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Background: The Free and Cued Selective Reminding Test (FCSRT), assessing verbal episodic memory with controlled learning and semantic cueing, has been recommended for detecting the genuine encoding and storage deficits characterizing AD-related memory disorders. Objective: The present study aims at investigating the ability of FCSRT in predicting cerebrospinal fluid (CSF) evidence of amyloid-β positivity in subjects with amnestic mild cognitive impairment (aMCI) and exploring its associations with amyloidopathy, tauopathy and neurodegeneration biomarkers. Methods: 120 aMCI subjects underwent comprehensive neurological and neuropsychological examinations, including the FCSRT assessment, and CSF collection; CSF Aβ42/40 ratio, p-tau181, and total-tau quantification were conducted by an automated CLEIA method on Lumipulse G1200. Based on the Aβ42/40 ratio value, subjects were classified as either A+ or A–. Results: All FCSRT subitem scores were significantly lower in A+ group and significantly predicted the amyloid-β status, with Immediate Total Recall (ITR) being the best predictor. No significant correlations were found between FCSRT and CSF biomarkers in the A– aMCI group, while in the A+ aMCI group, all FCSRT subitem scores were negatively correlated with CSF p-tau181 and total-tau, but not with the Aβ42/40 ratio. Conclusions: FCSRT confirms its validity as a tool for the diagnosis of AD, being able to predict the presence of amyloid-β deposition with high specificity. The associations between FCSRT subitem scores and CSF p-tau-181 and total-tau levels in aMCI due to AD could further encourage the clinical use of this simple and cost-effective test in the evaluation of individuals with aMCI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The analysis of co-citations, which occurs when two publications or authors are mentioned together in the same text, has long been established as a practice within scientometrics, particularly in the field of "science mapping". However, historiography has shown less openness to utilizing co-citation analysis for distant reading purposes. To address this gap, this article presents a comprehensive methodology for applying co-citation analysis to extensive collections of historical documents, specifically 17th-century letters indexed in the ePistolarium database. In science mapping, co-citation serves as an indicator for tracking the development of scientific fields. Similarly, I employ co-citation to map the Dutch socio-intellectual landscape during the Scientific Revolution period (1623–87) and evaluate the strengths and limitations of this approach. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Direct stimulation of peripheral nerves with implantable electrodes successfully provided sensory feedback to amputees while using hand prostheses. Longevity of the electrodes is key to success, which we have improved for the polyimide-based transverse intrafascicular multichannel electrode (TIME). The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months. We present a comprehensive assessment of the electrical properties of the thin-film metallization as well as material status post explantationem. The TIMEs stayed within the electrochemical safe limits while enabling consistent and precise amplitude modulation. This lead to a reliable performance in terms of eliciting sensation. No signs of corrosion or morphological change to the thin-film metallization of the probes was observed by means of electrochemical and optical analysis. The presented longevity demonstrates that thin-film electrodes are applicable in permanent implant systems. [ABSTRACT FROM AUTHOR]

Hyperventilation (HV) is a voluntary activity that causes changes in the neuronal firing characteristics noticeable in the electroencephalogram (EEG) signals. HV-related changes have been scribed to modulation of pO2/pCO2 blood contents. Therefore, an HV test is routinely used for highlighting brain abnormalities including those depending to neurobiological mechanisms at the basis of neurodegenerative disorders. The main aim of the present paper is to study the effectiveness of HV test in modifying the functional connectivity from the EEG signals that can be typical of a prodromal state of Alzheimer's disease (AD), the Mild Cognitive Impairment prodromal to Alzheimer condition. MCI subjects and a group of age-matched healthy elderly (Ctrl) were enrolled and subjected to EEG recording during HV, eyes-closed (EC), and eyes-open (EO) conditions. Since the cognitive decline in MCI seems to be a progressive disconnection syndrome, the approach we used in the present study is the graph theory, which allows to describe brain networks with a series of different parameters. Small world (SW), modularity (M), and global efficiency (GE) indexes were computed among the EC, EO, and HV conditions comparing the MCI group to the Ctrl one. All the three graph parameters, computed in the typical EEG frequency bands, showed significant changes among the three conditions, and more interestingly, a significant difference in the GE values between the MCI group and the Ctrl one was obtained, suggesting that the combination of HV test and graph theory parameters should be a powerful tool for the detection of possible cerebral dysfunction and alteration. [ABSTRACT FROM AUTHOR]

Aim: Congestive heart failure (CHF) is a very complex clinical syndrome that may lead to ischemic cerebral hypoxia condition. The aim of the present study is to analyze the effects of CHF on brain activity through electroencephalographic (EEG) complexity measures, like approximate entropy (ApEn). Methods: Twenty patients with CHF and 18 healthy elderly people were recruited. ApEn values were evaluated in the total spectrum (0.2–47 Hz) and main EEG frequency bands: delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–11 Hz), alpha 2 (11–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–45 Hz) to identify differences between CHF group and control. Moreover, a correlation analysis was performed between ApEn parameters and clinical data (i.e., B‐type natriuretic peptides (BNP), New York Heart Association (NYHA), and systolic blood pressure (SBP)) within the CHF group. Results: Statistical topographic maps showed statistically significant differences between the two groups in the total spectrum and theta frequency band. Within the CHF group, significant negative correlations were found between total ApEn and BNP in O2 channel and between theta ApEn and NYHA scores in Fp1, Fp2, and Fz channels; instead, a significant positive correlation was found between theta ApEn and SBP in C3 channel and a nearly significant positive correlation was obtained between theta ApEn and SBP in F4 channel. Conclusion: EEG abnormalities in CHF are very similar to those observed in cognitive‐impaired patients, suggesting analogies between the effects of neurodegeneration and brain chronic hypovolaemia due to heart disorder and underlying high brain sensitivity to CHF. [ABSTRACT FROM AUTHOR]

Aging is the inevitable biological process that results in a progressive structural and functional decline associated with alterations in the resting/task-related brain activity, morphology, plasticity, and functionality. In the present study, we analyzed the effects of physiological aging on the human brain through entropy measures of electroencephalographic (EEG) signals. One hundred sixty-one participants were recruited and divided according to their age into young (n = 72) and elderly (n = 89) groups. Approximate entropy (ApEn) values were calculated in each participant for each EEG recording channel and both for the total EEG spectrum and for each of the main EEG frequency rhythms: delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–11 Hz), alpha 2 (11–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–45 Hz), to identify eventual statistical differences between young and elderly. To demonstrate that the ApEn represents the age-related brain changes, the computed ApEn values were used as features in an age-related classification of subjects (young vs elderly), through linear, quadratic, and cubic support vector machine (SVM). Topographic maps of the statistical results showed statistically significant difference between the ApEn values of the two groups found in the total spectrum and in delta, theta, beta 2, and gamma. The classifiers (linear, quadratic, and cubic SVMs) revealed high levels of accuracy (respectively 93.20 ± 0.37, 93.16 ± 0.30, 90.62 ± 0.62) and area under the curve (respectively 0.95, 0.94, 0.93). ApEn seems to be a powerful, very sensitive–specific measure for the study of cognitive decline and global cortical alteration/degeneration in the elderly EEG activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of disability because of its motor and cognitive sequelae even when the acute phase of stabilization of vital parameters is overcome. The most important improvements occur in the first 8–12 weeks after stroke, indicating that it is crucial to improve our understanding of the dynamics of phenomena occurring in this time window to prospectively target rehabilitation procedures from the earliest stages after the event. Here, we studied the intracortical excitability properties of delivering transcranial magnetic stimulation (TMS) to the primary motor cortex (M1) of left and right hemispheres in 17 stroke patients who suffered a mono-lateral left hemispheric stroke, excluding pure cortical damage. All patients were studied within 10 days of symptom onset. TMS-evoked potentials (TEPs) were collected via a TMS-compatible electroencephalogram system (TMS–EEG) concurrently with motor-evoked responses (MEPs) induced in the contralateral first dorsal interosseous muscle. Comparison with age-matched healthy volunteers was made by collecting the same bilateral-stimulation data in nine healthy volunteers as controls. Excitability in the acute phase revealed relevant changes in the relationship between left lesioned and contralesionally right hemispheric homologous areas both for TEPs and MEPs. While the paretic hand displayed reduced MEPs compared to the non-paretic hand and to healthy volunteers, TEPs revealed an overexcitable lesioned hemisphere with respect to both healthy volunteers and the contra-lesion side. Our quantitative results advance the understanding of the impairment of intracortical inhibitory networks. The neuronal dysfunction most probably changes the excitatory/inhibitory on-center off-surround organization that supports already acquired learning and reorganization phenomena that support recovery from stroke sequelae. [ABSTRACT FROM AUTHOR]

Abbreviations MRI Magnetic resonance imaging CSF Cerebrospinal fluid AQP4-Ab Antibodies to aquaporin-4 MOG Myelin oligodendrocyte glycoprotein VEPs Visual evoked potentials RRMS Relapsing-remitting multiple sclerosis NMOSD Neuromyelitis optica spectrum disorder MS Multiple sclerosis IV Intravenous Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. While mechanisms of these acute symptoms still remain unclear, this patient had several predisposing factors for vision impairment such as age, polypharmacy, and diabetes, and we consider that this vaccine-induced side effect could be ascribed to an ischemic optic neuropathy. 9281418 4 Helmchen C, Buttler GM, Markewitz R. Acute bilateral optic/chiasm neuritis with longitudinal extensive transverse myelitis in longstanding stable multiple sclerosis following vector-based vaccination against the SARS-CoV-2. [Extracted from the article]

Background: Although people with late onset epilepsy of unknown etiology (LOEU) are at higher risk of cognitive decline compared to the general population, we still lack affordable tools to predict and stratify their risk of dementia.Objective: This pilot-study investigates the potential application of electroencephalography (EEG) network small-world (SW) properties in predicting cognitive decline among patients with LOEU.Methods: People diagnosed with LOEU and normal cognitive examination at the time of epilepsy diagnosis were included. Cerebrospinal fluid biomarkers, brain imaging, and neuropsychological assessment were performed at the time of epilepsy diagnosis. Baseline EEG was analyzed for SW properties. Patients were followed-up over time with neuropsychological testing to define the trajectory of cognitive decline.Results: Over 5.1 years of follow-up, among 24 patients diagnosed with LOEU, 62.5% were female, mean age was 65.3 years, thirteen developed mild cognitive impairment (MCI), and four developed dementia. Patients with LOEU developing MCI had lower values of SW coefficients in the delta (p = 0.03) band and higher SW values in the alpha frequency bands (p = 0.02) compared to patients having normal cognition at last follow-up. The two separate ANOVAs, for low and alpha bands, confirmed an interaction between SW and cognitive decline at follow-up. A similar gradient was confirmed for patients developing dementia compared to those with normal cognitive function as well as to those developing MCI.Conclusion: Baseline EEG analysis through SW is worth investigating as an affordable, widely available tool to stratify LOEU patients for their risk of cognitive decline. [ABSTRACT FROM AUTHOR]

The objective of the present study is to explore the brain resting state differences between Parkinson's disease (PD) patients and age- and gender-matched healthy controls (elderly) in terms of complexity of electroencephalographic (EEG) signals. One non-linear approach to determine the complexity of EEG is the entropy. In this pilot study, 28 resting state EEGs were analyzed from 13 PD patients and 15 elderly subjects, applying approximate entropy (ApEn) analysis to EEGs in ten regions of interest (ROIs), five for each brain hemisphere (frontal, central, parietal, occipital, temporal). Results showed that PD patients presented statistically higher ApEn values than elderly confirming the hypothesis that PD is characterized by a remarkable modification of brain complexity and globally modifies the underlying organization of the brain. The higher-than-normal entropy of PD patients may describe a condition of low order and consequently low information flow due to an alteration of cortical functioning and processing of information. Understanding the dynamics of brain applying ApEn could be a useful tool to help in diagnosis, follow the progression of Parkinson's disease, and set up personalized rehabilitation programs. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia that involves a progressive and irrevocable decline in cognitive abilities and social behavior, thus annihilating the patient's autonomy. The theoretical assumption that disease-modifying drugs are most effective in the early stages hopefully in the prodromal stage called mild cognitive impairment (MCI) urgently pushes toward the identification of robust and individualized markers of cognitive decline to establish an early pharmacological intervention. This requires the combination of well-established neural mechanisms and the development of increasingly sensitive methodologies. Among the neurophysiological markers of attention and cognition, one of the sub-components of the 'cognitive brain wave' P300 recordable in an odd-ball paradigm -namely the P3b- is extensively regarded as a sensitive indicator of cognitive performance. Several studies have reliably shown that changes in the amplitude and latency of the P3b are strongly related to cognitive decline and aging both healthy and pathological. Here, we used a P3b spatial filter to enhance the electroencephalographic (EEG) characteristics underlying 175 subjects divided into 135 MCI subjects, 20 elderly controls (EC), and 20 young volunteers (Y). The Y group served to extract the P3b spatial filter from EEG data, which was later applied to the other groups during resting conditions with eyes open and without being asked to perform any task. The group of 135 MCI subjects could be divided into two subgroups at the end of a month follow-up: 75 with stable MCI (MCI-S, not converted to AD), 60 converted to AD (MCI-C). The P3b spatial filter was built by means of a signal processing method called Functional Source Separation (FSS), which increases signal-to-noise ratio by using a weighted sum of all EEG recording channels rather than relying on a single, or a small sub-set, of channels. A clear difference was observed for the P3b dynamics at rest between groups. Moreover, a machine learning approach showed that P3b at rest could correctly distinguish MCI from EC (80.6% accuracy) and MCI-S from MCI-C (74.1% accuracy), with an accuracy as high as 93.8% in discriminating between MCI-C and EC. Finally, a comparison of the Bayes factor revealed that the group differences among MCI-S and MCI-C were 138 times more likely to be detected using the P3b dynamics compared with the best performing single electrode (Pz) approach. In conclusion, we propose that P3b as measured through spatial filters can be safely regarded as a simple and sensitive marker to predict the conversion from an MCI to AD status eventually combined with other non-neurophysiological biomarkers for a more precise definition of dementia having neuropathological Alzheimer characteristics. [ABSTRACT FROM AUTHOR]

We see mathematics as the foundation of natural sciences, whereas in the second half of the sixteenth century the question was whether mathematics was a science at all. Ever since its foundation in 1540, the Society of Jesus had had one mission - to restore order where Luther, Calvin and the other instigators of the Reformation had brought chaos. For a long time, historians have been under the impression that Renaissance mathematics was a pure science, the mathematician a scholar whose only job was to solve abstract problems (Roux [12]). Of course, Renaissance mathematics contained the seeds of what would later become modern mathematics. [Extracted from the article]

Brain state in the time preceding the task affects motor performance at single trial level. Aim of the study was to investigate, through a single trial analysis of the Power Spectral Density (PSD) of the cortical sources of EEG rhythms, whether there are EEG markers, which can predict trial-by-trial the subject's performance as measured by the reaction time (RT). 20 healthy adult volunteers performed a specific visuomotor task while continuously recorded with a 64 electrodes EEG. For each single trial, the PSD of the cortical sources of EEG rhythms was obtained from EEG data to cortical current density time series in 12 regions of interest at Brodmann areas level. Results showed a statistically significant increase of posterior and limbic alpha 1 and of frontal beta 2 power, and a reduction of frontal and limbic delta and of temporal alpha 1 power, during triggering stimulus presentation for better performance, namely faster responses. At single trial level, correlation analyses between RTs and significant PSD, revealed positive correlations in frontal delta, temporal alpha 1, and limbic delta bands, and negative ones in frontal beta 2, parietal alpha 1, and occipital alpha 1 bands. Furthermore, the subject's faster responses have been found as correlated with the similarity between the PSD values in parietal and occipital alpha 1. Predicting individual's performance at single trial level, might be extremely useful in the clinical context, since it could allow to launch rehabilitative therapies in the most efficient brain state, avoiding useless interventions. [ABSTRACT FROM AUTHOR]

In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for the study of functional connectivity in electrophysiological recordings is graph theory: it allows to describe the brain through a mathematic model, the graph, and provides a simple representation of a complex system. As Alzheimer's and Parkinson's disease are associated with synaptic disruptions and changes in the strength of functional connectivity, they can be well described by functional connectivity analysis computed via graph theory. The aim of the present review is to provide an overview of the most recent applications of the graph theory to electrophysiological data in the two by far most frequent neurodegenerative disorders, Alzheimer's and Parkinson's diseases. [ABSTRACT FROM AUTHOR]

Most studies of René Descartes's legacy have focused on the novelty of his ideas, but little has been done to uncover the conditions that allowed these ideas to spread. Seventeenth-century Europe was already a small world—it presented a high degree of connectedness with a few brokers bridging otherwise disparate regions. A communication network known as the Republic of Letters enabled scholars to trade ideas—including Descartes's—by means of correspondence. This article offers an analysis—both qualitative and quantitative—of a corpus of letters written during Descartes's lifetime and mentioning his name. The aim is to unveil the factors that drove the diffusion of Descartes's ideas. The results are twofold. First, a close reading of the letters reveals that they were not used to create awareness about Descartes and his works but rather to discuss his ideas. Second, a network analysis of the letters shows that ideas do not spread like viruses, thus undermining the 'social contagion' model, and that weak ties are not as effective in promoting innovations as they are in circulating information. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder in elderly subjects. Recent studies verified the effects of cognitive training combined with repetitive transcranial magnetic stimulation (rTMS-COG) in AD patients. Here, we analyzed neuropsychological and neurophysiological data, derived from electroencephalography (EEG), to evaluate the effects of a 6-week protocol of rTMS-COG in 72 AD. We designed a randomized, double-blind, sham-controlled trial to evaluate efficacy of rTMS on 6 brain regions obtained by an individual MRI combined with COG related to brain areas to stimulate (i.e., syntax and grammar tasks, comprehension of lexical meaning and categorization tasks, action naming, object naming, spatial memory, spatial attention). Patients underwent neuropsychological and EEG examination before (T0), after treatment (T1), and after 40 weeks (T2), to evaluate the effects of rehabilitation therapy. "Small World" (SW) graph approach was introduced allowing us to model the architecture of brain connectivity in order to correlate it with cognitive improvements. We found that following 6 weeks of intensive daily treatment the immediate results showed an improvement in cognitive scales among AD patients. SW present no differences before and after the treatment, whereas a crucial SW modulation emerges at 40-week follow-up, emphasizing the importance of rTMS-COG rehabilitation treatment for AD. Additional results demonstrated that the delta and alpha1 SW seem to be diagnostic biomarkers of AD, whereas alpha2 SW might represent a prognostic biomarker of cognitive recovery. Derived EEG parameters can be awarded the role of diagnostic and predictive biomarkers of AD progression, and rTMS-COG can be regarded as a potentially useful treatment for AD. [ABSTRACT FROM AUTHOR]

The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a visual memory task either over the left frontal cortex (LFC; experimental condition) or the cranial vertex (control condition). Subsequently, individuals underwent a recognition memory phase during a functional MRI acquisition. We included 43 young volunteers and classified them as 19 Met allele carriers and 24 as Val/Val individuals. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers. This genetic group also exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. We concluded that BDNF Val66Met gene polymorphism, known to exert a significant effect on neuroplasticity, modulates the impact of rTMS both at the cognitive as well as at the associated brain networks expression levels. This data provides new insights on the brain mechanisms explaining cognitive inter-individual differences to TMS, and may inform future, more individually-tailored rTMS interventions. [ABSTRACT FROM AUTHOR]

Evidence indicates that the transcranial direct current stimulation (tDCS) has the potential to transiently modulate cognitive function, including age-related changes in brain performance. Only a small number of studies have explored the interaction between the stimulation sites on the scalp, task performance, and brain network connectivity within the frame of physiological aging. We aimed to evaluate the spread of brain activation in both young and older adults in response to anodal tDCS applied to two different scalp stimulation sites: Prefrontal cortex (PFC) and posterior parietal cortex (PPC). EEG data were recorded during tDCS stimulation and evaluated using the Small World (SW) index as a graph theory metric. Before and after tDCS, participants performed a behavioral task; a performance accuracy index was computed and correlated with the SW index. Results showed that the SW index increased during tDCS of the PPC compared to the PFC at higher EEG frequencies only in young participants. tDCS at the PPC site did not exert significant effects on the performance, while tDCS at the PFC site appeared to influence task reaction times in the same direction in both young and older participants. In conclusion, studies using tDCS to modulate functional connectivity and influence behavior can help identify suitable protocols for the aging brain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer's disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD. [ABSTRACT FROM AUTHOR]

Argument: The purpose of this paper is to provide an analysis of Giordano Bruno's conception of mathematics. Specifically, it intends to highlight two aspects of this conception that have been neglected in previous studies. First, Bruno's conception of mathematics changed over time and in parallel with another concept that was central to his thought: the concept of infinity. Specifically, Bruno undertook a reform of mathematics in order to accommodate the concept of the infinitely small or "minimum," which was introduced at a later stage. Second, contrary to what Héléne Védrine claimed, Bruno believed that mathematical objects were mind-dependent. To chart the parallel development of the conceptions of mathematics and infinity, a seven-year time span is considered, from the publication of Bruno's first Italian dialogue (La cena de le ceneri, 1584) to the publication of one of his last Latin works (De minimo, 1591). [ABSTRACT FROM AUTHOR]

Background: Most common progressive brain diseases in the elderly are Alzheimer's disease (AD) and vascular dementia (VaD). They present with relatively similar clinical symptoms of cognitive decline, but the underlying pathophysiological mechanisms are different.Objective: The aim is to explore the brain connectivity differences between AD and VaD patients compared to mild cognitive impairment (MCI) and normal elderly (Nold) subjects applying graph theory, in particular the Small World (SW) analysis.Methods: 274 resting state EEGs were analyzed in 100 AD, 80 MCI, 40 VaD, and 54 Nold subjects. Graph theory analyses were applied to undirected and weighted networks obtained by lagged linear coherence evaluated by eLORETA tool.Results: VaD and AD patients presented more ordered low frequency structure (lower value of SW) than Nold and MCI subjects, and more random organization (higher value of SW) in low and high frequency alpha rhythms. Differences between patients have been found in high frequency alpha rhythms in VaD (higher value of SW) with respect to AD, and in theta band with a trend which is more similar to MCI and Nold than to AD. MCI subjects presented a network organization which is intermediate, in low frequency bands, between Nold and patients.Conclusion: Graph theory applied to EEG data has proved very useful in identifying differences in brain network patterns in subjects with dementia, proving to be a valid tool for differential diagnosis. Future studies will aim to validate this method to diagnose especially in the early stages of the disease and at single subject level. [ABSTRACT FROM AUTHOR]

Introduction: Hippocampal volume is one of the main biomarkers of Alzheimer's Dementia (AD). Over the years, advanced tools that performed automatic segmentation of Magnetic Resonance Imaging (MRI) T13D scans have been developed, such as FreeSurfer (FS) and ACM-Adaboost (AA). Hippocampal volume is considered abnormal when it is below the 5th percentile of the normative population. The aim of this study was to set norms, established from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, for hippocampal volume measured with FS v.6.0 and AA tools in the neuGRID platform (www.neugrid2.eu) and demonstrate their applicability for the Italian population. Methods: Norms were set from a large group of 545 healthy controls belonging to ADNI. For each pipeline, subjects with segmentation errors were discarded, resulting in 532 valid segmentations for FS and 421 for AA (age range 56–90 years). The comparability of ADNI and the Italian Brain Normative Archive (IBNA), representative of the Italian general population, was assessed testing clinical variables, neuropsychological scores and normalized hippocampal volumes. Finally, percentiles were validated using the Italian Alzheimer's disease Repository Without Borders (ARWiBo) as external independent data set to evaluate FS and AA generalizability. Results: Hippocampal percentiles were checked with the chi-square goodness of fit test. P -values were not significant, showing that FS and AA algorithm distributions fitted the data well. Clinical, neuropsychological and volumetric features were similar in ADNI and IBNA (p > 0.01). Hippocampal volumes measured with both FS and AA were associated with age (p < 0.001). The 5th percentile thresholds, indicating left/right hippocampal atrophy were respectively: (i) below 3,223/3,456 mm3 at 56 years and 2,506/2,415 mm3 at 90 years for FS; (ii) below 4,583/4,873 mm3 at 56 years and 3,831/3,870 mm3 at 90 years for AA. The average volumes computed on 100 cognitively intact healthy controls (CN) selected from ARWiBo were close to the 50th percentiles, while those for 100 AD patients were close to the abnormal percentiles. Discussion: Norms generated from ADNI through the automatic FS and AA segmentation tools may be used as normative references for Italian patients with suspected AD. [ABSTRACT FROM AUTHOR]

Background: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. Objective: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. Methods: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. Results: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. Conclusions: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials. NCT01418820 (clinicaltrials.gov) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Eventual confirmation of the Rossi et al. findings in a larger sample of patients during a multicenter and prospective study (see later) would trigger a revision of the current law. Stratifying patients for lesion type and age is relevant because in certain clinical conditions, as when extensive facial lesions are present, it may be difficult to explore cranial reflexes, and only the apnea test can be reliably carried out. Thus, at first sight, the authors consider that a relatively long time period of observation is not useful, but rather it may even be detrimental in terms of organ donation, as 1.4% of these patients died throughout the death ascertainment for a cardiac arrest despite ventilation support. [Extracted from the article]

Purpose. To evaluate whether limited vitrectomy is as effective as complete vitrectomy in eyes with epiretinal membrane (ERM) and to compare the surgical times and rates of complications. Methods. In this multicentre European study, data of eyes with ERM that underwent vitrectomy from January 2017 to July 2018 were analyzed retrospectively. In the limited vitrectomy group, a posterior vitreous detachment (PVD) was induced up till the equator as opposed to complete PVD induction till the vitreous base in the comparison group. Incidence of iatrogenic retinal breaks, retinal detachment, surgical time, and visual outcomes were compared between groups. Results. We included 139 eyes in the analysis with a mean age being 72.2 ± 6.9 years. In this, sixty-five eyes (47%) underwent limited vitrectomy and 74 eyes (53%) underwent complete vitrectomy. Iatrogenic retinal tears were seen in both groups (5% in limited vitrectomy versus 7% in complete vitrectomy, p = 0.49). Retinal detachment occurred in 2 eyes in the limited vitrectomy group (3%) compared to none in the complete vitrectomy group (p = 0.22). Best-corrected visual acuity (BCVA) and central macular thickness improved significantly with no intergroup differences (p = 0.18). Surgical time was significantly shorter in the limited vitrectomy group with 91% surgeries taking less than 1 hour compared to 71% in the complete vitrectomy group (p < 0.001). Conclusion. A limited vitrectomy is a time-efficient and effective surgical procedure for removal of epiretinal membrane with no additional complications. [ABSTRACT FROM AUTHOR]

Argument: The purpose of this paper is to provide an analysis of Giordano Bruno's conception of mathematics. Specifically, it intends to highlight two aspects of this conception that have been neglected in previous studies. First, Bruno's conception of mathematics changed over time and in parallel with another concept that was central to his thought: the concept of infinity. Specifically, Bruno undertook a reform of mathematics in order to accommodate the concept of the infinitely small or "minimum," which was introduced at a later stage. Second, contrary to what Héléne Védrine claimed, Bruno believed that mathematical objects were mind-dependent. To chart the parallel development of the conceptions of mathematics and infinity, a seven-year time span is considered, from the publication of Bruno's first Italian dialogue (La cena de le ceneri, 1584) to the publication of one of his last Latin works (De minimo, 1591). [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer's disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment. Methods: In this randomized, sham-controlled, multicenter clinical trial, 34 patients with AD were assigned to three experimental groups receiving 30 daily sessions of combinatory intervention. Participants in the real/real group (n = 16) received 10 Hz repetitive transcranial magnetic stimulation (rTMS) delivered separately to each of six cortical regions, interleaved with computerized cognitive training. Participants in the sham rTMS group (n = 18) received sham rTMS combined with either real (sham/real group, n = 10) or sham (sham/sham group, n = 8) cognitive training. Effects of treatment on neuropsychological (primary outcome) and neurophysiological function were compared between the 3 treatment groups. These, as well as imaging measures of brain atrophy, were compared at baseline to 14 healthy controls (HC). Results: At baseline, patients with AD had worse cognition, cerebral atrophy, and TMS measures of cortico-motor reactivity, excitability, and plasticity than HC. The real/real group showed significant cognitive improvement compared to the sham/sham, but not the real/sham group. TMS-induced plasticity at baseline was predictive of post-intervention changes in cognition, and was modified across treatment, in association with changes of cognition. Interpretation: Combined rTMS and cognitive training may improve the cognitive status of AD patients, with TMS-induced cortical plasticity at baseline serving as predictor of therapeutic outcome for this intervention, and potential mechanism of action. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01504958. [ABSTRACT FROM AUTHOR]

Background: Several studies investigated clinical and instrumental differences to make diagnosis of dementia in general and in Alzheimer's disease (AD) in particular with the aim to classify, at the individual level, AD patients and healthy controls cooperating with neuropsychological tests for an early diagnosis. Advanced network analysis of electroencephalographic (EEG) rhythms provides information on dynamic brain connectivity and could be used in classification processes. If successfully reached, this goal would add a low-cost, easily accessible, and non-invasive technique with neuropsychological tests.Objective: To investigate the possibility to automatically classify physiological versus pathological aging from cortical sources' connectivity based on a support vector machine (SVM) applied to EEG small-world parameter.Methods: A total of 295 subjects were recruited: 120 healthy volunteers and 175 AD. Graph theory functions were applied to undirected and weighted networks obtained by lagged linear coherence evaluated by eLORETA. A machine-learning classifier (SVM) was applied. EEG frequency bands were: delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz).Results: The receiver operating characteristic curve showed AUC of 0.97±0.03 (indicating very high classification accuracy). The classifier showed 95% ±5% sensitivity, 96% ±3% specificity, and 95% ±3% accuracy for the classification.Conclusion: EEG connectivity analysis via a combination of source/connectivity biomarkers, highly correlating with neuropsychological AD diagnosis, could represent a promising tool in identification of AD patients. This approach represents a low-cost and non-invasive method, one that utilizes widely available techniques which, when combined, reach high sensitivity/specificity and optimal classification accuracy on an individual basis (0.97 of AUC). [ABSTRACT FROM AUTHOR]

Moving from the hypothesis that aging processes modulate brain connectivity networks, 170 healthy elderly volunteers were submitted to EEG recordings in order to define age-related normative limits. Graph theory functions were applied to exact low-resolution electromagnetic tomography on cortical sources in order to evaluate the small-world parameter as a representative model of network architecture. The analyses were carried out in the whole brain—as well as for the left and the right hemispheres separately—and in three specific resting state subnetworks defined as follows: attentional network (AN), frontal network (FN), and default mode network (DMN) in the EEG frequency bands (delta, theta, alpha 1, alpha 2, beta 1, beta 2, gamma). To evaluate the stability of the investigated parameters, a subgroup of 32 subjects underwent three separate EEG recording sessions in identical environmental conditions after a few days interval. Results showed that the whole right/left hemispheric evaluation did not present side differences, but when individual subnetworks were considered, AN and DMN presented in general higher SW in low (delta and/or theta) and high (gamma) frequency bands in the left hemisphere, while for FN, the alpha 1 band was lower in the left with respect to the right hemisphere. It was also evident the test-retest reliability and reproducibility of the present methodology when carried out in clinically stable subjects. Evidences from the present study suggest that graph theory represents a reliable method to address brain connectivity patterns from EEG data and is particularly suitable to study the physiological impact of aging on brain functional connectivity networks. [ABSTRACT FROM AUTHOR]