Executive functioning, ADHD symptoms and resting state functional connectivity in children with perinatal stroke.

Perinatal stroke describes a group of focal, vascular brain injuries that occur early in development, often resulting in lifelong disability. Two types of perinatal stroke predominate, arterial ischemic stroke (AIS) and periventricular venous infarction (PVI). Though perinatal stroke is typically considered a motor disorder, other comorbidities commonly exist including attention-deficit hyperactivity disorder (ADHD) and deficits in executive function. Rates of ADHD symptoms are higher in children with perinatal stroke and deficits in executive function may also occur but underlying mechanisms are not known. We measured resting state functional connectivity in children with perinatal stroke using previously established dorsal attention, frontoparietal, and default mode network seeds. Associations with parental ratings of executive function and ADHD symptoms were examined. A total of 120 participants aged 6-19 years [AIS N = 31; PVI N = 30; Controls N = 59] were recruited. In comparison to typically developing peers, both the AIS and PVI groups showed lower intra- and inter-hemispheric functional connectivity values in the networks investigated. Group differences in between-network connectivity were also demonstrated, showing weaker anticorrelations between task-positive (frontoparietal and dorsal attention) and task-negative (default mode) networks in stroke groups compared to controls. Both within-network and between-network functional connectivity values were highly associated with parental reports of executive function and ADHD symptoms. These results suggest that differences in functional connectivity exist both within and between networks after perinatal stroke, the degree of which is associated with ADHD symptoms and executive function.

Functional Neuroplasticity and Motor Skill Change Following Gross Motor Interventions for Children With Diplegic Cerebral Palsy.

BACKGROUND: Gross motor intervention designs for children with diplegic cerebral palsy (DCP) require an improved understanding of the children's potential for neuroplasticity. OBJECTIVE: To identify relations between functional neuroplasticity and motor skill changes following gross motor interventions for children with DCP. METHODS: There were 17 participants with DCP (ages 8-16 years; 6 females; Gross Motor Function Classification System Level I [n = 9] and II [n = 8]). Each completed a 6-week gross motor intervention program that was directed toward achievement of individualized motor/physical activity goals. Outcomes were assessed pre/post and 4 to 6 months post-intervention (follow-up). An active ankle dorsiflexion task was completed during functional magnetic resonance imaging. The ratio of motor cortical activation volume in each hemisphere was calculated using a laterality index. The Challenge was the primary gross motor skill measure. Change over time and relations among outcomes were evaluated. RESULTS: Challenge scores improved post-intervention (4.57% points [SD 4.45], P = .004) and were maintained at follow-up (0.75% [SD 6.57], P = 1.000). The laterality index for dominant ankle dorsiflexion increased (P = .033), while non-dominant change was variable (P = .534). Contralateral activation (laterality index ≥+0.75) was most common for both ankles. Challenge improvements correlated with increased ipsilateral activity (negative laterality index) during non-dominant dorsiflexion (r = -.56, P = .045). Smaller activation volume during non-dominant dorsiflexion predicted continued gross motor gains at follow-up (R2 = .30, P = .040). CONCLUSIONS: Motor cortical activation during non-dominant ankle dorsiflexion is a modest indicator of the potential for gross motor skill change. Further investigation of patterns of neuroplastic change will improve our understanding of effects. CLINICALTRIALS.GOV REGISTRY: NCT02584491 and NCT02754128.

Structural brain network lateralization across childhood and adolescence.

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.

Structural connectivity of the sensorimotor network within the non-lesioned hemisphere of children with perinatal stroke.

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.

Comparison of sports skills movement training to lower limb strength training for independently ambulatory children with cerebral palsy: a randomised feasibility trial.

PURPOSE: The best approach to delivering advanced gross motor skills interventions for children with cerebral palsy (CP) is unknown. This study's aim was to assess trial feasibility and compare effectiveness of sports skills movement training (Brain change after Fun, Athletic Sports skills Training [BeFAST]) to conventional lower limb strength training (Brain change after Strength Training focusing ON Gait [BeSTRONG]) for improving advanced gross motor skills of children with CP. METHODS: Twenty independently ambulatory children with CP (mean age 12 ± 2.6 years) were randomly assigned to a 6-week programme of BeFAST or BeSTRONG, individualised to participant goals. Primary scientific outcome measures were the Challenge and Canadian Occupational Performance Measure (COPM) assessed pre/post and 4-month post-intervention. Process, resource, and management indicators assessed trial feasibility. RESULTS: There was no between group difference for the Challenge (p = 0.325), however significant post-intervention Challenge improvements were observed in BeFAST (p = 0.031) but not BeSTRONG (p = 0.055). Between group post-intervention scores were higher in BeFAST for COPM Performance (p = 0.001), and relative gains were maintained 4-month post-intervention. Pre-set criteria were met for 84% of feasibility indicators. CONCLUSIONS: Sports skills movement training may be an effective option to support advanced gross motor skill gains and target goals of independently ambulatory children with CP. Trial feasibility, including early evidence of effectiveness, indicates readiness for a full-scale randomised trial.Implications for rehabilitationChildren with cerebral palsy have potential to improve advanced gross motor skills.Strength training is a commonly used approach in gross motor therapy programmes.Sports skill training may be an effective option that better targets children's goals.

Frontal interhemispheric structural connectivity, attention, and executive function in children with perinatal stroke.

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.

Structural and functional connectivity of motor circuits after perinatal stroke: A machine learning study.

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.

Opening the Door to Physical Activity for Children With Cerebral Palsy: Experiences of Participants in the BeFAST or BeSTRONG Program.

This study explored children's experiences of participating in one-to-one physical training programs to identify how programs can best promote physical activity participation for children with cerebral palsy. A qualitative descriptive design with self-determination theory was used. Semistructured interviews were conducted with 6 children with cerebral palsy, age 8-14 years, who participated in a fundamental-movement-skills or lower-limb strength-training program. A hybrid approach of deductive and inductive analysis was used. Four themes developed: World around me (i.e., social/physical environments), Made for me (i.e., individualizing programs), Teach me how (i.e., teaching strategies facilitated skill learning), and I know me (i.e., sense of self). Results include recommendations for delivery of physical training programs. Using an individualized approach in a structured one-to-one program that employs skill-teaching strategies and self-reflection opportunities may provide a foundation to increase physical activity participation, related self-confidence, and desire to participate.

Comparison of a robotic-assisted gait training program with a program of functional gait training for children with cerebral palsy: design and methods of a two group randomized controlled cross-over trial.

BACKGROUND: Enhancement of functional ambulation is a key goal of rehabilitation for children with cerebral palsy (CP) who experience gross motor impairment. Physiotherapy (PT) approaches often involve overground and treadmill-based gait training to promote motor learning, typically as free walking or with body-weight support. Robotic-assisted gait training (RAGT), using a device such as the Lokomat®Pro, may permit longer training duration, faster and more variable gait speeds, and support walking pattern guidance more than overground/treadmill training to further capitalize on motor learning principles. Single group pre-/post-test studies have demonstrated an association between RAGT and moderate to large improvements in gross motor skills, gait velocity and endurance. A single published randomized controlled trial (RCT) comparing RAGT to a PT-only intervention showed no difference in gait kinematics. However, gross motor function and walking endurance were not evaluated and conclusions were limited by a large PT group drop-out rate. METHODS/DESIGN: In this two-group cross-over RCT, children are randomly allocated to the RAGT or PT arm (each with twice weekly sessions for eight weeks), with cross-over to the other intervention arm following a six-week break. Both interventions are grounded in motor learning principles with incorporation of individualized mobility-based goals. Sessions are fully operationalized through manualized, menu-based protocols and post-session documentation to enhance internal and external validity. Assessments occur pre/post each intervention arm (four time points total) by an independent assessor. The co-primary outcomes are gross motor functional ability (Gross Motor Function Measure (GMFM-66) and 6-minute walk test), with secondary outcome measures assessing: (a) individualized goals; (b) gait variables and daily walking amounts; and (c) functional abilities, participation and quality of life. Investigators and statisticians are blinded to study group allocation in the analyses, and assessors are blinded to treatment group. The primary analysis will be the pre- to post-test differences (change scores) of the GMFM-66 and 6MWT between RAGT and PT groups. DISCUSSION: This study is the first RCT comparing RAGT to an active gait-related PT intervention in paediatric CP that addresses gait-related gross motor, participation and individualized outcomes, and as such, is expected to provide comprehensive information as to the potential role of RAGT in clinical practice. Trial registration ClinicalTrials.gov NCT02196298.

Postural adjustments to support surface perturbations during reaching depend upon body-target reference frame.

We investigated whether target position relative to the body modifies the postural adjustments produced when reaching movements are perturbed by unexpected displacements of the support surface. Eleven healthy participants reached to a target located at their midline, acromion height and at 130% their outstretched arm length. They stood on two force plates mounted on a moveable platform, capable of delivering horizontal forward ramp-and-hold perturbations. Three types of trial were given: reach only (R), perturbations only (P) and reaching movements during which a perturbation was given at a random delay after reach onset (RP). The target could be mounted either on a frame suspended from the ceiling such that it remained world-fixed (exocentric target, RP/X) or at an equivalent position on the moving platform so that it moved with the body (egocentric target, RP/E). Arm and body 3D kinematics and muscle activity from the right tibialis anterior (rTA) and soleus (rSOL) muscles were recorded. Normalised rTA activity was significantly lower in RP than in P trials. Furthermore, long-latency rTA muscle activity was lower in RP/E than in RP/X conditions when perturbations were given during either the arm deceleration phase of reaching. The rSOL muscle activity was lowest for the RP/E (arm deceleration) condition. When balance is perturbed during reaching, the manner in which the target moves relative to the body determines the muscle activity produced in the lower-limb muscles. Furthermore, a target that moves with the body requires a different regulation of muscle activity compared with one that moves independently of the body.

Postural configuration does not alter unperturbed or perturbed reach movement kinematics.

This study investigated whether postural configuration has a significant effect upon the kinematics of arm movements when humans performed unconstrained reach movements to visual targets. Eight subjects were required to reach to static visual targets (unperturbed REACH movements) or correct reach movements when the position of a target unexpectedly changed during the execution of a planned movement (perturbed reaches, or online corrections, OC). Subjects were required to execute REACH and OC movements in sitting and standing (STAND) positions. The height of the targets, distance from the right shoulder (acromion) and eccentricity in terms of the body midline were standardized between the two postural conditions before movements begun. Unperturbed REACH movements were executed to a central target placed at 130 % of outstretched arm length, along the midline (0°). Perturbed (OC) movements involved subjects initiating an arm movement to the 0° target upon its illumination. Two hundred milliseconds after the onset of the hand movement, the 0° target was extinguished and the target at 60° to the right of the midline (still at 130% outstretched arm distance) illuminated. Subjects had to correct their reach movements online to the new target. Results demonstrated that, despite evident differences in postural kinematics between the four experimental conditions (e.g. pelvis obliquity and trunk/pelvis rotation), postural configuration had little or no effect upon the endpoint kinematics of the finger. Most importantly, the STAND position, with its greater postural constraints, did not affect the time taken to initiate an OC, nor did it lengthen the time taken to complete the REACH or OC movements. Our results suggest, therefore, that postural constraints are accounted for by the central nervous system when executing complex arm reaching movements.