Functional connectome reorganization relates to post-stroke motor recovery and structural and functional disconnection.
Ontology highlight
ABSTRACT:
SUBMITTER: Olafson ER
PROVIDER: S-EPMC8805675 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Stroke patients vary considerably in terms of outcomes: some patients present 'natural' recovery proportional to their initial impairment (fitters), while others do not (non-fitters). Thus, a key challenge in stroke rehabilitation is to identify individual recovery potential to make personalized decisions for neuro-rehabilitation, obviating the 'one-size-fits-all' approach. This goal requires (i) the prediction of individual courses of recovery in the acute stage; and (ii) an understanding of underlying neuronal network mechanisms. 'Natural' recovery is especially variable in severely impaired patients, underscoring the special clinical importance of prediction for this subgroup. Fractional anisotropy connectomes based on individual tractography of 92 patients were analysed 2 weeks after stroke (TA) and their changes to 3 months after stroke (TC - TA). Motor impairment was assessed using the Fugl-Meyer Upper Extremity (FMUE) scale. Support vector machine classifiers were trained to separate patients with natural recovery from patients without natural recovery based on their whole-brain structural connectomes and to define their respective underlying network patterns, focusing on severely impaired patients (FMUE < 20). Prediction accuracies were cross-validated internally, in one independent dataset and generalized in two independent datasets. The initial connectome 2 weeks after stroke was capable of segregating fitters from non-fitters, most importantly among severely impaired patients (TA: accuracy = 0.92, precision = 0.93). Secondary analyses studying recovery-relevant network characteristics based on the selected features revealed (i) relevant differences between networks contributing to recovery at 2 weeks and network changes over time (TC - TA); and (ii) network properties specific to severely impaired patients. Important features included the parietofrontal motor network including the intraparietal sulcus, premotor and primary motor cortices and beyond them also attentional, somatosensory or multimodal areas (e.g. the insula), strongly underscoring the importance of whole-brain connectome analyses for better predicting and understanding recovery from stroke. Computational approaches based on structural connectomes allowed the individual prediction of natural recovery 2 weeks after stroke onset, especially in the difficult to predict group of severely impaired patients, and identified the relevant underlying neuronal networks. This information will permit patients to be stratified into different recovery groups in clinical settings and will pave the way towards personalized precision neurorehabilitative treatment.
| S-EPMC8370413 | biostudies-literature
Project description:Behavioural deficits in stroke reflect both structural damage at the site of injury, and widespread network dysfunction caused by structural, functional, and metabolic disconnection. Two recent methods allow for the estimation of structural and functional disconnection from clinical structural imaging. This is achieved by embedding a patient's lesion into an atlas of functional and structural connections in healthy subjects, and deriving the ensemble of structural and functional connections that pass through the lesion, thus indirectly estimating its impact on the whole brain connectome. This indirect assessment of network dysfunction is more readily available than direct measures of functional and structural connectivity obtained with functional and diffusion MRI, respectively, and it is in theory applicable to a wide variety of disorders. To validate the clinical relevance of these methods, we quantified the prediction of behavioural deficits in a prospective cohort of 132 first-time stroke patients studied at 2 weeks post-injury (mean age 52.8 years, range 22-77; 63 females; 64 right hemispheres). Specifically, we used multivariate ridge regression to relate deficits in multiple functional domains (left and right visual, left and right motor, language, spatial attention, spatial and verbal memory) with the pattern of lesion and indirect structural or functional disconnection. In a subgroup of patients, we also measured direct alterations of functional connectivity with resting-state functional MRI. Both lesion and indirect structural disconnection maps were predictive of behavioural impairment in all domains (0.16 < R2 < 0.58) except for verbal memory (0.05 < R2 < 0.06). Prediction from indirect functional disconnection was scarce or negligible (0.01 < R2 < 0.18) except for the right visual field deficits (R2 = 0.38), even though multivariate maps were anatomically plausible in all domains. Prediction from direct measures of functional MRI functional connectivity in a subset of patients was clearly superior to indirect functional disconnection. In conclusion, the indirect estimation of structural connectivity damage successfully predicted behavioural deficits post-stroke to a level comparable to lesion information. However, indirect estimation of functional disconnection did not predict behavioural deficits, nor was a substitute for direct functional connectivity measurements, especially for cognitive disorders.
| S-EPMC7363494 | biostudies-literature
Project description:Epilepsy surgery consists of surgical resection of the epileptic focus and is recommended for patients with drug-resistant focal epilepsy. However, focal brain lesions can lead to effects in distant brain regions. Similarly, the focal resection in temporal lobe epilepsy surgery has been shown to lead to functional changes distant from the resection. Here we hypothesize that there are changes in brain function caused by temporal lobe epilepsy surgery in regions distant from the resection that are due to their structural disconnection from the resected epileptic focus. Therefore, the goal of this study was to localize changes in brain function caused by temporal lobe epilepsy surgery and relate them to the disconnection from the resected epileptic focus. This study takes advantage of the unique opportunity that epilepsy surgery provides to investigate the effects of focal disconnections on brain function in humans, which has implications in epilepsy and broader neuroscience. Changes in brain function from pre- to post-epilepsy surgery were quantified in a group of temporal lobe epilepsy patients (n = 36) using a measure of resting state functional MRI activity fluctuations. We identified regions with significant functional MRI changes that had high structural connectivity to the resected region in healthy controls (n = 96) and patients based on diffusion MRI. The structural disconnection from the resected epileptic focus was then estimated using presurgical diffusion MRI and related to the functional MRI changes from pre- to post-surgery in these regions. Functional MRI activity fluctuations increased from pre- to post-surgery in temporal lobe epilepsy in the two regions most highly structurally connected to the resected epileptic focus in healthy controls and patients-the thalamus and the fusiform gyrus ipsilateral to the side of surgery (PFWE < 0.05). Broader surgeries led to larger functional MRI changes in the thalamus than more selective surgeries (P < 0.05), but no other clinical variables were related to functional MRI changes in either the thalamus or fusiform. The magnitude of the functional MRI changes in both the thalamus and fusiform increased with a higher estimated structural disconnection from the resected epileptic focus when controlling for the type of surgery (P < 0.05). These results suggest that the structural disconnection from the resected epileptic focus may contribute to the functional changes seen after epilepsy surgery. Broadly, this study provides a novel link between focal disconnections in the structural brain network and downstream effects on function in distant brain regions.
| S-EPMC10473561 | biostudies-literature
Project description:IntroductionPost-stroke depressive symptoms (PSDS) are common and relevant for patient outcome, but their complex pathophysiology is ill understood. It likely involves social, psychological and biological factors. Lesion location is a readily available information in stroke patients, but it is unclear if the neurobiological substrates of PSDS are spatially localized. Building on previous analyses, we sought to determine if PSDS are associated with specific lesion locations, structural disconnection and/or localized functional diaschisis.MethodsIn a prospective observational study, we examined 270 patients with first-ever stroke with the Hospital Anxiety and Depression Scale (HADS) around 6 months post-stroke. Based on individual lesion locations and the depression subscale of the HADS we performed support vector regression lesion-symptom mapping, structural-disconnection-symptom mapping and functional lesion network-symptom-mapping, in a reanalysis of this previously published cohort to infer structure-function relationships.ResultsWe found that depressive symptoms were associated with (i) lesions in the right insula, right putamen, inferior frontal gyrus and right amygdala and (ii) structural disconnection in the right temporal lobe. In contrast, we found no association with localized functional diaschisis. In addition, we were unable to confirm a previously described association between depressive symptom load and a network damage score derived from functional disconnection maps.DiscussionBased on our results, and other recent lesion studies, we see growing evidence for a prominent role of right frontostriatal brain circuits in PSDS.
| S-EPMC10231644 | biostudies-literature
Project description:Central nervous system involvement in Fabry disease, a rare systemic X-linked lysosomal storage disorder, is characterized by the presence of heterogeneous but consistent functional and microstructural changes. Nevertheless, knowledge about the degree and extension of macro-scale brain connectivity modifications is to date missing. In this work, we performed connectomic analyses of diffusion and resting-state functional MRI to investigate changes of both structural and functional brain organization in Fabry disease, as well as to explore the relationship between the two and their clinical correlates. In this retrospective cross-sectional study, 46 patients with Fabry disease (28F, 42.2 ± 13.2years) and 49 healthy controls (21F, 42.3 ± 16.3years) were included. All subjects underwent an MRI examination including anatomical, diffusion and resting-state functional sequences. Images were processed to obtain quantitative structural and functional connectomes, where the connections between regions of interest were weighted by the total intra-axonal signal contribution of the corresponding bundle and by the correlation between blood-oxygen level-dependent time series, respectively. We explored between-group differences in terms of both global network properties, expressed with graph measures and specific connected subnetworks, identified using a network-based statistics approach. As exploratory analyses, we also investigated the possible association between cognitive performance and structural and functional connectome modifications at both global and subnetwork level in a subgroup of patients (n = 11). Compared with healthy controls, patients with Fabry disease showed a significantly reduced global efficiency (P = 0.005) and mean strength (P < 0.001) in structural connectomes, together with an increased modularity (P = 0.005) in functional networks. As for the network-based statistics analysis, a subnetwork with decreased structural connectivity in patients with Fabry disease compared with healthy controls emerged, with eight nodes mainly located at the level of frontal or deep grey-matter areas. When probing the relation between altered global network metrics and neuropsychological tests, correlations emerged between the structural and functional disruption with results at verbal and working memory tests, respectively. Furthermore, structural disruption at subnetwork level was associated with worse executive functioning, with a significant moderation effect of functional changes suggesting a compensation mechanism. Taken together, these results further expand the current knowledge about brain involvement in Fabry disease, showing widespread structural disconnection and functional reorganization, primarily sustained by loss in axonal integrity and correlating with cognitive performance.
| S-EPMC9327118 | biostudies-literature
Project description:BackgroundBiomarkers derived from neural activity of the brain present a vital tool for the prediction and evaluation of post-stroke motor recovery, as well as for real-time biofeedback opportunities.MethodsIn order to encapsulate recovery-related reorganization of brain networks into such biomarkers, we have utilized the generalized measure of association (GMA) and graph analyses, which include global and local efficiency, as well as hemispheric interdensity and intradensity. These methods were applied to electroencephalogram (EEG) data recorded during a study of 30 stroke survivors (21 male, mean age 57.9 years, mean stroke duration 22.4 months) undergoing 12 weeks of intensive therapeutic intervention.ResultsWe observed that decreases of the intradensity of the unaffected hemisphere are correlated (r s =-0.46;p<0.05) with functional recovery, as measured by the upper-extremity portion of the Fugl-Meyer Assessment (FMUE). In addition, high initial values of local efficiency predict greater improvement in FMUE (R 2=0.16;p<0.05). In a subset of 17 subjects possessing lesions of the cerebral cortex, reductions of global and local efficiency, as well as the intradensity of the unaffected hemisphere are found to be associated with functional improvement (r s =-0.60,-0.66,-0.75;p<0.05). Within the same subgroup, high initial values of global and local efficiency, are predictive of improved recovery (R 2=0.24,0.25;p<0.05). All significant findings were specific to the 12.5-25 Hz band.ConclusionsThese topological measures show promise for prognosis and evaluation of therapeutic outcomes, as well as potential application to BCI-enabled biofeedback.
| S-EPMC5501348 | biostudies-literature
Project description:BackgroundEvolution of motor function during the first months after stroke is stereotypically bifurcated, consisting of either recovery to about 70% of maximum possible improvement ("proportional recovery, PROP") or in little to no improvement ("poor recovery, POOR"). There is currently no evidence that any rehabilitation treatment will prevent POOR and favor PROP.ObjectiveTo perform a longitudinal and multimodal assessment of functional and structural changes in brain organization associated with PROP.MethodsFugl-Meyer Assessments of the upper extremity and high-density electroencephalography (EEG) were obtained from 63 patients, diffusion tensor imaging from 46 patients, at 2 and 4 weeks (T0) and at 3 months (T1) after stroke onset.ResultsWe confirmed the presence of 2 distinct recovery patterns (PROP and POOR) in our sample. At T0, PROP patients had greater integrity of the corticospinal tract (CST) and greater EEG functional connectivity (FC) between the affected hemisphere and rest of the brain, in particular between the ventral premotor and the primary motor cortex. POOR patients suffered from degradation of corticocortical and corticofugal fiber tracts in the affected hemisphere between T0 and T1, which was not observed in PROP patients. Better initial CST integrity correlated with greater initial global FC, which was in turn associated with less white matter degradation between T0 and T1.ConclusionsThese findings suggest links between initial CST integrity, systems-level cortical network plasticity, reduction of white matter atrophy, and clinical motor recovery after stroke. This identifies candidate treatment targets.
| S-EPMC6368856 | biostudies-literature
Project description:Structural connectivity analyses by means of diffusion-weighted imaging have substantially advanced the understanding of stroke-related network alterations and their implications for motor recovery processes and residual motor function. Analyses of the corticospinal tract, alternate corticofugal pathways as well as intrahemispheric and interhemispheric corticocortical connections have not only been related to residual motor function in cross-sectional studies, but have also been evaluated to predict functional recovery after stroke in longitudinal studies. This review will consist of an update on the available literature about structural connectivity analyses after ischemic motor stroke, followed by an outlook of possible future directions of research and applications.
| S-EPMC4774263 | biostudies-other
Project description:In this study, models based on quantitative imaging biomarkers of post-stroke structural connectome disruption were used to predict six-month outcomes in various domains. Demographic information and clinical MRIs were collected from 40 ischemic stroke subjects (age: 68.1 ± 13.2 years, 17 female, NIHSS: 6.8 ± 5.6). Diffusion-weighted images were used to create lesion masks, which were uploaded to the Network Modification (NeMo) Tool. The NeMo Tool, using only clinical MRIs, allows estimation of connectome disruption at three levels: whole brain, individual gray matter regions and between pairs of gray matter regions. Partial Least Squares Regression models were constructed for each level of connectome disruption and for each of the three six-month outcomes: applied cognitive, basic mobility and daily activity. Models based on lesion volume were created for comparison. Cross-validation, bootstrapping and multiple comparisons corrections were implemented to minimize over-fitting and Type I errors. The regional disconnection model best predicted applied cognitive (R(2) = 0.56) and basic mobility outcomes (R(2) = 0.70), while the pairwise disconnection model best predicted the daily activity measure (R(2) = 0.72). These results demonstrate that models based on connectome disruption metrics were more accurate than ones based on lesion volume and that increasing anatomical specificity of disconnection metrics does not always increase model accuracy, likely due to statistical adjustments for concomitant increases in data dimensionality. This work establishes that the NeMo Tool's measures of baseline connectome disruption, acquired using only routinely collected MRI scans, can predict 6-month post-stroke outcomes in various functional domains including cognition, motor function and daily activities. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC4905801 | biostudies-literature
Project description:BackgroundStroke remains one of the leading causes of long-term disability worldwide, and the development of effective restorative therapies is hindered by an incomplete understanding of intrinsic brain recovery mechanisms. Growing evidence indicates that the brain extracellular matrix (ECM) has major implications for neuroplasticity. Here we explored how perineuronal nets (PNNs), the facet-like ECM layers surrounding fast-spiking interneurons, contribute to neurological recovery after focal cerebral ischemia in mice with and without induced stroke tolerance.MethodsWe investigated the structural remodeling of PNNs after stroke using 3D superresolution stimulated emission depletion (STED) and structured illumination (SR-SIM) microscopy. Superresolution imaging allowed for the precise reconstruction of PNN morphology using graphs, which are mathematical constructs designed for topological analysis. Focal cerebral ischemia was induced by transient occlusion of the middle cerebral artery (tMCAO). PNN-associated synapses and contacts with microglia/macrophages were quantified using high-resolution confocal microscopy.ResultsPNNs undergo transient structural changes after stroke allowing for the dynamic reorganization of GABAergic input to motor cortical L5 interneurons. The coherent remodeling of PNNs and their perforating inhibitory synapses precedes the recovery of motor coordination after stroke and depends on the severity of the ischemic injury. Morphological alterations in PNNs correlate with the increased surface of contact between activated microglia/macrophages and PNN-coated neurons.ConclusionsOur data indicate a novel mechanism of post stroke neuroplasticity involving the tripartite interaction between PNNs, synapses, and microglia/macrophages. We propose that prolonging PNN loosening during the post-acute period can extend the opening neuroplasticity window into the chronic stroke phase.
| S-EPMC10474719 | biostudies-literature