TECHNOLOGIES FOR ENHANCING MOVEMENT THERAPY AND COMBINATION THERAPIES Reinkensmeyer and Boninger

Overview  Rationale  Analysis of current state of the field  Promising directions for technology-enhanced therapy – European insights  Combination therapies  Defined as strategies that combine drug or cell-based therapeutics with technology for therapy  Conclusions

Rationale – “the theory”  There is use-dependent plasticity in almost all motor system injuries and diseases  Technology has the potential to allow:  More therapy with less supervision  Better quantification of therapy and its outcomes  New types of therapy, improving outcomes

State of the Field – “the practice”  Rapid growth of technology for therapy  However, results are mixed, picture unclear  Three examples from robot-assisted therapy Estimate of number of articles on robotic therapy devices, as a function of year (from Marchal et al. JNER 2009) Sales of therapeutic technology by Hocoma A.G.

State of the Field – “the practice”  VA MIT-MANUS study (Lo et al., NEJM 2010)  Chronic stroke patients, n = 127  Robot-assisted therapy is about as effective as dose- matched, intense therapist-delivered training  However, effect size was small (~3 Fugl-Meyer points)  Surprisingly, cost of delivery was similar

State of the Field – “the practice”  Lokomat stroke study (Hornby et al. Stroke 2008)  Chronic stroke patients, n = 48, ambulatory at study start  Training with the Lokomat was less effective than therapist- delivered training  Perhaps due to patient slacking

State of the Field – “the practice”  T-WREX/ARMEO Study  Chronic stroke patients, n = 28 ( Housman et al NNR)  After 1 week of training, patients achieved 60 minutes of therapy with 4 minutes of therapist supervision  Patients much preferred training  Therapy was marginally more effective than conventional, self-supervised training

Comparing “theory” with “practice”  There is use-dependent plasticity in almost all motor system injuries and diseases  Technology has the potential to allow:  More therapy with less supervision But machines can be expensive, limiting cost-benefit X  Better quantification of therapy and its outcomes New science emerging, therapy with technology more motivating  New types of therapy improving outcomes X ? In many cases, technology is equal or even inferior to conventional training

Promising directions for technology- enhanced therapy: European insights  Earlier after injury  Lower cost devices  Incorporating BCI’s  Wearable robots  More degrees of freedom  Improved feedback and control  Integrated approach of Charité Hospital  Computational modeling

TECHNOLOGY FOR EARLY MOBILIZATION AFTER STROKE: NEREBOT Giulio Rosati, University of Padua

Etienne Burdet, Imperial College LOWER COST DEVICES

Herman van der Kooij, Biomechanical Engineering University of Twente Less constrained robotic lower limb trainer Investigate coupling between paretic and not paretic joint Combination of exoskeletal walker and EEG/EMG control to substitute for walking INCORPORATING BCI’S AND MORE DOFS

INCORPORATING BCI’S: Prof. Jose Pons, Madrid BETTER Project

WEARABLE ROBOTS Prof. Jose Pons, Madrid BETTER Project

Scuola Superiore Sant’Anna Multiple degree of freedom elbow exoskeleton for rehabilitation Constrained degrees of freedom impairs rehabilitation MORE DOF

Schmidt, Fraunhofer Institute, Hesse, Charité Hospital, Berlin MORE DOF + BETTER CONTROLLER

ISIR Paris/Garches/CEA/Roby-Brami/Morel Multiple degree of freedom exoskeleton for rehabilitation MORE DOF

Hocoma, Zurich MORE DOF: LOKOMAT With university collaborators, Hocoma is adding the following enhancements to the Lokomat: Active actuation of the ankle joint. Frontal plane trunk and pelvis motion (more physiological than sagittal plane motion alone). Force rather than position control of joints. Orthopaedic rehabilitation viewed as a potentially big future market.

ETH Zurich BETTER FEEDBACK (SHOW VIDEO)

VIRTUAL REALITY + ROBOTICS AALBORG UNIVERSITY, DENMARK

NEW CONTROL STRATEGIES: ADAPTIVE ASSISTANCE U. Genoa, Morasso, Masia, Sanguineti Robot-therapy of hemiparetic patients, with a minimally assistive & progressively decreasing strategy for tracking movements

INTEGRATED APPROACH Charité Hospital, Hesse, Berlin

Modeling motor learning due to interactions between humans and robots  We saw very little work focused on modeling learning in response to robot- assisted therapy  However, one model seems quite significant for predicting response to therapeutic robot forces

MODELING HUMAN- ROBOT INTERACTION Prof. Etienne Burdet, Imperial College, London

Modeling interaction forces between humans and robots

SPINAL MAPS Prof. Silvestro Micera, Pisa and Zurich Monaco et al., J Neurophysiol, 2010 Use spinal maps to identify how rehabilitation modifies muscle coordination in specific patients (e.g., stroke).

Combination therapies  Defined as strategies that combine drug or cell- based therapeutics with technology for therapy  Arguably, this is the future of rehabilitation therapy  Focus in context of NSF/WTEC study:  Is there an important role for technology to play in the development of combination therapies?  Is there a scientifically interesting interaction between the training and the drug- or cell-based therapy?

THERAPY+ PLASTICITY TREATMENT Prof. James Fawcett, Cambridge

Therapy + Plasticity Treatment  Chondroitinase ABC is a bacterial enzyme that digests molecules that form cartilage-like barriers to axonal growth  Chondroitinase without training is not very effective

Therapy + Plasticity Treatment  Specific forelimb reaching rehabilitation (1 hour/day) with chondroitinase leads to a dramatic recovery of forelimb function

Therapy + Plasticity Treatment  General environmental enrichment (1 hour/day) makes animals worse at skilled paw reaching

Therapy + Plasticity Treatment  Plasticity treatment induces sprouting; rehabilitation prunes and connects  Enhancing one form of behavior can impact negatively on the learning of other behaviors  What does this mean for rehabilitative technology?  Technologies may provide control over which functions are reprogrammed, given the limited new potential of the restored network  Need technology and models for understanding capacity of new sprouting

Conclusions  There is rapid growth in new technologies for rehabilitation therapy  We are in a sort of second phase in which there are many approaches to make this technology better  However, there is still very little scientific insight into how technology can best promote plasticity  Significantly, there will be a “science of combination therapies”. It will be important to base technological design on this science.