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1.
Neurology ; 101(23): e2401-e2410, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-37848334

ABSTRACT

BACKGROUND AND OBJECTIVES: Neonatal brain injury is a common and devastating diagnosis conferring lifelong challenges for children and families. The role of mechanical forces applied to the head, often referred to as "birth trauma," are often considered although evidence for this association is lacking. The objective of this study was to investigate the association between common types of neonatal brain injury and scalp swelling using a novel method to quantify scalp swelling as an unbiased proxy for mechanical forces applied to the head. METHODS: Case-control study using population-based, prospectively collected tertiary care center databases and healthy controls from the Human Connectome Development Project. Included were infants born 32-42 weeks gestational age and MRI in the first 9 days. Outcomes categories included healthy neonates, hypoxic ischemic encephalopathy (HIE) with or without brain injury, or stroke (ischemic or hemorrhagic). Volume of scalp swelling was objectively quantified by a novel imaging method blinded to brain injury. Variables included mode of delivery and use of instrumentation. Statistical tests included Kruskal-Wallis test, chi square, and multivariable and multinomial logistic regression. RESULTS: There were 309 infants included (55% male): 72 healthy controls, 77 HIE without brain injury on MRI, 78 HIE with brain injury, and 82 with stroke (60 ischemic, 22 hemorrhagic). Scalp swelling was present in 126 (40.8%, 95% confidence interval [CI] 35.2%-46.5%) with no difference in proportions between outcome groups. Compared to healthy controls, median volume was higher in those with HIE without brain injury (17.5 mL, 95% CI 6.8-28.2), HIE with brain injury (12.1 mL, 95% CI 5.5-18.6), but not ischemic stroke (4.7 mL, 95% CI -1.2-10.6) nor hemorrhagic stroke (8.3 mL, 95% CI -2.2-18.8). Scalp swelling was associated with instrumented delivery (OR 2.1, 95% CI 1.0-4.1), but not associated with increased odds of brain injury in those with HIE (OR 1.5, 95% CI 0.76-3.30). Scalp swelling measures were highly reliable (ICC = 0.97). DISCUSSION: "Birth trauma" quantified by scalp swelling volume was more common in infants with difficult deliveries, but not associated with greater odds of brain injury due to hypoxia or stroke. These results may help parents and practitioners to dissociate the appearance of trauma with the risk of brain injury.


Subject(s)
Brain Injuries , Craniocerebral Trauma , Hypoxia-Ischemia, Brain , Stroke , Infant, Newborn , Infant , Child , Humans , Male , Female , Case-Control Studies , Magnetic Resonance Imaging , Craniocerebral Trauma/complications , Brain Injuries/complications , Stroke/complications , Hypoxia-Ischemia, Brain/complications , Hypoxia-Ischemia, Brain/diagnostic imaging
2.
Soc Sci Res ; 114: 102916, 2023 08.
Article in English | MEDLINE | ID: mdl-37597930

ABSTRACT

Social ties between members of in- and outgroups are theorized to reduce individual levels of prejudice. However, instances of intergroup contact are not isolated events; cross-group interactions are embedded in broader networks defined by various social processes that guide the formation and maintenance of interpersonal relationships. This project reconsiders the potential benefits of intergroup contact by applying a network perspective to examine whether friendships between youth of different sexualities can shape individuals' homophobic attitudes. The impact of cross-sexuality ties is evaluated through the application of stochastic actor-oriented models (SAOMs) to a two-wave sample of Dutch adolescents. Results indicate that the benefits of cross-sexuality connections become negligible when we account for how patterns of network connectivity and segregation are informed by other individual-level traits, such as age, religious background, ethnicity, and gender. In other words, heterosexual adolescents who are situated in network positions that provide opportunities to form cross-sexuality friendships would be expected to report less homophobic attitudes even in the absence of this intergroup contact. These findings suggest that the cross-sexuality contact observed in the social world often represents instances of "preaching to the choir," limiting the potential for intergroup connections to challenge systems of social inequality.


Subject(s)
Friends , Sexual and Gender Minorities , Adolescent , Humans , Heterosexuality , Attitude , Social Networking
3.
Sci Rep ; 13(1): 11391, 2023 07 14.
Article in English | MEDLINE | ID: mdl-37452141

ABSTRACT

Perinatal stroke causes most hemiparetic cerebral palsy and cognitive dysfunction may co-occur. Compensatory developmental changes in the intact contralesional hemisphere may mediate residual function and represent targets for neuromodulation. We used morphometry to explore cortical thickness, grey matter volume, gyrification, and sulcal depth of the contralesional hemisphere in children, adolescents, and young adults after perinatal stroke and explored associations with motor, attention, and executive function. Participants aged 6-20 years (N = 109, 63% male) with unilateral perinatal stroke underwent T1-weighted imaging. Participants had arterial ischemic stroke (AIS; n = 36), periventricular venous infarction (PVI; n = 37) or were controls (n = 36). Morphometry was performed using the Computational Anatomy Toolbox (CAT12). Group differences and associations with motor and executive function (in a smaller subsample) were assessed. Group comparisons revealed areas of lower cortical thickness in contralesional hemispheres in both AIS and PVI and greater gyrification in AIS compared to controls. Areas of greater grey matter volume and sulcal depth were also seen for AIS. The PVI group showed lower grey matter volume in cingulate cortex and less volume in precuneus relative to controls. No associations were found between morphometry metrics, motor, attention, and executive function. Cortical structure of the intact contralesional hemisphere is altered after perinatal stroke. Alterations in contralesional cortical morphometry shown in perinatal stroke may be associated with different mechanisms of damage or timing of early injury. Further investigations with larger samples are required to more thoroughly explore associations with motor and cognitive function.


Subject(s)
Cerebral Palsy , Ischemic Stroke , Stroke , Pregnancy , Female , Humans , Male , Child , Adolescent , Young Adult , Attention , Ischemic Stroke/complications , Gray Matter/diagnostic imaging , Magnetic Resonance Imaging
4.
Hum Brain Mapp ; 44(4): 1711-1724, 2023 03.
Article in English | MEDLINE | ID: mdl-36478489

ABSTRACT

Developmental lateralization of brain function is imperative for behavioral specialization, yet few studies have investigated differences between hemispheres in structural connectivity patterns, especially over the course of development. The present study compares the lateralization of structural connectivity patterns, or topology, across children, adolescents, and young adults. We applied a graph theory approach to quantify key topological metrics in each hemisphere including efficiency of information transfer between regions (global efficiency), clustering of connections between regions (clustering coefficient [CC]), presence of hub-nodes (betweenness centrality [BC]), and connectivity between nodes of high and low complexity (hierarchical complexity [HC]) and investigated changes in these metrics during development. Further, we investigated BC and CC in seven functionally defined networks. Our cross-sectional study consisted of 211 participants between the ages of 6 and 21 years with 93% being right-handed and 51% female. Global efficiency, HC, and CC demonstrated a leftward lateralization, compared to a rightward lateralization of BC. The sensorimotor, default mode, salience, and language networks showed a leftward asymmetry of CC. BC was only lateralized in the salience (right lateralized) and dorsal attention (left lateralized) networks. Only a small number of metrics were associated with age, suggesting that topological organization may stay relatively constant throughout school-age development, despite known underlying changes in white matter properties. Unlike many other imaging biomarkers of brain development, our study suggests topological lateralization is consistent across age, highlighting potential nonlinear mechanisms underlying developmental specialization.


Subject(s)
Brain , White Matter , Young Adult , Humans , Child , Adolescent , Female , Adult , Male , Cross-Sectional Studies , Brain/diagnostic imaging , White Matter/diagnostic imaging , Brain Mapping/methods , Magnetic Resonance Imaging
5.
Sci Rep ; 12(1): 3866, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35264665

ABSTRACT

Perinatal stroke occurs early in life and often leads to a permanent, disabling weakness to one side of the body. To test the hypothesis that non-lesioned hemisphere sensorimotor network structural connectivity in children with perinatal stroke is different from controls, we used diffusion imaging and graph theory to explore structural topology between these populations. Children underwent diffusion and anatomical 3T MRI. Whole-brain tractography was constrained using a brain atlas creating an adjacency matrix containing connectivity values. Graph theory metrics including betweenness centrality, clustering coefficient, and both neighbourhood and hierarchical complexity of sensorimotor nodes were compared to controls. Relationships between these connectivity metrics and validated sensorimotor assessments were explored. Eighty-five participants included 27 with venous stroke (mean age = 11.5 ± 3.7 years), 26 with arterial stroke (mean age = 12.7 ± 4.0 years), and 32 controls (mean age = 13.3 ± 3.6 years). Non-lesioned primary motor (M1), somatosensory (S1) and supplementary motor (SMA) areas demonstrated lower betweenness centrality and higher clustering coefficient in stroke groups. Clustering coefficient of M1, S1, and SMA were inversely associated with clinical motor function. Hemispheric betweenness centrality and clustering coefficient were higher in stroke groups compared to controls. Hierarchical and average neighbourhood complexity across the hemisphere were lower in stroke groups. Developmental plasticity alters the connectivity of key nodes within the sensorimotor network of the non-lesioned hemisphere following perinatal stroke and contributes to clinical disability.


Subject(s)
Motor Cortex , Stroke , Adolescent , Brain , Child , Diffusion Tensor Imaging , Humans , Magnetic Resonance Imaging
6.
J Grad Med Educ ; 14(1): 53-59, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35222821

ABSTRACT

BACKGROUND: Under the single GME accreditation system, residency programs receive applicants from MD- and DO-granting medical schools, each of which have their own set of licensing examinations, making concordance studies increasingly relevant. Previous studies comparing Comprehensive Osteopathic Medical Licensing Examination of the United States (COMLEX-USA) and United States Medical Licensing Examination (USMLE) scores have been limited in sample size and examinee composition and have yielded comparisons that may not be generalizable across all applicants. Some osteopathic medical students take USMLE in addition to COMLEX-USA, often at considerable cost and effort, with the aim of making themselves more desirable to potential residency programs. Having more reliable comparisons of COMLEX-USA and USMLE scores would allow program directors to better estimate a score on the alternate examination. OBJECTIVE: To derive an accurate concordance between COMLEX-USA and USMLE scores, based on a large sample of osteopathic students who took both examinations. METHODS: Five colleges of osteopathic medicine, representing various regions of the United States, participated in this study. The data included demographics and COMLEX-USA and USMLE scores from September 2015 through August 2020 for students who took both examinations. We derived the concordance between COMLEX-USA and USMLE scores using equipercentile matching. RESULTS: Comparisons of demographic characteristics showed only minor differences between the sample and the overall population for COMLEX-USA takers, although scores for the study sample were, on average, greater. CONCLUSIONS: A strong association exists between the scores on the COMLEX-USA and USMLE examinations, allowing prediction of performance on USMLE from COMLEX-USA.


Subject(s)
Internship and Residency , Osteopathic Medicine , Osteopathic Physicians , Educational Measurement , Humans , Licensure, Medical , Osteopathic Medicine/education , United States
7.
Brain Behav ; 12(1): e2433, 2022 01.
Article in English | MEDLINE | ID: mdl-34825521

ABSTRACT

Perinatal stroke affects ∼1 in 1000 births and concomitant cognitive impairments are common but poorly understood. Rates of Attention Deficit/Hyperactivity Disorder (ADHD) are increased 5-10× and executive dysfunction can be disabling. We used diffusion imaging to investigate whether stroke-related differences in frontal white matter (WM) relate to cognitive impairments. Anterior forceps were isolated using tractography and sampled along the tract. Resulting metrics quantified frontal WM microstructure. Associations between WM metrics and parent ratings of ADHD symptoms (ADHD-5 rating scale) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)) were explored. Eighty-three children were recruited (arterial ischemic stroke [AIS] n = 26; periventricular venous infarction [PVI] n = 26; controls n = 31). WM metrics were altered for stroke groups compared to controls. Along-tract analyses showed differences in WM metrics in areas approximating the lesion as well as more remote differences at midline and in the nonlesioned hemisphere. WM metrics correlated with parental ratings of ADHD and executive function such that higher diffusivity values were associated with poorer function. These findings suggest that underlying microstructure of frontal white matter quantified via tractography may provide a relevant biomarker associated with cognition and behavior in children with perinatal stroke.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Stroke , White Matter , Attention Deficit Disorder with Hyperactivity/psychology , Child , Diffusion Tensor Imaging/methods , Executive Function , Female , Humans , Pregnancy , Stroke/complications , Stroke/diagnostic imaging , Stroke/pathology , White Matter/diagnostic imaging , White Matter/pathology
8.
Brain Imaging Behav ; 15(6): 2756-2765, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34386927

ABSTRACT

Developmental coordination disorder (DCD) is a neurodevelopmental disorder occurring in 5-6% of school-aged children. Converging evidence suggests that dysfunction within cortico-striatal and cortico-cerebellar networks may contribute to motor deficits in DCD, yet limited research has examined the brain morphology of these regions. Using T1-weighted magnetic resonance imaging the current study investigated cortical and subcortical volumes in 37 children with DCD, aged 8 to 12 years, and 48 controls of a similar age. Regional brain volumes of the thalamus, basal ganglia, cerebellum and primary motor and sensory cortices were extracted using the FreeSurfer recon-all pipeline and compared between groups. Reduced volumes within both the left and right pallidum (Left: F = 4.43, p = 0.039; Right: F = 5.24, p = 0.025) were observed in children with DCD; however, these results did not withstand correction for multiple comparisons. These findings provide preliminary evidence of altered subcortical brain structure in DCD. Future studies that examine the morphology of these subcortical regions are highly encouraged in order replicate these findings.


Subject(s)
Motor Skills Disorders , Basal Ganglia , Brain/diagnostic imaging , Cerebellum/diagnostic imaging , Child , Humans , Magnetic Resonance Imaging , Motor Skills Disorders/diagnostic imaging
9.
10.
Nat Rev Neurol ; 17(7): 415-432, 2021 07.
Article in English | MEDLINE | ID: mdl-34127850

ABSTRACT

Most cases of hemiparetic cerebral palsy are caused by perinatal stroke, resulting in lifelong disability for millions of people. However, our understanding of how the motor system develops following such early unilateral brain injury is increasing. Tools such as neuroimaging and brain stimulation are generating informed maps of the unique motor networks that emerge following perinatal stroke. As a focal injury of defined timing in an otherwise healthy brain, perinatal stroke represents an ideal human model of developmental plasticity. Here, we provide an introduction to perinatal stroke epidemiology and outcomes, before reviewing models of developmental plasticity after perinatal stroke. We then examine existing therapeutic approaches, including constraint, bimanual and other occupational therapies, and their potential synergy with non-invasive neurostimulation. We end by discussing the promise of exciting new therapies, including novel neurostimulation, brain-computer interfaces and robotics, all focused on improving outcomes after perinatal stroke.


Subject(s)
Brain Mapping/methods , Brain/growth & development , Neuronal Plasticity/physiology , Perinatal Care/methods , Stroke Rehabilitation/methods , Stroke/therapy , Brain/diagnostic imaging , Brain Mapping/trends , Brain-Computer Interfaces/trends , Cerebral Palsy/diagnostic imaging , Cerebral Palsy/etiology , Cerebral Palsy/therapy , Female , Humans , Infant, Newborn , Neuroimaging/methods , Neuroimaging/trends , Perinatal Care/trends , Pregnancy , Pregnancy Complications/diagnostic imaging , Pregnancy Complications/therapy , Robotics/methods , Robotics/trends , Stroke/diagnostic imaging , Stroke/etiology , Stroke Rehabilitation/trends
11.
J Osteopath Med ; 121(8): 687-691, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33979903

ABSTRACT

CONTEXT: The Comprehensive Osteopathic Medical Licensing Examination of the United States of America (COMLEX-USA) is a three level examination used as a pathway to licensure for students in osteopathic medical education programs. COMLEX-USA Level 2 includes a written assessment of Fundamental Clinical Sciences for Osteopathic Medical Practice (Level 2-Cognitive Evaluation [L2-CE]) delivered in a computer based format and separate performance evaluation (Level 2-Performance Evaluation [L2-PE]) administered through live encounters with standardized patients. L2-PE was designed to augment L2-CE. It is expected that the two examinations measure related yet distinct constructs. OBJECTIVES: To explore the concurrent validity of L2-CE with L2-PE. METHODS: First attempt test scores were obtained from the National Board of Osteopathic Medical Examiners database for 6,639 candidates who took L2-CE between June 2019 and May 2020 and matched to the students' L2-PE scores. The sample represented all colleges of osteopathic medicine and 97.5% of candidates who took L2-CE during the complete 2019-2020 test cycle. We calculated disattenuated correlations between the total score for L2-CE, the L2-CE scores for the seven competency domains (CD1 through CD7), and the L2-PE scores for the Humanistic Domain (HM) and Biomedical/Biomechanical Domain (BM). All scores were on continuous scales. RESULTS: Pearson correlations ranged from 0.10 to 0.88 and were all statically significant (p<0.01). L2-CE total score was most strongly correlated with CD2 (0.88) and CD3 (0.85). Pearson correlations between the L2-CE competency domain subscores ranged from 0.17 to 0.70, and correlations which included either HM or BM ranged from 0.10 to 0.34 with the strongest of those correlations being between BM and L2-CE total score (0.34) as well as between HM and BM (0.28).The largest increase between corresponding Pearson and disattenuated correlations was for pairs of scores with lower reliabilities such as CD5 and CD6, which had a Pearson correlation of 0.17 and a disattenuated correlation of 0.68. The smallest increase in correlations was observed in pairs of scores with larger reliabilities such as L2-CE total score and HM, which had a Pearson correlation of 0.23 and a disattenuated correlation of 0.28. The reliability of L2-CE was 0.87, 0.81 for HM, and 0.73 for BM. The reliabilities for the L2-CE competency domain scores ranged from 0.22 to 0.74. The small to moderate correlations between the L2-CE total score and the two L2-PE support the expectation that these examinations measure related but distinct constructs. The correlations between L2-PE and L2-CE competency domain subscores reflect the distribution of items defined by the L2-PE blueprint, providing evidence that the examinations are performing as designed. CONCLUSIONS: This study provides evidence supporting the validity of the blueprints for constructing COMLEX-USA Levels 2-CE and 2-PE examinations in concert with the purpose and nature of the examinations.


Subject(s)
Licensure, Medical , Osteopathic Medicine , Cognition , Educational Measurement , Humans , Osteopathic Medicine/education , Reproducibility of Results , United States
12.
Cortex ; 139: 27-42, 2021 06.
Article in English | MEDLINE | ID: mdl-33819679

ABSTRACT

The current study represents the first comprehensive examination of spatial, temporal and sustained attention following cerebellar damage. Results indicated that, compared to controls, cerebellar damage resulted in a larger cueing effect at the longest SOA - possibly reflecting a slowed the onset of inhibition of return (IOR) during a reflexive covert attention task, and reduced the ability to detect successive targets during an attentional blink task. However, there was little evidence to support the notion that cerebellar damage disrupted voluntary covert attention or the sustained attention to response task (SART). Lesion overlay data and supplementary voxel-based lesion symptom mapping (VLSM) analyses indicated that impaired performance on the reflexive covert attention and attentional blink tasks were related to damage to Crus II of the left posterior cerebellum. In addition, subsequent analyses indicated our results are not due to either general motor impairments or to damage to the deep cerebellar nuclei. Collectively these data demonstrate, for the first time, that the same cerebellar regions may be involved in both spatial and temporal visual attention.


Subject(s)
Attentional Blink , Cerebellum , Cerebellum/diagnostic imaging , Cues , Humans
13.
J Osteopath Med ; 121(7): 611-616, 2021 04 09.
Article in English | MEDLINE | ID: mdl-33831983

ABSTRACT

CONTEXT: The Comprehensive Osteopathic Medical Licensing Examination of the United States (COMLEX-USA) is a three level national standardized licensure examination for the practice of osteopathic medicine. The Comprehensive Medical Self Assessment Examination (COMSAE) is a three phase self assessment tool designed to gauge the base knowledge and ability of candidates preparing for COMLEX-USA. OBJECTIVES: To investigate how COMSAE Phase 1 (Phase 1) was used by candidates and how completing Phase 1 impacted their performance on the COMLEX-USA Level 1 (Level 1) examination. METHODS: Using data from the 2018-2019 administration of Level 1 and Phase 1 examinations, we counted the frequency of the unique Phase 1 forms taken by the candidates and calculated the correlation between the candidates' first attempt Phase 1 scores and the number of Phase 1 forms taken. We then calculated the correlation between the Level 1 scores and the Phase 1 scores. Next, we applied a multilevel regression model to examine the candidates' score improvement on the multiple Phase 1 forms taken. Finally, we investigated the effect of practicing through Phase 1 on the candidates' Level 1 performance using logistic regression models. RESULTS: The majority of candidates took one (2,414; 33.9%) to two (2,196; 30.8%) timed Phase 1 forms prior to the Level 1 examination. There was a significant negative correlation (r=-0.48, t(6,505)=-44.05, p<0.001) between the candidates' first attempt Phase 1 scores and the number of Phase 1 forms taken. There was a strong and positive correlation (r=0.66 to 0.74, p<0.001) between Phase 1 and Level 1 scores. With other variables controlled, on average, candidates' Phase 1 scores increased 23.2 points on one attempt from the previous attempt. Having the most recent Phase 1 score controlled, a greater number of Phase 1 forms taken was associated with an improvement on the Level 1 performance. CONCLUSIONS: The significant correlation between Phase 1 and Level 1 performance provided validity evidence for Phase 1. Moreover, our results suggested that candidates, especially those with lower performance on their initial Phase 1 attempt, might improve their Level 1 performance by taking multiple Phase 1 forms to monitor their academic improvement and gauge their readiness for Level 1.


Subject(s)
Osteopathic Medicine , Osteopathic Physicians , Educational Measurement , Humans , Licensure, Medical , Meaningful Use , Osteopathic Medicine/education , United States
14.
Can J Neurol Sci ; 48(2): 157-171, 2021 03.
Article in English | MEDLINE | ID: mdl-32727626

ABSTRACT

Perinatal stroke occurs around the time of birth and leads to lifelong neurological disabilities including hemiparetic cerebral palsy. Magnetic resonance imaging (MRI) has revolutionized our understanding of developmental neuroplasticity following early injury, quantifying volumetric, structural, functional, and metabolic compensatory changes after perinatal stroke. Such techniques can also be used to investigate how the brain responds to treatment (interventional neuroplasticity). Here, we review the current state of knowledge of how established and emerging neuroimaging modalities are informing neuroplasticity models in children with perinatal stroke. Specifically, we review structural imaging characterizing lesion characteristics and volumetrics, diffusion tensor imaging investigating white matter tracts and networks, task-based functional MRI for localizing function, resting state functional imaging for characterizing functional connectomes, and spectroscopy examining neurometabolic changes. Key challenges and exciting avenues for future investigations are also considered.


Subject(s)
Diffusion Tensor Imaging , Stroke , Brain/diagnostic imaging , Child , Humans , Magnetic Resonance Imaging , Neuroimaging , Neuronal Plasticity , Stroke/diagnostic imaging
15.
Front Hum Neurosci ; 14: 608131, 2020.
Article in English | MEDLINE | ID: mdl-33362497

ABSTRACT

Background and objectives: Developmental coordination disorder (DCD) is a neurodevelopmental motor disorder occurring in 5-6% of school-aged children. It is suggested that children with DCD show deficits in motor learning. Transcranial direct current stimulation (tDCS) enhances motor learning in adults and children but is unstudied in DCD. We aimed to investigate if tDCS, paired with motor skill training, facilitates motor learning in a pediatric sample with DCD. Methods: Twenty-eight children with diagnosed DCD (22 males, mean age: 10.62 ± 1.44 years) were randomized and placed into a treatment or sham group. Anodal tDCS was applied (1 mA, 20 min) in conjunction with fine manual training over 5 consecutive days. Children's motor functioning was assessed with the Purdue Pegboard Test and Jebsen-Taylor Hand Function Test at baseline, post-intervention and 6 weeks following intervention. Group differences in rates of motor learning and skill transfer/retention were examined using linear mixed modeling and repeated measures ANOVAs, respectively. Results: There were no serious adverse events or drop-outs and procedures were well-tolerated. Independent of group, all participants demonstrated improved motor scores over the 5 training days [F (69.280), p < 0.001, 95% CI (0.152, 0.376)], with no skill decay observed at retention. There was no interaction between intervention group and day [F (2.998), p = 0.086, 95% CI (-0.020, 0.297)]. Conclusion: Children with DCD demonstrate motor learning with long-term retention of acquired skill. Motor cortex tDCS did not enhance motor learning as seen in other populations. Before conclusions of tDCS efficacy can be drawn, additional carefully designed trials with reproducible results are required. Clinical Trial Registration: ClinicalTrials.gov: NCT03453983.

16.
Neurology ; 95(18): e2476-e2486, 2020 11 03.
Article in English | MEDLINE | ID: mdl-32887781

ABSTRACT

OBJECTIVE: To employ diffusion imaging connectome methods to explore network development in the contralesional hemisphere of children with perinatal stroke and its relationship to clinical function. We hypothesized alterations in global efficiency of the intact hemisphere would correlate with clinical disability. METHODS: Children with unilateral perinatal arterial (n = 26) or venous (n = 27) stroke and typically developing controls (n = 32) underwent 3T diffusion and T1 anatomical MRI and completed established motor assessments. A validated atlas coregistered to whole-brain tractography for each individual was used to estimate connectivity between 47 regions. Graph theory metrics (assortativity, hierarchical coefficient of regression, global and local efficiency, and small worldness) were calculated for the left hemisphere of controls and the intact contralesioned hemisphere of both stroke groups. Validated clinical motor assessments were then correlated with connectivity outcomes. RESULTS: Global efficiency was higher in arterial strokes compared to venous strokes (p < 0.001) and controls (p < 0.001) and was inversely associated with all motor assessments (all p < 0.012). Additional graph theory metrics including assortativity, hierarchical coefficient of regression, and local efficiency also demonstrated consistent differences in the intact hemisphere associated with clinical function. CONCLUSIONS: The structural connectome of the contralesional hemisphere is altered after perinatal stroke and correlates with clinical function. Connectomics represents a powerful tool to understand whole brain developmental plasticity in children with disease-specific cerebral palsy.


Subject(s)
Brain/growth & development , Connectome , Neuronal Plasticity/physiology , Stroke/physiopathology , White Matter/physiopathology , Adolescent , Brain/physiopathology , Case-Control Studies , Child , Diffusion Tensor Imaging , Female , Functional Laterality/physiology , Humans , Magnetic Resonance Imaging , Male , Young Adult
17.
Neuroimage Clin ; 28: 102508, 2020.
Article in English | MEDLINE | ID: mdl-33395997

ABSTRACT

Developmental neuroplasticity allows young brains to adapt via experiences early in life and also to compensate after injury. Why certain individuals are more adaptable remains underexplored. Perinatal stroke is an ideal human model of neuroplasticity with focal lesions acquired near birth in a healthy brain. Machine learning can identify complex patterns in multi-dimensional datasets. We used machine learning to identify structural and functional connectivity biomarkers most predictive of motor function. Forty-nine children with perinatal stroke and 27 controls were studied. Functional connectivity was quantified by fluctuations in blood oxygen-level dependent (BOLD) signal between regions. White matter tractography of corticospinal tracts quantified structural connectivity. Motor function was assessed using validated bimanual and unimanual tests. RELIEFF feature selection and random forest regression models identified predictors of each motor outcome using neuroimaging and demographic features. Unilateral motor outcomes were predicted with highest accuracy (8/54 features r = 0.58, 11/54 features, r = 0.34) but bimanual function required more features (51/54 features, r = 0.38). Connectivity of both hemispheres had important roles as did cortical and subcortical regions. Lesion size, age at scan, and type of stroke were predictive but not highly ranked. Machine learning regression models may represent a powerful tool in identifying neuroimaging biomarkers associated with clinical motor function in perinatal stroke and may inform personalized targets for neuromodulation.


Subject(s)
Stroke , White Matter , Brain/diagnostic imaging , Child , Humans , Machine Learning , Magnetic Resonance Imaging , Neuroimaging , Stroke/diagnostic imaging , White Matter/diagnostic imaging
18.
Neuroimage Clin ; 21: 101660, 2019.
Article in English | MEDLINE | ID: mdl-30639178

ABSTRACT

BACKGROUND: Perinatal stroke causes most hemiparetic cerebral palsy and leads to lifelong disability. Understanding developmental neuroplasticity following early stroke is increasingly translated into novel therapies. Diaschisis refers to alterations brain structures remote from, but connected to, stroke lesions. Ipsilesional thalamic diaschisis has been described following adult stroke but has not been investigated in perinatal stroke. We hypothesized that thalamic diaschisis occurs in perinatal stroke and its degree would be inversely correlated with clinical motor function. METHODS: Population-based, controlled cohort study. Participants were children (<19 years) with unilateral perinatal stroke (arterial ischemic stroke [AIS] or periventricular venous infarction [PVI]), anatomical magnetic resonance imaging (MRI) >6 months of age, symptomatic hemiparetic cerebral palsy, and no additional neurologic disorders. Typically developing controls had comparable age and gender proportions. T1-weighted anatomical scans were parcellated into 99 regions of interest followed by generation of regional volumes. The primary outcome was thalamic volume expressed as ipsilesional (ILTV), contralesional (CLTV) and thalamic ratio (CLTV/ILTV). Standardized clinical motor assessments were correlated with thalamic volume metrics. RESULTS: Fifty-nine participants (12.9 years old ±4.0 years, 46% female) included 20 AIS, 11 PVI, and 28 controls. ILTV was reduced in both AIS and PVI compared to controls (p < .001, p = .029, respectively). Ipsilesional thalamic diaschisis was not associated with clinical motor function. However, CLTV was significantly larger in AIS compared to both controls and PVI (p = .005, p < .001, respectively). CLTV was inversely correlated with all four clinical motor assessments (all p < .003). CONCLUSION: Bilateral thalamic volume changes occur after perinatal stroke. Ipsilesional volume loss is not associated with clinical motor function. Contralesional volume is inversely correlated with clinical motor function, suggesting the thalamus is involved in the known developmental plasticity that occurs in the contralesional hemisphere after early unilateral injury.


Subject(s)
Cerebral Palsy/physiopathology , Hand/physiopathology , Stroke/physiopathology , Thalamus/physiopathology , Adolescent , Adult , Brain/physiopathology , Child , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Retrospective Studies , Severity of Illness Index , Young Adult
19.
Stroke ; 50(1): 175-177, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30580726

ABSTRACT

Background and Purpose- Perinatal stroke causes most hemiparetic cerebral palsy and lifelong disability. Crossed cerebellar atrophy (CCA) is chronic cerebellar volume loss following contralateral motor pathway injury. We hypothesized that CCA is quantifiable in perinatal stroke and associated with poor motor outcome. Methods- Term-born children with perinatal stroke, magnetic resonance imaging beyond 6 months of age, and no additional neurological disorders were recruited. Blinded scorers measured cerebellar volumes expressed as ratios (contralesional/ipsilesional), with values <1 suggesting CCA. Motor outcomes including perinatal stroke outcome measure (PSOM) motor and cognitive scores (good/poor), Assisting Hand Assessment, and Melbourne Assessment were compared with cerebellar volume measures. Results- Seventy-three children met criteria (53% male). Mean cerebellar ratios were <1.0 (0.975±0.04; range, 0.885-1.079; P<0.001) suggesting occurrence of CCA. Cerebellar ratios did not differ between stroke types or across PSOM motor outcomes. Larger ipsilesional cerebellar volume was associated with poor PSOM cognitive outcome (P=0.042), possibly with poor PSOM motor outcome (P=0.063), and overall PSOM score (P=0.034). Conclusions- CCA occurs in perinatal stroke but is not strongly associated with motor outcome. However, ipsilesional cerebellar volume is associated with poor cognitive and overall outcomes.

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