Dataset Information

Functional Connectivity Alterations in Children with Spastic and Dyskinetic Cerebral Palsy.

ABSTRACT: Cerebral palsy (CP) has long been investigated to be associated with a range of motor and cognitive dysfunction. As the two most common CP subtypes, spastic cerebral palsy (SCP) and dyskinetic cerebral palsy (DCP) may share common and distinct elements in their pathophysiology. However, the common and distinct dysfunctional characteristics between SCP and DCP on the brain network level are less known. This study aims to detect the alteration of brain functional connectivity in children with SCP and DCP based on resting-state functional MRI (fMRI). Resting-state networks (RSNs) were established based on the independent component analysis (ICA), and the functional network connectivity (FNC) was performed on the fMRI data from 16 DCP, 18 bilateral SCP, and 18 healthy children. Compared with healthy controls, altered functional connectivity within the cerebellum network, sensorimotor network (SMN), left frontoparietal network (LFPN), and salience network (SN) were found in DCP and SCP groups. Furthermore, the disconnections of the FNC consistently focused on the visual pathway; covariance of the default mode network (DMN) with other networks was observed both in DCP and SCP groups, while the DCP group had a distinct connectivity abnormality in motor pathway and self-referential processing-related connections. Correlations between the functional disconnection and the motor-related clinical measurement in children with CP were also found. These findings indicate functional connectivity impairment and altered integration widely exist in children with CP, suggesting that the abnormal functional connectivity is a pathophysiological mechanism of motor and cognitive dysfunction of CP.

SUBMITTER: Qin Y

PROVIDER: S-EPMC6114065 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Functional Connectivity Alterations in Children with Spastic and Dyskinetic Cerebral Palsy.

Qin Yun Y Li Yanan Y Sun Bo B He Hui H Peng Rui R Zhang Tao T Li Jianfu J Luo Cheng C Sun Chengyan C Yao Dezhong D Yao Dezhong D

Neural plasticity 20180815

Cerebral palsy (CP) has long been investigated to be associated with a range of motor and cognitive dysfunction. As the two most common CP subtypes, spastic cerebral palsy (SCP) and dyskinetic cerebral palsy (DCP) may share common and distinct elements in their pathophysiology. However, the common and distinct dysfunctional characteristics between SCP and DCP on the brain network level are less known. This study aims to detect the alteration of brain functional connectivity in children with SCP ...[more]

PMID: 30186320

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Project description:AimTo compare anterior and posterior standing balance reactions, as measured by single-stepping thresholds, in children with and without spastic cerebral palsy (CP).MethodSeventeen ambulatory children with spastic CP (eight males, nine females) and 28 typically developing children (13 males, 15 females; age range 5-12y, mean [SD] 9y 2mo [2y 3mo]), were included in this cross-sectional, observational study. Balance reaction skill was quantified as anterior and posterior single-stepping thresholds, or the treadmill-induced perturbations that consistently elicited a step in that direction. In order to understand the underlying mechanisms of between-group differences in stepping thresholds, dynamic stability was quantified using the minimum margin of stability. Ankle muscle activation latency, magnitude, and co-contraction were assessed with surface electromyography.ResultsWe observed an age and group interaction for anterior thresholds (p=0.001, partial η2 =0.24). At older (≈11y; p<0.001, partial η2 =0.48), but not younger (≈7y; p=0.33, partial η2 =0.02) ages, typically developing children had larger anterior thresholds than those with CP. In response to near-threshold anterior perturbations, older typically developing children recovered from more instability than their peers with CP (p=0.004, partial η2 =0.18). Older children had no between-group differences in ankle muscle activity. No between-group differences were observed in posterior thresholds.InterpretationThe effects of CP on balance reactions are age- and direction-specific. Older typically developing children are more able or willing to withhold a step when unstable.What this paper addsChildren with spastic cerebral palsy have age- and direction-specific balance-reaction impairments. Lower anterior stepping thresholds were observed in older, but not younger children. Older typically developing children withheld a forward step at higher levels of instability. No between-group differences were seen in posterior stepping thresholds.

Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.

Project description:The interaction between brain damage and motor function is not yet fully understood in children with spastic cerebral palsy (CP). Therefore, a semi-quantitative MRI (sqMRI) scale was used to explore whether identified brain lesions related to functional abilities and gait pathology in this population. A retrospective cohort of ambulatory children with spastic CP was selected [N = 104; 52 bilateral (bCP) and 52 unilateral (uCP)]. Extent and location-specific scores were defined according to the sqMRI scale guidelines. The gross motor function classification system (GMFCS), the gait profile score (GPS), GPSs per motion plane, gait variable scores (GVS) and multiple-joint (MJ) gait patterns were related to brain lesion scores. In all groups, the global total brain scores correlated to the GPS (total: r s = 0.404, p ? 0.001; bCP: r s = 0.335, p ? 0.05; uCP: r s = 0.493, p ? 0.001). The global total hemispheric scores correlated to the GMFCS (total: r s = 0.392, p ? 0.001; bCP: r s = 0.316, p ? 0.05; uCP: r s = 0.331, p ? 0.05). The laterality scores of the hemispheres in the total group correlated negatively to the GMFCS level (r s = -0.523, p ? 0.001) and the GVS-knee sagittal (r s = -0.311, p ? 0.01). Lesion location, for the total group demonstrated positive correlations between parietal lobe involvement and the GPS (r s = 0.321, p ? 0.001) and between periventricular layer damage and the GMFCS (r s = 0.348, p ? 0.001). Involvement of the anterior part of the corpus callosum (CC) was associated with the GVS-hip sagittal in all groups (total: r pb = 0.495, p ? 0.001; bCP: r pb = 0.357, p ? 0.05; uCP: r pb = 0.641, p ? 0.001). The global total hemispheric and laterality of the hemispheres scores differentiated between the minor and both the extension (p ? 0.001 and p ? 0.001) and flexion (p = 0.016 and p = 0.013, respectively) MJ patterns in the total group. Maximal periventricular involvement and CC intactness were associated with extension patterns (p ? 0.05 and p ? 0.001, respectively). Current findings demonstrated relationships between brain structure and motor function as well as pathological gait, in this cohort of children with CP. These results might facilitate the timely identification of gait pathology and, ultimately, guide individualized treatment planning of gait impairments in children with CP.

Dataset Information

Functional Connectivity Alterations in Children with Spastic and Dyskinetic Cerebral Palsy.

Publications

Functional Connectivity Alterations in Children with Spastic and Dyskinetic Cerebral Palsy.

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