The neuropathic origin of a case of unilateral burning mouth syndrome, previously diagnosed as psychogenic, was ascertained by intra-oral mucosa biopsy, which showed a severe sensory fibers damage, probably caused by maxillary anesthetic block and dental surgery.

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

BJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM.

A learning test procedure based on operant principles may be useful in the diagnosis (and eventually rehabilitation) of post-coma persons with minimal responsiveness. This study was aimed at extending the evaluation of such a procedure with seven participants who presented with very limited behavior and apparently severe disorders of consciousness. The procedure was evaluated through an ABACB design, in which A represented baseline phases without stimulation, B intervention phases with brief stimulation periods contingent on specific responses of the participants, and C a control phase in which stimulation was available all the time. Increased responding during the B phases, as opposed to the A and C phases, was taken to indicate learning and possibly a non-reflective expression of phenomenal consciousness. All participants were also evaluated with the coma recovery scale-revised (CRS-R) prior to the start of the learning test procedure and at the end of it. The results of the learning test showed that all participants had significantly higher responding levels during the B phases. The CRS-R scores suggested minimally conscious state for four of them prior to the learning test and for five of them after the completion of the learning test. The implications of the findings are discussed in terms of potential and time cost of the learning test

Our previous study assessed the prevalence of fibromyalgia (FM) syndrome in migraine and tension-type headache. We aimed to update our previous results, considering a larger cohort of primary headache patients who came for the first time at our tertiary headache ambulatory. A consecutive sample of 1,123 patients was screened. Frequency of FM in the main groups and types of primary headaches; discriminating factor for FM comorbidity derived from headache frequency and duration, age, anxiety, depression, headache disability, allodynia, pericranial tenderness, fatigue, quality of life and sleep, and probability of FM membership in groups; and types of primary headaches were assessed. FM was present in 174 among a total of 889 included patients. It prevailed in the tensiontype headache main group (35%, p\0.0001) and chronic tension-type headache subtype (44.3%, p\0.0001). Headache frequency, anxiety, pericranial tenderness, poor sleep quality, and physical disability were the best discriminating variables for FM comorbidity, with 81.2% sensitivity. Patients presenting with chronic migraine and chronic tension-type headache had a higher probability of sharing the FM profile (Bonferroni test, p\0.01). A phenotypic profile where headache frequency concurs with anxiety, sleep disturbance, and pericranial tenderness should be individuated to detect the development of diffuse pain in headache patients.

This study tested whether resting state alpha rhythms (8-13 Hz) may characterize mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (<4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery.

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

Sex hormonal variations have been shown to affect functional cerebral asymmetries in cognitive domains, contributing to sex-related differences in functional cerebral organization. The aim of this study was to investigate spatial attention by means of a bisection line test and computer-supported attention task during the menstrual cycle in healthy women compared to men, in basal condition and under Transcranial Direct Current Stimulation (TDCS) of the left parietal cortex. Women were studied during the menses, follicular and luteal phases, ascertained by transvaginal ultrasounds. In basal conditions, women showed a clear deviation toward the right in the bisection line test during the menstrual phase, similarly to men. The midpoint recognition in the computer-supported attention task was not influenced by the menstrual cycle for women, while men showed a significant increase in errors toward the left side. The anodal activation of the left parietal cortex did not affect the line bisection task, while in men it reduced the total amount of errors in midpoint recognition observed in the computer supported attention task. The hand-use effect demonstrated by the bisection-line test could be influenced by estrogen fluctuations, while the right hemisphere prevalence in spatial attention appears to be gender-related and scarcely influenced by the menstrual cycle. The left parietal cortex seems to exert a scarce effect on hand-use effect, while its activation is able to revert sex related right hemisphere supremacy.

Background Transcutaneous external supraorbital nerve stimulation has emerged as a treatment option for primary headache disorders, though its action mechanism is still unclear. Study aim In this randomized, sham-controlled pilot study we aimed to test the effects of a single external transcutaneous nerve stimulation session on pain perception and cortical responses induced by painful laser stimuli delivered to the right forehead and the right hand in a cohort of migraine without aura patients and healthy controls. Methods Seventeen migraine without aura patients and 21 age- and sex-matched controls were selected and randomly assigned to a real or sham external transcutaneous nerve stimulation single stimulation session. The external transcutaneous nerve stimulation was delivered with a self-adhesive electrode placed on the forehead and generating a 60 Hz pulse at 16 mA intensity for 20 minutes. For sham stimulation, we used 2 mA intensity. Laser evoked responses were recorded from 21 scalp electrodes in basal condition (T0), during external transcutaneous nerve stimulation and sham stimulation (T1), and immediately after these (T2). The laser evoked responses were analyzed by LORETA software. Results The real external transcutaneous nerve stimulation reduced the trigeminal N2P2 amplitude in migraine and control groups significantly in respect to placebo. The real stimulation was associated with lower activity in the anterior cingulate cortex under trigeminal laser stimuli. The pattern of LEP-reduced habituation was reverted by real and sham transcutaneous stimulation in migraine patients. Conclusions The present results could suggest that the external transcutaneous nerve stimulation may interfere with the threshold and the extent of trigeminal system activation, with a mechanism of potential utility in the resolution and prevention of migraine attacks.

The study aimed to test the modulation induced by 1Hz repetitive Transcranial Magnetic Stimulation (rTMS) of the occipital cortex on the alpha phase synchronization under repetitive flash stimuli in 15 migraine without aura patients compared to 10 controls. The EEG was recorded by 7 channels, while flash stimuli were delivered at 9, 18, 21 and 24 Hz in basal, rTMS (15 min of 1Hz stimulation of the occipital cortex) and sham conditions. Migraine patients displayed increased alpha-band phase synchronization under visual stimulation, while an overall desynchronizing effect was evident in controls. The rTMS resulted in a slight increase of synchronization index in migraine patients, which did not cause significant differences in respect to the basal and sham conditions. The synchronizing–desynchronizing changes of alpha rhythm under repetitive flash stimulation, seem independent from the state of occipital cortex excitability. Other mechanisms beyond cortical excitability may contribute to explain migraine pathogenesis.

The pathophysiological mechanism of the pain in ALS is still unclear. The aim of the study was to evaluate the laser evoked potentials (LEPs) in ALS patients in relation to their clinical features. Twenty-four ALS patients were selected. Pain features were assessed and their intensity was measured by a 0–10 VAS. LEPs were recorded in all patients and in 23 healthy subjects. The dorsum of both hands was stimulated, at laser stimuli intensity of 7.5 W, with 10 s inter-stimulus interval and 25 ms duration. Four electrodes were placed at Cz, T3, T4 and Fz positions, with the reference electrode at the nasion; T3 and T4 electrodes were referred offline to Fz, in order to detect the N1 component. Latencies of N2, P2 and N1 waves were significantly higher in ALS than in controls. N1 amplitude was significantly increased in ALS patients compared to controls, with a similar trend for the N2–P2 complex. No correlation was found between LEP abnormalities, pain intensity and clinical features. A degeneration of subcortical structures may subtend a delay in the afferent input to the nociceptive cortex in ALS. On the other hand, an increase of pain processing at the cortical level may derive from a potential sensory compensation to motor cortex dysfunction

Few studies have addressed central sensitization symptoms and pain processing in childhood migraine. Our aims were to examine pain sensitivity and responses, including habituation, evoked by CO2 laser stimuli (laser-evoked potentials (LEPs)) in a cohort of children with migraine compared to non-migraine controls and to determine the correlation between LEP features and signs of central sensitization.

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD.

Reduced habituation of the nociceptive blink reflex (NBR) is considered a trait marker for genetic predisposition to migraine. In this open-label randomized controlled study, we aimed to test the efficacy of a biofeedback training based on learning of habituation of the NBR (NBR biofeedback) compared with pharmacological (topiramate) treatment and NBR biofeedback plus topiramate treatment in a cohort of migraine without aura patients eligible for prophylaxis. Thirty-three migraine patients were randomly assigned to three months of treatment with: 1) NBR biofeedback, 2) NBR biofeedback plus topiramate 50 mg (b.i.d.), or 3) topiramate 50 mg (b.i.d.). Frequency of headache and disability changes were the main study outcomes. Anxiety, depression, sleep, fatigue, quality of life, allodynia and pericranial tenderness were also evaluated. NBR biofeedback reduced the R2 area, without improving R2 habituation. However, it reduced the frequency of headache and disability, similarly to the combined treatment and topiramate alone. Reduced habituation of the NBR is a stable neurophysiological pattern, scarcely modifiable by learning procedures. Training methods able to act on stress-related responses may modulate cortical mechanisms inducing migraine onset and trigeminal activation under stressful trigger factors.

The aim of the present study was to evaluate pain perception and evoked responses by laser stimuli (LEPs) in mild not demented Huntington's Disease (HD) patients. Twenty-eight HD patients and 30 control subjects were selected. LEPs were obtained by four scalp electrodes, (Fz, Cz, referred to the nasion; T3, T4, referred to Fz), stimulating the dorsum of both hands. All patients were also evaluated by somatosensory evoked potentials (SEPs) by median nerve stimulation. Only 3 patients referred pain of arthralgic type. Laser pain perception was similar between HD patients and controls. An abnormal N2, P2 and N1 latency increase was evident in the majority of HD patients. LEPs features were similar between patients taking and not taking neuroleptics. The N2 and P2 latencies, showed a negative correlation with functional score and Mini Mental State Examination, and a positive correlation with the severity of hyperkinetic movements. A delay in nociceptive input processing emerged in HD, concurring with the main features of the disease, in absence of clinical evidence of abnormalities in pain perception. The dysfunction of pain signals transmission in HD may induce sub-clinical changes of sensory functions, which may probably interfere with sensory-motor integration and contribute to functional impairment.

BACKGROUND: Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The visual line-bisection task administered to normally cycling women showed different patterns of the interhemispheric interactions during menses and the midluteal cycle phase. However, the contribution of estrogens and progestins hormones to this phenomenon is still unclear. STUDY DESIGN: The aim of our study was to show a variation of FCAs in women administered oral contraceptives (OCs) using the visual line-bisection task. Visual line-bisection task with three horizontal lines was administered to 36 healthy women taking a 21-day OC. Twenty-nine patients were right handed. The task was administered during OC intake (day 10) and at the end of the pill-free period. RESULTS: The right-handed women showed a significant leftward bias of veridical center on the first and third lines during OC intake compared with an opposite rightward bias during the pill-free period. The same phenomenon of contralateral deviation was observed in left-handed women on day 10 of OC intake. CONCLUSIONS: The results of this study confirm a hormonal modulation on interhemispheric interaction and suggest that OCs may improve the interhemispheric interaction reducing FCAs compared with the low hormone level period. This opens new insights in OC prescription and choice of administration schedule in order to improve cognitive performances. Copyright © 2011 Elsevier Inc. All rights reserved.

INTRODUCTION: Pain perception is currently an open question in patients suffering from prolonged disorders of consciousness. The aim of the present study was to examine nociceptive specific laser evoked responses (LEPs) in view of long-latency evoked potentials by non-painful electrical stimuli (SEPs) and auditory mismatch negativity (MM). METHODS: Three vegetative state (VS), four minimal Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, stimulating the dorsum of the right hand by noxious laser and innocuous electrical stimulus, according to normal controls subjective rating. An auditory paradigm for MM was also employed. RESULTS: The MM was present in all patients. The LEP vertex complex was recognizable in all cases, with a significant latency increase of both N2 and P2 which displayed changes of topographic representation. Late SEPs were absent in all patients except in one MCS case, who showed a significant N2 and P2 latency increase. DISCUSSION: The results may suggest that high relevant stimuli may be processed even in patients with severe brain damage. Larger series and multimodal approaches may contribute to confirm that cortical arousal toward pain salience may be a primary function for life persistence

Fibromyalgia syndrome (FM) is frequently associated with migraine. In this study we aimed to compare personality profiles and coping styles across 23 migraine without aura patients sharing FM comorbidity (MWA-FM), 28 migraine without aura patients without FM symptoms (MWA) and 51 age- and sex-matched controls, by means of Big Five Questionnaire (BFQ) and Coping Orientation to Problem Experienced (COPE), and to correlate main results with clinical features. The "Energy" personality factor was significantly reduced in patients presenting with FM symptoms, compared to both migraine without aura patients and controls. A low score in "Dynamism" sub-item with a high score in denial coping style was able to distinguish MWA from MW-FM groups with an accuracy of 82.35% (Wilks lambda=0.98; chi-square=8.99, DF=1, p=0.005). In particular, lower "Dynamism" scores corresponded to a major expression of allodynia, fatigue, anxiety, depression, headache frequency and poor quality of sleep and life. Avoidance from active coping with stressful events may facilitate worsening of migraine and fibromyalgia comorbidity.

Fibromyalgia (FM) syndrome is predominantly related to generation and persistence of central sensitization, which is an aggravating factor for chronic headaches. This review aims to examine the last 11 years of studies on FM and primary headache comorbidity, focusing on prevalence, clinical features and treatments. Chronic forms of migraine and tension-type headache show a high frequency of FM comorbidity. The symptoms characterizing headache patients presenting with FM comorbidity are high headache frequency, poor sleep quality, pericranial tenderness, anxiety and reduction of physical performances. The effects of headache-preventive drugs on factors favoring FM comorbidity were poorly evaluated. Nonpharmacological approaches such as transcranial magnetic stimulation may be an option for treatment of chronic migraine associated with FM.

Fibromyalgia (FM) is a rheumatic disease which affects fibrous tissues and muscles; it is characterized by chronic pain and it is often associated with craniomandibular disorders (CMD). 31 patients were assessed from March 2012 to October 2012 through the administration of specific questionnaires and following neurologic and gnatologic assessment. A relevant corre-lation between FM and CMD emerges from the present study, as 80.6% of our patients report CMD symptoms with high prevalence of myofascial pain (84%). Multivariate regression analysis revealed that the patients in the present study did not differ in score of quality of life questionnaires from patients with fibromyalgia. The neuropathic pain diagnostic question-naire (DN4) scores were positively affected by belonging to group II of Research Diagnostic Criteria of Temporomandibular Disorders (RDC/ TDM) classification, suggesting the possibility of a neuropathic component in chronic pain in this CMD group, as already speculated in our study on the correlation between burning mouth syndrome and CMD and by other au-thors in studies on chronic low back pain. However, further clinic and instrumental studies are needed in order to test this as-sumption.

Serum levels of N-acetyl-aspartate (NAA) may be considered a useful marker of neuronal functioning. We aimed to measure serum NAA in cohorts of migraine and tension-type headache patients versus controls, performing correlations with main clinical features. A total of 147 migraine patients (including migraine without aura, with aura and chronic migraine), 65 tension-type headache (including chronic and frequent episodic tension-type headache) and 34 sex- and age-matched controls were selected. Serum was stored at -80 °C. Quantification of NAA was achieved by the standard addition approach and analysis was performed with liquid-chromatography-mass-spectrometry (LC/MS) technique. The NAA levels were significantly decreased in migraine group (0.065 ± 0.019 mol/L), compared with both tension-type headache patients (0.078 ± 0.016 mol/L) and controls (0.085 ± 0.013 mol/L). Control subjects were significantly different from migraine with and without aura and chronic migraine, who differed significantly from episodic and chronic tension-type headache. Migraine with aura patients showed lower NAA levels when compared to all the other headache subtypes, including migraine without aura and chronic migraine. In the migraine group, no significant correlation was found between NAA serum levels, and headache frequency, allodynia and interval from the last and the next attack. The low NAA in the serum may be a sign of neuronal dysfunction predisposing to migraine, probably based on reduced mitochondria function

BACKGROUND: Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain. METHODS: One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM). RESULTS: Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration. CONCLUSION: Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development

Belief and expectation are part of placebo effect. Migraine patients are characterized by a dysfunctional modulation of pain processing, though a clear placebo effect emerges in clinical trials. The aim of the study was to evaluate the effect of visual and verbal suggestion on subjective pain sensation and cortical responses evoked by CO2 painful laser stimuli in migraine without aura patients vs healthy controls. Twenty-six patients were recorded during the inter-ictal phase and compared to 26 sex and age-matched controls. The right hand and the right supraorbital zone were stimulated during a not conditioned and a conditioned task, where laser stimuli were delivered after a verbal and visual cues of decreased (D), increased (I) or basal (B) intensity, which was left unmodified during the entire task. In control subjects pain rating changed, according to the announced intensity, while in migraine patients the basal hyper-algesia remained unmodified. The N1 and N2 amplitudes tended to change coherently with the stimulus cue in controls, while an opposite paradoxical increase in decreasing condition emerged in migraine. The P2 amplitude modulation was also reduced in migraine, differently from controls. The altered pattern of pain rating and N2 amplitude modulation concurred with frequency of migraine, disability and allodynia. In controls suggestion influenced cortical pain processing and subjective pain rating, while in migraine a peculiar pattern of cortical activation contrasted external cues in order to maintain the basal hyper-algesia. This scarce influence of induced suggestion on pain experience seemed to characterize patients with more severe migraine and central sensitization.

Post-coma persons affected by extensive motor impairment and lack of speech, with or without disorders of consciousness, need special support to manage leisure engagement and communication. These two studies extended research efforts aimed at assessing basic technology-aided programs to provide such support. Specifically, Study I assessed a program for promoting independent stimulation choice in four post-coma persons who combined motor and speech disabilities with disorders of consciousness (i.e., were rated between the minimally conscious state and the emergence from such state). Study II assessed a program for promoting independent television operation and basic communication in three post-coma participants who, contrary to those involved in Study I, did not have disorders of consciousness (i.e., had emerged from a minimally conscious state). The results of the studies were largely positive with substantial levels of independent stimulation choice and access for the participants of Study I and independent television operation and communication for the participants of Study II. The results were analyzed in relation to previous data in the area and in terms of their implications for daily contexts dealing with these persons.

This study assessed technology-aided programs for helping two post-coma persons, who had emerged from a minimally conscious state and were affected by multiple disabilities, to (a) engage with leisure stimuli and request caregiver's procedures, (b) send out and listen to text messages for communication with distant partners, and (c) combine leisure engagement and procedure requests with text messaging within the same sessions. The program for leisure engagement and procedure requests relied on the use of a portable computer with commercial software, and a microswitch for the participants' response. The program for text messaging communication involved the use of a portable computer, a GSM modem, a microswitch for the participants' response, and specifically developed software. Results indicated that the participants were successful at each of the three stages of the study, thus providing relevant evidence concerning performance achievements only minimally documented. The implications of the findings in terms of technology and practical opportunities for post-coma persons with multiple disabilities are discussed.

Event-related potentials (ERPs) are usually obtained by averaging thus neglecting the trial-to-trial latency variability in cognitive electroencephalography (EEG) responses. As a consequence the shape and the peak amplitude of the averaged ERP are smeared and reduced, respectively, when the single-trial latencies show a relevant variability. To date, the majority of the methodologies for single-trial latencies inference are iterative schemes providing suboptimal solutions, the most commonly used being the Woody's algorithm.

Environmental context has an important impact on health and well being. We aimed to test the effects of a visual distraction induced by classical hospital waiting room (RH) versus an ideal room with a sea view (IH), both represented in virtual reality (VR), on subjective sensation and cortical responses induced by painful laser stimuli (LEPs) in healthy volunteers and patients with chronic migraine (CM). Sixteen CM and 16 controls underwent 62 channels LEPs from the right hand, during a fully immersive VR experience, where two types of waiting rooms were simulated. The RH simulated a classical hospital waiting room while the IH represented a room with sea viewing. CM patients showed a reduction of laser pain rating and vertex LEPs during the IH vision. The sLORETA analysis confirmed that in CM patients the two VR simulations induced a different modulation of bilateral parietal cortical areas (precuneus and superior parietal lobe), and superior frontal and cingulate girus, in respect to controls. The architectural context may interfere with pain perception, depending upon the status of subject. Many variables may change patients' outcome and support the use of VR technology to test the best conditions for their management