Immersive Virtual Environments and Wearable Haptic Devices in rehabilitation of children with neuromotor impairments: a single-blind randomized controlled crossover pilot study.

BACKGROUND: The past decade has seen the emergence of rehabilitation treatments using virtual reality. One of the advantages in using this technology is the potential to create positive motivation, by means of engaging environments and tasks shaped in the form of serious games. The aim of this study is to determine the efficacy of immersive Virtual Environments and weaRable hAptic devices (VERA) for rehabilitation of upper limb in children with Cerebral Palsy (CP) and Developmental Dyspraxia (DD). METHODS: A two period cross-over design was adopted for determining the differences between the proposed therapy and a conventional treatment. Eight children were randomized into two groups: one group received the VERA treatment in the first period and the manual therapy in the second period, and viceversa for the other group. Children were assessed at the beginning and the end of each period through both the Nine Hole Peg Test (9-HPT, primary outcome) and Kinesiological Measurements obtained during the performing of similar tasks in a real setting scenario (secondary outcomes). RESULTS: All subjects, not depending from which group they come from, significantly improved in both the performance of the 9-HPT and in the parameters of the kinesiological measurements (movement error and smoothness). No statistically significant differences have been found between the two groups. CONCLUSIONS: These findings suggest that immersive VE and wearable haptic devices is a viable alternative to conventional therapy for improving upper extremity function in children with neuromotor impairments. Trial registration ClinicalTrials, NCT03353623. Registered 27 November 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03353623.

Caregiver burden and family functioning in different neurological diseases.

Aim of this study is to examine caregiver burden and family functioning in different neurological conditions. Forty-two primary caregivers of patients with Amyotrophic Lateral Sclerosis (ALS), Alzheimer's Disease and other dementia (AD), Parkinson's Disease (PD), Acquired Brain Injuries (ABI) and Multiple Sclerosis (MS) were administered scales for the evaluation of caregiver burden (CBI) and family functioning (FACES IV). Caregiver burden was overall high, with caregivers of patients with ALS and ABI having exceeded the CBI cut-off score for possible burn-out. The average scores of caregivers of patients with AD or other dementia and PD were close to the cut-off score, whereas those of caregivers of patients with MS were significantly lower than the others. Family cohesion, family satisfaction and the quality of family communication were associated with reduced levels of caregiver burden, whereas disengagement was associated with a higher burden. The data from the present study confirm that caregiver burden is a relevant issue in the context of neurological diseases, especially for those causing higher degrees of impairment. Significant correlations with family functioning emerged as well, highlighting the importance of studying and treating caregiver burden within the context of family relations.

Effects of a Home-Based Family-Centred Early Habilitation Program on Neurobehavioural Outcomes of Very Preterm Born Infants: A Retrospective Cohort Study.

Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years' corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months' corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant's developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps.

Family functioning in severe brain injuries: correlations with caregivers' burden, perceived social support and quality of life.

Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

N400-like responses to three-chord harmonic sequences with unexpected out of key endings: scalp topography, cortical sources, and perspectives for a clinical use.

A series of ERP components, each provided with both a precise timing with respect to stimulation and a specific cortical localization, reflects the temporal succession of processing stages of music information. This makes the musical stimulus potentially usable to probe residual brain functions in non-communicating patients with disorders of consciousness. In an attempt to find a simple stimulation protocol that was suitable for use in a clinical setting, the purpose of this study was to verify whether a minimum-length musical stimulus, provided with a definite music-syntactic connotation, was still able to elicit musical ERPs in a group of eight healthy subjects. The stimulus was composed of the minimum number of chords necessary and sufficient to enable the subject to predict a plausible closure of the sequence (priming) and, at the same time, to provide him/her with the closing chord of the sequence (target), either congruous (probable closing) or not (improbable closing) to the tonal context. The subject's task was to discriminate and recognize the irregular targets. The components that were expected to be elicited, in this experimental situation, were ERAN, N5, P600/LPC. Conversely, in addition to these former components, we unexpectedly observed a N400-like component. To determine whether this component was a real N400, we submitted our data to a sLORETA analysis in order to identify its cortical generators. Irregular chords showed higher current densities with respect to regular ones on the right-sided medial and superior temporal gyri, superior and inferior parietal lobules, fusiform and parahippocampal gyri, and on the bilateral posterior cingulate cortex. In particular, the N400-like wave seems to share with the word-primed music-elicited N400 certain generators that are located in cortical areas BA 21/37 and BA 22. This suggests that even chord-primed chord targets can convey extra-musical meanings and that, consequently, they might be useful in assessing residual higher-order information-processing capabilities in non-communicating patients with disorders of consciousness.

Cortical source of blink-related delta oscillations and their correlation with levels of consciousness.

Recently, blink-related delta oscillations (delta BROs) have been observed in healthy subjects during spontaneous blinking at rest. Delta BROs have been linked with continuous gathering of information from the surrounding environment, which is classically attributed to the precuneus. Furthermore, fMRI studies have shown that precuneal activity is reduced or missing when consciousness is low or absent. We therefore hypothesized that the source of delta BROs in healthy subjects could be located in the precuneus and that delta BROs could be absent or reduced in patients with disorders of consciousness (DOC). To test these hypotheses, electroencephalographic (EEG) activity at rest was recorded in 12 healthy controls and nine patients with DOC (four vegetative states, and five minimally conscious states). Three-second-lasting EEG epochs centred on each blink instance were analyzed in both time- (BROs) and frequency domains (event-related spectral perturbation or ERSP and intertrial coherence or ITC). Cortical sources of the maximum blink-related delta power, corresponding to the positive peak of the delta BROs, were estimated by standardized Low Resolution Electromagnetic Tomography. In control subjects, as expected, the source of delta BROs was located in the precuneus, whereas in DOC patients, delta BROs were not recognizable and no precuneal localization was possible. Furthermore, we observed a direct relationship between spectral indexes and levels of cognitive functioning in all subjects participating in the study. This reinforces the hypothesis that delta BROs reflect neural processes linked with awareness of the self and of the environment.

Neuronal correlates of eyeblinks are an expression of primary consciousness phenomena.

The blinking rate far exceeds that required for moistening the cornea and changes depending on whether a person is resting or engaged in cognitive tasks. During ecological cognitive tasks (such as speaking, reading, and watching videos), blinks occur at breakpoints of attention suggesting a role in information segmentation, but the close relationship between cognition dynamics and blink timing still escapes a full understanding. The aim of the present study is to seek (1) if there is a temporal relationship between blink events and the consecutive steps of cognitive processing, and (2) if blink timing and the intensity of blink-related EEG responses are affected by task-relevance of stimuli. Our results show that, in a classical visual oddball task, (i) the occurrence of blinks is influenced by stimuli, irrespective of their relevance, (ii) blinks following relevant stimuli are only apparently delayed due to the need of finalizing a behavioural response, and (iii) stimulus relevance does not affect the intensity of the blink-related EEG response. This evidence reinforce the idea that blinks are not emitted until the last step of the processing sequence has been completed and suggests that blink-related EEG responses are generated by primary consciousness phenomena which are considered by their nature non-modulable (all-or-nothing) phenomena.

Case report: Intensive rehabilitation program delivered before and after single-event multilevel surgery in a girl with diplegic cerebral palsy.

Introduction: Diplegic cerebral palsy (CP) is often associated with musculoskeletal disorders that contribute to worsen walking function. The standard care in these cases is single-event multilevel surgery (SEMLS) followed by rehabilitation. Our aim was to investigate whether a rehabilitation program starting even before SEML could add a benefit with respect to standard postoperative programs considered by previous research. Methods: From 2 months before to 13 months after SEMLS (except for the first month after surgery), the participant underwent a motor training focused on ROM exercises with tactile and kinaesthetic feedback. Walking performance, walking capacity, and quality-of-life were assessed before and after SEMLS at different follow-up times. Results: Walking capacity improved 3 months after SEMLS (i.e., earlier than in current literature) and walking performance improved 12 months after SEMLS (instead of simply returning to baseline as previously reported), with a positive impact on quality-of-life. Conclusions: This case suggests that a rehabilitation program starting even before SEMLS could add benefits over walking function and quality-of-life of children with diplegic CP compared to postoperative programs only.

Pointing in cervical dystonia patients.

Introduction: The normal hemispheric balance can be altered by the asymmetric sensorimotor signal elicited by Cervical Dystonia (CD), leading to motor and cognitive deficits. Methods: Directional errors, peak velocities, movement and reaction times of pointing towards out-of-reach targets in the horizontal plane were analysed in 18 CD patients and in 11 aged-matched healthy controls. Results: CD patients displayed a larger scatter of individual trials around the average pointing direction (variable error) than normal subjects, whatever the arm used, and the target pointed. When pointing in the left hemispace, all subjects showed a left deviation (constant error) with respect to the target position, which was significantly larger in CD patients than controls, whatever the direction of the abnormal neck torsion could be. Reaction times were larger and peak velocities lower in CD patients than controls. Discussion: Deficits in the pointing precision of CD patients may arise from a disruption of motor commands related to the sensorimotor imbalance, from a subtle increase in shoulder rigidity or from a reduced agonists activation. Their larger left bias in pointing to left targets could be due to an increased right parietal dominance, independently upon the direction of head roll/jaw rotation which expands the left space representation and/or increases left spatial attention. These deficits may potentially extend to tracking and gazing objects in the left hemispace, leading to reduced skills in spatial-dependent motor and cognitive performance.

Positive effects of robotic exoskeleton training of upper limb reaching movements after stroke.

This study, conducted in a group of nine chronic patients with right-side hemiparesis after stroke, investigated the effects of a robotic-assisted rehabilitation training with an upper limb robotic exoskeleton for the restoration of motor function in spatial reaching movements. The robotic assisted rehabilitation training was administered for a period of 6 weeks including reaching and spatial antigravity movements. To assess the carry-over of the observed improvements in movement during training into improved function, a kinesiologic assessment of the effects of the training was performed by means of motion and dynamic electromyographic analysis of reaching movements performed before and after training. The same kinesiologic measurements were performed in a healthy control group of seven volunteers, to determine a benchmark for the experimental observations in the patients' group. Moreover degree of functional impairment at the enrolment and discharge was measured by clinical evaluation with upper limb Fugl-Meyer Assessment scale (FMA, 0-66 points), Modified Ashworth scale (MA, 0-60 pts) and active ranges of motion. The robot aided training induced, independently by time of stroke, statistical significant improvements of kinesiologic (movement time, smoothness of motion) and clinical (4.6 ± 4.2 increase in FMA, 3.2 ± 2.1 decrease in MA) parameters, as a result of the increased active ranges of motion and improved co-contraction index for shoulder extension/flexion. Kinesiologic parameters correlated significantly with clinical assessment values, and their changes after the training were affected by the direction of motion (inward vs. outward movement) and position of target to be reached (ipsilateral, central and contralateral peripersonal space). These changes can be explained as a result of the motor recovery induced by the robotic training, in terms of regained ability to execute single joint movements and of improved interjoint coordination of elbow and shoulder joints.

Blink-related delta oscillations in the resting-state EEG: a wavelet analysis.

Over the past decades, many studies have linked the variations in frequency of spontaneous blinking with certain aspects of information processing and in particular with attention and working memory functions. On the other hand, according to the theory postulated by Crick and Koch, the actual function of primary consciousness is based on the reciprocal interaction between attention and working memory in the automatic and serial mode. The purpose of this study was to investigate for electrophysiological correlates compatible with the cognitive nature of spontaneous blinking, by using the EEG recordings obtained in a group of seven healthy volunteers while they rested quietly though awake, with their eyes open, but not actively engaged in attention-demanding goal-directed behaviours. The global wavelet analysis - at total of 189 three-second EEG epochs time-locked to the blink - revealed an increase in the delta band signal corresponding to the blink. In particular, a reconstruction of the EEG signal by means of inverse-wavelet transform (IWT) showed a blink-related P300-like wave at mid-parietal site. We assumed this phenomenon to represent an electrophysiological sign of the automatic processing of contextual environmental information. This might play a role in maintaining perceptive awareness of the environment at a low level of processing, while the subject is not engaged in attention-demanding tasks but rather introspectively oriented mental activities or free association(s).

Higher level gait disorders in subcortical chronic vascular encephalopathy: a single photon emission computed tomography study.

BACKGROUND: the so-called higher level gait disorders include several types of gait disorders in which there are no major modifications in strength, tone, sensitivity, coordination and balance. Brain activation sites related to walking have been investigated using SPECT in humans. The aim of the study was to investigate brain activation during walking in subjects with high-level gait disorders due to chronic subcortical vascular encephalopathy. SUBJECTS: twelve patients with a chronic vascular encephalopathy were enrolled in the study. Seven subjects had apraxic gait while in the other five the gait was normal. All patients had undergone a recent cerebral magnetic resonance that revealed diffused chronic ischemic lesions within the white matter. METHODS: all 12 patients underwent a regional cerebral blood flow (rCBF) brain SPECT study with (99m)Tc-Bicisate on two separate days and under two different conditions: at rest (baseline) and while walking (functional). RESULTS: the rCBF increase induced by the treadmill test (functional-baseline), bilaterally in the medial frontal gyrus and in the anterior lobes of the cerebellum, resulted significantly (P < 0.001) lower in patients with gait apraxia versus those without it. CONCLUSIONS: this study of the brain with SPECT records the areas of perfusion deficit that appear in apraxic subjects when they walk, compared with the recordings obtained with the same investigation performed at rest.

A Case of Carbon Monoxide-Induced Delayed Neurological Sequelae Successfully Treated with Hyperbaric Oxygen Therapy, N-Acetylcysteine, and Glucocorticoids: Clinical and Neuroimaging Follow-Up.

Carbon monoxide (CO) poisoning is a leading cause of intentional and unintentional poisoning worldwide, associated with mortality and severe morbidity. Some survivors of CO poisoning develop, after a lucid interval, a potentially permanent encephalopathy in the form of cognitive impairment and movement disorders, such as Parkinsonism. One of the most frequent neuroimaging findings is a cerebral white matter damage, but so far its precise cause and specific therapy are still debated. We here report the case of a 33-year-old woman with severe carbon monoxide poisoning who, after a period of lucid interval, presented symptoms of declining motor and cognitive functions. She was treated with 40 sessions of Hyperbaric Oxygen Therapy (HBOT). The therapeutic use of oxygen at supraphysiological pressures might either increase systemic oxidative stress or cause an overproduction of oxygen free radicals as drawbacks. Concurrent use of antioxidants and anti-inflammatory drugs may prevent the side effects of oxygen therapy at supraphysiological pressure due to oxidative stress. For this reason, the patient was also treated with high-dose N-Acetylcysteine and glucocorticoids. Here, we describe the longitudinal monitoring of patient's cognitive abilities and leukoencephalopathy associated with her positive clinical outcome.

Wearable Haptics and Immersive Virtual Reality Rehabilitation Training in Children With Neuromotor Impairments.

The past decade has seen the emergence of rehabilitation treatments using virtual reality (VR) environments although translation into clinical practice has been limited so far. In this paper, an immersive VR rehabilitation training system endowed with wearable haptics is proposed for children with neuromotor impairments: it aims to enhance involvement and engagement of patients, to provide congruent multi-sensory afferent feedback during motor exercises and to benefit from the flexibility of VR in adapting exercises to the patient's need. An experimental rehabilitation session conducted with children with cerebral palsy (CP) and developmental dyspraxia (DD) has been performed to evaluate the usability of the system and proof of concept trial of the proposed approach. We compared CP/DD performance with both typically developing children and adult control group. Results show the system was compliant with different levels of motor skills and allowed patients to complete the experimental rehabilitation session, with performance varying according to the expected motor abilities of different groups. Moreover, a kinematic assessmentbased on the presented system has been designed. Obtained results reflected different motor abilities of patients and participants, suggesting suitability of the proposed kinematic assessment as a motor function outcome.

Integration of serious games and wearable haptic interfaces for Neuro Rehabilitation of children with movement disorders: A feasibility study.

The past decade has seen the emergence of rehabilitation treatments using virtual reality environments. One of the advantages in using this technology is the potential to create positive motivation, by means of engaging environments and tasks shaped in the form of serious games. In this work, we propose a novel Neuro Rehabilitation System for children with movement disorders, that is based on serious games in immersive virtual reality with haptic feedback. The system design aims to enhance involvement and engagement of patients, to provide congruent multi-sensory afferent feedback during motor exercises, and to benefit from the flexibility of virtual reality in adapting exercises to the patient's needs. We present a feasibility study of the method conducted through an experimental rehabilitation session in a group of 4 children with Cerebral Palsy and Developmental Dyspraxia, 4 Typically Developing children and 4 healthy adults. Subjects and patients were able to accomplish the proposed rehabilitation session and average performance of the motor exercises in patients were lower, although comparable, to healthy subjects. Together with positive comments reported by children after the rehabilitation session, results are encouraging for application of the method in a prolonged rehabilitation treatment.

Defective chromatic and achromatic visual pathways in developmental dyslexia: Cues for an integrated intervention programme.

PURPOSE: As well as obtaining confirmation of the magnocellular system involvement in developmental dyslexia (DD); the aim was primarily to search for a possible involvement of the parvocellular system; and, furthermore, to complete the assessment of the visual chromatic axis by also analysing the koniocellular system. METHODS: Visual evoked potentials (VEPs) in response to achromatic stimuli with low luminance contrast and low spatial frequency, and isoluminant red/green and blue/yellow stimuli with high spatial frequency were recorded in 10 dyslexic children and 10 age- and sex-matched, healthy subjects. RESULTS: Dyslexic children showed delayed VEPs to both achromatic stimuli (magnocellular-dorsal stream) and isoluminant red/green and blue/yellow stimuli (parvocellular-ventral and koniocellular streams). To our knowledge, this is the first time that a dysfunction of colour vision has been brought to light in an objective way (i.e., by means of electrophysiological methods) in children with DD. CONCLUSION: These results give rise to speculation concerning the need for a putative approach for promoting both learning how to read and/or improving existing reading skills of children with or at risk of DD. The working hypothesis would be to combine two integrated interventions in a single programme aimed at fostering the function of both the magnocellular and the parvocellular streams.

Prolonged intracortical delay of long-latency reflexes: electrophysiological evidence for a cortical dysfunction in multiple sclerosis.

Convincing evidence suggests that long-latency reflexes (LLRs) are capable of testing the transcortical sensorimotor reflex arch. By subtracting the sum of the latencies of N20 (afferent branch) and transcranially elicited motor evoked potentials (MEP; efferent branch) from the LLR II latency, the cortical relay time (CRT) can also be obtained, which is alleged to represent the time required for the cortical sensorimotor integration. The aim of the present study was to investigate if a cortical dysfunction occurs in multiple sclerosis (MS). Median nerve somatosensory evoked potentials (SEPs), MEPs and LLRs were recorded from the upper limbs of 23, not severely disabled MS patients in acute phases of the disease. Eighteen age and sex matched healthy volunteers served as controls. N20, MEP, LLR II latencies were measured, and the CRT was calculated for each limb. The statistical comparison between patients and controls was only weakly significant by taking into account conduction times along either the afferent (N20) or the efferent (MEP) pathways. On the contrary, it turned out to be considerably significant if both branches of the transcortical sensorimotor reflex arch, together with the intracortical pathway, were simultaneously tested by means of the LLRs. Moreover, the patients showed a significantly higher CRT compared with that found in the control subjects. These findings are consistent with a prolonged intracortical delay of LLRs in the MS group and suggest the occurrence of conduction velocity slowing and/or synaptic transmission impairment along the sensorimotor intracortical pathway in MS.

EEG Theta Dynamics within Frontal and Parietal Cortices for Error Processing during Reaching Movements in a Prism Adaptation Study Altering Visuo-Motor Predictive Planning.

Modulation of frontal midline theta (fmθ) is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error), at the time when visual feedback (hand appearance) became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP) time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects) suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi-naturalistic motor behaviours.

Effects of 50 Hz electromagnetic fields on electroencephalographic alpha activity, dental pain threshold and cardiovascular parameters in humans.

Recent studies indicate that exposure to extremely low frequency magnetic fields (ELF MFs) influences human electroencephalographic (EEG) alpha activity and pain perception. In the present study we analyse the effect on electrical EEG activity in the alpha band (8-13 Hz) and on nociception in 40 healthy male volunteers after 90-min exposure of the head to 50 Hz ELF MFs at a flux density of 40 or 80 microT in a double-blind randomized sham-controlled study. Since cardiovascular regulation is functionally related to pain modulation, we also measured blood pressure (BP) and heart rate (HR) during treatment. Alpha activity after 80 microT magnetic treatment almost doubled compared to sham treatment. Pain threshold after 40 microT magnetic treatment was significantly lower than after sham treatment. No effects were found for BP and HR. We suggest that these results may be explained by a modulation of sensory gating processes through the opioidergic system, that in turn is influenced by magnetic exposure.