| 1. |
- Ahrens, Angelica P., et al.
(author)
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Infant microbes and metabolites point to childhood neurodevelopmental disorders
- 2024
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In: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 187:8, s. 1853-1873.e15
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Journal article (peer-reviewed)abstract
- This study has followed a birth cohort for over 20 years to find factors associated with neurodevelopmental disorder (ND) diagnosis. Detailed, early-life longitudinal questionnaires captured infection and antibiotic events, stress, prenatal factors, family history, and more. Biomarkers including cord serum metabolome and lipidome, human leukocyte antigen (HLA) genotype, infant microbiota, and stool metabolome were assessed. Among the 16,440 Swedish children followed across time, 1,197 developed an ND. Significant associations emerged for future ND diagnosis in general and for specific ND subtypes, spanning intellectual disability, speech disorder, attention-deficit/hyperactivity disorder, and autism. This investigation revealed microbiome connections to future diagnosis as well as early emerging mood and gastrointestinal problems. The findings suggest links to immunodysregulation and metabolism, compounded by stress, early-life infection, and antibiotics. The convergence of infant biomarkers and risk factors in this prospective, longitudinal study on a large-scale population establishes a foundation for early-life prediction and intervention in neurodevelopment.
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| 2. |
- Bang, Peter, 1992-
(author)
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Beyond Categories : A Dimensional Approach to Autism and Sensorimotor Differences
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Autism spectrum conditions (ASC) encompass a range of sensory, motor, and social-communicative differences, reflecting the considerable heterogeneity within the autism spectrum. This diversity underscores the limitations of categorical diagnostic approaches, which often fail to capture the individualized manifestations of autism. Advances in genetics and neuroscience have driven a shift towards dimensional frameworks that emphasize the spectrum nature of autism and the broad autism phenotype (BAP). BAP encapsulates subclinical traits that mirror those of autism in the general population, challenging the conventional boundaries between clinical and non-clinical populations. Furthermore, sensorimotor differences, which are particularly prevalent in individuals with ASC, follow a spectrum-like pattern similar to the BAP and are predictive of developmental outcomes related to social participation, communication, and overall quality of life in people with and without ASC. However, specific descriptions of these relationships are lacking.This dissertation investigated the complex relationships between sensorimotor differences and autistic traits (ATs). Through a series of five interconnected studies, we examined broad sensory processing patterns and specific sensory modalities, namely auditory processing and motor/proprioception, to explore their roles in autistic phenotypes.Study 1 of the dissertation validated a Swedish translation of the Broad Autism Phenotype Questionnaire (BAPQ). By examining parents' BAP traits, the study highlighted significant associations between higher ATs and having a child with ASC. Furthermore, it confirmed the presence of all three AT domains—social interaction (ATSOC), communication (ATCOM), and cognitive rigidity (ATRIG), reinforcing the genetic and phenotypic continuity between clinical and subclinical ATs.Study 2 and Study 3 served as broader investigations into all seven sensory modalities and their associations with ATs. Study 2 explored these modality-specific associations, using Bayesian stochastic search variable selection (SSVS) and dominance analysis. This study highlighted auditory processing difficulties as the most consistent predictor of all three AT domains. Additionally, proprioceptive and tactile processing difficulties were specifically associated with ATCOM and ATSOC, respectively.Study 3 extended this analysis to a developing population, focusing on the relationship between sensorimotor processing, ATs, and anxiety in children aged 6-11 years. Identical to Study 2, we found tactile symptoms as a predictor of ATSOC, proprioceptive symptoms for ATCOM, and auditory symptoms for ATRIG. In addition, olfactory symptoms were selected as a predictor of ATCOM, and motor coordination was a consistent predictor of all AT domains. Using SSVS, this study also identified that auditory and olfactory processing difficulties were strong predictors of anxiety symptoms.Building on the previous studies, Study 4 narrowed the focus to auditory processing differences, investigating specific auditory problems and their associations with the AT domains. All AT domains significantly predicted affective reactions to sounds, while difficulties with speech perception, spatial perception, and auditory stream segregation were most strongly predicted by ATCOM.Study 5 focused on the previously found links between motor coordination and proprioceptive processing and ATCOM. Using causal mediation analysis within a counterfactual framework, this study found that cerebellar error correction deficits, measured through a finger tapping task, significantly impacted ATCOM through motor skills in childhood.Together, this dissertation provides a comprehensive overview of the sensory processing dimensions related to the core AT domains. Specifically, the studies underscored the clinical significance of monitoring auditory and olfactory complaints in children, as these were predictive of anxiety, and emphasized that early motor deficits impact social communication development. The findings advocate for the inclusion of detailed sensory and motor assessments in neurodevelopmental evaluations to identify children at risk for poor mental health outcomes. Future research should continue to explore the mechanisms underlying sensory processing differences. Particular focus should be placed on auditory and motor/proprioceptive functions and their contributions to ATs and clinical outcomes, such as anxiety. Emphasis should also be given to longitudinal studies that track these relationships over time.
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| 3. |
- Bang, Peter, et al.
(author)
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Brief Report : The Broad Autism Phenotype in Swedish Parents of Children With and Without Autism Spectrum Conditions
- 2022
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In: Journal of autism and developmental disorders. - : Springer-Verlag New York. - 0162-3257 .- 1573-3432. ; 52:10, s. 4575-4582
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Journal article (peer-reviewed)abstract
- The broad autism phenotype (BAP) is a set of characteristics often observed in typically developing people with a genetic load for autism, such as parents of autistic children. The Broad Autism Phenotypic Questionnaire (BAPQ) is a 36-item questionnaire developed to identify the BAP in first-degree relatives of autistic people. We translated the BAPQ into Swedish and examined its psychometric properties in a Swedish sample consisting of 45 parents of children with ASC and 74 parents of non-autistic children. We found support for the original 3-factor structure (aloof, pragmatic language and rigid), good internal consistency and convergent validity with the Autism Quotient. Thus, the Swedish BAPQ exhibits acceptable psychometric properties and may be useful for assessing the BAP in non-clinical populations.
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| 4. |
- Bang, Peter, et al.
(author)
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Modality-specific associations between sensory differences and autistic traits
- 2023
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In: Autism. - : SAGE PUBLICATIONS LTD. - 1362-3613 .- 1461-7005. ; 27:7, s. 2158-2172
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Journal article (peer-reviewed)abstract
- Sensory processing differences measured by self- or parent-report co-segregate with quantitative autistic traits and have potential endophenotypic properties. It is not known to what extent this reflects generalized sensory dysfunction versus more specific associations involving individual senses or autistic trait domains. We combined Bayesian variable selection with dominance analysis to obtain a more nuanced understanding of modality-specific associations. We recruited two independent samples of adults to complete the Broad Autism Phenotype Questionnaire and the Glasgow Sensory Questionnaire. For each domain of autistic traits (social interaction, communication, cognitive rigidity), we performed stochastic search variable selection using Glasgow Sensory Questionnaire modality subscales as predictors while controlling for uncertainty in other variables. Dominance analysis was applied to the reduced models to evaluate the relative importance of predictors. Only auditory scores reliably predicted all three autistic traits when other modalities were accounted for. The proprioceptive scale, which included motor and interoceptive deficits, predicted communicative autistic traits more than other trait domains. The tactile scale appeared most specific for social autistic traits. Although the findings must be interpreted in light of the limitations of the questionnaires, the study suggests that auditory differences may be more likely than differences in other senses to be a robust sensory endophenotype relevant to autism. Lay abstract Sensory symptoms are a major source of distress for many autistic people, causing anxiety, stress, and avoidance. Sensory problems are thought to be passed on genetically together with other autistic characteristics, such as social preferences. This means that people who report cognitive rigidity and autistic-like social function are more likely to suffer from sensory issues. We do not know what role the individual senses, such as vision, hearing, smell, or touch, play in this relationship, because sensory processing is generally measured with questionnaires that target general, multisensory issues. This study aimed to investigate the individual importance of the different senses (vision, hearing, touch, smell, taste, balance, and proprioception) in the correlation with autistic traits. To ensure the results were replicable, we repeated the experiment in two large groups of adults. The first group contained 40% autistic participants, whereas the second group resembled the general population. We found that problems with auditory processing were more strongly predictive of general autistic characteristics than were problems with the other senses. Problems with touch were specifically related to differences in social interaction, such as avoiding social settings. We also found a specific relationship between proprioceptive differences and autistic-like communication preferences. The sensory questionnaire had limited reliability, so our results may underestimate the contribution of some senses. With that reservation in mind, we conclude that auditory differences are dominant over other modalities in predicting genetically based autistic traits and may therefore be of special interest for further genetic and neurobiological studies.
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| 5. |
- Bang, Peter, et al.
(author)
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Relationships Between Autistic Trait Dimensions and Speech Understanding, Affective Sound Intolerance, and Self-Reported Hearing Difficulties
- 2024
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In: AUTISM IN ADULTHOOD. - : MARY ANN LIEBERT, INC. - 2573-9581.
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Journal article (peer-reviewed)abstract
- Background: Decreased sound tolerance (DST) is a disabling transdiagnostic phenomenon with high clinical relevance in autism. Neurodevelopmental DST is often studied as part of a general multisensory construct that includes both hyper- and hyposensitivity. Therefore, knowledge about the potential relevance of individual differences in the auditory modality is lacking. The purpose of the study was to begin to differentiate between commonly pooled auditory functions, by incorporating psychometric tools from the field of audiology.Methods: In a pilot sample (N = 520 adults, 23% autistic), we used Bayesian correlations to quantify the contribution of individual auditory items from the Glasgow Sensory Questionnaire to the degree of social, communicative, and rigid autistic traits measured with the Broad Autism Phenotype Questionnaire (BAPQ) subscales. Then, we recruited an independent sample (N = 175 adults, 18% autistic) to measure, more specifically, (1) emotional reactions to sounds (affective DST), (2) speech understanding difficulties, and (3) nonsocial auditory processing (spatial perception and stream segregation), using self-report questionnaires. We used multiple regression to test for associations with the autistic trait domains.Results: We found that all autistic traits measured by the BAPQ (social, communicative, and rigid) linearly predicted affective DST, and these associations remained when autistic participants were excluded. Difficulties with speech perception, as well as spatial perception and auditory stream segregation, were most strongly predicted by communication differences.Conclusion: The robust relationship between autistic traits and emotional sound reactivity suggests that affective DST falls on a spectrum just like autism. This argues against strict dichotomization and encourages the use of continuous measures. The results support a dominant role for emotional and stress systems in autism-related DST and may suggest that detailed audiological tests are clinically useful, in particular, in the context of pragmatic language difficulties. Community Brief Why is this an important issue? Differences in sensory perception go hand in hand with an autistic neurotype. Many individuals find everyday noises intolerable or difficult to understand, but there is little knowledge of how these experiences vary among individuals. What was the purpose of this study? To understand which aspects of auditory processing are related to autistic characteristics, using assessment tools from the audiology field. What did the researchers do? They studied 175 adults with different levels of autistic-like social function, communication style, and rigid thinking (18% with an autism diagnosis). They used clinical questionnaires to measure emotional reactions to sounds, speech understanding, auditory space perception, and the ability to distinguish overlapping sounds. What were the results of the study? All autistic characteristics were linked to strong emotional reactions to sounds. Those with an autistic communication style also reported difficulties with speech perception, auditory space perception, and separating overlapping sounds. What do these findings add to what was already known? The results highlight a role of emotional and stress responses in autistic sound sensitivity. In addition, they point to the existence of broader auditory difficulties in adults with an autistic communication style. What are potential weaknesses in the study? It did not include laboratory measurements of auditory function. How will these findings help autistic adults now or in the future? This study helps by breaking down specific hearing challenges in autism, such as trouble understanding speech or reacting strongly to everyday sounds, rather than looking at sensory issues as a whole. This can lead to better support and solutions for these specific difficulties.
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| 6. |
- Bang, Peter, et al.
(author)
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Sensory symptoms associated with autistic traits and anxiety levels in children aged 6–11 years
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Other publication (other academic/artistic)abstract
- Autism spectrum conditions (ASC) and quantitative autistic traits (QATs) are associated with sensory symptoms, which may contribute to anxiety and adversely affect social and cognitive development. Although sensory symptoms can occur across all senses, the relative roles of specific sensory modalities as contributors to the autistic phenotype and to anxiety are not well understood. The objective of this study was to examine which sensory symptoms were most predictive of high anxiety. We recruited 257 female primary caregivers of children aged 6 to 11 years (49 % girls) to a questionnaire study comprising parent-report measures for classical QATs (social, communicative, and rigid), autism-related sensorimotor symptoms (visual, auditory, tactile, olfactory, gustatory, vestibular, proprioceptive, and motor), and anxiety symptoms. First, Bayesian stochastic search variable selection (SSVS) was used to identify the most probable sensorimotor predictors of specific QATs as well as diagnosed ASC. Then, the selected predictors were used in another SSVS, using anxiety symptoms as a dependent variable, to identify which of the autism-relevant sensorimotor symptoms were most robustly predictive of anxiety. Finally, the effect sizes of anxiety-related sensory symptoms were estimated with linear regressions. We found that auditory symptoms and motor difficulties were most predictive of ASC diagnosis. Developmental motor difficulties were also strongly related to all individual QATs, whereas auditory symptoms were more selectively predictive of rigid traits. Tactile symptoms robustly predicted social interaction QATs, and proprioceptive symptoms predicted communicative QATs. Anxiety outcomes were most predicted by difficulties with auditory and olfactory processing. The results support the clinical importance of being alert to complaints about sounds and hearing in neurodevelopmental populations, and that auditory processing difficulties may be evaluated as an early marker of poor mental health in children with and without diagnosed autism. Olfactory processing differences appeared to be an anxiety marker less strongly associated with ASC or QATs, while motor difficulties were highly autism-relevant but not equally strongly associated with anxiety outcomes. We suggest that future studies may focus on the mechanisms and consequences of neurodevelopmental central auditory processing dysfunction and its potential relationship to anxiety disorders.
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| 7. |
- Bang, Peter, 1992-, et al.
(author)
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The mediating role of childhood motor skills on the association between error correction and social pragmatic communication in adulthood
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Other publication (other academic/artistic)abstract
- Early motor function is important for emerging social pragmatic communication (SPC) skills in both typical and atypical development. However, the nature of motor impairments relevant for higher-level communication is not well understood. Inefficient cerebellar error correction might directly cause both developmental coordination disorder (DCD) symptoms and SPC difficulties, through the extensive communication between cerebellar zones and brain-wide sensorimotor and higher-order networks. DCD symptoms related to cerebellar deficits could also impact SPC through affecting the developmental trajectory of social development, which requires motor skills. This study aimed to test the hypothesis that error correction deficits affect SPC outcomes through childhood DCD symptoms, by using contemporary causal inference methodology. We used a finger tapping task and computational modeling to measure cerebellar error correction in adult participants (n = 138), and quantified childhood DCD symptoms and SPC skills using psychometric measures. The results confirmed that error correction ability likely affects SPC skills, and indicated that childhood motor skills significantly mediated this. These results argue against a direct effect of domain-general error correction deficits on SPC, and instead suggest that cerebellum-related DCD symptoms affect sociocommunicative development more directly through motor deficits during development. Further research is required to test whether cerebellar error correction could be used as an early marker to identify children in need for early SPC interventions.
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| 8. |
- Barry, Melissa, et al.
(author)
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Utility of intracerebral theta burst electrical stimulation to attenuate interhemispheric inhibition and to promote motor recovery after cortical injury in an animal model
- 2014
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In: Experimental Neurology. - : Academic Press. - 0014-4886 .- 1090-2430. ; 261, s. 258-266
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Journal article (peer-reviewed)abstract
- Following a cerebral cortex injury such as stroke, excessive inhibition around the core of the injury is thought to reduce the potential for new motor learning. In part, this may be caused by an imbalance of interhemispheric inhibition (IHI); therefore, treatments that relieve the inhibitory drive from the healthy hemisphere to the peri-lesional area may enhance motor recovery. Theta burst stimulation delivered by transcranial magnetic stimulation has been tested as a means of normalizing IHI, but clinical results have been variable. Here we use a new rat model of synaptic IHI to demonstrate that electrical intracranial theta burst stimulation causes long-lasting changes in motor cortex excitability. Further, we show that contralateral intermittent theta burst stimulation (iTBS) blocks IHI via a mechanism involving cannabinoid receptors. Finally, we show that contralesional iTBS applied during recovery from cortical injury in rats improves the recovery of motor function. These findings suggest that theta burst stimulation delivered through implanted electrodes may be a promising avenue to explore for augmenting rehabilitation from brain injury.
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| 9. |
- Högstedt, Erika, 1980-, et al.
(author)
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'It's like it is designed to keep me stressed' - Working sustainably with ADHD or autism
- 2023
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In: Scandinavian Journal of Occupational Therapy. - : Taylor & Francis Group. - 1103-8128 .- 1651-2014. ; 30:8, s. 1280-1291
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Journal article (peer-reviewed)abstract
- Background Adults with attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) face multiple challenges in obtaining and maintaining employment. Aims To identify and describe how adults with ADHD or ASD experienced their ability to work and what factors affected their ability to find a sustainable work situation over time. Methods Individual in-depth interviews were performed with 20 purposively sampled participants with ADHD/ASD. Data were analysed inductively using reflexive thematic analysis. Results Three themes were identified, describing (1) one's own cognitive abilities and challenges, (2) enablement by flexibility and acceptance in the work environment, and (3) accumulated stress that makes the work situation unsustainable over time. Conclusions Over time, a lack of continuity and predictability of support measures caused great stress and exhaustion, with severe consequences for working life and in life in general. Adaptations needed to be individually tailored and include nonoccupational factors. Significance The study shows that adults with ADHD/ASD need long-term interventions that flexibly adapt to individual needs, as they vary over time. The findings suggest that occupational therapists and other health care providers, employers, employment services and other involved agencies should pay a greater deal of attention to stability and predictability over time.
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| 10. |
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