Contralesional Cortex Research Articles

The differential roles of contralesional frontoparietal areas in cortical reorganization after stroke

BackgroundStudies examining the contribution of contralesional brain regions to motor recovery after stroke have revealed conflicting results comprising both supporting and disturbing influences. Especially the relevance of contralesional brain regions beyond primary motor cortex (M1) has rarely been studied, particularly concerning the temporal dynamics post-stroke. MethodsWe, therefore, used online transcranial magnetic stimulation (TMS) interference to longitudinally assess the role of contralesional (right) frontoparietal areas for recovery of hand motor function after left hemispheric stroke: contralesional M1, contralesional dorsal premotor cortex (dPMC), and contralesional anterior intraparietal sulcus (IPS). Fourteen stroke patients and sixteen age-matched healthy subjects performed motor tasks of varying complexity with their (paretic) right hand. Motor performance was quantified using three-dimensional kinematic data. All patients were assessed twice, (i) in the first week, and (ii) after more than three months post-stroke. ResultsWhile we did not observe a significant effect of TMS interference on movement kinematics following the stimulation of contralesional M1 and dPMC in the first week post-stroke, we found improvements of motor performance upon interference with contralesional IPS across motor tasks early after stroke, an effect that persisted into the later phase. By contrast, for dPMC, TMS-induced deterioration of motor performance was only evident three months post-stroke, suggesting that a supportive role of contralesional premotor cortex might evolve with reorganization. ConclusionWe here highlight time-sensitive and region-specific effects of contralesional frontoparietal areas after left hemisphere stroke, which may influence on neuromodulation regimes aiming at supporting recovery of motor function post-stroke.

Targeted tPA overexpression in denervated spinal motor neurons promotes stroke recovery in mice

Our previous studies demonstrated that axonal remodeling of the corticospinal tract (CST) contributes to neurological recovery after stroke in rodents. The present study employed a novel non-invasive peripheral approach, to over-express tPA in denervated spinal motor neurons via recombinant adeno-associated virus (AAV) intramuscular injection in transgenic mice subjected to permanent middle cerebral artery occlusion (MCAo), in which the CST axons are specifically and completely labeled with yellow fluorescent protein (YFP). One day after surgery, mice were randomly selected to receive saline, AAV5-RFP, or tPA (1 × 1010 viral particles) injected into the stroke-impaired forelimb muscles (n = 10/group). Functional deficits and recovery were monitored with foot-fault and single pellet reaching tests. At day 28 after MCAo, mice received intramuscular injection of PRV-614-mRFP (1.52 × 107 pfu) as above, and were euthanized four days later. Compared with saline or AAV-RFP-treated mice, AAV-tPA significantly enhanced behavioral recovery (p < 0.01, both tests), as well as increased CST axonal density in the denervated gray matter of the cervical cord (p < 0.001), and RFP-positive pyramidal neurons in both ipsilesional and contralesional cortices (p < 0.001). Behavioral outcomes were significantly correlated to neural remodeling (p < 0.05). Our results provide a fundamental basis for the development of therapeutic approaches aimed at promoting corticospinal innervation for stroke treatment.

Pyramidal tract and alternate motor fibers complementarily mediate motor compensation in patients after hemispherotomy

Motor function after hemispheric lesions has been associated with the structural integrity of either the pyramidal tract (PT) or alternate motor fibers (aMF). In this study, we aimed to differentially characterize the roles of PT and aMF in motor compensation by relating diffusion-tensor-imaging-derived parameters of white matter microstructure to measures of proximal and distal motor function in patients after hemispherotomy. Twenty-five patients (13 women; mean age: 21.1 years) after hemispherotomy (at mean age: 12.4 years) underwent Diffusion Tensor Imaging and evaluation of motor function using the Fugl-Meyer Assessment and the index finger tapping test. Regression analyses revealed that fractional anisotropy of the PT explained (p = 0.050) distal motor function including finger tapping rate (p = 0.027), whereas fractional anisotropy of aMF originating in the contralesional cortex and crossing to the ipsilesional hemisphere in the pons explained proximal motor function (p = 0.001). Age at surgery was found to be the only clinical variable to explain motor function (p < 0.001). Our results are indicative of complementary roles of the PT and of aMF in motor compensation of hemispherotomy mediating distal and proximal motor compensation of the upper limb, respectively.

Efficacy of Low-Frequency Repetitive Transcranial Magnetic Stimulation in Ischemic Stroke: A Double-Blind Randomized Controlled Trial

ObjectiveTo investigate the role of low-frequency repetitive transcranial magnetic stimulation (rTMS) along with conventional physiotherapy in the functional recovery of patients with subacute ischemic stroke. DesignDouble-blind, parallel group, randomized controlled trial. SettingThe outpatient department of a tertiary hospital participants: first ever ischemic stroke patients (N=96) in the previous 15 days were recruited and were randomized after a run-in period of 75±7 days into real rTMS (n=47) and sham rTMS (n=49) groups. InterventionConventional physical therapy was given to both the groups for 90±7 days postrecruitment. Total 10 sessions of low-frequency rTMS on contralesional premotor cortex was administered to real rTMS group (n=47) over a period of 2 weeks followed by physiotherapy regime for 45-50 minutes. Main Outcome MeasuresThe primary efficacy outcomes were change in modified Barthel Index (mBI) score (pre- to postscore) and proportion of participants with mBI score more than 90, measured at 90±7 days postrecruitment. The secondary outcomes were change in Fugl-Meyer Assessment–upper extremity, Fugl-Meyer Assessment–lower extremity, Hamilton Depression Scale, modified Rankin Scale, and National Institute of Health and Stroke Scale (pre- to post-rTMS) scores at 90±7 days post recruitment. ResultsModified intention to treat analysis showed a significant increase in the mBI score from pre- to post-rTMS in real rTMS group (4.96±4.06) versus sham rTMS group (2.65±3.25). There was no significant difference in proportion of patients with mBI>90 (55% vs 59%; P=.86) at 3 months between the groups. ConclusionIn patients with subacute ischemic stroke, 1-Hz low-frequency rTMS on contralesional premotor cortex along with conventional physical therapy resulted in significant change in mBI score.

Modulating Effects of Whole-body Vibration on Cortical Activity and Gait Function in Chronic Stroke Patients.

ClinicalTrials.gov Identifier: NCT03375346.

Short-Chain Fatty Acids Improve Poststroke Recovery via Immunological Mechanisms.

Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut-brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut-brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFAs induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells.SIGNIFICANCE STATEMENT Previous studies have shown a bidirectional communication along the gut-brain axis after stroke. Stroke alters the gut microbiota composition, and in turn, microbiota dysbiosis has a substantial impact on stroke outcome by modulating the immune response. However, until now, the mediators derived from the gut microbiome affecting the gut-immune-brain axis and the molecular mechanisms involved in this process were unknown. Here, we demonstrate that short-chain fatty acids, fermentation products of the gut microbiome, are potent and proregenerative modulators of poststroke neuronal plasticity at various structural levels. We identified that this effect was mediated via circulating lymphocytes on microglial activation. These results identify short-chain fatty acids as a missing link along the gut-brain axis and as a potential therapeutic to improve recovery after stroke.

Influence of Motor Deficiency and Spatial Neglect on the Contralesional Posterior Parietal Cortex Functional and Structural Connectivity in Stroke Patients.

The posterior parietal cortex (PPC) is a key structure for visual attention and upper limb function, two features that could be impaired after stroke, and could be implied in their recovery. If it is well established that stroke is responsible for intra- and interhemispheric connectivity troubles, little is known about those existing for the contralesional PPC. In this study, we aimed at mapping the functional (using resting state fMRI) and structural (using diffusion tensor imagery) networks from 3 subparts of the PPC of the contralesional hemisphere (the anterior intraparietal sulcus), the posterior intraparietal sulcus and the superior parieto-occipital cortex to bilateral frontal areas and ipsilesional homologous PPC parts in 11 chronic stroke patients compared to 13 healthy controls. We also aimed at assessing the relationship between connectivity and the severity of visuospatial and motor deficiencies. We showed that interhemispheric functional and structural connectivity between PPCs was altered in stroke patients compared to controls, without any specificity among seeds. Alterations of parieto-frontal intra- and interhemispheric connectivity were less observed. Neglect severity was associated with several alterations in intra- and interhemispheric connectivity, whereas we did not find any behavioral/connectivity correlations for motor deficiency. The results of this exploratory study shed a new light on the influence of the contralesional PPC in post-stroke patients, they have to be confirmed and refined in further larger studies.

What Kind of Brain Structural Connectivity Remodeling Can Relate to Residual Motor Function After Stroke?

Recent findings showed that brain networks far away from a lesion could be altered to adapt changes after stroke. This study examined 13 chronic stroke patients with moderate to severe motor impairment and 13 age-comparable healthy controls using diffusion tensor imaging to investigate the stroke impact on the reorganization of structural connectivity. Each subject's brain was segmented into 68 cortical and 12 subcortical regions of interest (ROIs), and connectivity measures including fractional anisotropy (FA), regional FA (rFA), connection weight (CW) and connection strength (CS) were adopted to compare two subject groups. Correlations between these measures and clinical scores of motor functions (Action Research Arm Test and Fugl-Meyer Assessment for upper extremity) were done. Network-based statistic (NBS) was conducted to identify the connectivity differences between patients and controls from the perspective of whole-brain network. The results showed that both rFAs and CSs demonstrated significant differences between patients and controls in the ipsilesional sensory-motor areas and subcortical network, and bilateral attention and default mode networks. Significant positive correlations were found between the paretic motor functions and the rFAs/CSs of the contralesional medial orbitofrontal cortex (mOFC) and rostral anterior cingulate cortex (rACC), and remained significant even after removing the effect of the ipsilesional corticospinal tract. Additionally, all the connections linked with the contralesional mOFC and rACC showed significantly higher FA/CW values in the stroke patients compared to the healthy controls from the NBS results. These findings indicated that these contralesional prefrontal areas exhibited stronger connections after stroke and strongly related to the residual motor function of the stroke patients.

Axonal regeneration and functional recovery driven by endogenous Nogo receptor antagonist LOTUS in a rat model of unilateral pyramidotomy

The adult mammalian central nervous system (CNS) rarely recovers from injury. Myelin fragments contain axonal growth inhibitors that limit axonal regeneration, thus playing a major role in determining neural recovery. Nogo receptor-1 (NgR1) and its ligands are among the inhibitors that limit axonal regeneration. It has been previously shown that the endogenous protein, lateral olfactory tract usher substance (LOTUS), antagonizes NgR1-mediated signaling and accelerates neuronal plasticity after spinal cord injury and cerebral ischemia in mice. However, it remained unclear whether LOTUS-mediated reorganization of descending motor pathways in the adult brain is physiologically functional and contributes to functional recovery. Here, we generated LOTUS-overexpressing transgenic (LOTUS-Tg) rats to investigate the role of LOTUS in neuronal function after damage. After unilateral pyramidotomy, motor function in LOTUS-Tg rats recovered significantly compared to that in wild-type animals. In a retrograde tracing study, labeled axons spanning from the impaired side of the cervical spinal cord to the unlesioned hemisphere of the red nucleus and sensorimotor cortex were increased in LOTUS-Tg rats. Anterograde tracing from the unlesioned cortex also revealed enhanced ipsilateral connectivity to the impaired side of the cervical spinal cord in LOTUS-Tg rats. Moreover, electrophysiological analysis showed that contralesional cortex stimulation significantly increased ipsilateral forelimb movement in LOTUS-Tg rats, which was consistent with the histological findings. According to these data, LOTUS overexpression accelerates ipsilateral projection from the unlesioned cortex and promotes functional recovery after unilateral pyramidotomy. LOTUS could be a future therapeutic option for CNS injury.

Acute changes in cortical activation during active ankle movement after whole-body vibration for spasticity in hemiplegic legs of stroke patients: a functional near-infrared spectroscopy study

ABSTRACTBackground: A recent study revealed that whole-body vibration (WBV) tends to decrease spasticity in stroke-related hemiplegic legs. However, acute changes in cortical activation after WBV are unclear.Objective: To examine whether WBV induces acute changes in sensorimotor cortical activation in patients with stroke-related hemiplegic legs.Methods: Eleven stroke patients (mean age 52.6 [SD 15.4] years; median time after stroke 3 [25th and 75th percentiles; 3 and 10.5, respectively] months) participated in a comparative before-and-after intervention trial. Six healthy adults were also studied. WBV at 30 Hz was applied for 5 min to the hamstrings, gastrocnemius, and soleus muscles. Spasticity was assessed according to the modified Ashworth scale (MAS). Active and passive range of motion (A-ROM and P-ROM, respectively) were also measured. Change in Oxy-Hb concentration in bilateral sensorimotor cortex associated with voluntary ankle dorsiflexion of the affected limb was assessed via functional near-infrared spectroscopy (fNIRS) before and immediately after WBV.Results: MAS score, A-ROM, and P-ROM improved immediately after WBV. In the patients, while there was no significant interaction between effects of region (ipsilesional and contralesional sensorimotor cortex) and the WBV intervention (before and immediately after WBV) (F1,10 = 0.702, p = .422), there was a significant main effect of the WBV intervention (F1,10 = 6.971, p = .025). In the healthy participants, there was no association with the WBV intervention or region.Conclusions: In patients with stroke-related spastic-hemiplegic legs, WBV might result not only in clinical improvement but also in acute increase in sensorimotor cortical activation.

Combined Rehabilitation Promotes the Recovery of Structural and Functional Features of Healthy Neuronal Networks after Stroke

Rehabilitation is considered the most effective treatment for promoting the recovery of motor deficits after stroke. One of the most challenging experimental goals is to unambiguously link brain rewiring to motor improvement prompted by rehabilitative therapy. Previous work showed that robotic training combined with transient inactivation of the contralesional cortex promotes a generalized recovery in a mouse model of stroke. Here, we use advanced optical imaging and manipulation tools to study cortical remodeling induced by this rehabilitation paradigm. We show that the stabilization of peri-infarct synaptic contacts accompanies increased vascular density induced by angiogenesis. Furthermore, temporal and spatial features of cortical activation recover toward pre-stroke conditions through the progressive formation of a new motor representation in the peri-infarct area. In the same animals, we observe reinforcement of inter-hemispheric connectivity. Our results provide evidence that combined rehabilitation promotes the restoration of structural and functional features distinctive of healthy neuronal networks.

Study of the activation in sensorimotor cortex and topological properties of functional brain network following focal vibration on healthy subjects and subacute stroke patients: An EEG study

Modulation on cerebral cortex and cerebral networks can induce reorganization of the brain, which contributes to rehabilitation. Previous studies have proved that focal vibration (FV) on limb muscles can modulate the activities of sensorimotor cortex in healthy subjects (HS). The objective of this paper is to study the modulatory effects of FV on the sensorimotor cortex and cerebral network in HS and subacute stroke patients (SP). An experiment was designed and conducted, during which FV of 75 Hz was applied over biceps muscle of right limb of 10 HS and 10 SP with right hemiplegia. Electroencephalography (EEG) was recorded in the following phases: before FV, control condition and three sessions of FV. EEG analysis showed a significant decrease in motor-related power desynchronization (MRPD) of contralesional primary sensorimotor cortex (contralesional S1-M1) in the beta2 band (18–21 Hz) for SP during FV sessions, as well as in MRPD of bilateral S1-M1 in the beta1 (13–18 Hz) and the beta2 band for HS. Moreover, MRPD of contralesional S1-M1 was significantly lower than MRPD of ipsilesional S1-M1 during FV. Besides, a significant increase of global efficiency (E) and decrease of characteristic path length (L) were identified in the beta1 band for SP, whereas a significant increase of L was identified for HS. The results indicated that FV could enhance the excitability of contralesional S1-M1 and alter topological properties of functional brain network for SP, which was different in HS. This indication can contribute to understanding the modulatory effects of FV on cerebral cortex and cerebral network.

The effects of five sessions of continuous theta burst stimulation over contralesional sensorimotor cortex paired with paretic skilled motor practice in people with chronic stroke.

In individuals with chronic stroke, impairment of the paretic arm may be exacerbated by increased contralesional transcallosal inhibition (TCI). Continuous theta burst stimulation (cTBS) can decrease primary motor cortex (M1) excitability and TCI. However, contralesional cTBS shows inconsistent effects after stroke. Variable effects of cTBS could stem from failure to pair stimulation with skilled motor practice or a focus of applying cTBS over M1. Here, we investigated the effects of pairing cTBS with skilled practice on motor learning and arm function. We considered the differential effects of stimulation over two different brain regions: contralesional M1 (M1c) or contralesional primary somatosensory cortex (S1c). 37 individuals with chronic stroke participated in five sessions of cTBS and paretic arm skilled practice of a serial targeting task (STT); participants received either cTBS over M1c or S1c or sham before STT practice. Changes in STT performance and Wolf Motor Function Test (WMFT) were assessed as primary outcomes. Assessment of bilateral corticospinal, intracortical excitability and TCI were secondary outcomes. cTBS over sensorimotor cortex did not improve STT performance and paretic WMFT-rate beyond sham cTBS. TCI was reduced bi-directionally following the intervention, regardless of stimulation group. In addition, we observed an association between STT performance change and paretic WMFT-rate change in the M1c stimulation group only. Multiple sessions of STT practice can improve paretic arm function and decrease TCI bilaterally, with no additional benefit of prior cTBS. Our results suggest that improvement in STT practice following M1c cTBS scaled with change in paretic arm function in some individuals. Our results highlight the need for a better understanding of the mechanisms of cTBS to effectively identify who may benefit from this form of brain stimulation.

Constraint induced movement therapy promotes contralesional-oriented structural and bihemispheric functional neuroplasticity after stroke

The mechanism behind constraint-induced movement therapy (CIMT) in promoting motor recovery after stroke remains unclear. We explored the bilateral structural and functional reorganization of the brain induced by CIMT after left middle cerebral artery occlusion (MCAO) in rats. CIMT started on the 8th day (D8) after MCAO surgery and lasted for 3 weeks. Skilled walking was assessed by Foot-Fault tests. The efferent neuron network innervating the paralyzed forelimb was labeled by pseudorabies virus (PRV) to explore neuron recruitment. Synapsin Ⅰ was used as an indicator of the number of synapses. Additionally, C-fos expression 1 h after walking was detected to explore the activation of the brain. As a result, CIMT significantly improved skilled walking and elicited more neuron recruitment into the innervating network of a paralyzed forelimb in the contralesional rather than the ipsilesional motor cortex and red nucleus. CIMT also increased the synapse number in the contralesional cortex but there was no corresponding effect in the intact ipsilesional cortex. Furthermore, MCAO decreased ipsilesional motor cortex activation, but CIMT partially compensated for this by increasing the number of activated neurons (c-fos+) in both the left and right motor cortex. In conclusion, the contralesional motor cortex and red nucleus might play more important roles than corresponding ipsilesional regions in structural reorganization during CIMT-induced motor recovery after stroke. However, CIMT promotes bilateral motor cortex activity without a side preference.

Not all brain regions are created equal for improving bimanual coordination in individuals with chronic stroke

ObjectiveThe now standard cortical stimulation approach of inhibiting contralesional primary motor cortex (cM1) disrupts bimanual coordination while facilitating ipsilesional M1 (iM1) fails to enhance paretic arm function, in severely impaired individuals. We propose an alternative target, enhancing contralesional dorsal premotor cortex (cPMd) to improve bimanual coordination and compare its effects to iM1. MethodsFourteen participants with stroke received 5-Hz repetitive transcranial magnetic stimulation (rTMS) on cPMd or iM1 in a repeated cross-over design. Bimanual force/neuromuscular coordination and cortical excitability were assessed. We also examined the relationship of baseline motor function/interhemispheric inhibition (IHI) to participant’s responses to each stimulation target. ResultsWe identified two patterns of responses. Participants with more severe impairment and weaker IHI improved bimanual force/neuromuscular coordination, ipsilesional activations and reduced IHI after cPMd-rTMS; whereas, those with milder impairment and stronger IHI improved only after iM1-rTMS. ConclusionsCortical stimulation protocols could be tailored to the types of tasks and to individuals’ severity of impairment. Facilitation of cPMd may improve bimanual coordination especially for individuals with limited arm/hand function. SignificanceOur study is the first to identify cortical stimulation strategies for improving bimanual coordination for individuals with different level of severity of stroke.

A Unifying Pathophysiological Account for Post-stroke Spasticity and Disordered Motor Control.

Cortical and subcortical plastic reorganization occurs in the course of motor recovery after stroke. It is largely accepted that plasticity of ipsilesional motor cortex primarily contributes to recovery of motor function, while the contributions of contralesional motor cortex are not completely understood. As a result of damages to motor cortex and its descending pathways and subsequent unmasking of inhibition, there is evidence of upregulation of reticulospinal tract (RST) excitability in the contralesional side. Both animal studies and human studies with stroke survivors suggest and support the role of RST hyperexcitability in post-stroke spasticity. Findings from animal studies demonstrate the compensatory role of RST hyperexcitability in recovery of motor function. In contrast, RST hyperexcitability appears to be related more to abnormal motor synergy and disordered motor control in stroke survivors. It does not contribute to recovery of normal motor function. Recent animal studies highlight laterality dominance of corticoreticular projections. In particular, there exists upregulation of ipsilateral corticoreticular projections from contralesional premotor cortex (PM) and supplementary motor area (SMA) to medial reticular nuclei. We revisit and revise the previous theoretical framework and propose a unifying account. This account highlights the importance of ipsilateral PM/SMA-cortico-reticulospinal tract hyperexcitability from the contralesional motor cortex as a result of disinhibition after stroke. This account provides a pathophysiological basis for post-stroke spasticity and related movement impairments, such as abnormal motor synergy and disordered motor control. However, further research is needed to examine this pathway in stroke survivors to better understand its potential roles, especially in muscle strength and motor recovery. This account could provide a pathophysiological target for developing neuromodulatory interventions to manage spasticity and thus possibly to facilitate motor recovery.

Determinants of IQ outcome after focal epilepsy surgery in childhood: A longitudinal case-control neuroimaging study.

Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as brain development and resection location. This study examines clinical and neuroimaging factors associated with cognitive outcome after epilepsy surgery in childhood. Fifty-two children (28 boys, 24 girls) were evaluated for epilepsy surgery and reassessed on average 7.7years later. In the intervening time, 13 were treated pharmacologically and 39 underwent focal surgery (17 temporal, 16 extratemporal, six multilobar; mean age at surgery = 14.0years). Pre- and postsurgical assessments included IQ tests and T1-weighted brain images. Predictors of IQ change were investigated, including voxel-based analyses of resection location, and gray and white matter volume change. Overall modest IQ improvement was seen in children treated surgically, but not in those treated pharmacologically only. Applying a ≥10-point change threshold, 39% of the surgically treated children improved, whereas 10% declined. Clinical factors associated with IQ increases were lower preoperative IQ and longer follow-up duration, whereas seizure and antiepileptic medication cessation were not predictive. Among neuroimaging factors, we observed that left anterior temporal resections impacted negatively on verbal reasoning, linked to full-scale IQ decline. In contrast, gray matter volume change in ipsi- and contralesional hemispheres was positively correlated with IQ change. Voxel-based morphometry identified the gray matter volume change in the contralesional dorsolateral frontal cortex as most strongly associated with IQ improvement. We show that a variety of factors are likely to contribute to patterns of postsurgical change in IQ. Neuroimaging results indicate that left anterior temporal resections constrain development of verbal cognition, whereas simultaneously cortical growth after surgical treatment can support improvements in IQ.

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

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Diverse functional connectivity patterns of resting-state brain networks associated with good and poor hand outcomes following stroke

Motor stroke has been characterized by disruptions in multiple large-scale functional brain networks. However, it remains unclear whether stroke patients with good hand outcomes show different connectivity profiles within and between networks from those with poor hand outcomes. In this cross-sectional study, we recruited 52 chronic subcortical stroke patients [illness duration (mean±SD): 16±16.2 months] and 52 healthy controls from the local hospital and community from June 2010 to August 2016. We first performed independent component analysis (ICA) on resting-state fMRI data to extract fifteen resting-state networks. Then, we compared the functional connectivity within and between networks across 52 healthy controls, 26 patients with a partially paralyzed hand (PPH), and 26 patients with a completely paralyzed hand (CPH). Compared to the patients with a PPH, the patients with a CPH showed increased connectivity in the contralesional sensorimotor cortex within the contralesional sensorimotor network; the increased connectivity was negatively correlated with the performance of the paretic hand. Moreover, the patients with a CPH, compared to those with a PPH, showed decreased strengths of connectivity between the ipsilesional sensorimotor network and both the dorsal sensorimotor network and ventral visual network; the decreased strengths of connectivity were positively correlated with the performance of the paretic hand. Collectively, our findings suggest that stroke patients with different hand outcomes show distinct functional reorganization patterns in large-scale brain networks. These findings shed light on the network-level neuromechanisms that help explain why stroke survivors in the chronic stage show different hand outcomes.