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Background There is conflict regarding the benefits of greater amounts of intensive upper limb rehabilitation in the early period post-stroke. This study was conducted to test the feasibility of providing intensive therapy during the early period post-stroke and to develop a randomized control trial that is currently in process. Specifically, the study investigated whether an additional 8 h of specialized, intensive (200–300 separate hand or arm movements per hour) virtual reality (VR)/robotic based upper limb training introduced within 1-month post-stroke resulted in greater improvement in impairment and behavior, and distinct changes in cortical reorganization measured via Transcranial Magnetic Stimulation (TMS), compared to that of a control group. Methods Seven subjects received 8–1 h sessions of upper limb VR/robotic training in addition to their inpatient therapy (PT, OT, ST). Six subjects only received their inpatient therapy. All were tested on measures of impairment [Upper Extremity Fugl-Meyer Assessment (UEFMA), Wrist AROM, Maximum Pinch Force], behavior [Wolf Motor Function Test (WMFT)], and also received TMS mapping until 6 months post training. ANOVAs were conducted to measure differences between groups across time for all outcome measures. Associations between changes in ipsilesional cortical maps during the early period of enhanced neuroplasticity and long-term changes in upper limb impairment and behavior measures were evaluated. Results The VR/robotic group made significantly greater improvements on UEFMA and Wrist AROM scores compared to the usual care group. There was also less variability in the association between changes in the First Dorsal Interosseus (FDI) muscle map area and WMFT and Maximum Force change scores for the VR/robotic group. Conclusions An additional 8 h of intensive VR/robotic based upper limb training initiated within the first month post-stroke may promote greater gains in impairment compared to usual care alone. Importantly, the data presented demonstrated the feasibility of conducting this intervention and multiple outcome measures (impairment, behavioral, neurophysiological) in the early period post-stroke.

•The Dorsolateral grasping pathway responds to size and distance target perturbations.•The Dorsomedial pathway did not exhibit responses to perturbations of object position.•Virtual reality and TMS can be combined to study cortical responses to visual perturbations. Traditional research approaches to the reach-to-grasp movement have employed real-world perturbations involving physical objects. Recent technological advances provide new avenues for the investigation of sensorimotor control including the use of Virtual Reality Environments (VE). In this study, we used an immersive VE to produce compelling perturbations of target object size and position and Transcranial Magnetic Stimulation (TMS) to probe the neural bases of compensatory responses during grasping movements. Extensive research has identified a Dorsolateral (DL) and a Dorsomedial (DM) pathway as the likely neural bases for the sensorimotor coordination underlying grasping movements. In order to test the causal involvement of the parietal and premotor nodes of both pathways, we implemented visual perturbations of object size and distance at two different latencies (100 and 300 ms after movement onset) with concurrent TMS in a fully randomized design. The kinematic profiles of the grasping movements exhibited clear effects of the visual perturbations, particularly the late ones. We found that TMS stimulation of aIPS during the late perturbation of object size modified the timing of aperture closing. Similarly, TMS to PMv during the late perturbation of object distance reduced transport velocity during the compensatory double-peak. Our results support the involvement of the DL pathway when quick modifications including complex digit control are required. Against our expectations, sudden changes in target position did not elicit activity in the DM pathway. This study supports the notion that VE can be successfully employed for the study of the neural substrates of motor control.

Virtual reality (VR) has garnered much interest as a training environment for motor skill acquisition, including for neurological rehabilitation of upper extremities. While the focus has been on gross upper limb motion, VR applications that involve reaching for, and interacting with, virtual objects are growing. The absence of true haptics in VR when it comes to hand-object interactions raises a fundamentally important question: can haptic-free immersive virtual environments (hf-VEs) support naturalistic coordination of reach-to-grasp movements? This issue has been grossly understudied, and yet is of significant importance in the development and application of VR across a number of sectors. In a previous study (Furmanek et al., J Neuroeng Rehabil 16:78, 2019), we reported that reach-to-grasp movements are similarly coordinated in both the physical environment (PE) and hf-VE. The most noteworthy difference was that the closure phase—which begins at maximum aperture and lasts through the end of the movement—was longer in hf-VE than in PE, suggesting that different control laws might govern the initiation of closure between the two environments. To do so, we reanalyzed data from Furmanek et al. (J Neuroeng Rehabil 16:78, 2019), in which the participants reached to grasp three differently sized physical objects, and matching 3D virtual object renderings, placed at three different locations. Our analysis revealed two key findings pertaining to the initiation of closure in PE and hf-VE. First, the respective control laws governing the initiation of aperture closure in PE and hf-VE both included state estimates of transport velocity and acceleration, supporting a general unified control policy for implementing reach-to-grasp across physical and virtual environments. Second, the aperture was less informative to the control law in hf-VE. We suggest that the latter was likely because transport velocity at closure onset and aperture at closure onset were less independent in hf-VE than in PE, ultimately resulting in an aperture at closure onset having a weaker influence on the initiation of closure. In this way, the excess time and muscular effort needed to actively bring the fingers to a stop at the interface of a virtual object was factored into the control law governing the initiation of closure in hf-VE. Critically, this control law remained applicable, albeit with different weights in hf-VE, despite the absence of terminal haptic feedback and potential perceptual differences.

The purpose of this study was to investigate whether the anticipation of a mechanical perturbation applied to the arm during a reach-to-grasp movement elicits anticipatory adjustments in the reach and grasp components. Additionally, we aimed to evaluate whether anticipatory adjustments in the upper limb might be global or specific to the direction of the perturbation. Thirteen healthy participants performed reach-to-grasp with perturbations randomly applied to their dominant limb. Participants were presented with three types of trials: unperturbed (control), trials perturbed in a predictable manner (either Up or Down), or perturbed in a partially predictable manner (knowledge about the perturbation but not its specific direction). EMG activity of 16 muscles, as well as the kinematics of wrist, thumb, and index finger, were acquired and analyzed. When the perturbation was expected, EMG activity of the and muscles significantly increased about 50 - 200 ms before the perturbation onset. Peak acceleration of the reach was significantly higher and occurred earlier relative to control trials. Similar adjustments were observed in the grasp kinematics, reflected as significantly shorter time to peak aperture velocity and acceleration, as well as in increased activity of and 100-200 ms before perturbation onset. In summary, our data demonstrate that knowledge of an upcoming perturbation of reach during reach-to-grasp action triggers anticipatory adjustments not only in the muscles controlling the reach component, but also in those controlling grasp. Furthermore, our data revealed that the preparatory activations were generalized, rather than direction specific.

Background Virtual reality (VR) offers unprecedented opportunity as a scientific tool to study visuomotor interactions, training, and rehabilitation applications. However, it remains unclear if haptic-free hand-object interactions in a virtual environment (VE) may differ from those performed in the physical environment (PE). We therefore sought to establish if the coordination structure between the transport and grasp components remain similar whether a reach-to-grasp movement is performed in PE and VE. Method Reach-to-grasp kinematics were examined in 13 healthy right-handed young adults. Subjects were instructed to reach-to-grasp-to-lift three differently sized rectangular objects located at three different distances from the starting position. Object size and location were matched between the two environments. Contact with the virtual objects was based on a custom collision detection algorithm. Differences between the environments were evaluated by comparing movement kinematics of the transport and grasp components. Results Correlation coefficients, and the slope of the regression lines, between the reach and grasp components were similar for the two environments. Likewise, the kinematic profiles of the transport velocity and grasp aperture were strongly correlated across the two environments. A rmANOVA further identified some similarities and differences in the movement kinematics between the two environments - most prominently that the closure phase of reach-to-grasp movement was prolonged when movements were performed in VE. Conclusions Reach-to-grasp movement patterns performed in a VE showed both similarities and specific differences compared to those performed in PE. Additionally, we demonstrate a novel approach for parsing the reach-to-grasp movement into three phases- initiation, shaping, closure- based on established kinematic variables, and demonstrate that the differences in performance between the environments are attributed to the closure phase. We discuss this in the context of how collision detection parameters may modify hand-object interactions in VE. Our study shows that haptic-free VE may be a useful platform to study reach-to-grasp movements, with potential implications for haptic-free VR in neurorehabilitation.

Current research shows promise in restoring impaired hand function after stroke with the help of Mirror Visual Feedback (MVF), putatively by facilitating activation of sensorimotor areas of the brain ipsilateral to the moving limb. However, the MVF related clinical effects show variability across studies. MVF tasks that have been used place varying amounts of visuomotor demand on one's ability to complete the task. Therefore, we ask here whether varying visuomotor demand during MVF may translate to differences in brain activation patterns. If so, we argue that this may provide a mechanistic explanation for variable clinical effects. To address this, we used functional magnetic resonance imaging (fMRI) to investigate the interaction of target directed movement and MVF on the activation of, and functional connectivity between, regions within the visuomotor network. In an event-related fMRI design, twenty healthy subjects performed finger flexion movements using their dominant right hand, with feedback presented in a virtual reality (VR) environment. Visual feedback was presented in real time VR as either veridical feedback with and without a target (VT+ and VT-, respectively), or MVF with and without a target (MT+ and MT-, respectively). fMRI contrasts revealed predominantly activation in the ipsilateral intraparietal sulcus for the main effect of MVF and bilateral superior parietal activation for the main effect of target. Importantly, we noted significant and robust activation lateralized to the ipsilateral parietal cortex alone in the MT+ contrast with respect to the other conditions. This suggests that combining MVF with targeted movements performed using the right hand may redirect enhanced bilateral parietal activation due to target presentation to the ipsilateral cortex. Moreover, functional connectivity analysis revealed that the interaction between the ipsilateral parietal lobe and the motor cortex was significantly greater during target-directed movements with mirror feedback compared to veridical feedback. These findings provide a normative basis to investigate the integrity of these networks in patient populations. Identification of the brain regions involved in target directed movement with MVF in stroke may have important implications for optimal delivery of MVF based therapy.

Gradient mapping is an important technique to summarize high dimensional biological features as low dimensional manifold representations in exploring brain structure-function relationships at various levels of the cerebral cortex. While recent studies have characterized the major gradients of functional connectivity in several brain structures using this technique, very few have systematically examined the correspondence of such gradients across structures under a common systems-level framework. Using resting-state functional magnetic resonance imaging, here we show that the organizing principles of the isocortex, and those of the cerebellum and hippocampus in relation to the isocortex, can be described using two common functional gradients. We suggest that the similarity in functional connectivity gradients across these structures can be meaningfully interpreted within a common computational framework based on the principles of predictive processing. The present results, and the specific hypotheses that they suggest, represent an important step toward an integrative account of brain function. Analysis of functional MRI data from the Human Connectome Project and Brain Genomics Superstruct Project reveals common functional gradients among the human isocortex, cerebellum, and hippocampus.

Adaptive motor behavior requires efficient error detection and correction. The posterior parietal cortex is critical for on-line control of reach-to-grasp movements. Here we show a causal relationship between disruption of cortical activity within the anterior intraparietal sulcus (aIPS) by transcranial magnetic stimulation (TMS) and disruption of goal-directed prehensile actions (either grip size or forearm rotation, depending on the task goal, with reaching preserved in either case). Deficits were elicited by applying TMS within 65 ms after object perturbation, which attributes a rapid control process on the basis of visual feedback to aIPS. No aperture deficits were produced when TMS was applied to a more caudal region within the intraparietal sulcus, to the parieto-occipital complex (putative V6, V6A) or to the hand area of primary motor cortex. We contend that aIPS is critical for dynamic error detection during goal-dependent reach-to-grasp action that is visually guided.

Control of reach-to-grasp movements for deft and robust interactions with objects requires rapid sensorimotor updating that enables online adjustments to changing external goals (e.g., perturbations or instability of objects we interact with). Rarely do we appreciate the remarkable coordination in reach-to-grasp, until control becomes impaired by neurological injuries such as stroke, neurodegenerative diseases, or even aging. Modeling online control of human reach-to-grasp movements is a challenging problem but fundamental to several domains, including behavioral and computational neuroscience, neurorehabilitation, neural prostheses, and robotics. Currently, there are no publicly available datasets that include online adjustment of reach-to-grasp movements to object perturbations. This work aims to advance modeling efforts of reach-to-grasp movements by making publicly available a large kinematic and EMG dataset of online adjustment of reach-to-grasp movements to instantaneous perturbations of object size and distance performed in immersive haptic-free virtual environment (hf-VE). The presented dataset is composed of a large number of perturbation types (10 for both object size and distance) applied at three different latencies after the start of the movement.Measurement(s)kinematics • reach-to-grasp movementsTechnology Type(s)motion capture system • virtual reality • electromyographyFactor Type(s)movement time [ms] • peak transport velocity [cm/s] • time to peak transport velocity [ms] • peak transport acceleration [cm/s2] • time to peak transport acceleration [ms] • peak transport deceleration [cm/s2] • time to peak transport deceleration [ms] • peak aperture [cm] • peak aperture velocity [cm/s] • time to peak aperture velocity [ms] • peak aperture deceleration [cm/s2] • time to peak aperture deceleration [ms] • opening time [ms] • closure time [ms] • opening distance [cm] • closure distance [cm] • transport velocity at CO [cm/s] • transport acceleration at CO [cm/s2] • peak closure velocity [cm/s] • peak closure deceleration [cm/s2]Sample Characteristic - OrganismHomo sapiensMachine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16786258

Mirror visual feedback (MVF) training is a promising technique to promote activation in the lesioned hemisphere following stroke, and aid recovery. However, current outcomes of MVF training are mixed, in part, due to variability in the task undertaken during MVF. The present study investigated the hypothesis that movements directed toward visual targets may enhance MVF modulation of motor cortex (M1) excitability ipsilateral to the trained hand compared to movements without visual targets. Ten healthy subjects participated in a 2 × 2 factorial design in which feedback (veridical, mirror) and presence of a visual target (target present, target absent) for a right index-finger flexion task were systematically manipulated in a virtual environment. To measure M1 excitability, transcranial magnetic stimulation (TMS) was applied to the hemisphere ipsilateral to the trained hand to elicit motor evoked potentials (MEPs) in the untrained first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles at rest prior to and following each of four 2-min blocks of 30 movements (B1-B4). Targeted movement kinematics without visual feedback was measured before and after training to assess learning and transfer. FDI MEPs were decreased in B1 and B2 when movements were made with veridical feedback and visual targets were absent. FDI MEPs were decreased in B2 and B3 when movements were made with mirror feedback and visual targets were absent. FDI MEPs were increased in B3 when movements were made with mirror feedback and visual targets were present. Significant MEP changes were not present for the uninvolved ADM, suggesting a task-specific effect. Analysis of kinematics revealed learning occurred in visual target-directed conditions, but transfer was not sensitive to mirror feedback. Results are discussed with respect to current theoretical mechanisms underlying MVF-induced changes in ipsilateral excitability.