Contralesional Areas Research Articles

Individual contralesional recruitment in the context of structural reserve in early motor reorganization after stroke

The concept of structural reserve in stroke reorganization assumes that the relevance of the contralesional hemisphere strongly depends on the brain tissue spared by the lesion in the affected hemisphere. Recent studies, however, have indicated that the contralesional hemisphere's impact exhibits region-specific variability with concurrently existing maladaptive and supportive influences. This challenges traditional views, necessitating a nuanced investigation of contralesional motor areas and their interaction with ipsilesional networks.Our study focused on the functional role of contralesional key motor areas and lesion-induced connectome disruption early after stroke.Online TMS data of twenty-five stroke patients was analyzed to disentangle interindividual differences in the functional roles of contralesional primary motor cortex (M1), dorsal premotor cortex (dPMC), and anterior interparietal sulcus (aIPS) for motor function. Connectome-based lesion symptom mapping and corticospinal tract lesion quantification were used to investigate how TMS effects depend on ipsilesional structural network properties.At group and individual levels, TMS interference with contralesional M1 and aIPS but not dPMC led to improved performance early after stroke. At the connectome level, a more disturbing role of contralesional M1 was related to a more severe disruption of the structural integrity of ipsilesional M1 in the affected motor network. In contrast, a detrimental influence of contralesional aIPS was linked to less disruption of the ipsilesional M1 connectivity.Our findings indicate that contralesional areas distinctively interfere with motor performance early after stroke depending on ipsilesional structural integrity, extending the concept of structural reserve to regional specificity in recovery of function.

Longitudinal, Quantitative, Multimodal MRI Evaluation of Patients With Intracerebral Hemorrhage Over the First Year.

In most patients with intracerebral hemorrhage (ICH), the hematoma and perihematomal area decrease over the subsequent months but patients continue to exhibit neurological impairments. In this serial imaging study, we characterized microstructural and neurophysiological changes in the ICH-affected brain tissues and collected the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Score (mRS), two clinical stroke scale scores. Twelve ICH patients were serially imaged on a 3T MRI at 1, 3, and 12 months (M) after injury. The hematoma and perihematomal volume masks were created and segmented using FLAIR imaging at 1 month which were applied to compute the susceptibilities (χ), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF) in the same tissues over time and in the matching contralesional tissues. At 3 M, there was a significant (p < 0.001) reduction in hematoma and perihematomal volumes. At 1 M, the χ, FA, and CBF were decreased in the perihematomal tissues as compared to the contralateral side, whereas MD increased. In the hematomal tissues, the χ increased whereas FA, MD, and CBF decreased as compared to the contralesional area at 1 M. Temporally, CBF in the hematoma and perihematomal tissues remained significantly (p < 0.05) lower compared with the contralesional areas whereas MD in the hematoma and χ in the perihematomal area increased. The NIHSS and mRS significantly correlated with hematoma and perihematomal volume but not with microstructural integrity. Our serial imaging studies provide new information on the long-term changes within the brain after ICH and our findings may have clinical significance that warrants future studies.

Structural connectivity changes in the motor execution network after stroke rehabilitation.

Background:Although quite a very few studies have tested structural connectivity changes following an intervention, it reflects only selected key brain regions in the motor network. Thus, the understanding of structural connectivity changes related to the motor recovery process remains unclear.Objective:This study investigated structural connectivity changes of the motor execution network following a combined intervention of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (OT) after a stroke using graph theory approach.Methods:Fifty-six stroke patients underwent Fugl-Meyer Assessment (FMA), Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS), diffusion tensor imaging (DTI), and T1 weighted imaging before and after the intervention. We examined graph theory measures related to twenty brain regions using structural connectomes.Results:The ipsilesional and contralesional hemisphere showed structural connectivity changes post-intervention after stroke. We found significantly increased regional centralities and nodal efficiency within the frontal pole and decreased degree centrality and nodal efficiency in the ipsilesional thalamus. Correlations were found between network measures and clinical assessments in the cuneus, postcentral gyrus, precentral gyrus, and putamen of the ipsilesional hemisphere. The contralesional areas such as the caudate, cerebellum, and frontal pole also showed significant correlations.Conclusions:This study was helpful to expand the understanding of structural connectivity changes in both hemispheric networks during the motor recovery process following LF-rTMS and intensive OT after stroke.

Disrupted resting-state EEG alpha-band interactions as a novel marker for the severity of visual field deficits after brain lesion

ObjectiveHomonymous visual field deficits (HFVDs) are frequent following brain lesions. Current restoration treatments aim at activating areas of residual vision through numerous stimuli, but show limited effect. Recent findings suggest that spontaneous neural α-band coupling is more efficient for enabling visual perception in healthy humans than task-induced activations. Here, we evaluated whether it is also associated with the severity of HFVD. MethodsTen patients with HFVDs after brain damage in the subacute to chronic stage and ten matched healthy controls underwent visual stimulation with alternating checkerboards and electroencephalography recordings of stimulation-induced power changes and of spontaneous neural interactions during rest. ResultsVisual areas of the affected hemisphere showed reduced event-related power decrease in α and β frequency bands, but also reduced spontaneous α-band interactions during rest, as compared to contralesional areas and healthy controls. A multivariate stepwise regression retained the degree of disruption of spontaneous interactions, but not the reduced task-induced power changes as predictor for the severity of the visual deficit. ConclusionsSpontaneous α-band interactions of visual areas appear as a better marker for the severity of HFVDs than task-induced activations. SignificanceTreatment attempts of HFVDs should try to enhance spontaneous α-band coupling of structurally intact ipsilesional areas.

Abstract P193: Effects of Biaxial Ankle Passive Movement Therapy on Cortical Activations in Patients With Chronic Stroke a Functional Near-Infrared Spectroscopy Pilot Study

Introduction: The objective of this study was to investigate the effect of passive biaxial ankle movement therapy on cortical activities. We hypothesized that biaxial ankle passive movement therapy changes patterns of sensorimotor cortical activations during ankle passive movement in chronic stroke. Methods: Seventeen patients with stroke were randomized to either experimental or control group. The experimental group (n=11) received the biaxial ankle training and the control group (n=6) had conventional therapies on affected ankle for a 30-minute daily session, five times a week for a month. Outcome measure was cortical activations by measuring the relative changes of oxygenated hemoglobin concentration between ipsilesional-/contralesional hemisphere during passive ankle movement using functional near-infrared spectroscopy(fNIRS)(Figure 1). All assessments was conducted before and after the training. Significance level was 0.05. Results: fNIRS images showed that ipsilesional oxyhemoglobin concentration increased around primary sensorimotor cortex (SMC) area in both control and experimental groups at the baseline ( P &lt;0.05). After the ankle training, the ipsilesional oxyhemoglobin concentration significantly increased around somatosensory area for both control and experimental groups ( P &lt;0.05, Figure 2). Conclusions: The results of this study showed significant ipsilesional cortical activation in SMC during biaxial ankle movement before and after the ankle training. Further study on the analysis according to the direction of ankle movement for both ipsilesional and contralesional brain area is needed.

Modulation of Functional Connectivity and Low-Frequency Fluctuations After Brain-Computer Interface-Guided Robot Hand Training in Chronic Stroke: A 6-Month Follow-Up Study.

Hand function improvement in stroke survivors in the chronic stage usually plateaus by 6 months. Brain-computer interface (BCI)-guided robot-assisted training has been shown to be effective for facilitating upper-limb motor function recovery in chronic stroke. However, the underlying neuroplasticity change is not well understood. This study aimed to investigate the whole-brain neuroplasticity changes after 20-session BCI-guided robot hand training, and whether the changes could be maintained at the 6-month follow-up. Therefore, the clinical improvement and the neurological changes before, immediately after, and 6 months after training were explored in 14 chronic stroke subjects. The upper-limb motor function was assessed by Action Research Arm Test (ARAT) and Fugl-Meyer Assessment for Upper-Limb (FMA), and the neurological changes were assessed using resting-state functional magnetic resonance imaging. Repeated-measure ANOVAs indicated that long-term motor improvement was found by both FMA (F[2,26] = 6.367, p = 0.006) and ARAT (F[2,26] = 7.230, p = 0.003). Seed-based functional connectivity analysis exhibited that significantly modulated FC was observed between ipsilesional motor regions (primary motor cortex and supplementary motor area) and contralesional areas (supplementary motor area, premotor cortex, and superior parietal lobule), and the effects were sustained after 6 months. The fALFF analysis showed that local neuronal activities significantly increased in central, frontal and parietal regions, and the effects were also sustained after 6 months. Consistent results in FC and fALFF analyses demonstrated the increase of neural activities in sensorimotor and fronto-parietal regions, which were highly involved in the BCI-guided training.Clinical Trial Registration: This study has been registered at ClinicalTrials.gov with clinical trial registration number NCT02323061.

Interhemispheric Functional Reorganization and its Structural Base After BCI-Guided Upper-Limb Training in Chronic Stroke.

Brain-computer interface (BCI)-guided robot-assisted upper-limb training has been increasingly applied to stroke rehabilitation. However, the induced long-term neuroplasticity modulation still needs to be further characterized. This study investigated the functional reorganization and its structural base after BCI-guided robot-assisted training using resting-state fMRI, task-based fMRI, and diffusion tensor imaging (DTI) data. The clinical improvement and the neurological changes before, immediately after, and six months after 20-session BCI-guided robot hand training were explored in 14 chronic stroke subjects. The structural base of the induced functional reorganization and motor improvement were also investigated using DTI. Repeated measure ANOVA indicated long-term motor improvement was found (F[2, 26] = 6.367, p = 0.006). Significantly modulated functional connectivity (FC) was observed between ipsilesional motor regions (M1 and SMA) and some contralesional areas (SMA, PMd, SPL) in the seed-based analysis. Modulated FC with ipsilesional M1 was significantly correlated with motor function improvement (r = 0.6455, p = 0.0276). Besides, increased interhemispheric FC among the sensorimotor area from resting-state data and increased laterality index from task-based data together indicated the re-balance of the two hemispheres during the recovery. Multiple linear regression models suggested that both motor function improvement and the functional change between ipsilesional M1 and contralesional premotor area were significantly associated with the ipsilesional corticospinal tract integrity. The results in the current study provided solid support for stroke recovery mechanism in terms of interhemispheric interaction and its structural substrates, which could further enhance the understanding of BCI training in stroke rehabilitation. This study was registered at https://clinicaltrials.gov (NCT02323061).

Slow Waves Promote Sleep-Dependent Plasticity and Functional Recovery after Stroke.

Functional recovery after stroke is associated with a remapping of neural circuits. This reorganization is often associated with low-frequency, high-amplitude oscillations in the peri-infarct zone in both rodents and humans. These oscillations are reminiscent of sleep slow waves (SW) and suggestive of a role for sleep in brain plasticity that occur during stroke recovery; however, direct evidence is missing. Using a stroke model in male mice, we showed that stroke was followed by a transient increase in NREM sleep accompanied by reduced amplitude and slope of ipsilateral NREM sleep SW. We next used 5 ms optical activation of Channelrhodopsin 2-expressing pyramidal neurons, or 200 ms silencing of Archeorhodopsin T-expressing pyramidal neurons, to generate local cortical UP, or DOWN, states, respectively, both sharing similarities with spontaneous NREM SW in freely moving mice. Importantly, we found that single optogenetically evoked SW (SWopto) in the peri-infarct zone, randomly distributed during sleep, significantly improved fine motor movements of the limb corresponding to the sensorimotor stroke lesion site compared with spontaneous recovery and control conditions, while motor strength remained unchanged. In contrast, SWopto during wakefulness had no effect. Furthermore, chronic SWopto during sleep were associated with local axonal sprouting as revealed by the increase of anatomic presynaptic and postsynaptic markers in the peri-infarct zone and corresponding contralesional areas to cortical circuit reorganization during stroke recovery. These results support a role for sleep SW in cortical circuit plasticity and sensorimotor recovery after stroke and provide a clinically relevant framework for rehabilitation strategies using neuromodulation during sleep.SIGNIFICANCE STATEMENT Brain stroke is one of the leading causes of death and major disabilities in the elderly worldwide. A better understanding of the pathophysiological mechanisms underlying spontaneous brain plasticity after stroke, together with an optimization of rehabilitative strategies, are essential to improve stroke treatments. Here, we investigate the role of optogenetically induced sleep slow waves in an animal model of ischemic stroke and identify sleep as a window for poststroke intervention that promotes neuroplasticity and facilitates sensorimotor recovery.

Neural bases of visual processing of moving and stationary stimuli presented to the blind hemifield of hemianopic patients

Unilateral damage to post-chiasmatic visual pathways or cortical areas results in the loss of vision in the contralateral hemifield, known as hemianopia. Some patients, however, may retain the ability to perform an above chance unconscious detection or discrimination of visual stimuli presented to the blind hemifield, known as “blindsight”. An important finding in blindsight research is that it can often be elicited by moving stimuli. Therefore, in the present study, we wanted to test whether moving stimuli might yield blindsight phenomena in patients with cortical lesions resulting in hemianopia, in a discrimination task where stimulus movement is orthogonal to the feature of interest. This could represent an important strategy for rehabilitation because it might improve discrimination ability of stimulus features different but related to movement, e.g. line orientation.We tested eight hemianopic patients and eight age-matched healthy controls in an orientation discrimination task with moving or static visual stimuli. During performance of the task we carried out fMRI scanning and tractography. Behaviourally, we did not find a reliable main effect of motion on orientation discrimination; however, an important result was that in different patients blindsight could occur only with moving or stationary stimuli or with both. As to brain imaging results, following presentation of moving stimuli to the blind hemifield, a widespread fronto-parietal bilateral network was recruited including areas of the dorsal stream and in particular bilateral motion area hMT + whose activation positively correlated with behavioural performance. This bilateral network was not activated in controls suggesting that it represents a compensatory functional change following brain damage. Moreover, there was a higher activation of ipsilesional area hMT+ in patients who performed above chance in the moving condition. By contrast, in patients who performed above chance in the static condition, we found a higher activation of contralesional area V1 and extrastriate visual areas. Finally, we found a linear relationship between structural integrity of the ipsilesional pathway connecting lateral geniculate nucleus (LGN) with motion area hMT+ and both behavioural performance and ipsilesional hMT + activation. These results support the role of LGN in modulating performance as well as BOLD amplitude in the absence of visual awareness in ipsilesional area hMT+ during an orientation discrimination task with moving stimuli.

Abstract TP152: Sensory Function Improvement is Related to White Matter Changes During Rehabilitation

Objective: Structural changes related to recovery of sensory function are not well understood. Previously, we demonstrated a relationship between improved sensory function and increased cortical thickness in ipsilesional occipitoparietal and contralesional temporoparietal areas following rehabilitation of patients with chronic stroke(Pundik et al, 2018). The objective of the current work was to evaluate changes in white matter (WM) tracts originating in these cortical regions where thickness changes were related to enhanced sensory function after rehabilitation in chronic stroke. Methods: Chronic stroke survivors (n=18) received 12 weeks of upper limb sensory-motor rehabilitation. Outcome measures were sensory acuity (monofilament test, a sum over 9 locations on the hand; best score 25.47) and DTI measures of diffusivity [mean (MD), radial (RD), axial (AD)] and fractional anisotropy (FA). DTI analysis included: probabilistic tractography from seeds where cortical thickness changes correlated with sensory recovery, creation of a group-based tract by combining individual tracts, tract-based analysis using Spearman correlation, significance at p&lt;0.05 with Bonferroni correction, and voxel-based analysis permutation inference for general linear modeling. Results: Subjects were 53.9±12.1 years old, 1.9±1.2 years after stroke and 27.8% female. Monofilament score improved from 46.6±13.1 to 43.9±12.9. Improved sensory acuity correlated with increased AD (rho=0.69, p=0.002), RD (rho=0.59, p=0.0093) and MD (rho=0.63, p=0.005) in the tract originating in the ipsilesional occipital pole. Voxel-based analysis between changes in MD and in monofilament identified a statistically significant cluster (family-wise error corrected p=0.03) within a subcortical region of the tract originating in the ipsilesional occipital pole. Conclusion: Improved sensory acuity after rehabilitation was related to DTI-measured microstructural changes in WM tracts. These findings further support the notion of structural plasticity associated with sensory function improvement during rehabilitation in chronic stroke.

Effects of Mnemonic Strategy Training on Brain Activity and Cognitive Functioning of Left-Hemisphere Ischemic Stroke Patients.

Memory dysfunction is one of the main cognitive impairments caused by stroke, especially associative memory. Therefore, cognitive training, such as face-name mnemonic strategy training, could be an important intervention for this group of patients. The goal of this study was to evaluate the behavioral effects of face-name mnemonic strategy training, along with the neural substrate behind these effects, in the left frontoparietal lobe stroke patients. Volunteers underwent 2 sessions of functional magnetic resonance imaging (fMRI) during face-name association task: one prior and the other after the cognitive training. The fMRI followed a block design task with three active conditions: trained face-name pairs, untrained face-name pairs, and a couple of repeated face-name pairs. Prior to each fMRI session, volunteers underwent neuropsychological assessment. Training resulted in better performance on delayed memory scores of HVLT-R, and on recognition on a generalization strategy task, as well as better performance in the fMRI task. Also, trained face-name pairs presented higher activation after training in default-mode network regions, such as the posterior cingulate cortex, precuneus, and angular gyrus, as well as in lateral occipital and temporal regions. Similarly, untrained face-name pairs also showed a nonspecific training effect in the right superior parietal cortex, right supramarginal gyrus, anterior intraparietal sulcus, and lateral occipital cortex. A correlation between brain activation and task performance was also found in the angular gyrus, superior parietal cortex, anterior intraparietal sulcus, and lateral occipital cortex. In conclusion, these results suggest that face-name mnemonic strategy training has the potential to improve memory performance and to foster brain activation changes, by the recruitment of contralesional areas from default-mode, frontoparietal, and dorsal attention networks as a possible compensation mechanism.

The effects of motor imagery training and conventional therapy on the functioning of stroke survivors: A resting-state fMRI study

Objective To measure the efficacy of combining motor imagery training (MIT) with conventional therapy in improving stroke patients′ upper-extremity function. And to seek a cortical reorganization mechanism associated with the improvement using resting-state functional magnetic resonance imaging (rs-fMRI). Methods Ten stroke survivors were selected as an experimental group. They were given motor imagery training for four weeks (30 minutes a day, 5 days a week) and conventional rehabilitation therapy (40 minutes a day, 5 days a week). Another 10 healthy counterparts were the control group. Before and after the four weeks of treatment, both groups were assessed using the upper extremity Fugl-Meyer assessment (FMA-UE) and the modified Barthel index (MBI). Moreover, rs-fMRI was conducted to assess functional connectivity between cortical regions and the ipsilesional primary motor cortex (M1) before and after the intervention. The laterality index (LI) of the primary motor or sensory cortex was also calculated. Results After the intervention, the average FMA-UE and MBI scores of the experimental group had increased significantly. After MIT and conventional therapy there was increased functional connectivity between the ipsilesional and contralesional M1 areas, and between the ipsilesional M1 and contralesional primary sensory cortex (S1) and frontal lobe, the functional connection between the ipsilesional M1 and the ipsilesional paracentral lobule and the anterior cingutate was also increased. More specifically, the LI relating M1 and S1 decreased after the intervention, tending toward the normal level. LIMI decreased significantly. Conclusion The 4-week regimen of motor imagery training and conventional therapy resulted in functional improvement in the upper limbs and greater ability in the activities of daily living. The observed improvements may be due to cortical reorganization, including better functional connectivity between the bilateral M1 areas and increased connectivity between the ipsilesional M1 area and some non-motor areas. There is some recovery of symmetry in the bilateral primary motor cortex. Key words: Resting-state functional magnetic resonance imaging; Functional magnetic resonance imaging; Motor imagery training; Stroke; Cortical reorganization

P28. The functional role of the anterior intraparietal sulcus for recovery of hand function in chronic stroke patients – A combined fMRI-TMS study

Introduction After stroke, neuroimaging studies frequently show increased activation of contralesional regions such as the primary motor cortex (M1) and the anterior intraparietal sulcus (aIPS) during movements of the impaired hand ( Rehme et al., 2012 ). There is evidence that these areas may adopt either supportive or disturbing implications for motor control, depending on multiple factors, such as age, stroke severity, and lesion location ( Di Pino et al., 2014 ). Importantly, previous research has mainly focused on investigating this question in the contralesional M1, while other areas involved in motor control, such as the aIPS have often been neglected despite considerable changes in post-stroke activity. Hence, we here examined the role of both ipsi- and contralesional aIPS for recovered motor function in the chronic phase post stroke using neuronavigated ‘online-TMS’ guided by individual fMRI activation maps. Methods First, we assessed structural and functional MRI data of chronic stroke patients and age-matched controls. During fMRI, participants performed an index finger tapping task to localize motor-related activation. The coordinates of peak activity in bilateral aIPS were identified in each participant and subsequently used as stimulation targets to apply short trains of rTMS (10 Hz trains, 90% of resting motor threshold, rMT) time locked to hand movements of different complexity: Participants performed (i) index finger tapping, (ii) pointing between two targets, and (iii) reach-to-grasp movements while ipsilateral M1, aIPS, or contralateral aIPS were transiently disturbed by rTMS. Sham stimulation served as control with the coil being tilted over the parieto-occipital vertex. Task performance was measured using a 3D motion analysis system (Zebris). Results TMS interference with aIPS contralateral to the moving hand led to altered kinematics across all tasks modulating finger tapping amplitudes, pointing accuracy and maximum grip aperture during grasping, highlighting the role of this region for hand motor control in patients and healthy controls. In contrast, interference with aIPS and M1 ipsilateral to the moving hand revealed differential effects in patients. Preliminary data suggest distinct roles of these contralesional areas for recovered hand function in chronic stroke. Conclusions The present findings provide proof-of-principle for the use of fMRI-guided TMS allowing to assess target regions’ functions for hand motor control on the single-subject level. Implementing this approach in a larger cohort of stroke patients provides a promising strategy to individually characterize maladaptive or supportive roles in bilateral aIPS and the contralesional M1 in relation to patient’s motor impairment and lesion topology.

S144. 1-Hz repetitive transcranial magnetic stimulation over contralesional triceps area improves kinematic parameters of reaching movements in chronic stroke patients

Introduction The inhibition of the contralesional primary motor cortex (CM1) through repetitive transcranial magnetic stimulation (rTMS) has been shown to improve motor recovery in stroke patients. These data have been obtained through the stimulation of the contralesional cortical representation of the hand’s muscles. Nonetheless, and there is no evidence on the effects of contralesional inhibitory rTMS on the proximal muscles of the upper extremity. The aim of this study was to assess the effects of the low frequency-rTMS over the contralesional triceps area on reaching movements of chronic stroke patients. Methods Ten chronic, first ever stroke patients having different motor impairment have been enrolled in this perspective, randomized cross-over study. Patients undergone five daily sessions consisting of 1200 stimuli at 1 Hz, 90% of resting motor threshold, over the contralesional triceps area, and five daily sessions of sham stimulation, in a randomized sequence. The primary outcome measure was the change of kinematic parameters of reaching movement between the five baseline- and the five post-rTMS assessments. Results After rTMS, responding patients showed improved accuracy, smoothness, and velocity of reaching movements. These indices improved by no more than 10% (p Conclusion 1-Hz rTMS of the contralesional triceps area improved the execution of reaching movements of paretic limb in a sample of chronic stroke patients.

Stroke causes a transient imbalance of interhemispheric information flow in EEG during non-REM sleep

ObjectiveLarge-scale connectivity, especially interhemispheric connections, plays a crucial role for recovery after stroke. Here we used methods from information theory to characterize interhemispheric information flow in wake- and sleep-EEG after cerebral ischemia. Methods34 patients with unilateral ischemic stroke were included. Symbolic Transfer Entropy (STE) was applied between bipolar EEG signals on the left and the right cerebral hemisphere during polysomnographic recordings in the acute phase and 3 months after stroke. ResultsIn the acute phase, we found a sleep stage-dependent preferred interhemispheric asymmetry: during non-REM sleep the information flow was predominantly directed from the contralesional toward the ipsilesional hemisphere. This effect was greatly reduced in a follow-up recording 3 months after stroke onset. ConclusionOur findings are consistent with functional imaging studies showing a transient hyperactivity of contralesional areas after stroke. We conclude that STE is a robust method for detecting post-stroke connectivity reorganizations, and that sleep stages have to be taken into account when assessing functional connectivity. SignificanceEEG is more widely available than functional MRI. Future studies will have to confirm whether EEG derived STE can be useful in a clinical setting during rehabilitation after stroke.

Aromatase and neuroinflammation in rat focal brain ischemia

Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase expression in male focal ischemia.

O204 Simultaneous bi-hemispheric repetitive transcranial magnetic stimulation for upper limb motor recovery in chronic stroke: A double blind placebo controlled study

Objective repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for the treatment of post-stroke motor deficits. Since the crucial role of non-primary motor cortices and contralesional brain areas is emerging for motor recovery in chronic stroke; we assessed safety and efficacy of bilateral rTMS over the motor areas associated to physical training (PT) on upper extremity (UE) motor function. Methods double-blind, placebo-controlled trial on 20 patients with chronic stroke conditioning moderate to mild upper limb motor impairment. Eleven sessions of high frequency rTMS were delivered with the H-coil over the motor areas bilaterally. Subjects were randomly allocated to the real rTMS plus PT or the placebo (sham) rTMS plus PT. UE impairment was evaluated by the Fugl-Meyer assessment for UE (FM-UE), Modified Ashworth Scale (MAS) and hand grip strength at baseline (T0), after treatment (T1) and one-month follow-up (T2). Results no serious adverse events were reported. At T1 FM-UE significantly improved in both groups, while at T2 the improvement was significant only for the real group. The improvement was significantly higher in the real compared with the sham group. In the real group, greater improvement in FM-UE was found in patients moderately impaired compared with less impaired at baseline. Spasticity and hand grip strength also significantly improved in the real group at T1 and amelioration of spasticity persisted also at T2. Conclusion bilateral high-frequency rTMS with H-coil associated with PT is safe and enhances the effect of PT alone. Although plegic patients were not included, subjects with moderate rather than mild motor impairment may mainly benefit from this stimulation protocol.

Manipulating laterality and polarity of transcranial direct current stimulation to optimise outcomes for anomia therapy in an individual with chronic Broca’s aphasia

ABSTRACTBackground: Previous research indicates that combining behavioural therapy with transcranial direct current stimulation (tDCS) may be more effective than therapy alone in increasing naming ability in stroke survivors with chronic anomia. Anodal (excitatory) stimulation targeting left perilesional areas and/or cathodal (inhibitory) stimulation targeting right contralesional areas may particularly benefit non-fluent patients with localised damage to the left frontal lobe. However, studies have yet to systematically compare the effects of varying the laterality and polarity of tDCS within individual patients in order to determine optimal stimulation parameters.Aims: The primary purpose of the current study was to determine which tDCS parameters would result in the greatest improvements in naming ability in an individual (JSc) with chronic Broca’s aphasia (9 years post-stroke) due to a left frontal lesion. A range of secondary outcome measures were also collected to explore the potential effects of therapy on JSc’s connected speech, emotional well-being, and communicative effectiveness.Methods & Procedures: Following baseline naming assessment, JSc completed six, 4-week long cycles of therapy, each involving a different stimulation condition: four active (perilesional anodal, perilesional cathodal, contralesional anodal, and contralesional cathodal) and two sham control conditions (perilesional and contralesional). In the first week of each cycle, he completed three, 20-min therapy sessions, during which he carried out a personalised picture name repetition therapy task at the same time as receiving tDCS. Naming ability was measured before, immediately after, 1 week after, and 3 weeks after each week of therapy. The secondary outcome measures were completed before, 1 week after, and 3 weeks after each week of therapy.Outcomes & Results: Naming accuracy immediately after stimulation increased significantly more following perilesional anodal stimulation than following perilesional sham stimulation, and this effect remained significant at 3 weeks post-therapy. Treatment effects on the secondary outcome measures were less consistent.Conclusions: The results agree with previous work demonstrating the importance of activation in left frontal perilesional regions for accurate picture naming in stroke survivors with non-fluent aphasia. We have shown that the effectiveness of a total of 1 h of behavioural anomia therapy can be significantly increased when combined with perilesional anodal tDCS and demonstrated the feasibility of a longitudinal, repeated measures design with multiple outcome measures. Greater understanding of the optimal tDCS parameters to enhance anomia therapy outcomes in individual patients with differing lesion and behavioural profiles may one day assist with the translation of therapy plus tDCS protocols into everyday clinical practice.

P260 Modulating motor learning using cathodal tDCS

Following a stroke, anatomically distinct regions of the motor network including both ipsi- and contralesional areas have been demonstrated to increase when moving the stroke-affected arm. However, it is not clear what this increase in activity represents. Increased activity has been shown to be related to residual hand function in chronic stroke patients, however those patients with the highest levels of activity in these regions also show the worst recovery. Transcranial direct current stimulation (tDCS) is being increasingly investigated for its potential as an adjunct therapeutic tool for rehabilitation due to its ability to modulate underlying cortical excitability and induce the neurochemical changes thought to contribute to plasticity. For optimisation of this tool, a complete understanding of the wider motor network and the regions that could provide compensatory activity is needed. Studies in chronic stroke patients are inherently limited due to the inhomogeneity of lesion volume and location. An alternative is investigated here: the modelling of a stroke-type lesion in healthy participants using cathodal tDCS to temporarily down-regulate activity in a target area of the cortex. Combining cathodal tDCS with a model of motor recovery (a simple motor learning task) during BOLD functional MRI, we hoped to identify candidate regions that might demonstrate compensatory activity. Cathodal tDCS applied to left motor cortex (M1) during an explicit sequence-learning task performed with the right hand, resulted in down-regulation of activity within left M1, with a concurrent, possibly compensatory, increase in activity in the right M1. By contrast, delivery of tDCS prior to the task led to greater learning-related activity changes in left M1, Supplementary Motor Area (SMA) and dorsal premotor cortex (PMd) compared to concurrent and sham stimulation. These results, combined with no significant difference in behavioural performance across the stimulation groups identify that cathodal tDCS induced “virtual lesions” could be a suitable model for stroke lesions and that both ipsi- and contralateral regions could be considered as therapeutic targets for compensatory up-regulation using tDCS in stroke recovery.

Abstract TP406: Ipsilesional Myelination is Impaired in Children With Perinatal Arterial Stroke

Introduction: Stroke is a leading cause of perinatal brain injury and cerebral palsy. Current therapeutic efforts focus on optimizing developmental curves but the biological processes dictating these outcomes are poorly understood. Alterations in myelination are recognized as a major determinant of outcome in preterm brain injury but are unexplored in perinatal stroke (PS). Hypothesis: Ipsilesional delays in myelination occur in children with PS and are associated with poor developmental outcome. Methods: Participants were identified through the Alberta Perinatal Stroke Project, a population-based research cohort. Inclusion criteria were: 1) MRI-confirmed, unilateral arterial PS, 2) T1-weighted MRI &gt;6mo, 3) absence of other neurological disorders, 4) neurological outcome (Pediatric Stroke Outcome Measure, PSOM), and 5) motor assessments (Assisting Hand Assessment, AHA; Melbourne Assessment). FreeSurfer software measured hemispheric asymmetry in myelination intensity. A second method using ImageJ validated the detection of myelination asymmetry. Overall PSOM scores were classified as poor (&gt;1) or not. Repeated measures ANOVA compared perilesional, ipsilesional remote, and contralesional homologous regions. Myelination ratios for stroke cases were compared to typically developing controls (t-test), PSOM scores (t-test), and motor assessments (Pearson’s correlation). Results: Nineteen arterial stroke cases (mean age: 13.73±4.0yo) and 27 controls (mean age: 12.52±3.7yo) were studied. Stroke cases showed a greater degree of asymmetry with lower myelination in the lesioned hemisphere, compared to controls (p&lt;0.001). Myelination in perilesional regions was decreased compared to ipsilesional remote (p&lt;0.001) and contralesional homologous areas (p&lt;0.001). Ipsilesional remote regions were decreased compared to homologous regions on the contralesional hemisphere (p=0.009). Contralesional myelination was also less than controls (p&lt;0.001). Myelination ratios were not associated with PSOM, AHA, or Melbourne scores (p=0.144, 0.218, 0.366 respectively). Conclusion: Myelination of uninjured brain in the lesioned hemisphere is altered in children with PS. Further study is required to determine clinical significance.