Article Summaries

The Autism Biomarkers Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG Biomarkers
Webb SJ, Naples AJ, Levin AR, Hellemann G, Borland H, Benton J, Carlos C, McAllister T, Santhosh M, Seow H, Atyabi A, Bernier R, Chawarska K, Dawson G, Dziura J, Faja S, Jeste S, Murias M, Nelson CA, Sabatos-DeVito M, Senturk D, Shic F, Sugar CA, McPartland JC. Am J Psychiatry. 2023 Jan 1; 2022 Aug 24. PMID: 36000217.

Autistic individuals often struggle with social and communication skills based on their own descriptions and those of caregivers and clinicians. However, these observations can be subjective and do not provide an objective measure of brain function, or a biomarker, corresponding to autism. This study measured brain activity at the scalp in autistic and neurotypical children across two time points when viewing faces and other common objects (e.g., house, cars). Autistic children showed slower brain activity when viewing faces in comparison to neurotypical children. This finding was consistent over six weeks. These results suggest that the electrical activity produced in response to faces can be reliably measured in autistic children and may hold promise to improve clinical research, such as predicting who may benefit from specific interventions.

Neural correlates of eye contact and social function in autism spectrum disorder
Hirsch J, Zhang X, Noah JA, Dravida S, Naples A, Tiede M, Wolf JM, McPartland JC. PLoS One. 2022; 2022 Nov 9. PMID: 36350848.

Autistic individuals can have trouble making eye contact with others, which may be the result of differences in brain function. In this study, autistic and non-autistic participants made eye contact with real people and “virtual” faces on a computer screen. We measured brain activity and eye movements during these tasks. When making eye contact with a real person, autistic people showed different patterns of brain activity than non-autistic people. We also found that autistic people looked less to faces making eye contact and their pupils changed more than non-autistic people. These differences were associated with social behavior in autistic people. These results help us understand the brain basis for the differences in eye contact observed in many autistic people.

Predictability modulates neural response to eye contact in ASD
Naples AJ, Foss-Feig JH, Wolf JM, Srihari VH, McPartland JC. Mol Autism. 2022 Oct 29; 2022 Oct 29. PMID: 36309762.

Making eye contact is a common difficulty for autistic individuals. This study explores how the brain responds to eye contact in autistic and neurotypical adults. We measured participants eye movements to know when they were making eye contact with faces presented on a computer screen. We also measured brain activity while participants viewed these faces. We found that brain activity was different when the faces looked back at the participant compared to when they did not necessarily look back at the participants and that the predictability of the onscreen face’s behavior made a significant difference in how autistic people responded. These results suggest that considering patterns of eye contact, such as predictable versus unpredictable, may be very important when considering what influences eye contact in autistic people.

Identifying Age Based Maturation in the ERP Response to Faces in Children With Autism: Implications for Developing Biomarkers for Use in Clinical Trials
Webb SJ, Emerman I, Sugar C, Senturk D, Naples AJ, Faja S, Benton J, Borland H, Carlos C, Levin AR, McAllister T, Santhosh M, Bernier RA, Chawarska K, Dawson G, Dziura J, Jeste S, Kleinhans N, Murias M, Sabatos-DeVito M, Shic F, McPartland JC. Front Psychiatry. 2022; 2022 May 9. PMID: 35615454.

The human brain is highly responsive to faces. This response tends to get stronger as we age and spend more time looking at faces. However, we know less about the maturation of this brain response to faces in autistic individuals. In this study, autistic and non-autistic children viewed faces on the computer screen while we measured their brain response. Compared to children without autism, we found that the brain response to faces was slower in autistic children. Specifically, autistic children were more likely to show slower response to faces than would be expected for a non-autistic child of the same age. Having a slower brain response to faces was related to having a lower IQ score and poorer face memory.

The Autism Biomarkers Consortium for Clinical Trials: evaluation of a battery of candidate eye-tracking biomarkers for use in autism clinical trials
Shic F, Naples AJ, Barney EC, Chang SA, Li B, McAllister T, Kim M, Dommer KJ, Hasselmo S, Atyabi A, Wang Q, Helleman G, Levin AR, Seow H, Bernier R, Charwaska K, Dawson G, Dziura J, Faja S, Jeste SS, Johnson SP, Murias M, Nelson CA, Sabatos-DeVito M, Senturk D, Sugar CA, Webb SJ, McPartland JC. Mol Autism. 2022 Mar 21; 2022 Mar 21. PMID: 35313957.

Measuring where people look may help us understand how people process information in their environment. Many people with autism look less at social information, including other people’s faces and eyes. Many researchers think that looking less at faces might lead to some of the social differences seen in autistic people. To test this question, we studied 399 children with and without autism who viewed social scenes and short videos of social interactions. Children who looked at faces more had better memory for faces, better communication skills, and fewer autism-related challenges. This study shows that eye tracking is a useful measure to understand social differences in autistic people.

Higher Depressive Symptoms Predict Lower Social Adaptive Functioning in Children and Adolescents with ASD
Duan S, Lee M, Wolf J, Naples AJ, McPartland JC. J Clin Child Adolesc Psychol. 2022 Mar-Apr; 2020 Apr 29. PMID: 32347746.

Adaptive skills describe how a person talks with others (communication skills), takes care of themselves (daily living skills), and works, lives, and plays with others (socialization skills) in everyday situations. Many autistic people develop their adaptive skills more slowly than non-autistic people. It is important for clinicians to understand what might affect the development of an autistic person’s adaptive skills so they can help that person strengthen those skills, which can help them make friends and live on their own later in life. Other researchers have found that non-autistic people with depression experience difficulties at school and in their relationships with their family and friends, which can make it harder for them to socialize and therefore make their symptoms of depression worse. In this study we wanted to know if symptoms of depression would also affect the adaptive skills of autistic individuals. To answer this question, we studied the relationship between adaptive skills and depression symptoms in autistic and non-autistic children and adolescents. We learned that autistic and non-autistic children and adolescents who had more symptoms of depression also had lower socialization skills. On the other hand, there were no relationships between children’s symptoms of depression and their communication and daily living skills. This might mean that depression makes it harder for autistic children to socialize with others, or it might mean that autistic children who have more difficulty socializing with others are more likely to develop depression. When clinicians are treating depression in autistic people, it may be important to include interventions that help autistic people develop their social skills because this might also lessen their symptoms of depression.

Concomitant medication use in children with autism spectrum disorder: Data from the Autism Biomarkers Consortium for Clinical Trials
Shurtz L, Schwartz C, DiStefano C, McPartland JC, Levin AR, Dawson G, Kleinhans NM, Faja S, Webb SJ, Shic F, Naples AJ, Seow H, Bernier RA, Chawarska K, Sugar CA, Dziura J, Senturk D, Santhosh M, Jeste SS. Autism. 2022 Sep 9; 2022 Sep 9. PMID: 36086805.

Autistic children are often prescribed medications to help with their behavior and mood; these are called psychotropic medications. Children taking psychotropic medications are often excluded from research studies because the effects of the medication might impact the results of the study. However, since many autistic children take these kinds of medication, this may mean that the children allowed to participate in these research studies may not represent most autistic children. We asked 280 parents of school aged autistic children what kinds of medications they were prescribed. We found that, of the 280 children in the study, 42.5% were taking at least one psychotropic medication and 21% were taking more than one psychotropic medication. The most common psychotropic medications were melatonin, stimulants, selective serotonin reuptake inhibitors (SSRIs), alpha agonists, and antipsychotics. Our findings suggest that excluding children who are taking psychotropic medications from participating in research studies could limit how much these studies can tell us about autistic children by restricting information to a small subgroup of autistic children that may not represent autistic children overall.

Distinct Symptom Network Structure and Shared Central Social Communication Symptomatology in Autism and Schizophrenia: A Bayesian Network Analysis
Han GT, Trevisan DA, Foss-Feig J, Srihari V, McPartland JC. J Autism Dev Disord. 2022 Jun 25; 2022 Jun 25. PMID: 35752729.

Autism and schizophrenia are mental health conditions that have some symptoms in common. The tools clinicians use to understand a person’s symptoms do not always do a good job of separating autism symptoms and schizophrenia symptoms. This can make it difficult to determine who has which condition and how to help. We used a new method, “network analysis,” to compare symptoms between autistic people and people with schizophrenia. A network analysis looks at the symptoms that people are experiencing and how these symptoms relate to each other. We found that social difficulties were important and common in both autism and schizophrenia. Restricted interests were an important symptom only for autism. Thinking challenges and eccentric behavior were important symptoms only for schizophrenia. Looking at how symptoms relate to one other can help clinicians better understand how conditions affect people in different ways. This is important so that clinicians can accurately diagnose their patients and provide them with the best support as soon as possible.

Patterns of Intervention Utilization Among School-Aged Children with Autism Spectrum Disorder: Findings from a Multi-Site Research Consortium
Sridhar A, Kuhn J, Faja S, Sabatos-DeVito M, Nikolaeva JI, Dawson G, Nelson CA, Webb SJ, Bernier R, Jeste S, Chawarska K, Sugar CA, Shic F, Naples A, Dziura J, McPartland JC. Res Autism Spectr Disord. 2022 Jun; 2022 Mar 24. PMID: 35444715.

Autistic youth often receive many types of supports and services, sometimes called interventions. These interventions are meant to help autistic youth improve their well-being, such as lowering their anxiety or increasing their social skills. It is important to understand what interventions autistic youth are receiving and whether youth receive different interventions based on child and family factors (location, income, etc.). We asked 280 parents of school-age autistic children about the types of interventions their autistic children received over the past six weeks. We learned that autistic children received an extremely wide variety of different interventions. Some interventions that children received were based on scientific evidence, called “evidence-based practice”, while other interventions youth received were not evidence-based. We also learned that autistic children received a wide range of hours of intervention per week, ranging from no time to almost 80 hours in a week. Children that had more symptoms of autism, were non-Hispanic, and lived in certain states were more likely to get more hours of evidence-based interventions. Children with more symptoms of autism, lower IQ, and who were younger were more likely to have multiple types of interventions. It is important for clinicians to know that family factors like location and ethnicity might be related to which services autistic children receive so that they can provide needed evidence-based interventions to youth that may not have enough access.

First-Hand Accounts of Interoceptive Difficulties in Autistic Adults
Trevisan DA, Parker T, McPartland JC. J Autism Dev Disord. 2021 Oct; 2021 Jan 3. PMID: 33389300.

Autistic individuals often express difficulty recognizing and responding to their own bodily sensations. In this study, we reviewed online posts from self-identifying autistic individuals. Many people wrote about not being aware of hunger, thirst, and fullness. In some individuals, this was related to trouble recognizing when to eat or when to stop eating. Another difficulty that people reported was noticing pain or sickness and determining when to be concerned about these feelings. In sum, our findings showed that difficulty interpreting internal feelings is common among autistic individuals. Our work demonstrates the need to create new ways to measure this difficulty.

Resting state EEG in youth with ASD: age, sex, and relation to phenotype
Neuhaus E, Lowry SJ, Santhosh M, Kresse A, Edwards LA, Keller J, Libsack EJ, Kang VY, Naples A, Jack A, Jeste S, McPartland JC, Aylward E, Bernier R, Bookheimer S, Dapretto M, Van Horn JD, Pelphrey K, Webb SJ. J Neurodev Disord. 2021 Sep 13; 2021 Sep 13. PMID: 34517813.

Experiences and behavior differ across autistic children. Brain activity may also differ across autistic children. This study measured brain activity in children with and without autism. Brain waves were recorded as children watched screensaver videos. We studied five types of brain activity with different frequencies. Frequency is the number of brain waves that happen in one second. Girls and older children had less activity for certain frequencies. Autistic children had less low-frequency activity than non-autistic children. In other words, autistic children may have more brain activity during rest. Autistic boys with less activity at certain frequencies had stronger social skills and higher IQ. They also showed fewer repetitive behaviors. These patterns were not seen in autistic girls. Studying brain activity while children relax may help us learn about biological differences in autistic children. They also emphasize the importance of considering sex differences when studying biological differences in autism.

The gap between IQ and adaptive functioning in autism spectrum disorder: Disentangling diagnostic and sex differences
McQuaid GA, Pelphrey KA, Bookheimer SY, Dapretto M, Webb SJ, Bernier RA, McPartland JC, Van Horn JD, Wallace GL. Autism. 2021 Aug; 2021 Mar 15. PMID: 33715473.

Adaptive functioning refers to the ability to be self-sufficient in daily life. It is important to quality of life and influences how people live, communicate, and socialize. Caregivers of autistic children often report difficulties with adaptive functioning. There also tends to be a gap between IQ and adaptive functioning for autistic people in that adaptive functioning may be lower than expected for their IQ. This gap increases with age. Most of these studies have been done with autistic boys. This study looked at whether this gap between adaptive functioning and IQ exists for autistic females. The study showed that the previously observed pattern of lower adaptive skills relative to overall intelligence was similar in males and females. These results emphasize the importance of supporting autistic people in development of daily living skills to maximize self-sufficiency.

The N170 event-related potential reflects delayed neural response to faces when visual attention is directed to the eyes in youths with ASD
Parker TC, Crowley MJ, Naples AJ, Rolison MJ, Wu J, Trapani JA, McPartland JC. Autism Res. 2021 Jul; 2021 Mar 22. PMID: 33749161.

This study looked at how children's and adolescents' brains respond when looking at different parts of a face. Typically developing children and adolescents processed eyes faster than other parts of the face, whereas this pattern was not seen in ASD. Children and adolescents with ASD processed eyes more slowly than typically developing children. These findings suggest that observed inefficiencies in face processing in ASD are not simply reflective of failure to attend to the eyes.

Brief Report: Preliminary Evidence of the N170 as a Biomarker of Response to Treatment in Autism Spectrum Disorder
Kala S, Rolison MJ, Trevisan DA, Naples AJ, Pelphrey K, Ventola P, McPartland JC. Front Psychiatry. 2021; 2021 Jun 29. PMID: 34267691.

Individuals with Autism Spectrum Disorder (ASD) often experience difficulties with social communication, such as identifying and understanding faces. Currently, most autism research relies on descriptions provided by clinicians, parents, or caregivers. While important, such observer ratings may be subjective and miss important or unobservable information, such as neural activity. Previous research has shown that brain activity in response to pictures of human faces is less pronounced and slower in people with ASD compared to the general population. In this study, we wanted to explore whether and how Pivotal Response Treatment (PRT), a commonly used behavioral intervention for autism, would change brain activity in response to faces in children with ASD. To do this, we measured brain waves using a tool called electroencephalography (EEG) before and after PRT. We found that brain activity in response to viewing faces changed and became faster for children who had completed 16 weeks of PRT, while it did not change for children who did not receive the intervention. Understanding how brain activity relates to behavioral treatments in autism may help inform the development of more objective markers to assess the effectiveness of autism treatment programs.

Face perception predicts affective theory of mind in autism spectrum disorder but not schizophrenia or typical development
Altschuler MR, Trevisan DA, Wolf JM, Naples AJ, Foss-Feig JH, Srihari VH, McPartland JC. J Abnorm Psychol. 2021 May. PMID: 34180705.

People with autism spectrum disorder (ASD) and people with schizophrenia spectrum disorder (SCZ) often describe having difficulty understanding social situations. In this study, we wanted to improve our scientific understanding of how people with ASD, people with SCZ, and typically developing (TD) people process social information. To do this, we gave adults with ASD, adults with SCZ, and TD adults the Benton Facial Recognition Test, which measures how well individuals can recognize faces, and the Reading the Mind in the Eyes Test (RMET), which measures how well individuals can recognize other people’s emotions. We found that adults with either ASD or SCZ performed similarly on the RMET, and both groups had more difficulty recognizing emotions than TD adults. However, adults with ASD who had better facial recognition abilities were better able to recognize emotions, indicating a connection between facial recognition and emotion recognition that we did not find in other adult groups. This finding suggests that helping people improve their facial recognition skills may reduce social difficulties experienced by people with ASD, but not for people with SCZ. This is important because understanding the different reasons that people have difficulty with social interactions can help clinicians choose the best treatment targets for each patient’s situation.

Autism Spectrum Disorder and Schizophrenia Are Better Differentiated by Positive Symptoms Than Negative Symptoms
Trevisan DA, Foss-Feig JH, Naples AJ, Srihari V, Anticevic A, McPartland JC. Front Psychiatry. 2020; 2020 Jun 11. PMID: 32595540.

Individuals with autism spectrum disorder (ASD) and individuals with schizophrenia (SZ) sometimes present with similar symptoms. This study aimed to identify specific symptoms that most effectively differentiate the two conditions. To do this, we considered both “positive” symptoms (the presence of behavior that is unexpected in neurotypical development) and “negative” symptoms (the absence of behavior that is expected in neurotypical development). Results showed that ASD and SZ both showed similar negative symptoms in social behavior, such as reduced facial expression of emotion, reduced eye contact, and reduced communication. However, positive symptoms were very different between the groups. In adults with ASD, positive symptoms related to repetitive behaviors or speech, while, in adults with SZ, positive symptoms related to the presence of delusions or hallucinations. These findings are helpful to clinicians by providing guidance on the symptoms that are most informative when evaluating ASD and SZ in their patients.

The Presence of Another Person Influences Oscillatory Cortical Dynamics During Dual Brain EEG Recording
Rolison MJ, Naples AJ, Rutherford HJV, McPartland JC. Front Psychiatry. 2020; 2020 Apr 17. PMID: 32362842.

It is known that social interaction is central to human behavior and important in brain development. However, little is understood about how brain activity actually changes when in the presence of another person. To examine how brain activity is modified based on the presence of another person, we measured brain waves using a tool called electroencephalography (EEG) in three situations: two adults seated in separate rooms, two adults seated in the same room back-to-back, and two adults in the same room facing one other. We found that brain activity was different when people were together or apart, though it did not matter whether they were facing one another or back-to-back. We also found that brain activity was related to the level of autistic traits that participants self-reported. This shows us that our brain patterns are different, just because another person is in the room with us. We hope this might be helpful in finding new ways to measure whether a brain is responding to others as expected and be potentially useful in detecting brain patterns in young children who might benefit from increased social exposure.

The Autism Biomarkers Consortium for Clinical Trials (ABC-CT): Scientific Context, Study Design, and Progress
McPartland JC, Bernier RA, Jeste SS, Dawson G, Nelson CA, Chawarska K, Earl R, Faja S, Johnson SP, Sikich L, Brandt CA, Dziura JD, Rozenblit L, Hellemann G, Levin AR, Murias M, Naples AJ, Platt ML, Sabatos-DeVito M, Shic F, Senturk D, Sugar CA, Webb SJ. Front Integr Neurosci. 2020; 2020 Apr 9. PMID: 32346363.

At the present time, most autism research relies on descriptions provided by clinicians or parents or caregivers. This information is very important, but it may be subjective or fail to provide information about things that can’t be readily observed. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a five site study designed to identify objective and sensitive biological markers, or “biomarkers”, of social and communicative behavior that may be relevant to autism spectrum disorder (ASD). The ABC-CT used the electroencephalogram (EEG) and eye-tracking (ET) because these are ways of measuring brain function that are cost effective and very tolerable for children. The study is ongoing but has shown great promise, with two biomarkers accepted into the FDA's Biomarker Qualification Program for the purpose of identifying potential subgroups within ASD. The ABC-CT’s ongoing work aims to provide clinicians and treatment developers with better biomarkers to develop more effective ways of measuring outcomes in ASD.

A meta-analysis on the relationship between interoceptive awareness and alexithymia: Distinguishing interoceptive accuracy and sensibility
Trevisan DA, Altschuler MR, Bagdasarov A, Carlos C, Duan S, Hamo E, Kala S, McNair ML, Parker T, Stahl D, Winkelman T, Zhou M, McPartland JC. J Abnorm Psychol. 2019 Nov; 2019 Aug 5. PMID: 31380655.

“Alexithymia” is a condition in which a person has difficulty understanding their own emotions. Scientists do not completely understand why this occurs, but one theory is that people with alexithymia have reduced “interoceptive awareness”, or the ability to detect, monitor, and regulate internal bodily processes such as hunger, thirst, temperature, and emotional arousal. In this study, we analyzed all the prior research that had examined alexithymia and interoceptive awareness. Across 66 different studies, alexithymia was related to decreased interoceptive awareness. The relationship between alexithymia and interoceptive awareness was strongest in samples of people with ASD and other conditions. These results suggest that alexithymia and interoceptive awareness may be relevant across different diagnostic categories and offer a promising means of studying a reported area of difficulty for many adults with ASD.

Resting-state alpha power is selectively associated with autistic traits reflecting behavioral rigidity
Carter Leno V, Tomlinson SB, Chang SA, Naples AJ, McPartland JC. Sci Rep. 2018 Aug 10; 2018 Aug 10. PMID: 30097597.

Past research studies have shown that brain activity while at rest is related to specific symptom domains of ASD. In this study, we hoped to link patterns of brain activity with autistic traits in typically developing individuals. We used electroencephalography (EEG) to study brain waves of 37 typically developing adults at rest, and we measured social interest, rigidity, and pragmatic language difficulties (i.e., difficulties using language for social purposes) with the Broad Autism Phenotype Questionnaire (BAPQ). Our analyses revealed that of the various autistic traits assessed, rigidity was particularly associated with notable patterns of at rest brain activity. Findings suggest that autistic traits are present in the general population and brain activity at rest is related to such traits, even in individuals who do not meet full clinical criteria for ASD.

Atypicality of the N170 Event-Related Potential in Autism Spectrum Disorder: A Meta-analysis
Kang E, Keifer CM, Levy EJ, Foss-Feig JH, McPartland JC, Lerner MD. Biol Psychiatry Neuroimaging. 2018 Aug; 2017 Nov 21. PMID: 30092916.

Previous research has suggested that people with autism have difficulty processing faces. One way to measure this is to look at brain activity in response to seeing pictures of human faces. In this study, we combined data from 23 different studies that used electroencephalography (EEG) to measure brain waves when people looked at human faces. Results showed that brain activity was different in people with autism compared to people without autism when looking at faces; specifically, people with autism processed faces more slowly. This is important because it tells us that brain activity when looking at faces could be a biomarker of social communication difficulties in autism.

Autistic traits modulate conscious and nonconscious face perception
Stavropoulos KKM, Viktorinova M, Naples A, Foss-Feig J, McPartland JC. Soc Neurosci. 2018 Feb; 2016 Nov 10. PMID: 27750521.

Many people with autism spectrum disorder (ASD) describe the process of recognizing emotions as challenging. In this study, we looked at conscious and non-conscious perception of emotion by individuals who did not have diagnosed ASD but reported some level of autism traits. In order to do this, we observed participants’ brain activity while showing them emotional faces too quickly to be consciously observed or slow enough to be consciously observed. We found that non-consciously perceived emotional faces brought on stronger, faster brain responses, regardless of a person’s level of autism traits. Additionally, we discovered that individuals with higher levels of autism traits were less efficient in perceiving faces. These data suggest that difficulty in processing emotions may relate to level of autistic traits, even among those who do not meet criteria for an ASD diagnosis. Understanding the importance of conscious versus nonconscious perception in relation to autistic traits may inform development of new techniques to teach emotion perception in individuals experiencing difficulty in this area.