Sabina Hotz-Boendermaker

Preservation of motor programs in paraplegics as demonstrated by attempted and imagined foot movements

Execution and imagination of movement activate distinct neural circuits, partially overlapping in premotor and parietal areas, basal ganglia and cerebellum. Can long-term deafferented/deefferented patients still differentiate attempted from imagined movements? The attempted execution and motor imagery network of foot movements have been investigated in nine chronic complete spinal cord-injured (SCI) patients using fMRI. Thorough behavioral assessment showed that these patients were able to differentiate between attempted execution and motor imagery. Supporting the outcome of the behavioral assessment, fMRI disclosed specific patterns of activation for movement attempt and for motor imagery. Compared with motor execution data of healthy controls, movement attempt in SCI patients revealed reduced primary motor cortex activation at the group level, although activation was found in all single subjects with a high variability. Further comparisons with healthy subjects revealed that during attempt and motor imagery, SCI patients show enhanced activation and recruitment of additional regions in the parietal lobe and cerebellum that are important in sensorimotor integration. These findings reflect central plastic changes due to altered input and output and suggest that SCI patients may require additional cognitive resources to perform these tasks that may be one and the same phenomenon, or two versions of the same phenomenon, with quantitative differences between the two. Nevertheless, the retained integrity of movement attempt and motor imagery networks in SCI patients demonstrates that chronic paraplegics can still dispose of the full motor programs for foot movements and that therefore, attempted and imagined movements should be integrated in rehabilitative strategies.

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.

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.

Movement Observation Activates Lower Limb Motor Networks in Chronic Complete Paraplegia

Background. In healthy subjects, observation of actions activates a motor network similar to that involved in the performance of the observed actions. Movement observation could perhaps be applied to functionally sustain brain motor functions when efferent motor commands and proprioceptive feedbacks are disconnected. Objective. The authors examined whether observation-induced brain activation is preserved in people with chronic complete spinal cord injury (SCI). Methods. Nine patients and 12 healthy subjects underwent behavioral assessment and functional magnetic resonance imaging. The SCI patients attempted to perform dorsal and plantar flexions of the right foot, and the controls also executed the same movement. Both groups observed subsequent video clips showing the same movement. Results. In the SCI group, attempted and observed foot movements activated a common observation–execution network including ventral premotor, parietal cortex, and cerebellum as in healthy subjects. Conclusions. Long after onset of complete SCI, the brain maintains its ability to respond to task-specific visual inputs, which suggests preservation of motor programs. This persistence might be a prerequisite for repair strategies of the spinal cord that rely on appropriate activation of the brain to try to restore limb function. The preserved cortical network may offer an additional motor rehabilitation approach for people with SCI.

Neural Correlates of Fear of Movement in Patients with Chronic Low Back Pain vs. Pain-Free Individuals

Fear of movement (FOM) can be acquired by a direct aversive experience such as pain or by social learning through observation and instruction. Excessive FOM results in heightened disability and is an obstacle for recovery from acute, subacute, and chronic low back pain (cLBP). FOM has further been identified as a significant explanatory factor in the Fear Avoidance (FA) model of cLBP that describes how individuals experiencing acute back pain may become trapped into a vicious circle of chronic disability and suffering. Despite a wealth of evidence emphasizing the importance of FOM in cLBP, to date, no related neural correlates in patients were found and this therefore has initiated a debate about the precise contribution of fear in the FA model. In the current fMRI study, we applied a novel approach encompassing: (1) video clips of potentially harmful activities for the back as FOM inducing stimuli; and (2) the assessment of FOM in both, cLBP patients (N = 20) and age- and gender-matched pain-free subjects (N = 20). Derived from the FA model, we hypothesized that FOM differentially affects brain regions involved in fear processing in patients with cLBP compared to pain-free individuals due to the recurrent pain and subsequent avoidance behavior. The results of the whole brain voxel-wise regression analysis revealed that: (1) FOM positively correlated with brain activity in fear-related brain regions such as the amygdala and the insula; and (2) differential effects of FOM between patients with cLBP and pain-free subjects were found in the extended amygdala and in its connectivity to the anterior insula. Current findings support the FOM component of the FA model in cLBP.

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.

Neural responses of posterior to anterior movement on lumbar vertebrae: a functional magnetic resonance imaging study.

OBJECTIVE The purpose of this study was to develop and test a clinically relevant method to mechanically stimulate lumbar functional spinal units while recording brain activity by means of functional magnetic resonance imaging (MRI). METHODS Subjects were investigated in the prone position with their face lying on a modified stabilization pillow. To minimize head motion, the pillow was fixed to the MRI headrest, and supporting straps were attached around the shoulders. An experienced manual therapist applied controlled, nonpainful pressure stimuli to 10 healthy subjects at 3 different lumbar vertebrae (L1, L3, and L5). Pressure applied to the thumb was used as a control. The stimulation consisted of posterior to anterior (PA) pressure movement. The therapist followed a randomized stimulation protocol projected onto a screen in the MRI room. Blood oxygenation level-dependent responses were analyzed in relation to the lumbar and the thumb stimulations. The study was conducted by the Chiropractic Department, Faculty of Medicine, University of Zürich, Switzerland. RESULTS No participant reported any discomfort due to the prone-lying position or use of the pillow. Importantly, PA-induced pressure produced only minimal head movements. Stimulation of the lumbar spinous processes revealed bilateral neural responses in medial parts of the postcentral gyrus (S1). Additional activity was observed in the secondary somatosensory cortex (S2), posterior parts of the insular cortex, different parts of the cingulate cortex, and the cerebellum. Thumb stimulations revealed activation only in lateral parts of the contralateral S1. CONCLUSION The current study demonstrates the feasibility of the application of PA pressure on lumbar spinous processes in an MRI environment. This approach may serve as a promising tool for further investigations regarding neuroplastic changes in chronic low back pain subjects.

Mismatch Between Investigator-Determined and Patient-Reported Independence After Spinal Cord Injury Consequences for Rehabilitation and Trials

Objective. This study investigated the course and relationship between investigator-determined and patient-reported level of independence within the first year after spinal cord injury (SCI). The authors examined variables that contributed to these scores. Methods. In this observational cohort study, 73 patients with traumatic SCI were evaluated at 1, 3, and 6 months (and 40 subjects at 1 to 12 months). The investigator-determined independence was quantified using the Spinal Cord Independence Measure (SCIM). The subjective, patient-reported independence was determined by asking how their general restrictions influenced everyday life activities. Several variables were used to explain these 2 scores. Results. The SCIM score was higher than the patient-reported independence and improved significantly more over time (up to about 70/100 at 12 months), whereas the perceived independence remained below 50/100. The correlations between the 2 measures were at most moderate (rs ≤ 0.51), but in general somewhat higher for subjects with tetraplegia. Age and muscle strength predicted the SCIM score well. No variable predicted the patient-reported level of independence. Conclusions. Investigator-determined and patient-reported outcomes can differ considerably and evolve differently. A patient-reported outcome measure may not detect actual functional improvement. It is likely that changes in patient-reported outcomes are influenced by many factors in addition to those associated with functional recovery, including psychological factors.

Fear avoidance beliefs in back pain-free subjects are reflected by amygdala-cingulate responses

In most individuals suffering from chronic low back pain, psychosocial factors, specifically fear avoidance beliefs (FABs), play central roles in the absence of identifiable organic pathology. On a neurobiological level, encouraging research has shown brain system correlates of somatic and psychological factors during the transition from (sub) acute to chronic low back pain. The characterization of brain imaging signatures in pain-free individuals before any injury will be of high importance regarding the identification of relevant networks for low back pain (LBP) vulnerability. Fear-avoidance beliefs serve as strong predictors of disability and chronification in LBP and current research indicates that back pain related FABs already exist in the general and pain-free population. Therefore, we aimed at investigating possible differential neural functioning between high- and low fear-avoidant individuals in the general population using functional magnetic resonance imaging. Results revealed that pain-free individuals without a history of chronic pain episodes could be differentiated in amygdala activity and connectivity to the pregenual anterior cingulate cortex by their level of back pain related FABs. These results shed new light on brain networks underlying psychological factors that may become relevant for enhanced disability in a future LBP episode.