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Assessment of consciousness following severe brain-injury is challenging. Our hypothesis is that electroencephalography (EEG) can provide information on awareness, in terms of oscillatory activity and network task–related modifications, in people with disorders of consciousness. Similar results were obtained with neuroimaging techniques; we aim at demonstrating the use of EEG, which is low cost and routinely implemented, to the same goal. Nineteen-channel EEG was recorded in 7 persons with unresponsive wakefulness syndrome (UWS) and in 10 healthy subjects during the execution of active (attempted movement) and passive motor tasks as well as 2 mental imagery tasks. Event-related synchronization/desynchronization (ERS/ERD), coherence and network parameters were calculated in delta (1-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), and beta (13-30 Hz) ranges. In UWS subjects, passive movement induced a weak alpha2 ERD over contralateral sensorimotor area. During motor imagery, ERD was detected over the frontal and motor contralateral brain areas; during spatial imagery, ERS in lower alpha band over the right temporo-parietal regions was missing. In UWS, functional connectivity provided evidence of network disruption and isolation of the motor areas, which cannot dialog with adjacent network nodes, likely suggesting a diffuse structural alteration. Our findings suggest that people with a clinical diagnosis of UWS were able to modulate their brain activity when prompted to perform movement tasks and thus suggest EEG as a potential tool to support diagnosis of disorders of consciousness.

Objectives Left dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity. Methods 12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session. Results An increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham. Conclusions tDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost. Significance Our results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.

Contains fulltext : 150727.pdf (Publisher’s version ) (Closed access) Objective We investigated neurophysiological brain responses elicited by a tactile event-related potential paradigm in a sample of ALS patients. Underlying cognitive processes and neurophysiological signatures for brain-computer interface (BCI) are addressed. Methods We stimulated the palm of the hand in a group of fourteen ALS patients and a control group of ten healthy participants and recorded electroencephalographic signals in eyes-closed condition. Target and non-target brain responses were analyzed and classified offline. Classification errors served as the basis for neurophysiological brain response sub-grouping. Results A combined behavioral and quantitative neurophysiological analysis of sub-grouped data showed neither significant between-group differences, nor significant correlations between classification performance and the ALS patients’ clinical state. Taking sequential effects of stimuli presentation into account, analyses revealed mean classification errors of 19.4% and 24.3% in healthy participants and ALS patients respectively. Conclusions Neurophysiological correlates of tactile stimuli presentation are not altered by ALS. Tactile event-related potentials can be used to monitor attention level and task performance in ALS and may constitute a viable basis for future BCIs. Significance Implications for brain-computer interface implementation of the proposed method for patients in critical conditions, such as the late stage of ALS and the (completely) locked-in state, are discussed. 10 p.

Based on available evidence, muscle strengthening and cardiovascular exercises can help maintain function and not adversely affect the progression of disease in patients with ALS. However, this evidence is not sufficiently detailed to recommend a specific exercise prescription. The purpose of this project was to assess clinical outcomes of a combined exercise programme to increase knowledge of rehabilitation in ALS patients. 38 ALS patients were assigned randomly to two groups: one group underwent a specific exercise programme (ALS-EP) based on a moderate aerobic workout and isometric contractions, and the second group followed a standard neuromotor rehabilitation treatment. Objective evaluation consisted of cardiovascular measures, muscle strength and fatigue. Some positive effects of physical activity on ALS patients were found. Among the benefits, an overall improvement of functional independence in all patients, independently of the type of exercise conducted was seen. In addition, improvements in muscle power, oxygen consumption and fatigue were specifically observed in the ALS-EP group, all hallmarks of a training effect for the specific exercises. In conclusion, moderate intensity exercise is beneficial in ALS, helping in avoiding deconditioning and muscle atrophy resulting from progressive inactivity.

The effect of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) on psychopathological symptoms and resting state brain activity was assessed in a patient with obsessive-compulsive disorder (OCD). tDCS and rTMS had no effect on OC symptoms. tDCS, however, improved depression and anxiety. Functional magnetic resonance imaging at baseline showed an interhemispheric asymmetry with hyperactivation of the left and hypoactivation of the right anterior neural circuits. A reduction of interhemispheric imbalance was detected after tDCS but not after rTMS. tDCS seems to be more effective than rTMS in restoring interhemispheric imbalance and improving anxiety and depression in OCD.

Background In the last decade transcranial direct current stimulation (tDCS) has been introduced in aphasia post-stroke recovery as a tool for modulating neuroplasticity. However, it is still unclear whether tDCS should be applied at rest ( off-line ) or combined with behavioral treatment strategies ( on-line ), therefore, this study investigates the effect of repeated sessions of off-line tDCS on language recovery in post-stroke chronic aphasic patients. Methodology Eight post-stroke patients with different type and degree of chronic aphasia underwent two weeks of off-line anodal tDCS (2 mA intensity for 20 min a day) on Broca's area and two weeks of sham stimulation as a control condition. Language recovery was measured assessing object and action naming abilities with a computerized picture naming task. Results No significant difference between anodal tDCS and sham stimulation, both for object and action naming tasks, was found. Descriptive analysis of single cases showed that after tDCS only one patient improved substantially on action naming task. Conclusion With the exception of one patient, the overall results suggest that in chronic aphasic patients the off-line tDCS protocol applied in this study is not effective in improving noun and verb naming abilities.

Magnetoencephalography (MEG) is a non-invasive neurophysiological technique used to study the cerebral cortex. Currently, MEG is mainly used clinically to localize epileptic foci and eloquent brain areas in order to avoid damage during neurosurgery. MEG might, however, also be of help in monitoring stroke recovery and rehabilitation. This review focuses on experimental use of MEG in Neurorehabilitation. MEG has been employed to detect early modifications in neuroplasticity and connectivity, but there is insufficient evidence as to whether these methods are sensitive enough to be used as a clinical diagnostic test. MEG has also been exploited to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface (BCI). In the current body of experimental research MEG appears to be a powerful tool in neurorehabilitation, but it is necessary to produce new data to confirm its clinical utility.

Objective of this study was to evaluate attentional control mechanisms in amyotrophic lateral sclerosis (ALS) using an auditory event-related potentials (ERPs) paradigm. Fifteen mild to moderate ALS patients and 15 healthy controls were administered a brief neuropsychological test battery and an ERPs paradigm assessing selective attention. Four types of auditory stimuli were presented in random order: short standard (200 Hz, 200 ms), long standard (200 Hz, 500 ms), short deviant (1000 Hz, 200 ms) and long deviant (1000 Hz, 500 ms). Participants had to respond to the long deviant stimuli only. During the task the electroencephalogram (EEG) was recorded. The N200, P300 and re-orienting negativity (RON) ERP components were analysed. Compared to controls ALS patients showed reduced amplitudes and delayed latencies of N200, P300 and RON. These results could be attributable to both an alteration in change detection resulting in a reduction of the allocation and re-orientation of attentional resources or a general slowing or reduction of neural processing efficiency in the same system. The ERPs results support the hypothesis that ALS involves extramotor cognitive functions including auditory attentional processing at all processing stages, early (200 ms) and late (300-600 ms). These data prove the usefulness and sensitivity of the auditory ERPs in detection of cognitive functions in ALS patients.

Electroencephalography (EEG) is a powerful and inexpensive bedside tool for the assessment of residual brain function in prolonged disorders of consciousness. Here we review a range of methods for EEG interpretation, including reactivity, perturbation by transcranial magnetic stimulation, evoked potentials, and oscillatory changes. We show that, in combination, these methods can form a reliable picture of each patient’s structural impairments and residual sensory and cognitive functioning, thereby leading to more accurate diagnoses and prognoses and stratification of patients for experimental neuro-stimulation therapies.

Aim of this study is to investigate working memory functions in nondemented patients with amyotrophic lateral sclerosis (ALS) using neuropsychological testing and auditory event-related potentials. Twenty-four patients with ALS and 17 age- and education-matched controls underwent a comprehensive neuropsychological assessment, with particular emphasis on working memory functions. Event-related potentials were assessed with an active auditory oddball paradigm. In a subsample (67%) of patients with ALS, the neuropsychological assessment revealed impaired performance on working memory tests (semantic and letter verbal fluency, modified card sorting test, trail making test, digit span, Corsi blocks tapping test, and prose memory). The analysis of event-related potentials showed a significant delay of the N100, P200, and N200 latency in ALS compared with controls. Correlation analysis showed a relation between clinical parameters (disease duration and functional rating scale) and neuropsychological test results (letter fluency and trail making test) and between disease duration and P300 amplitude. The neuropsychological and event-related potentials profile of patients with ALS at an average is consistent with a mild dysfunction of the central executive component of working memory. In conclusion, the results support previously published reports that indicate the involvement of the extramotor functions in a significant subsample of ALS.

Evoked potentials allow one to assess functional integrity of sensory pathways projecting to primary sensory cortices and event-related potentials assess higher order cortical functions associated with stimulus detection and decision-making. Evoked and event-related potentials have been used to predict emergence from coma. This study aimed to determine whether they can help prediction of consciousness recovery in post-traumatic vegetative state (VS).Thirty-four patients in post-traumatic VS were assessed clinically and neurophysiologically at 2-3 months after injury and followed up to 1 year. Patients were assessed with the Disability Rating Scale (DRS) and with electroencephalogram (EEG), brainstem auditory (BAEP) and somatosensory evoked potentials (SEP) and P300. Demographic, clinical and neurophysiological measures were analysed by descriptive and logistic regression techniques.At 1 year from injury, 26 patients (76%) had recovered consciousness and eight patients (24%) had not. In univariate analyses, a detectable P300, a reactive EEG and lower DRS scores were found at entry assessment more frequently (p0.05) in patients who later recovered consciousness than in those who did not. Logistic regression analysis revealed that P300 was the only factor contributing to prediction of conscious recovery with an area under the ROC curve of 0.94 (95% CI, 0.80-0.99).P300 is a strong predictor of conscious recovery in VS.

In patients without a behavioral response, non-invasive techniques and new methods of data analysis can complement existing diagnostic tools by providing a method for detecting covert signs of residual cognitive function and awareness. The aim of this study was to investigate the brain oscillatory activities synchronized by single-pulse transcranial magnetic stimulation (TMS) delivered over the primary motor area in the time–frequency domain in patients with the unresponsive wakefulness syndrome or in a minimally conscious state as compared to healthy controls. A time–frequency analysis based on the wavelet transform was used to characterize rapid modifications of oscillatory EEG rhythms induced by TMS in patients as compared to healthy controls. The pattern of EEG changes in the patients differed from that of healthy controls. In the controls there was an early synchronization of slow waves immediately followed by a desynchronization of alpha and beta frequency bands over the frontal and centro-parietal electrodes, whereas an opposite early synchronization, particularly over motor areas for alpha and beta and over the frontal and parietal electrodes for beta power, was seen in the patients. In addition, no relevant modification in slow rhythms (delta and theta) after TMS was noted in patients. The clinical impact of these findings could be relevant in neurorehabilitation settings for increasing the awareness of these patients and defining new treatment procedures.

Evaluation of consciousness needs to be supported by the evidence of brain activation during external stimulation in patients with unresponsive wakefulness syndrome (UWS). Assessment of patients should include techniques that do not depend on overt motor responses and allow an objective investigation of the spontaneous patterns of brain activity. In particular, electroencephalography (EEG) coherence allows to easily measure functional relationships between pairs of neocortical regions and seems to be closely correlated with cognitive or behavioral measures. Here, we show the contribution of higher order associative cortices of patients with disorder of consciousness (N = 26) in response to simple sensory stimuli, such as visual, auditory and noxious stimulation. In all stimulus modalities an increase of short-range parietal and long-range fronto-parietal coherences in gamma frequencies were seen in the controls and minimally conscious patients. By contrast, UWS patients showed no significant modifications in the EEG patterns after stimulation. Our results suggest that UWS patients can not activate associative cortical networks, suggesting a lack of information integration. In fact, fronto-parietal circuits result to be connectively disrupted, conversely to patients that exhibit some form of consciousness. In the light of this, EEG coherence can be considered a powerful tool to quantify the involvement of cognitive processing giving information about the integrity of fronto-parietal network. This measure can represent a new neurophysiological marker of unconsciousness and help in determining an accurate diagnosis and rehabilitative intervention in each patient.

Motor rehabilitation after stroke injury is highly important since the number of people suffering this disease is constantly increasing. Brain-Computer Interfaces (BCIs) have been recently used in the recovery of motor functions: in particular, the closed loop involving sensorimotor brain rhythms, assist-ive-robot training and proprioceptive feedback in an operant learning fashion might be potentially one of the most effective ways to promote the neural plasticity of the ipsilesional brain hemisphere and to restore motor abilities. This study aimed at implementing such a scheme: one chronic stroke patient was recruited and underwent the experiment using both the damaged and the healthy arm, considered as control during the following analysis. Kinematic and neurophysiological outcomes confirmed the efficacy of this treatment and supported the hypothesis that a contingent force feedback can improve motor functions of the upper limb.

Our objective was to investigate the relationship between brain-computer interface (BCI) communication skill and disease progression in amyotrophic lateral sclerosis (ALS). We sought also to assess stability of BCI communication performance over time and whether it is related to the progression of neurological impairment before entering the locked-in state. A three years follow-up, BCI evaluation in a group of ALS patients (n = 24) was conducted. For a variety of reasons only three patients completed the three years follow-up. BCI communication skill and disability level, using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, were assessed at admission and at each of the three follow-ups. Multiple non-parametric statistical methods were used to ensure reliability of the dependent variables: correlations, paired test and factor analysis of variance. Results demonstrated no significant relationship between BCI communication skill (BCI-CS) and disease evolution. The patients who performed the follow-up evaluations preserved their BCI-CS over time. Patients' age at admission correlated positively with the ability to achieve control over a BCI. In conclusion, disease evolution in ALS does not affect the ability to control a BCI for communication. BCI performance can be maintained in the different stages of the illness.

Background Repetitive transcranial magnetic stimulation (rTMS) induces prolonged functional changes in the cerebral cortex in normal conditions and in altered states of consciousness. Its therapeutic effects have been variously documented. Objective The aim of this study was to investigate the reactivity of electroencephalography (EEG) and the clinical response in six severely brain-injured patients in an altered state of consciousness (minimally conscious state [MCS] or vegetative state [VS]). EEG rhythm and brain excitability were measured before and after a protocol of high-frequency rTMS. Methods All six patients underwent clinical and neurophysiological evaluation before rTMS and immediately thereafter. EEG data in resting state were acquired at the beginning of the exam ( T 0 ), after rTMS ( T 1 ), and 38 min after rTMS ( T 2 ). From these data the power values were computed using Fast Fourier Transform. Results rTMS over the motor cortex induced long-lasting behavioral and neurophysiological modifications in only one patient in MCS. No significant clinical or EEG modifications were detected in any of the other patients, except for changes in motor threshold and motor evoked potential amplitude over the stimulated motor areas. Conclusions The main finding of the study is the correlation between EEG reactivity and clinical response after rTMS. Reappearance of fast activity and an increase in slow activity were noted in the one patient with transitory arousal, whereas no significant reliable changes were observed in the other patients showing no clinical reactivity.

Brain-computer interface (BCI) technology has been used for rehabilitation after stroke and there are a number of reports involving stroke patients in BCI-feedback training. Most publications have demonstrated the efficacy of BCI technology in post-stroke rehabilitation using output devices such as Functional Electrical Stimulation, robot, and orthosis. The aim of this review is to focus on the progress of BCI-based rehabilitation strategies and to underline future challenges. A brief history of clinical BCI-approaches is presented focusing on stroke motor rehabilitation. A context for three approaches of a BCI-based motor rehabilitation program is outlined: the substitutive strategy, classical conditioning and operant conditioning. Furthermore, we include an overview of a pilot study concerning a new neuro-forcefeedback strategy. This pilot study involved healthy participants. Finally we address some challenges for future BCI-based rehabilitation.

Our objective was to assess the autonomic function of ALS patients with and without bulbar signs to characterize dysautonomia in ALS disease. Standard autonomic tests and spectral analysis of heart rate variability (HRV), reflecting changes in the sympathovagal balance, were examined in 33 ALS patients (14 with bulbar signs) and 30 controls. Results showed that in the supine position, ALS patients had significantly lower total power and absolute values of high-frequency power indicating a depressed sinus arrhythmia. Patients with bulbar signs showed more marked autonomic alterations at rest. Tilting did not induce the expected increase in low-frequency and decrease in high-frequency power of HRV in all patients. No correlation was found between autonomic tests and clinical parameters. Our findings suggest an early subclinical involvement of the autonomic system in ALS, particularly affecting parasympathetic cardiac control. Patients with prominent bulbar signs show a more severe autonomic dysfunction under resting conditions.

The aim of this study was to determine what made people want to change their choice of general practitioners (GP). Furthermore, the study aimed to correlate the perceived quality of patient-GP communication with the motives inducing individuals to change their doctors. All people requesting to change their GPs were asked by the office staff to complete a questionnaire. The study identifies the following main reasons for changing GP: patients perceived the doctor as unwilling to listen to them; patients did not receive the services that they considered useful for their health; and patients perceived the doctor’s disorganization as an obstacle to accessibility. These findings suggest several actions to improve the doctor–patient relationship, including training for physicians to develop their communication skills; involving public health operators in helping to understand the rights and obligations of patients and doctors; and a reorganization of the GP’s workload.

Background. In 2007, Schiff et al reported a patient in a minimally conscious state (MCS) who responded to deep brain stimulation (DBS), but clinicians cannot predict which patients might respond prior to the implantation of electrodes. Methods. A patient in a MCS for 5 years participated in an ABA design alternating between repetitive transcranial magnetic stimulation (rTMS) and peripheral nerve stimulation. rTMS (condition A) involved the delivery of 10 trains of 100 stimuli at 20 Hz using a stimulator with a 70-mm figure-of-eight coil to elicit a contraction of the abductor pollicis brevis. Condition B used median nerve electrical stimulation. Results. After peripheral stimulation, the patient did not exhibit clinical, behavioral, or electroencephalographic (EEG) changes. The frequency of specific and meaningful behaviors increased after rTMS, along with the absolute and relative power of the EEG δ, β, and α bands. Conclusion. These results suggest that rTMS may improve awareness and arousal in MCS. If these results are reproducible, rTMS may identify subgroups of MCS patients who might benefit from DBS.

Objective The limited evidence and inconsistency of purposeful behaviors in patients in a minimally conscious state (MCS) asks for objective electrophysiological marker of the level of consciousness. Here, a comparison between event-related potentials (ERPs) was investigated using different level of stimulus complexity. Methods ERPs were recorded in seventeen patients, 6 of which in vegetative state (VS), 11 in MCS, and 10 controls. Three oddball paradigms with different level of complexity were applied: sine tones, the subject’s own name versus sine tones and other first names. Latencies and amplitudes of N1 and P3 waves were compared. Results Cortical responses were found in all MCS patients, and in 6 of 11 patients in VS. Healthy controls and MCS patients showed a progressive increase of P3 latency in relation to the level of stimulus complexity. No modulation of P3 latency was observed in the vegetative patients. Conclusions These results suggest that the modulation of P3 latency related to stimulus complexity may represent an objective index of higher-order processing integration that predicts the recovery of consciousness from VS to MCS when clinical manifestations are inconsistent. Significance Modulation of P3 latency related to stimulus complexity could provide valuable information about the cognitive capabilities of unresponsive patients.

The limited evidence and inconsistency of purposeful behaviors in patients in a minimally conscious state (MCS) asks for objective electrophysiological marker of the level of consciousness. Here, a comparison between event-related potentials (ERPs) was investigated using different level of stimulus complexity. ERPs were recorded in 17 patients, 11 of which in vegetative state (VS), 6 in MCS, and 10 controls. Three oddball paradigms with different level of complexity were applied: sine tones, the subject’s own name vs. sine tones and other first names. Latencies and amplitudes of N1 and P3 waves were compared using a semi-automated peak detection algorithm. Cortical responses were found in all MCS patients, and in 6 of 11 patients in VS. Healthy controls and MCS patients showed a progressive increase of P3 latency in relation to the level of stimulus complexity. No modulation of P3 latency was observed in the vegetative patients. These results suggest that the modulation of P3 latency related to stimulus complexity may represent an objective index of higher-order processing integration that predicts the recovery of consciousness from VS to MCS when clinical manifestations are inconsistent. P3 latency modulation may help differentiate between different states of consciousness.

The aim of the present study was to assess the effect of transcranial direct current stimulation (TDCS) applied to the dorso-lateral prefrontal cortex (DLPF) on the behavioral responses and brain oscillations in 15 patients in vegetative (VS) and minimally conscious state (MCS). 10 daily sessions of anodal tcds were applied to the left dlpf. A sham stimulation was used as a control condition. 19-channels EEG was recorded before and after stimulation. The EEG coherence and spectral pattern differences before and after each treatment were analyzed. EEG data analysis showed a significant increase of coherence over the frontal and fronto-parietal areas in beta and gamma frequencies after tdcs. No significant effects were observed after sham stimulation. Clinical assessment of patients showed no significant changes. However all caregivers reported a reduction of oscillations of arousal level. Our study suggests that tdcs could influence the EEG coherence of rapid frequencies allowing the interaction between frontal and parietal areas. This interaction represents a fundamental prerequisite for all conscious perception mechanisms. TDCS may represent an useful new tool for cognitive rehabilitation.

Motor rehabilitation after stroke injury is highly important since the number of people suffering this disease is constantly increasing. Brain-Computer Interfaces (BCIs) have been recently used in the recovery of motor functions: in particular, the closed loop involving sensorimotor brain rhythms, assist-ive-robot training and proprioceptive feedback in an operant learning fashion might be potentially one of the most effective ways to promote the neural plasticity of the ipsilesional brain hemisphere and to restore motor abilities. This study aimed at implementing such a scheme: one chronic stroke patient was recruited and underwent the experiment using both the damaged and the healthy arm, considered as control during the following analysis. Kinematic and neurophysiological outcomes confirmed the efficacy of this treatment and supported the hypothesis that a contingent force feedback can improve motor functions of the upper limb.