Contralesional Hemisphere Research Articles

Large-scale resculpting of cortical circuits in children\xa0after surgical resection

Despite the relative successes in the surgical treatment of pharmacoresistant epilepsy, there is rather little research on the neural (re)organization that potentially subserves behavioral compensation. Here, we examined the post-surgical functional connectivity (FC) in children and adolescents who have undergone unilateral cortical resection and, yet, display remarkably normal behavior. Conventionally, FC has been investigated in terms of the mean correlation of the BOLD time courses extracted from different brain regions. Here, we demonstrated the value of segregating the voxel-wise relationships into mutually exclusive populations that were either positively or negatively correlated. While, relative to controls, the positive correlations were largely normal, negative correlations among networks were increased. Together, our results point to reorganization in the contralesional hemisphere, possibly suggesting competition for cortical territory due to the demand for representation of function. Conceivably, the ubiquitous negative correlations enable the differentiation of function in the reduced cortical volume following a unilateral resection.

Lesion Induced Error on Automated Measures of Brain Volume: Data From a Pediatric Traumatic Brain Injury Cohort.

Structural segmentation of T1-weighted (T1w) MRI has shown morphometric differences, both compared to controls and longitudinally, following a traumatic brain injury (TBI). While many patients with TBI present with abnormalities on structural MRI images, most neuroimaging software packages have not been systematically evaluated for accuracy in the presence of these pathology-related MRI abnormalities. The current study aimed to assess whether acute MRI lesions (MRI acquired 7–71 days post-injury) cause error in the estimates of brain volume produced by the semi-automated segmentation tool, Freesurfer. More specifically, to investigate whether this error was global, the presence of lesion-induced error in the contralesional hemisphere, where no abnormal signal was present, was measured. A dataset of 176 simulated lesion cases was generated using actual lesions from 16 pediatric TBI (pTBI) cases recruited from the emergency department and 11 typically-developing controls. Simulated lesion cases were compared to the “ground truth” of the non-lesion control-case T1w images. Using linear mixed-effects models, results showed that hemispheric measures of cortex volume were significantly lower in the contralesional-hemisphere compared to the ground truth. Interestingly, however, cortex volume (and cerebral white matter volume) were not significantly different in the lesioned hemisphere. However, percent volume difference (PVD) between the simulated lesion and ground truth showed that the magnitude of difference of cortex volume in the contralesional-hemisphere (mean PVD = 0.37%) was significantly smaller than that in the lesioned hemisphere (mean PVD = 0.47%), suggesting a small, but systematic lesion-induced error. Lesion characteristics that could explain variance in the PVD for each hemisphere were investigated. Taken together, these results suggest that the lesion-induced error caused by simulated lesions was not focal, but globally distributed. Previous post-processing approaches to adjust for lesions in structural analyses address the focal region where the lesion was located however, our results suggest that focal correction approaches are insufficient for the global error in morphometric measures of the injured brain.

Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

The modulatory effects of bilateral arm training (BAT) on the brain in stroke patients: a systematic review.

To systematically review the modulatory effects of bilateral arm training (BAT) on the brain of stroke patients in contrast to unilateral arm training (UAT) or regular motor training. We conducted a literature search using PubMed, EMBASE, MEDLINE, and Science Citation Index Expanded databases from the inception to March 2019 for identifying any relevant studies. Two authors independently screened the literature, extracted data, and qualitatively described the included studies. Eleven studies with a total of 225 stroke patients were included in this review. 156 out of those participants received neuroimaging or neurophysiological examinations. Six studies reported enhanced activation of the ipsilesional primary motor area (M1) induced by BAT, as measured by MEP and fMRI. Beyond the M1, three studies showed that supplementary motor area (SMA) was activated, and three studies found the primary sensory cortex area (S1) was activated by BAT in stroke patients, as measured by fMRI. One article showed that the inter-/intra-hemispheric functional connections of the sensorimotor network were more highly strengthened after BAT than regular motor training, in particular the functional connectivity between the SMA and the M1 in the bi-hemispheres. Three studies reported that BAT increased the inhibitory flow from the ipsilesional hemisphere to the contralesional hemisphere, as measured by interhemispheric transcallosal inhibition (IHI). However, the superiority of BAT in inducing a symmetric IHI than UAT was controversial. BAT is potentially more effective than UAT in improving upper limb recovery after stroke by activating the ipsilesional primary motor area (M1), supplementary motor area (SMA), and primary sensory cortex (S1) and enhancing the intra-hemispheric and interhemispheric connectivity within the sensorimotor network and the cortical motor system.

White Matter Hyperintensity Burden Is Associated With Hippocampal Subfield Volume in Stroke.

White matter hyperintensities of presumed vascular origin (WMH) are a prevalent form of cerebral small-vessel disease and an important risk factor for post-stroke cognitive dysfunction. Despite this prevalence, it is not well understood how WMH contributes to post-stroke cognitive dysfunction. Preliminary findings suggest that increasing WMH volume is associated with total hippocampal volume in chronic stroke patients. The hippocampus, however, is a complex structure with distinct subfields that have varying roles in the function of the hippocampal circuitry and unique anatomical projections to different brain regions. For these reasons, an investigation into the relationship between WMH and hippocampal subfield volume may further delineate how WMH predispose to post-stroke cognitive dysfunction. In a prospective study of acute ischemic stroke patients with moderate/severe WMH burden, we assessed the relationship between quantitative WMH burden and hippocampal subfield volumes. Patients underwent a 3T MRI brain within 2–5 days of stroke onset. Total WMH volume was calculated in a semi-automated manner. Mean cortical thickness and hippocampal volumes were measured in the contralesional hemisphere. Total and subfield hippocampal volumes were measured using an automated, high-resolution, ex vivo computational atlas. Linear regression analyses were performed for predictors of total and subfield hippocampal volumes. Forty patients with acute ischemic stroke and moderate/severe white matter hyperintensity burden were included in this analysis. Median WMH volume was 9.0 cm3. Adjusting for intracranial volume and stroke laterality, age (β = −3.7, P < 0.001), hypertension (β = −44.7, P = 0.04), WMH volume (β = −0.89, P = 0.049), and mean cortical thickness (β = 286.2, P = 0.006) were associated with total hippocampal volume. In multivariable analysis, age (β = −3.3, P < 0.001) and cortical thickness (β = 205.2, P = 0.028) remained independently associated with total hippocampal volume. In linear regression for predictors of hippocampal subfield volume, increasing WMH volume was associated with decreased hippocampal-amygdala transition area volume (β = −0.04, P = 0.001). These finding suggest that in ischemic stroke patients, increased WMH burden is associated with selective hippocampal subfield degeneration in the hippocampal-amygdala transition area.

Connectivity-Related Roles of Contralesional Brain Regions for Motor Performance Early after Stroke.

Hemiparesis after stroke is associated with increased neural activity not only in the lesioned but also in the contralesional hemisphere. While most studies have focused on the role of contralesional primary motor cortex (M1) activity for motor performance, data on other areas within the unaffected hemisphere are scarce, especially early after stroke. We here combined functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to elucidate the contribution of contralesional M1, dorsal premotor cortex (dPMC), and anterior intraparietal sulcus (aIPS) for the stroke-affected hand within the first 10 days after stroke. We used "online" TMS to interfere with neural activity at subject-specific fMRI coordinates while recording 3D movement kinematics. Interfering with aIPS activity improved tapping performance in patients, but not healthy controls, suggesting a maladaptive role of this region early poststroke. Analyzing effective connectivity parameters using a Lasso prediction model revealed that behavioral TMS effects were predicted by the coupling of the stimulated aIPS with dPMC and ipsilesional M1. In conclusion, we found a strong link between patterns of frontoparietal connectivity and TMS effects, indicating a detrimental influence of the contralesional aIPS on motor performance early after stroke.

Electroencephalography Mu Rhythm Changes and Decreased Spasticity After Repetitive Peripheral Magnetic Stimulation in Patients Following Stroke.

Background: Spasticity is common among patients with stroke. Repetitive peripheral magnetic stimulation (rPMS) is a painless and noninvasive therapy that is a promising approach to reducing spasticity. However, the central mechanism of this therapy remains unclear. Changes in cortical activity and decreased spasticity after rPMS intervention require further exploration. The aim of this study was to explore the electroencephalography (EEG) mu rhythm change and decrease in spasticity after rPMS intervention in patients with stroke.Materials and methods: A total of 32 patients with spasticity following stroke were recruited in this study and assigned to the rPMS group (n = 16) or sham group (n = 16). The modified Ashworth scale, modified Tardieu scale, and Fugl–Meyer assessment of the upper extremity were used to assess changes in upper limb spasticity and motor function. Before and after the rPMS intervention, EEG evaluation was performed to detect EEG mu rhythm changes in the brain.Results: After one session of rPMS intervention, spasticity was reduced in elbow flexors (p < 0.05) and wrist flexors (p < 0.05). Upper limb motor function measured according to the Fugl–Meyer assessment was improved (p < 0.05). In the rPMS group, the power of event-related desynchronization decreased in the mu rhythm band (8–12 Hz) in the contralesional hemisphere (p < 0.05).Conclusions: The results indicate that rPMS intervention reduced spasticity. Cortical activity changes may suggest this favorable change in terms of its neurological effects on the central nervous system.

Neural correlates of spontaneous language production in two patients with right hemispheric language dominance

ABSTRACT Background It is not conclusively explored what kind of reorganisation processes are set off after a stroke with resulting aphasia. Since the development of functional Magnetic Resonance Imaging (fMRI), linguistic processes and their neural representation have been researched, especially in aphasic patients after left hemispheric insult. The situation differs in aphasic patients with crossed aphasia or aphasia after a right hemispheric lesion, for which only few studies have been carried out. In order to close this gap, the present study deals with the localisation of language functions in the brain of patients with crossed aphasia and right hemispheric language dominance. Aim The objective of the current study was to provide insights into the neural correlates of continuous aphasic language production of patients with right hemispheric language dominance. Based on the current state of research, a mirror image representation was expected. Methods & Procedures Two patients with fluent aphasia due to right hemisphere lesions, one presenting with crossed aphasia, described complex pictures. The continuous language output was transcribed and categorised into events. Lexical search (i.e. the difference between unimpaired speaking and word-finding difficulties) was analysed using fMRI. The neural activation clusters were compared with the corresponding areas of a control group consisting of 12 patients with left hemispheric aphasia. Outcomes & Results The analysis of the behavioural data revealed word-finding difficulties as one of the most limiting factors in the spontaneous language output of the patients. The neural correlates of lexical search (unimpaired minus impaired) were observed in four activation clusters both patients had in common. Each cluster was predominantly localised in the contra-lesional hemisphere. Compared to the corresponding areas of the control group, in general, a mirrored image representation could be confirmed. Conclusions The combination of detailed linguistic analysis and fMRI confirmed the assumption of mirrored language organisation for anomia in continuous language production. Moreover, the study might add to a more general understanding of the contribution of the contra-lesional hemisphere to language recovery in aphasia after left or right hemisphere damage.

Functional Mapping before and after Low-Grade Glioma Surgery: A New Way to Decipher Various Spatiotemporal Patterns of Individual Neuroplastic Potential in Brain Tumor Patients.

Simple SummaryBeyond intraoperative electrostimulation mapping in awake patients (the gold-standard for brain tumor surgery), non-invasive FNI/TMS can be repeated before and after resection(s). These techniques enable longitudinal investigation of neural reorganization, especially in low-grade gliomas, which can generate neuroplasticity in patients with usually no or slight neurological deficits, despite neoplasm within “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time were evidenced, with structural changes as well as modifications of intra-hemispheric and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation.Intraoperative direct electrostimulation mapping (DEM) is currently the gold-standard for glioma surgery, since functional-based resection allows an optimization of the onco-functional balance (increased resection with preserved quality of life). Besides intrasurgical awake mapping of conation, cognition, and behavior, preoperative mapping by means of functional neuroimaging (FNI) and transcranial magnetic stimulation (TMS) has increasingly been utilized for surgical selection and planning. However, because these techniques suffer from several limitations, particularly for direct functional mapping of subcortical white matter pathways, DEM remains crucial to map neural connectivity. On the other hand, non-invasive FNI and TMS can be repeated before and after surgical resection(s), enabling longitudinal investigation of brain reorganization, especially in slow-growing tumors like low-grade gliomas. Indeed, these neoplasms generate neuroplastic phenomena in patients with usually no or only slight neurological deficits at diagnosis, despite gliomas involving the so-called “eloquent” structures. Here, data gained from perioperative FNI/TMS mapping methods are reviewed, in order to decipher mechanisms underpinning functional cerebral reshaping induced by the tumor and its possible relapse, (re)operation(s), and postoperative rehabilitation. Heterogeneous spatiotemporal patterns of rearrangement across patients and in a single patient over time have been evidenced, with structural changes as well as modifications of intra-hemispheric (in the ipsi-lesional and/or contra-lesional hemisphere) and inter-hemispheric functional connectivity. Such various fingerprints of neural reconfiguration were correlated to different levels of cognitive compensation. Serial multimodal studies exploring neuroplasticity might lead to new management strategies based upon multistage therapeutic approaches adapted to the individual profile of functional reallocation.

Developmental neuroplasticity of the white matter connectome in children with perinatal stroke.

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. Children 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 coregistered 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. Global 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. The 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.

Variable Interhemispheric Asymmetry in Layer V of the Supplementary Motor Area following Cervical Hemisection in Adult Macaque Monkeys.

Motor cortical areas from both hemispheres play a role during functional recovery after a unilateral spinal cord injury (SCI). However, little is known about the morphologic and phenotypical differences that a SCI could trigger in corticospinal (CS) neurons of the ipsilesional and contralesional hemisphere. Using an SMI-32 antibody which specifically labeled pyramidal neurons in cortical Layers V, we investigated the impact of a unilateral cervical cord lesion on the rostral part (F6) and caudal part (F3) of the supplementary motor area (SMA) in both hemispheres of eight adult macaque monkeys compared with four intact control monkeys. We observed in F3 (but not in F6) interindividual variable and adaptive interhemispheric asymmetries of SMI-32-positive Layer V neuronal density and dendritic arborization, which are strongly correlated with the extent of the SCI as well as the duration of functional recovery, but not with the extent (percentage) of functional recovery.

Intracortical Circuits in the Contralesional Primary Motor Cortex in Patients With Chronic Stroke After Botulinum Toxin Type A Injection: Case Studies.

Spasticity and motor recovery are both related to neural plasticity after stroke. A balance of activity in the primary motor cortex (M1) in both hemispheres is essential for functional recovery. In this study, we assessed the intracortical inhibitory and facilitatory circuits in the contralesional M1 area in four patients with severe upper limb spasticity after chronic stroke and treated with botulinum toxin-A (BoNT-A) injection and 12 weeks of upper limb rehabilitation. There was little to no change in the level of spasticity post-injection, and only one participant experienced a small improvement in arm function. All reported improvements in quality of life. However, the levels of intracortical inhibition and facilitation in the contralesional hemisphere were different at baseline for all four participants, and there was no clear pattern in the response to the intervention. Further investigation is needed to understand how BoNT-A injections affect inhibitory and facilitatory circuits in the contralesional hemisphere, the severity of spasticity, and functional improvement.

Changes in electroencephalography complexity and functional magnetic resonance imaging connectivity following robotic hand training in chronic stroke

ABSTRACT Introduction: In recent years, robotic training has been utilized for recovery of motor control in patients with motor deficits. Along with clinical assessment, electrical patterns in the brain have emerged as a marker for studying changes in the brain associated with brain injury and rehabilitation. These changes mainly involve an imbalance between the two hemispheres. We aimed to study the effect of brain computer interface (BCI)-based robotic hand training on stroke subjects using clinical assessment, electroencephalographic (EEG) complexity analysis, and functional magnetic resonance imaging (fMRI) connectivity analysis. Method: Resting-state simultaneous EEG-fMRI was conducted on 14 stroke subjects before and after training who underwent 20 sessions robot hand training. Fractal dimension (FD) analysis was used to assess neuronal impairment and functional recovery using the EEG data, and fMRI connectivity analysis was performed to assess changes in the connectivity of brain networks. Results: FD results indicated a significant asymmetric difference between the ipsilesional and contralesional hemispheres before training, which was reduced after robotic hand training. Moreover, a positive correlation between interhemispheric asymmetry change for central brain region and change in Fugl Meyer Assessment (FMA) scores for upper limb was observed. Connectivity results showed a significant difference between pre-training interhemispheric connectivity and post-training interhemispheric connectivity. Moreover, the change in connectivity correlated with the change in FMA scores. Results also indicated a correlation between the increase in connectivity for motor regions and decrease in FD interhemispheric asymmetry for central brain region covering the motor area. Conclusion: In conclusion, robotic hand training significantly facilitated stroke motor recovery, and FD, along with connectivity analysis can detect neuroplasticity changes.

Contralesional White Matter Alterations in Patients After Hemispherotomy.

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.

Neurobiology of Recovery of Motor Function after Stroke: The Central Nervous System Biomarker Effects of Constraint-Induced Movement Therapy.

Recovery of motor function after stroke involves many biomarkers. This review attempts to identify the biomarker effects responsible for recovery of motor function following the use of Constraint-Induced Movement Therapy (CIMT) and discuss their implications for research and practice. From the studies reviewed, the biomarker effects identified include improved perfusion of motor areas and brain glucose metabolism; increased expression of proteins, namely, Brain-Derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and Growth-Associated Protein 43 (GAP-43); and decreased level of Gamma-Aminobutyric Acid (GABA). Others include increased cortical activation, increased motor map size, and decreased interhemispheric inhibition of the ipsilesional hemisphere by the contralesional hemisphere. Interestingly, the biomarker effects correlated well with improved motor function. However, some of the biomarker effects have not yet been investigated in humans, and they require that CIMT starts early on poststroke. In addition, one study seems to suggest the combined use of CIMT with other rehabilitation techniques such as Transcortical Direct Stimulation (tDCs) in patients with chronic stroke to achieve the biomarker effects. Unfortunately, there are few studies in humans that implemented CIMT during early poststroke. Thus, it is important that more studies in humans are carried out to determine the biomarker effects of CIMT especially early on poststroke, when there is a greater opportunity for recovery. Furthermore, it should be noted that these effects are mainly in ischaemic stroke.

Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats.

Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for “oxidative phosphorylation” was significantly upregulated while fourteen other gene sets including “apoptosis”, “hypoxia” and “reactive oxygen species” showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

Biochemical and structural magnetic resonance imaging in chronic stroke and the relationship with upper extremity motor function

BackgroundRecovery of upper extremity (UE) motor function after stroke is variable from one to another due to heterogeneity of stroke pathology. Structural and biochemical magnetic resonance imaging of the primary motor cortex (M1) have been used to document reorganization of neural activity after stroke.ObjectiveTo assess cortical biochemical and structural causes of delayed recovery of UE motor function impairment in chronic subcortical ischemic stroke patients.MethodologyA cross-sectional study with fifty patients were enrolled: thirty patients with chronic (> 6 months) subcortical ischemic stroke suffering from persistent UE motor function impairment (not improved group) and twenty patients with chronic subcortical ischemic stroke and improved UE motor function (improved group). We recruited a group of (16) age-matched healthy subjects. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed to measure n-acetylaspartate (NAA) and glutamate+glutamine (Glx) ratios relative to creatine (Cr) in the precentral gyrus which represent M1of hand area in both ipsilesional and contralesional hemispheres. Brain magnetic resonance imaging (MRI) to measure precentral gyral thickness is representing the M1of hand area. UE motor function assessment is using the Fugl Meyer Assessment (FMA-UE) Scale.ResultsThe current study found that ipslesional cortical thickness was significantly lower than contralesional cortical thickness among all stroke patients. Our study found that ipsilesional NAA/Cr ratio was lower than contralesional NAA/Cr among stroke patients. UE and hand motor function by FMA-UE showed highly statistically significant correlation with ipsilesional cortical thickness and ipsilesional NAA/Cr ratio, more powerful with NAA/Cr ratio.ConclusionWe concluded that persistent motor impairment in individuals with chronic subcortical stroke may be at least in part related to ipsilesional structural and biochemical changes in motor areas remote from infarction in form of decreased cortical thickness and NAA/Cr ratio which had the strongest relationship with that impairment.

Altered Corticomuscular Coherence (CMCoh) Pattern in the Upper Limb During Finger Movements After Stroke.

Background: Proximal compensation to the distal movements is commonly observed in the affected upper extremity (UE) of patients with chronic stroke. However, the cortical origin of this compensation has not been well-understood. In this study, corticomuscular coherence (CMCoh) and electromyography (EMG) analysis were adopted to investigate the corticomuscular coordinating pattern of proximal UE compensatory activities when conducting distal UE movements in chronic stroke.Method: Fourteen chronic stroke subjects and 10 age-matched unimpaired controls conducted isometric finger extensions and flexions at 20 and 40% of maximal voluntary contractions. Electroencephalogram (EEG) data were recorded from the sensorimotor area and EMG signals were captured from extensor digitorum (ED), flexor digitorum (FD), triceps brachii (TRI), and biceps brachii (BIC) to investigate the CMCoh peak values in the Beta band. EMG parameters, i.e., the EMG activation level and co-contraction index (CI), were analyzed to evaluate the compensatory muscular patterns in the upper limb.Result: The peak CMCoh with statistical significance (P < 0.05) was found shifted from the ipsilesional side to the contralesional side in the proximal UE muscles, while to the central regions in the distal UE muscle in chronic strokes. Significant differences (P < 0.05) were observed in both peak ED and FD CMCohs during finger extensions between the two groups. The unimpaired controls exhibited significant intragroup differences between 20 and 40% levels in extensions for peak ED and FD CMCohs (P < 0.05). The stroke subjects showed significant differences in peak TRI and BIC CMCohs (P < 0.01). No significant inter- or intra-group difference was observed in peak CMCoh during finger flexions. EMG parameters showed higher EMG activation levels in TRI and BIC muscles (P < 0.05), and higher CI values in the muscle pairs involving TRI and BIC during all the extension and flexion tasks in the stroke group than those in the control group (P < 0.05).Conclusion: The post-stroke proximal muscular compensations from the elbow to the finger movements were cortically originated, with the center mainly located in the contralesional hemisphere.

Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional near-infrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fNIRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.

Differential corticomotor mechanisms of ankle motor control in post stroke individuals with and without motor evoked potentials

ObjectiveDeficits in ankle motor control has been identified as a significant contributor to impaired walking after stroke. Corticomotor excitability has been related to impaired upper limb motor control and poor recovery in stroke, however contributions to lower limb function are still unclear. This study used transcranial magnetic stimulation (TMS) to determine the influence of corticomotor characteristics on lower limb motor control in chronic stroke survivors. MethodsThis retrospective study assessed 28 individuals with post stroke hemiparesis. Motor evoked potentials (MEP) measured from the paretic and non-paretic tibialis anterior (TA) muscles were used to calculate corticomotor excitability symmetry (CMEsym) and relative ipsilateral corticomotor excitability (ICE). Participants were assigned to MEP+ and MEP− groups depending on the presence (+) or absence (−) of MEPs. Ankle motor control was quantified by the ability of participants to track a sinusoidal target using dorsiflexion-plantarflexion movements of the paretic ankle and tracking error was calculated using root mean square error (RMSE). ResultsMultiple linear regression model for all participants revealed only CMEsym and FMLE (p < 0.01) to significantly predict RMSE. In the MEP+ group, CMEsym significantly predicted RMSE (p = 0.03) while FMLE (p = 0.02) was a significant predictor for the MEP−. ConclusionOur results indicate that CMEsym between the ipsilesional and contralesional hemispheres does not necessarily translate to better paretic ankle motor control in chronic stroke. Presence or absence of a MEP in the TA muscle did not affect the ankle tracking performance, however, it was noted that different strategies maybe used by those with and without a MEP.