Giulia Liberati

Assistive Device With Conventional, Alternative, and Brain-Computer Interface Inputs to Enhance Interaction With the Environment for People With Amyotrophic Lateral Sclerosis: A Feasibility and Usability Study

OBJECTIVE To evaluate the feasibility and usability of an assistive technology (AT) prototype designed to be operated with conventional/alternative input channels and a P300-based brain-computer interface (BCI) in order to provide users who have different degrees of muscular impairment resulting from amyotrophic lateral sclerosis (ALS) with communication and environmental control applications. DESIGN Proof-of-principle study with a convenience sample. SETTING An apartment-like space designed to be fully accessible by people with motor disabilities for occupational therapy, placed in a neurologic rehabilitation hospital. PARTICIPANTS End-users with ALS (N=8; 5 men, 3 women; mean age ± SD, 60 ± 12 y) recruited by a clinical team from an ALS center. INTERVENTIONS Three experimental conditions based on (1) a widely validated P300-based BCI alone; (2) the AT prototype operated by a conventional/alternative input device tailored to the specific end-users residual motor abilities; and (3) the AT prototype accessed by a P300-based BCI. These 3 conditions were presented to all participants in 3 different sessions. MAIN OUTCOME MEASURES System usability was evaluated in terms of effectiveness (accuracy), efficiency (written symbol rate, time for correct selection, workload), and end-user satisfaction (overall satisfaction) domains. A comparison of the data collected in the 3 conditions was performed. RESULTS Effectiveness and end-user satisfaction did not significantly differ among the 3 experimental conditions. Condition III was less efficient than condition II as expressed by the longer time for correct selection. CONCLUSIONS A BCI can be used as an input channel to access an AT by persons with ALS, with no significant reduction of usability.

Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception

The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral recordings, we investigated whether the human insula exhibits local field potentials (LFPs) specific for pain. Forty-seven insular sites were investigated. Participants received brief stimuli belonging to four different modalities (nociceptive, vibrotactile, auditory, and visual). Both nociceptive stimuli and non-nociceptive vibrotactile, auditory, and visual stimuli elicited consistent LFPs in the posterior and anterior insula, with matching spatial distributions. Furthermore, a blind source separation procedure showed that nociceptive LFPs are largely explained by multimodal neural activity also contributing to non-nociceptive LFPs. By revealing that LFPs elicited by nociceptive stimuli reflect activity unrelated to nociception and pain, our results confute the widespread assumption that these brain responses are a signature for pain perception and its modulation.

Questioning the dichotomy between vegetative state and minimally conscious state: a review of the statistical evidence

Given the enormous consequences that the diagnosis of vegetative state (VS) vs. minimally conscious state (MCS) may have for the treatment of patients with disorders of consciousness, it is particularly important to empirically legitimate the distinction between these two discrete levels of consciousness. Therefore, the aim of this contribution is to review all the articles reporting statistical evidence concerning the performance of patients in VS vs. patients in MCS, on behavioral or neurophysiological measures. Twenty-three articles matched these inclusion criteria, and comprised behavioral, electroencephalographic (EEG), positron emission tomography (PET) and magnetic resonance imaging (MRI) measures. The analysis of these articles yielded 47 different statistical findings. More than half of these findings (n = 24) did not reveal any statistically significant difference between VS and MCS. Overall, there was no combination of variables that allowed reliably discriminating between VS and MCS. This pattern of results casts doubt on the empirical validity of the distinction between VS and MCS.

Developing brain-computer interfaces from a user-centered perspective: Assessing the needs of persons with amyotrophic lateral sclerosis, caregivers, and professionals

By focus group methodology, we examined the opinions and requirements of persons with ALS, their caregivers, and health care assistants with regard to developing a brain-computer interface (BCI) system that fulfills the users needs. Four overarching topics emerged from this analysis: 1) lack of information on BCI and its everyday applications; 2) importance of a customizable system that supports individuals throughout the various stages of the disease; 3) relationship between affectivity and technology use; and 4) importance of individuals retaining a sense of agency. These findings should be considered when developing new assistive technology. Moreover, the BCI community should acknowledge the need to bridge experimental results and its everyday application.

Gamma-band oscillations preferential for nociception can be recorded in the human insula

Abstract Transient nociceptive stimuli elicit robust phase‐locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non‐nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma‐band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception‐evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non‐nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non‐nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150‐300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Insula and inferior frontal triangularis activations distinguish between conditioned brain responses using emotional sounds for basic BCI communication

In order to enable communication through a brain-computer interface (BCI), it is necessary to discriminate between distinct brain responses. As a first step, we probed the possibility to discriminate between affirmative (“yes”) and negative (“no”) responses using a semantic classical conditioning paradigm, within an fMRI setting. Subjects were presented with congruent and incongruent word-pairs as conditioned stimuli (CS), respectively eliciting affirmative and negative responses. Incongruent word-pairs were associated to an unpleasant unconditioned stimulus (scream, US1) and congruent word-pairs were associated to a pleasant unconditioned stimulus (baby-laughter, US2), in order to elicit emotional conditioned responses (CR). The aim was to discriminate between affirmative and negative responses, enabled by their association with the positive and negative affective stimuli. In the late acquisition phase, when the US were not present anymore, there was a strong significant differential activation for incongruent and congruent word-pairs in a cluster comprising the left insula and the inferior frontal triangularis. This association was not found in the habituation phase. These results suggest that the difference in affirmative and negative brain responses was established as an effect of conditioning, allowing to further investigate the possibility of using this paradigm for a binary choice BCI.

Residual upper arm motor function primes innervation of paretic forearm muscles in chronic stroke after Brain-Machine Interface (BMI) training

Background Abnormal upper arm-forearm muscle synergies after stroke are poorly understood. We investigated whether upper arm function primes paralyzed forearm muscles in chronic stroke patients after Brain-Machine Interface (BMI)-based rehabilitation. Shaping upper arm-forearm muscle synergies may support individualized motor rehabilitation strategies. Methods Thirty-two chronic stroke patients with no active finger extensions were randomly assigned to experimental or sham groups and underwent daily BMI training followed by physiotherapy during four weeks. BMI sessions included desynchronization of ipsilesional brain activity and a robotic orthosis to move the paretic limb (experimental group, n = 16). In the sham group (n = 16) orthosis movements were random. Motor function was evaluated with electromyography (EMG) of forearm extensors, and upper arm and hand Fugl-Meyer assessment (FMA) scores. Patients performed distinct upper arm (e.g., shoulder flexion) and hand movements (finger extensions). Forearm EMG activity significantly higher during upper arm movements as compared to finger extensions was considered facilitation of forearm EMG activity. Intraclass correlation coefficient (ICC) was used to test inter-session reliability of facilitation of forearm EMG activity. Results Facilitation of forearm EMG activity ICC ranges from 0.52 to 0.83, indicating fair to high reliability before intervention in both limbs. Facilitation of forearm muscles is higher in the paretic as compared to the healthy limb (p<0.001). Upper arm FMA scores predict facilitation of forearm muscles after intervention in both groups (significant correlations ranged from R = 0.752, p = 0.002 to R = 0.779, p = 0.001), but only in the experimental group upper arm FMA scores predict changes in facilitation of forearm muscles after intervention (R = 0.709, p = 0.002; R = 0.827, p<0.001). Conclusions Residual upper arm motor function primes recruitment of paralyzed forearm muscles in chronic stroke patients and predicts changes in their recruitment after BMI training. This study suggests that changes in upper arm-forearm synergies contribute to stroke motor recovery, and provides candidacy guidelines for similar BMI-based clinical practice.

EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors

Abstract The recording of event‐related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly‐adapting thermonociceptors. In fact, except if the activation of A&dgr; fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly‐adapting A fiber mechano‐heat nociceptors (AMH‐2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat‐sensitive thermonociceptors, using very slow (0.2 Hz) and long‐lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50 °C. In a first experiment, we show that when such long‐lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions.

Classical conditioning of the BOLD signal as a paradigm for basic BCI communication in Alzheimer patients

Background Alzheimer patients express their need of social interaction even when their communication abilities are highly impaired. (Mayhew et al., 2001). Brain-computer interfaces (BCI), already used with severely paralyzed patients, may be adapted for communicating with Alzheimer patients by shifting the paradigm from instrumental-operant learning to classical conditioning (Birbaumer, 2006), e.g. by associating “yes” thinking to a positive emotion and “no” thinking to a negative emotion. We designed an fMRI-based BCI setting aimed at conditioning subjects to associate positive and negative emotional stimuli with respectively congruent and incongruent word pairs, in view of a BCI application for basic yes/no communication. Methods fMRI was performed on 6 healthy subjects during a classical conditioning session, comprising the phases of habituation, acquisition and extinction. The unconditioned stimuli consisted of a positive (baby laughter) and negative (scream) emotional sound. The conditioned stimuli, presented aurally, were congruent (e.g. “animal-elephant”) and incongruent (e.g. “animal-Germany”) word pairs. During the conditioning acquisition phase, congruent word pairs were associated to the baby laughter and incongruent word pairs were associated to the scream. A linear Support Vector Machine was implemented to classify the BOLD signal corresponding to congruent and incongruent word pairs. To investigate the relative importance of distinct brain areas in decoding different brain states, feature vectors from the frontal cortex were also used as input to build a separate classifier. Results Participants rated in the Self Assessment Manikin (SAM) the scream and the laughter as having, respectively, negative and positive valence. Moreover, the scream was associated to higher arousal compared to the baby laughter. Classification of the BOLD signal as a response to the congruent and incongruent word pairs immediately followed by the emotional unconditioned stimuli showed above chance level performance (57-64%) in one subject, while the performance was chance level on the remaining subjects (44-56%). Conclusions We presented a possible paradigm for basic yes/no communication, based on the conditioning of BOLD signal by the repeated association of emotional and semantic stimuli. The performance of the classifier by feature selection needs to be improved before being tested with Alzheimer patients. Future developments also comprise an online implementation of the system.

Habituation of phase-locked local field potentials and gamma-band oscillations recorded from the human insula

Salient nociceptive and non-nociceptive stimuli elicit low-frequency local field potentials (LFPs) in the human insula. Nociceptive stimuli also elicit insular gamma-band oscillations (GBOs), possibly preferential for thermonociception, which have been suggested to reflect the intensity of perceived pain. To shed light on the functional significance of these two responses, we investigated whether they would be modulated by stimulation intensity and temporal expectation – two factors contributing to stimulus saliency. Insular activity was recorded from 8 depth electrodes (41 contacts) implanted in the left insula of 6 patients investigated for epilepsy. Thermonociceptive, vibrotactile, and auditory stimuli were delivered using two intensities. To investigate the effects of temporal expectation, the stimuli were delivered in trains of three identical stimuli (S1-S2-S3) separated by a constant 1-s interval. Stimulation intensity affected intensity of perception, the magnitude of low-frequency LFPs, and the magnitude of nociceptive GBOs. Stimulus repetition did not affect perception. In contrast, both low-frequency LFPs and nociceptive GBOs showed a marked habituation of the responses to S2 and S3 as compared to S1 and, hence, a dissociation with intensity of perception. Most importantly, although insular nociceptive GBOs appear to be preferential for thermonociception, they cannot be considered as a correlate of perceived pain.