A New, High-Efficacy, Noninvasive Transcranial Electric Stimulation Tuned to Local Neurodynamics.

In this paper, we pose the following working hypothesis: in humans, transcranial electric stimulation (tES) with a time course that mimics the endogenous activity of its target is capable of altering the target's excitability. In our case, the target was the primary motor cortex (M1). We identified the endogenous neurodynamics of hand M1's subgroups of pyramidal neuronal pools in each of our subjects by applying Functional Source Separation (FSS) to their EEG recordings.

Functional Semi-Blind Source Separation Identifies Primary Motor Area Without Active Motor Execution.

High time resolution techniques are crucial for investigating the brain in action. Here, we propose a method to identify a section of the upper-limb motor area representation (FS_M1) by means of electroencephalographic (EEG) signals recorded during a completely passive condition (FS_M1bySS). We delivered a galvanic stimulation to the median nerve and we applied to EEG the semi-Blind Source Separation (s-BSS) algorithm named Functional Source Separation (FSS).

Neuronal electrical ongoing activity as a signature of cortical areas.

Brodmann's pioneering work resulted in the classification of cortical areas based on their cytoarchitecture and topology. Here, we aim at documenting that diverse cortical areas also display different neuronal electric activities. We investigated this notion in the hand-controlling sections of the primary somatosensory (S1) and motor (M1) areas, in both hemispheres.

Magnetic Susceptibility from Quantitative Susceptibility Mapping Can Differentiate New Enhancing from Nonenhancing Multiple Sclerosis Lesions without Gadolinium Injection.

Background And Purpose: Magnetic susceptibility values of multiple sclerosis lesions increase as they change from gadolinium-enhancing to nonenhancing. Can susceptibility values measured on quantitative susceptibility mapping without gadolinium injection be used to identify the status of lesion enhancement in surveillance MR imaging used to monitor patients with MS?

Materials And Methods: In patients who had prior MR imaging and quantitative susceptibility mapping in a current MR imaging, new T2-weighted lesions were evaluated for enhancement on conventional T1-weighted imaging with gadolinium, and their susceptibility values were measured on quantitative susceptibility mapping. Receiver operating characteristic analysis was used to assess the diagnostic accuracy of using quantitative susceptibility mapping in distinguishing new gadolinium-enhancing from new nonenhancing lesions.

Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue.

Rationale: We recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments.

Objective: The present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas.

Algorithm for fast monoexponential fitting based on Auto-Regression on Linear Operations (ARLO) of data.

Purpose: To develop a fast and accurate monoexponential fitting algorithm based on Auto-Regression on Linear Operations (ARLO) of data, and to validate its accuracy and computational speed by comparing it with the conventional Levenberg-Marquardt (LM) and Log-Linear (LL) algorithms.

Methods: ARLO, LM, and LL performances for T2* mapping were evaluated in simulation and in vivo imaging of liver (n=15) and myocardial (n=1) iron overload patients and the brain (two healthy volunteers).

Results: In simulations, ARLO consistently delivered accuracy similar to LM and significantly superior to LL.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study.

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimer's disease (AD) patients. Methods.

Intracranial calcifications and hemorrhages: characterization with quantitative susceptibility mapping.

Purpose: To compare gradient-echo (GRE) phase magnetic resonance (MR) imaging and quantitative susceptibility mapping (QSM) in the detection of intracranial calcifications and hemorrhages.

Materials And Methods: This retrospective study was approved by the institutional review board. Thirty-eight patients (24 male, 14 female; mean age, 33 years ± 16 [standard deviation]) with intracranial calcifications and/or hemorrhages diagnosed on the basis of computed tomography (CT), MR imaging (interval between examinations, 1.

Multiple frequency functional connectivity in the hand somatosensory network: an EEG study.

Objective: To investigate the dynamics of communication within the primary somatosensory neuronal network.

Methods: Multichannel EEG responses evoked by median nerve stimulation were recorded from six healthy participants. We investigated the directional connectivity of the evoked responses by assessing the Partial Directed Coherence (PDC) among five neuronal nodes (brainstem, thalamus and three in the primary sensorimotor cortex), which had been identified by using the Functional Source Separation (FSS) algorithm.

Antioxidant status and APOE genotype as susceptibility factors for neurodegeneration in Alzheimer's disease and vascular dementia.

Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the ε4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes.

Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease.

The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls.

Association of K832R and R952K SNPs of Wilson's disease gene with Alzheimer's disease.

Copper homeostasis appears abnormal in Alzheimer's disease (AD) patients. The aim of this study was to assess whether loci of susceptibility for AD lie in the Wilson's disease (WD) ATP7B gene. We studied single nucleotide polymorphisms (SNPs) K832R (c.

Glutamate-mediated primary somatosensory cortex excitability correlated with circulating copper and ceruloplasmin.

Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20) of the somatosensory magnetic fields (SEFs) evoked by right median nerve stimulation at wrist.

Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease.

It is now accepted that transition metals, such as iron and copper, are involved in the pathogenesis of the Alzheimer's disease (AD) through their participation in toxic oxidative phenomena. In this context, hemochromatosis (Hfe) and transferrin (Tf) genes are of particular importance, since they play a key role in iron homeostasis. Also, signs of liver distress which accompany metal dysmetabolisms have been shown to be linked to AD.

Ceruloplasmin/Transferrin ratio changes in Alzheimer's disease.

The link between iron and Alzheimer's disease (AD) has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf).

Copper in Alzheimer's disease: a meta-analysis of serum,plasma, and cerebrospinal fluid studies.

There is an ongoing debate on the involvement of systemic copper (Cu) dysfunctions in Alzheimer's disease (AD), and clinical studies comparing Cu levels in serum, plasma, and cerebrospinal fluid (CSF) of AD patients with those of healthy controls have delivered non-univocal and often conflicting results. In an attempt to evaluate whether Cu should be considered a potential marker of AD, we applied meta-analysis to a selection of 26 studies published in the literature. Meta-analysis is a quantitative method that combines the results of independent reports to distinguish between small effects and no effects, random variations, variations in sample used, or in different analytical approaches.

Oxidative stress and brain glutamate-mediated excitability in depressed patients.

Background: Several neuropsychiatric pathologies have been recently linked to oxidative stress. In this study, we investigated the relationship between depression, markers of oxidative stress and neurotransmission, as expressed by sensory cortex excitability.

Methods: Serum levels of oxidative stress markers and somatosensory magnetic fields, evoked by external galvanic stimulation, were measured in 13 depressed patients and 13 controls.

Is cognitive function linked to serum free copper levels? A cohort study in a normal population.

Objective: Much research on copper-dependent neurodegeneration has focused on the study of total copper levels in the organism. However, recent evidence suggests that the portion of copper that does not bind to ceruloplasmin and is loosely transported by micronutrients (free copper) may play a more significant role than copper as a whole. In this paper, we measured markers of copper metabolism in the sera of a group of cognitively normal women to test whether abnormal amounts of free copper have detectable effects on the mental state of clinically normal people.

Agents complexing copper as a therapeutic strategy for the treatment of Alzheimer's disease.

The notion that a copper dysfunction is implicated in Alzheimer's disease (AD) is based on a number of observations from in vitro and clinical studies, as well as animal models. However, there is still significant controversy over whether it is an excess or a deficiency of copper to be involved in the pathogenesis of AD. Numerous studies support the hypothesis that an excess of copper contributes to AD, but experimental evidence in transgenic mouse models seems to suggest the contrary, and at least one clinical study shows that cognitive decline correlates positively with low copper levels.

Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer's disease.

A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e.

An observational study on the influence of the APOE-epsilon4 allele on the correlation between 'free' copper toxicosis and EEG activity in Alzheimer disease.

Since many years the apolipoprotein E epsilon4 allele (APOE-epsilon4) is known to be associated with Alzheimer disease (AD) but the mechanisms of these associations remained unclear. In the last years, the potential pathogenetic role of 'free' copper (i.e.

High-gamma band activity of primary hand cortical areas: a sensorimotor feedback efficiency index.

Sensory feedback in motor control is widely recognized to be the key link between the activity of the primary motor cortex to the motor behavior. Through an ad-hoc developed procedure for source extraction (functional source separation), the primary sensory and motor cortex activities (FS(S1) and FS(M1)) were obtained from magnetoencephalographic recordings during a sensorimotor task sequence, and sensorimotor interaction was assessed. Source activity spectral powers were evaluated in the alpha (8-13 Hz), beta (14-32 Hz), gamma1 (33-60 Hz) and gamma2 (61-90 Hz) frequency bands.

Cortical excitability and rest activity properties in patients with depression.

Objective: Results of recent studies suggest a link between neuronal excitatory or inhibitory unbalance and depression. To investigate this relation, we studied the rest activity and the cortical excitability of the cerebral areas dedicated to hand control in 12 patients with depression.

Methods: Brain activity was recorded from the Rolandic region in both hemispheres of 12 depression patients and 11 control subjects by means of magnetoencephalography.

Ceruloplasmin (2-D PAGE) Pattern and Copper Content in Serum and Brain of Alzheimer Disease Patients.

A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We previously evidenced that an excess of non-ceruloplasmin-copper (NCC) correlated with the main functional, anatomical as well as cerebrospinal markers of the disease. Aim of our study was to investigate ceruloplasmin isoforms as potential actors in this AD copper dysfunction.