Prevalence and Risk Factors of Deep Venous Thrombosis in Intensive Inpatient Neurorehabilitation Unit.

Venous thromboembolism (VTE) (deep vein thrombosis and its complication, pulmonary embolism) is a major cause of morbidity and mortality in hospitalized patients and about 7% of these cases are due to immobility secondary to a neurological impairment. Acquired brain injury (ABI) has also been recognized as one of the main risk factors for VTE. Numerous epidemiological studies have been conducted to assess the risk factors for VTE in institutionalized polytrauma patients, although there is a lack of information about neurorehabilitation wards. Since VTE is often undiagnosed, this prospective study aimed to determine the prevalence and clinical characteristics of lower-limb deep venous thrombosis (DVT) in ABI patients at neurorehabilitation admission. METHODS: ABI patients were screened for DVT on admission to the intensive rehabilitation unit (IRU) with compression ultrasonography and basal D-dimer assay and were daily clinically monitored until discharge. A total of 127 consecutive ABI patients (mean age: 60.1 ± 17.6 years; 63% male; time from event: 30.9 ± 22.1 days; rehabilitation time in IRU: 84.6 ± 58.4 days) were enrolled. RESULTS: On admission to the IRU, the DVT prevalence was about 8.6%. The mean D-dimer level in patients with DVT was significantly higher than in patients without DVT (6 ± 0.9 vs. 1.97 ± 1.61, p-value = 0.0001). ABI patients with DVT did not show any significant clinical characteristics with respect to ABI without DVT, although a prevalence of hemorrhagic strokes and patients originating from the Intensive Care Unit and Neurosurgery ward was revealed. During the rehabilitation period, patients with DVT showed a significant difference in pharmacological DVT prophylaxis (high prevalence of nadroparin with 27.3% vs. 1.7%, p-value = 0.04) and a prevalence of transfers in critical awards (36% versus 9.5% of patients without DVT, p-value = 0.05). The mortality rate was similar in the two groups. CONCLUSIONS: Our research offers a more comprehensive view of the clinical development of DVT patients and confirms the prevalence rate of DVT in ABI patients as determined upon IRU admission. According to our findings, screening these individuals regularly at the time of rehabilitation admission may help identify asymptomatic DVT quickly and initiate the proper treatment to avoid potentially fatal consequences. However, to avoid time-consuming general ultrasonography observation, a more precise selection of patients entering the rehabilitation ward is required.

Italian adaptation of the Multidimensional Iowa Suggestibility Scale (MISS).

Background: Suggestibility is a personality trait that reflects a general tendency to accept messages. The Multidimensional Iowa Suggestibility Scale (MISS) is a self-report scale developed to measure the degree of individuals' perceptions of their suggestibility. This study aimed to adapt the MISS in an Italian sample. Methods: We conducted two studies. In the first study, 345 subjects (270 females (78%), mean age = 36.21 years ± 14.06 SD) completed the translated Italian version of the MISS, composed of five subscales (consumer suggestibility; persuadability; sensation contagion; physiological reactivity; peer conformity). We investigated the structural validity of the scale through confirmatory factor analysis (CFA) testing four measurement models (unidimensional, four-factor, hierarchical four factors, and bifactor) and explored reliability in terms of internal consistency through the McDonald's omega. In the second study, we cross-validated the MISS on a new independent sample. We enrolled 277 participants (196 females (71%), mean age 30.56, SD = 12.58) who underwent the new version of the scale. We performed factor analyses to test structural validity and compared four measurement models. Then, we investigated reliability and conducted a latent variable analysis to explore divergent validity. Results: The CFA in the first study revealed a bifactor solution of the MISS. This structure was interpretable and provided an adequate fit for the data. The final version of the scale was reduced to forty-six items with globally good indices of adaptation. The scale also demonstrated acceptable reliability in terms of internal consistency through the McDonald's Hierarchical Omega. In the second study, we found that the bifactor structure was confirmed. Factor loadings inspection revealed that there was no justification to report only the separate scores for the subscales. We also found that the scale showed good internal consistency, but mixed evidence for divergent validity. Conclusions: In the end, the Italian version of the MISS demonstrated good psychometric properties which will be discussed in detail below.

Combining computer-based rehabilitative approach with tDCS for recovering of aphasia: Implications from a single case study.

We present a case of a single left hemisphere temporal-parietal stroke with subacute global aphasia and severe verbal apraxia and moderate dysphagia. The patient underwent a combined transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) and language stimulation with Virtual Reality Rehabilitation System (VRRS). Patient was treated in a 1-h session, for 5 days a week, for 4 consecutive weeks. After treatment, evident improvements in the comprehension of oral and written language, swallowing abilities, and caregiver burden were detected. Power spectrum analysis of EEG data revealed significant enhancements of θ, α, and ß waves from baseline to follow-up. These preliminary results seem to confirm the reliability of the tDCS translational application in conjunction with computer-based cognitive treatment for language disorders in a patient with stroke-induced aphasia.

Neuroanatomical correlates of peripersonal space: bridging the gap between perception, action, emotion and social cognition.

Peripersonal space (PPS) is a construct referring to the portion of space immediately surrounding our bodies, where most of the interactions between the subject and the environment, including other individuals, take place. Decades of animal and human neuroscience research have revealed that the brain holds a separate representation of this region of space: this distinct spatial representation has evolved to ensure proper relevance to stimuli that are close to the body and prompt an appropriate behavioral response. The neural underpinnings of such construct have been thoroughly investigated by different generations of studies involving anatomical and electrophysiological investigations in animal models, and, recently, neuroimaging experiments in human subjects. Here, we provide a comprehensive anatomical overview of the anatomical circuitry underlying PPS representation in the human brain. Gathering evidence from multiple areas of research, we identified cortical and subcortical regions that are involved in specific aspects of PPS encoding.We show how these regions are part of segregated, yet integrated functional networks within the brain, which are in turn involved in higher-order integration of information. This wide-scale circuitry accounts for the relevance of PPS encoding in multiple brain functions, including not only motor planning and visuospatial attention but also emotional and social cognitive aspects. A complete characterization of these circuits may clarify the derangements of PPS representation observed in different neurological and neuropsychiatric diseases.

The Role of Treatment-Related Parameters and Brain Morphology in the Lesion Volume of Magnetic-Resonance-Guided Focused Ultrasound Thalamotomy in Patients with Tremor-Dominant Neurological Conditions.

PURPOSE: To determine the best predictor of lesion volume induced by magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy in patients with tremor-dominant symptoms in Parkinson's disease (PD) and essential tremor (ET) patients. METHODS: Thirty-six neurological patients with medication-refractory tremor (n°19 PD; n°17 ET) were treated using a commercial MRgFUS brain system (Exablate Neuro 4000, Insightec) integrated with a 1.5 T MRI unit (Sigma HDxt; GE Medical System). Linear regression analysis was used to determine how the demographic, clinical, radiological (Fazekas scale), volumetric (total GM/WM/CSF volume, cortical thickness), and MRgFUS-related parameters [Skull Density Ratio (SDR), n° of transducer elements, n° of sonications, skull area, maximal energy delivered (watt), maximal power delivered (joule), maximal sonication time delivered, maximal mean temperature reached (T°C_max), accumulated thermal dose (ATD)] impact on ventral intermediate (VIM)-thalamotomy-related 3D volumetric lesions of necrosis and edema. RESULTS: The VIM thalamotomy was clinically efficacious in improving the tremor symptoms of all the patients as measured at 1 week after treatment. Multiple regression analysis revealed that T°C_max and n° of transducer elements were the best predictors of the necrosis and edema volumes. Moreover, total WM volume also predicted the size of necrosis. CONCLUSIONS: Our study provides new insights into the clinical MRgFUS procedures that can be used to forecast brain lesion size and improve treatment outcomes.

Electrophysiological Screening to Assess Foot Drop Syndrome in Severe Acquired Brain Injury in Rehabilitative Settings.

BACKGROUND: Foot drop syndrome (FDS), characterized by severe weakness and atrophy of the dorsiflexion muscles of the feet, is commonly found in patients with severe acquired brain injury (ABI). If the syndrome is unilateral, the cause is often a peroneal neuropathy (PN), due to compression of the nervous trunk on the neck of the fibula at the knee level; less frequently, the cause is a previous or concomitant lumbar radiculopathy. Bilateral syndromes are caused by polyneuropathies and myopathies. Central causes, due to brain or spinal injury, mimic this syndrome but are usually accompanied by other symptoms, such as spasticity. Critical illness polyneuropathy (CIP) and myopathy (CIM), isolated or in combination (critical illness polyneuromyopathy, CIPNM), have been shown to constitute an important cause of FDS in patients with ABI. Assessing the causes of FDS in the intensive rehabilitation unit (IRU) has several limitations, which include the complexity of the electrophysiological tests, limited availability of neurophysiology consultants, and the severe disturbance in consciousness and lack of cooperation from patients. OBJECTIVES: We sought to propose a simplified electrophysiological screening that identifies FDS causes, particularly PN and CIPNM, to help clinicians to recognize the significant clinical predictors of poor outcomes in severe ABI at admission to IRU. METHODS: This prospective, single-center study included 20 severe ABI patients with FDS (11 females/9 males, mean age 55.10 + 16.26; CRS-R= 11.90 + 6.32; LCF: 3.30 + 1.30; DRS: 21.45 + 3.33), with prolonged rehabilitation treatment (≥2 months). We applied direct tibialis anterior muscle stimulation (DMS) associated with peroneal nerve motor conduction evaluation, across the fibular head (NCS), to identify CIP and/or CIM and to exclude demyelinating or compressive unilateral PN. RESULTS: At admission to IRU, simplified electrophysiological screening reported four unilateral PN, four CIP and six CIM with a CIPNM overall prevalence estimate of about 50%. After 2 months, the CIPNM group showed significantly poorer outcomes compared to other ABI patients without CIPNM, as demonstrated by the lower probability of achieving endotracheal-tube weaning (20% versus 90%) and lower CRS-R and DRS scores. Due to the subacute rehabilitation setting of our study, it was not possible to evaluate the motor results of recovery of the standing position, functional walking and balance, impaired by the presence of unilateral PN. CONCLUSIONS: The implementation of the proposed simplified electrophysiological screening may enable the early identification of unilateral PN or CIPNM in severe ABI patients, thereby contributing to better functional prognosis in rehabilitative settings.

Metaverse in Mental Health: The Beginning of a Long History.

PURPOSE OF REVIEW: We review the first pilot studies applying metaverse-related technologies in psychiatric patients and discuss the rationale for using this complex federation of technologies to treat mental diseases. Concerning previous virtual-reality applications in medical care, metaverse technologies provide the unique opportunity to define, control, and shape virtual scenarios shared by multi-users to exploit the "synchronized brains" potential exacerbated by social interactions. RECENT FINDINGS: The application of an avatar-based sexual therapy program conducted on a metaverse platform has been demonstrated to be more effective concerning traditional sexual coaching for treating female orgasm disorders. Again, a metaverse-based social skills training program has been tested on children with autism spectrum disorders, demonstrating a significant impact on social interaction abilities. Metaverse-related technologies could enable us to develop new reliable approaches for treating diseases where behavioral symptoms can be addressed using socio-attentive tasks and social-interaction strategies.

Artificial neural network analysis of factors affecting functional independence recovery in patients with lumbar stenosis after neurosurgery treatment: An observational cohort study.

Background and aim: Lumbar spinal stenosis (LSS) is a leading cause of low back pain and lower limbs pain often associated with functional impairment which entails the loss or the impairment of independence in older adults. Conservative treatment is effective in a small percentage of patients, while a significant percentage undergo surgery, even if often without a complete resolution of clinical symptoms and motor deficits. The aim of the study is to identify clinical and demographic prognostic factors characterising the patients who would benefit most from surgical treatment in relation to the functional independence recovery using an innovative approach based on an artificial neural network. Methods: Adult patients with LSS and indication of neurosurgical treatment were enrolled in the study. Clinical evaluation was performed in the preoperative-phase (into the 48 h before surgery) and after two months. Clinical battery investigated the motor, functional, cognitive, behavioural, and pain status. Demographics and clinical characteristics were analysed via Artificial Neural Network (ANN) using 24 input variables, 2 hidden layers and a single final output layer to predict the outcome. ANN results were compared with those of a multiple linear regression. Results: 108 patients were included in the study and 90 of them [66.5 ± 12.8 years; 27.8 % F] were submitted to surgery treatment and completed longitudinal evaluation. Statistically significant improvement was recorded in all clinical scales comparing pre- and post-surgery. The ANN results showed a prediction ability up to 81 %. Disability, functional limitations, and pain concerning clinical assessment and stature, onset and age about demographic characteristics are the main variables impacting on surgical outcome. Conclusions: ANN can support clinical decision making, using clinical and demographic characteristics of patients with LSS identifying the characteristics of those who might benefit more from the surgical treatment in terms of global functional recovery.

Fractals in Neuropsychology and Cognitive Neuroscience.

The fractal dimension of cognition refers to the idea that the cognitive processes of the human brain exhibit fractal properties. This means that certain patterns of cognitive activity, such as visual perception, memory, language, or problem-solving, can be described using the mathematical concept of fractal dimension.The idea that cognition is fractal has been proposed by some researchers as a way to understand the complex, self-similar nature of the human brain. However, it's a relatively new idea and is still under investigation, so it's not yet clear to what extent cognitive processes exhibit fractal properties or what implications this might have for our understanding of the brain and clinical practice. Indeed, the mission of the "fractal neuroscience" field is to define the characteristics of fractality in human cognition in order to differently characterize the emergence of brain disorders.

Psycho-Neuroendocrinology in the Rehabilitation Field: Focus on the Complex Interplay between Stress and Pain.

Chronic stress and chronic pain share neuro-anatomical, endocrinological, and biological features. However, stress prepares the body for challenging situations or mitigates tissue damage, while pain is an unpleasant sensation due to nociceptive receptor stimulation. When pain is chronic, it might lead to an allostatic overload in the body and brain due to the chronic dysregulation of the physiological systems that are normally involved in adapting to environmental challenges. Managing stress and chronic pain (CP) in neurorehabilitation presents a significant challenge for healthcare professionals and researchers, as there is no definitive and effective solution for these issues. Patients suffering from neurological disorders often complain of CP, which significantly reduces their quality of life. The aim of this narrative review is to examine the correlation between stress and pain and their potential negative impact on the rehabilitation process. Moreover, we described the most relevant interventions used to manage stress and pain in the neurological population. In conclusion, this review sheds light on the connection between chronic stress and chronic pain and their impact on the neurorehabilitation pathway. Our results emphasize the need for tailored rehabilitation protocols to effectively manage pain, improve treatment adherence, and ensure comprehensive patient care.

Evolution of Severe Closed Head Injury: Assessing Ventricular Volume and Behavioral Measures at 30 and 90 Days Post-Injury.

Background: Assessing functional outcomes in Severe Closed Head Injury (SCHI) is complex due to brain parenchymal changes. This study examines the Ventricles to Intracranial Volume Ratio (VBR) as a metric for these changes and its correlation with behavioral scales. Methods: Thirty-one SCHI patients were included. VBR was derived from CT scans at 3, 30, and 90 days post-injury and compared with Levels of Cognitive Functioning (LCF), Disability Rating Scale (DRS), and Early Rehabilitation Barthel Index (ERBI) assessments at 30 and 90 days. Results: Ten patients were excluded post-decompressive craniectomy or ventriculoperitoneal shunt. Findings indicated a VBR decrease at 3 days, suggesting acute phase compression, followed by an increase from 30 to 90 days, indicative of post-acute brain atrophy. VBR correlated positively with the Marshall score in the initial 72 h, positioning it as an early indicator of subsequent brain atrophy. Nevertheless, in contrast to the Marshall score, VBR had stronger associations with DRS and ERBI at 90 days. Conclusions: VBR, alongside behavioral assessments, presents a robust framework for evaluating SCHI progression. It supports early functional outcome correlations informing therapeutic approaches. VBR's reliability underscores its utility in neurorehabilitation for ongoing SCHI assessment and aiding clinical decisions.

Inducing Cough Reflex by Capsaicin Spray Stimulation in Patients with Acquired Brain Injury: A Preliminary Test and Proof of Concept.

Individuals with acquired brain injuries (ABIs) may experience various complications related to poor coughing or impaired cough reflex (including risk of aspiration pneumonia or respiratory infections). For this reason, cough assessment is an important component in the clinical evaluation since patients with ABI are not able to cough voluntarily due to severe motor deficits. When voluntarily coughing is not possible, it is essential for clinical practices to find a quick and minimally invasive way to induce a cough reflex. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. In total, 150 healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve reflexive cough modulation in ABI patients.

Transient Worsening of Dysphagia and Dysarthria after Treatment with Botulinum Toxin in Patients with Acquired Brain Injury.

Although botulinum toxin is widely considered an effective and safe treatment for a variety of neurological conditions (such as disabling spasticity), local or systemic adverse effects have often been reported. This study describes three cases of patients with severe acquired brain injury who were receiving speech therapy for recovering dysphagia and dysarthria but showed worsening of these symptoms after receiving BoNT treatment for motor spasticity. To increase clinicians' knowledge of these adverse effects, we present our cases and explore their significance to avoid major complications such as aspiration pneumonia.

Robot- and Technology-Boosting Neuroplasticity-Dependent Motor-Cognitive Functional Recovery: Looking towards the Future of Neurorehabilitation.

The sequelae of neurological disorders are the leading causes of disability in all industrialized countries [...].

MR-Guided Focused Ultrasound for Refractory Epilepsy: Where Are We Now?

Epilepsy is one of the most common neurological diseases in both adults and children. Despite improvements in medical care, 20 to 30% of patients are still resistant to the best medical treatment. The quality of life, neurologic morbidity, and even mortality of patients are significantly impacted by medically intractable epilepsy. Nowadays, conservative therapeutic approaches consist of increasing medication dosage, changing to a different anti-seizure drug as monotherapy, and combining different antiseizure drugs using an add-on strategy. However, such measures may not be sufficient to efficiently control seizure recurrence. Resective surgery, ablative procedures and non-resective neuromodulatory (deep-brain stimulation, vagus nerve stimulation) treatments are the available treatments for these kinds of patients. However, invasive procedures may involve lengthy inpatient stays for the patients, risks of long-term neurological impairment, general anesthesia, and other possible surgery-related complications (i.e., hemorrhage or infection). In the last few years, MR-guided focused ultrasound (MRgFUS) has been proposed as an emerging treatment for neurological diseases because of technological advancements and the goal of minimally invasive neurosurgery. By outlining the current knowledge obtained from both preclinical and clinical studies and discussing the technical opportunities of this therapy for particular epileptic phenotypes, in this perspective review, we explore the various mechanisms and potential applications (thermoablation, blood-brain barrier opening for drug delivery, neuromodulation) of high- and low-intensity ultrasound, highlighting possible novel strategies to treat drug-resistant epileptic patients who are not eligible or do not accept currently established surgical approaches. Taken together, the available studies support a possible role for lesional treatment over the anterior thalamus with high-intensity ultrasound and neuromodulation of the hippocampus via low-intensity ultrasound in refractory epilepsy. However, more studies, likely conceiving epilepsy as a network disorder and bridging together different scales and modalities, are required to make ultrasound delivery strategies meaningful, effective, and safe.

Computer-assisted cognitive rehabilitation in neurological patients: state-of-art and future perspectives.

Background and aim: Advances in computing technology enabled researchers and clinicians to exploit technological devices for cognitive training and rehabilitation interventions. This expert review aims to describe the available software and device used for cognitive training or rehabilitation interventions of patients with neurological disorders. Methods: A scoping review was carried out to analyze commercial devices/software for computerized cognitive training (CCT) in terms of feasibility and efficacy in both clinical and home settings. Several cognitive domains responding to the different patients' needs are covered. Results: This review showed that cognitive training for patients with neurological diseases is largely covered by several devices that are widely used and validated in the hospital setting but with few translations to remote/home applications. It has been demonstrated that technology and software-based devices are potential and valuable tools to administer remotely cognitive rehabilitation with accessible costs. Conclusion: According to our results, CCT entails the possibility to continue cognitive training also in different settings, such as home, which is a significant breakthrough for the improvement of community care. Other possible areas of use should be the increase in the amount of cognitive therapy in the free time during the hospital stay.

Application of Machine Learning Algorithms for Prognostic Assessment in Rotator Cuff Pathologies: A Clinical Data-Based Approach.

AIM: The overall aim of this proposal is to ameliorate the care of rotator cuff (RC) tear patients by applying an innovative machine learning approach for outcome prediction after arthroscopic repair. MATERIALS AND METHODS: We applied state-of-the-art machine learning algorithms to evaluate the best predictors of the outcome, and 100 RC patients were evaluated at baseline (T0), after 1 month (T1), 3 months (T2), 6 months (T3), and 1 year (T4) from surgical intervention. The outcome measure was the Costant-Murley Shoulder Score, whereas age, sex, BMI, the 36-Item Short-Form Survey, the Simple Shoulder Test, the Hospital Anxiety and Depression Scale, the American Shoulder and Elbow Surgeons Score, the Oxford Shoulder Score, and the Shoulder Pain and Disability Index were considered as predictive factors. Support vector machine (SVM), k-nearest neighbors (k-NN), naïve Bayes (NB), and random forest (RF) algorithms were employed. RESULTS: Across all sessions, the classifiers demonstrated suboptimal performance when using both the complete and shrunken sets of features. Specifically, the logistic regression (LR) classifier achieved a mean accuracy of 46.5% ± 6%, while the random forest (RF) classifier achieved 51.25% ± 4%. For the shrunken set of features, LR obtained a mean accuracy of 48.5% ± 6%, and RF achieved 45.5% ± 4.5%. No statistical differences were found when comparing the performance metrics of ML algorithms. CONCLUSIONS: This study underlines the importance of extending the application of AI methods to new predictors, such as neuroimaging and kinematic data, in order to better record significant shifts in RC patients' prognosis. LIMITATIONS: The data quality within the cohort could represent a limitation, since certain variables, such as smoking, diabetes, and work injury, are known to have an impact on the outcome.

Lowered Delta Activity in Post-COVID-19 Patients with Fatigue and Cognitive Impairment.

In post-COVID-19 syndrome (PCS), neurocognitive symptoms and fatigue are often associated with alterations in electroencephalographic (EEG) activity. The present study investigates the brain source activity at rest in PCS patients (PCS-pts) perceiving cognitive deficits and fatigue. A total of 18 PCS-pts and 18 healthy controls (HCs) were enrolled. A Montreal Cognitive Assessment (MoCA), Perceived Cognitive Difficulties Scale (PDCS) and Fatigue Severity Scale (FSS) were administered for assessing the symptoms' severity. Brain activity at rest, both with open (OE) and closed eyes (CE), was recorded by high-density EEG (Hd-EEG) and localized by source estimation. Compared to HCs, PCS-pts exhibited worse performance in executive functions, language and memory, and reported higher levels of fatigue. At resting OE state, PCS-pts showed lower delta source activity over brain regions known to be associated with executive processes, and these changes were negatively associated with PDCS scores. Consistent with recent literature data, our findings could indicate a dysfunction in the neuronal networks involved in executive functions in PCS-pts complaining of fatigue and cognitive impairment.

Neural Plasticity Changes Induced by Motor Robotic Rehabilitation in Stroke Patients: The Contribution of Functional Neuroimaging.

Robotic rehabilitation is one of the most advanced treatments helping people with stroke to faster recovery from motor deficits. The clinical impact of this type of treatment has been widely defined and established using clinical scales. The neurofunctional indicators of motor recovery following conventional rehabilitation treatments have already been identified by previous meta-analytic investigations. However, a clear definition of the neural correlates associated with robotic neurorehabilitation treatment has never been performed. This systematic review assesses the neurofunctional correlates (fMRI, fNIRS) of cutting-edge robotic therapies in enhancing motor recovery of stroke populations in accordance with PRISMA standards. A total of 7, of the initial yield of 150 articles, have been included in this review. Lessons from these studies suggest that neural plasticity within the ipsilateral primary motor cortex, the contralateral sensorimotor cortex, and the premotor cortices are more sensitive to compensation strategies reflecting upper and lower limbs' motor recovery despite the high heterogeneity in robotic devices, clinical status, and neuroimaging procedures. Unfortunately, the paucity of RCT studies prevents us from understanding the neurobiological differences induced by robotic devices with respect to traditional rehabilitation approaches. Despite this technology dating to the early 1990s, there is a need to translate more functional neuroimaging markers in clinical settings since they provide a unique opportunity to examine, in-depth, the brain plasticity changes induced by robotic rehabilitation.