for identifying autism spectrum disorder: evidence from EEG analysis. Child Adolesc Psychiatry Ment Health 2023; 17:138. [PMID: 38098032 PMCID: PMC10722789 DOI: 10.1186/s13034-023-00690-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 12/04/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects individuals across their lifespan. Early diagnosis and intervention are crucial for improving outcomes. However, current diagnostic methods are often time-consuming, and costly, making them inaccessible to many families. In the current study, we aim to test caregiver-child interaction as a potential tool for screening children with ASD in clinic. METHODS We enrolled 85 preschool children (Mean age: 4.90 ± 0.65 years, 70.6% male), including ASD children with or without developmental delay (DD), and typical development (TD) children, along with their caregivers. ASD core symptoms were evaluated by Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule-Calibrated Severity Scores (ADOS-CSS). Behavioral indicators were derived from video encoding of caregiver-child interaction, including social involvement of children (SIC), interaction time (IT), response of children to social cues (RSC), time for caregiver initiated social interactions (GIS) and time for children initiated social interactions (CIS)). Power spectral density (PSD) values were calculated by EEG signals simultaneously recorded. Partial Pearson correlation analysis was used in both ASD groups to investigate the correlation among behavioral indicators scores and ASD symptom severity and PSD values. Receiver operating characteristic (ROC) analysis was used to describe the discrimination accuracy of behavioral indicators. RESULTS Compared to TD group, both ASD groups demonstrated significant lower scores of SIC, IT, RSC, CIS (all p values < 0.05), and significant higher time for GIS (all p values < 0.01). SIC scores negatively correlated with CARS (p = 0.006) and ADOS-CSS (p = 0.023) in the ASD with DD group. Compared to TD group, PSD values elevated in ASD groups (all p values < 0.05), and was associated with SIC (theta band: p = 0.005; alpha band: p = 0.003) but not IQ levels. SIC was effective in identifying both ASD groups (sensitivity/specificity: ASD children with DD, 76.5%/66.7%; ASD children without DD, 82.6%/82.2%). CONCLUSION Our results verified the behavioral paradigm of caregiver-child interaction as an efficient tool for early ASD screening.
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Affiliation(s)
- Lin Deng
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Wei-Zhong He
- Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China
| | - Qing-Li Zhang
- Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Ling Wei
- College of Medical Imaging, Shanghai University of Medicine & Health Science, Shanghai, China
| | - Yuan Dai
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Yu-Qi Liu
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Zi-Lin Chen
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Tai Ren
- Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Lin-Li Zhang
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Jing-Bo Gong
- Shanghai Changning Mental Health Center, Shanghai, 200335, China.
| | - Fei Li
- Department of Developmental and Behavioral Pediatric and Child Primary Care & Ministry of Education, Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
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Cardon G, McQuarrie M, Calton S, Gabrielsen TP. Similar overall expression, but different profiles, of autistic traits, sensory processing, and mental health between young adult males and females. RESEARCH IN AUTISM SPECTRUM DISORDERS 2023; 109:102263. [PMID: 37990737 PMCID: PMC10659573 DOI: 10.1016/j.rasd.2023.102263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2023]
Abstract
Recent trends suggest that autism is more common in females than traditionally held. Additionally, some argue that females express autistic traits differently than males. Dimensional views of autism could shed light on these issues, especially with regards to understudied behavioral areas, such as sensory processing. We examined autistic traits, sensory processing, anxiety, and related behaviors in a large sample of neurotypical young adult males and females (n = 1,122; 556 female; ages 19-26). Participants completed an online survey containing questionnaires related to the above. Between groups statistical analyses, as well as within groups correlations and mediation analyses containing these constructs were then computed. We also carried out a cluster analysis to establish groups with behavioral similarities and estimate within-cluster male/female ratios. Results showed modest differences in the overall expression of autistic traits and sensory processing, if any, between males and females. Conversely, more detailed examination of survey subtests and mediation analyses revealed differing profiles between these groups. Cluster analysis uncovered a group comprised of both males (69.8%) and females (30.2%) who exhibited elevated degrees of autism-related behaviors, suggesting a higher proportion of females than would be predicted by traditional ratios. Taken together, these findings suggest that males and females may not differ as much as previously thought in their general levels of autistic traits or sensory processing, but may present with distinct profiles of such behaviors. These novel results add to our understanding of autistic traits in females and have the potential to positively influence diagnostic and support practices.
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12
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Schwartz S, Wang L, Uribe S, Shinn-Cunningham B, Tager-Flusberg H. Auditory evoked potentials in adolescents with autism: An investigation of brain development, intellectual impairment, and neural encoding. Autism Res 2023; 16:1859-1876. [PMID: 37735966 PMCID: PMC10676753 DOI: 10.1002/aur.3003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 07/21/2023] [Indexed: 09/23/2023]
Abstract
Limited research has evaluated neural encoding of sounds from a developmental perspective in individuals with autism (ASD), especially among those with intellectual disability. We compared auditory evoked potentials (AEPs) in autistic adolescents with a wide range of intellectual abilities (n = 40, NVIQ 30-160) to both age-matched cognitively able neurotypical adolescent controls (NT-A, n = 37) and younger neurotypical children (NT-C, n = 27) to assess potential developmental delays. In addition to a classic measure of peak amplitude, we calculated a continuous measure of intra-class correlation (ICC) between each adolescent participant's AEP and the age-normative, average AEP waveforms calculated from NT-C and NT-A to study differences in signal morphology. We found that peak amplitudes of neural responses were significantly smaller in autistic adolescents compared to NT-A. We also found that the AEP morphology of autistic adolescents looked more like NT-A peers than NT-C but was still significantly different from NT-A AEP waveforms. Results suggest that AEPs of autistic adolescents present differently from NTs, regardless of age, and differences cannot be accounted for by developmental delay. Nonverbal intelligence significantly predicted how closely each adolescent's AEP resembled the age-normed waveform. These results support an evolving theory that the degree of disruption in early neural responses to low-level inputs is reflected in the severity of intellectual impairments in autism.
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Affiliation(s)
- Sophie Schwartz
- Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
| | - Le Wang
- Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
| | - Sofia Uribe
- Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
- Department of Psychology, Southern Methodist University, Dallas, TX, USA
| | | | - Helen Tager-Flusberg
- Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA
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McGlade A, Whittingham K, Barfoot J, Taylor L, Boyd RN. Efficacy of very early interventions on neurodevelopmental outcomes for infants and toddlers at increased likelihood of or diagnosed with autism: A systematic review and meta-analysis. Autism Res 2023; 16:1145-1160. [PMID: 37036800 PMCID: PMC10946707 DOI: 10.1002/aur.2924] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 03/18/2023] [Indexed: 04/11/2023]
Abstract
The aim of this systematic review was to determine the efficacy of very early interventions for infants and toddlers at increased likelihood of or diagnosed with autism for autism symptomatology, developmental outcomes and/or neurocognitive markers. Eight databases were searched (14 April 2022) with inclusion criteria: (i) RCTs with care as usual (CAU) comparison group, (ii) participants at increased likelihood of or diagnosed with autism and aged <24 months corrected age (CA), (iii) parent-mediated and/or clinician directed interventions, and (iv) outcome measures were autism symptomatology, cognition, language, adaptive skills, or neurocognitive assessments (EEG and eye tracking). Quality was assessed using Risk of Bias 2 and GRADE. Nineteen publications from 12 studies reported on 715 infants and toddlers. There was low to moderate certainty evidence that clinician-assessed outcomes did not show significant treatment effects for: autism symptomatology (ADOS CSS: MD -0.08, 95% CI -0.61, 0.44, p = 0.75), cognitive outcome (Mullen Scales of Early Learning-Early Learning Composite (MSEL-ELC): SMD 0.05, 95% CI -0.19, 0.29, p = 0.67), receptive language (MSEL-Receptive Language: SMD 0.04, 95% CI -0.21, 0.3, p = 0.74) or expressive language (MSEL-Expressive Language: SMD 0.06, 95% CI -0.1, 0.23, p = 0.45). Neurocognitive outcomes (EEG and eye tracking) were heterogeneous, with inconsistent findings. There is low to moderate certainty evidence that very early interventions have limited impact on neurodevelopmental outcomes by age 3 years.
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Affiliation(s)
- Andrea McGlade
- Faculty of MedicineThe University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research CentreBrisbaneQueenslandAustralia
| | - Koa Whittingham
- Faculty of MedicineThe University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research CentreBrisbaneQueenslandAustralia
| | - Jacqui Barfoot
- Faculty of MedicineThe University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research CentreBrisbaneQueenslandAustralia
| | - Leisa Taylor
- Department of Humanities EducationUniversity of New EnglandArmidaleNew South WalesAustralia
| | - Roslyn N. Boyd
- Faculty of MedicineThe University of Queensland, Queensland Cerebral Palsy and Rehabilitation Research CentreBrisbaneQueenslandAustralia
- Queensland Paediatric Rehabilitation ServiceQueensland Children's HospitalBrisbaneQueenslandAustralia
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14
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Advancing research on early autism through an integrated risk and resilience perspective. Dev Psychopathol 2023; 35:44-61. [PMID: 35379370 DOI: 10.1017/s0954579421001437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
To date, a deficit-oriented approach dominates autism spectrum disorder (ASD) research, including studies of infant siblings of children with ASD at high risk (HR) for the disabilities associated with this disorder. Despite scientific advances regarding early ASD-related risk, there remains little systematic investigation of positive development, limiting the scope of research and quite possibly a deeper understanding of pathways toward and away from ASD-related impairments. In this paper, we argue that integrating a resilience framework into early ASD research has the potential to enhance knowledge on prodromal course, phenotypic heterogeneity, and developmental processes of risk and adaptation. We delineate a developmental systems resilience framework with particular reference to HR infants. To illustrate the utility of a resilience perspective, we consider the "female protective effect" and other evidence of adaptation in the face of ASD-related risk. We suggest that a resilience framework invites focal questions about the nature, timing, levels, interactions, and mechanisms by which positive adaptation occurs in relation to risk and developmental pathways toward and away from ASD-related difficulties. We conclude with recommendations for future research, including more focus on adaptive development and multisystem processes, pathways away from disorder, and reconsideration of extant evidence within an integrated risk-and-resilience framework.
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15
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Zhai J, Li X, Zhou Y, Fan L, Xia W, Wang X, Li Y, Hou M, Wang J, Wu L. Correlation and predictive ability of sensory characteristics and social interaction in children with autism spectrum disorder. Front Psychiatry 2023; 14:1056051. [PMID: 37091701 PMCID: PMC10117963 DOI: 10.3389/fpsyt.2023.1056051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 03/13/2023] [Indexed: 04/25/2023] Open
Abstract
Background Individuals with autism spectrum disorder (ASD) often have different social characteristics and particular sensory processing patterns, and these sensory behaviors may affect their social functioning. The objective of our study is to investigate the sensory profiles of children with ASD and their association with social behavior. Specifically, we aim to identify the predictive role of sensory processing in social functioning. Methods The Short Sensory Profile (SSP) was utilized to analyze sensory differences between ASD children and their peers. The Social Responsiveness Scale (SRS) and other clinical scales were employed to assess the social functioning of children with ASD. Additionally, the predictive ability of sensory perception on social performance was discussed using random forest and support vector machine (SVM) models. Results The SSP scores of ASD children were lower than those of the control group, and there was a significant negative correlation between SSP scores and clinical scale scores (P < 0.05). The random forest and SVM models, using all the features, showed higher sensitivity, while the random forest model with 7-feature factors had the highest specificity. The area under the receiver operating characteristic (ROC) curve (AUC) for all the models was higher than 0.8. Conclusion Autistic children in our study have different patterns of sensory processing than their peers, which are significantly related to their patterns of social functioning. Sensory features can serve as a good predictor of social functioning in individuals with ASD.
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Affiliation(s)
- Jinhe Zhai
- School of Public Health, Harbin Medical University, Harbin, China
| | - Xiaoxue Li
- School of Public Health, Harbin Medical University, Harbin, China
| | - Yong Zhou
- Heilongjiang Provincial Center for Disease Control and Prevention, Harbin, China
| | - Lili Fan
- School of Public Health, Harbin Medical University, Harbin, China
| | - Wei Xia
- School of Public Health, Harbin Medical University, Harbin, China
| | - Xiaomin Wang
- School of Public Health, Harbin Medical University, Harbin, China
| | - Yutong Li
- School of Public Health, Harbin Medical University, Harbin, China
| | - Meiru Hou
- School of Public Health, Harbin Medical University, Harbin, China
| | - Jia Wang
- School of Public Health, Harbin Medical University, Harbin, China
- *Correspondence: Jia Wang,
| | - Lijie Wu
- School of Public Health, Harbin Medical University, Harbin, China
- Lijie Wu,
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Derakhshanrad SA, Piven E, Zeynalzadeh Ghoochani B. The relationship between sensory experiences and social functioning in children with autism spectrum disorder. INTERNATIONAL JOURNAL OF DEVELOPMENTAL DISABILITIES 2022; 70:632-640. [PMID: 38983486 PMCID: PMC11229742 DOI: 10.1080/20473869.2022.2128553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 09/20/2022] [Indexed: 07/11/2024]
Abstract
Objective: This study was undertaken to substantiate the connection between sensory experiences and social functioning among 142 children ages 4-10 years with autism spectrum disorder. Methods: Using an online cross-sectional survey, mothers' perceptions of sensory and social characteristics of their children on parent-reported measures of sensory experiences and social functioning were collected. Findings: Using SPSS software to follow the related descriptive statistics and correlational analysis, the results indicated that children had different levels of challenging sensory experiences and social interaction difficulties. It was revealed that higher intensities of sensory issues were associated with lower levels of functioning and greater social interaction difficulties. Further analysis revealed that less awkward, unpleasant experiences in the auditory and tactile sensory functioning correlated with less social difficulties. Conclusions: Given that no causal relationship could be drawn in this study, the findings complemented those of earlier studies, which suggest engagement in social interactions may be correlated with sensory response patterns.
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Affiliation(s)
- Seyed Alireza Derakhshanrad
- Department of Occupational Therapy, School of Rehabilitation Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Emily Piven
- Occupational Therapy Doctoral Program, University of St. Augustine for Health Sciences, St Augustine, FL, USA
| | - Bahareh Zeynalzadeh Ghoochani
- Department of Occupational Therapy, School of Rehabilitation Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
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17
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VAN Rooijen R, Ward EK, DE Jonge M, Kemner C, Junge C. Two-year-olds at elevated risk for ASD can learn novel words from their parents. JOURNAL OF CHILD LANGUAGE 2022; 49:1052-1063. [PMID: 34227461 DOI: 10.1017/s0305000921000428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
Children diagnosed with autism spectrum disorder (ASD) often have smaller vocabularies in infancy compared to typically-developing children. To understand whether their smaller vocabularies stem from problems in learning, our study compared a prospective risk sample of 18 elevated risk and 11 lower risk 24-month-olds on current vocabulary size and word learning ability using a paradigm in which parents teach their child words. Results revealed that both groups learned novel words, even though parents indicated that infants at elevated risk of ASD knew fewer words. This suggests that these early compromised vocabularies cannot be solely linked to difficulties in word formations.
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Affiliation(s)
- Rianne VAN Rooijen
- Experimental Psychology, Helmholtz Institute, Utrecht University, Netherlands
- Developmental Psychology, Utrecht University, Netherlands
| | - Emma Kate Ward
- Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
| | - Maretha DE Jonge
- Clinical Neurodevelopmental Sciences, Leiden University, Netherlands
- Brain Center Rudolf Magnus, University Medical Center Utrecht, Netherlands
| | - Chantal Kemner
- Experimental Psychology, Helmholtz Institute, Utrecht University, Netherlands
- Developmental Psychology, Utrecht University, Netherlands
- Brain Center Rudolf Magnus, University Medical Center Utrecht, Netherlands
| | - Caroline Junge
- Experimental Psychology, Helmholtz Institute, Utrecht University, Netherlands
- Developmental Psychology, Utrecht University, Netherlands
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18
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De Laet A, Piccardi ES, Begum-Ali J, Charman T, Johnson MH, Jones EJH, Bedford R, Gliga T. Neuronal gating of tactile input and sleep in 10-month-old infants at typical and elevated likelihood for autism spectrum disorder. Sci Rep 2022; 12:14188. [PMID: 35986046 PMCID: PMC9391390 DOI: 10.1038/s41598-022-18018-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/04/2022] [Indexed: 12/23/2022] Open
Abstract
Sleep problems in Autism Spectrum Disorder (ASD) emerge early in development, yet the origin remains unclear. Here, we characterise developmental trajectories in sleep onset latency (SOL) and night awakenings in infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) and infants at typical likelihood (TL) for ASD. Further, we test whether the ability to gate tactile input, using an EEG tactile suppression index (TSI), associates with variation in SOL and night awakenings. Parent-reported night awakenings and SOL from 124 infants (97 at EL for ASD) at 5, 10 and 14 months were analyzed using generalized estimating equations. Compared to TL infants, infants at EL had significantly more awakenings and longer SOL at 10 and 14 months. The TSI predicted SOL concurrently at 10 months, independent of ASD likelihood status, but not longitudinally at 14 months. The TSI did not predict night awakenings concurrently or longitudinally. These results imply that infants at EL for ASD wake up more frequently during the night and take longer to fall asleep from 10 months of age. At 10 months, sensory gating predicts SOL, but not night awakenings, suggesting sensory gating differentially affects neural mechanisms of sleep initiation and maintenance.
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Affiliation(s)
- Anna De Laet
- School of Psychology, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
| | - Elena Serena Piccardi
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
- School of Psychology, Department of Psychological Sciences, University of East London, London, UK
| | - Jannath Begum-Ali
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | - Tony Charman
- Psychology Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Mark H Johnson
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
- Department of Psychology, University of Cambridge, Cambridge, UK
| | - Emily J H Jones
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | | | - Teodora Gliga
- School of Psychology, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
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19
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From Genes to Therapy in Autism Spectrum Disorder. Genes (Basel) 2022; 13:genes13081377. [PMID: 36011288 PMCID: PMC9407279 DOI: 10.3390/genes13081377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/19/2022] [Indexed: 02/04/2023] Open
Abstract
In recent years, findings from genetic and other biological studies are starting to reveal the role of various molecular mechanisms that contribute to the etiology of ASD [...]
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20
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Talge NM, Adkins M, Kileny PR, Frownfelter I. Click-evoked auditory brainstem responses and autism spectrum disorder: a meta-analytic investigation of disorder specificity. Pediatr Res 2022; 92:40-46. [PMID: 34497358 PMCID: PMC8901768 DOI: 10.1038/s41390-021-01730-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 08/16/2021] [Accepted: 08/17/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Click-evoked auditory brainstem response (ABR) alterations are associated with autism spectrum disorder (ASD), but the specificity of these findings to the disorder is unclear. We therefore performed a meta-analysis on ABRs and attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder that shares some etiologic and symptom overlap with ASD. METHODS Seven papers compared ABR latency components (I, III, V, I-III, III-V, and I-V) between participants with and without ADHD. We used random-effects regression to generate component-specific estimates (Hedges's g) that adjusted for study sample sizes and the number of studies contributing to each estimate. We compared these estimates to our recently published meta-analysis of ABRs and ASD. RESULTS All ADHD studies employed cross-sectional designs. ADHD was associated with longer latencies for waves III and V (g = 0.6, 95% confidence interval (CI) 0.3, 1.0 and g = 0.6, 95% CI 0.3, 0.9) and waves I-III and I-V (g = 0.7, 95% CI 0.2, 1.3 and g = 0.6, 95% CI 0.3, 1.0). Effect sizes from the ASD and ADHD meta-analyses did not differ from each other. CONCLUSIONS Similar patterns of ABR alterations are observed in ADHD and ASD. However, studies rarely screen for middle ear dysfunction or hearing loss and rely upon cross-sectional designs. Addressing these issues will inform the viability of ABRs as a prognostic and/or etiologic biomarker for these disorders. IMPACT Click-evoked ABR alterations are associated with ASD, but the specificity of these findings to the disorder is unclear. We therefore performed a meta-analysis of the association between ABRs and ADHD, a disorder that shares some etiologic and symptom overlap with ASD. ADHD was associated with longer ABR latencies for several components. These components are identical to those implicated in ASD. Effect sizes were similar in magnitude across disorders. The viability of ABRs as prognostic and/or etiologic biomarkers for neurodevelopmental risk requires addressing limitations in the literature (e.g., cross-sectional data, non-standardized ABR protocols, minimal characterization of symptom heterogeneity).
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Affiliation(s)
- Nicole M. Talge
- Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI 48824,College of Human Medicine, Michigan State University, East Lansing, MI 48824
| | - Melanie Adkins
- Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI 48824,College of Human Medicine, Michigan State University, East Lansing, MI 48824
| | - Paul R. Kileny
- Dept. of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI 48109
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21
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Executive Functions in Children and Adolescents with Autism Spectrum Disorder, Grade 1 and 2, vs. Neurotypical Development: A School View. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19137987. [PMID: 35805641 PMCID: PMC9265427 DOI: 10.3390/ijerph19137987] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 06/24/2022] [Accepted: 06/26/2022] [Indexed: 12/03/2022]
Abstract
Background: Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social and communication functioning. Previous studies suggest that people with autism spectrum disorders have deficits in executive functions, having found a relationship with cognitive flexibility, planning, working memory, inhibition or self-control, but it is especially with respect to cognitive flexibility where the greatest dysfunctions have been found. The objective of this research was to compare the executive functioning of a group of children and adolescents diagnosed with autism spectrum disorders with another with neurotypical development in an educational context. Methods: This was a cross-sectional, descriptive and multicenter confirmatory study in which 121 people who participated acted as informants, with 70 of them being education professionals who work with people with autism spectrum disorders grade 1 and 2 and 51 of them being teachers who work with people of neurotypical development; these individuals were selected through non-probabilistic sampling. Results: People diagnosed with autism spectrum disorders obtained significantly higher scores on the Behavior Rating Inventory of Executive Function-2 scale for the nine clinical scales and the four indexes that compose it compared to the group of people with neurotypical development; in addition, the average scores obtained are clinically significant, with them being elevated for the group with autism spectrum disorders. This study confirms that children and adolescents with autism spectrum disorders experience greater difficulties with respect to their executive functions than children with neurotypical development.
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22
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Application of Machine Learning Techniques to Detect the Children with Autism Spectrum Disorder. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:9340027. [PMID: 35368925 PMCID: PMC8975630 DOI: 10.1155/2022/9340027] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/05/2022] [Accepted: 03/08/2022] [Indexed: 11/17/2022]
Abstract
Early detection of autism spectrum disorder (ASD) is highly beneficial to the health sustainability of children. Existing detection methods depend on the assessment of experts, which are subjective and costly. In this study, we proposed a machine learning approach that fuses physiological data (electroencephalography, EEG) and behavioral data (eye fixation and facial expression) to detect children with ASD. Its implementation can improve detection efficiency and reduce costs. First, we used an innovative approach to extract features of eye fixation, facial expression, and EEG data. Then, a hybrid fusion approach based on a weighted naive Bayes algorithm was presented for multimodal data fusion with a classification accuracy of 87.50%. Results suggest that the machine learning classification approach in this study is effective for the early detection of ASD. Confusion matrices and graphs demonstrate that eye fixation, facial expression, and EEG have different discriminative powers for the detection of ASD and typically developing children, and EEG may be the most discriminative information. The physiological and behavioral data have important complementary characteristics. Thus, the machine learning approach proposed in this study, which combines the complementary information, can significantly improve classification accuracy.
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23
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Farooq RK, Alamoudi W, Alhibshi A, Rehman S, Sharma AR, Abdulla FA. Varied Composition and Underlying Mechanisms of Gut Microbiome in Neuroinflammation. Microorganisms 2022; 10:705. [PMID: 35456757 PMCID: PMC9032006 DOI: 10.3390/microorganisms10040705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/21/2022] [Accepted: 03/17/2022] [Indexed: 11/16/2022] Open
Abstract
The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.
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Affiliation(s)
- Rai Khalid Farooq
- Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdul Rahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (W.A.); (A.A.); (F.A.A.)
| | - Widyan Alamoudi
- Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdul Rahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (W.A.); (A.A.); (F.A.A.)
| | - Amani Alhibshi
- Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdul Rahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (W.A.); (A.A.); (F.A.A.)
| | - Suriya Rehman
- Department of Epidemic Diseases Research, Institute of Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
| | - Ashish Ranjan Sharma
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Korea;
| | - Fuad A. Abdulla
- Department of Neuroscience Research, Institute of Research and Medical Consultations, Imam Abdul Rahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia; (W.A.); (A.A.); (F.A.A.)
- Department of Physical Therapy, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, P.O. Box 2435, Dammam 31441, Saudi Arabia
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Rochat MJ, Gallese V. The Blurred Vital Contours of Intersubjectivity in Autism Spectrum Disorder: Early Signs and Neurophysiological Hypotheses. PSYCHOANALYTIC INQUIRY 2022. [DOI: 10.1080/07351690.2022.2007022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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25
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Williams OOF, Coppolino M, Perreault ML. Sex differences in neuronal systems function and behaviour: beyond a single diagnosis in autism spectrum disorders. Transl Psychiatry 2021; 11:625. [PMID: 34887388 PMCID: PMC8660826 DOI: 10.1038/s41398-021-01757-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 11/30/2021] [Indexed: 12/12/2022] Open
Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is associated with functional brain alterations that underlie the expression of behaviour. Males are diagnosed up to four times more than females, and sex differences have been identified in memory, cognitive flexibility, verbal fluency, and social communication. Unfortunately, there exists a lack of information on the sex-dependent mechanisms of ASD, as well as biological markers to distinguish sex-specific symptoms in ASD. This can often result in a standardized diagnosis for individuals across the spectrum, despite significant differences in the various ASD subtypes. Alterations in neuronal connectivity and oscillatory activity, such as is observed in ASD, are highly coupled to behavioural states. Yet, despite the well-identified sexual dimorphisms that exist in ASD, these functional patterns have rarely been analyzed in the context of sex differences or symptomology. This review summarizes alterations in neuronal oscillatory function in ASD, discusses the age, region, symptom and sex-specific differences that are currently observed across the spectrum, and potential targets for regulating neuronal oscillatory activity in ASD. The need to identify sex-specific biomarkers, in order to facilitate specific diagnostic criteria and allow for more targeted therapeutic approaches for ASD will also be discussed.
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Affiliation(s)
| | | | - Melissa L Perreault
- Department of Biomedical Sciences, University of Guelph, Guelph, ON, Canada.
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Kulke L, Pasqualette L. Emotional content influences eye-movements under natural but not under instructed conditions. Cogn Emot 2021; 36:332-344. [PMID: 34886742 DOI: 10.1080/02699931.2021.2009446] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
ABSTRACTIn everyday life, people can freely decide if and where they would like to move their attention and gaze, often influenced by physical and emotional salience of stimuli. However, many laboratory paradigms explicitly instruct participants when and how to move their eyes, leading to unnatural instructed eye-movements. The current preregistered study compared eye-movements to peripherally appearing faces with happy, angry and neutral expressions under natural and instructed conditions. Participants reliably moved their eyes towards peripheral faces, even when they were not instructed to do so; however, eye-movements were significantly slower under natural than under instructed conditions. Competing central stimuli decelerated eye-movements independently of instructions. Unexpectedly, the emotional salience only affected eye-movements under natural conditions, with faster saccades towards emotional than towards neutral faces. No effects of emotional expression occurred when participants were instructed to move their eyes. The study shows that natural eye-movements significantly differ from instructed eye-movements and emotion-driven attention effects are reduced when participants are artificially instructed to move their eyes, suggesting that research should investigate eye-movements under natural conditions.
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Affiliation(s)
- Louisa Kulke
- Neurocognitive Developmental Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen Germany
| | - Laura Pasqualette
- Neurocognitive Developmental Psychology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen Germany
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27
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Cheung WC, Meadan H, Xia Y. A Longitudinal Analysis of the Relationships Between Social, Communication, and Motor Skills Among Students with Autism. J Autism Dev Disord 2021; 52:4505-4518. [PMID: 34677754 DOI: 10.1007/s10803-021-05328-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2021] [Indexed: 10/20/2022]
Abstract
Many students with autism have difficulties engaging with their classroom environments and forming friendships, which are mostly affected by deficits in social, communication, and motor skills. The Special Education Elementary Longitudinal Study (SEELS, 2000) data set was used, focusing on elementary age students with autism, to explore the longitudinal relationships between social, communication, and motor skills and the mediating role of motor skills in between communication and social skills by using structural equational modeling analyses. Results show that (a) motor skills mediate the relationship between communication and social skills in elementary school, (b) there are significant longitudinal relationships among these skills in elementary school. Increased motor skills may improve social skills for students with autism in elementary school.
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Affiliation(s)
- W C Cheung
- Department of Special Education, University of Illinois at Urbana-Champaign, 288 Education, 1310 S. Sixth St., Champaign, IL, 61820, USA.
| | - H Meadan
- Department of Special Education, University of Illinois at Urbana-Champaign, 288 Education, 1310 S. Sixth St., Champaign, IL, 61820, USA
| | - Y Xia
- Department of Educational Psychology, University of Illinois at Urbana-Champaign, 230B Education, 1310 S. Sixth St., Champaign, IL, 61820, USA
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Park S, Haak KV, Cho HB, Valk SL, Bethlehem RAI, Milham MP, Bernhardt BC, Di Martino A, Hong SJ. Atypical Integration of Sensory-to-Transmodal Functional Systems Mediates Symptom Severity in Autism. Front Psychiatry 2021; 12:699813. [PMID: 34489757 PMCID: PMC8417581 DOI: 10.3389/fpsyt.2021.699813] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/16/2021] [Indexed: 12/12/2022] Open
Abstract
A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology.
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Affiliation(s)
- Shinwon Park
- Institute for Basic Science, Center for Neuroscience Imaging Research, Sungkyunkwan University, Suwon, South Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea
| | - Koen V. Haak
- Donders Institute of Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
| | - Han Byul Cho
- Institute for Basic Science, Center for Neuroscience Imaging Research, Sungkyunkwan University, Suwon, South Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea
| | - Sofie L. Valk
- Otto Hahn Group Cognitive Neurogenetics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
- Institute of Neuroscience and Medicine (INM-7), Forschungszentrum Jülich, Jülich, Germany
| | - Richard A. I. Bethlehem
- Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom
- Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
| | - Michael P. Milham
- Center for the Developing Brain, Child Mind Institute, New York, NY, United States
- Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, New York, NY, United States
| | - Boris C. Bernhardt
- McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
| | | | - Seok-Jun Hong
- Institute for Basic Science, Center for Neuroscience Imaging Research, Sungkyunkwan University, Suwon, South Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea
- Center for the Developing Brain, Child Mind Institute, New York, NY, United States
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Del Bianco T, Mason L, Charman T, Tillman J, Loth E, Hayward H, Shic F, Buitelaar J, Johnson MH, Jones EJH. Temporal Profiles of Social Attention Are Different Across Development in Autistic and Neurotypical People. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2021; 6:813-824. [PMID: 33191160 DOI: 10.1016/j.bpsc.2020.09.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/11/2020] [Accepted: 09/01/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Sociocommunicative difficulties, including abnormalities in eye contact, are core diagnostic features of autism spectrum disorder (ASD). Many studies have used eye tracking to measure reduced attention to faces in autistic people; however, most of this work has not taken advantage of eye-tracking temporal resolution to examine temporal profiles of attention. METHODS We used growth curve analysis to model attention to static social scenes as a function of time in a large (N = 650) sample of autistic participants and neurotypical participants across a wide age range (6-30 years). RESULTS The model yielded distinct temporal profiles of attention to faces in the groups. Initially, both groups showed a relatively high probability of attending to faces, followed by decline after several seconds. The neurotypical participants, however, were significantly more likely to return their attention to faces in the latter part of each 20-second trial, with increasing probability with age. In contrast, the probability of returning to the face in the autistic participants remained low across development. In participants with ASD, more atypical profiles of attention were associated with lower Vineland Adaptive Behavior Scales communication scores and a higher curvature in one data-driven cluster correlated with symptom severity. CONCLUSIONS These findings show that social attention not only is reduced in ASD, but also differs in its temporal dynamics. The neurotypical participants became more sophisticated in how they deployed their social attention across age, a pattern that was significantly reduced in the participants with ASD, possibly reflecting delayed acquisition of social expertise.
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Affiliation(s)
- Teresa Del Bianco
- Centre of Brain and Cognitive Development, Birkbeck College, University of London, London, United Kingdom.
| | - Luke Mason
- Centre of Brain and Cognitive Development, Birkbeck College, University of London, London, United Kingdom
| | - Tony Charman
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Julian Tillman
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Eva Loth
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Hannah Hayward
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Frederick Shic
- Department of Pediatrics, School of Medicine, University of Washington, Seattle, Washington
| | - Jan Buitelaar
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands
| | - Mark H Johnson
- Centre of Brain and Cognitive Development, Birkbeck College, University of London, London, United Kingdom; Department of Psychology, University of Cambridge, Cambridge, United Kingdom
| | - Emily J H Jones
- Centre of Brain and Cognitive Development, Birkbeck College, University of London, London, United Kingdom
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Osório JMA, Rodríguez-Herreros B, Richetin S, Junod V, Romascano D, Pittet V, Chabane N, Jequier Gygax M, Maillard AM. Sex differences in sensory processing in children with autism spectrum disorder. Autism Res 2021; 14:2412-2423. [PMID: 34288517 PMCID: PMC9290069 DOI: 10.1002/aur.2580] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 05/12/2021] [Accepted: 07/08/2021] [Indexed: 12/13/2022]
Abstract
Despite the high prevalence of sensory processing difficulties in children with autism spectrum disorder (ASD), little research has focused on the sex differences in sensory processing. Furthermore, there is a lack of knowledge on the female‐specific symptoms of ASD, contributing to later referral, diagnosis and intervention. In this study, we examined the sex differences in sensory processing symptoms in large cohorts of ASD children (N = 168; 26 females, 142 males) and typically developing (TD) children (N = 439; 209 females, 230 males). For this, we translated the sensory processing measure (SPM) and SPM – Preschool (SPM‐P) Home Forms to French. The SPM/SPM‐P are parent/caregiver questionnaires that assess typical behavioral responses to sensory stimuli. Overall, our results showed that the magnitude of the differences in sensory processing between males and females is larger in ASD children relative to TD children, with females showing more severe symptoms in Hearing, as well as Balance and Motion subscales. Additionally, linear discriminant analysis showed that the SPM/SPM‐P are good at discriminating TD children from ASD, children with higher accuracy rates for females than for males. These findings are discussed in light of the heterogeneity of sensory processing difficulties present in ASD. Overall, our results suggest that there seem to be female‐specific profiles in sensory processing difficulties in ASD. Implications of findings concerning sex differences in sensory processing and their potential for improving identification and diagnosis of ASD females are discussed.
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Affiliation(s)
- Joana Maria Almeida Osório
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Borja Rodríguez-Herreros
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Sonia Richetin
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Vincent Junod
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - David Romascano
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Valérie Pittet
- Department Epidemiology and Health Systems, Center for Primary Care and Public Health - University of Lausanne, Lausanne, Switzerland
| | - Nadia Chabane
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Marine Jequier Gygax
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
| | - Anne Manuela Maillard
- Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Lausanne, Switzerland
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31
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Gui A, Bussu G, Tye C, Elsabbagh M, Pasco G, Charman T, Johnson MH, Jones EJH. Attentive brain states in infants with and without later autism. Transl Psychiatry 2021; 11:196. [PMID: 33785730 PMCID: PMC8009890 DOI: 10.1038/s41398-021-01315-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 02/01/2023] Open
Abstract
Early difficulties in engaging attentive brain states in social settings could affect learning and have cascading effects on social development. We investigated this possibility using multichannel electroencephalography during a face/non-face paradigm in 8-month-old infants with (FH, n = 91) and without (noFH, n = 40) a family history of autism spectrum disorder (ASD). An event-related potential component reflecting attention engagement, the Nc, was compared between FH infants who received a diagnosis of ASD at 3 years of age (FH-ASD; n = 19), FH infants who did not (FH-noASD; n = 72) and noFH infants (who also did not, hereafter noFH-noASD; n = 40). 'Prototypical' microstates during social attention were extracted from the noFH-noASD group and examined in relation to later categorical and dimensional outcome. Machine-learning was used to identify the microstate features that best predicted ASD and social adaptive skills at three years. Results suggested that whilst measures of brain state timing were related to categorical ASD outcome, brain state strength was related to dimensional measures of social functioning. Specifically, the FH-ASD group showed shorter Nc latency relative to other groups, and duration of the attentive microstate responses to faces was informative for categorical outcome prediction. Reduced Nc amplitude difference between faces with direct gaze and a non-social control stimulus and strength of the attentive microstate to faces contributed to the prediction of dimensional variation in social skills. Taken together, this provides consistent evidence that atypical attention engagement precedes the emergence of difficulties in socialization and indicates that using the spatio-temporal characteristics of whole-brain activation to define brain states in infancy provides an important new approach to understanding of the neurodevelopmental mechanisms that lead to ASD.
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Affiliation(s)
- Anna Gui
- Centre for Brain and Cognitive Development, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, UK.
| | - Giorgia Bussu
- Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Kapittelweg 29, 6525 EN, Nijmegen, The Netherlands
| | - Charlotte Tye
- Department of Child & Adolescent Psychiatry & Department of Psychology, King's College London, De Crespigny Park, London, SE5 8AF, UK
| | - Mayada Elsabbagh
- Montreal Neurological Institute, McGill University, 3801 Rue University, Montréal, QC, H3A 2B4, Canada
| | - Greg Pasco
- Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK
| | - Tony Charman
- Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK
| | - Mark H Johnson
- Department of Psychology, Cambridge University, Downing Street, Cambridge, CB2 3EB, UK
| | - Emily J H Jones
- Centre for Brain and Cognitive Development, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, UK.
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32
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Idei H, Murata S, Yamashita Y, Ogata T. Paradoxical sensory reactivity induced by functional disconnection in a robot model of neurodevelopmental disorder. Neural Netw 2021; 138:150-163. [PMID: 33652371 DOI: 10.1016/j.neunet.2021.01.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 12/19/2020] [Accepted: 01/29/2021] [Indexed: 10/22/2022]
Abstract
Neurodevelopmental disorders are characterized by heterogeneous and non-specific nature of their clinical symptoms. In particular, hyper- and hypo-reactivity to sensory stimuli are diagnostic features of autism spectrum disorder and are reported across many neurodevelopmental disorders. However, computational mechanisms underlying the unusual paradoxical behaviors remain unclear. In this study, using a robot controlled by a hierarchical recurrent neural network model with predictive processing and learning mechanism, we simulated how functional disconnection altered the learning process and subsequent behavioral reactivity to environmental change. The results show that, through the learning process, long-range functional disconnection between distinct network levels could simultaneously lower the precision of sensory information and higher-level prediction. The alteration caused a robot to exhibit sensory-dominated and sensory-ignoring behaviors ascribed to sensory hyper- and hypo-reactivity, respectively. As long-range functional disconnection became more severe, a frequency shift from hyporeactivity to hyperreactivity was observed, paralleling an early sign of autism spectrum disorder. Furthermore, local functional disconnection at the level of sensory processing similarly induced hyporeactivity due to low sensory precision. These findings suggest a computational explanation for paradoxical sensory behaviors in neurodevelopmental disorders, such as coexisting hyper- and hypo-reactivity to sensory stimulus. A neurorobotics approach may be useful for bridging various levels of understanding in neurodevelopmental disorders and providing insights into mechanisms underlying complex clinical symptoms.
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Affiliation(s)
- Hayato Idei
- Department of Intermedia Studies, Waseda University, Tokyo, 169-8555, Japan.
| | - Shingo Murata
- Department of Electronics and Electrical Engineering, Keio University, Kanagawa, 223-8522, Japan.
| | - Yuichi Yamashita
- Department of Information Medicine, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
| | - Tetsuya Ogata
- Department of Intermedia Art and Science, Waseda University, Tokyo, 169-8555, Japan.
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33
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Osório JMA, Rodríguez-Herreros B, Romascano D, Junod V, Habegger A, Pain A, Richetin S, Yu P, Isidor B, Van Maldergem L, Pons L, Manificat S, Chabane N, Jequier Gygax M, Maillard AM. Touch and olfaction/taste differentiate children carrying a 16p11.2 deletion from children with ASD. Mol Autism 2021; 12:8. [PMID: 33546725 PMCID: PMC7863523 DOI: 10.1186/s13229-020-00410-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/22/2020] [Indexed: 11/24/2022] Open
Abstract
Background Sensory processing atypicalities are frequent in Autism Spectrum Disorder (ASD) and neurodevelopmental disorders (NDD). Different domains of sensory processing appear to be differentially altered in these disorders. In this study, we explored the sensory profile of two clinical cohorts, in comparison with a sample of typically developing children. Methods Behavioral responses to sensory stimuli were assessed using the Sensory Processing Measure (parent-report questionnaire). We included 121 ASD children, 17 carriers of the 16p11.2 deletion (Del 16p11.2) and 45 typically developing (TD) children. All participants were aged between 2 and 12 years. Additional measures included the Tactile Defensiveness and Discrimination Test-Revised, Wechsler Intelligence Scales and Autism Diagnostic Observation Schedule (ADOS-2). Statistical analyses included MANCOVA and regression analyses. Results ASD children score significantly higher on all SPM subscales compared to TD. Del16p11.2 also scored higher than TD on all subscales except for tactile and olfactory/taste processing, in which they score similarly to TD. When assessing sensory modulation patterns (hyper-, hypo-responsiveness and seeking), ASD did not significantly differ from del16p11.2. Both groups had significantly higher scores across all patterns than the TD group. There was no significant association between the SPM Touch subscale and the TDDT-R. Limitations Sensory processing was assessed using a parent-report questionnaire. Even though it captures observable behavior, a questionnaire does not assess sensory processing in all its complexity. The sample size of the genetic cohort and the small subset of ASD children with TDDT-R data render some of our results exploratory. Divergence between SPM Touch and TDDT-R raises important questions about the nature of the process that is assessed. Conclusions Touch and olfaction/taste seem to be particularly affected in ASD children compared to del16p11.2. These results indicate that parent report measures can provide a useful perspective on behavioral expression. Sensory phenotyping, when combined with neurobiological and psychophysical methods, might have the potential to provide a better understanding of the sensory processing in ASD and in other NDD.
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Affiliation(s)
- Joana Maria Almeida Osório
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Borja Rodríguez-Herreros
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - David Romascano
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Vincent Junod
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Aline Habegger
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Aurélie Pain
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Sonia Richetin
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Paola Yu
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland.,Laboratory for Investigative Neurophysiology (LINE), Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | | | - Lionel Van Maldergem
- Centre de Génétique Humaine, Centre Hospitalier Régional Universitaire, Université de Franche-Comté, Besançon, France.,Unité de recherche en neurosciences intégratives et cognitives EA481, Université de Franche-Comté, Besançon, France.,Centre d'investigation clinique 1431, INSERM, Besançon, France
| | - Linda Pons
- Service Génopsy - Pôle Hospitalo-Universitaire ADIS, Centre hospitalier Le Vinatier, Bron, France
| | - Sabine Manificat
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Nadia Chabane
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Marine Jequier Gygax
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland
| | - Anne Manuela Maillard
- CHUV-Centre Hospitalier Universitaire Vaudois, Service des Troubles du Spectre de l'Autisme et apparentés, Lausanne University Hospital, Les Allières - Av. Beaumont 23, 1011, Lausanne, Switzerland.
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Attunement in Music Therapy for Young Children with Autism: Revisiting Qualities of Relationship as Mechanisms of Change. J Autism Dev Disord 2021; 50:3921-3934. [PMID: 32189227 PMCID: PMC7560932 DOI: 10.1007/s10803-020-04448-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
This study examined whether musical and emotional attunement predicts changes in improvisational music therapy with children with autism (4–7 years, N = 101, majority: no/limited speech, low IQ), assessed over 12 months. Attunement, as observed from session videos, and changes in generalized social skills, judged by blinded assessors and parents, were evaluated using standardized tools (Assessment of the Quality of Relationship, Improvisational Music Therapy Principles, ADOS, SRS). In contrast to the smaller pilot, we did not find significant effects between attunement and changes in outcomes, only tendencies in the same direction are observed. Findings suggest that symptom severity is associated with the therapist’s ability to attune to the child. They further raise questions concerning outcome selection and user involvement.
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35
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Piccardi ES, Begum Ali J, Jones EJH, Mason L, Charman T, Johnson MH, Gliga T. Behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of autism spectrum disorder and/or attention deficit hyperactivity disorder. J Neurodev Disord 2021; 13:1. [PMID: 33390154 PMCID: PMC7780639 DOI: 10.1186/s11689-020-09334-1] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 11/04/2020] [Indexed: 12/29/2022] Open
Abstract
Backgrounds Atypicalities in tactile processing are reported in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) but it remains unknown if they precede and associate with the traits of these disorders emerging in childhood. We investigated behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of ASD and/or ADHD compared to infants at typical likelihood of the disorders. Further, we assessed the specificity of associations between infant markers and later ASD or ADHD traits. Methods Ninety-one 10-month-old infants participated in the study (n = 44 infants at elevated likelihood of ASD; n = 20 infants at elevated likelihood of ADHD; n = 9 infants at elevated likelihood of ASD and ADHD; n = 18 infants at typical likelihood of the disorders). Behavioural and EEG responses to pairs of tactile stimuli were experimentally recorded and concurrent parental reports of tactile responsiveness were collected. ASD and ADHD traits were measured at 24 months through standardized assessment (ADOS-2) and parental report (ECBQ), respectively. Results There was no effect of infants’ likelihood status on behavioural markers of tactile sensory processing. Conversely, increased ASD likelihood associated with reduced neural repetition suppression to tactile input. Reduced neural repetition suppression at 10 months significantly predicted ASD (but not ADHD) traits at 24 months across the entire sample. Elevated tactile sensory seeking at 10 months moderated the relationship between early reduced neural repetition suppression and later ASD traits. Conclusions Reduced tactile neural repetition suppression is an early marker of later ASD traits in infants at elevated likelihood of ASD or ADHD, suggesting that a common pathway to later ASD traits exists despite different familial backgrounds. Elevated tactile sensory seeking may act as a protective factor, mitigating the relationship between early tactile neural repetition suppression and later ASD traits.
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Affiliation(s)
- Elena Serena Piccardi
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK.
| | - Jannath Begum Ali
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | - Emily J H Jones
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | - Luke Mason
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK
| | - Tony Charman
- Institute of Psychiatry, Psychology & Neuroscience, Psychology Department, King's College London, London, UK
| | - Mark H Johnson
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK.,Department of Psychology, Cambridge University, Cambridge, UK
| | - Teodora Gliga
- Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK.,Department of Psychology, University of East Anglia, Norwich, UK
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36
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Kaliukhovich DA, Manyakov NV, Bangerter A, Ness S, Skalkin A, Goodwin MS, Dawson G, Hendren RL, Leventhal B, Hudac CM, Bradshaw J, Shic F, Pandina G. Social attention to activities in children and adults with autism spectrum disorder: effects of context and age. Mol Autism 2020; 11:79. [PMID: 33076994 PMCID: PMC7574440 DOI: 10.1186/s13229-020-00388-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 10/01/2020] [Indexed: 11/10/2022] Open
Abstract
Background Diminished visual monitoring of faces and activities of others is an early feature of autism spectrum disorder (ASD). It is uncertain whether deficits in activity monitoring, identified using a homogeneous set of stimuli, persist throughout the lifespan in ASD, and thus, whether they could serve as a biological indicator (“biomarker”) of ASD. We investigated differences in visual attention during activity monitoring in children and adult participants with autism compared to a control group of participants without autism. Methods Eye movements of participants with autism (n = 122; mean age [SD] = 14.5 [8.0] years) and typically developing (TD) controls (n = 40, age = 16.4 [13.3] years) were recorded while they viewed a series of videos depicting two female actors conversing while interacting with their hands over a shared task. Actors either continuously focused their gaze on each other’s face (mutual gaze) or on the shared activity area (shared focus). Mean percentage looking time was computed for the activity area, actors’ heads, and their bodies. Results Compared to TD participants, participants with ASD looked longer at the activity area (mean % looking time: 58.5% vs. 53.8%, p < 0.005) but less at the heads (15.2% vs. 23.7%, p < 0.0001). Additionally, within-group differences in looking time were observed between the mutual gaze and shared focus conditions in both participants without ASD (activity: Δ = − 6.4%, p < 0.004; heads: Δ = + 3.5%, p < 0.02) and participants with ASD (bodies: Δ = + 1.6%, p < 0.002). Limitations The TD participants were not as well characterized as the participants with ASD. Inclusion criteria regarding the cognitive ability [intelligence quotient (IQ) > 60] limited the ability to include individuals with substantial intellectual disability. Conclusions Differences in attention to faces could constitute a feature discriminative between individuals with and without ASD across the lifespan, whereas between-group differences in looking at activities may shift with development. These findings may have applications in the search for underlying biological indicators specific to ASD. Trial registration ClinicalTrials.gov identifier NCT02668991.
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Affiliation(s)
| | | | - Abigail Bangerter
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Seth Ness
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
| | - Andrew Skalkin
- Datagrok, INC, 1800 JFK Blvd Suite 300 PMB 90078, Philadelphia, PA, 19103, USA
| | - Matthew S Goodwin
- 312E Robinson Hall, Department of Health Sciences, Bouvé College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA
| | - Geraldine Dawson
- Duke Center for Autism and Brain Development and Duke Institute for Brain Sciences, Duke University School of Medicine, 2608 Erwin Road, Suite 30, Durham, NC, 27705, USA
| | - Robert L Hendren
- Benioff Children's Hospital, University of California, San Francisco, 401 Parnassus Avenue, Langley Porter, San Francisco, CA, 94143-0984, USA
| | - Bennett Leventhal
- Benioff Children's Hospital, University of California, San Francisco, 401 Parnassus Avenue, Langley Porter, San Francisco, CA, 94143-0984, USA
| | - Caitlin M Hudac
- Center for Youth Development and Intervention, University of Alabama, Box 870348, Tuscaloosa, AL, 35487-0348, USA
| | - Jessica Bradshaw
- Department of Psychology, University of South Carolina, 1512 Pendleton Street, Columbia, SC, 29201, USA
| | - Frederick Shic
- Department of Pediatrics, Seattle Children's Research Institute, Center for Child Health, Behavior and Development, University of Washington, 6200 NE 74th Street, Ste 110, Seattle, WA, 98115-8160, USA
| | - Gahan Pandina
- Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USA
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37
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Look duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD. Dev Psychopathol 2020; 32:1303-1322. [DOI: 10.1017/s0954579420000930] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AbstractIdentifying 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.
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38
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Is Earlier Better? The Relationship between Age When Starting Early Intervention and Outcomes for Children with Autism Spectrum Disorder: A Selective Review. AUTISM RESEARCH AND TREATMENT 2020; 2020:7605876. [PMID: 32832154 PMCID: PMC7421097 DOI: 10.1155/2020/7605876] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 06/26/2020] [Indexed: 11/17/2022]
Abstract
Although the conventional wisdom is that “earlier is better” when it comes to intervention for children with ASD, it is not clear what evidence exists to support this notion. This review examined a group of studies that addressed outcomes for young children with ASD who started early intervention at a range of ages. The review was selective by including only papers that examined the age of initiation of treatment as well as baseline cognitive, language, or adaptive level and, in addition, employed a method to control for the covariance between early ability level and age of beginning intervention. Fourteen studies were identified and then compared on methods and outcomes. The support for “earlier is better” was mixed, but it was clear that complex relationships among predictor variables need to be explored in order to understand the role of age of starting early intervention for later outcomes.
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39
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Gui A, Jones EJH, Wong CCY, Meaburn E, Xia B, Pasco G, Lloyd-Fox S, Charman T, Bolton P, Johnson MH. Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism. Infant Behav Dev 2020; 60:101409. [PMID: 32623100 DOI: 10.1016/j.infbeh.2019.101409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 12/05/2019] [Accepted: 12/06/2019] [Indexed: 12/15/2022]
Abstract
Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD. Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography. Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results. In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.
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Affiliation(s)
- Anna Gui
- Department of Psychological Sciences, Birkbeck College, University of London, UK.
| | - Emily J H Jones
- Department of Psychological Sciences, Birkbeck College, University of London, UK
| | - Chloe C Y Wong
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
| | - Emma Meaburn
- Department of Psychological Sciences, Birkbeck College, University of London, UK
| | - Baocong Xia
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
| | - Greg Pasco
- Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
| | | | - Tony Charman
- Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
| | - Patrick Bolton
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK
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40
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Vettori S, Dzhelyova M, Van der Donck S, Jacques C, Steyaert J, Rossion B, Boets B. Frequency-Tagging Electroencephalography of Superimposed Social and Non-Social Visual Stimulation Streams Reveals Reduced Saliency of Faces in Autism Spectrum Disorder. Front Psychiatry 2020; 11:332. [PMID: 32411029 PMCID: PMC7199527 DOI: 10.3389/fpsyt.2020.00332] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 04/02/2020] [Indexed: 12/30/2022] Open
Abstract
Individuals with autism spectrum disorder (ASD) have difficulties with social communication and interaction. The social motivation hypothesis states that a reduced interest in social stimuli may partly underlie these difficulties. Thus far, however, it has been challenging to quantify individual differences in social orientation and interest, and to pinpoint the neural underpinnings of it. In this study, we tested the neural sensitivity for social versus non-social information in 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ, while children were engaged in an orthogonal task. We recorded electroencephalography (EEG) during fast periodic visual stimulation (FPVS) of social versus non-social stimuli to obtain an objective implicit neural measure of relative social bias. Streams of variable images of faces and houses were superimposed, and each stream of stimuli was tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). This frequency-tagging method allows disentangling the respective neural responses evoked by the different streams of stimuli. Moreover, by using superimposed stimuli, we controlled for possible effects of preferential looking, spatial attention, and disengagement. Based on four trials of 60 s, we observed a significant three-way interaction. In the control group, the frequency-tagged neural responses to faces were larger than those to houses, especially in lateral occipito-temporal channels, while the responses to houses were larger over medial occipital channels. In the ASD group, however, faces and houses did not elicit significantly different neural responses in any of the regions. Given the short recording time of the frequency-tagging paradigm with multiple simultaneous inputs and the robustness of the individual responses, the method could be used as a sensitive marker of social preference in a wide range of populations, including younger and challenging populations.
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Affiliation(s)
- Sofie Vettori
- Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium
| | - Milena Dzhelyova
- Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium
- Institute of Research in Psychological Science, Institute of Neuroscience, University of Louvain, Louvain-La-Neuve, Belgium
| | - Stephanie Van der Donck
- Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium
| | - Corentin Jacques
- Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Institute of Research in Psychological Science, Institute of Neuroscience, University of Louvain, Louvain-La-Neuve, Belgium
| | - Jean Steyaert
- Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium
| | - Bruno Rossion
- Institute of Research in Psychological Science, Institute of Neuroscience, University of Louvain, Louvain-La-Neuve, Belgium
- Université de Lorraine, CNRS, CRAN-UMR 7039, Nancy, France
- Université de Lorraine, CHRU-Service de Neurologie, Nancy, France
| | - Bart Boets
- Center for Developmental Psychiatry, Department of Neurosciences, KU Leuven, Leuven, Belgium
- Leuven Autism Research (LAuRes), KU Leuven, Leuven, Belgium
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Ruel A, Chiarella SS, Crivello C, Poulin-Dubois D. Concurrent Validity of the Modified Checklist for Autism in Toddlers (M-CHAT): Socio-cognitive and Verbal Skills in 18-Month-Old Infants. J Autism Dev Disord 2020; 51:933-949. [DOI: 10.1007/s10803-020-04379-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Balasco L, Provenzano G, Bozzi Y. Sensory Abnormalities in Autism Spectrum Disorders: A Focus on the Tactile Domain, From Genetic Mouse Models to the Clinic. Front Psychiatry 2020; 10:1016. [PMID: 32047448 PMCID: PMC6997554 DOI: 10.3389/fpsyt.2019.01016] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 12/20/2019] [Indexed: 12/20/2022] Open
Abstract
Sensory abnormalities are commonly recognized as diagnostic criteria in autism spectrum disorder (ASD), as reported in the last edition of the Diagnostic and Statistical Manual of Mental Disorder (DSM-V). About 90% of ASD individuals have atypical sensory experiences, described as both hyper- and hypo-reactivity, with abnormal responses to tactile stimulation representing a very frequent finding. In this review, we will address the neurobiological bases of sensory processing in ASD, with a specific focus of tactile sensitivity. In the first part, we will review the most relevant sensory abnormalities detected in ASD, and then focus on tactile processing deficits through the discussion of recent clinical and experimental studies. In the search for the neurobiological bases of ASD, several mouse models have been generated with knockout and humanized knockin mutations in many ASD-associated genes. Here, we will therefore give a brief overview of the anatomical structure of the mouse somatosensory system, and describe the somatosensory abnormalities so far reported in different mouse models of ASD. Understanding the neurobiological bases of sensory processing in ASD mouse models may represent an opportunity for a better comprehension of the mechanisms underlying sensory abnormalities, and for the development of novel effective therapeutic strategies.
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Affiliation(s)
- Luigi Balasco
- Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy
| | - Giovanni Provenzano
- Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy
| | - Yuri Bozzi
- Center for Mind/Brain Sciences (CIMeC), University of Trento, Rovereto, Italy
- CNR Neuroscience Institute, Pisa, Italy
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Riccio A, Kapp SK, Daou N, Shane J, Gillespie-Lynch K. What are Replicable Aspects of the Broader Autism Phenotype among College Students? COLLABRA: PSYCHOLOGY 2020. [DOI: 10.1525/collabra.271] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Are people with heightened autistic traits less likely to help other people? Recent research suggests that heightened autistic traits are associated with reduced self-reported prosocial behavior among college students. However, the growing literature examining sub-clinical traits associated with autism, or the Broader Autism Phenotype (BAP), among college students has invested insufficient attention in replication of findings, potential interrelationships between constructs, or the degree to which social desirability bias may contribute to findings. To identify replicable aspects of the BAP, we administered a battery of measures to 391 undergraduate students. Replicating prior work, findings suggested that self-reported difficulties understanding the self and others (but not less feeling for others) and sensory atypicalities are core aspects of the BAP. Reduced social desirability bias was also associated with the BAP. Prior associations between reduced prosocial tendencies and the BAP were not replicated. Findings highlight the importance of assessing multiple potential aspects of the BAP, particularly reduced susceptibility to the social desirability bias, when using self-report measures.
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Affiliation(s)
- Ariana Riccio
- Department of Psychology, The Graduate Center, CUNY, New York, NY, US
| | - Steven K. Kapp
- Egenis, University of Exeter, Exeter, Devon, UK
- Department of Psychology, University of Portsmouth, Portsmouth, Hampshire, UK
| | - Nidal Daou
- Department of Psychology, American University of Beirut, Beirut, LB
- Department of Psychology, McNeese State University, Lake Charles, LA, US
| | - Jacob Shane
- Department of Psychology, The Graduate Center, CUNY, New York, NY, US
- Department of Psychology, Brooklyn College, CUNY, Brooklyn, NY, US
| | - Kristen Gillespie-Lynch
- Department of Psychology, The Graduate Center, CUNY, New York, NY, US
- Department of Psychology, College of Staten Island, CUNY, Staten Island, NY, US
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44
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Pinato L, Galina Spilla CS, Markus RP, da Silveira Cruz-Machado S. Dysregulation of Circadian Rhythms in Autism Spectrum Disorders. Curr Pharm Des 2020; 25:4379-4393. [DOI: 10.2174/1381612825666191102170450] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 10/31/2019] [Indexed: 12/12/2022]
Abstract
Background:
The alterations in neurological and neuroendocrine functions observed in the autism
spectrum disorder (ASD) involves environmentally dependent dysregulation of neurodevelopment, in interaction
with multiple coding gene defects. Disturbed sleep-wake patterns, as well as abnormal melatonin and glucocorticoid
secretion, show the relevance of an underlying impairment of the circadian timing system to the behavioral
phenotype of ASD. Thus, understanding the mechanisms involved in the circadian dysregulation in ASD could
help to identify early biomarkers to improve the diagnosis and therapeutics as well as providing a significant
impact on the lifelong prognosis.
Objective:
In this review, we discuss the organization of the circadian timing system and explore the connection
between neuroanatomic, molecular, and neuroendocrine responses of ASD and its clinical manifestations. Here
we propose interconnections between circadian dysregulation, inflammatory baseline and behavioral changes in
ASD. Taking into account, the high relevancy of melatonin in orchestrating both circadian timing and the maintenance
of physiological immune quiescence, we raise the hypothesis that melatonin or analogs should be considered
as a pharmacological approach to suppress inflammation and circadian misalignment in ASD patients.
Strategy:
This review provides a comprehensive update on the state-of-art of studies related to inflammatory
states and ASD with a special focus on the relationship with melatonin and clock genes. The hypothesis raised
above was analyzed according to the published data.
Conclusion:
Current evidence supports the existence of associations between ASD to circadian dysregulation,
behavior problems, increased inflammatory levels of cytokines, sleep disorders, as well as reduced circadian
neuroendocrine responses. Indeed, major effects may be related to a low melatonin rhythm. We propose that
maintaining the proper rhythm of the circadian timing system may be helpful to improve the health and to cope
with several behavioral changes observed in ASD subjects.
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Affiliation(s)
- Luciana Pinato
- Department of Speech, Language and Hearing Sciences, São Paulo State University (UNESP), 17525-900, Marilia, SP, Brazil
| | - Caio Sergio Galina Spilla
- Department of Speech, Language and Hearing Sciences, São Paulo State University (UNESP), 17525-900, Marilia, SP, Brazil
| | - Regina Pekelmann Markus
- Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil
| | - Sanseray da Silveira Cruz-Machado
- Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo (USP), 05508-090, São Paulo, SP, Brazil
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Kojovic N, Ben Hadid L, Franchini M, Schaer M. Sensory Processing Issues and Their Association with Social Difficulties in Children with Autism Spectrum Disorders. J Clin Med 2019; 8:E1508. [PMID: 31547076 PMCID: PMC6833094 DOI: 10.3390/jcm8101508] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Revised: 09/11/2019] [Accepted: 09/18/2019] [Indexed: 01/08/2023] Open
Abstract
Sensory processing issues have been frequently reported in individuals with Autism Spectrum Disorders (ASD), but their relationship with social and overall adaptive functioning has not been extensively characterized to date. Here, we investigate how sensory processing atypicalities relate with deficits in social skills, impaired social cognition, and general adaptive functioning in a group of preschoolers with ASD. Sixty-four children with ASD aged 3 to 6 were included in this study, along with 36 age-matched typically-developing (TD) peers. Parent-reported measures of sensory processing, social difficulties and overall adaptive functioning were collected for all children. We also obtained precise measures of social attention deployment using a custom-design eye-tracking task depicting naturalistic social scenes. Within the group of children with ASD, higher intensities of sensory issues were associated with more prominent social difficulties and lower adaptive functioning. We also found that children with ASD who had more sensory issues showed visual exploration patterns of social scenes that strongly deviated from the one seen in the TD group. The association of sensory processing atypicalities with "higher-order" functional domains such as social and adaptive functioning in children with ASD stresses the importance of further research on sensory symptoms in autism.
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Affiliation(s)
- Nada Kojovic
- University of Geneva, 1211 Geneva, Switzerland (M.S.)
| | | | | | - Marie Schaer
- University of Geneva, 1211 Geneva, Switzerland (M.S.)
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Zhang D, Krieber-Tomantschger I, Poustka L, Roeyers H, Sigafoos J, Bölte S, Marschik PB, Einspieler C. Identifying Atypical Development: A Role of Day-Care Workers? J Autism Dev Disord 2019; 49:3685-3694. [PMID: 31144232 PMCID: PMC6667412 DOI: 10.1007/s10803-019-04056-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Identifying the early signs of developmental disability is important for ensuring timely diagnosis and early intervention. Day-care workers may be in a prime position to notice potential developmental deviations, but it is unclear if they can accurately recognize subtle early signs of atypical development. Sixty day-care workers examined home-videos of very young children with fragile X syndrome and typically developing children. Results indicated that most day-care workers can distinguish typical and atypical development in general and might therefore have an important role in early identification. Special work experience and advanced pedagogical training appeared to boost day-care workers' sensitivity to detect atypical features in early development and to provide effective daily surveillance.
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Affiliation(s)
- Dajie Zhang
- Department of Child and Adolescent Psychiatry, iDN, interdisciplinary Developmental Neuroscience, University Medical Center Goettingen, 37075, Goettingen, Germany
- Division of Phoniatrics, iDN, interdisciplinary Developmental Neuroscience, Medical University of Graz, Graz, Austria
| | - Iris Krieber-Tomantschger
- Division of Phoniatrics, iDN, interdisciplinary Developmental Neuroscience, Medical University of Graz, Graz, Austria
| | - Luise Poustka
- Department of Child and Adolescent Psychiatry, iDN, interdisciplinary Developmental Neuroscience, University Medical Center Goettingen, 37075, Goettingen, Germany
| | - Herbert Roeyers
- Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium
| | - Jeff Sigafoos
- School of Education, Victoria University of Wellington, Wellington, New Zealand
| | - Sven Bölte
- Center of Neurodevelopmental Disorders (KIND), Center for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
- Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia
| | - Peter B Marschik
- Department of Child and Adolescent Psychiatry, iDN, interdisciplinary Developmental Neuroscience, University Medical Center Goettingen, 37075, Goettingen, Germany.
- Division of Phoniatrics, iDN, interdisciplinary Developmental Neuroscience, Medical University of Graz, Graz, Austria.
- Center of Neurodevelopmental Disorders (KIND), Center for Psychiatry Research; Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
| | - Christa Einspieler
- Division of Phoniatrics, iDN, interdisciplinary Developmental Neuroscience, Medical University of Graz, Graz, Austria
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Expanding the critique of the social motivation theory of autism with participatory and developmental research. Behav Brain Sci 2019. [DOI: 10.1017/s0140525x18002479] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
AbstractWe argue that understanding of autism can be strengthened by increasing involvement of autistic individuals as researchers and by exploring cascading impacts of early sensory, perceptual, attentional, and motor atypicalities on social and communicative developmental trajectories. Participatory action research that includes diverse participants or researchers may help combat stigma while expanding research foci to better address autistic people's needs.
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48
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Bedford R, Gliga T, Hendry A, Jones EJH, Pasco G, Charman T, Johnson MH, Pickles A. Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits. J Neurodev Disord 2019; 11:14. [PMID: 31351456 PMCID: PMC6660706 DOI: 10.1186/s11689-019-9274-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 07/08/2019] [Indexed: 11/10/2022] Open
Abstract
Background Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. Methods Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). Results Infant RF was negatively associated with later traits of ASD (B = − 0.5, p = 0.01) and ADHD inattention (B = − 0.24, p = 0.02) but not hyperactivity (B = − 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. Conclusions Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. Electronic supplementary material The online version of this article (10.1186/s11689-019-9274-0) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Rachael Bedford
- Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
| | - Teodora Gliga
- Centre for Brain and Cognitive Development, Birkbeck College, University of London, London, UK
| | - Alexandra Hendry
- Experimental Psychology Department, Oxford University, Oxford, UK
| | - Emily J H Jones
- Centre for Brain and Cognitive Development, Birkbeck College, University of London, London, UK
| | - Greg Pasco
- Psychology Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Tony Charman
- Psychology Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Mark H Johnson
- Centre for Brain and Cognitive Development, Birkbeck College, University of London, London, UK.,Psychology Department, Cambridge University, Cambridge, UK
| | - Andrew Pickles
- Biostatistics and Health Informatics Department, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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Wong CCY, Smith RG, Hannon E, Ramaswami G, Parikshak NN, Assary E, Troakes C, Poschmann J, Schalkwyk LC, Sun W, Prabhakar S, Geschwind DH, Mill J. Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic autism in post-mortem human brain tissue. Hum Mol Genet 2019; 28:2201-2211. [PMID: 31220268 PMCID: PMC6602383 DOI: 10.1093/hmg/ddz052] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 03/04/2019] [Accepted: 03/04/2019] [Indexed: 12/13/2022] Open
Abstract
Autism spectrum disorder (ASD) encompasses a collection of complex neuropsychiatric disorders characterized by deficits in social functioning, communication and repetitive behaviour. Building on recent studies supporting a role for developmentally moderated regulatory genomic variation in the molecular aetiology of ASD, we quantified genome-wide patterns of DNA methylation in 223 post-mortem tissues samples isolated from three brain regions [prefrontal cortex, temporal cortex and cerebellum (CB)] dissected from 43 ASD patients and 38 non-psychiatric control donors. We identified widespread differences in DNA methylation associated with idiopathic ASD (iASD), with consistent signals in both cortical regions that were distinct to those observed in the CB. Individuals carrying a duplication on chromosome 15q (dup15q), representing a genetically defined subtype of ASD, were characterized by striking differences in DNA methylationacross a discrete domain spanning an imprinted gene cluster within the duplicated region. In addition to the dramatic cis-effects on DNA methylation observed in dup15q carriers, we identified convergent methylomic signatures associated with both iASD and dup15q, reflecting the findings from previous studies of gene expression and H3K27ac. Cortical co-methylation network analysis identified a number of co-methylated modules significantly associated with ASD that are enriched for genomic regions annotated to genes involved in the immune system, synaptic signalling and neuronal regulation. Our study represents the first systematic analysis of DNA methylation associated with ASD across multiple brain regions, providing novel evidence for convergent molecular signatures associated with both idiopathic and syndromic autism.
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Affiliation(s)
- Chloe C Y Wong
- King’s College London, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK
| | - Rebecca G Smith
- University of Exeter Medical School, University of Exeter, Exeter, UK
| | - Eilis Hannon
- University of Exeter Medical School, University of Exeter, Exeter, UK
| | - Gokul Ramaswami
- Center for Autism Research and Treatment, and Program in Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Neelroop N Parikshak
- Center for Autism Research and Treatment, and Program in Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Elham Assary
- Department of Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, London, UK
| | - Claire Troakes
- King’s College London, Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London, UK
| | - Jeremie Poschmann
- Centre de Recherche en Transplantation et Immunologie, Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Inserm, Université de Nantes, Nantes, France
| | | | - Wenjie Sun
- Computational and Systems Biology, Genome Institute of Singapore, Singapore
| | - Shyam Prabhakar
- Computational and Systems Biology, Genome Institute of Singapore, Singapore
| | - Daniel H Geschwind
- Center for Autism Research and Treatment, and Program in Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, USA
- Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Jonathan Mill
- University of Exeter Medical School, University of Exeter, Exeter, UK
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Bussu G, Jones EJH, Charman T, Johnson MH, Buitelaar JK. Prediction of Autism at 3 Years from Behavioural and Developmental Measures in High-Risk Infants: A Longitudinal Cross-Domain Classifier Analysis. J Autism Dev Disord 2019; 48:2418-2433. [PMID: 29453709 PMCID: PMC5996007 DOI: 10.1007/s10803-018-3509-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months.
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Affiliation(s)
- G Bussu
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Kapittelweg 29, 6525 EN, Nijmegen, The Netherlands.
| | - E J H Jones
- Centre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL, UK
| | - T Charman
- Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK
| | - M H Johnson
- Centre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7JL, UK
| | - J K Buitelaar
- Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Kapittelweg 29, 6525 EN, Nijmegen, The Netherlands
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