Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic.
Epilepsy is a common neurological disorder with many causes. For temporal lobe epilepsy, antecedent insults are typically found. These risk factors include trauma or history of long fever-associated seizures (febrile status epilepticus) in childhood. Whereas the mechanisms by which such insults promote temporal lobe epilepsy are unknown, an extensive body of work has implicated inflammation and inflammatory mediators in both human and animal models of the disorder. However, direct evidence for an epileptogenic role for inflammation is lacking. Here we capitalized on a model where only a subgroup of insult-experiencing rodents develops epilepsy. We reasoned that if inflammation was important for generating epilepsy, then early inflammation should be more prominent in individuals destined to become epileptic compared with those that will not become epileptic. In addition, the molecular and temporal profile of inflammatory mediators would provide insights into which inflammatory pathways might be involved in the disease process. We examined inflammatory profiles in hippocampus and amygdala of individual rats and correlated them with a concurrent noninvasive, amygdalar magnetic resonance imaging epilepsy-predictive marker. We found significant individual variability in the expression of several important inflammatory mediators, but not in others. Of interest, a higher expression of a subset of hippocampal and amygdalar inflammatory markers within the first few hours following an insult correlated with the epilepsy-predictive signal. These findings suggest that some components of the inflammatory gene network might contribute to the process by which insults promote the development of temporal lobe epilepsy.
The muscle synergy concept provides a widely-accepted paradigm to break down the complexity of motor control. In order to identify the synergies, different matrix factorisation techniques have been used in a repertoire of fields such as prosthesis control and biomechanical and clinical studies. However, the relevance of these matrix factorisation techniques is still open for discussion since there is no ground truth for the underlying synergies. Here, we evaluate factorisation techniques and investigate the factors that affect the quality of estimated synergies. We compared commonly used matrix factorisation methods: Principal component analysis (PCA), Independent component analysis (ICA), Non-negative matrix factorization (NMF) and second-order blind identification (SOBI). Publicly available real data were used to assess the synergies extracted by each factorisation method in the classification of wrist movements. Synthetic datasets were utilised to explore the effect of muscle synergy sparsity, level of noise and number of channels on the extracted synergies. Results suggest that the sparse synergy model and a higher number of channels would result in better estimated synergies. Without dimensionality reduction, SOBI showed better results than other factorisation methods. This suggests that SOBI would be an alternative when a limited number of electrodes is available but its performance was still poor in that case. Otherwise, NMF had the best performance when the number of channels was higher than the number of synergies. Therefore, NMF would be the best method for muscle synergy extraction.
The role of the cerebrovascular network and its acute response to TBI is poorly defined and emerging evidence suggests that cerebrovascular reactivity is altered. We explored how cortical vessels are physically altered following TBI using a newly developed technique, vessel painting. We tested our hypothesis that a focal moderate TBI results in global decrements to structural aspects of the vasculature. Rats (naïve, sham-operated, TBI) underwent a moderate controlled cortical impact. Animals underwent vessel painting perfusion to label the entire cortex at 1 day post TBI followed by whole brain axial and coronal images using a wide-field fluorescence microscope. Cortical vessel network characteristics were analyzed for classical angiographic features (junctions, lengths) wherein we observed significant global (both hemispheres) reductions in vessel junctions and vessel lengths of 33% and 22%, respectively. Biological complexity can be quantified using fractal geometric features where we observed that fractal measures were also reduced significantly by 33%, 16% and 13% for kurtosis, peak value frequency and skewness, respectively. Acutely after TBI there is a reduction in vascular network and vascular complexity that are exacerbated at the lesion site and provide structural evidence for the bilateral hemodynamic alterations that have been reported in patients after TBI.
The described methods are a promising tool for identifying latent developmental features occurring throughout childhood EEG.
ObjectiveWe aimed 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.MethodsChildren 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 co-registered 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.ResultsGlobal 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.ConclusionsThe 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.
Rehabilitation applications using brain-computer interfaces (BCI) have recently shown encouraging results for motor recovery. Effective BCI neurorehabilitation has been shown to exploit neuroplastic properties of the brain through mental imagery tasks. However, these applications and results are currently restricted to adults. A systematic search reveals there is essentially no literature describing motor rehabilitative BCI applications that use electroencephalograms (EEG) in children, despite advances in such applications with adults. Further inspection highlights limited literature pursuing research in the field, especially outside of neurofeedback paradigms. Then the question naturally arises, do current literature trends indicate that EEG based BCI motor rehabilitation applications could be translated to children? To provide further evidence beyond the available literature for this particular topic, we present an exploratory survey examining some of the indirect literature related to motor rehabilitation BCI in children. Our goal is to establish if evidence in the related literature supports research on this topic and if the related studies can help explain the dearth of current research in this area. The investigation found positive literature trends in the indirect studies which support translating these BCI applications to children and provide insight into potential pitfalls perhaps responsible for the limited literature. Careful consideration of these pitfalls in conjunction with support from the literature emphasize that fully realized motor rehabilitation BCI applications for children are feasible and would be beneficial. • BCI intervention has improved motor recovery in adult patients and offer supplementary rehabilitation options to patients. • A systematic literature search revealed that essentially no research has been conducted bringing motor rehabilitation BCI applications to children, despite advances in BCI. • Indirect studies discovered from the systematic literature search, i.e. neurorehabilitation in children via BCI for autism spectrum disorder, provide insight into translating motor rehabilitation BCI applications to children. • Translating BCI applications to children is a relevant, important area of research which is relatively barren.
Higher-order tensor decompositions have hardly been used in muscle activity analysis despite multichannel electromyography (EMG) datasets naturally occurring as multi-way structures. Here, we seek to demonstrate and discuss the potential of tensor decompositions as a framework to estimate muscle synergies from 3 rd -order EMG tensors built by stacking repetitions of multi-channel EMG for several tasks. We compare the two most widespread tensor decomposition models -Parallel Factor Analysis (PARAFAC) and Tucker -in muscle synergy analysis of the wrist's three main Degree of Freedoms (DoFs) using the public first Ninapro database. Furthermore, we proposed a constrained Tucker decomposition (consTD) method for efficient synergy extraction building on the power of tensor decompositions. This method is proposed as a direct novel approach for shared and task-specific synergy estimation from two biomechanically related tasks. Our approach is compared with the current standard approach of repetitively applying non-negative matrix factorisation (NMF) to a series of the movements. The results show that the consTD method is suitable for synergy extraction compared to PARAFAC and Tucker. Moreover, exploiting the multi-way structure of muscle activity, the proposed methods successfully identified shared and taskspecific synergies for all three DoFs tensors. These were found to be robust to disarrangement with regard to task-repetition information, unlike the commonly used NMF. In summary, we demonstrate how to use tensors to characterise muscle activity and develop a new consTD method for muscle synergy extraction that could be used for shared and task-specific synergies identification. We expect that this study will pave the way for the development of novel muscle activity analysis methods based on higher-order techniques.
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