Auditory Personalization of EMDR Treatment to Relieve Trauma Effects: A Feasibility Study [EMDR+].

According to the WHO (World Health Organization), Eye Movement Desensitization and Reprocessing (EMDR) is an elective therapy to treat people with post-traumatic stress disorders (PTSD). In line with the personalization of therapeutic strategies, through this pilot study, we assessed in people suffering from the effects of trauma the feasibility, safety, acceptance, and efficacy of EMDR enriched with sound stimulation (by administering neutral sounds synchronized with the guided bilateral alternating stimulation of the gaze) and musical reward (musical listening based on the patients' predisposition and personal tastes). Feasibility, quantified by the number of patients who completed the treatment, was excellent as this was the case in 12 out of the 12 enrolled people with psychological trauma. Safety and acceptance, assessed by self-compiled questionnaires, were excellent, with an absence of side effects and high satisfaction. Efficacy, quantified by the number of EMDR treatment sessions required to reach the optimal scores on the Subjective Units of Disturbance (SUD) and Validity of Cognition (VOC) scales typical of EMDR protocols, revealed an average duration of 8.5 (SD 1.2) sessions, which is well below the 12 sessions considered a standard EMDR treatment duration. EMDR+ appears to be a relevant personalization of EMDR, particularly in music-sensitive people, consolidating the therapeutic alliance through a multisensory communicative bond for trauma treatment.

On the Homology of the Dominant and Non-Dominant Corticospinal Tracts: A Novel Neurophysiological Assessment.

OBJECTIVES: The homology of hemispheric cortical areas plays a crucial role in brain functionality. Here, we extend this concept to the homology of the dominant and non-dominant hemi-bodies, investigating the relationship of the two corticospinal tracts (CSTs). The evoked responses provide an estimate of the number of in-phase recruitments via their amplitude as a suitable indicator of the neuronal projections' integrity. An innovative concept derived from experience in the somatosensory system is that their morphology reflects the recruitment pattern of the whole circuit. METHODS: CST homology was assessed via the Fréchet distance between the morphologies of motor-evoked potentials (MEPs) using a transcranial magnetic stimulation (TMS) in the homologous left- and right-hand first dorsal interosseous muscles of 40 healthy volunteers (HVs). We tested the working hypothesis that the inter-side Fréchet distance was higher than the two intra-side distances. RESULTS: In addition to a clear confirmation of the working hypothesis (p < 0.0001 for both hemi-bodies) verified in all single subjects, we observed that the intra-side Fréchet distance was higher for the dominant than the non-dominant one. Interhemispheric morphology similarity increased with right-handedness prevalence (p = 0.004). CONCLUSIONS: The newly introduced measure of circuit recruitment patterning represents a potential benchmark for the evaluation of inter-lateral mechanisms expressing the relationship between homologous hemilateral structures subtending learning and suggests that variability in recruitment patterning physiologically increases in circuits expressing greater functionality.

Local neurodynamics as a signature of cortical areas: new insights from sleep.

Sleep crucial for the animal survival is accompanied by huge changes in neuronal electrical activity over time, the neurodynamics. Here, drawing on intracranial stereo-electroencephalographic (sEEG) recordings from the Montreal Neurological Institute (MNI), we analyzed local neurodynamics in the waking state at rest and during the N2, N3, and rapid eye movement (REM) sleep phases. Higuchi fractal dimension (HFD)-a measure of signal complexity-was studied as a feature of the local neurodynamics of the primary motor (M1), somatosensory (S1), and auditory (A1) cortices. The key working hypothesis, that the relationships between local neurodynamics preserve in all sleep phases despite the neurodynamics complexity reduces in sleep compared with wakefulness, was supported by the results. In fact, while HFD awake > REM > N2 > N3 (P < 0.001 consistently), HFD in M1 > S1 > A1 in awake and all sleep stages (P < 0.05 consistently). Also power spectral density was studied for consistency with previous investigations. Meaningfully, we found a local specificity of neurodynamics, well quantified by the fractal dimension, expressed in wakefulness and during sleep. We reinforce the idea that neurodynamic may become a new criterion for cortical parcellation, prospectively improving the understanding and ability of compensatory interventions for behavioral disorders.

Functional balance at rest of hemispheric homologs assessed via normalized compression distance.

Introduction: The formation and functioning of neural networks hinge critically on the balance between structurally homologous areas in the hemispheres. This balance, reflecting their physiological relationship, is fundamental for learning processes. In our study, we explore this functional homology in the resting state, employing a complexity measure that accounts for the temporal patterns in neurodynamics. Methods: We used Normalized Compression Distance (NCD) to assess the similarity over time, neurodynamics, of the somatosensory areas associated with hand perception (S1). This assessment was conducted using magnetoencephalography (MEG) in conjunction with Functional Source Separation (FSS). Our primary hypothesis posited that neurodynamic similarity would be more pronounced within individual subjects than across different individuals. Additionally, we investigated whether this similarity is influenced by hemisphere or age at a population level. Results: Our findings validate the hypothesis, indicating that NCD is a robust tool for capturing balanced functional homology between hemispheric regions. Notably, we observed a higher degree of neurodynamic similarity in the population within the left hemisphere compared to the right. Also, we found that intra-subject functional homology displayed greater variability in older individuals than in younger ones. Discussion: Our approach could be instrumental in investigating chronic neurological conditions marked by imbalances in brain activity, such as depression, addiction, fatigue, and epilepsy. It holds potential for aiding in the development of new therapeutic strategies tailored to these complex conditions, though further research is needed to fully realize this potential.

Normalized compression distance to measure cortico-muscular synchronization.

The neuronal functional connectivity is a complex and non-stationary phenomenon creating dynamic networks synchronization determining the brain states and needed to produce tasks. Here, as a measure that quantifies the synchronization between the neuronal electrical activity of two brain regions, we used the normalized compression distance (NCD), which is the length of the compressed file constituted by the concatenated two signals, normalized by the length of the two compressed files including each single signal. To test the NCD sensitivity to physiological properties, we used NCD to measure the cortico-muscular synchronization, a well-known mechanism to control movements, in 15 healthy volunteers during a weak handgrip. Independently of NCD compressor (Huffman or Lempel Ziv), we found out that the resulting measure is sensitive to the dominant-non dominant asymmetry when novelty management is required (p = 0.011; p = 0.007, respectively) and depends on the level of novelty when moving the non-dominant hand (p = 0.012; p = 0.024). Showing lower synchronization levels for less dexterous networks, NCD seems to be a measure able to enrich the estimate of functional two-node connectivity within the neuronal networks that control the body.

Functional Source Separation-Identified Epileptic Network: Analysis Pipeline.

This proof-of-concept (PoC) study presents a pipeline made by two blocks: 1. the identification of the network that generates interictal epileptic activity; and 2. the study of the time course of the electrical activity that it generates, called neurodynamics, and the study of its functional connectivity to the other parts of the brain. Network identification is achieved with the Functional Source Separation (FSS) algorithm applied to electroencephalographic (EEG) recordings, the neurodynamics quantified through signal complexity with the Higuchi Fractal Dimension (HFD), and functional connectivity with the Directed Transfer Function (DTF). This PoC is enhanced by the data collected before and after neuromodulation via transcranial Direct Current Stimulation (tDCS, both Real and Sham) in a single drug-resistant epileptic person. We observed that the signal complexity of the epileptogenic network, reduced in the pre-Real, pre-Sham, and post-Sham, reached the level of the rest of the brain post-Real tDCS. DTF changes post-Real tDCS were maintained after one month. The proposed approach can represent a valuable tool to enhance understanding of the relationship between brain neurodynamics characteristics, the effects of non-invasive brain stimulation, and epileptic symptoms.

Home treatment against fatigue in multiple sclerosis by a personalized, bilateral whole-body somatosensory cortex stimulation.

BACKGROUND: Fatigue in multiple sclerosis (MS) is a highly invalidating symptom with no pharmacological efficacious therapies, which furthermore present frequent severe side effects. In two previous randomized controlled trials we observed the efficacy of a personalized neuromodulation treatment consisting of a personalized transcranial Direct Current Stimulation (tDCS) for 15 min per day for 5 days (Faremus). METHODS: By this medical-device phase II study, we aimed at assessing the feasibility, acceptance, safety and efficacy of Faremus treatment when applied at patients' home. We considered the efficacy as primary outcome assessed by a reduction of fatigue levels measured by Modified Fatigue Impact Scale (mFIS) scored before and after the treatment. Primary outcome determined the sample size estimate. Individual ad-hoc questionnaires quantified the acceptance, safety and side effects during the treatment. RESULTS: All 15 patients completed the treatment, reporting optimal acceptance and safety on using Faremus at their home without side-effects. The treatment ameliorated fatigue symptoms more than 20% of baseline in 10 out of the 15 patients and of 37% on average, with a corresponding effect size 1.21. CONCLUSIONS: Faremus personalized electroceutical intervention, a 5-days anodal tDCS over the bilateral whole-body somatosensory cortex, is well accepted and can be feasibly, safely, and efficaciously applied at patients' home, offering a comfortable treatment by reducing the need to travel when fatigue-related symptoms hamper the quality of life.

Neuronal Electrical Ongoing Activity as Cortical Areas Signature: An Insight from MNI Intracerebral Recording Atlas.

The time course of the neuronal activity in the brain network, the neurodynamics, reflects the structure and functionality of the generating neuronal pools. Here, using the intracranial stereo-electroencephalographic (sEEG) recordings of the public Montreal Neurological Institute (MNI) atlas, we investigated the neurodynamics of primary motor (M1), somatosensory (S1) and auditory (A1) cortices measuring power spectral densities (PSD) and Higuchi fractal dimension (HFD) in the same subject (M1 vs. S1 in 16 subjects, M1 vs. A1 in 9, S1 vs. A1 in 6). We observed specific spectral features in M1, which prevailed above beta band, S1 in the alpha band, and A1 in the delta band. M1 HFD was higher than S1, both higher than A1. A clear distinction of neurodynamics properties of specific primary cortices supports the efforts in cortical parceling based on this expression of the local cytoarchitecture and connectivity. In this perspective, we selected within the MNI intracortical database a first set of primary motor, somatosensory and auditory cortices' representatives to query in recognizing ongoing patterns of neuronal communication. Potential clinical impact stands primarily in exploiting such exchange patterns to enhance the efficacy of neuromodulation intervention to cure symptoms secondary to neuronal activity unbalances.

tDCS randomized controlled trials in no-structural diseases: a quantitative review.

The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in Multiple Sclerosis ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15 min/5 days against MS fatigue. An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions. High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations.

Knowledge and attitude of pregnant women toward flu vaccination: a cross-sectional survey.

OBJECTIVE: The study was conducted to explore the knowledge of pregnant women about influenza, influenza vaccine during pregnancy and the attitudes regarding immunization. METHODS: A questionnaire based on the model proposed by Yudin in 2009 was translated, adapted and administered to 309 pregnant women in the third trimester of pregnancy between October 1 and December 1, 2013 at San Giovanni Calibita Fatebenefratelli hospital of Rome (Italy). RESULTS: Most of the interviewed women (68.9%) answered that influenza is highly contagious, 34.6% of them believed that pregnant women have the same risk of complications as non-pregnant women. Only 5.8% were aware that the vaccine is recommended for women in the second and third trimester of pregnancy and only 14.2% of women answered that the vaccine is safe during pregnancy. Only 3/309 women reported recommendation and offer of vaccination during current pregnancy, but none of them was vaccinated. CONCLUSIONS: Overall, knowledge regarding influenza, implications during pregnancy and influenza vaccine was poor among pregnant women. In Italy, the National Vaccine Prevention Plan 2012-2014 recommends influenza vaccine during pregnancy, but only 18/309 were aware of this recommendation. These results suggest that in order to increase influenza vaccine acceptance it is necessary to improve pregnant women knowledge about influenza and to offer education to healthcare providers.

Quality measurement and benchmarking of HPV vaccination services: a new approach.

BACKGROUND: A new measurement process based upon a well-defined mathematical model was applied to evaluate the quality of human papillomavirus (HPV) vaccination centers in 3 of 12 Local Health Units (ASLs) within the Lazio Region of Italy. The quality aspects considered for evaluation were communicational efficiency, organizational efficiency and comfort. RESULTS: The overall maximum achievable value was 86.10%, while the HPV vaccination quality scores for ASL1, ASL2 and ASL3 were 73.07%, 71.08%, and 67.21%, respectively. CONCLUSIONS: With this new approach it is possible to represent the probabilistic reasoning of a stakeholder who evaluates the quality of a healthcare provider. All ASLs had margins for improvements and optimal quality results can be assessed in terms of better performance conditions, confirming the relationship between the resulting quality scores and HPV vaccination coverage. METHODS: The measurement process was structured into three steps and involved four stakeholder categories: doctors, nurses, parents and vaccinated women. In Step 1, questionnaires were administered to collect different stakeholders' points of view (i.e., subjective data) that were elaborated to obtain the best and worst performance conditions when delivering a healthcare service. Step 2 of the process involved the gathering of performance data during the service delivery (i.e., objective data collection). Step 3 of the process involved the elaboration of all data: subjective data from step 1 are used to define a "standard" to test objective data from step 2. This entire process led to the creation of a set of scorecards. Benchmarking is presented as a result of the probabilistic meaning of the evaluated scores.

[Epidemiology of third molar extractions: the experience of the S.G.C. Fatebenefratelli Hospital in Rome (Italy)]. / L'epidemiologia degli interventi sui terzi molari:l'esperienza dell'Ospedale S.G.C. Fatebenefratelli di Roma.

The extraction of third molars (wisdom teeth) is one of the main surgical procedures performed in dentistry. The aim of this study was to describe the characteristics of patients undergoing the procedure in the SGC Fatebenefratelli Hospital, a large hospital in Rome (Italy), where about 20% of all third molar extractions in the Lazio Region are performed. Hospital discharge forms were analysed for patients discharged in the years 2010 and 2011 with a Diagnosis Related Group (DRG) code 169, used for the procedure. Study results indicate that the extraction of third molars is a relevant public health issue considering its frequency and associated yearly costs at the national level. The appropriateness of third molar extraction, especially when performed prophylactically in young persons, should be further explored.

Ultrasonographic markers of vascular risk in patients with asymptomatic carotid stenosis.

Six-hundred twenty-one subjects with unilateral asymptomatic severe internal carotid artery (ICA) stenosis were prospectively evaluated with a median follow-up of 27 months (min=6, max=68). Vascular risk profile, plaque characteristic, stenosis progression, and common carotid artery intima-media thickness (IMT) were investigated in all patients. Outcome measures were occurrence of ischemic stroke ipsilateral to ICA stenosis and vascular death, while myocardial infarction, contralateral strokes, and transient ischemic attack were considered as competing events. A total of 99 subjects (15.9%) suffered from a vascular event. Among them, 39 were strokes ipsilateral to the stenosis (6.3%). Degree of stenosis, stenosis progression, and common carotid artery IMT resulted as independent predictive factors of ipsilateral stroke. Considering a stenosis of 60% to 70% as reference, a degree between 71% and 90% increased the risk by 2.45, while a degree between 91% and 99% increased the risk by 3.26. The progression of stenosis was a strong risk factor (hazard ratio=4.32). Finally, the role of carotid IMT was confirmed as crucial additional measure, with an increased risk by 25% for each 0.1 mm IMT increase. Our data suggest that IMT, stenosis progression and severity should be considered as risk factors for cerebrovascular events in asymptomatic subjects with severe ICA stenosis.

[Application of the QuavaTAR model to vaccination services in Latium, Italy]. / Sistema di misura della qualità QuaVaTar: dal modello matematico all'applicazione nei servizi vaccinali del Lazio.

Definition, categorization, and measuring of Quality have become increasingly important concerns in the era of managed care and cost containment. Most attempts to develop quality indicators have been based on outcome measures. The Donabedian model of Structure-Process-Outcome has been universally accepted and used as the basis for much of the work addressing quality and outcomes. Adequate indicators for vaccination services are scant therefore are applied to this setting a new quality measurement process based on a probabilistic approach called MQS (Misure di Qualità in Sanità-Quality Measures in Healthcare), developed by our working group since 2005 in several hospital settings. This new application, called "Quality in Vaccination Theory and Research"(QuaVaTAR), was used to measure the efficiency of the vaccination centers of three Local Health Units (ASL RM B, RM F, RM H) in Lazio Region (Italy). The measure method combines the evidences obtained from the supplied services (objective measurements) and the judgments of the services' stakeholders collected by an "ad hoc" questionnaire (subjective measurements). The subjective evaluations were expressed with a number (between 0-100) representing a personal judgment on the organizational and the communicational efficiency and the comfort of the "ideal" vaccination center. The objective measurements were collected in performance grids on the same points investigated with the questionnaire. Combining objective and subjective measures we obtained "Quality Scores", useful to make improvements in the vaccination centers and to compare different services.

A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease.

BACKGROUND AND AIMS: Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimer's disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD. METHODS: This was a 12-month multicenter, randomized, double-blind, placebo-controlled, parallel group trial. Participants with mild-moderate AD (Mini-Mental State Examination score >15, <26; Clinical Dementia Rating= 0.5-1), 65 years or older, with reliable caregivers, were recruited between April 2003 and September 2004. Seven AD Outpatient Treatment Centers screened 530 patients, 132 of whom were enrolled. Intervention consisted of 400 mg ibuprofen twice a day or placebo, together with 20 mg once a day of esomeprazol, or placebo. The primary measure was any one-year change in the Alzheimer Disease Assessment Scale- Cognitive (ADAS-Cog) subscale score. Secondary measures included changes in MMSE, CDR, Basic and Instrumental Activities of Daily Living scales, and Neuropsychiatric Inventory (NPI). RESULTS: Fifty-one patients (77%) in the ibuprofen vs 46 (70%) in the placebo group completed the protocol (p>0.20). In intention-to- treat analysis, ADAS-Cog score worsening was similar in the two groups (p=0.951, treatment difference= 0.1, CI -2.7; 2.9). No differences were found for any secondary outcomes. In a subsample of genotyped patients, ApoE epsilon4 carriers treated with ibuprofen (n=27) were the only group without significant cognitive decline. CONCLUSIONS: Ibuprofen, if used for relatively short periods of time and although well tolerated thanks to gastroprotection, does not seem to be effective in tertiary prevention of mild-moderate AD. Our results suggest the need to examine whether differences in the response to NSAIDs exist, based on ApoE epsilon4 carrier status.