Publications

Visual attention can be spatially oriented, even in the absence of saccadic eye-movements, to facilitate the processing of incoming visual information. One behavioral proxy for this so-called covert visuospatial attention (CVSA) is the validity effect (VE): the reduction in reaction time (RT) to visual stimuli at attended locations and the increase in RT to stimuli at unattended locations. At the electrophysiological level, one correlate of CVSA is the lateralization in the occipital α-band oscillations, resulting from α-power increases ipsilateral and decreases contralateral to the attended hemifield. While this α-band lateralization has been considerably studied using electroencephalography (EEG) or magnetoencephalography (MEG), little is known about whether it can be trained to improve CVSA behaviorally. In this cross-over sham-controlled study we used continuous real-time feedback of the occipital α-lateralization to modulate behavioral and electrophysiological markers of covert attention. Fourteen subjects performed a cued CVSA task, involving fast responses to covertly attended stimuli. During real-time feedback runs, trials extended in time if subjects reached states of high α-lateralization. Crucially, the ongoing α-lateralization was fed back to the subject by changing the color of the attended stimulus. We hypothesized that this ability to self-monitor lapses in CVSA and thus being able to refocus attention accordingly would lead to improved CVSA performance during subsequent testing. We probed the effect of the intervention by evaluating the pre-post changes in the VE and the α-lateralization. Behaviorally, results showed a significant interaction between feedback (experimental–sham) and time (pre-post) for the validity effect, with an increase in performance only for the experimental condition. We did not find corresponding pre-post changes in the α-lateralization. Our findings suggest that EEG-based real-time feedback is a promising tool to enhance the level of covert visuospatial attention, especially with respect to behavioral changes. This opens up the exploration of applications of the proposed training method for the cognitive rehabilitation of attentional disorders.

Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years’ experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience. Materials and methods: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up. Results: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic. Discussion and conclusions: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well.

The original version of this Article contained an error in the spelling of the authors Francesco Piccione, Paolo Tonin, Antonio Cerasa and Stefano Masiero, which were incorrectly given as Piccione Francesco, Tonin Paolo, Cerasa Antonio, and Masiero Stefano, respectively. This has now been corrected in both the PDF and HTML versions of the Article.

Background: Four main clinical phenotypes have been traditionally described in patients mutated in SCN4A, including sodium-channel myotonia (SCM), paramyotonia congenita (PMC), Hypokaliemic type II (HypoPP2), and Hyperkaliemic/Normokaliemic periodic paralysis (HyperPP/NormoPP); in addition, rare phenotypes associated with mutations in SCN4A are congenital myasthenic syndrome and congenital myopathy. However, only scarce data have been reported in literature on large patient cohorts including phenotypes characterized by myotonia and episodes of paralysis. Methods: We retrospectively investigated clinical and molecular features of 80 patients fulfilling the following criteria: (1) clinical and neurophysiological diagnosis of myotonia, or clinical diagnosis of PP, and (2) presence of a pathogenic SCN4A gene variant. Patients presenting at birth with episodic laryngospasm or congenital myopathy-like phenotype with later onset of myotonia were considered as neonatal SCN4A. Results: PMC was observed in 36 (45%) patients, SCM in 30 (37.5%), Hyper/NormoPP in 7 (8.7%), HypoPP2 in 3 (3.7%), and neonatal SCN4A in 4 (5%). The median age at onset was significantly earlier in PMC than in SCM (p < 0.01) and in Hyper/NormoPP than in HypoPP2 (p = 0.02). Cold-induced myotonia was more frequently observed in PMC (n = 34) than in SCM (n = 23) (p = 0.04). No significant difference was found in age at onset of episodes of paralysis among PMC and PP or in frequency of permanent weakness between PP (n = 4), SCM (n = 5), and PMC (n = 10). PP was more frequently associated with mutations in the S4 region of the NaV1.4 channel protein compared to SCM and PMC (p < 0.01); mutations causing PMC were concentrated in the C-terminal region of the protein, while SCM-associated mutations were detected in all the protein domains. Conclusions: Our data suggest that skeletal muscle channelopathies associated with mutations in SCN4A represent a continuum in the clinical spectrum.

Introduction. Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the “lockdown”. The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic. Methods. We developed an electronic survey that was sent to neuromuscular centers affiliated with the Italian Association of Myology, assessing changes in pharmacological therapies provision, outpatient clinical and instrumental services, support services (physiotherapy, nursing care, psychological support) and clinical trials. Results. 40% of surveyed neuromuscular centers reported a reduction in outpatient visit and examinations (44.5% of centers in Northern regions; 25% of centers in Central regions; 50% of centers in Southern regions). Twenty-two% of centers postponed in-hospital administration of therapies for neuromuscular diseases (23.4% in Northern regions; 13.0% in Central regions; 20% in Southern regions). Diagnostic and support services (physiotherapy, nursing care, psychological support) were suspended in 57% of centers (66/43/44% in Northern, Central and Southern centers respectively) Overall, the most affected services were rehabilitative services and on-site outpatient visits, which were suspended in 93% of centers. Strategies adopted by neuromuscular centers to overcome these changes included maintaining urgent on-site visits, addressing patients to available services and promoting remote contact and telemedicine. Conclusions. Overall, COVID-19 pandemic resulted in a significant disruption of clinical and support services for patients with neuromuscular diseases. Despite the efforts to provide telemedicine consults to patients, this option could be promoted and improved further. A close collaboration between the different neuromuscular centers and service providers as well as further implementation of telehealth platforms are necessary to ensure quality care to NMD patients in the near future and in case of recurrent pandemic waves.

Study design: Single-blind pilot study. Objectives: (1) To evaluate combined BoNT-A injection of spastic antagonistic muscles and ES of wrist extensors in order to improve hand function in incomplete cervical SCI patients. (2) To identify prognostic indicators of hand improvements, as a function of motor levels of injury. Setting: Ten incomplete asymmetric SCI tetraplegics admitted to San Camillo Hospital (Venezia, Italy), who were not able to perform automatic grasping, were enrolled in the study. A better motor level (BML) C6–C7 and worse motor level (WML) C5–C6 were assigned to take into account asymmetric motor strength. Methods: Administration of 100–200 UI BoNT-A per limb into flexor carpi radialis (FCR), extensor digitorum communis (EDC), brachial biceps (BB), and pectoralis major (PM) was performed. This was in conjunction with 6 weeks of 30-min ES sessions repeated three times a day for 6 days a week in wrist extensor muscles, and 6 weeks of 30-min hand rehabilitation for 6 days a week. Assessments included wrist Range of Motion (w-RoM), Modified Ashworth Score (MAS), Functional Independence Measure motor scores (FIM motor), and Nine Hole Peg Test (NHPT). Results: Treatments produced a significant reduction in motor spasticity (MAS) and better dexterity (NHPT) in the C6–C7 BML with respect to the WML cases (p level = 0.007; p = 0.01, respectively). FIM motor scores improved more in BML (median: 20; range 20/22) than in WML (median: 10; range 8/17). Conclusions: Hand function improvement, determined by combined BONT-A and ES, was better in C6–C7 than in C5–C6 SCI patients.

Advances in sports sciences and neurosciences offer new opportunities to design efficient and motivating sport training tools. For instance, using NeuroFeedback (NF), athletes can learn to self-regulate specific brain rhythms and consequently improve their performances. Here, we focused on soccer goalkeepers’ Covert Visual Spatial Attention (CVSA) abilities, which are essential for these athletes to reach high performances. We looked for Electroencephalography (EEG) markers of CVSA usable for virtual reality-based NF training procedures, i.e., markers that comply with the following criteria: (1) specific to CVSA, (2) detectable in real-time and (3) related to goalkeepers’ performance/expertise. Our results revealed that the best-known EEG marker of CVSA—increased α-power ipsilateral to the attended hemi-field— was not usable since it did not comply with criteria 2 and 3. Nonetheless, we highlighted a significant positive correlation between athletes’ improvement in CVSA abilities and the increase of their α-power at rest. While the specificity of this marker remains to be demonstrated, it complied with both criteria 2 and 3. This result suggests that it may be possible to design innovative ecological training procedures for goalkeepers, for instance using a combination of NF and cognitive tasks performed in virtual reality.

Multiple acyl-CoA dehydrogenase deficiency, or glutaric aciduria type II, is an autosomal recessive disorder of fatty acid oxidation due to defects in electron transfer flavoprotein (ETF) encoded by ETFA and ETFB, or in electron transfer flavoprotein dehydrogenase (ETFDH) encoded by the ETFDH gene. The disease may present as a severe neonatal onset form and a mild late-onset form which is heterogeneous for the age at onset and clinical presentation. We describe two patients in their seventies, referred for a nonspecific myopathy, which resulted to manifest carriers of ETFDH gene mutation. Treatment with riboflavin and l-carnitine improved the clinical picture and the biochemical profile. This condition should be included in the differential diagnosis of myopathies even at an old age.

This work proposes a general formulation for the Object Sorting problem, suitable to describe any non-deterministic environment characterized by friendly and adversarial interference. Such an approach, coupled with a Deep Reinforcement Learning algorithm, allows training policies to solve different sorting tasks without adjusting the architecture or modifying the learning method. Briefly, the environment is subdivided into a clutter, where objects are freely located, and a set of clusters, where objects should be placed according to predefined ordering and classification rules. A 3D grid discretizes such environment: the properties of an object within a cell depict its state. Such attributes include object category and order. A Markov Decision Process formulates the problem: at each time step, the state of the cells fully defines the environment’s one. Users can custom-define object classes, ordering priorities, and failure rules. The latter by assigning a non-uniform risk probability to each cell. Performed experiments successfully trained and validated a Deep Reinforcement Learning model to solve several sorting tasks while minimizing the number of moves and failure probability. Obtained results demonstrate the capability of the system to handle non-deterministic events, like failures, and unpredictable external disturbances, like human user interventions.

Recently, the complexity analysis of brain activity has shown the possibility to provide additional information to discriminate between rest and motion in real-time. In this work, we propose a novel entropy-based machine learning method to classify between standing and walking conditions from the sole brain activity. The Shannon entropy has been used as a complexity measure of electroencephalography (EEG) signals and subject-specific features for classification have been selected by Common Spatial Patterns (CSP) filter. Exploiting these features with a linear classifier, we achieved > 85% of classification accuracy over a long period (≈ 25 min) of standing and treadmill walking on 11 healthy subjects. Moreover, we implemented the proposed approach to successfully discriminate in real-time between standing and over-ground walking on one healthy subject. We suggest that the reliable discrimination of rest against walking conditions achieved by the proposed method may be exploited to have more stable control of devices to restore locomotion, avoiding unpredictable and dangerous behaviors due to the delivery of undesired control commands.