Stefano Silvoni

Stability of muscle synergies for voluntary actions after cortical stroke in humans

Production of voluntary movements relies critically on the functional integration of several motor cortical areas, such as the primary motor cortex, and the spinal circuitries. Surprisingly, after almost 40 years of research, how the motor cortices specify descending neural signals destined for the downstream interneurons and motoneurons has remained elusive. In light of the many recent experimental demonstrations that the motor system may coordinate muscle activations through a linear combination of muscle synergies, we hypothesize that the motor cortices may function to select and activate fixed muscle synergies specified by the spinal or brainstem networks. To test this hypothesis, we recorded electromyograms (EMGs) from 12–16 upper arm and shoulder muscles from both the unaffected and the stroke-affected arms of stroke patients having moderate-to-severe unilateral ischemic lesions in the frontal motor cortical areas. Analyses of EMGs using a nonnegative matrix factorization algorithm revealed that in seven of eight patients the muscular compositions of the synergies for both the unaffected and the affected arms were strikingly similar to each other despite differences in motor performance between the arms, and differences in cerebral lesion sizes and locations between patients. This robustness of muscle synergies that we observed supports the notion that descending cortical signals represent neuronal drives that select, activate, and flexibly combine muscle synergies specified by networks in the spinal cord and/or brainstem. Our conclusion also suggests an approach to stroke rehabilitation by focusing on those synergies with altered activations after stroke.

Muscle synergy patterns as physiological markers of motor cortical damage.

The experimental findings herein reported are aimed at gaining a perspective on the complex neural events that follow lesions of the motor cortical areas. Cortical damage, whether by trauma or stroke, interferes with the flow of descending signals to the modular interneuronal structures of the spinal cord. These spinal modules subserve normal motor behaviors by activating groups of muscles as individual units (muscle synergies). Damage to the motor cortical areas disrupts the orchestration of the modules, resulting in abnormal movements. To gain insights into this complex process, we recorded myoelectric signals from multiple upper-limb muscles in subjects with cortical lesions. We used a factorization algorithm to identify the muscle synergies. Our factorization analysis revealed, in a quantitative way, three distinct patterns of muscle coordination—including preservation, merging, and fractionation of muscle synergies—that reflect the multiple neural responses that occur after cortical damage. These patterns varied as a function of both the severity of functional impairment and the temporal distance from stroke onset. We think these muscle-synergy patterns can be used as physiological markers of the status of any patient with stroke or trauma, thereby guiding the development of different rehabilitation approaches, as well as future physiological experiments for a further understanding of postinjury mechanisms of motor control and recovery.

Brain-Computer Interface in Stroke: A Review of Progress

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.

P300-Based Brain–Computer Interface Communication: Evaluation and Follow-up in Amyotrophic Lateral Sclerosis

To describe results of training and 1-year follow-up of brain-communication in a larger group of early and middle stage amyotrophic lateral sclerosis (ALS) patients using a P300-based brain–computer interface (BCI), and to investigate the relationship between clinical status, age and BCI performance. A group of 21 ALS patients were tested with a BCI-system using two-dimensional cursor movements. A four choice visual paradigm was employed to training and test the brain-communication abilities. The task consisted of reaching with the cursor one out of four icons representing four basic needs. Five patients performed a follow-up test 1u2009year later. The clinical severity in all patients were assessed with a battery of clinical tests. A comparable control group of nine healthy subjects was employed to investigate performance differences. Nineteen patients and nine healthy subjects were able to achieve good and excellent cursor movements control, acquiring at least communication abilities above chance level; during follow-up the patients maintained their BCI-skill. We found mild cognitive impairments in the ALS group which may be attributed to motor deficiencies, while no relevant correlation has been found between clinical data and BCI performance. A positive correlation between age and the BCI-skill in patients was found. Time since training acquisition and clinical status did not affect the patients brain-communication skill at early and middle stage of the disease. A brain-communication tool can be used in most ALS patients at early and middle stage of the disease before entering the locked-in stage.

Brain–Computer Interface–Based Communication in the Completely Locked-In State

Despite partial success, communication has remained impossible for persons suffering from complete motor paralysis but intact cognitive and emotional processing, a state called complete locked-in state (CLIS). Based on a motor learning theoretical context and on the failure of neuroelectric brain–computer interface (BCI) communication attempts in CLIS, we here report BCI communication using functional near-infrared spectroscopy (fNIRS) and an implicit attentional processing procedure. Four patients suffering from advanced amyotrophic lateral sclerosis (ALS)—two of them in permanent CLIS and two entering the CLIS without reliable means of communication—learned to answer personal questions with known answers and open questions all requiring a “yes” or “no” thought using frontocentral oxygenation changes measured with fNIRS. Three patients completed more than 46 sessions spread over several weeks, and one patient (patient W) completed 20 sessions. Online fNIRS classification of personal questions with known answers and open questions using linear support vector machine (SVM) resulted in an above-chance-level correct response rate over 70%. Electroencephalographic oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication despite occasional differences between the physiological signals representing a “yes” or “no” response. However, electroencephalogram (EEG) changes in the theta-frequency band correlated with inferior communication performance, probably because of decreased vigilance and attention. If replicated with ALS patients in CLIS, these positive results could indicate the first step towards abolition of complete locked-in states, at least for ALS.

Brain communication in the locked-in state

Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) yes and no responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifiers performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional variations or variations of circadian period as important factors in brain-computer interface communication with locked-in state and completely locked-in state.

Event-related brain potential modulation in patients with severe brain damage

OBJECTIVEnThe 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.nnnMETHODSnThe patients in vegetative state were 11 and the MCS patients were 6 [corrected]. Three oddball paradigms with different level of complexity were applied: sine tones, the subjects own name versus sine tones and other first names. Latencies and amplitudes of N1 and P3 waves were compared.nnnRESULTSnCortical 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.nnnCONCLUSIONSnThese 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.nnnSIGNIFICANCEnModulation of P3 latency related to stimulus complexity could provide valuable information about the cognitive capabilities of unresponsive patients.

Amyotrophic lateral sclerosis progression and stability of brain-computer interface communication

Abstract 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.

Direct Brain Control and Communication in Paralysis

Despite considerable growth in the field of brain-computer or brain-machine interface (BCI/BMI) research reflected in several hundred publications each year, little progress was made to enable patients in complete locked-in state (CLIS) to reliably communicate using their brain activity. Independent of the invasiveness of the BCI systems tested, no sustained direct brain control and communication was demonstrated in a patient in CLIS so far. This suggested a more fundamental theoretical problem of learning and attention in brain communication with BCI/BMI, formulated in the extinction-of-thought hypothesis. While operant conditioning and goal-directed thinking seems impaired in complete paralysis, classical conditioning of brain responses might represent the only alternative. First experimental studies in CLIS using semantic conditioning support this assumption. Evidence that quality-of-life in locked-in-state is not as limited and poor as generally believed draise doubts that “patient wills” or “advanced directives”signed long-before the locked-in-state are useful. On the contrary, they might be used as an excuse to shorten anticipated long periods of care for these patients avoiding associated financial and social burdens. Current state and availability of BCI/BMI systems urge a broader societal discourse on the pressing ethical challenges associated with the advancements in neurotechnology and BCI/BMI research.

Ideomotor silence: the case of complete paralysis and brain-computer interfaces (BCI)

The paper presents some speculations on the loss of voluntary responses and operant learning in long-term paralysis in human patients and curarized rats. Based on a reformulation of the ideomotor thinking hypothesis already described in the 19th century, we present evidence that instrumentally learned responses and intentional cognitive processes extinguish as a consequence of long-term complete paralysis in patients with amyotrophic lateral sclerosis (ALS). Preliminary data collected with ALS patients during extended and complete paralysis suggest semantic classical conditioning of brain activity as the only remaining communication possibility in those states.