Michael Villiger

Enhanced Activation of Motor Execution Networks Using Action Observation Combined with Imagination of Lower Limb Movements

The combination of first-person observation and motor imagery, i.e. first-person observation of limbs with online motor imagination, is commonly used in interactive 3D computer gaming and in some movie scenes. These scenarios are designed to induce a cognitive process in which a subject imagines himself/herself acting as the agent in the displayed movement situation. Despite the ubiquity of this type of interaction and its therapeutic potential, its relationship to passive observation and imitation during observation has not been directly studied using an interactive paradigm. In the present study we show activation resulting from observation, coupled with online imagination and with online imitation of a goal-directed lower limb movement using functional MRI (fMRI) in a mixed block/event-related design. Healthy volunteers viewed a video (first-person perspective) of a foot kicking a ball. They were instructed to observe-only the action (O), observe and simultaneously imagine performing the action (O-MI), or imitate the action (O-IMIT). We found that when O-MI was compared to O, activation was enhanced in the ventralpremotor cortex bilaterally, left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions shared many activation foci in motor relevant areas as confirmed by conjunction analysis. These results show that (i) combining observation with motor imagery (O-MI) enhances activation compared to observation-only (O) in the relevant foot motor network and in regions responsible for attention, for control of goal-directed movements and for the awareness of causing an action, and (ii) it is possible to extensively activate the motor execution network using O-MI, even in the absence of overt movement. Our results may have implications for the development of novel virtual reality interactions for neurorehabilitation interventions and other applications involving training of motor tasks.

Virtual Reality–Augmented Neurorehabilitation Improves Motor Function and Reduces Neuropathic Pain in Patients With Incomplete Spinal Cord Injury:

Background. Neurorehabilitation interventions to improve lower limb function and neuropathic pain have had limited success in people with chronic, incomplete spinal cord injury (iSCI). Objective. We hypothesized that intense virtual reality (VR)–augmented training of observed and executed leg movements would improve limb function and neuropathic pain. Methods. Patients used a VR system with a first-person view of virtual lower limbs, controlled via movement sensors fitted to the patient’s own shoes. Four tasks were used to deliver intensive training of individual muscles (tibialis anterior, quadriceps, leg ad-/abductors). The tasks engaged motivation through feedback of task success. Fourteen chronic iSCI patients were treated over 4 weeks in 16 to 20 sessions of 45 minutes. Outcome measures were 10 Meter Walking Test, Berg Balance Scale, Lower Extremity Motor Score, Spinal Cord Independence Measure, Locomotion and Neuropathic Pain Scale (NPS), obtained at the start and at 4 to 6 weeks before intervention. Results. In addition to positive changes reported by the patients (Patients’ Global Impression of Change), measures of walking capacity, balance, and strength revealed improvements in lower limb function. Intensity and unpleasantness of neuropathic pain in half of the affected participants were reduced on the NPS test. Overall findings remained stable 12 to 16 weeks after termination of the training. Conclusions. In a pretest/posttest, uncontrolled design, VR-augmented training was associated with improvements in motor function and neuropathic pain in persons with chronic iSCI, several of which reached the level of a minimal clinically important change. A controlled trial is needed to compare this intervention to active training alone or in combination.

Activity of human motor system during action observation is modulated by object presence.

Neurons in the monkey mirror neuron system (MNS) become active when actions are observed or executed. Increases in activity are greater when objects are engaged than when the actions are mimed. This modulation occurs even when object manipulation is hidden from view. We examined whether human motor systems are similarly modulated during action observation because such observation-related modulations are potentially mediated by a putative human MNS. Transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) of a grasping muscle while participants observed actual or pantomimed grasping movements whose endpoints were sometimes hidden from view. MEP amplitudes were found to be modulated by object presence. Critically, the object-based modulation was found when the participant directly observed object manipulation and when the object manipulation had to be inferred because it was hidden. These findings parallel studies of MNS activity in monkeys and support the hypothesis that the MNS influences motor system activity during action observation. Although the object-based modulation of MEP amplitudes was consistent with the hypotheses, the direction of the modulation was not—MEP amplitudes decreased during action observation in contrast to the increase that has previously been observed. We suggest that the decrease in MEP amplitude on object-present trials resulted from inhibitory mechanisms that were activated to suppress the observation-evoked response codes from generating overt muscle activity.

Relationship between structural brainstem and brain plasticity and lower-limb training in spinal cord injury: a longitudinal pilot study

Rehabilitative training has shown to improve significantly motor outcomes and functional walking capacity in patients with incomplete spinal cord injury (iSCI). However, whether performance improvements during rehabilitation relate to brain plasticity or whether it is based on functional adaptation of movement strategies remain uncertain. This study assessed training improvement-induced structural brain plasticity in chronic iSCI patients using longitudinal MRI. We used tensor-based morphometry (TBM) to analyze longitudinal brain volume changes associated with intensive virtual reality (VR)-augmented lower limb training in nine traumatic iSCI patients. The MRI data was acquired before and after a 4-week training period (16–20 training sessions). Before training, voxel-based morphometry (VBM) and voxel-based cortical thickness (VBCT) assessed baseline morphometric differences in nine iSCI patients compared to 14 healthy controls. The intense VR-augmented training of limb control improved significantly balance, walking speed, ambulation, and muscle strength in patients. Retention of clinical improvements was confirmed by the 3–4 months follow-up. In patients relative to controls, VBM revealed reductions of white matter volume within the brainstem and cerebellum and VBCT showed cortical thinning in the primary motor cortex. Over time, TBM revealed significant improvement-induced volume increases in the left middle temporal and occipital gyrus, left temporal pole and fusiform gyrus, both hippocampi, cerebellum, corpus callosum, and brainstem in iSCI patients. This study demonstrates structural plasticity at the cortical and brainstem level as a consequence of VR-augmented training in iSCI patients. These structural changes may serve as neuroimaging biomarkers of VR-augmented lower limb neurorehabilitation in addition to performance measures to detect improvements in rehabilitative training.

Virtual reality rehabilitation system for neuropathic pain and motor dysfunction in spinal cord injury patients

Spinal cord injury (SCI) causes both lower limb motor dysfunction and associated neuropathic pain. Although these two conditions share related cortical mechanisms, different interventions are currently used to treat each condition. With intensive training using entertaining virtual reality (VR) scenarios, it may be possible to reshape cortical networks thereby reducing neuropathic pain and improving motor function. We have created the first VR training system combining action observation and execution addressing lower limb function in incomplete SCI (iSCI) patients. A particular feature of the system is the use of size-adjustable shoes with integrated motion sensors. A pilot single-case clinical study is currently being conducted on six iSCI patients. Two patients tested to date were highly motivated to perform and reported improved physical well-being. They improved in playing skill and in controlling the virtual lower limbs. There were post-intervention indications of neuropathic pain decrease, muscle strength increase, faster walking speed and improved performance on items relevant for ambulation. In addition functional MRI before and after treatment revealed a decreased activation pattern. We interpret this result as an improvement of neuronal synergies for this task. These results suggest that our VR system may be beneficial for both reducing neuropathic pain and improving motor function in iSCI patients.

Spinal cord injury affects the interplay between visual and sensorimotor representations of the body

The brain integrates multiple sensory inputs, including somatosensory and visual inputs, to produce a representation of the body. Spinal cord injury (SCI) interrupts the communication between brain and body and the effects of this deafferentation on body representation are poorly understood. We investigated whether the relative weight of somatosensory and visual frames of reference for body representation is altered in individuals with incomplete or complete SCI (affecting lower limbs’ somatosensation), with respect to controls. To study the influence of afferent somatosensory information on body representation, participants verbally judged the laterality of rotated images of feet, hands, and whole-bodies (mental rotation task) in two different postures (participants’ body parts were hidden from view). We found that (i) complete SCI disrupts the influence of postural changes on the representation of the deafferented body parts (feet, but not hands) and (ii) regardless of posture, whole-body representation progressively deteriorates proportionally to SCI completeness. These results demonstrate that the cortical representation of the body is dynamic, responsive, and adaptable to contingent conditions, in that the role of somatosensation is altered and partially compensated with a change in the relative weight of somatosensory versus visual bodily representations.

A reliability study on brain activation during active and passive arm movements supported by an MRI-compatible robot

In neurorehabilitation, longitudinal assessment of arm movement related brain function in patients with motor disability is challenging due to variability in task performance. MRI-compatible robots monitor and control task performance, yielding more reliable evaluation of brain function over time. The main goals of the present study were first to define the brain network activated while performing active and passive elbow movements with an MRI-compatible arm robot (MaRIA) in healthy subjects, and second to test the reproducibility of this activation over time. For the fMRI analysis two models were compared. In model 1 movement onset and duration were included, whereas in model 2 force and range of motion were added to the analysis. Reliability of brain activation was tested with several statistical approaches applied on individual and group activation maps and on summary statistics. The activated network included mainly the primary motor cortex, primary and secondary somatosensory cortex, superior and inferior parietal cortex, medial and lateral premotor regions, and subcortical structures. Reliability analyses revealed robust activation for active movements with both fMRI models and all the statistical methods used. Imposed passive movements also elicited mainly robust brain activation for individual and group activation maps, and reliability was improved by including additional force and range of motion using model 2. These findings demonstrate that the use of robotic devices, such as MaRIA, can be useful to reliably assess arm movement related brain activation in longitudinal studies and may contribute in studies evaluating therapies and brain plasticity following injury in the nervous system.

Home-Based Virtual Reality-Augmented Training Improves Lower Limb Muscle Strength, Balance and Functional Mobility Following Chronic Incomplete Spinal Cord Injury

Key factors positively influencing rehabilitation and functional recovery after spinal cord injury (SCI) include training variety, intensive movement repetition, and motivating training tasks. Systems supporting these aspects may provide profound gains in rehabilitation, independent of the subject’s treatment location. In the present study, we test the hypotheses that virtual reality (VR)-augmented training at home (i.e., unsupervised) is feasible with subjects with an incomplete SCI (iSCI) and that it improves motor functions such as lower limb muscle strength, balance, and functional mobility. In the study, 12 chronic iSCI subjects used a home-based, mobile version of a lower limb VR training system. The system included motivating training scenarios and combined action observation and execution. Virtual representations of the legs and feet were controlled via movement sensors. The subjects performed home-based training over 4 weeks, with 16–20 sessions of 30–45 min each. The outcome measures assessed were the Lower Extremity Motor Score (LEMS), Berg Balance Scale (BBS), Timed Up and Go (TUG), Spinal Cord Independence Measure mobility, Walking Index for Spinal Cord Injury II, and 10 m and 6 min walking tests. Two pre-treatment assessment time points were chosen for outcome stability: 4 weeks before treatment and immediately before treatment. At post-assessment (i.e., immediately after treatment), high motivation and positive changes were reported by the subjects (adapted Patients’ Global Impression of Change). Significant improvements were shown in lower limb muscle strength (LEMS, P = 0.008), balance (BBS, P = 0.008), and functional mobility (TUG, P = 0.007). At follow-up assessment (i.e., 2–3 months after treatment), functional mobility (TUG) remained significantly improved (P = 0.005) in contrast to the other outcome measures. In summary, unsupervised exercises at home with the VR training system led to beneficial functional training effects in subjects with chronic iSCI, suggesting that it may be useful as a neurorehabilitation tool. Trial registration Canton of Zurich ethics committee (EK-24/2009, PB_2016-00545), ClinicalTrials.gov: NCT02149186. Registered 24 April 2014.

Corrigendum: Spinal cord injury affects the interplay between visual and sensorimotor representations of the body.

Corrigendum: Spinal cord injury affects the interplay between visual and sensorimotor representations of the body