Association that Neuroimaging and Clinical Measures Have with Change in Arm Impairment in a Phase 3 Stroke Recovery Trial.

Objective: Vagus nerve stimulation (VNS) paired with rehabilitation therapy improved motor status compared to rehabilitation alone in the phase III VNS-REHAB stroke trial, but treatment response was variable and not associated with any clinical measures acquired at baseline, such as age or side of paresis. We hypothesized that neuroimaging measures would be associated with treatment-related gains, examining performance of regional injury measures versus global brain health measures in parallel with clinical measures.

Methods: Baseline magnetic resonance imaging (MRI) scans in the VNS-REHAB trial were used to derive regional injury measures (extent of injury to corticospinal tract, the primary regional measure; plus extent of injury to precentral gyrus and postcentral gyrus; lesion volume; and lesion topography) and global brain health measures (degree of white matter hyperintensities, the primary global brain measure; plus volumes of cerebrospinal fluid, cortical gray matter, white matter, each thalamus, and total brain).

Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Blinded, Pivotal, VNS-REHAB Device Trial.

Background: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

Objective: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

Methods: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control).

Motor adaptation and internal model formation in a robot-mediated forcefield.

Background: Motor adaptation relies on error-based learning for accurate movements in changing environments. However, the neurophysiological mechanisms driving individual differences in performance are unclear. Transcranial magnetic stimulation (TMS)-evoked potential can provide a direct measure of cortical excitability.

Economic evaluation of robot-assisted training versus an enhanced upper limb therapy programme or usual care for patients with moderate or severe upper limb functional limitation due to stroke: results from the RATULS randomised controlled trial.

Objective: To determine whether robot-assisted training is cost-effective compared with an enhanced upper limb therapy (EULT) programme or usual care.

Design: Economic evaluation within a randomised controlled trial.

Setting: Four National Health Service (NHS) centres in the UK: Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust; Northwick Park Hospital, London Northwest Healthcare NHS Trust; Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde; and North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

Background: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke.

Methods: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group).

Robot-assisted training compared with an enhanced upper limb therapy programme and with usual care for upper limb functional limitation after stroke: the RATULS three-group RCT.

Background: Loss of arm function is common after stroke. Robot-assisted training may improve arm outcomes.

Objective: The objectives were to determine the clinical effectiveness and cost-effectiveness of robot-assisted training, compared with an enhanced upper limb therapy programme and with usual care.

Evaluation of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after Stroke trial: descriptive analysis of intervention fidelity, goal selection and goal achievement.

Objective: To report the fidelity of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after stroke (RATULS) randomized controlled trial, the types of goals selected and the proportion of goals achieved.

Design: Descriptive analysis of data on fidelity, goal selection and achievement from an intervention group within a randomized controlled trial.

Setting: Out-patient stroke rehabilitation within four UK NHS centres.

Graded fMRI Neurofeedback Training of Motor Imagery in Middle Cerebral Artery Stroke Patients: A Preregistered Proof-of-Concept Study.

Ischemic stroke of the middle cerebral artery (MCA), a major brain vessel that supplies the primary motor and premotor cortex, is one of the most common causes for severe upper limb impairment. Currently available motor rehabilitation training largely lacks satisfying efficacy with over 70% of stroke survivors showing residual upper limb dysfunction. Motor imagery-based functional magnetic resonance imaging neurofeedback (fMRI-NF) has been suggested as a potential therapeutic technique to improve motor impairment in stroke survivors.

Robot assisted training for the upper limb after stroke (RATULS): a multicentre randomised controlled trial.

Background: Loss of arm function is a common problem after stroke. Robot-assisted training might improve arm function and activities of daily living. We compared the clinical effectiveness of robot-assisted training using the MIT-Manus robotic gym with an enhanced upper limb therapy (EULT) programme based on repetitive functional task practice and with usual care.

Dynamics of brain connectivity after stroke.

Recovery from a stroke is a dynamic time-dependent process, in which the central nervous system reorganises to accommodate for the impact of the injury. The purpose of this paper is to review recent longitudinal studies of changes in brain connectivity after stroke. A systematic review of research papers reporting functional or effective connectivity at two or more time points in stroke patients was conducted.

The BOLD response in primary motor cortex and supplementary motor area during kinesthetic motor imagery based graded fMRI neurofeedback.

There is increasing interest in exploring the use of functional MRI neurofeedback (fMRI-NF) as a therapeutic technique for a range of neurological conditions such as stroke and Parkinson's disease (PD). One main therapeutic potential of fMRI-NF is to enhance volitional control of damaged or dysfunctional neural nodes and networks via a closed-loop feedback model using mental imagery as the catalyst of self-regulation. The choice of target node/network and direction of regulation (increase or decrease activity) are central design considerations in fMRI-NF studies.

Resting-state functional connectivity predicts the ability to adapt arm reaching in a robot-mediated force field.

Motor deficits are common outcomes of neurological conditions such as stroke. In order to design personalised motor rehabilitation programmes such as robot-assisted therapy, it would be advantageous to predict how a patient might respond to such treatment. Spontaneous neural activity has been observed to predict differences in the ability to learn a new motor behaviour in both healthy and stroke populations.

Neural predictors of gait stability when walking freely in the real-world.

Background: Gait impairments during real-world locomotion are common in neurological diseases. However, very little is currently known about the neural correlates of walking in the real world and on which regions of the brain are involved in regulating gait stability and performance. As a first step to understanding how neural control of gait may be impaired in neurological conditions such as Parkinson's disease, we investigated how regional brain activation might predict walking performance in the urban environment and whilst engaging with secondary tasks in healthy subjects.

Neural Correlates of Single- and Dual-Task Walking in the Real World.

Recent developments in mobile brain-body imaging (MoBI) technologies have enabled studies of human locomotion where subjects are able to move freely in more ecologically valid scenarios. In this study, MoBI was employed to describe the behavioral and neurophysiological aspects of three different commonly occurring walking conditions in healthy adults. The experimental conditions were self-paced walking, walking while conversing with a friend and lastly walking while texting with a smartphone.

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

Background: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke.

Methods/design: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation.

Muscle co-contraction patterns in robot-mediated force field learning to guide specific muscle group training.

Background: Muscle co-contraction is a strategy of increasing movement accuracy and stability employed in dealing with force perturbation of movement. It is often seen in neuropathological populations. The direction of movement influences the pattern of co-contraction, but not all movements are easily achievable for populations with motor deficits.

High-Frequency Intermuscular Coherence between Arm Muscles during Robot-Mediated Motor Adaptation.

Adaptation of arm reaching in a novel force field involves co-contraction of upper limb muscles, but it is not known how the co-ordination of multiple muscle activation is orchestrated. We have used intermuscular coherence (IMC) to test whether a coherent intermuscular coupling between muscle pairs is responsible for novel patterns of activation during adaptation of reaching in a force field. Subjects ( = 16) performed reaching trials during a null force field, then during a velocity-dependent force field and then again during a null force field.

Functional Magnetic Resonance Imaging Neurofeedback-guided Motor Imagery Training and Motor Training for Parkinson's Disease: Randomized Trial.

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient's own brain activity to self-regulate brain networks which in turn could lead to a change in behavior and clinical symptoms. The objective was to determine the effect of NF and motor training (MOT) alone on motor and non-motor functions in Parkinson's Disease (PD) in a 10-week small Phase I randomized controlled trial.

Methods: Thirty patients with Parkinson's disease (PD; Hoehn and Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups.

Real-time functional magnetic resonance imaging neurofeedback in motor neurorehabilitation.

Purpose Of Review: Recent developments in functional magnetic resonance imaging (fMRI) have catalyzed a new field of translational neuroscience. Using fMRI to monitor the aspects of task-related changes in neural activation or brain connectivity, investigators can offer feedback of simple or complex neural signals/patterns back to the participant on a quasireal-time basis [real-time-fMRI-based neurofeedback (rt-fMRI-NF)]. Here, we introduce some background methodology of the new developments in this field and give a perspective on how they may be used in neurorehabilitation in the future.

Spinal plasticity in robot-mediated therapy for the lower limbs.

Robot-mediated therapy can help improve walking ability in patients following injuries to the central nervous system. However, the efficacy of this treatment varies between patients, and evidence for the mechanisms underlying functional improvements in humans is poor, particularly in terms of neural changes in the spinal cord. Here, we review the recent literature on spinal plasticity induced by robotic-based training in humans and propose recommendations for the measurement of spinal plasticity using robotic devices.

Neurophysiology of robot-mediated training and therapy: a perspective for future use in clinical populations.

The recovery of functional movements following injury to the central nervous system (CNS) is multifaceted and is accompanied by processes occurring in the injured and non-injured hemispheres of the brain or above/below a spinal cord lesion. The changes in the CNS are the consequence of functional and structural processes collectively termed neuroplasticity and these may occur spontaneously and/or be induced by movement practice. The neurophysiological mechanisms underlying such brain plasticity may take different forms in different types of injury, for example stroke vs.

Recovery of submaximal upper limb force production is correlated with better arm position control and motor impairment early after a stroke.

Objective: This study determined whether recovery of upper limb position control using submaximal force production correlates with an improvement in functional arm impairment during early recovery from stroke.

Methods: Ten consecutive inpatients were recruited from a stroke unit. Each patient was in early recovery (<8 weeks post-lesion) from their first ever stroke.

Energy turnover in relation to slowing of contractile properties during fatiguing contractions of the human anterior tibialis muscle.

Slowing and loss of muscle power are major factors limiting physical performance but little is known about the molecular mechanisms involved. The slowing might be a consequence of slow detachment of cross bridges and, if this were the case, then a reduction in the ATP cost of an isometric contraction would be expected as the muscle fatigued. The human anterior tibialis muscle was stimulated repeatedly under ischaemic conditions at 50 Hz for 1.

Modulation of internal model formation during force field-induced motor learning by anodal transcranial direct current stimulation of primary motor cortex.

Human subjects can quickly adapt and maintain performance of arm reaching when experiencing novel physical environments such as robot-induced velocity-dependent force fields. Using anodal transcranial direct current stimulation (tDCS) this study showed that the primary motor cortex may play a role in motor adaptation of this sort. Subjects performed arm reaching movement trials in three phases: in a null force field (baseline), in a velocity-dependent force field (adaptation; 25 N s m(-1)) and once again in a null force field (de-adaptation).