Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration.
Following an ischemic insult within the motor cortex, one or more body parts contralateral to the infarct result impaired or paretic. The degree of the motor impairment depends on many factors, such as the extent of the infarct, the identity of the damaged region(s) and the effectiveness of the early medical care. Substantial functional recovery can occur in the first weeks after stroke, mainly due to spontaneous mechanisms (Kwakkel et al., 2004; Cramer, 2008; Darling et al., 2011; Ward, 2011; Grefkes and Fink, 2014). About 26% of stroke survivors are able to carry on everyday activities (Activity of Daily Living or ADLs, i.e., eating, drinking, walking, dressing, bathing, cooking, writing) without any help, but another 26% is forced to shelter in a nursing home (Carmichael, 2005). Impairments of upper and lower limbs are particularly disabling as they impact on the degree of independence in ADLs. Overall, a significant percentage of the patients exhibit persistent disability following ischemic attacks. Therefore, it is critical to increase our knowledge of post-stroke neuroplasticity for implementing novel rehabilitative strategies. In this review we summarize data about plastic reorganizations after injury, both in the ipsilesional and contralesional hemisphere. We also describe non-invasive brain stimulation (NIBS) techniques and robotic devices for stimulating functional recovery in humans and rodent stroke models.
Neuroplasticity After Stroke
The term brain plasticity defines all the modifications in the organization of neural components occurring in the central nervous system during the entire life span of an individual (Sale et al., 2009). Such changes are thought to be highly involved in mechanisms of aging, adaptation to environment and learning. Moreover, neuronal plastic phenomena are likely to be at the basis of adaptive modifications in response to anatomical or functional deficit or brain damage (Nudo, 2006). Ischemic damage causes a dramatic alteration of the entire complex neural network within the affected area. It has been amply demonstrated, by many studies, that the cerebral cortex exhibits spontaneous phenomena of brain plasticity in response to damage (Gerloff et al., 2006; Nudo, 2007). The destruction of neural networks indeed stimulates a reorganization of the connections and this rewiring is highly sensitive to the experience following the damage (Stroemer et al., 1993; Li and Carmichael, 2006). Such plastic phenomena involve particularly the perilesional tissue in the injured hemisphere, but also the contralateral hemisphere, subcortical and spinal regions.
Figure 3. Example of a novel robotic system that integrates functional grasping, active reaching arm training and bimanual tasks. An example of a novel robotic system that integrates functional grasping, active reaching arm training and bimanual tasks, consisting of: (i) Virtual Reality: software applications composed of rehabilitative and evaluation tasks; (ii) TrackHold: robotic device to support the weight of the user’s limb during tasks execution; (iii) Robotic Hand Exos: active hand exoskeleton to assist grasping tasks; and (iv) Handgrip sensors to support the bilateral grasping training and evaluation (modified from Sgherri et al., 2017).
Background. Stroke is a major cause of disability worldwide, and effective rehabilitation is crucial to regain skills for independent living. Recently, novel therapeutic approaches manipulating the excitatory-inhibitory balance of the motor cortex have been introduced to boost recovery after stroke. However, stroke-induced neurophysiological changes of the motor cortex may vary despite of similar clinical symptoms. Therefore, better understanding of excitability changes after stroke is essential when developing and targeting novel therapeutic approaches.
Objective and Methods. We identified recovery-related alterations in motor cortex excitability after stroke using magnetoencephalography. Dynamics (suppression and rebound) of the ~20-Hz motor cortex rhythm were monitored during passive movement of the index finger in 23 stroke patients with upper limb paresis at acute phase, 1 month, and 1 year after stroke.
Results. After stroke, the strength of the ~20-Hz rebound to stimulation of both impaired and healthy hand was decreased with respect to the controls in the affected (AH) and unaffected (UH) hemispheres, and increased during recovery. Importantly, the rebound strength was lower than that of the controls in the AH and UH also to healthy-hand stimulation despite of intact afferent input. In the AH, the rebound strength to impaired-hand stimulation correlated with hand motor recovery.
Conclusions. Motor cortex excitability is increased bilaterally after stroke and decreases concomitantly with recovery. Motor cortex excitability changes are related to both alterations in local excitatory-inhibitory circuits and changes in afferent input. Fluent sensorimotor integration, which is closely coupled with excitability changes, seems to be a key factor for motor recovery.
Walking is a complex motor behavior with a special relevance in clinical neurology. Many neurological diseases, such as Parkinson’s disease and stroke, are characterized by gait disorders whose neurofunctional correlates are poorly investigated. Indeed, the analysis of real walking with the standard neuroimaging techniques poses strong challenges, and only a few studies on motor imagery or walking observation have been performed so far. Functional near-infrared spectroscopy (fNIRS) is becoming an important research tool to assess functional activity in neurological populations or for special tasks, such as walking, because it allows investigating brain hemodynamic activity in an ecological setting, without strong immobility constraints. A systematic review following PRISMA guidelines was conducted on the fNIRS-based examination of gait disorders. Twelve of the initial yield of 489 articles have been included in this review. The lesson learnt from these studies suggest that oxy-hemoglobin levels within the prefrontal and premotor cortices are more sensitive to compensation strategies reflecting postural control and restoration of gait disorders. Although this field of study is in its relative infancy, the evidence provided encourages the translation of fNIRS in clinical practice, as it offers a unique opportunity to explore in depth the activity of the cortical motor system during real walking in neurological patients. We also discuss to what extent fNIRS may be applied for assessing the effectiveness of rehabilitation programs.
Walking is one of the most fundamental motor functions in humans,1–3 often impaired in some focal neurological conditions (ie, stroke), or neurodegenerative diseases, such as Parkinson’s disease (PD).4 Worldwide almost two thirds of people over 70 years old suffer from gait disorders, and because of the progressively ageing population, an increasing pressure on health care systems is expected in the coming years.5
Although the physiological basis of walking is well understood, pathophysiological mechanisms in neurological patients have been poorly described. This is caused by the difficulty to assess in vivo neuronal processes during overt movements.
During the past 20 years, functional magnetic resonance imaging (fMRI) has been the preferred instrument to investigate mechanisms underlying movement control6 as well as movement disorders.7 fMRI allows measuring the blood oxygenation level-dependent (BOLD) signal that, relying on variations in deoxy-hemoglobin (deoxyHb) concentrations, provides an indirect measure of functional activity of the human brain.8 Patterns of activation/deactivation and connectivity across brain regions can be detected with a very high spatial resolution for both cortical and subcortical structures. This technique, however, is characterized by severe limitations and constraints about motion artifacts and only small movements are allowed inside the scanner. This entails dramatic compromises on the experimental design and on the inclusion/exclusion criteria. Multiple solutions have been attempted to overcome such limitations. For instance, many neuroimaging studies have been performed on the motor imagery,9,10 but imaging can be different from subject to subject,11 and imagined walking and actual walking engage different brain networks.12 Other authors have suggested the application of virtual reality,13 and there have been a few attempts to allow an almost real-walking sequence while scanning with fMRI.14,15Additional opportunities to investigate the mechanisms sustaining walking control include the use of surrogate tasks in the scanner as proxy of walking tasks,16 or to “freeze” brain activations during walking using positron emission tomography (PET) radiotracers, which allow the retrospective identification of activation patterns, albeit with some uncertainties and low spatial and temporal resolution.12
Therefore, until now there has not been an ecological way to noninvasively assess neurophysiological correlates of walking processes in gait disorders.
Functional near-infrared spectroscopy (fNIRS) is becoming an important research tool to assess functional activity in special populations (neurological and psychiatric patients)17 or for special tasks.18–21 fNIRS is a noninvasive optical imaging technique that, similarly to fMRI, measures the hemodynamic response to infer the underlying neural activity. Optical imaging is based on near-infrared (650-1000 nm) light propagation into scattering tissues and its absorption by 2 major chromophores in the brain, oxy-hemoglobin (oxyHb) and deoxyHb, which show specific absorption spectra depending on the wavelength of the photons.22 Typically, an fNIRS apparatus is composed of a light source that is coupled to the participant’s head via either light-emitting diodes (LEDs) or through fiber-optical bundles with a detector that receives the light after it has been scattered through the tissue. A variation of the optical density of the photons measured by detectors depends on the absorption of the biological tissues (Figure 1A). Using more than one wavelength and applying the modified Beer-Lambert law, it is possible to infer on the changes of oxyHb and deoxyHb concentrations.23 fNIRS has a number of definite advantages compared to fMRI, its major competitor: (a) it does not pose immobility constrains,25 (b) is portable,26 (c) allows recording during real walking,27 (d) allows long-lasting recordings, (e) it does not produce any noise, (f) it makes possible the investigation of brain activity during sleep,28 (f) it allows to obtain a richer picture of the neurovascular coupling as it measures changes in both oxyHb and deoxyHb concentration with high temporal resolution (up to milliseconds). High temporal resolution is usually not mandatory for the investigation of the hemodynamic response whose dynamic takes at least 3 to 5 seconds, but it can be useful for the study of transient hemodynamic activity like the initial dip29 or to detect subtle temporal variations in the latency of the hemodynamic response across different experimental conditions.19,21,30 The major drawback of fNIRS in comparison to fMRI is its lower spatial resolution (few centimeters under the skull) and its lack of sensitivity to subcortical regions.18,19 However, this might be considered a minor limitation, as there is a large body of evidence suggesting that (a) cortical mechanisms take place in walking,31 (b) the organization of the motor system is distributed along large brain regions,32and (c) the function of subcortical structures is mirrored in the cerebral cortex.33
Figure 1. Illustration of penetration depth of near-infrared light into the tissue in a probe configuration used to investigate motor performances during walking task (upper row). The picture shows brain reconstruction from a high-resolution anatomical MRI. The spheres placed over the skull correspond to vitamin E capsules employed during the MRI to mark the positions of the optodes and to allow the coregistration of the individual anatomy together with the optode position. In this illustration, only the photons propagation from one source (S) to one detector (D) have been simulated. The yellow-red scale indicates the degree of sensitivity74 for the considered source-detector pair to the head/brain structures. (A, B, and C) Lower row: Examples of fNIRS experimental device used for assessing brain activity during real walking tasks. These fNIRS approaches included either commercial device, such as (A) wireless portable fNIRS system (NIRx; Germany) or support systems for treadmill walking activity with body weight support24 (B) or with free movement range (C).
While motor recovery following mild stroke has been extensively studied with neuroimaging, mechanisms of recovery after moderate to severe strokes of the types that are often the focus for novel restorative therapies remain obscure. We used fMRI to: 1) characterize reorganization occurring after moderate to severe subacute stroke, 2) identify brain regions associated with motor recovery and 3) to test whether brain activity associated with passive movement measured in the subacute period could predict motor outcome six months later.
Because many patients with large strokes involving sensorimotor regions cannot engage in voluntary movement, we used passive flexion-extension of the paretic wrist to compare 21 patients with subacute ischemic stroke to 24 healthy controls one month after stroke. Clinical motor outcome was assessed with Fugl-Meyer motor scores (motor-FMS) six months later. Multiple regression, with predictors including baseline (one-month) motor-FMS and sensorimotor network regional activity (ROI) measures, was used to determine optimal variable selection for motor outcome prediction. Sensorimotor network ROIs were derived from a meta-analysis of arm voluntary movement tasks. Bootstrapping with 1000 replications was used for internal model validation.
During passive movement, both control and patient groups exhibited activity increases in multiple bilateral sensorimotor network regions, including the primary motor (MI), premotor and supplementary motor areas (SMA), cerebellar cortex, putamen, thalamus, insula, Brodmann area (BA) 44 and parietal operculum (OP1-OP4). Compared to controls, patients showed: 1) lower task-related activity in ipsilesional MI, SMA and contralesional cerebellum (lobules V-VI) and 2) higher activity in contralesional MI, superior temporal gyrus and OP1-OP4. Using multiple regression, we found that the combination of baseline motor-FMS, activity in ipsilesional MI (BA4a), putamen and ipsilesional OP1 predicted motor outcome measured 6 months later (adjusted-R2 = 0.85; bootstrap p < 0.001). Baseline motor-FMS alone predicted only 54% of the variance. When baseline motor-FMS was removed, the combination of increased activity in ipsilesional MI-BA4a, ipsilesional thalamus, contralesional mid-cingulum, contralesional OP4 and decreased activity in ipsilesional OP1, predicted better motor outcome (djusted-R2 = 0.96; bootstrap p < 0.001).
In subacute stroke, fMRI brain activity related to passive movement measured in a sensorimotor network defined by activity during voluntary movement predicted motor recovery better than baseline motor-FMS alone. Furthermore, fMRI sensorimotor network activity measures considered alone allowed excellent clinical recovery prediction and may provide reliable biomarkers for assessing new therapies in clinical trial contexts. Our findings suggest that neural reorganization related to motor recovery from moderate to severe stroke results from balanced changes in ipsilesional MI (BA4a) and a set of phylogenetically more archaic sensorimotor regions in the ventral sensorimotor trend. OP1 and OP4 processes may complement the ipsilesional dorsal motor cortex in achieving compensatory sensorimotor recovery.
Fig. 2. Four axial slices representative showing stroke lesion extent in 21 patients (FLAIR images).
The capacity for functional restitution after brain damage is quite different in the sensory and motor systems. This series of presentations highlights the potential for adaptation, plasticity, and perceptual learning from an interdisciplinary perspective. The chances for restitution in the primary visual cortex are limited. Some patterns of visual field loss and recovery after stroke are common, whereas others are impossible, which can be explained by the arrangement and plasticity of the cortical map. On the other hand, compensatory mechanisms are effective, can occur spontaneously, and can be enhanced by training. In contrast to the human visual system, the motor system is highly flexible. This is based on special relationships between perception and action and between cognition and action. In addition, the healthy adult brain can learn new functions, e.g. increasing resolution above the retinal one. The significance of these studies for rehabilitation after brain damage will be discussed.
Introduction by S. Trauzettel-Klosinski
This symposium highlighted the potential for learning and re-learning after visual and motor cortex lesions in the adult brain from an interdisciplinary perspective. We considered mechanisms such as adaptation, plasticity, and perceptual learning of different brain functions, as well as their applications for rehabilitation in patients with brain damage. Additionally, the potential for visual learning in the normal human brain was demonstrated.
In the visual system, the potential for recovery in the primary visual cortex is limited (part 1 by Jonathan Horton). Visual field defects caused by embolic stroke are constrained by the organization of the blood supply of the occipital lobe with respect to the retinotopic map. In terms of the arrangement and plasticity of the cortical map, it will be explained why some patterns of visual field loss and recovery following stroke are common, whereas others are essentially impossible. This is especially true along a visual field strip of constant width along the vertical meridian.
While the restitutive capacities of the primary visual cortex are limited, compensatory mechanisms can be very effective (part 2 by Susanne Trauzettel-Klosinski). They can occur spontaneously and can further be enhanced by training. In hemianopia, for example, fixational eye movements and scanning saccades can shift the visual field border towards the hemianopic side and improve spatial orientation and mobility.
In contrast to the visual system, the human motor system is highly flexible (part 3 by Theo Mulder). It is updated continuously by itself on the basis of sensory input and activity. The plasticity of the motor system is based on a special relationship between perception and action, as well as between cognition and action. New approaches to rehabilitation, for example by motor imagery, give an outlook on future possibilities.
Additionally, the healthy adult brain can learn new visual functions (part 4 by Manfred Fahle), for example the enhancement of resolution, which is higher than that of the retina. These functions, especially hyperacuity, can also be trained.
The authors will present a summary for each of the four talks.
Part 1: visual field recovery after lesions of the occipital lobe by Jonathan C. Horton
Recently, I attended a 60-year-old woman who had a spontaneous left parietal hemorrhage (Fig. 1). She underwent an emergency craniotomy to evacuate the hematoma. Her main deficit was a severe aphasia, which improved slowly. Once she regained sufficient ability to communicate, she complained about her vision on the right side. Her examination showed a total, macula-splitting right homonymous hemianopia. She has made nearly a complete recovery from her stroke, except for this devastating visual field cut. It has made reading a chore, forced her to give up driving, and will prevent her from returning to her job. This is a common scenario: after surviving a neurological disaster, patients discover that vision loss represents their most serious and enduring deficit. Why does central vision loss persist, and remain so stubbornly resistant to treatment?
Fig. 1 CT scan showing an acute left parietal hematoma, causing a right homonymous hemianopia. A CT scan performed 5 months later shows damage to the left optic radiations. The visual field cut never recovered
The answer lies in the organization of the visual pathway from eye to cortex. Retinal ganglion cell axons that are responsible for conscious perception project to the lateral geniculate nucleus. It serves as a relay station, boosting the information content of outgoing spikes compared with incoming spikes by integrating and filtering retinal signals . Geniculate neurons send their projection to layer 4 of the primary visual cortex. Simply by crossing a single synapse in the thalamus, retinal output is conveyed directly to the primary visual cortex. In a sense, the retino-geniculo-cortical pathway is the aorta of our visual system (Fig. 2). After initial processing in the primary visual cortex, signals are analyzed in surrounding cortical areas that are specialized for different attributes, allowing us to perceive the images that impinge upon our retinae.
Fig. 2 Retinal input is conveyed to the primary (striate) cortex by a two-neuron chain, crossing a single relay in the lateral geniculate nucleus. Injury at any point cuts off visual perception, although a small projection (green shading) from the lateral geniculate to area MT allows “blindsight” in patients with homonymous hemianopia caused by a post-chiasmal lesion (pink shading). After Polyak (1957)
Transcranial magnetic stimulation (TMS) has been first described 30 years ago, and since then has gained enormous attention by neurologists, psychiatrists, neurosurgeons, clinical neurophysiologists, psychologists, and neuroscientist alike. In the early days, it was primarily used to test integrity of the corticospinal tract. Beyond further developments of TMS in diagnostics, mapping and monitoring of the motor system, major other applications expanded into using TMS as research tool in the cognitive neurosciences, and as therapeutic tool in neurological and psychiatric disease by virtue of inducing long-term change in excitability and connectivity of the stimulated brain networks. This mini-review will highlight these developments by reviewing the 10 most frequently cited TMS publications. Despite the tremendous popularity and success of TMS as a non-invasive technique to stimulate the human brain, several aims remain unresolved. This review will end with highlighting those 10 most frequently cited papers that have been published in 2014–2016 to indicate the currently hottest topics in TMS research and major avenues of development.
Loss of hand function after stroke is a major cause of long-term disability. Hand function can be partitioned into strength and independent control of fingers (individuation).
Here we developed a novel paradigm, which independently quantifies these two aspects of hand function, to track hand recovery in 54 patients with hemiparesis over the first year after their stroke. Most recovery of both strength and individuation occurred in the first three months after stroke. Improvement in strength and individuation were tightly correlated up to a strength level of approximately 60% of the unaffected side. Beyond this threshold, further gains in strength were not accompanied by improvements in individuation. Any observed improvements in individuation beyond the 60% threshold were attributable instead to a second independent stable factor.
Lesion analysis revealed that damage to the hand area in motor cortex and the corticospinal tract (CST) correlated more with individuation than with strength. CST involvement correlated with individuation even after factoring out the strength-individuation correlation. The most parsimonious explanation for these behavioral and lesion-based findings is that most strength recovery, along with some individuation, can be attributed to descending systems other than the CST, whereas further recovery of individuation is CST dependent. (Note: Jing Xu and Naveed Ejaz contributed equally to this work.)
tDCS can enhance the coordinated motor output during walking in healthy subjects, but there is large inter-individual variability in response.
Dual-hemispheric tDCS tends to have a larger effect on the coordinated motor output than uni-hemispheric tDCS.
tDCS did not result in improved coordinated motor output in the paretic leg of chronic stroke survivors.
Background: Transcranial direct current stimulation (tDCS) can augment force generation and control in single leg joints in healthy subjects and stroke survivors. However, it is unknown whether these effects also result in improved force production and coordination during walking and whether electrode configuration influences these effects.
Objective: We investigated the effect of tDCS using different electrode configurations on coordinated force production during walking in a group of healthy subjects and chronic stroke survivors.
Methods: Ten healthy subjects and ten chronic stroke survivors participated in a randomized double-blinded crossover study. Subjects walked on an instrumented treadmill before and after 10 minutes of uni-hemispheric (UNI), dual-hemispheric (DUAL) or sham tDCS applied to the primary motor cortex.
Resultst: DCS responses showed large inter-individual variability in both subject populations. In healthy subjects tDCS enhanced the coordinated output during walking as reflected in an increased positive work generation during propulsion. The effects of DUAL tDCS were clearer but still small (4.4% increase) compared to UNI tDCS (2.8% increase). In the chronic stroke survivors no significant effects of tDCS in the targeted paretic leg were observed.
Conclusionst: DCS has potential to augment multi-joint coordinated force production during walking. The relative small contribution of the motor cortex in controlling walking might explain why the observed effects are rather small. Furthermore, a better understanding of the inter-individual variability is needed to optimize the effects of tDCS in healthy but especially stroke survivors. The latter is a prerequisite for clinical applicability.
Weekly sessions of non-invasive repetitive transcranial magnetic stimulation provided sufficient long-term pain relief in 61 percent of patients with central post-stroke pain, and delivered long-term relief for patients who continued for one year, according to a study presented at the International Neuromodulation Society 12th World Congress by Masahito Kobayashi, MD, PhD, of the Department of Neurosurgery, Saitama Medical University – Department of Neurology, Institute of Brain and Blood Vessels, Mihara Memorial Hospital in Saitama, Japan.
Of 18 patients in the open-label series, 11 patients achieved satisfactory-to-excellent pain relief. Pain relief was sustained in six patients who continued treatment for one year. All patients received repetitive transcranial magnetic stimulation (rTMS) to their primary motor cortex once a week for at least 12 weeks.
Satisfactory relief was considered a 40 – 69 percent reduction in pain scores (6 patients) and excellent relief, pain reduction of 70 percent or more (5 patients). Overall, 8 patients who had severe stroke-caused dysesthesias, such as uncomfortable numbness or prickling, experienced less relief than patients without severe dysesthesias, suggesting possible neural circuit damage was inhibiting response to treatment.
The study participants had all been treated medically after a blood clot or bleed in one side of the brain (unilateral ischemic or hemorrhagic stroke). Several weeks into their recovery, they had begun to experience severe hand or leg pain as a consequence of brain damage from the stroke. Such central post-stroke pain can be extremely disabling and difficult to treat, impacting general functioning, mood, and overall quality of life.
Since the 1990s, Japan has been an active center of research into the study of electrical motor cortex stimulation (EMCS) to treat post-stroke pain using surgically implanted devices. The study reported at the INS 12th World Congress builds on observations that electrical motor cortex stimulation’s effectiveness in relieving central post-stroke pain can be predicted by rTMS, suggesting the techniques share similar pain-relief mechanisms.
However, Kobayashi and colleagues point out in their peer-reviewed online publication of this study, “Repetitive Transcranial Magnetic Stimulation Once a Week Induces Sustainable Long-Term Relief of Central Poststroke Pain” (Neuromodulation: Technology at the Neural Interface: April 23, 2015) that there has still been controversy about the efficacy of rTMS in post-stroke pain. Kobayashi said in comparison to EMCS, his impression is rTMS efficacy seemed almost the same, without requiring surgery.
In the last decade, important advances in the field of cognitive science, psychology and neuroscience have largely contributed to improve our knowledge on brain functioning.
More recently, a line of research has been developed that aims at using musical training and practice as alternative tools for boosting specific perceptual, motor, cognitive and emotional skills both in healthy population and in neurologic patients. These findings are of great hope for a better treatment of language-based learning disorders or motor impairment in chronic non-communicative diseases.
In the first part of this review, we highlight several studies showing that learning to play a musical instrument can induce substantial neuroplastic changes in cortical and subcortical regions of motor, auditory and speech processing networks in healthy population. In a second part, we provide an overview of the evidence showing that musical training can be an alternative, low-cost and effective method for the treatment of language-based learning impaired populations.
We then report results of the few studies showing that training with musical instruments can have positive effects on motor, emotional and cognitive deficits observed in patients with noncommunicable diseases such as stroke or Parkinson Disease. Despite inherent differences between musical training in educational and rehabilitation contexts, these results favour the idea that the structural, multimodal and emotional properties of musical training can play an important role in developing new, creative and cost effective intervention programs for education and rehabilitation in the next future.