Neurophysiological and Psychometric Outcomes in Minimal Consciousness State after Advanced Audio-Video Emotional Stimulation: A Retrospective Study.

In the last ten years, technological innovations have led to the development of new, advanced sensory stimulation (SS) tools, such as PC-based rehabilitative programs or virtual reality training. These are meant to stimulate residual cognitive abilities and, at the same time, assess cognition and awareness, also in patients with a minimally conscious state (MCS). Our purpose was to evaluate the clinical and neurophysiological effects of multi-sensory and emotional stimulation provided by Neurowave in patients with MCS, as compared to a conventional SS treatment. The psychological status of their caregivers was also monitored. In this retrospective study, we have included forty-two MCS patients and their caregivers. Each MCS subject was included in either the control group (CG), receiving a conventional SS, or the experimental group (EG), who was submitted to the experimental training with the Neurowave. They were assessed before (T0) and after the training (T1) through a specific clinical battery, including both motor and cognitive outcomes. Moreover, in the EG, we also monitored the brain electrophysiological activity (EEG and P300). In both study groups (EG and CG), the psychological caregiver's aspects, including anxiety levels, were measured using the Zung Self-Rating Anxiety Scale (SAS). The intra-group analysis (T0-T1) of the EG showed statistical significances in all patients' outcome measures, while in the CG, we found statistical significances in consciousness and awareness outcomes. The inter-group analysis between the EG and the CG showed no statistical differences, except for global communication skills. In conclusion, the multi-sensory stimulation approach through Neurowave was found to be an innovative rehabilitation treatment, also allowing the registration of brain activity during treatment.

Effects of Virtual Reality Cognitive Training on Neuroplasticity: A Quasi-Randomized Clinical Trial in Patients with Stroke.

Cognitive Rehabilitation (CR) is a therapeutic approach designed to improve cognitive functioning after a brain injury, including stroke. Two major categories of techniques, namely traditional and advanced (including virtual reality-VR), are widely used in CR for patients with various neurological disorders. More objective outcome measures are needed to better investigate cognitive recovery after a stroke. In the last ten years, the application of electroencephalography (EEG) as a non-invasive and portable neuroimaging method has been explored to extract the hallmarks of neuroplasticity induced by VR rehabilitation approaches, particularly within the chronic stroke population. The aim of this study is to investigate the neurophysiological effects of CR conducted in a virtual environment using the VRRS device. Thirty patients with moderate-to-severe ischemic stroke in the chronic phase (at least 6 months after the event), with a mean age of 58.13 (±8.33) for the experimental group and 57.33 (±11.06) for the control group, were enrolled. They were divided into two groups: an experimental group and a control group, receiving neurocognitive stimulation using VR and the same amount of conventional neurorehabilitation, respectively. To study neuroplasticity changes after the training, we focused on the power band spectra of theta, alpha, and beta EEG rhythms in both groups. We observed that when VR technology was employed to amplify the effects of treatments on cognitive recovery, significant EEG-related neural improvements were detected in the primary motor circuit in terms of power spectral density and time-frequency domains. Indeed, EEG analysis suggested that VR resulted in a significant increase in both the alpha band power in the occipital areas and the beta band power in the frontal areas, while no significant variations were observed in the theta band power. Our data suggest the potential effectiveness of a VR-based rehabilitation approach in promoting neuroplastic changes even in the chronic phase of ischemic stroke.

'Online therapy' to reduce caregiver's distress and to stimulate post-severe acquired brain injury motor and cognitive recovery: A Sicilian hospital experience in the COVID era.

INTRODUCTION: Severe acquired brain injury(SABI) often results in the deterioration of physical, cognitive and emotional functions in the patient and a significant caregiver's distress syndrome, which is now amplified by the social isolation, depression and financial difficulties related to the COVID-19 pandemic. The use of web-based online-therapy has been shown to be useful to overcome caregiver's distress syndrome and further stimulate cognitive-motor recovery of SABI-patients. Our study aimed to investigate whether a systematic online Skype-therapy(OLST) may be of support in favoring global cognitive and sensory-motor recovery in SABI-patients and reducing caregiver distress. METHODS: Twenty-five SABI-subjects in inpatient regimen were provided with intensive OLST with the caregiver for 12 weeks in addition to standard neurorehabilitation. Each subject and caregiver was evaluated before and after the treatment by administering an ad hoc battery. Furthermore, 18 of 27 patients were provided with EEG recording in resting state. RESULTS: We found a significant reduction in caregiver's anxiety (p<0.0001) and burden(p<0.0001). Patients showed significant improvement in trunk control (p<0.0001), functional independence (p = 0.005), functional (p = 0.01) and global communication (p = 0.004), cognitive functioning (p = 0.001), and behavioral responsiveness (p = 0.0004). The training yielded a significant connectivity change within the fronto-centro-parietal areas in the delta frequency band (p<0.0001) and the centro-parieto-occipital areas in the alpha range (p = 0.004). DISCUSSION: OLST may be a useful and complementary treatment to optimize global cognitive and functional recovery in SABI-subjects and reduce caregivers' concerns in the Covid-era. OLST can foster cognitive-motor recovery potentially by favoring the plasticity-dependent functional recovery. Therefore, OLST could be proposed as a tool allowing social conversations also in the hospital setting.

Toward Improving Functional Recovery in AIDS-associated Progressive Multifocal Leukoencephalopathy: A Single Case Pilot Study on a Novel Neuromodulation Approach.

Patients with progressive multifocal leukoencephalopathy (PML) in the context of human immunodeficiency virus-acquired immunodeficiency syndrome (HIV-AIDS) show a partial improvement following rehabilitation; however, this improvement is rapidly lost if the patient is not provided with intensive rehabilitation. A 42-year-old patient affected by HIV-AIDS had a clinical worsening within a few months following PML onset, despite being treated with antiretroviral drugs and conventional rehabilitation. He developed severe paraparesis and significant dependency in the activities of daily life. A first cycle of intensive rehabilitation provided the patient with some significant functional outcomes, although he experienced a worsening of the clinical condition after two months of rest, before admission to our rehabilitation unit. We thus sought to evaluate the effects of intensive robot-aided gait training (RAGT) coupled with transcranial direct current stimulation (tDCS). The patient significantly improved when provided with intensive RAGT coupled with tDCS (as per 10-meter Walk Test [10MWT] and 6-minute Walk Test [6MWT]), and the improvement was maintained at three-month follow-up. As this advanced approach was feasible, safe, and potentially effective, this case suggests that patients with PML-HIV require prolonged multidisciplinary rehabilitation treatment. We can speculate that individuals with PML should also be treated with innovative technology to improve their functional outcomes and therefore quality of life.

Finding the Way to Improve Motor Recovery of Patients with Spinal Cord Lesions: A Case-Control Pilot Study on a Novel Neuromodulation Approach.

Robot-assisted rehabilitation (RAR) and non-invasive brain stimulation (NIBS) are interventions that, both individually and combined, can significantly enhance motor performance after spinal cord injury (SCI). We sought to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with active transvertebral direct current stimulation (tvDCS) (namely, NIBS) in association with RAR (RAR + NIBS) improves lower extremity motor function more than RAR alone in subjects with motor incomplete SCI (iSCI). Fifteen adults with iSCI received one daily session of RAR+NIBS in the early afternoon, six sessions weekly, for eight consecutive weeks. Outcome measures included the 6 min walk test (6MWT), the 10 m walk test (10MWT), the timed up and go (TUG) to test mobility and balance, the Walking Index for Spinal Cord Injury (WISCI II), the Functional Independence Measure-Locomotion (FIM-L), the manual muscle testing for lower extremity motor score (LEMS), the modified Ashworth scale for lower limbs (MAS), and the visual analog scale (VAS) for pain. The data of these subjects were compared with those of 20 individuals matched for clinical and demographic features who previously received the same amount or RAR without NIBS (RAR - NIBS). All patients completed the trial, and none reported any side effects either during or following the training. The 10MWT improved in both groups, but the increase was significantly greater following RAR + NIBS than RAR - NIBS. The same occurred for the FIM-L, LEMS, and WISCI II. No significant differences were appreciable concerning the 6MWT and TUG. Conversely, RAR - NIBS outperformed RAR + NIBS regarding the MAS and VAS. Pairing tvDCS with rTMS during RAR can improve lower extremity motor function more than RAR alone can do. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.

Breaking the ice to improve motor outcomes in patients with chronic stroke: a retrospective clinical study on neuromodulation plus robotics.

BACKGROUND: Stroke is one of the main causes of impairment affecting daily activities and quality of life. There is a growing effort to potentiate the recovery of functional gait and to enable stroke patients to walk independently. AIM: To estimate the effects of dual-site transcranial direct current stimulation (dstDCS) on gait recovery in chronic stroke patients provided with robot-aided gait training (RAGT). METHODS: Thirty-seven patients were included in this retrospective clinical study. Nine patients were provided with dstDCS during the first 10 min of RAGT by using Lokomat®Pro (on-RAGT), 15 patients immediately after RAGT (post-RAGT), and 13 patients immediately before RAGT (pre-RAGT). RESULTS: Each group improved over time concerning disability burden and lower limb strength. on-RAGT and post-RAGT experienced better improvement in balance (p < 0.001) and, moderately, gait endurance (p = 0.04) as compared to pre-RAGT. Furthermore, all treatments decreased the facilitation of the unaffected hemisphere (p < 0.001) and the inhibition of the affected hemisphere (p < 0.001). The duration of such aftereffects was found to be greater for post-RAGT. DISCUSSION AND CONCLUSION: This is the first trial with dstDCS coupled with RAGT in chronic stroke patients with gait impairment. When timely coupled with RAGT, dstDCS may be considered an effective tool for the recovery of lower limb function in patients with first unilateral stroke in the chronic phase. Moreover, our data suggest the ductility of dstDCS concerning RAGT timing, thus making this intervention suitable in a neurorehabilitation setting and well adaptable to patients' needs.

Virtual Reality Based Cognitive Rehabilitation in Minimally Conscious State: A Case Report with EEG Findings and Systematic Literature Review.

Chronic disorders of consciousness cause a total or partial and fluctuating unawareness of the surrounding environment. Virtual reality (VR) can be useful as a diagnostic and/or a neurorehabilitation tool, and its effects can be monitored by means of both clinical and electroencephalography (EEG) data recording of brain activity. We reported on the case of a 17-year-old patient with a disorder of consciousness (DoC) who was provided with VR training to improve her cognitive-behavioral outcomes, which were assessed using clinical scales (the Coma Recovery Scale-Revised, the Disability Rating Scale, and the Rancho Los Amigos Levels of Cognitive Functioning), as well as EEG recording, during VR training sessions. At the end of the training, significant improvements in both clinical and neurophysiological outcomes were achieved. Then, we carried out a systematic review of the literature to investigate the role of EEG and VR in the management of patients with DoC. A search on PubMed, Web of Science, Scopus, and Google Scholar databases was performed, using the keywords: "disorders of consciousness" and "virtual reality", or "EEG". The results of the literature review suggest that neurophysiological data in combination with VR could be useful in evaluating the reactions induced by different paradigms in DoC patients, helping in the differential diagnosis. In conclusion, the EEG plus VR approach used with our patient could be promising to define the most appropriate stimulation protocol, so as to promote a better personalization of the rehabilitation program. However, further clinical trials, as well as meta-analysis of the literature, are needed to be affirmative on the role of VR in patients with DoC.

New Horizons in Early Dementia Diagnosis: Can Cerebellar Stimulation Untangle the Knot?

Differentiating Mild Cognitive Impairment (MCI) from dementia and estimating the risk of MCI-to-dementia conversion (MDC) are challenging tasks. Thus, objective tools are mandatory to get early diagnosis and prognosis. About that, there is a growing interest on the role of cerebellum-cerebrum connectivity (CCC). The aim of this study was to differentiate patients with an early diagnosis of dementia and MCI depending on the effects of a transcranial magnetic stimulation protocol (intermittent theta-burst stimulation -iTBS) delivered on the cerebellum able to modify cortico-cortical connectivity. Indeed, the risk of MDC is related to the response to iTBS, being higher in non-responder individuals. All patients with MCI, but eight (labelled as MCI-), showed preserved iTBS aftereffect. Contrariwise, none of the patients with dementia showed iTBS aftereffects. None of the patients showed EEG aftereffects following a sham TBS protocol. Five among the MCI- patients converted to dementia at 6-month follow-up. Our data suggest that cerebellar stimulation by means of iTBS may support the differential diagnosis between MCI and dementia and potentially identify the individuals with MCI who may be at risk of MDC. These findings may help clinicians to adopt a better prevention/follow-up strategy in such patients.

Toward understanding the neurophysiological basis of peripersonal space: An EEG study on healthy individuals.

The subcortical mechanisms subtending the sensorimotor processes related to the peripersonal space (PPS) have been well characterized, whereas less evidence is available concerning the cortical mechanisms. We investigated the theta, alpha and beta event-related spectral perturbations (ERSP) while holding the forearm in different positions into the PPS of the face. Fifty healthy individuals were subjected to EEG recording while being provided with median nerve electric stimulation at the wrist of the right hand held at different hand-to-face distances. Theta and beta rhythms were significantly perturbed depending on the hand-to-face distance, whereas alpha oscillations reflected a more general, non-specific oscillatory response to the motor task. The perturbation of theta and beta frequency bands may reflect the processes of top-down modulation overseeing the conscious spatiotemporal encoding of sensory-motor information within the PPS. In other words, such perturbation reflects the continuous update of the conscious internal representations of the PPS to build up a purposeful and reflexive motor response.

Looking toward predicting functional recovery in disorders of consciousness: can sensorimotor integration help us?

PRIMARY OBJECTIVE: Only a few objective prognostic markers are available for patients with disorders of consciousness (DoC). We assessed whether the magnitude of short-latency afferent inhibition (SAI) might be a useful predictor of responsiveness recovery and functional outcome in patients with DoC. RESEARCH DESIGN: We enrolled 40 patients with prolonged Minimally Conscious State (MCS) and Unresponsive Wakefulness Syndrome (UWS) in a longitudinal, observational study. METHODS AND PROCEDURES: Clinical features (including Coma Recovery Scale-Revised, CRS-R, and Glasgow Outcome Scale, GOS) and SAI were collected at the study entry and after 18 months from study inclusion, to assess a correlation between SAI and the clinical outcome. MAIN OUTCOMES AND RESULTS: At the follow-up, 19 patients remained in their baseline condition, whereas 7 UWS evolved into MCS or emerged-from-MCS (EMCS), eight MCS evolved into EMCS, and two MCS- evolved into MCS+. Two UWS and one MCS+ died for cardiopulmonary complications. The patients who showed the highest GOS, the highest CRS-R and the lowest SAI strength at study entry, improved at the follow-up. CONCLUSIONS: Our findings suggest that an objective and simple neurophysiologic measure as SAI strength could provide useful information to predict the outcome and the behavioral responsiveness of patients with DoC.

Detecting peripersonal space: The promising role of ultrasonics.

INTRODUCTION: The approach of an external stimulus to the peripersonal space (PPS) modifies some physiological measures, including the cerebral blood flow (CBF) in the supplementary motor area and premotor cortex. CBF measurement may be useful to assess brain activations when producing specific motor responses, likely mediated by cortical and subcortical neural circuits. METHODS: This study investigated PPS in 15 healthy humans by characterizing the hemodynamic responses (pulsatility index, PI; and heart rate, HR) related to different directions of movements of individual's hand toward and backward his/her own face, so to perturb PPS). RESULTS: We observed that the CBF and HR were enhanced more when the stimulated hand was inside the PPS of the face in the passive and active condition than when the hand was outside the PPS and during motor imagery task. CONCLUSIONS: These results suggest that the modulation of PPS-related brain responses depends on specific sensory-motor integration processes related to the location and the final position of a target in the PPS. We may thus propose TCD as a rapid and easy approach to get information concerning brain responses related to stimuli approaching the PPS. Understanding the modulations of brain activations during tasks targeting PPS can help to understand the results of psychophysical and behavioral trials and to plan patient-tailored cognitive rehabilitative training.