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

Introduction: Adolescence is a period of remarkable development as children’s brains change to resemble adult brains. Resting state fMRI measures fluctuations in blood-oxygen signal from which we can infer functional connectivity (FC). Graph theory is a branch of mathematics that can quantify the complex patterns of connectivity and network architecture inherent in the functional connectome. An ideal graph theory analysis explores edges that are weighted, directional, and heterogenous (can be positive or negative). Recent developmental studies have applied graph theory to the functional connectome, yet due to the considerable complexity added by each facet, most ignore one or more aspects of an ideal graph theory analysis (directionality and heterogeneity). Methods: The present cross-sectional study measured FC in typically developing children, adolescents, and young adults (age 6-24 years) using 150+ echo-planar volumes (3.6mm isotropic voxels, repetition/echo time=2000/30ms) acquired at rest. A standard pre-processing pipeline was used, and the functional connectome was quantified using a weighted, directed graph analysis, including both positive and negative connections. Five different graph theory metrics were utilized to quantify developmental trajectories: connection density, modularity, clustering coefficient, global efficiency, and betweenness centrality. Positive and negative connections were analyzed separately, and age and sex associations were explored. Results: The total sample comprised 219 participants (mean age (SD) [range] = 14.1 (3.3) [6.5-24.0] years, 50% female). For positive connections, modularity and betweenness centrality increased with age (both p<0.001), while connection density, clustering coefficient, and global efficiency decreased with age (all p<0.001). By contrast, for negative connections, modularity and betweenness centrality decreased with age (p=0.002, p=0.003), while connection density, clustering coefficient , and global efficiency increased with age (p<0.001, p<0.001, p=0.003). Effects of sex, hemisphere, and their interaction were minimal, though global efficiency for negative connections was higher in the right hemisphere than the left (p<0.001). Conclusion: Graph theory appears to be a useful tool for quantifying the complex development of the functional connectome. The developmental changes presented here may be driven by an intrinsic pressure to balance functionality with low metabolic cost to maintain the network. The positive connection network appears to shift towards a more efficient conformation resembling “small-world” architecture. In contrast, the negative connection network seems to shift away from such efficient architecture, possibly to prioritize improving functionality before later refinement.

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.

Patient and public involvement (PPI) in the design and conduct of clinical trials has been increasingly encouraged by funders as an essential ingredient in

Objective: Characterize the structural organization of the afferent visual system in children with perinatal stroke (PS). Background: PS is a leading cause of lifelong disability, including cerebral palsy. Cerebral visual impairment (CVI) is another common outcome, yet mechanisms and developmental plasticity of the visual system after PS are not well understood. CVI can negatively impact how children engage with their environments, consequently affecting development, learning, therapy, play, and future independence. Methods: Fifty-one children with PS (22 arterial ischemic stroke (AIS), 29 periventricular venous infarction (PVI), mean 10.4 SD 2.5 years) were recruited from a large population-based sample along with 43 typically developing controls (TDC; mean age 11.3, SD 3.5 years). Diffusion weighted images were acquired from all children and the afferent visual tracts (optic chiasm to primary visual cortex) of both hemispheres were isolated using constrained spherical deconvolution (CSD)-based probabilistic tractography. Diffusion metrics of fractional anisotropy (FA) and mean diffusivity (MD) were extracted. Differences in visual pathway microstructure were examined between hemispheres and compared to TDCs. Results: Both stroke subtypes showed higher MD and lower FA compared to TDC (p<0.001) in the lesioned hemisphere and lower FA (p<0.001) in the non-lesioned hemisphere. Between-hemisphere differences showed lower FA in the AIS group (p<0.001) and higher MD (p<0.001) in children with PS. Conclusion: Visual pathway microstructure is altered in both hemispheres of children with PS, particularly those with AIS. Understanding the structural development of the visual pathways after PS may inform diagnostic, prognostic, and therapeutic strategies.

Visuoperceptual skills are crucial for childhood development yet remain poorly understood in children with perinatal arterial ischemic stroke (PAIS). This study examined visuoperceptual performance and structural connectivity of visual pathways in children with perinatal arterial ischemic stroke and typically developing controls. Participants completed the Motor-Free Visual Perceptual Test (MVPT), Apples Test, Jerry John's Basic Reading Inventory (BRI), and diffusion-weighted magnetic resonance imaging (MRI) with tractography of optic pathways. Visuoperceptual and reading scores were compared by group and lesion laterality. Twenty-six perinatal arterial ischemic stroke and 27 typically developing controls were recruited. Perinatal arterial ischemic stroke children scored significantly lower on the Motor-Free Visual Perceptual Test and Jerry John’s Basic Reading Inventory and took longer on the Apples Test. Right hemisphere lesions were associated with greater deficits in visuoperceptual and reading than left-sided lesions. No correlations were found between white matter microstructure and visuoperceptual scores. Findings highlight the need for early visuoperceptual screening in perinatal arterial ischemic stroke, regardless of motor status, and further investigation by lesion laterality.