Assessing the integrity of corticospinal pathways from primary and secondary cortical motor areas after stroke.
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ABSTRACT:
SUBMITTER: Schulz R
PROVIDER: S-EPMC3477824 | biostudies-literature | 2012 Aug
REPOSITORIES: biostudies-literature
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Assessing the integrity of corticospinal pathways from primary and secondary cortical motor areas after stroke.
Schulz Robert R Park Chang-Hyun CH Boudrias Marie-Hélène MH Gerloff Christian C Hummel Friedhelm C FC Ward Nick S NS
Stroke 20120703 8
<h4>Background and purpose</h4>Aside from the primary motor cortex, the corticospinal tract (CST) also receives fibers from dorsal and ventral premotor cortices and supplementary motor area, all of which might potentially contribute to motor function after stroke. We sought to quantify the microstructural integrity of CST originating from the hand representations in these 4 motor cortices separately and examined how these values related to hand motor impairment.<h4>Methods</h4>Probabilistic trac ...[more]
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Project description:ObjectiveMotor impairment after stroke has been related to infarct size, infarct location, and integrity of motor tracts. To determine the value of diffusion tensor imaging (DTI) as a predictor of motor outcome and its role as a structural surrogate marker of impairment in chronic stroke, we tested correlations between motor impairment and DTI-derived measures of motor tract integrity.MethodsThirty-five chronic stroke patients with varying degrees of recovery underwent DTI and motor impairment assessments. Fibers originating from the precentral gyrus were traced and separated into pyramidal tract (PT) and alternate motor fibers (aMF). Asymmetry indices of fiber number and regional fractional anisotropy (FA) values comparing lesional with nonlesional hemispheres were correlated with motor impairment scores and compared to an age-matched control group.ResultsFiber number and regional FA value asymmetry significantly differed between the groups with lower values in the patients' lesional hemispheres. Both measures significantly predicted motor impairment with stronger predictions when all motor tracts were combined as compared to predictions using only the PT. The pattern of motor tract damage (PT only vs PT and aMF) led to a classification of mild, moderate, or severe impairment with significant between-group differences in motor impairment scores.ConclusionsDiffusion tensor imaging-derived measures are valid structural markers of motor impairment. The integrity of all descending motor tracts, not merely the pyramidal tract, appears to account for stroke recovery. A 3-tier, hierarchical classification of impairment categories based on the pattern of motor tract damage is proposed that might be helpful in predicting recovery potential.
| S-EPMC3122304 | biostudies-literature
Project description:Movement-related brain activation patterns after subcortical stroke are characterized by relative overactivations in cortical motor areas compared with controls. In patients able to perform a motor task, overactivations are greater in those with more motor impairment. We hypothesized that recruitment of motor regions would shift from primary to secondary motor networks in response to impaired functional integrity of the corticospinal system (CSS). We measured the magnitude of brain activation using functional MRI during a motor task in eight chronic subcortical stroke patients. CSS functional integrity was assessed using transcranial magnetic stimulation to obtain stimulus/response curves for the affected first dorsal interosseus muscle, with a shallower gradient representing increasing disruption of CSS functional integrity. A negative correlation between the gradient of stimulus/response curve and magnitude of task-related brain activation was found in several motor-related regions, including ipsilesional posterior primary motor cortex [Brodmann area (BA) 4p], contralesional anterior primary motor cortex (BA 4a), bilateral premotor cortex, supplementary motor area, intraparietal sulcus, dorsolateral prefrontal cortex and contralesional superior cingulate sulcus. There were no significant positive correlations in any brain region. These results suggest that impaired functional integrity of the CSS is associated with recruitment of secondary motor networks in both hemispheres in an attempt to generate motor output to spinal cord motoneurons. Secondary motor regions are less efficient at generating motor output so this reorganization can only be considered partially successful in reducing motor impairment after stroke.
| S-EPMC3717515 | biostudies-literature
Project description:The structural integrity of the corticospinal tract (CST) after stroke is closely linked to the degree of motor impairment. Simple and reliable methods of assessing white matter integrity within the CST would facilitate the use of this measure in routine clinical practice. Commonly, diffusion tensor imaging is used to measure voxel-wise fractional anisotropy (FA) in a variety of regions of interest (ROIs) representing the CST. Several methods are currently in use with no consensus about which approach is best. ROIs are usually either the whole CST or the posterior limb of the internal capsule (PLIC). These are created manually on brain images or with reference to an individual's CST determined by tractography. Once the ROI has been defined, the FA can be reported as an absolute measure from the ipsilesional side or as a ratio in comparison to the contralesional side. Both corticospinal tracking and manual ROI definition in individual stroke patients are time consuming and subject to bias. Here, we investigated whether using a CST template derived from healthy volunteers was a feasible method for defining the appropriate ROI within which to measure changes in FA. We reconstructed the CST connecting the primary motor cortex to the ipsilateral pons in 23 age-matched control subjects and 21 stroke patients. An average healthy CST template was created from the 23 control subjects. For each patient, FA values were then calculated for both the template CST and for their own CST. We compared patients' FA metrics between the two tracts by considering four measures (FA in the ipsilesional side, FA in the contralesional side, FA ratio of the ipsilesional side to the contralesional side and FA asymmetry between the two sides) and in two tract-based ROIs (whole tract and tract section traversing the PLIC). There were no significant differences in FA metrics for either method, except for contralesional FA. Furthermore, we found that FA metrics relating to CST damage all correlated with motor ability post-stroke equally well. These results suggest that the healthy CST template could be a surrogate structure for defining tract-based ROIs with which to measure stroke patients' FA metrics, avoiding the necessity for CST tracking in individual patients. CST template-based automated quantification of structural integrity would greatly facilitate implementation of practical clinical applications of diffusion tensor imaging.
| S-EPMC3777681 | biostudies-literature
Project description:BackgroundPreserved integrity of the corticospinal tract (CST) is a marker of good upper-limb behavior and recovery following stroke. However, there is less understanding of neural mechanisms that might help facilitate upper-limb motor recovery in stroke survivors with extensive CST damage.ObjectiveThe purpose of this study was to investigate resting state functional connectivity in chronic stroke survivors with different levels of CST damage and to explore neural correlates of greater upper-limb motor performance in stroke survivors with compromised ipsilesional CST integrity.MethodsThirty chronic stroke survivors (24 males, aged 64.7 ± 10.8 years) participated in this study. Three experimental sessions were conducted to: 1) obtain anatomical (T1, T2) structural (diffusion) and functional (resting state) MRI sequences, 2) determine CST integrity with transcranial magnetic stimulation (TMS) and conduct assessments of upper-limb behavior, and 3) reconfirm CST integrity status. Participants were divided into groups according to the extent of CST damage. Those in the extensive CST damage group did not show TMS evoked responses and had significantly lower ipsilesional fractional anisotropy.ResultsOf the 30 chronic stroke survivors, 12 were categorized as having extensive CST damage. Stroke survivors with extensive CST damage had weaker functional connectivity in the ipsilesional sensorimotor network and greater functional connectivity in the ipsilesional fronto-parietal network compared to those with preserved CST integrity. For participants with extensive CST damage, improved motor performance was associated with greater functional connectivity of the ipsilesional fronto-parietal network and higher fractional anisotropy of the ipsilesional rostral superior longitudinal fasciculus.ConclusionsStroke survivors with extensive CST damage have greater resting state functional connectivity of an ipsilesional fronto-parietal network that appears to be a behaviorally relevant neural mechanism that improves upper-limb motor performance.
| S-EPMC7841401 | biostudies-literature
Project description:Anisotropy of descending motor pathways has repeatedly been linked to the severity of motor impairment following stroke-related damage to the corticospinal tract. Despite promising findings consistently tying anisotropy of the ipsilesional corticospinal tract to motor outcome, anisotropy is not yet utilized as a biomarker for motor recovery in clinical practice as several methodological constraints hinder a conclusive understanding of degenerative processes in the ipsilesional corticospinal tract and compensatory roles of other descending motor pathways. These constraints include estimating anisotropy in voxels with multiple fibre directions, sampling biases and confounds due to ageing-related atrophy. The present study addressed these issues by combining diffusion spectrum imaging with a novel compartmentwise analysis approach differentiating voxels with one dominant fibre direction (one-directional voxels) from voxels with multiple fibre directions. Compartmentwise anisotropy for bihemispheric corticospinal and extrapyramidal tracts was compared between 25 chronic stroke patients, 22 healthy age-matched controls, and 24 healthy young controls and its associations with motor performance of the upper and lower limbs were assessed. Our results provide direct evidence for Wallerian degeneration along the entire length of the ipsilesional corticospinal tract reflected by decreased anisotropy in descending fibres compared with age-matched controls, while ageing-related atrophy was observed more ubiquitously across compartments. Anisotropy of descending ipsilesional corticospinal tract voxels showed highly robust correlations with various aspects of upper and lower limb motor impairment, highlighting the behavioural relevance of Wallerian degeneration. Moreover, anisotropy measures of two-directional voxels within bihemispheric rubrospinal and reticulospinal tracts were linked to lower limb deficits, while anisotropy of two-directional contralesional rubrospinal voxels explained gross motor performance of the affected hand. Of note, the relevant extrapyramidal structures contained fibres crossing the midline, fibres potentially mitigating output from brain stem nuclei, and fibres transferring signals between the extrapyramidal system and the cerebellum. Thus, specific parts of extrapyramidal pathways seem to compensate for impaired gross arm and leg movements incurred through stroke-related corticospinal tract lesions, while fine motor control of the paretic hand critically relies on ipsilesional corticospinal tract integrity. Importantly, our findings suggest that the extrapyramidal system may serve as a compensatory structural reserve independent of post-stroke reorganization of extrapyramidal tracts. In summary, compartment-specific anisotropy of ipsilesional corticospinal tract and extrapyramidal tracts explained distinct aspects of motor impairment, with both systems representing different pathophysiological mechanisms contributing to motor control post-stroke. Considering both systems in concert may help to develop diffusion imaging biomarkers for specific motor functions after stroke.
| S-EPMC9798285 | biostudies-literature
Project description:Lesion load of the corticospinal tract (CST-LL), a measure of overlap between a stroke lesion and the CST, is one of the strongest predictors of motor outcomes following stroke. CST-LL is typically calculated by using a probabilistic map of the CST originating from the primary motor cortex (M1). However, higher order motor areas also have projections that contribute to the CST and motor control. In this retrospective study, we examined whether evaluating CST-LL from additional motor origins is more strongly associated with post-stroke motor severity than using CST-LL originating from M1 only. We found that lesion load to both the ventral premotor (PMv) cortex and M1 were more strongly related to stroke motor severity indexed by Fugl-Meyer Assessment cut-off scores than CST-LL of M1 alone, suggesting that higher order motor regions add clinical relevance to motor impairment.
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Project description:Background: The clinical outcome of patients suffering from stroke is dependent on multiple factors. The features of the lesion itself play an important role but clinical recovery is remarkably influenced by the plasticity mechanisms triggered by the stroke and occurring at a distance from the lesion. The latter translate into functional and structural changes of which cortical thickness might be easy to quantify one of the main players. However, studies on the changes of cortical thickness in brain areas beyond stroke lesion and their relationship to sensory-motor recovery are sparse. Objectives: To evaluate the effects of cerebral stroke on cortical thickness (CT) beyond the stroke lesion and its association with sensory-motor recovery. Materials and Methods: Five electronic databases (PubMed, Embase, Web of Science, Scopus and the Cochrane Library) were searched. Methodological quality of the included studies was assessed with the Newcastle-Ottawa Scale for non-randomized controlled trials and the Risk of Bias Cochrane tool for randomized controlled trials. Results: The search strategy retrieved 821 records, 12 studies were included and risk of bias assessed. In most of the included studies, cortical thinning was seen at the ipsilesional motor area (M1). Cortical thinning can occur beyond the stroke lesion, typically in regions anatomically connected because of anterograde degeneration. Nonetheless, studies also reported cortical thickening of regions of the unaffected hemisphere, likely related to compensatory plasticity. Some studies revealed a significant correlation between changes in cortical thickness of M1 or somatosensory (S1) cortical areas and motor function recovery. Discussion and Conclusions: Following a stroke, changes in cortical thickness occur both in regions directly connected to the stroke lesion and in contralateral hemisphere areas as well as in the cerebellum. The underlying mechanisms leading to these changes in cortical thickness are still to be fully understood and further research in the field is needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020200539; PROSPERO 2020, identifier: CRD42020200539.
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Project description:BackgroundPrognosis of long-term motor outcome of acute stroke patients with severe motor impairment is difficult to determine.ObjectiveOur primary goal was to evaluate the prognostic value of corticospinal tract (CST) injury on motor outcome of the upper limb compared with motor impairment level and lesion volume.MethodsIn all, 10 acute stroke patients with moderately severe to severe motor impairment of the upper limb underwent diffusion tensor imaging (DTI) and testing of upper limb strength and dexterity at acute, subacute, and chronic poststroke time points. A density-weighted CST atlas was constructed using DTI tractography data from normal participants. This CST atlas was applied, using a largely automated process, to DTI data from patients to quantify CST injury at each time point. Differences in axial diffusivity (AD), radial diffusivity (RD), and fractional anisotropy (FA) of the ipsilesional CST relative to the contralesional CST were measured.ResultsAcute loss in CST AD correlated most strongly and significantly with subacute and chronic strength and dexterity and remained significant after adjusting for acute motor impairment or lesion volume. Subacute loss in CST FA correlated most strongly with chronic dexterity, whereas subacute behavioral measures of limb strength correlated most strongly with chronic strength measures.ConclusionsLoss in acute CST AD and subacute CST FA are strong prognostic indicators of future motor functions of the upper limb for stroke patients with substantial initial motor impairment. DTI-derived measure of CST injury early after stroke may have utility in health care planning and in design of acute stroke clinical trials.
| S-EPMC4128905 | biostudies-literature
Project description:The rapid decline of injury-induced neuronal circuit remodelling after birth is paralleled by the accumulation of chondroitin sulphate proteoglycans (CSPGs) in the extracellular matrix, culminating with the appearance of perineuronal nets (PNNs) around parvalbumin-expressing GABAergic interneurons. We used a spinal cord injury (SCI) model to study the interplay between integrity of PNN CSPGs in the sensorimotor cortex, anatomical remodelling of the corticospinal tract (CST) and motor recovery in adult mice. We showed that thoracic SCI resulted in an atrophy of GABAergic interneurons in the axotomized hindlimb cortex, as well as in a more widespread downregulation of parvalbumin expression. In parallel, spontaneous changes in the integrity of CSPG glycosaminoglycan (GAG) chains associated with PNNs occurred at the boundary between motor forelimb and sensorimotor hindlimb cortex, a region previously showed to undergo reorganization after thoracic SCI. Surprisingly, full digestion of CSPG GAG chains by intracortical chondroitinase ABC injection resulted in an aggravation of motor deficits and reduced sprouting of the axotomized CST above the lesion. Altogether, our data show that changes in the expression pattern of GABAergic markers and PNNs occur in regions of the sensorimotor cortex undergoing spontaneous reorganization after SCI, but suggest that these changes have to be tightly controlled to be of functional benefit.
| S-EPMC4341008 | biostudies-literature
Project description:ObjectiveStudies on upper limb recovery following stroke have highlighted the importance of the structural and functional integrity of the corticospinal tract (CST) in determining clinical outcomes. However, such relationships have not been fully explored for the lower limb. We aimed to test whether variation in walking impairment was associated with variation in the structural or functional integrity of the CST.MethodsTranscranial magnetic stimulation was used to stimulate each motor cortex while EMG recordings were taken from the vastus lateralis (VL) bilaterally; these EMG measures were used to calculate both ipsilateral and contralateral recruitment curves for each lower limb. The slope of these recruitment curves was used to examine the strength of functional connectivity from the motor cortex in each hemisphere to the lower limbs in chronic stroke patients and to calculate a ratio between ipsilateral and contralateral outputs referred to as the functional connectivity ratio (FCR). The structural integrity of the CST was assessed using diffusion tensor MRI to measure the asymmetry in fractional anisotropy (FA) of the internal capsule. Lower limb impairment and walking speed were also measured.ResultsThe FCR for the paretic leg correlated with walking impairment, such that greater relative ipsilateral connectivity was associated with slower walking speeds. Asymmetrical FA values, reflecting reduced structural integrity of the lesioned CST, were associated with greater walking impairment. FCR and FA asymmetry were strongly positively correlated with each other.ConclusionsPatients with relatively greater ipsilateral connectivity between the contralesional motor cortex and the paretic lower limb were more behaviorally impaired and had more structural damage to their ipsilesional hemisphere CST.SignificanceMeasures of structural and functional damage may be useful in the selection of therapeutic strategies, allowing for more tailored and potentially more beneficial treatments.
| S-EPMC3778984 | biostudies-literature