Combining motor learning and brain stimulation to enhance post-stroke neurorehabilitation

摘要

Worldwide, stroke is a leading cause of life-long disability resulting in dramatic restrictions in patient's independence and in a growing economic burden for the community. The majority of stroke survivors suffers from chronic sequels among which hemiparesis is one of the most debilitating. Despite quick progresses over the last 20 years, the impact of neurorehabilitation on post-stroke recovery remains unsatisfactory. Developing new ways to enhance neurorehabilitation could thus benefit to millions of patients. A better insight into the physiology of the normal motor system and the mechanisms driving post-stroke recovery and neural plasticity should permit to develop a new science of neurorehabilitation. Motor recovery and motor learning after stroke: The recovery of motor function after stroke builds upon several partly overlapping processes: oedema reduction, inflammatory changes, dynamical modulation of the excitability in the perilesional zone with connectivity modulations throughout the brain, use-dependent selection of the residual motor pathways, plastic reorganisation of the (pre-)motor areas with functional and structural remodelling, development of compensatory strategies,…(Nudo, 2013). Over the last 20 years, brain imaging studies – especially those using functional magnetic resonance imaging (fMRI) – started to unveil post-stroke neuroplasticity i.e., how the brain reorganizes itself after a stroke. However, the main conclusion is desperately self-evident: the more the reorganised patterns tend towards those observed in healthy individuals, the better the recovery. Nevertheless, the “abnormal” activations found in the perilesional zone or in remote areas of the damaged and/or undamaged hemispheres may reflect the adaptive recruitment of spared neural resources, i.e., compensatory neuroplasticity. The precise involvement of the undamaged hemisphere in the recovery process is still debated (Grefkes and Ward 2014). Beyond force training, spasticity reduction or repeating movements, the recovery of some level of skilled aptitudes and the development of alternative motor strategies are likely acquired through experience-dependent training and retained through residual motor learning aptitudes. In other words, without the involvement of (some forms of) motor learning, neurorehabilitation programs could not lead to long-term gains in stroke patients (Zeiler et al., 2013). Therefore, any intervention improving motor learning potential of stroke patients should enhance the impact of neurorehabilitation. Dual-transcranial direct current stimulation (tDCS) enhances motor learning and retention: Non-invasive brain stimulations (NIBS) transiently modulate cortical excitability and behavioural performance in healthy individuals and stroke patients (Stagg and Nitsche, 2011; Orban and Shadmehr, 2014). Transcranial direct current stimulation (tDCS, a promising form of NIBS) can enhance motor skill learning in healthy individuals and the impact of neurorehabilitation after stroke (Reis et al., 2009; Madhavan and Shah, 2012). The mechanisms of tDCS are still not fully elucidated but entail a transient modulation of the resting membrane potential of cortical neurones leading to hyperpolarisation (cathode)/depolarisation (anode), reducing/increasing in turns the responsiveness of the target neurones to the on-going afferent brain activity. This allows longer-lasting changes in strength/coupling of GABAergic (γ-aminobutyric acid) and glutamatergic synapses, which could be the basis for the after-effects that last up to 1 hour (Stagg and Nitsche, 2011; Orban and Shadmehr, 2014). After a stroke, the balance between interhemispheric interactions can be deregulated, leading to excessive inhibitory drive from the undamaged towards the damaged hemisphere, which can impede the recovery potential of the damaged hemisphere (Murase et al., 2004). To correct this deregulated interhemispheric interactions, three neuro-modulation strategies based