Background Mirrored feedback has potential as a therapeutic intervention to restore hand function after stroke. However, the functional (effective) connectivity of neural networks involved in processing mirrored feedback after stroke is not known. Objective To determine if regions recruited by mirrored feedback topographically overlap with those involved in control of the paretic hand and to identify the effective connectivity of activated nodes within the mirrored feedback network. Methods Fifteen patients with chronic stroke performed a finger flexion task with their unaffected hand during event-related functional magnetic resonance imaging (fMRI). Real-time hand kinematics was recorded during fMRI and used to actuate hand models presented in virtual reality (VR). Visual feedback of the unaffected hand motion was manipulated pseudorandomly by either actuating the VR hand corresponding to the moving unaffected side (veridical feedback) or the affected side (mirrored feedback). In 2 control conditions, the VR hands were replaced with moving nonanthropomorphic shapes. Results Mirrored feedback was associated with significant activation of regions within and outside the ipsilesional sensorimotor cortex, overlapping with areas engaged when patients performed the task with their affected hand. Effective connectivity analysis showed a significantly interconnected ipsilesional somatosensory and motor cortex in the mirrored feedback condition. Conclusions Mirrored feedback recruits ipsilesional brain areas relevant for control of the affected hand. These data provide a neurophysiological basis by which mirrored feedback may be beneficial as a therapy for restoring function after stroke.

Several approaches to rehabilitation of the hand following a stroke have emerged over the last two decades. These treatments, including repetitive task practice (RTP), robotically assisted rehabilitation and virtual rehabilitation activities, produce improvements in hand function but have yet to reinstate function to pre-stroke levels—which likely depends on developing the therapies to impact cortical reorganization in a manner that favors or supports recovery. Understanding cortical reorganization that underlies the above interventions is therefore critical to inform how such therapies can be utilized and improved and is the focus of the current investigation. Specifically, we compare neural reorganization elicited in stroke patients participating in two interventions: a hybrid of robot-assisted virtual reality (RAVR) rehabilitation training and a program of RTP training. Ten chronic stroke subjects participated in eight 3-h sessions of RAVR therapy. Another group of nine stroke subjects participated in eight sessions of matched RTP therapy. Functional magnetic resonance imaging (fMRI) data were acquired during paretic hand movement, before and after training. We compared the difference between groups and sessions (before and after training) in terms of BOLD intensity, laterality index of activation in sensorimotor areas, and the effective connectivity between ipsilesional motor cortex (iMC), contralesional motor cortex, ipsilesional primary somatosensory cortex (iS1), ipsilesional ventral premotor area (iPMv), and ipsilesional supplementary motor area. Last, we analyzed the relationship between changes in fMRI data and functional improvement measured by the Jebsen Taylor Hand Function Test (JTHFT), in an attempt to identify how neurophysiological changes are related to motor improvement. Subjects in both groups demonstrated motor recovery after training, but fMRI data revealed RAVR-specific changes in neural reorganization patterns. First, BOLD signal in multiple regions of interest was reduced and re-lateralized to the ipsilesional side. Second, these changes correlated with improvement in JTHFT scores. Our findings suggest that RAVR training may lead to different neurophysiological changes when compared with traditional therapy. This effect may be attributed to the influence that augmented visual and haptic feedback during RAVR training exerts over higher-order somatosensory and visuomotor areas.

Mirror visual feedback (MVF) is potentially a powerful tool to facilitate recovery of disordered movement and stimulate activation of under-active brain areas due to stroke. The neural mechanisms underlying MVF have therefore been a focus of recent inquiry. Although it is known that sensorimotor areas can be activated via mirror feedback, the network interactions driving this effect remain unknown. The aim of the current study was to fill this gap by using dynamic causal modeling to test the interactions between regions in the frontal and parietal lobes that may be important for modulating the activation of the ipsilesional motor cortex during mirror visual feedback of unaffected hand movement in stroke patients. Our intent was to distinguish between two theoretical neural mechanisms that might mediate ipsilateral activation in response to mirror-feedback: transfer of information between bilateral motor cortices versus recruitment of regions comprising an action observation network which in turn modulate the motor cortex. In an event-related fMRI design, fourteen chronic stroke subjects performed goal-directed finger flexion movements with their unaffected hand while observing real-time visual feedback of the corresponding (veridical) or opposite (mirror) hand in virtual reality. Among 30 plausible network models that were tested, the winning model revealed significant mirror feedback-based modulation of the ipsilesional motor cortex arising from the contralesional parietal cortex, in a region along the rostral extent of the intraparietal sulcus. No winning model was identified for the veridical feedback condition. We discuss our findings in the context of supporting the latter hypothesis, that mirror feedback-based activation of motor cortex may be attributed to engagement of a contralateral (contralesional) action observation network. These findings may have important implications for identifying putative cortical areas, which may be targeted with non-invasive brain stimulation as a means of potentiating the effects of mirror training.

BackgroundRecovery of upper extremity function is particularly recalcitrant to successful rehabilitation. Robotic-assisted arm training devices integrated with virtual targets or complex virtual reality gaming simulations are being developed to deal with this problem. Neural control mechanisms indicate that reaching and hand-object manipulation are interdependent, suggesting that training on tasks requiring coordinated effort of both the upper arm and hand may be a more effective method for improving recovery of real world function. However, most robotic therapies have focused on training the proximal, rather than distal effectors of the upper extremity. This paper describes the effects of robotically-assisted, integrated upper extremity training.MethodsTwelve subjects post-stroke were trained for eight days on four upper extremity gaming simulations using adaptive robots during 2-3 hour sessions.ResultsThe subjects demonstrated improved proximal stability, smoothness and efficiency of the movement path. This was in concert with improvement in the distal kinematic measures of finger individuation and improved speed. Importantly, these changes were accompanied by a robust 16-second decrease in overall time in the Wolf Motor Function Test and a 24-second decrease in the Jebsen Test of Hand Function.ConclusionsComplex gaming simulations interfaced with adaptive robots requiring integrated control of shoulder, elbow, forearm, wrist and finger movements appear to have a substantial effect on improving hemiparetic hand function. We believe that the magnitude of the changes and the stability of the patient's function prior to training, along with maintenance of several aspects of the gains demonstrated at retention make a compelling argument for this approach to training.

BackgroundWe hypothesize that the integration of virtual reality (VR) with robot assisted rehabilitation could be successful if applied to children with hemiparetic CP. The combined benefits of increased attention provided by VR and the larger training stimulus afforded by adaptive robotics may increase the beneficial effects of these two approaches synergistically. This paper will describe the NJIT-RAVR system, which combines adaptive robotics with complex VR simulations for the rehabilitation of upper extremity impairments and function in children with CP and examine the feasibility of this system in the context of a two subject training study.MethodsThe NJIT-RAVR system consists of the Haptic Master, a 6 degrees of freedom, admittance controlled robot and a suite of rehabilitation simulations that provide adaptive algorithms for the Haptic Master, allowing the user to interact with rich virtual environments. Two children, a ten year old boy and a seven year old girl, both with spastic hemiplegia secondary to Cerebral Palsy were recruited from the outpatient center of a comprehensive pediatric rehabilitation facility. Subjects performed a battery of clinical testing and kinematic measurements of reaching collected by the NJIT-RAVR system. Subjects trained with the NJIT-RAVR System for one hour, 3 days a week for three weeks. The subjects played a combination of four or five simulations depending on their therapeutic goals, tolerances and preferences. Games were modified to increase difficulty in order to challenge the subjects as their performance improved. The testing battery was repeated following the training period.ResultsBoth participants completed 9 hours of training in 3 weeks. No untoward events occurred and no adverse responses to treatment or complaints of cyber sickness were reported. One participant showed improvements in overall performance on the functional aspects of the testing battery. The second subject made improvements in upper extremity active range of motion and in kinematic measures of reaching movements.ConclusionWe feel that this study establishes the feasibility of integrating robotics and rich virtual environments to address functional limitations and decreased motor performance in children with mild to moderate cerebral palsy.