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Neural desynchronization was shown as a key mechanism of vagus nerve stimulation (VNS) action in epilepsy, and EEG synchronization measures are explored as possible response biomarkers. Since brain functional organization in sleep shows different synchrony and network properties compared to wakefulness, we aimed to explore the effects of acute VNS on EEG-derived measures in the two different states of vigilance. EEG epochs were retrospectively analyzed from twenty-four VNS-treated epileptic patients (11 responders, 13 non-responders) in calm wakefulness and stage N2 sleep. Weighted Phase Lag Index (wPLI) was computed as connectivity measure of synchronization, for VNS OFF and VNS ON conditions. Global efficiency (GE) was computed as a network measure of integration. Ratios OFF/ON were obtained as desynchronization/de-integration index. Values were compared between responders and non-responders, and between EEG states. ROC curve and area-under-the-curve (AUC) analysis was performed for response classification. In responders, stronger VNS-induced theta desynchronization (p < 0.05) and decreased GE (p < 0.05) were found in sleep, but not in wakefulness. Theta sleep wPLI Ratio OFF/ON yielded an AUC of 0.825, and 79% accuracy as a response biomarker if a cut-off value is set at 1.05. Considering all patients, the VNS-induced GE decrease was significantly more important in sleep compared to awake EEG state (p < 0.01). In conclusion, stronger sleep EEG desynchronization in theta band distinguishes responders to VNS therapy from non-responders. VNS-induced reduction of network integration occurs significantly more in sleep than in wakefulness., SCOPUS: ar.j, info:eu-repo/semantics/published

The human insula is an important target for spinothalamic input, but there is still no consensus on its role in pain perception and nociception. In this study, we show that the human insula exhibits activity preferential for sustained thermonociception. Using intracerebral EEG recorded from the insula of 8 patients (2 females) undergoing a presurgical evaluation of focal epilepsy (53 contacts: 27 anterior, 26 posterior), we “frequency-tagged” the insular activity elicited by sustained thermonociceptive and vibrotactile stimuli, by periodically modulating stimulation intensity at a fixed frequency of 0.2 Hz during 75 s. Both types of stimuli elicited an insular response at the frequency of stimulation (0.2 Hz) and its harmonics, whose magnitude was significantly greater in the posterior insula compared to the anterior insula. Compared to vibrotactile stimulation, thermonociceptive stimulation exerted a markedly greater 0.2 Hz modulation of ongoing theta-band (4–8 Hz) and alpha-band (8–12 Hz) oscillations. These modulations were also more prominent in the posterior insula compared to the anterior insula. The identification of oscillatory activities preferential for thermonociception could lead to new insights into the physiological mechanisms of nociception and pain perception in humans.

Background. Brain-machine interfaces (BMIs) have been recently proposed as a new tool to induce functional recovery in stroke patients. Objective. Here we evaluated long-term effects of BMI training and physiotherapy in motor function of severely paralyzed chronic stroke patients 6 months after intervention. Methods. A total of 30 chronic stroke patients with severe hand paresis from our previous study were invited, and 28 underwent follow-up assessments. BMI training included voluntary desynchronization of ipsilesional EEG-sensorimotor rhythms triggering paretic upper-limb movements via robotic orthoses (experimental group, n = 16) or random orthoses movements (sham group, n = 12). Both groups received identical physiotherapy following BMI sessions and a home-based training program after intervention. Upper-limb motor assessment scores, electromyography (EMG), and functional magnetic resonance imaging (fMRI) were assessed before (Pre), immediately after (Post1), and 6 months after intervention (Post2). Results. The experimental group presented with upper-limb Fugl-Meyer assessment (cFMA) scores significantly higher in Post2 (13.44 ± 1.96) as compared with the Pre session (11.16 ± 1.73; P = .015) and no significant changes between Post1 and Post2 sessions. The Sham group showed no significant changes on cFMA scores. Ashworth scores and EMG activity in both groups increased from Post1 to Post2. Moreover, fMRI-BOLD laterality index showed no significant difference from Pre or Post1 to Post2 sessions. Conclusions. BMI-based rehabilitation promotes long-lasting improvements in motor function of chronic stroke patients with severe paresis and represents a promising strategy in severe stroke neurorehabilitation.

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts). All four types of stimuli elicited consistent low-frequency phase-locked LFPs throughout the insula, possibly reflecting supramodal activity. The latencies of thermo-nociceptive and cool low-frequency phase-locked LFPs were shorter in the posterior insula compared to the anterior insula, suggesting a similar processing of thermal input initiating in the posterior insula, regardless of whether the input produces pain and regardless of thermal modality. In contrast, only thermo-nociceptive stimuli elicited an enhancement of insular GBOs, suggesting that these activities are not simply related to the activation of the spinothalamic system or to the conveyance of thermal information.

Background Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive neurostimulation technique with potential analgesic effects. Several studies based on subjective behavioral responses suggest that taVNS modulates nociception differently with either pro-nociceptive or anti-nociceptive effects. Objective This study aimed to characterize how taVNS alters pain perception, by investigating its effects on event-related potentials (ERPs) elicited by different types of spinothalamic and lemniscal somatosensory stimuli, combined with quantitative sensory testing (detection threshold and intensity ratings). Methods We performed 3 experiments designed to study the time-dependent effects of taVNS and compare with standard cervical VNS (cVNS). In Experiment 1, we assessed the effects of taVNS after 3 hours of stimulation. In Experiment 2, we focused on the immediate effects of the duty cycle (OFF vs. ON phases). Experiments 1 and 2 included 22 and 15 healthy participants respectively. Both experiments consisted of a 2-day cross-over protocol, in which subjects received taVNS and sham stimulation sequentially. In addition, subjects received a set of nociceptive (thermonociceptive CO2 laser, mechanical pinprick) and non-nociceptive (vibrotactile, cool) stimuli, for which we recorded detection thresholds, intensity of perception and ERPs. Finally, in Experiment 3, we tested 13 epileptic patients with an implanted cVNS by comparing OFF vs. ON cycles, using a similar experimental procedure. Results Neither taVNS nor cVNS appeared to modulate the cerebral and behavioral aspects of somatosensory perception. Conclusion The potential effect of taVNS on nociception requires a cautious interpretation, as we found no objective change in behavioral and cerebral responses to spinothalamic and lemniscal somatosensory stimulations.

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.

BACKGROUND Brain-computer interfaces (BCIs) allow persons with impaired mobility to communicate and interact with the environment, supporting goal-directed thinking and cognitive function. Ideally, a BCI should be able to recognize a user's internal state and adapt to it in real-time, to improve interaction. OBJECTIVE Our aim was to examine studies investigating the recognition of affective states from neurophysiological signals, evaluating how current achievements can be applied to improve BCIs. METHODS Following the PRISMA guidelines, we performed a literature search using PubMed and ProQuest databases. We considered peer-reviewed research articles in English, focusing on the recognition of emotions from neurophysiological signals in view of enhancing BCI use. RESULTS Of the 526 identified records, 30 articles comprising 32 studies were eligible for review. Their analysis shows that the affective BCI field is developing, with a variety of combinations of neuroimaging techniques, selected neurophysiological features, and classification algorithms currently being tested. Nevertheless, there is a gap between laboratory experiments and their translation to everyday situations. CONCLUSIONS BCI developers should focus on testing emotion classification with patients in ecological settings and in real-time, with more precise definitions of what they are investigating, and communicating results in a standardized way.

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 user's 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.

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.

OBJECTIVE: Chronic stroke patients with severe hand weakness respond poorly to rehabilitation efforts. Here, we evaluated efficacy of daily brain-machine interface (BMI) training to increase the hypothesized beneficial effects of physiotherapy alone in patients with severe paresis in a double-blind sham-controlled design proof of concept study. METHODS: Thirty-two chronic stroke patients with severe hand weakness were randomly assigned to 2 matched groups and participated in 17.8 ± 1.4 days of training rewarding desynchronization of ipsilesional oscillatory sensorimotor rhythms with contingent online movements of hand and arm orthoses (experimental group, n = 16). In the control group (sham group, n = 16), movements of the orthoses occurred randomly. Both groups received identical behavioral physiotherapy immediately following BMI training or the control intervention. Upper limb motor function scores, electromyography from arm and hand muscles, placebo-expectancy effects, and functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent activity were assessed before and after intervention. RESULTS: A significant group × time interaction in upper limb (combined hand and modified arm) Fugl-Meyer assessment (cFMA) motor scores was found. cFMA scores improved more in the experimental than in the control group, presenting a significant improvement of cFMA scores (3.41 ± 0.563-point difference, p = 0.018) reflecting a clinically meaningful change from no activity to some in paretic muscles. cFMA improvements in the experimental group correlated with changes in fMRI laterality index and with paretic hand electromyography activity. Placebo-expectancy scores were comparable for both groups. INTERPRETATION: The addition of BMI training to behaviorally oriented physiotherapy can be used to induce functional improvements in motor function in chronic stroke patients without residual finger movements and may open a new door in stroke neurorehabilitation.

Two brothers were referred to our clinic for reevaluation of neurofibromatosis type 1 (NF1). Both brothers presented a peculiarity that is not so common in NF1: poliosis overlying plexiform neurofibromas on the scalp. Poliosis overlying plexiform neurofibromas is rarely reported in the literature. The peculiarity of our cases is the familiarity and the presence of poliosis in the same location.

One of the aims of Evidence-Based Medicine is to improve quality and appropriateness of care by the expedition of the knowledge transfer process. Computerized Decision Support Systems (CDSSs) are computer programs that provide alerts to the prescribing doctor directly at the moment of medical examination. In fact, alerts are integrated within the single patient electronic health record. CDSS based on the best available and updated evidence and guidelines may be an efficient tool to facilitate the transfer of the latest results from clinical research directly at the bedside, thus supporting decision-making.The CODES (COmputerized DEcision Support) trial is a research program funded by the Italian Ministry of Health and the Lombardy Region. It aims to evaluate the feasibility of the implementation of a CDSS at the hospital level and to assess its efficacy in daily clinical practice.The CODES project includes two pragmatic RCTs testing a CDSS (i.e. the EBMeDS - MediDSS) in two large Italian hospitals: the first is a general hospital in Vimercate (Lombardy), the second is an oncologic research center in Meldola (Emilia Romagna). The CDSS supports a full spectrum of decisions: therapy, drug interactions, diagnosis, and management of health care services are covered by a hundreds of reminders. However only few reminders are activated per patient, highlighting crucial problems in the delivery of high-quality care. The two trials have similar design and primary outcome, the rate at which alerts detected by the software are resolved by a decision of the clinicians. The project also includes the assessment of barriers and facilitators in the adoption of these new technologies by hospital staff members and the retrospective evaluation of the repeated risks in prescription habits.The trials are ongoing and currently more than 10,000 patients have been randomized. The qualitative analysis revealed a progressive shift in the perception of the tool. Doctors are now seeing it as a trusted second opinion, available 24/7, which is tailored to the needs of the patient. The retrospective analysis showed the opportunity to achieve a better healthcare quality through an active risk management. Aggregating data from whole hospitals emerge rare drug interactions that otherwise would not be recognizable.CDSS are promising tools to support clinicians in everyday practice. They can be used as a real time app or to perform retrospective analyses. These data can provide unique resources to hospital management.

According to the Cognitive reserve hypothesis, several factors related to mental engagement, such as level of education, type of occupation, leisure activities and social network, appear to affect the risk of developing clinical dementia. The present article provides an overview of the studies that have investigated the effects of mental engagement and cognitive stimulation specifically on dementia of the Alzheimer's type (AD). Mental training and cognitive stimulation interventions in AD have been shown to be useful in increasing patients' ability in performing activities of daily living (ADL), allowing them to maintain relative independence. Since cognitive engagement and stimulation are known to modify the brain processes to perform tasks, by recruiting alternative and more efficient networks, this review is especially focused on cognitive rehabilitation in AD patients, which has been shown to improve their global functioning and cognition. This perspective stresses the idea that cognitive reserve is not a fixed factor, but can be continuously modified by life experiences, even when the brain is already affected by neuropathology.

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., Local field potentials elicited in the human insular cortex by painful stimuli reflect cortical activity that is unrelated to pain perception and so cannot be used as an objective measure of pain., Author Summary A widely accepted notion is that the insula, especially its posterior portion, plays a specific role in the perception of pain. This has led a number of researchers to consider activity recorded from this so-called “ouch zone” as an objective correlate of pain perception. We provide compelling evidence to the contrary. Using direct intracerebral recordings, we demonstrate that painful and nonpainful stimuli elicit very similar responses throughout the human insula. This observation argues against the notion that these responses reflect the brain activity through which pain emerges from nociception in the human brain. These findings have implications for basic theories, as well as for the development of diagnostic tests and the identification of therapeutic targets for the treatment of chronic pain. They question the use of these insular responses to assess the effects of pharmacological treatment or to assess pain in patients unable to communicate. Furthermore, they have legal implications, as they contradict the proposal that these responses could be used to determine unequivocally whether plaintiffs are truly experiencing the pain for which they are seeking redress. Finally, they undermine the rationale for neurosurgical procedures aiming at alleviating pain by targeting the posterior insula.

A 4-day-old boy was referred for evaluation of an oval patch of occipital alopecia associated with caput succedaneum and ipsilateral eyelid ecchymoses. Based on the history of a prolonged, difficult labor with vacuum-assisted delivery, the diagnosis of neonatal alopecia associated with birth trauma was made. Trichoscopy showed purple dots corresponding to blood extravasation and follicular ostia. We also review the trichoscopic differential diagnosis of focal neonatal alopecia.

We present a patient with HPV 70/85-positive widespread cutaneous warts characterized by clinical and histological features atypical for classic generalized verrucosis or epidermodysplasia verruciformis. The cutaneous HPV infection is characterized by verrucous papules or plaques variable in size, number, and distribution depending on the genotype of HPV involved and the immune status of the patient. Human papillomaviruses comprise five genera (alpha, beta, gamma, mu, and nu papillomavirus) with different life-cycle characteristics, epithelial tropisms, and disease associations. Epidermodysplasia verruciformis (EV) is a rare, lifelong, autosomal recessive skin disease characterized by persistent cutaneous human papillomavirus infection not necessarily associated with immune system defects. The disease results from an unusual genetic susceptibility to infections with various types of HPVs (especially β-HPV), some of which cause malignant transformation. Conversely, generalized verrucosis has been more typically associated with generalized warts, which are associated with immunocompromised conditions.

Computerized Decision Support Systems (CDSSs) connect health care professionals with high-quality, evidence-based information at the point-of-care to guide clinical decision-making. Current research shows the potential of CDSSs to improve the efficiency and quality of patient care. The mere provision of the technology, however, does not guarantee its uptake. This qualitative study aims to explore the barriers and facilitators to the use of CDSSs as identified by health providers.The study was performed in three Italian hospitals, each characterized by a different level of familiarity with the CDSS technology. We interviewed frontline physicians, nurses, information technology staff, and members of the hospital board of directors (n=24). A grounded theory approach informed our sampling criteria as well as the data collection and analysis.The adoption of CDSSs by health care professionals can be represented as a process that consists of six "positionings," each corresponding to an individual's use and perceived mastery of the technology. In conditions of low mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is difficult to control. On the other hand, individuals in conditions of high mastery view the CDSS as a helpful tool that can be locally adapted and integrated with clinicians' competences to fulfil their needs. In the first positionings, the uptake of CDSSs is hindered by representational obstacles. The last positionings, alternatively, featured technical obstacles to CDSS uptake.Our model of CDSS adoption can guide hospital administrators interested in the future integration of CDSSs to evaluate their organizational contexts, identify potential challenges to the implementation of the technology, and develop an effective strategy to address them. Our findings also allow reflections concerning the misalignment between most Italian hospitals and the current innovation trends toward the uptake of computerized decision support technologies.

Darier-White Disease (DW), otherwise known as keratosis follicularis, is a rare genodermatosis with autosomal dominant inheritance, characterized by loss of adhesion between epidermal cells and abnormal keratinization. The distinctives lesions of DW Disease include rough papules in seborrheic areas, palmoplantar pits, mucosal involvement, and nail changes. DW Disease can be occasionally associated with bacterial complications, but rarely with viral ones. Kaposi's varicelliform eruption (KVE) is a secondary herpes simplex virus infection that affects patients in the setting of primary dermatologic conditions. KVE, frequently misdiagnosed as impetigo, can be severe, progressing to disseminated infections and potentially life threatening. It occurs with a variety of skin disorders, although association with DW Disease has rarely been reported in the literature. This report describes a case of KVE in a patient suffering from DW Disease, focusing on its clinical course. A review of the literature on KVE including disease associations, pathogenesis, and treatment has been also reported.

With the aim of developing a brain-computer interface for the communication of basic mental states, a classical conditioning paradigm with affective stimuli was used, assessing the possibility to discriminate between affirmative and negative thinking in an fMRI-BCI setting. 6 Alzheimer patients and 7 healthy control subjects participated to the study. Congruent and incongruent word-pairs were respectively associated to pleasant (baby laughter) and unpleasant (scream) affective stimuli. A Support Vector Machine classifier focusing on insula, amygdala and anterior cingulate cortex was used to discriminate between the activations relative to congruent and incongruent word-pairs (eliciting respectively affirmative and negative thinking), following the conditioning process. Classification accuracy was on average 71% for Alzheimer patients, reaching 85%, and on average 69% for control subjects, reaching 83%. This study shows that it is possible to extract information on individuals' mental states by exploiting affective responses, overcoming the typical obstacles of traditional BCIs, which generally require time-consuming trainings and intact cognition.

Minimally conscious state (MCS) is a condition of severely altered consciousness, in which patients appear to be wakeful and exhibit fluctuating but reproducible signs of awareness. MCS patients do not respond and are therefore dependent on others. In agreement with the embodied cognition assumption that motor actions influence our cognition, the absence of movement and the decrease in consequences for any type of covert or overt response may cause an extinction of goal-directed thinking. Brain-computer interfaces, which allow a direct output without muscular involvement, may be used to promote goal-directed thinking by allowing the performance of spatial and motor imagery tasks and could facilitate the interaction of MCS patients with their environment, possibly regaining some degree of communication and autonomy.

Background Alzheimer's Disease (AD) patients who have lost the ability to communicate verbally may benefit from a Brain-Computer Interface (BCI), which could allow them to convey basic thoughts and emotions, e.g. by associating affirmative and non-affirmative thinking to a positive and a negative emotion, respectively. One possibility to develop a BCI that can be used with AD patients is to modulate brain responses with a semantic classical conditioning paradigm, in order to associate congruent and incongruent word pairs with emotionally positive and negative stimuli, facilitating the discrimination between “affirmative” and “non-affirmative” thinking. Using a classical conditioning paradigm is convenient, since it does not require AD patients to put active effort in learning how the BCI works. Methods In our classical conditioning paradigm, already tested on 11 healthy subjects, the unconditioned stimuli consist of a positive and negative emotional sound (a baby laugh and a scream, respectively). The conditioned stimuli, presented aurally, are congruent (e.g. 'fruit-apple') and incongruent (e.g. 'fruit-dog') word pairs. During the conditioning acquisition, congruent and incongruent word pairs are associated to the baby laugh and the scream respectively. Functional magnetic resonance imaging (fMRI) will be performed on AD patients (Mini Mental State Examination score: 18-24; intact auditory system) on a 3T scanner. To classify the signals corresponding to congruent and incongruent word pairs, both univariate (General Linear Model) and multivariate (Support Vector Machine, SVM) analyses will be performed. Results Both univariate and multivatiate analyses on healthy subjects confirmed the possibility to discriminate between affirmative and non-affirmative responses. We hypothesize that a similar differentiation may be found in AD patients, since classical conditioning was demonstrated to be possible, at least to some extent, in these patients.The study with AD patients is ongoing, and preliminary results will be presented during the conference. Conclusions The encouraging results obtained with healthy subjects show that basic affirmative/non affirmative thinking discrimination is possible within an fMRI-BCI setting. The development of a BCI for AD patients could be an important step for allowing not only basic communication, but possibly lending a path for rehabilitation and diagnosis.

Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.

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.

Psoriasis is a chronic, immune-mediated, inflammatory dermatosis whose aetiopathogenesis remains unclear, although tumour necrosis factor alpha (TNFalpha) appears to play a crucial role. The biological potential of TNFalpha inhibitors, such as etanercept, which reduce the inflammatory cascade, has radically changed the therapeutic management of patients with psoriasis and other immunomediated inflammatory diseases, associated with TNFalpha. The pathogenesis of the selective destruction of melanocytes in vitiligo is not fully understood, although there is growing evidence that several T helper type 1 cytokines, particularly TNFalpha, may be involved in the depigmentation process. A patient is described who presented with both psoriasis and vitiligo, and was treated with etanercept. After 24 weeks of therapy, the patient's psoriasis had improved markedly and the patient noted a mild improvement of vitiligo, with a reduction in macules and repigmentation in the scapular region.