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Egorova, O., Myte, R., Schneede, J., Hägglöf, B., Bölte, S., Domellöf, E., . . . Silfverdal, S.-A. (2020). Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers. Molecular Autism, 11, Article ID 7.
Open this publication in new window or tab >>Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers
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2020 (English)In: Molecular Autism, ISSN 2040-2392, Vol. 11, article id 7Article in journal (Refereed) Published
Abstract [en]

Background: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis.

Methods: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation.

Results: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22–2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring.

Conclusions: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

Place, publisher, year, edition, pages
BioMed Central, 2020
Keywords
Autism, Pregnancy, One-carbon metabolism, Folate, Vitamin B, Vitamin D, Vitamin A, Inflammation
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:umu:diva-167467 (URN)10.1186/s13229-020-0315-z (DOI)000513660200001 ()
Available from: 2020-01-22 Created: 2020-01-22 Last updated: 2020-03-20Bibliographically approved
Domellöf, E. & Säfström, D. (2020). Prefrontal engagement during sequential manual actions in children at early adolescence compared with adults. NeuroImage, 211, Article ID 116623.
Open this publication in new window or tab >>Prefrontal engagement during sequential manual actions in children at early adolescence compared with adults
2020 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 211, article id 116623Article in journal (Refereed) Published
Abstract [en]

In everyday behavior, we perform numerous goal-directed manual tasks that contain a sequence of actions. However, knowledge is limited regarding developmental aspects of predictive control mechanisms in such tasks, particularly with regard to brain activations supporting sequential manual actions in children. We investigated these issues in typically developing children at early adolescence (11–14 years) compared with previously collected data from adults. While lying in a magnetic resonance imaging (MRI) scanner, the participants steered a cursor on a computer screen towards sequentially presented targets using a hand-held manipulandum. The next target was either revealed after completion of the ongoing target (one-target condition), in which case forthcoming movements could not be planned ahead, or displayed in advance (two-target condition), which allowed the use of a predictive control strategy. The adults completed more targets in the two- than one-target condition, displaying an efficient predictive control strategy. The children, in contrast, completed fewer targets in the two- than one-target condition, and difficulties implementing a predictive strategy were found due to a limited capacity to inhibit premature movements. Brain areas with increased activation in children, compared with the adults, included prefrontal and posterior parietal regions, suggesting an increased demand for higher-level cognitive processing in the children due to inhibitory challenges. Thus, regarding predictive mechanisms during sequential manual tasks, crucial development likely occurs beyond early adolescence. This is at a later age than what has previously been reported from other manual tasks, suggesting that predictive phase transitions are difficult to master.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Sensorimotor control, Sequential actions, Motor prediction, fMRI, Children
National Category
Neurosciences
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-168932 (URN)10.1016/j.neuroimage.2020.116623 (DOI)000519983000029 ()
Funder
Sven Jerring FoundationMagnus Bergvall FoundationVästerbotten County CouncilKnut and Alice Wallenberg Foundation, 2015.0192
Available from: 2020-03-12 Created: 2020-03-12 Last updated: 2020-05-14Bibliographically approved
Bäckström, A., Johansson, A.-M., Rönnqvist, L., Rosander, K., von Hofsten, C. & Domellöf, E. (2019). Action planning in relation to movement performance in 6-year-old children with autism spectrum disorder. In: : . Paper presented at 31st Annual Meeting of the European Academy of Childhood Disability, Paris, France, May 23-25 2019.
Open this publication in new window or tab >>Action planning in relation to movement performance in 6-year-old children with autism spectrum disorder
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2019 (English)Conference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

Introduction: Recent research proposes problems with action planning as part of atypical motor functioning in children with autism spectrum disorder (ASD), although findings are inconsistent. This study investigated relations between action planning and movement performance in 6-year-old children with and without ASD.

Patients and methods: 3D kinematic recordings of preferred arm/hand performance on a sequential peg rotation task with varying complexity of goal insertion (four endpoints and either visual or occluded goal display at onset) were conducted in 6 children with ASD (MAge = 6.4) and 6 typically developing (TD) controls (MAge = 6.5).

Results: Analyses revealed significant (p < .05) group and task-endpoint differences for movement segmentation (number of movement units, MUs) and 3D movement distance. Children with ASD generally displayed more MUs and longer distances than controls and all children showed increased MUs and movement distance on more complex task-endpoints. TD controls showed significantly shorter movement initiation latency (MIL) durations than ASD in the visual condition and evidently longer MILs in the occluded than visual condition. In contrast, no difference between goal display conditions was shown for the ASD group.

Conclusion: Children with ASD generally had longer movement distances and more segmented movements than controls, suggesting less efficient movement performance. Movement performance was not evidently affected by goal display condition in either group. However, the lack of MIL differences between goal display conditions within the ASD group indicates reduced pre-planning, possibly affecting movement execution efficiency.

National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-160514 (URN)
Conference
31st Annual Meeting of the European Academy of Childhood Disability, Paris, France, May 23-25 2019
Funder
Knut and Alice Wallenberg Foundation, 2015.0192
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-07-29Bibliographically approved
Rönnqvist, L., Domellöf, E., Johansson, A.-M., Riklund, K., Warntjes, M. J. B. & Lenfeldt, N. (2019). Associations between brain volumes, myelin and upper-limb kinematics in children born preterm. Developmental Medicine & Child Neurology, 61(S2), 53-54, Article ID OP 130.
Open this publication in new window or tab >>Associations between brain volumes, myelin and upper-limb kinematics in children born preterm
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2019 (English)In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 61, no S2, p. 53-54, article id OP 130Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Introduction: Long-term outcomes linked to preterm (PT) births have generally found an increased amount of neuromotor-developmental delays and/or disabilities. Few studies have addressed how upper-limb kinematics associates with brain volumes and myelination. This study aimed to investigate such possible relationships within children born PT compared with term-born controls at early school age, in relation to gestational age (GA) and birth-weight (BW).

Material and methods: This sub-study, part of a multidisciplinary project exploring long-term effects of PT births, included 27 children (Mean age= 8.2y) born PT (Mean GA= 32-weeks, range 22-35), and 33 age-matched born term. Kinematics of task-specific head and bi-/uni-manual upper-limb-movements was measured by a 3D-registration system (ProReflex). Brain volumes and myelin content were investigated by a 3-Tesla, magnetic resonance imaging (MRI)-scanner with a 7-min Synthetic MRI (SyMRI) acquisition-sequence.

Results: Significantly (p < .05) less efficient upper-limb kinematics with more segmented and longer movement paths was found in PT-born compared with term-born, particularly evident for those extremely-/very PT-born (<32 GA). Smaller total brain volumes and regional white-matter reduction with less myelin were significantly correlated with more segmented and longer arm- and head-trajectories, and with lower GA and BW.

Discussion-conclusion: The present findings show that an extremely- and very-PT-birth may cause long-term effects on neuromotor-mechanisms involved in goal-directed movements and that these effects are associated with generally delayed brain development and myelination. Additionally, SyMRI stands out as a suitable and cost-effective method for longitudinal/follow-up of brain development and changes, reducing distress in children due to a decreased scan time.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
preterm, neuro-motor-mechanisms, myelin, SyMRI, kinematics
National Category
Social Sciences Neurosciences
Research subject
Psychology; Pediatrics; Radiology
Identifiers
urn:nbn:se:umu:diva-159820 (URN)10.1111/dmcn.14244 (DOI)
Projects
hjärnaarvmiljö
Funder
Swedish Research Council, 2011-179
Available from: 2019-06-09 Created: 2019-06-09 Last updated: 2020-03-03Bibliographically approved
Domellöf, E., Bäckström, A., Johansson, A.-M., Rönnqvist, L., von Hofsten, C. & Rosander, K. (2019). Kinematic characteristics of second‐order motor planning and performance in 6‐ and 10‐year‐old children and adults: Effects of age and task constraints. Developmental Psychobiology
Open this publication in new window or tab >>Kinematic characteristics of second‐order motor planning and performance in 6‐ and 10‐year‐old children and adults: Effects of age and task constraints
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2019 (English)In: Developmental Psychobiology, ISSN 0012-1630, E-ISSN 1098-2302Article in journal (Refereed) Epub ahead of print
Abstract [en]

This study explored age‐related differences in motor planning as expressed in arm‐hand kinematics during a sequential peg moving task with varying demands on goal insertion complexity (second‐order planning). The peg was a vertical cylinder with either a circular or semicircular base. The task was to transport the peg between two positions and rotate it various amounts horizontally before fitting into its final position. The amount of rotation required was either 0°, 90°, 180°, or −90°. The reaching for the peg, the displacement of it, and the way the rotation was accomplished was analyzed. Assessments of end state comfort, goal interpretation errors, and type of grip used were also included. Participants were two groups of typically developing children, one younger (Mage = 6.7 years) and one older (Mage = 10.3 years), and one adult group (Mage = 34.9 years). The children, particularly 6‐year‐olds, displayed less efficient prehensile movement organization than adults. Related to less efficient motor planning, 6‐year‐olds, mainly, had shorter reach‐to‐grasp onset latencies, higher velocities, and shorter time to peak velocities, and longer grasp durations than adults. Importantly, the adults rotated the peg during transport. In contrast, the children made corrective rotations after the hand had arrived at the goal.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
action prediction, children, end state comfort, kinematics, motor planning
National Category
Psychology (excluding Applied Psychology)
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-163269 (URN)10.1002/dev.21911 (DOI)000486098900001 ()31502277 (PubMedID)2-s2.0-85072010300 (Scopus ID)
Projects
Children and Motor Planning (CHAMP)
Funder
Knut and Alice Wallenberg Foundation, 2015.0192Swedish Research Council, 2011-179
Available from: 2019-09-12 Created: 2019-09-12 Last updated: 2019-11-07
Andersson, G., Renström, B., Blaszczyk, I. & Domellöf, E. (2019). Upper-extremity Spasticity-reducing Treatment in Adjunct to Movement Training and Orthoses in Children with Cerebral Palsy at Gross Motor Function- and Manual Ability Classification System Levels IV-V: A Descriptive Study. Developmental Neurorehabilitation
Open this publication in new window or tab >>Upper-extremity Spasticity-reducing Treatment in Adjunct to Movement Training and Orthoses in Children with Cerebral Palsy at Gross Motor Function- and Manual Ability Classification System Levels IV-V: A Descriptive Study
2019 (English)In: Developmental Neurorehabilitation, ISSN 1751-8423, E-ISSN 1751-8431Article in journal (Refereed) Epub ahead of print
Abstract [en]

Covering a 20-year period of work with children with severe cerebral palsy (CP) within a Swedish habilitation service, changes in passive wrist extension with fingers extended (PWE-FE) and current hand function are described and compared between children receiving systematic upper-extremity treatment with botulinum neurotoxin type A and intervention programs from before 7 years of age (Group 1, n = 7), those whom for various reasons did not undergo this treatment (Group 2, n = 10), and those not having the option to receive treatment until later during childhood/adolescence (Group 3, n = 8). Group 3 showed more critical and less normal PWE-FE values for both wrists, and poorer hand function scores, particularly compared with Group 1. Findings cautiously suggest that repeated upper-extremity spasticity-reducing treatment and movement training/orthoses from an early age may help prevent critical loss of passive range of motion of the wrist joint flexion/extension and promote hand function development in children with severe CP.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Severe cerebral palsy, botulinum toxin, upper-extremity interventions, passive wrist extension, hand function, development
National Category
Pediatrics
Research subject
Rehabilitation Medicine
Identifiers
urn:nbn:se:umu:diva-163315 (URN)10.1080/17518423.2019.1655677 (DOI)000482720500001 ()31437072 (PubMedID)2-s2.0-85071011008 (Scopus ID)
Funder
Västerbotten County CouncilKnut and Alice Wallenberg Foundation, 2015.0192
Available from: 2019-09-13 Created: 2019-09-13 Last updated: 2019-09-20
Säfström, D. & Domellöf, E. (2018). Brain activations supporting linking of action phases in a sequential manual task. NeuroImage, 172, 608-619
Open this publication in new window or tab >>Brain activations supporting linking of action phases in a sequential manual task
2018 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, ., Vol. 172, p. 608-619Article in journal (Refereed) Published
Abstract [en]

Most everyday manual tasks, like grabbing a cup of coffee to drink, are comprised of a sequence of action phases. Efficient phase transitions, or linking, are achieved using a predictive control policy where motor commands for the next phase are specified and released in anticipation of sensory confirmation of goal completion of the current phase. If there is a discrepancy between predicted and actual sensory feedback about goal completion, corrective actions are employed to complete the current action phase before proceeding to the next. However, we lack understanding about brain activations supporting such predictive linking and corrective actions in manual tasks. In this study, during 3-T MRI-scanning, sixteen participants (5 males, 11 females; mean age 27.3 years, range 23–37) performed a sequential manual task, with or without the possibility for predictive linking. We found that predictive linking of action phases was associated with increased activation in a network that included right-sided fronto-parietal areas related to visuospatial attention, eye movements and motor planning, left-sided parietal areas related to implicit timing and shifts of motor attention, occipital regions bilaterally reflecting visual processing related to the attended next target, and finally, the anterior midcingulate cortex involved in continuous performance monitoring. Corrective actions were associated with increased activation in the left dorsolateral prefrontal cortex involved in reestablishing executive control over previously automatized behavior.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Sensorimotor control, Sequential actions, Motor prediction, Error detection, fMRI
National Category
Medical Biotechnology
Research subject
Biomedical Radiation Science
Identifiers
urn:nbn:se:umu:diva-145639 (URN)10.1016/j.neuroimage.2018.02.014 (DOI)29428579 (PubMedID)
Available from: 2018-03-12 Created: 2018-03-12 Last updated: 2019-09-16Bibliographically approved
Domellöf, E., Johansson, A.-M. & Rönnqvist, L. (2018). Developmental progression and side specialization in upper-limb movements from 4 to 8 years in children born preterm and fullterm. Developmental Neuropsychology, 43(3), 219-234
Open this publication in new window or tab >>Developmental progression and side specialization in upper-limb movements from 4 to 8 years in children born preterm and fullterm
2018 (English)In: Developmental Neuropsychology, ISSN 8756-5641, E-ISSN 1532-6942, Vol. 43, no 3, p. 219-234Article in journal (Refereed) Published
Abstract [en]

This study investigated developmental changes and differences in upper-limb movement organization from 4 to 8 years of age in children born preterm (PT) and fullterm (FT). Kinematic recordings of precision-demanding unimanual movements and lateral assessments were carried out in 37 children (18 PT). All children, particularly children born PT, displayed considerable gain in movement kinematics. Contrary to controls, children born PT displayed persistently less-evident side preference. Gestational age (GA) contributed significantly to kinematic differences shown, with larger upper-limb deviances in the lowest GAs, in agreement with cross-sectional findings of altered hemispheric connections and delayed side-specialization among children born very PT.

Place, publisher, year, edition, pages
Routledge, 2018
National Category
Psychology (excluding Applied Psychology) Neurosciences
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-145742 (URN)10.1080/87565641.2018.1426765 (DOI)000427940500005 ()29377727 (PubMedID)
Available from: 2018-03-16 Created: 2018-03-16 Last updated: 2019-09-16Bibliographically approved
Domellöf, E., Bäckström, A., Johansson, A.-M., Rosander, K., von Hofsten, C. & Rönnqvist, L. (2018). Sequential upper-limb action planning in children with autism spectrum disorder: a kinematic pilot study. Paper presented at Annual Meeting of the European Academy of Childhood Disability (EACD), Tbilisi, Georgia, May 28–31, 2018. Developmental Medicine & Child Neurology, 60(S2), 34-34
Open this publication in new window or tab >>Sequential upper-limb action planning in children with autism spectrum disorder: a kinematic pilot study
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2018 (English)In: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 60, no S2, p. 34-34Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Introduction: Recent research on sensory-motor skill in children with autism spectrum disorder (ASD) suggest that problems with planning sequential actions may explain difficulties with motor execution in this population. The present pilot study investigated upper-limb movement kinematics during a goal-directed manual task requiring sequential action planning in children with and without ASD at 6-7 years.

Patients and method: 3D kinematic recordings of performance with the preferred arm/hand during a sequential peg moving task with varying complexity of goal insertion (five endpoint conditions, open/revealed goal presentation) were carried out in 3 children with ASD (2 girls, mean age 6.3 years) and 3 typically developing children (3 girls, mean age 7 years). End state comfort and trial errors were also assessed.

Results: Preliminary analyses of whole movement spatiotemporal segmentation (movement units, MUs) at trial level revealed significant main effects for group and endpoint condition. Overall, children with ASD consistently performed less proficiently (more MUs) than controls for all conditions across hand/arm and head. Independent of group, all children displayed increased MUs for the more complex endpoints. Children with ASD also showed evidently poorer planning behavior (less end state comfort and increased trial errors) than controls.

Conclusion: Findings suggest difficulties with sequential movement planning in children with ASD in terms of suboptimal movement organization together with reduced end state comfort and inaccurate goal interpretations. In contrast to controls, children with ASD did not seem to have planned the onward action prior to action execution, contributing to the observed less proficient movement kinematics.

Place, publisher, year, edition, pages
Mac Keith Press, 2018
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:umu:diva-151247 (URN)10.1111/dmcn.13790 (DOI)
Conference
Annual Meeting of the European Academy of Childhood Disability (EACD), Tbilisi, Georgia, May 28–31, 2018
Funder
Knut and Alice Wallenberg Foundation, KAW 2015.0192
Note

Special Issue: Abstracts of the 30th Annual Meeting of the European Academy of Childhood Disability (EACD), Tbilisi, Georgia, 28–31 May 2018

Available from: 2018-08-30 Created: 2018-08-30 Last updated: 2020-03-11Bibliographically approved
Lenfeldt, N., Johansson, A.-M., Domellöf, E., Riklund, K. & Rönnqvist, L. (2017). Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm. Human Brain Mapping, 38(10), 5051-5068
Open this publication in new window or tab >>Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm
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2017 (English)In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 38, no 10, p. 5051-5068Article in journal (Refereed) Published
Abstract [en]

Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upperlimb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25–27 weeks, N = 10), very PT (V-PT; GA = 28–32 weeks, N = 13), and moderately PT (M-PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements.

Place, publisher, year, edition, pages
Hoboken: Wiley-Blackwell, 2017
Keywords
diffusion tensor imaging, anisotropy, sensorimotor, corticospinal, internal capsule, laterality
National Category
Psychology
Research subject
Radiology; Psychology; Pediatrics
Identifiers
urn:nbn:se:umu:diva-139528 (URN)10.1002/hbm.23714 (DOI)000417002000017 ()28685893 (PubMedID)
Funder
Swedish Research Council, 2011-179
Available from: 2017-09-15 Created: 2017-09-15 Last updated: 2019-01-08Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0240-3690

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