Non Invasive Neuromodulation in Motor Recovery after Stroke: State of the Art, Open Questions and Future Perspectives

Stroke is a leading cause of adult disability in the western world [1]. Sensorimotor and cognitive impairments often have a great impact on quality of life in post stroke survivors. It is well known that the human brain continues to adjust throughout life. After ischemic brain injury, neuroplasticity is particularly active in the first months [2]. However, it has been demonstrated that, even years after stroke, the human brain still retains the capacity to reorganize in response to interventions influencing motor recovery [3]. Several efforts have focused on the development of new restorative therapies. In particular, non invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), constitute an extensive chapter on this topic. The rationale for the application of NIBS for rehabilitation of neurological deficits is its capacity of modulate cortical excitability and induce plasticity in humans. Repetitive TMS (rTMS) refers to regularly repeated single TMS pulses delivered in trains at specific frequencies. In general, low-frequency rTMS (≤ 1 Hz) usually results in cortical excitability reduction [4] in healthy subjects, whereas with higher frequencies (5 Hz or more) cortical excitability is usually increased [5]. Modulation by rTMS does not only depend on pulses frequency. Intensity of stimulation, trains duration and inter-train wait time can be all manipulated to influence neuroplasticity [6]. Theta-burst stimulation (TBS) is a relative more recent technique, consisting in brief bursts of theta frequency low intensity stimuli. TBS delivered in a continuous pattern (cTBS) produces a decrease in motor cortex excitability, while an intermitted paradigm (iTBS) produces an opposite effect [7]. The so called tDCS consists in the application of weak electrical currents through the scalp. This technique utilizes two surface electrodes (anode and cathode), which placement is fundamental for outcome, by determining the direction of the current flow. The montage with anode on the brain region of interest (anodal tDCS) has an excitatory effect (and cathodal tDCS the opposite), possibly through mechanisms involving neuronal membrane depolarization or hyperpolarization respectively [8,9].