The impact of virtual reality and distractors on attentional processes: insights from EEG.

Virtual reality (VR) allows to create controlled scenarios in which the quantity of stimuli can be modulated, as happen in real-life, where humans are subjected to various multisensory-often overlapping-stimuli. The present research aimed to study changes in attentional processes within an auditory oddball paradigm during a virtual exploration, while varying the amount of distractors. Twenty healthy volunteers underwent electroencephalography (EEG) during three different experimental conditions: an auditory oddball without VR (No-VR condition), an auditory oddball during VR exploration without distractors (VR-Empty condition), and an auditory oddball during VR exploration with a high level of distractors (VR-Full condition). Event-related potentials (ERPs) were computed averaging epochs of EEGs and analyzing peaks at 100 ms (N100) and 300 ms (P300) latencies. Results showed modulation of N100 amplitude in Fz and of P300 amplitude in Pz. Statistically significant differences in latency were observed only for P300 where the latency results delayed from the No-VR to VR-Full. The scalp topography revealed for P100 no significant differences between frequent and rare stimuli in either the No-VR and VR-Empty conditions. However, significant results were found in N100 in VR-Full condition. For P300, results showed differences between frequent and rare stimuli, in every condition. However, this difference is gradually less widespread from No-VR condition to the VR-Full. The emerging integration of VR with EEG may have important implications for studying brain attentional processing.

The role of the sleep K-complex on the conversion from mild cognitive impairment to Alzheimer's disease.

The present literature points to an alteration of the human K-complex during non-rapid eye movement sleep in Alzheimer's disease. Nevertheless, the few findings on the K-complex changes in mild cognitive impairment and their possible predictive role on the Alzheimer's disease conversion show mixed findings, lack of replication, and a main interest for the frontal region. The aim of the present study was to assess K-complex measures in amnesic mild cognitive impairment subsequently converted in Alzheimer's disease over different cortical regions, comparing them with healthy controls and stable amnesic mild cognitive impairment. We assessed baseline K-complex density, amplitude, area under the curve and overnight changes in frontal, central and parietal midline derivations of 12 amnesic mild cognitive impairment subsequently converted in Alzheimer's disease, 12 stable amnesic mild cognitive impairment and 12 healthy controls. We also assessed delta electroencephalogram power, to determine if K-complex alterations in amnesic mild cognitive impairment occur with modification of the electroencephalogram power in the frequency range of the slow-wave activity. We found a reduced parietal K-complex density in amnesic mild cognitive impairment subsequently converted in Alzheimer's disease compared with stable amnesic mild cognitive impairment and healthy controls, without changes in K-complex morphology and overnight modulation. Both amnesic mild cognitive impairment groups showed decreased slow-wave sleep percentage compared with healthy controls. No differences between groups were observed in slow-wave activity power. Our findings suggest that K-complex alterations in mild cognitive impairment may be observed earlier in parietal regions, likely mirroring the topographical progression of Alzheimer's disease-related brain pathology, and express a frontal predominance only in a full-blown phase of Alzheimer's disease. Consistently with previous results, such K-complex modification occurs in the absence of significant electroencephalogram power changes in the slow oscillations range.

Small World derived index to distinguish Alzheimer's type dementia and healthy subjects.

BACKGROUND: This article introduces a novel index aimed at uncovering specific brain connectivity patterns associated with Alzheimer's disease (AD), defined according to neuropsychological patterns. METHODS: Electroencephalographic (EEG) recordings of 370 people, including 170 healthy subjects and 200 mild-AD patients, were acquired in different clinical centres using different acquisition equipment by harmonising acquisition settings. The study employed a new derived Small World (SW) index, SWcomb, that serves as a comprehensive metric designed to integrate the seven SW parameters, computed across the typical EEG frequency bands. The objective is to create a unified index that effectively distinguishes individuals with a neuropsychological pattern compatible with AD from healthy ones. RESULTS: Results showed that the healthy group exhibited the lowest SWcomb values, while the AD group displayed the highest SWcomb ones. CONCLUSIONS: These findings suggest that SWcomb index represents an easy-to-perform, low-cost, widely available and non-invasive biomarker for distinguishing between healthy individuals and AD patients.

Cognitive resilience/reserve: Myth or reality? A review of definitions and measurement methods.

INTRODUCTION: This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR. METHODS: We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives. RESULTS: We evaluate-also in a critical way-the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR. CONCLUSIONS: The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals. HIGHLIGHTS: This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages. We have evaluated the methods commonly used to define and measure cognitive reserve. Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed. The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.

Prognostic Role of Hemispherical Functional Connectivity in Stroke: A Study via Graph Theory Versus Coherence of Electroencephalography Rhythms.

BACKGROUND: The objective of the present study is to explore whether acute stroke may result in changes in brain network architecture by electroencephalography functional coupling analysis and graph theory. METHODS: Ninety acute stroke patients and 110 healthy subjects were enrolled in different clinical centers in Rome, Italy, starting from 2013, and for each one electroencephalographies were recorded within <15 days from stroke onset. All patients were clinically evaluated through National Institutes of Health Stroke Scale, Barthel Index, and Action Research Arm Test in the acute stage and during the follow-up. Functional connectivity was assessed using Total Coherence and Small World (SW) by comparing the affected and the unaffected hemisphere between groups (Stroke versus Healthy). Correlations between connectivity and poststroke recovery scores have been carried out. RESULTS: In stroke patients, network hemispheric asymmetry, in terms of Total Coherence, was mainly detected in the affected hemisphere with lower values in Delta, Theta, Alpha1, and Alpha2 (P=0.000001), whereas the unaffected hemisphere showed lower Total Coherence only in Delta and Theta (P=0.000001). SW revealed a significant difference only in the affected hemisphere in all electroencephalography bands (lower SW in Delta (P=0.000003), Theta (P=0.000003), Alpha1 (P=0.000203), and Alpha2 (P=0.028) and higher SW in Beta2 (P=0.000002) and Gamma (P=0.000002)). We also found significant correlations between SW and improvement in National Institutes of Health Stroke Scale (Theta SW: r=-0.2808), Barthel Index (Delta SW: r=0.3692; Theta SW: r=0.3844, Beta2 SW: r=-0.3589; Gamma SW: r=-04948), and Action Research Arm Test (Beta2 SW: r=-0.4274; Gamma SW: r=-0.4370). CONCLUSIONS: These findings demonstrated changes in global functional connectivity and in the balance of network segregation and integration induced by acute stroke. The findings on the correlations between clinical outcome(s) and poststroke network architecture indicate the possibility to identify a predictive index of recovery useful to address and personalize the rehabilitation program.

Cerebrospinal fluid neurofilament light chain and total-tau as biomarkers of neurodegeneration in Alzheimer's disease and frontotemporal dementia.

INTRODUCTION: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. METHODS: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aß42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. RESULTS: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aß42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aß pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.

The Effects of Directional and Non-Directional Stimuli during a Visuomotor Task and Their Correlation with Reaction Time: An ERP Study.

Different visual stimuli can capture and shift attention into different directions. Few studies have explored differences in brain response due to directional (DS) and non-directional visual stimuli (nDS). To explore the latter, event-related potentials (ERP) and contingent negative variation (CNV) during a visuomotor task were evaluated in 19 adults. To examine the relation between task performance and ERPs, the participants were divided into faster (F) and slower (S) groups based on their reaction times (RTs). Moreover, to reveal ERP modulation within the same subject, each recording from the single participants was subdivided into F and S trials based on the specific RT. ERP latencies were analysed between conditions ((DS, nDS); (F, S subjects); (F, S trials)). Correlation was analysed between CNV and RTs. Our results reveal that the ERPs' late components are modulated differently by DS and nDS conditions in terms of amplitude and location. Differences in ERP amplitude, location and latency, were also found according to subjects' performance, i.e., between F and S subjects and trials. In addition, results show that the CNV slope is modulated by the directionality of the stimulus and contributes to motor performance. A better understanding of brain dynamics through ERPs could be useful to explain brain states in healthy subjects and to support diagnoses and personalized rehabilitation in patients with neurological diseases.

Global estimates on the number of persons across the Alzheimer's disease continuum.

INTRODUCTION: Global estimates on numbers of persons in early stages of Alzheimer's disease (AD), including prodromal and preclinical, are lacking, yet are needed to inform policy decisions on preventive measures and planning for future therapies targeting AD pathology. METHODS: We synthesized the literature on prevalence across the AD continuum and derived a model estimating the number of persons, stratified by 5-year age groups, sex, and disease stage (AD dementia, prodromal AD, and preclinical AD). RESULTS: The global number of persons with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together they constituted 416 million across the AD continuum, or 22% of all persons aged 50 and above. DISCUSSION: Considering predementia stages, the number of persons with AD is much larger than conveyed in available literature. Our estimates are uncertain, especially for predementia stages in low- and middle-income regions where biomarker studies are missing.

Informal caregiver's socio demographic profile for community-dwelling women and men with mild to moderate Alzheimer's disease, compliance, and satisfaction to treatment: A post-hoc analysis of the AXEPT study.

In this post-hoc analysis of the AXEPT study, 855 patients were analyzed, 544 (63.6%) females. The mean (± SD) MMSE score in women vs men was 20.8 ± 2.6 vs. 21.2 ± 2.5; p = 0.0087, and women were more likely affected by psychiatric disorders (n = 76, 14.0% women vs. n = 21, 6.8% men; p = 0.0015). Men were mainly assisted by their wives (n = 207, 66.6%), women mainly by their daughters (n = 243, 44.7%) and only in a minority of cases by their husbands (n = 92, 16.9%). Women less frequently cohabited with their caregivers than men (n = 233, 43.1% vs. n = 240, 77.9%, p < 0.0001), and received less daily time of caregiving (mean (± SD): 10.0 ± 7.2 vs. 15.2 ± 8.2; p < 0.0001). No gender differences were highlighted in compliance to treatment and caregiver satisfaction, while gender differences in caregiving were found at disadvantage of women affected by more severe cognitive and psychiatric conditions.

Transcranial Direct Current Stimulation Enhances Neuroplasticity and Accelerates Motor Recovery in a Stroke Mouse Model.

BACKGROUND: More effective strategies are needed to promote poststroke functional recovery. Here, we evaluated the impact of bihemispheric transcranial direct current stimulation (tDCS) on forelimb motor function recovery and the underlying mechanisms in mice subjected to focal ischemia of the motor cortex. METHODS: Photothrombotic stroke was induced in the forelimb brain motor area, and tDCS was applied once per day for 3 consecutive days, starting 72 hours after stroke. Grid-walking, single pellet reaching, and grip strength tests were conducted to assess motor function. Local field potentials were recorded to evaluate brain connectivity. Western immunoblotting, ELISA, quantitative real-time polymerase chain reaction, and Golgi-Cox staining were used to uncover tDCS-mediated stroke recovery mechanisms. RESULTS: Among our results, tDCS increased the rate of motor recovery, anticipating it at the early subacute stage. In this window, tDCS enhanced BDNF (brain-derived neurotrophic factor) expression and dendritic spine density in the peri-infarct motor cortex, along with increasing functional connectivity between motor and somatosensory cortices. Treatment with the BDNF TrkB (tropomyosin-related tyrosine kinase B) receptor inhibitor, ANA-12, prevented tDCS effects on motor recovery and connectivity as well as the increase of spine density, pERK (phosphorylated extracellular signal-regulated kinase), pCaMKII (phosphorylated calcium/calmodulin-dependent protein kinase II), pMEF (phosphorylated myocyte-enhancer factor), and PSD (postsynaptic density)-95. The tDCS-promoted rescue was paralleled by enhanced plasma BDNF level, suggesting its potential role as circulating prognostic biomarker. CONCLUSIONS: The rate of motor recovery is accelerated by tDCS applied in the subacute phase of stroke. Anticipation of motor recovery via vicariate pathways or neural reserve recruitment would potentially enhance the efficacy of standard treatments, such as physical therapy, which is often delayed to a later stage when plastic responses are progressively lower.

Early dementia diagnosis, MCI-to-dementia risk prediction, and the role of machine learning methods for feature extraction from integrated biomarkers, in particular for EEG signal analysis.

INTRODUCTION: Dementia in its various forms represents one of the most frightening emergencies for the aging population. Cognitive decline-including Alzheimer's disease (AD) dementia-does not develop in few days; disease mechanisms act progressively for several years before clinical evidence. METHODS: A preclinical stage, characterized by measurable cognitive impairment, but not overt dementia, is represented by mild cognitive impairment (MCI), which progresses to-or, more accurately, is already in a prodromal form of-AD in about half cases; people with MCI are therefore considered the population at risk for AD deserving special attention for validating screening methods. RESULTS: Graph analysis tools, combined with machine learning methods, represent an interesting probe to identify the distinctive features of physiological/pathological brain aging focusing on functional connectivity networks evaluated on electroencephalographic data and neuropsychological/imaging/genetic/metabolic/cerebrospinal fluid/blood biomarkers. DISCUSSION: On clinical data, this innovative approach for early diagnosis might provide more insight into pathophysiological processes underlying degenerative changes, as well as toward a personalized risk evaluation for pharmacological, nonpharmacological, and rehabilitation treatments.

tDCS effects on brain network properties during physiological aging.

Brain neural networks undergo relevant changes during physiological aging, which affect cognitive and behavioral functions. Currently, non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), are proposed as tools able to modulate cognitive functions in brain aging, acting on networks properties and connectivity. Segregation and integration measures are used and evaluated by means of local clustering (segregation) and path length (integration). Moreover, to assess the balancing between them, the Small World (SW) parameter is employed, evaluating functional coupling in normal brain aging and in pathological conditions including neurodegeneration. The aim of this study was to systematically investigate the tDCS-induced effects on brain network proprieties in physiological aging. In order to reach this aim, cortical activity was acquired from healthy young and elderly subjects by means of EEG recorded before, during, and after anodal, cathodal, and sham tDCS sessions. Specifically, the aim to exploring tDCS polarity-dependent changes in the age-dependent network dynamics was based on a network graph theory application on two groups divided in young and elderly subjects. Eighteen healthy young (9 females; mean age = 24.7, SD = 3.2) and fifteen elderly subjects (9 females; mean = 70.1, SD = 5.1) were enrolled. Each participant received anodal, cathodal, or sham tDCS over the left prefrontal cortex (PFC) in three separate experimental sessions performed 1 week apart. SW was computed to evaluate brain network organization. The present study demonstrates that tDCS delivered in PFC can change brain network dynamics, and tDCS-EEG coregistration data can be analyzed using graph theory to understand the induced effects of different tDCS polarities in physiological and pathological brain aging.

Direct and indirect neurological, cognitive, and behavioral effects of COVID-19 on the healthy elderly, mild-cognitive-impairment, and Alzheimer's disease populations.

INTRODUCTION: Healthy elderly, mild cognitive impairment and Alzheimer's disease populations have been among the most affected in the early stages of the COVID-19 pandemic due to the direct effects of the virus, and numerous indirect effects now emerge and will have to be carefully assessed over time. METHODS: This article reviews the main articles that have been published so far about the direct and indirect effects of the COVID-19 pandemic on these particularly fragile populations. RESULTS: The pandemic associated to COVID-19 has shifted most of the health resources to the emergency area and has consequently left the three main medical areas dealing with the elderly population (oncology, time-dependent diseases and degenerative disease) temporarily "uncovered". In the phase following the emergency, it will be crucial to guarantee to each area the economic and organizational resources to quickly return to the level of support of the prepandemic state. CONCLUSIONS: The emergency phase represented a significant occasion of discussion on the possibilities of telemedicine which will inevitably become increasingly important, but all the limits of its use in the elderly population have to be considered. In the post-lockdown recovery phase, alongside the classic medical evaluation, the psychological evaluation must become even more important for doctors caring about people with cognitive decline as well as with their caregivers.

Brain network modulation in transradial amputee with finger perception restored through biomimetic intraneural stimulation.

INTRODUCTION/AIMS: The hand is a sophisticated tool which allows humans to interact with the external world mainly via the sense of touch. Previous evidences demonstrated that electrical stimulations of the nerve trunks governing the hand are able to restore touch perception in transradial amputees. The aim of this study was to evaluate the neurological correlates of restored perception by the evaluation of network characteristics of the brain connectome via EEG recordings in amputees utilizing a fully sensorized bionic hand. METHODS: A 48-year-old female with a left wrist traumatic disarticulation incurred 23 years prior to the study was enrolled for 6 months, during which experimental sessions were randomized. The control group included 12 healthy subjects performing a similar protocol. RESULTS: Results showed that in both amputee and control group, a trend of SW in delta and beta 1 is recognizable (Delta and Beta 1 opposite spread) selectively in the hemisphere contralateral to the stimulus. DISCUSSION: Delta increases (less orderly network) while Beta 1 decreases (more ordered network). It could be seen as a sign of higher attention and concentration of subjects to understand the perception and this monolateral modulation is similar to the bilateral attention given to the mathematical task difficulty's increment.

Graph Theory on Brain Cortical Sources in Parkinson's Disease: The Analysis of 'Small World' Organization from EEG.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly population. Similarly to other neurodegenerative diseases, the early diagnosis of PD is quite difficult. The current pilot study aimed to explore the differences in brain connectivity between PD and NOrmal eLDerly (Nold) subjects to evaluate whether connectivity analysis may speed up and support early diagnosis. A total of 26 resting state EEGs were analyzed from 13 PD patients and 13 age-matched Nold subjects, applying to cortical reconstructions the graph theory analyses, a mathematical representation of brain architecture. Results showed that PD patients presented a more ordered structure at slow-frequency EEG rhythms (lower value of SW) than Nold subjects, particularly in the theta band, whereas in the high-frequency alpha, PD patients presented more random organization (higher SW) than Nold subjects. The current results suggest that PD could globally modulate the cortical connectivity of the brain, modifying the functional network organization and resulting in motor and non-motor signs. Future studies could validate whether such an approach, based on a low-cost and non-invasive technique, could be useful for early diagnosis, for the follow-up of PD progression, as well as for evaluating pharmacological and neurorehabilitation treatments.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. METHODS: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback.

OBJECTIVE: Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. METHODS: To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. RESULTS: All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state. INTERPRETATION: The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154.

Sural nerve biopsy in peripheral neuropathies: 30-year experience from a single center.

INTRODUCTION: Nerve biopsy has been widely used to investigate patients with peripheral neuropathy, and in many centers, it is still a useful diagnostic tool in this setting. In this study, we reviewed the histopathological spectrum of the nerve biopsies performed in our center in a 30-year period and we analyzed their relevance in the clinical setting. MATERIALS AND METHODS: Retrospective analysis of the retrieved data was done for cases of nerve biopsies performed in our institute between 1988 and 2018. Surgical technique and histopathological analysis were done accordingly to standard protocol. RESULTS: Complete clinical and pathological data were available only for 717 cases. The procedure was generally safe, with only 0.3% superimposed infection. Main pathological results were "unspecific" axonal polyneuropathy (49.8%), vasculitis neuropathy (9.3%), acquired demyelinating neuropathy (8.9%), and Charcot-Marie-Tooth (8.2%). Considering clinical-neurophysiological suspicion of vasculitis, nerve biopsy confirmed the diagnosis in 60.9% of cases. DISCUSSION: In conclusion, for inherited neuropathies, we do not recommend this invasive procedure, but we strongly suggest a genetic test. Conversely, in vasculitic neuropathies or in dysimmune neuropathies not clearly confirmed by neurophysiological examination, nerve biopsy continues to represent a useful and irreplaceable tool.

Sensitivity to temporal parameters of intraneural tactile sensory feedback.

BACKGROUND: Recent studies have shown that neural stimulation can be used to provide artificial sensory feedback to amputees eliciting sensations referred on the amputated hand. The temporal properties of the neural stimulation modulate aspects of evoked sensations that can be exploited in a bidirectional hand prosthesis. METHODS: We previously collected evidence that the derivative of the amplitude of the stimulation (intra-digit temporal dynamics) allows subjects to recognize object compliance and that the time delay among stimuli injected through electrodes implanted in different nerves (inter-digit temporal distance) allows to recognize object shapes. Nevertheless, a detailed characterization of the subjects' sensitivity to variations of intra-digit temporal dynamic and inter-digit temporal distance of the intraneural tactile feedback has not been executed. An exhaustive understanding of the overall potentials and limits of intraneural stimulation to deliver sensory feedback is of paramount importance to bring this approach closer and closer to the natural situation. To this aim, here we asked two trans-radial amputees to identify stimuli with different temporal characteristics delivered to the same active site (intra-digit temporal Dynamic Recognition (DR)) or between two active sites (inter-digit Temporal distance Recognition (TR)). Finally, we compared the results achieved for (simulated) TR with conceptually similar experiments with real objects with one subject. RESULTS: We found that the subjects were able to identify stimuli with temporal differences (perceptual thresholds) larger than 0.25 s for DR and larger than 0.125 s for TR, respectively. Moreover, we also found no statistically significant differences when the subjects were asked to identify three objects during simulated 'open-loop' TR experiments or real 'closed-loop' tests while controlling robotic hand. CONCLUSIONS: This study is a new step towards a more detailed analysis of the overall potentials and limits of intraneural sensory feedback. A full characterization is necessary to develop more advanced prostheses capable of restoring all lost functions and of being perceived more as a natural limb by users.

Approximate Entropy of Brain Network in the Study of Hemispheric Differences.

Human brain, a dynamic complex system, can be studied with different approaches, including linear and nonlinear ones. One of the nonlinear approaches widely used in electroencephalographic (EEG) analyses is the entropy, the measurement of disorder in a system. The present study investigates brain networks applying approximate entropy (ApEn) measure for assessing the hemispheric EEG differences; reproducibility and stability of ApEn data across separate recording sessions were evaluated. Twenty healthy adult volunteers were submitted to eyes-closed resting EEG recordings, for 80 recordings. Significant differences in the occipital region, with higher values of entropy in the left hemisphere than in the right one, show that the hemispheres become active with different intensities according to the performed function. Besides, the present methodology proved to be reproducible and stable, when carried out on relatively brief EEG epochs but also at a 1-week distance in a group of 36 subjects. Nonlinear approaches represent an interesting probe to study the dynamics of brain networks. ApEn technique might provide more insight into the pathophysiological processes underlying age-related brain disconnection as well as for monitoring the impact of pharmacological and rehabilitation treatments.