Project description:BackgroundRestoring movement after hemiparesis caused by stroke is an ongoing challenge in the field of rehabilitation. With several therapies in use, there is no definitive prescription that optimally maps parameters of rehabilitation with patient condition. Recovery gets further complicated once patients enter chronic phase. In this paper, we propose a rehabilitation framework based on computational modeling, capable of mapping patient characteristics to parameters of rehabilitation therapy.MethodTo build such a system, we used a simple convolutional neural network capable of performing bilateral reaching movements in 3D space using stereovision. The network was designed to have bilateral symmetry to reflect the bilaterality of the cerebral hemispheres with the two halves joined by cross-connections. This network was then modified according to 3 chosen patient characteristics-lesion size, stage of recovery (acute or chronic) and structural integrity of cross-connections (analogous to Corpus Callosum). Similarly, 3 parameters were used to define rehabilitation paradigms-movement complexity (Exploratory vs Stereotypic), hand selection mode (move only affected arm, CIMT vs move both arms, BMT), and extent of plasticity (local vs global). For each stroke condition, performance under each setting of the rehabilitation parameters was measured and results were analyzed to find the corresponding optimal rehabilitation protocol.ResultsUpon analysis, we found that regardless of patient characteristics network showed better recovery when high complexity movements were used and no significant difference was found between the two hand selection modes. Contrary to these two parameters, optimal extent of plasticity was influenced by patient characteristics. For acute stroke, global plasticity is preferred only for larger lesions. However, for chronic, plasticity varies with structural integrity of cross-connections. Under high integrity, chronic prefers global plasticity regardless of lesion size, but with low integrity local plasticity is preferred.ConclusionClinically translating the results obtained, optimal recovery may be observed when paretic arm explores the available workspace irrespective of the hand selection mode adopted. However, the extent of plasticity to be used depends on characteristics of the patient mainly stage of stroke and structural integrity. By using systems as developed in this study and modifying rehabilitation paradigms accordingly it is expected post-stroke recovery can be maximized.
Project description:Central post-stroke pain (CPSP) is a debilitating, severe disorder affecting patient quality of life. Since CPSP is refractory to medication, various treatment modalities have been tried with marginal results. Following the first report of epidural motor cortex (M1) stimulation (MCS) for CPSP, many researchers have investigated the mechanisms of electrical stimulation of the M1. CPSP is currently considered to be a maladapted network reorganization problem following stroke, and recent studies have revealed that the activities of the impaired hemisphere after stroke may be inhibited by the contralesional hemisphere. Even though this interhemispheric inhibition (IHI) theory was originally proposed to explain the motor recovery process in stroke patients, we considered that IHI may also contribute to the CPSP mechanism. Based on the IHI theory and the fact that electrical stimulation of the M1 suppresses CPSP, we hypothesized that the inhibitory signals from the contralesional hemisphere may suppress the activities of the M1 in the ipsilesional hemisphere, and therefore pain suppression mechanisms may be malfunctioning in CPSP patients. In this context, transcranial direct current stimulation (tDCS) was considered to be a reasonable procedure to address the interhemispheric imbalance, as the bilateral M1 can be simultaneously stimulated using an anode (excitatory) and cathode (inhibitory). In this article, we review the potential mechanisms and propose a new model of CPSP. We also report two cases where CPSP was addressed with tDCS, discuss the potential roles of tDCS in the treatment of CPSP, and make recommendations for future studies.
Project description:Brain-machine interfaces (BMI) permit bypass motor system disruption by coupling contingent neuroelectric signals related to motor activity with prosthetic devices that enhance afferent and proprioceptive feedback to the somatosensory cortex. In this study, we investigated neural plasticity in the motor network of severely impaired chronic stroke patients after an EEG-BMI-based treatment reinforcing sensorimotor contingency of ipsilesional motor commands. Our structural connectivity analysis revealed decreased fractional anisotropy in the splenium and body of the corpus callosum, and in the contralesional hemisphere in the posterior limb of the internal capsule, the posterior thalamic radiation, and the superior corona radiata. Functional connectivity analysis showed decreased negative interhemispheric coupling between contralesional and ipsilesional sensorimotor regions, and decreased positive intrahemispheric coupling among contralesional sensorimotor regions. These findings indicate that BMI reinforcing ipsilesional brain activity and enhancing proprioceptive function of the affected hand elicits reorganization of contralesional and ipsilesional somatosensory and motor-assemblies as well as afferent and efferent connection-related motor circuits that support the partial re-establishment of the original neurophysiology of the motor system even in severe chronic stroke.
Project description:Post-stroke depression (PSD) is a serious complication of stroke that significantly restricts rehabilitation. The use of immersive virtual reality for stroke survivors is promising. Herein, we investigated the effects of a novel immersive virtual reality training system on PSD and explored induced effective connectivity alterations in emotional networks using multivariate Granger causality analysis (GCA). Forty-four patients with PSD were equally allocated into an immersive-virtual reality group and a control group. In addition to their usual rehabilitation treatments, the participants in the immersive-virtual reality group participated in an immersive-virtual reality rehabilitation program, while the patients in the control group received 2D virtual reality rehabilitation training. The Hamilton Depression Rating Scale, modified Barthel Index (MBI), and resting-state functional magnetic resonance imaging (rsfMRI) data were collected before and after a 4-week intervention. rsfMRI data were analyzed using multivariate GCA. We found that the immersive virtual reality training was more effective in improving depression in patients with PSD but had no statistically significant improvement in MBI scores compared to the control group. The GCA showed that the following causal connectivities were strengthened after immersive virtual reality training: from the amygdala, insula, middle temporal gyrus, and caudate nucleus to the dorsolateral prefrontal cortex; from the insula to the medial prefrontal cortex; and from the thalamus to the posterior superior temporal sulcus. These causal connectivities were weakened after treatment in the control group. Our results indicated the neurotherapeutic use of immersive virtual reality rehabilitation as an effective non-pharmacological intervention for PSD; the alteration of causal connectivity in emotional networks might constitute the neural mechanisms underlying immersive-virtual reality rehabilitation in PSD.
Project description:The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl-Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.
Project description:ObjectivePeople who have survived stroke may have motor and cognitive impairments. High dose of motor rehabilitation was found to provide clinically relevant improvement to upper limb (UL) motor function. Besides, mounting evidence suggests that clinical, neural, and neurophysiological features are associated with spontaneous recovery. However, the association between these features and rehabilitation-induced, rather than spontaneous, recovery has never been fully investigated. The objective was to explore the association between rehabilitation dose and UL motor outcome after stroke, as well as to identify which variables can be considered potential candidate predictors of motor recovery.MethodsPeople who survived stroke were assessed before and after a period of rehabilitation using motor, cognitive, neuroanatomical, and neurophysiological measures. We investigated the association between dose of rehabilitation and UL response (ie, Fugl-Meyer Assessment for upper extremity [FMA-UE]), using ordinary least squares regression as the primary analysis. To obtain unbiased estimates, adjusting covariates were selected using a directed acyclic graph.ResultsBaseline FMA-UE was the only factor associated with motor recovery (b = 0.99; 95% CI = 0.83 to 1.15 points). Attention emerged as a confounder of the association between rehabilitation and final FMA-UE (b = 5.5; 95% CI = -0.8 to 11.9 points), influencing both rehabilitation and UL response.ConclusionPreserved attention in people who have survived stroke might lead to greater UL motor recovery, albeit estimates have high levels of variability. Moreover, the increase in the dose of rehabilitation can lead to 5.5 points improvement on the FMA-UE, a nonsignificant but potentially meaningful finding. The approach described here discloses a new framework for investigating the effect of rehabilitation treatment as a potential driver of recovery.ImpactAttentional resources could play a key role in UL motor recovery. There is a potential association between amount of UL recovery and dose of rehabilitation delivered, needing further exploration. Preserved attention and rehabilitation dose are candidate predictors of UL motor recovery.
Project description:Background and purposeIn many neurologic diagnoses, significant interindividual variability exists in the outcomes of rehabilitation. One factor that may impact response to rehabilitation interventions is genetic variation. Genetic variation refers to the presence of differences in the DNA sequence among individuals in a population. Genetic polymorphisms are variations that occur relatively commonly and, while not disease-causing, can impact the function of biological systems. The purpose of this article is to describe genetic polymorphisms that may impact neuroplasticity, motor learning, and recovery after stroke.Summary of key pointsGenetic polymorphisms for brain-derived neurotrophic factor (BDNF), dopamine, and apolipoprotein E have been shown to impact neuroplasticity and motor learning. Rehabilitation interventions that rely on the molecular and cellular pathways of these factors may be impacted by the presence of the polymorphism. For example, it has been hypothesized that individuals with the BDNF polymorphism may show a decreased response to neuroplasticity-based interventions, decreased rate of learning, and overall less recovery after stroke. However, research to date has been limited and additional work is needed to fully understand the role of genetic variation in learning and recovery.Recommendations for clinical practiceGenetic polymorphisms should be considered as possible predictors or covariates in studies that investigate neuroplasticity, motor learning, or motor recovery after stroke. Future predictive models of stroke recovery will likely include a combination of genetic factors and other traditional factors (eg, age, lesion type, corticospinal tract integrity) to determine an individual's expected response to a specific rehabilitation intervention.
Project description:Motor disability is a critical impairment in stroke patients. Rehabilitation has a limited effect on recovery; but there is no medical therapy for post-stroke recovery. The biological mechanisms of rehabilitation in the brain remain unknown. Here, using a photothrombotic stroke model in male mice, we demonstrate that rehabilitation after stroke selectively enhances synapse formation in presynaptic parvalbumin interneurons and postsynaptic neurons in the rostral forelimb motor area with axonal projections to the caudal forelimb motor area where stroke was induced (stroke-projecting neuron). Rehabilitation improves motor performance and neuronal functional connectivity, while inhibition of stroke-projecting neurons diminishes motor recovery. Stroke-projecting neurons show decreased dendritic spine density, reduced external synaptic inputs, and a lower proportion of parvalbumin synapse in the total GABAergic input. Parvalbumin interneurons regulate neuronal functional connectivity, and their activation during training is necessary for recovery. Furthermore, gamma oscillation, a parvalbumin-regulated rhythm, is increased with rehabilitation-induced recovery in animals after stroke and stroke patients. Pharmacological enhancement of parvalbumin interneuron function improves motor recovery after stroke, reproducing rehabilitation recovery. These findings identify brain circuits that mediate rehabilitation-recovery and the possibility for rational selection of pharmacological agents to deliver the first molecular-rehabilitation therapeutic.
Project description:BackgroundPeople post-stroke are at risk of not being able to participate in valued activities. It is important that rehabilitation professionals prepare people post-stroke for the transition home and provide needed support when they live at home. Several authors have suggested that members of the broad social network should play an active role in rehabilitation. This includes informing them about the importance of activity (re)engagement post-stroke and learning strategies to provide support. It is not clear when and how the broad social network can best be equipped to provide adequate activity support. This study aimed to explore stroke professionals' perspectives on strategies that establish a social network that supports activity (re)engagement of people post-stroke, when strategies are best implemented, and the factors that influence the implementation of these strategies.MethodsTwo focus groups were executed. Content analysis was used to analyze the transcripts of the recorded conversations.ResultsEighteen professionals with various professional backgrounds and roles in treating people post-stroke participated. Strategies to establish a supportive social network included identifying, expanding, informing, and actively engaging network members. Working with the network in the immediate post-stroke phase was regarded as important for improving long-term activity outcomes. Participants expressed that most strategies to equip the social network to support people post-stroke need to take place within community care. However, the participants experienced difficulties in implementing network strategies. Perceived barriers included interprofessional collaboration, professional knowledge, self-efficacy, and financial structures.ConclusionsStrategies to involve the social network of people post-stroke are not fully implemented. Although identifying members of a social network should begin during inpatient rehabilitation, the main part of actively engaging the network will have to take place when the people post-stroke return home. Implementing social network strategies requires a systematic process focusing on collaboration, knowledge, attitude, and skill development.