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Find video protocols related to scientific articles indexed in Pubmed.
Distinct lymphocytes subsets in IgM-related neuropathy: clinical-immunological correlations.
Neurol. Sci.
PUBLISHED: 09-06-2014
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IgM-related neuropathy generally presents as a late-onset demyelinating polyneuropathy with predominant sensory loss and ataxia. However, we recently reported the clinical, neurophysiological and pathological findings from our cohort and identified in about a third of patients an atypical phenotype. We analyzed by flow cytometry the different lymphocytes subsets in the peripheral blood of patients affected by IgM-related neuropathy, chronic inflammatory demyelinating polyneuropathy (CIDP), monoclonal gammopathy of undetermined significance and healthy subjects, to investigate whether different immunological patterns may differentiate the classical phenotype from atypical forms. IFN-gamma producing CD4+ and CD8+ T lymphocytes, as well as CD4+ and CD8+ T cells expressing T-bet (T-helper type 1, Th1) were increased in CIDP patients. The percentage of circulating CD4+ and CD8+ T cells producing IL-10 as well as the percentage of CD19+ cells expressing Blimp-1 were higher in patients with IgM-neuropathy. We did not find any significant differences in the different lymphocytes subsets in the IgM-related neuropathy between patients with classical and atypical phenotype. Th1 cells are increased in CIDP patients while a T helper type 2-phenotype seems to prevail in patients with IgM-neuropathy. Further studies involving a larger patient population are needed to evaluate if different lymphocytes subset may be involved in different clinical phenotypes of IgM-related neuropathy.
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Electromagnetic fields and EEG spiking rate in patients with focal epilepsy.
Clin Neurophysiol
PUBLISHED: 08-11-2014
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Despite the increase in mobile telephone technology use and possible effects on brain excitability, no studies have investigated the impact of GSM like (Global System for Mobile Communications) signal on the ongoing spiking activity in human epileptic patients.
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Human brain networks in physiological aging: a graph theoretical analysis of cortical connectivity from EEG data.
J. Alzheimers Dis.
PUBLISHED: 05-14-2014
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Modern analysis of electroencephalographic (EEG) rhythms provides information on dynamic brain connectivity. To test the hypothesis that aging processes modulate the brain connectivity network, EEG recording was conducted on 113 healthy volunteers. They were divided into three groups in accordance with their ages: 36 Young (15-45 years), 46 Adult (50-70 years), and 31 Elderly (>70 years). To evaluate the stability of the investigated parameters, a subgroup of 10 subjects underwent a second EEG recording two weeks later. Graph theory functions were applied to the undirected and weighted networks obtained by the lagged linear coherence evaluated by eLORETA on cortical sources. EEG frequency bands of interest 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). The spectral connectivity analysis of cortical sources showed that the normalized Characteristic Path Length (?) presented the pattern Young > Adult>Elderly in the higher alpha band. Elderly also showed a greater increase in delta and theta bands than Young. The correlation between age and ? showed that higher ages corresponded to higher ? in delta and theta and lower in the alpha2 band; this pattern reflects the age-related modulation of higher (alpha) and decreased (delta) connectivity. The Normalized Clustering coefficient (?) and small-world network modeling (?) showed non-significant age-modulation. Evidence from the present study suggests that graph theory can aid in the analysis of connectivity patterns estimated from EEG and can facilitate the study of the physiological and pathological brain aging features of functional connectivity networks.
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Sleep deprivation affects somatosensory cortex excitability as tested through median nerve stimulation.
Brain Stimul
PUBLISHED: 04-17-2014
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Changes of cortical excitability after sleep deprivation (SD) in humans have been investigated mostly in motor cortex, while there is little empirical evidence concerning somatosensory cortex, and its plastic changes across SD.
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Topographic electroencephalogram changes associated with psychomotor vigilance task performance after sleep deprivation.
Sleep Med.
PUBLISHED: 04-11-2014
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The psychomotor vigilance task (PVT) is a widely used method for the assessment of vigilance after sleep deprivation (SDEP). However, the neural basis of PVT performance during SDEP has not been fully understood. In particular, no studies have investigated the possible relation between EEG topographical changes after sleep loss and PVT performance. The aim of the present study is to assess the EEG topographic correlates of PVT performance after SDEP.
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Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS).
Clin Neurophysiol
PUBLISHED: 04-09-2014
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A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.
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Jitter of corticospinal neurons during repetitive transcranial magnetic stimulation. Method and possible clinical implications.
Brain Stimul
PUBLISHED: 04-08-2014
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Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex activates corticospinal neurons mainly through the depolarization of cortico-cortical axons belonging to interneurons of superficial layers.
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Neurophysiological features of motor cortex excitability and plasticity in Subcortical Ischemic Vascular Dementia: A TMS mapping study.
Clin Neurophysiol
PUBLISHED: 04-02-2014
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To evaluate neurophysiological features of M1 excitability and plasticity in Subcortical Ischemic Vascular Dementia (SIVD), by means of a TMS mapping study.
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Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation.
J. Neurol.
PUBLISHED: 03-26-2014
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Multiple sclerosis-related fatigue is highly common and often refractory to medical therapy. Ten fatigued multiple sclerosis patients received two blocks of 5-day anodal bilateral primary somatosensory areas transcranial direct current stimulation in a randomized, double-blind sham-controlled, cross-over study. The real neuromodulation by a personalized electrode, shaped on the MR-derived primary somatosensory cortical strip, reduced fatigue in all patients, by 26 % in average (p = 0.002), which did not change after sham (p = 0.901). Anodal tDCS over bilateral somatosensory areas was able to relief fatigue in mildly disabled MS patients, when the fatigue-related symptoms severely hamper their quality of life. These small-scale study results support the concept that interventions modifying the sensorimotor network activity balances could be a suitable non-pharmacological treatment for multiple sclerosis fatigue.
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Prestimulus interhemispheric coupling of brain rhythms predicts cognitive-motor performance in healthy humans.
J Cogn Neurosci
PUBLISHED: 03-25-2014
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Physiological and neuroimaging studies suggest that human actions are characterized by time-varying engagement of functional distributed networks within the brain. In this study, we investigated whether specific prestimulus interhemispheric connectivity, as a measure of synchronized network between the two hemispheres, could lead to a better performance (as revealed by RT) in a simple visuomotor task. Eighteen healthy adults underwent EEG recording during a visual go/no-go task. In the go/no-go task, a central fixation stimulus was followed by a green (50% of probability) or red visual stimulus. Participants had to press the mouse button after the green stimuli (go trials). Interhemispheric coupling was evaluated by the spectral coherence among all the electrodes covering one hemisphere and matched with those on the other. The frequency bands of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). The task-related results showed that interhemispheric connectivity decreased in delta and increased in alpha band. Furthermore, we observed positive delta and negative alpha correlations with the RT; namely, the faster the RT, the lower delta and the higher alpha connection between the two hemispheres. These results suggested that the best performance is anticipated by the better functional coupling of cortical circuits involved during the processing of the sensorimotor information, occurring between the two hemispheres pending cognitive go/no-go task.
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Second-Line Therapy with Fingolimod for Relapsing-Remitting Multiple Sclerosis in Clinical Practice: The Effect of Previous Exposure to Natalizumab.
Eur. Neurol.
PUBLISHED: 03-17-2014
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Background: To evaluate efficacy and safety of fingolimod for relapsing-remitting multiple sclerosis, particularly in patients previously exposed to natalizumab. Method: Prospective observational single-centre second-line cohort study. Results: Among 71 patients treated with fingolimod 0.5 mg/day for a mean duration of 21.75 ± 12.60 months, the annualized relapse rate was 0.66 (C.I. 95% 0.27-1.05) with a significant difference between 26 patients with prior natalizumab exposure (1.15; C.I. 95% 0.12-2.17) and 45 not exposed (0.38; C.I. 95% 0.18-0.57; p = 0.002). In a multivariate negative regression model, only previous exposure to natalizumab (p = 0.049) and duration of fingolimod treatment (p < 0.001) significantly correlated with the annualized relapse rate. Previous exposure to natalizumab (p = 0.028) and duration of treatment with fingolimod (p < 0.001) were confirmed by restricting the analysis to the first 12 months of treatment with fingolimod, but were no longer statistically significant by analysing only patients (n = 51) with at least 12 months of treatment with fingolimod (0.32; C.I. 95% 0.08-0.55 vs. 0.22; C.I. 95% 0.11-0.32; p = NS). No differences were observed in neuroradiological outcomes and disability progression in patients exposed to natalizumab and not exposed. The rate of discontinuation due to adverse events was 11.3%, with no differences between the two groups. Conclusions: Our study confirms efficacy and side effects of fingolimod in a second-line clinical practice cohort. Prior natalizumab exposure and duration of treatment with fingolimod are independent predictors of annualized relapse rate during the first 12 months of treatment with fingolimod, but not in the long-term, and may be influenced by the 3 months washout period between the two drugs. © 2014 S. Karger AG, Basel.
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A systems medicine clinical platform for understanding and managing non- communicable diseases.
Curr. Pharm. Des.
PUBLISHED: 03-12-2014
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Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.
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Cortical EEG alpha rhythms reflect task-specific somatosensory and motor interactions in humans.
Clin Neurophysiol
PUBLISHED: 03-10-2014
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Anticipating sensorimotor events allows adaptive reactions to environment with crucial implications for self-protection and survival. Here we review several studies of our group that aimed to test the hypothesis that the cortical processes preparing the elaboration of sensorimotor interaction is reflected by the reduction of anticipatory electroencephalographic alpha power (about 8-12Hz; event-related desynchronization, ERD), as an index that regulate task-specific sensorimotor processes, accounted by high-alpha sub-band (10-12Hz), rather than a general tonic alertness, accounted by low-alpha sub-band (8-10Hz). In this line, we propose a model for human cortical processes anticipating warned sensorimotor interactions. Overall, we reported a stronger high-alpha ERD before painful than non-painful somatosensory stimuli that is also predictive of the subjective evaluation of pain intensity. Furthermore, we showed that anticipatory high-alpha ERD increased before sensorimotor interactions between non-painful or painful stimuli and motor demands involving opposite hands. In contrast, sensorimotor interactions between painful somatosensory and sensorimotor demands involving the same hand decreased anticipatory high-alpha ERD, due to a sort of sensorimotor "gating" effect. In conclusion, we suggest that anticipatory cortical high-alpha rhythms reflect the central interference and/or integration of ascending (sensory) and descending (motor) signals relative to one or two hands before non-painful and painful sensorimotor interactions.
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Rivastigmine for refractory REM behavior disorder in mild cognitive impairment.
Curr Alzheimer Res
PUBLISHED: 03-07-2014
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Mild Cognitive Impairment (MCI) and REM Behavior Disorder (RBD) are both associated with a degeneration of ponto-medullary cholinergic pathways.
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Human brain networks in cognitive decline: a graph theoretical analysis of cortical connectivity from EEG data.
J. Alzheimers Dis.
PUBLISHED: 03-01-2014
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The aim of this study was to investigate the neuronal network characteristics in physiological and pathological brain aging. A database of 378 participants divided in three groups was analyzed: Alzheimer's disease (AD), mild cognitive impairment (MCI), and normal elderly (Nold) subjects. Through EEG recordings, cortical sources were evaluated by sLORETA software, while graph theory parameters (Characteristic Path Length ?, Clustering coefficient ?, and small-world network ?) were computed to the undirected and weighted networks, obtained by the lagged linear coherence evaluated by eLORETA software. EEG cortical sources from spectral analysis showed significant differences in delta, theta, and alpha 1 bands. Furthermore, the analysis of eLORETA cortical connectivity suggested that for the normalized Characteristic Path Length (?) the pattern differences between normal cognition and dementia were observed in the theta band (MCI subjects are find similar to healthy subjects), while for the normalized Clustering coefficient (?) a significant increment was found for AD group in delta, theta, and alpha 1 bands; finally, the small world (?) parameter presented a significant interaction between AD and MCI groups showing a theta increase in MCI. The fact that AD patients respect the MCI subjects were significantly impaired in theta but not in alpha bands connectivity are in line with the hypothesis of an intermediate status of MCI between normal condition and overt dementia.
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Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects.
Neuroimage
PUBLISHED: 02-19-2014
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Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.
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Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: a systematic review and meta-analysis.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 02-12-2014
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Electroconvulsive therapy (ECT) is the most effective treatment of depression. During the last decades repetitive transcranial magnetic stimulation (rTMS), an alternative method using electric stimulation of the brain, has revealed possible alternative to ECT in the treatment of depression. There are some clinical trials comparing their efficacies and safeties but without clear conclusions, mainly due to their small sample sizes. In the present study, a meta-analysis had been carried out to gain statistical power. Outcomes were response, remission, acceptability and cognitive effects in depression. Following a comprehensive literature search that included both English and Chinese language databases, we identified all randomized controlled trials that directly compared rTMS and ECT for major depression. 10 articles (9 trials) with a total of 425 patients were identified. Methodological quality, heterogeneity, sensitivity and publication bias were systematically evaluated. ECT was superior to high frequency rTMS in terms of response (64.4% vs. 48.7%, RR = 1.41, p = 0.03), remission (52.9% vs. 33.6%, RR = 1.38, p = 0.006) while discontinuation was not significantly different between the two treatments (8.3% vs. 9.4%, RR = 1.11, p = 0.80). According to the subgroup analysis, the superiority of ECT was more apparent in those with psychotic depression, while high frequency rTMS was as effective as ECT in those with non-psychotic depression. The same results were obtained in the comparison of ECT with low frequency rTMS. ECT had a non-significant advantage over high frequency rTMS on the overall improvement in HAMD scores (p = 0.11). There was insufficient data on medium or long term efficacy. Both rTMS and ECT were well tolerated with only minor side effects reported. Results based on 3 studies suggested that specific cognitive domains such as visual memory and verbal fluency were more impaired in patients receiving ECT. In conclusion, ECT seemed more effective than and at least as acceptable as rTMS in the short term, especially in the presence of psychotic depression. This review identified the lack of good quality trials comparing the long-term outcome and cognitive effects of rTMS and ECT, especially using approaches to optimize stimulus delivery and reduce clinical heterogeneity.
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Restoring natural sensory feedback in real-time bidirectional hand prostheses.
Sci Transl Med
PUBLISHED: 02-07-2014
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Hand loss is a highly disabling event that markedly affects the quality of life. To achieve a close to natural replacement for the lost hand, the user should be provided with the rich sensations that we naturally perceive when grasping or manipulating an object. Ideal bidirectional hand prostheses should involve both a reliable decoding of the user's intentions and the delivery of nearly "natural" sensory feedback through remnant afferent pathways, simultaneously and in real time. However, current hand prostheses fail to achieve these requirements, particularly because they lack any sensory feedback. We show that by stimulating the median and ulnar nerve fascicles using transversal multichannel intrafascicular electrodes, according to the information provided by the artificial sensors from a hand prosthesis, physiologically appropriate (near-natural) sensory information can be provided to an amputee during the real-time decoding of different grasping tasks to control a dexterous hand prosthesis. This feedback enabled the participant to effectively modulate the grasping force of the prosthesis with no visual or auditory feedback. Three different force levels were distinguished and consistently used by the subject. The results also demonstrate that a high complexity of perception can be obtained, allowing the subject to identify the stiffness and shape of three different objects by exploiting different characteristics of the elicited sensations. This approach could improve the efficacy and "life-like" quality of hand prostheses, resulting in a keystone strategy for the near-natural replacement of missing hands.
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Does Semantic Memory Impairment in Amnestic MCI with Hippocampal Atrophy Conform to a Distinctive Pattern of Progression?
Curr Alzheimer Res
PUBLISHED: 02-05-2014
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Subjects with Mild Cognitive Impairment (MCI) are normally classified according to the presence of episodic memory deficits associated or not to disturbances of other cognitive domains. The present study had two aims: to identify discrete subtypes of amnestic MCI (a-MCI) with hippocampal atrophy; and to assess if the identified subtypes show different rates of progression to dementia. Sixty-seven a-MCI subjects were enrolled, all showing significant hippocampal atrophy on MRI. The subjects underwent at baseline and at follow-up a comprehensive neuropsychological examination, and were followed-up for five years to detect the conversion to dementia. An exploratory factor analysis on neuropsychological performances at baseline identified three main factors that were subsequently used to perform a k-means cluster analysis. Three cluster of a-MCI subjects were identified: "pure amnestic" (N=29), "multiple domain"(N=16), and "amnestic/semantic"(N=22). The successive discriminant functions were able to correctly classify 88% of the subjects. During the follow-up, 33 subjects converted to dementia (49.2%), 14 "pure amnestic" (48.3%), 11 "multiple domain" (68.5%) and 8 "amnestic/semantic" (36.4%; log-rank: p=0.016); median survival was respectively 36, 22, and 39 months. On Cox proportional hazard model, baseline MMSE (HR=0,709; p=0.006), education (HR=1,115; p=0.011) and belonging to the "multiple domain" subgroup (HR=2,706; p=0.013) were significantly associated to higher rate of conversion to dementia. Our findings confirm the tendency to worst outcome of subjects with multiple domain MCI, and show that the association of episodic and semantic memory deficits, without other cognitive disturbances, could identify a specific cognitive pattern associated to slower cognitive decline, as previously reported in Alzheimer's Disease.
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Deactivation of distant pain-related regions induced by 20-day rTMS: a case study of one-week pain relief for long-term intractable deafferentation pain.
Pain Physician
PUBLISHED: 01-24-2014
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Deafferentation pain secondary to brachial plexus avulsion, spinal cord injury, and other peripheral nerve injuries is often refractory to conventional treatments. Stimulation of the primary motor cortex (M1) has been proven to be an effective treatment for intractable deafferentation pain. The mechanisms underlying the attenuation of deafferentation pain by motor cortex stimulation remain hypothetical.
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Ultrasound evaluation in transthyretin-related amyloid neuropathy.
Muscle Nerve
PUBLISHED: 01-05-2014
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Familial amyloid polyneuropathy is a rare condition caused by mutations of the transthyretin gene (TTR). We assessed the pattern of nerve ultrasound (US) abnormalities in patients with TTR-related neuropathy.
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Clinical, neurophysiological and pathological findings of HNPP patients with 17p12 deletion: a single-centre experience.
J. Neurol. Sci.
PUBLISHED: 01-01-2014
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Classic clinical manifestations of HNPP are characterized by recurrent painless mononeuropathies, but a minority of patients present with an atypical clinical pattern, including CMT-like neuropathy, acute or chronic inflammatory demyelinating neuropathy-like polyneuropathy, and carpal tunnel syndrome. Electrophysiological examination plays a central role in the diagnosis of HNPP, disclosing a non-uniform conduction slowing, more pronounced at entrapment sites.
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Metal-score as a potential non-invasive diagnostic test for Alzheimers disease.
Curr Alzheimer Res
PUBLISHED: 09-07-2013
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The link between biometals and Alzheimers 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. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.
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Linkage disequilibrium and haplotype analysis of the ATP7B gene in Alzheimers disease.
Rejuvenation Res
PUBLISHED: 08-02-2013
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Copper dyshomeostasis leading to a labile Cu(2+) not bound to ceruloplasmin ("free" copper) may influence Alzheimers disease (AD) onset or progression. To investigate this hypothesis, we investigated ATP7B, the gene that controls copper excretion through the bile and concentrations of free copper in systemic circulation. Our study analyzed informative ATP7B single-nucleotide polymorphisms (SNPs) in a case-control population (n=515). In particular, we evaluated the genetic structure of the ATP7B gene using the HapMap database and carried out a genetic association investigation. Linkage disequilibrium (LD) analysis highlighted that our informative SNPs and their LD SNPs covered 96% of the ATP7B gene sequence, distinguishing two "strong LD" blocks. The first LD block contains the gene region encoding for transmembrane and copper-binding, whereas the second LD block encodes for copper-binding domains. The genetic association analysis showed significant results after multiple testing correction for all investigated variants (rs1801243, odds ratio [OR]=1.52, 95% confidence interval [CI]=1.10-2.09, p=0.010; rs2147363, OR=1.58, 95% CI=1.11-2.25, p=0.010; rs1061472, OR=1.73, 95% CI=1.23-2.43, p=0.002; rs732774, OR=2.31, 95% CI=1.41-3.77, p<0.001), indicating that SNPs in transmembrane domains may have a stronger association with AD risk than variants in copper-binding domains. Our study provides novel insights that confirm the role of ATP7B as a potential genetic risk factor for AD. The analysis of ATP7B informative SNPs confirms our previous hypothesis about the absence of ATP7B in the significant loci of genome-wide association studies of AD and the genetic association study suggests that transmembrane and adenosine triphosphate (ATP) domains in the ATP7B gene may harbor variants/haplotypes associated with AD risk.
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Mutations in the 3 untranslated region of FUS causing FUS overexpression are associated with amyotrophic lateral sclerosis.
Hum. Mol. Genet.
PUBLISHED: 07-11-2013
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Mutations in the gene encoding fused-in-sarcoma (FUS) have been identified in a subset of patients with sporadic and familial amyotrophic lateral sclerosis (ALS). Variants in the 3 untranslated region (3UTR) of FUS have also been reported in ALS patients, but their pathogenic role has not been assessed. We sequenced the whole 3UTR of FUS in 420 ALS patients who were negative for mutations in the currently known ALS genes and in 480 ethnically matched controls. We detected four 3UTR variants (c.*48 G>A, c.*59 G>A, c.*108 C>T and c.*110 G>A) in four sporadic and in one familial ALS patients compared with none in controls (P = 0.02).We investigated whether these variants impaired FUS expression in primary fibroblast cultures from three patients harbouring the c.*59 G>A, c.*108 C>T and c.*110 G>A variants, respectively. The pattern of FUS expression was also investigated in fibroblasts from one ALS patient with FUS R521C mutation, in two ALS patients without mutations in the known ALS genes and in four control individuals. By immunostaining and immunoblotting, large amounts of FUS were observed in both the cytoplasm and nuclei of mutant 3UTR FUS fibroblasts. In FUS R521C mutant fibroblasts, we observed a slight increase of FUS in the cytoplasm associated with a remarkable loss of detection in nuclei. Our findings show that mutations in 3UTR of FUS are overrepresented in ALS patients and result into translation de-regulation of FUS. Overexpression and mislocalization of wild-type FUS likely contribute to ALS pathogenesis in these cases.
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Complex fasciculation potentials and survival in amyotrophic lateral sclerosis.
Clin Neurophysiol
PUBLISHED: 06-28-2013
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We investigated the relationship between fasciculation potentials (FPs) and survival in patients with ALS.
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TMS and TMS-EEG techniques in the study of the excitability, connectivity, and plasticity of the human motor cortex.
Rev Neurosci
PUBLISHED: 06-05-2013
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Increasing evidence supports the notion that brain plasticity involves distinct functional and structural components, each entailing a number of cellular mechanisms operating at different time scales, synaptic loci, and developmental phases within an extremely complex framework. However, the exact relationship between functional and structural components of brain plasticity/connectivity phenomena is still unclear and its explanation is a major challenge within modern neuroscience. Transcranial magnetic stimulation (TMS), with or without electroencephalography (EEG), is a sensitive and objective measure of the effect of different kinds of noninvasive manipulation of the brains activity, particularly of the motor cortex. Moreover, the key feature of TMS and TMS-EEG coregistration is their crucial role in tracking temporal dynamics and inner hierarchies of brain functional and effective connectivities, possibly clarifying some essential issues underlying brain plasticity. All together, the findings presented here are significant for the adoption of the TMS and TMS-EEG coregistration techniques as a tool for basic neurophysiologic research and, in the future, even for clinical diagnostics purposes.
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Unilateral cortical hyperexcitability in congenital hydrocephalus: A TMS study.
Neurocase
PUBLISHED: 05-17-2013
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Introduction: Changes in cortical excitability are considered to play an important role in promoting brain plasticity both in healthy people and in neurological diseases. Hydrocephalus is a brain development disorder related to an excessive accumulation of cerebrospinal fluid (CSF) in the ventricular system. The functional relevance of cortical structural changes described in this disease is largely unexplored in human. We investigated cortical excitability using multimodal transcranial magnetic stimulation (TMS) in a case of congenital hydrocephalus with almost no neurological signs. Methods: A caucasian 40 years old, ambidextrous and multilingual woman affected by occult spina bifida and congenital symmetrical hydrocephalous underwent a TMS study. The intracortical and interhemispheric paired pulse paradigms were used, together with the mapping technique. Results: No significant differences were found in the resting motor thresholds between the two hemispheres. Instead, the intracortical excitability curves were statistically different between the two hemispheres (with short intracortical inhibition (SICI) being strongly reduced and intracortical facilitation (ICF) enhanced in the right one), and the interhemispheric curves showed a general hyper-excitability on the right hemisphere (when conditioned by the left one) and a general hypo-excitability in the left hemisphere (when conditioned by the right one). It is noteworthy that an asymmetric right hemisphere (RH) change of excitability was observed by means of mapping technique. Conclusion: We hypothesize that in this ambidextrous subject, the observed RH hyper-excitability could represent a mechanism of plasticity to preserve functionality of specific brain areas possibly devoted to some special skills, such as multilingualism.
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fNIRS evaluation during a phonemic verbal task reveals prefrontal hypometabolism in patients affected by myotonic dystrophy type 1.
Clin Neurophysiol
PUBLISHED: 05-16-2013
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Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, is characterized by a multisystem involvement. Cognitive involvement predominantly affecting frono-temporal functions is an established clinical feature in this disorder. Brain imaging and metabolic studies showed a predominant involvement of fronto-temporal regions in DM1 patients, yet correlation studies among these findings and neuropsychological data gave contrasting results. In order to contribute to clarify the relationship between the metabolic changes documented in the frontal cortex of DM1 patients and a related cognitive task, we applied the functional near-infrared spectroscopy (fNIRS) during the execution of a phonemic verbal fluency task (pVFT).
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ATP7B variants as modulators of copper dyshomeostasis in Alzheimers disease.
Neuromolecular Med.
PUBLISHED: 04-03-2013
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To understand the role of the key copper-regulating gene, ATP7B, in copper dyshomeostasis associated with Alzheimers disease (AD), we analyzed the serum levels of copper, ceruloplasmin and free (i.e., non-ceruloplasmin bound) copper in 399 patients with AD and 303 elderly healthy controls. We also performed analyses of informative variants of ATP7B. AD patients had higher levels of copper and free copper than controls. Individuals with free copper levels higher than 1.6 ?mol/L (the upper value of the normal reference range) were more frequent among cases (p < 0.001). Among these individuals, those who were carriers of the ATP7B variants accounted for a large proportion of the free copper levels, specifically in the AD group (p < 0.01). Our results suggest the existence of a copper dysfunction phenotype of sporadic AD which has a genetic basis. They also suggest that free copper is a risk factor for this disorder, modulating additional pathways leading to the disease cascade.
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Hypercapnia affects the functional coupling of resting state electroencephalographic rhythms and cerebral haemodynamics in healthy elderly subjects and in patients with amnestic mild cognitive impairment.
Clin Neurophysiol
PUBLISHED: 03-28-2013
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Cerebral vasomotor reactivity (VMR) and coherence of resting state electroencephalographic (EEG) rhythms are impaired in Alzheimers disease (AD) patients. Here we tested the hypothesis that these two variables could be related.
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Time-varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: An EEG-TMS study.
Hum Brain Mapp
PUBLISHED: 03-03-2013
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Motor evoked potentials (MEPs) elicited by a train of consecutive, individual transcranial magnetic stimuli demonstrate fluctuations in amplitude with respect to time when recorded from a relaxed muscle. The influence of time-varying, instantaneous modifications of the electroencephalography (EEG) properties immediately preceding the transcranial magnetic stimulation (TMS) has rarely been explored. The aim of this study was to investigate the influence of the pre-TMS motor cortex and related areas EEG profile on time variants of the MEPs amplitude.
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Is sleep essential for neural plasticity in humans, and how does it affect motor and cognitive recovery?
Neural Plast.
PUBLISHED: 02-26-2013
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There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the "synaptic homeostasis hypothesis" and the "consolidation" hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.
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The spontaneous fluctuation of the excitability of a single node modulates the internodes connectivity: A TMS-EEG study.
Hum Brain Mapp
PUBLISHED: 02-15-2013
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Brain effective connectivity can be tracked by cerebral recruitments evoked by transcranial magnetic stimulation (TMS), as measured by simultaneous electroencephalography (TMS-EEG). When TMS is targeting the primary motor area, motor evoked potentials (MEPs) can be collected from the "target" muscles. The aim of this study was to measure whether or not effective brain connectivity changes with the excitability level of the corticospinal motor pathway (CSMP) as parameterized by MEP amplitude. After averaging two subgroups of EEG-evoked responses corresponding to high and low MEP amplitudes, we calculated the individual differences between them and submitted the grand average to sLORETA algorithm obtaining localized regions of interest (RoIs). Statistical differences of RoI recruitment strength between low and high CSMP excitation was assessed in single subjects. Preceding the feedback arrival, neural recruitment for stronger CSMP activation were weaker at 6-10 ms of homotopic sensorimotor areas BA3/4/5 of the right nonstimulated hemisphere (trend), weaker at 18-25 ms of left parietal BA2/3/40, and stronger at 26-32 ms of bilateral frontal motor areas BA6/8. The proposed method enables the tracking of brain network connectivity during stimulation of one node by measuring the strength of the connected recruited node activations. Spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. The effective connectivity within bilateral circuits orchestrating hand control appeared dynamically modulated in time even in resting state as probed by TMS. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
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Pulmonary embolism in a stroke patient after systemic thrombolysis: clinical decisions and literature review.
J Stroke Cerebrovasc Dis
PUBLISHED: 02-12-2013
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Pulmonary embolism can be a catastrophic event that can result in early death or serious hemodynamic dysfunction. The dehydration, immobility, and infections occurring in acute stroke patients puts these patients at risk of developing deep vein thrombosis and pulmonary embolism. Recombinant tissue-type plasminogen activator (rt-PA) is the established therapy for acute ischemic stroke, and its prompt administration results in a better outcome in stroke patients. We describe a 73-year-old man who arrived at the emergency room within 2 hours of acute onset of left hemiparesis who was treated with rt-PA and suffered a pulmonary embolism 3 days after acute stroke therapy. rt-PA is also a current therapy for pulmonary embolism, but an ischemic stroke in the previous 3 months is an absolute contraindication to thrombolysis because of the high risk of intracranial hemorrhage. We discuss clinical and therapeutic decisions and review the current literature.
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Clinical-neurophysiological correlations in a series of patients with IgM-related neuropathy.
Clin Neurophysiol
PUBLISHED: 02-03-2013
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We aim to draw clinical-neurophysiological correlations in our cohort of patients affected by IgM-related neuropathy to investigate whether neurophysiological parameters may help differentiate the classical phenotype from atypical forms.
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Clinical neurophysiology of brain plasticity in aging brain.
Curr. Pharm. Des.
PUBLISHED: 01-17-2013
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The pathophysiological mechanisms underlying normal aging and neurodegenerative disorders represent the focus of a bulk of recent research. Physiological brain aging is characterized by a progressive dysfunction and loss of synaptic contacts and neuronal abnormal apoptosis. Neural and synaptic redundancy as well as functional and structural plastic remodeling of brain networking promote maintenance of brain activity in healthy elderly for everyday life but are not sufficient to face the pathologic scenario of excessive synaptic/ neuronal loss as in dementias. It is, then, important to implement techniques that are able to measure changes in normal aging brain and to discriminate the threshold from neurodegenerative processes. Rhythmic electromagnetic brain oscillatory activity is a hallmark of neuronal function and it contains relevant traces of neuronal assemblies cooperation across different brain functions; an integrated approach utilizing modern neurophysiological techniques, including electroencephalography (EEG), event-related potentials (ERPs), and transcranial magnetic stimulation (TMS), together with biological markers and structural and functional imaging is promising for largescale, affordable, and non-invasive intercept of at-risk populations both at a group and probably also at a single-subject level. This approach might also guarantee the possibility of studying drug-induced changes in the electrical properties of the human cortex, developing and testing models of brain connectivity and treating neuropsychiatric diseases. In this paper some neurophysiological cutting-edge techniques will be presented that provide innovative information and deal with the broad issue of the role of neurophysiology for the assessment of patho-physiological aging and dementia also providing new insight to the actions of central nervous system drugs at the cortical level.
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GSTO1*E155del polymorphism associated with increased risk for late-onset Alzheimers disease: association hypothesis for an uncommon genetic variant.
Neurosci. Lett.
PUBLISHED: 09-04-2011
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Glutathione S-transferases are multifunctional enzymes involved in cellular detoxification. A genetic linkage was found between Alzheimers Disease (AD) and the chromosome 10q, where the GSTO1 and GSTO2 genes are located, leading to the hypothesis that GST Omega class (GSTO) genes may be an AD risk factor. Since it is still controversial, we decided to explore GSTO polymorphisms in Italian cohorts. We analyzed 119 AD patients and 114 healthy controls for the GSTO gene polymorphisms. In particular we investigated two common polymorphisms (GSTO1*A140D, GSTO2*N142D) and two uncommon variants (GSTO1*E155del, GSTO1*E208K) to find loci associated with AD risk. Detection of GSTO1*A140D and GSTO2*N142D was performed by PCR-RFLP, while GSTO1*E155del and GSTO1*E208K were detected using confronting two-pair primer and allele specific PCR, respectively. While GSTO1*A140D, GSTO1*E208K and GSTO2*N142D polymorphisms did not show significant outcomes, the GSTO1*E155del polymorphism is associated with AD [P=0.003; adjusted OR=3.70 (1.57-8.75)]. Our results suggest that GSTO1-1 plays a role in AD since the GSTO1*del155 variant is involved in changes in GSTO1-1 activities decreasing in enzyme stability. Specifically, three hypotheses may explain the role of GSTO1-1 in the pathophysiology of AD: the antioxidant activity of GSTO1-1 may protect brain tissue against oxidative stress; GSTO1-1 activity regulate interleukin-1? activation and its genetic variation may act to modulate inflammation in AD; GSTO1-1 is involved in the arsenic biotransformation pathway and gene polymorphisms may be implicated in the modulation of arsenic neurotoxicity. In conclusion, we hypothesized that GSTO1*E155del is an uncommon genetic variant associated with AD risk.
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Intra-hemispheric functional coupling of alpha rhythms is related to golfers performance: a coherence EEG study.
Int J Psychophysiol
PUBLISHED: 08-29-2011
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It has been shown that frontocentral electroencephalographic (EEG) alpha rhythms (about 10-12 Hz) were higher in amplitude in expert golfers in successful than unsuccessful putts, possibly reflecting the idea that amplitude regulation of frontocentral alpha rhythms is a physiological mechanism implied in motor control and golfers performance (Babiloni et al., 2008). Here, we tested the ancillary hypothesis that golfers performance is also associated to an improved coordination of cortical activity, as reflected by functional coupling of alpha rhythms across cortical regions. To this aim, between-electrodes spectral coherence was computed from spatially enhanced EEG data of the mentioned study (i.e. right handed 12 expert golfers; augmented 10-20 system; surface Laplacian estimation). Low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha sub-bands were considered with reference to individual alpha frequency peak. Statistical results showed that intra-hemispheric low-frequency alpha coherence in bilateral parietal-frontal (P3-F3 and P4-F4 electrodes) and parietal-central (P3-C3 and P4-C4 electrodes) was higher in amplitude in successful than unsuccessful putts (p<0.004). The same was true for intra-hemispheric high-frequency alpha coherence in bilateral parietal-frontal regions (p<0.004). These findings suggest that intra-hemispheric functional coupling of cortical alpha rhythms between "visuo-spatial" parietal area and other cortical areas is implicated in fine motor control of golfers performance.
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Combined analysis of cortical (EEG) and nerve stump signals improves robotic hand control.
Neurorehabil Neural Repair
PUBLISHED: 07-05-2011
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Interfacing an amputees upper-extremity stump nerves to control a robotic hand requires training of the individual and algorithms to process interactions between cortical and peripheral signals.
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Transcranial magnetic stimulation in cognitive rehabilitation.
Neuropsychol Rehabil
PUBLISHED: 06-24-2011
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Repetitive transcranial magnetic stimulation (rTMS) can generate an increase or a decrease of neuronal excitability, which can modulate cognition and behaviour. Transcranial magnetic stimulation-induced cortical changes have been shown to result in neural plasticity. Thus, TMS provides an important opportunity to gain more insight into the mechanisms responsible for the remarkable flexibility of the central nervous system. The aim of this review was to cover the topics that could be useful when using TMS in the cognitive rehabilitation field after brain damage. The basic TMS principles are introduced, together with the clinical application for diagnosis and prognosis, the biological aspects, and the use in cognitive neuroscience studies. Finally, several hypotheses are discussed to explain the likely mechanisms induced by TMS that favour the recovery of a function after brain damage and cause the adult brain to undergo plasticity. The possibility of non-invasively interacting with the functioning of the brain and its plasticity mechanisms - a possibility that may eventually lead to cognitive and behavioural modifications - opens new and exciting scenarios in the cognitive neurorehabilitation field.
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The 894G > T (Glu298Asp) variant in the endothelial NOS gene and MTHFR polymorphisms influence homocysteine levels in patients with cognitive decline.
Neuromolecular Med.
PUBLISHED: 05-10-2011
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The presence and severity of cerebrovascular pathological findings have been shown to increase the risk and stage of cognitive decline observed in Alzheimers disease and vascular dementia. Thus, the modification of vascular risk factors seems useful to reduce the risk of dementia regardless of type. Hyperhomocysteinemia has long been known as a major independent risk factor for vascular dysfunction. In this study, we evaluated the relationships between plasma homocysteine levels and genetic risk factors for hyperhomocysteinemia, i.e., the presence of gene variants for methylenetetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (eNOS) in patients with cognitive impairment. Genotyping for MTHFR C677T and eNOS 894G > T polymorphisms was carried out in 69 patients with probable diagnosis of AD and anamnestic mild cognitive impairment, matched for age and gender with 69 healthy volunteers. Patients with MTHFR TT677 genotype showed higher plasma Hcy levels than controls, even after adjustment for folate levels (P < 0.05). Moreover, Hcy plasma levels were higher in cases than controls for any given eNOS genotype. In particular, the presence of eNOS TT894 genotype in patients with cognitive decline resulted significantly associated with increased plasma Hcy levels when compared with controls having the same genotype or patients having other eNOS genotypes (P = 0.02). These data suggest that both MTHFR C677T and eNOS G894T variants should be regarded as genetic risk factors for hyperhomocysteinemia in patients with cognitive decline.
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Mobile phone emission modulates event-related desynchronization of ? rhythms and cognitive-motor performance in healthy humans.
Clin Neurophysiol
PUBLISHED: 03-02-2011
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It has been shown that electromagnetic fields of Global System for Mobile Communications phone (GSM-EMFs) affect human brain rhythms (Vecchio et al., 2007, 2010), but it is not yet clear whether these effects are related to alterations of cognitive functions.
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Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 02-26-2011
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It is now accepted that transition metals, such as iron and copper, are involved in the pathogenesis of the Alzheimers 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. In order to investigate whether and how all these factors are interconnected, in this study we have explored the relationship of the gene variants of Hfe H63D and C282Y and of Tf C2 with serum markers of iron status (iron, ferritin, TF, TF-saturation, ceruloplasmin -CP-, CP and TF serum concentrations (CP/TF) ratio), and of liver function (albumin, transaminases, prothrombin time-prothrombin time (PT)) in a sample of 160 AD patients and 79 healthy elderly controls. Albumin resulted in lower, PT longer and AST/ALT higher ratios in AD patients than in controls, indicating a distress of the liver. Also TF was lower and ferritin higher in AD. Multiple logistic regression backward analyses, performed to evaluate the effects of our biochemical variables upon the probability of developing AD, revealed that a one-unit TF serum-decrease increases the probability of AD by 80%, a one-unit albumin serum-decrease reduces this probability by 20%, and a one-unit increase of AST/ALT ratio generates a 4-fold probability increase. Patients who were carriers of the H63D mutation showed higher levels of iron, lower levels of TF and CP and higher CP/TF ratios, a panel resembling hemochromatosis. This picture was found neither in H63D non-carrier patients, nor in healthy controls. Our results suggest the existence of a link between Hfe mutations and iron abnormalities that increases the probability of developing AD when accompanied by a distress of the liver.
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Effects of mobile phone signals over BOLD response while performing a cognitive task.
Clin Neurophysiol
PUBLISHED: 02-02-2011
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The aim of this study was to investigate the effects induced by an exposure to a GSM signal (Global System for Mobile Communication) on brain BOLD (blood-oxygen-level dependent) response, as well as its time course while performing a Go-NoGo task.
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Motor cortex excitability in Alzheimers disease: a transcranial magnetic stimulation follow-up study.
Neurosci. Lett.
PUBLISHED: 01-20-2011
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Transient cognitive and behavioral stabilization of patients with Alzheimers disease (AD) is the main goal of acetylcholinesterase inhibitor (AChEI) therapy. Response to treatment is variable and it is usually assessed clinically via neuropsychological scales. Functional neuroimaging could ideally permit the objective evaluation of the topographic correlates of therapy on brain functioning, but is expensive and little available on a large scale. On the other hand, neurophysiological methods such as transcranial magnetic stimulation (TMS) could offer an alternative, low-cost and risk free tool of assessing response to treatment in AD. Previous TMS studies have demonstrated hyperexcitability and asymptomatic motor cortex reorganization in the early stages of AD in patients with normal motor function. The aim of this study was to compare motor cortex functionality in 10 AD patients before and after long-term AchEIs therapy in order to monitor potential drug-related changes in cortical excitability and organization. Examined parameters of motor cortex physiology were found to be unchanged in patients with stabilized cognitive performance during the therapy. TMS, along with clinical, neuropsychological, and neuroimaging data, could be an inexpensive measure of biological progression in AD and it might supplement traditional methods to assess the effects of therapy.
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Cortical neuromodulation modifies cerebral vasomotor reactivity.
Stroke
PUBLISHED: 07-29-2010
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Cerebral vasomotor reactivity (VMR) is a capability of cerebral vessels to dilate in response to hypercapnia. Transcranial direct current stimulation (tDCS) effects on cerebral hemodynamics have been poorly studied.
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Anodal transcranial direct current stimulation enhances procedural consolidation.
J. Neurophysiol.
PUBLISHED: 06-10-2010
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The primary motor cortex (M1) area recruitment enlarges while learning a finger tapping sequence. Also M1 excitability increases during procedural consolidation. Our aim was to investigate whether increasing M1 excitability by anodal transcranial DC stimulation (AtDCS) when procedural consolidation occurs was able to induce an early consolidation improvement. Forty-seven right-handed healthy participants were trained in a nine-element serial finger tapping task (SFTT) executed with the left hand. Random series blocks were interspersed with training series blocks. Anodal or sham tDCS was administered over the right M1 after the end of the training session. After stimulation, the motor skills of both trained and a new untrained sequential series blocks were tested again. For each block, performance was estimated as the median execution time of correct series. Early consolidation of the trained series, assessed by the performance difference between the first block after and the last block before stimulation normalized by the random, was enhanced by anodal and not by sham tDCS. Stimulation did not affect random series execution. No stimulation effect was found on the on-line learning of the trained and new untrained series. Our results suggest that AtDCS applied on M1 soon after training improves early consolidation of procedural learning. Our data highlight the importance of neuromodulation procedures for understanding learning processes and support their use in the motor rehabilitation setting, focusing on the timing of the application.
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Human brain connectivity during single and paired pulse transcranial magnetic stimulation.
Neuroimage
PUBLISHED: 06-02-2010
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Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration.
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Cerebral restorative plasticity from normal ageing to brain diseases: a "never ending story".
Restor. Neurol. Neurosci.
PUBLISHED: 05-19-2010
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Brain plasticity can be considered the main result of brain communication with the external and internal environment. Learning new skills as well as endogenous brain function recovery following a lesion are based on neural plasticity, a dynamic phenomenon occurring in response to modification of conscious and pre- or sub-conscious experiences as they progressively stabilize at the synaptic and neural networks level. In spite of previously accepted theory, brain plasticity occurs throughout lifespan being an inner property of the system. Different models of brain plasticity are examined in relation with different modifications of the CNS: healthy brain ageing, neurodegenerative disorders, ischemic stroke and multiple sclerosis. A clarification of advantageous as well as of aberrant brain plasticity mechanisms in pathological conditions may help to improve the development of rehabilitation methods to better address and facilitate such processes.
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Passive tactile recognition of geometrical shape in humans: An fMRI study.
Brain Res. Bull.
PUBLISHED: 04-28-2010
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Tactile shape discrimination involves frontal other than somatosensory cortex (Palva et al., 2005 [48]), but it is unclear if this frontal activity is related to exploratory concomitants. In this study, we investigated topographical details of prefrontal, premotor, and parietal areas during passive tactile recognition of 2D geometrical shapes in conditions avoiding exploratory movements. Functional magnetic resonance imaging (fMRI) was performed while the same wooden 2D geometrical shapes were blindly pressed on subjects passive right palm in three conditions. In the RAW condition, shapes were pressed while subjects were asked to attend to the stimuli but were not trained to recognize them. After a brief training, in the SHAPE condition subjects were asked to covertly recognize shapes. In the RECOGNITION condition, they were asked to overtly recognize shapes, using response buttons with their opposite hand. Results showed that somatosensory cortex including contralateral SII, contralateral SI, and left insula was active in all conditions, confirming its importance in processing tactile shapes. In the RAW vs. SHAPE contrast, bilateral posterior parietal, insular, premotor, prefrontal, and (left) Brocas areas were more active in the latter. In the RECOGNITION, activation of (left) Brocas area correlated with correct responses. These results suggest that, even without exploratory movements, passive recognition of tactile geometrical shapes involves prefrontal and premotor as well as somatosensory regions. In this framework, Brocas area might be involved in a successful selection and/or execution of the correct responses.
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Effects of somatosensory stimulation and attention on human somatosensory cortex: an fMRI study.
Neuroimage
PUBLISHED: 03-26-2010
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It is well known that primary and non-primary areas of human somatosensory cortex are involved in the processing of adequate deviant/rare stimuli and omission of frequent stimuli. However, the relative weight and interaction of these variables is poorly known. This functional magnetic resonance imaging (fMRI) study tested the hypothesis that somatosensory stimulus processing and attention especially interact in non-primary somatosensory areas including secondary somatosensory cortex (SII) and insula. To test this hypothesis, responses of somatosensory cortex were mapped during four conditions of an oddball paradigm: DELIVERED COUNT and IGNORE (count or ignore deviant/rare electrical stimuli, respectively); OMITTED COUNT and IGNORE (count or ignore the rare omission of frequent electrical stimuli, respectively). The deviant/rare and frequent electrical stimuli were delivered to median and ulnar nerve, respectively. It was observed that contralateral (left) primary somatosensory responses were not markedly modulated by the mentioned deviant/rare events. Furthermore, contralateral SII and insula responded to all but not OMITTED IGNORE (purely attentive) condition, whereas ipsilateral (right) SII responded to all conditions. Finally, ipsilateral insula responded to the COUNT (attentive) conditions, regardless of the physical presence of the deviant/rare stimuli. The results suggest that in somatosensory modality, bilateral SII and left (contralateral) insula reflect complex integrative processes of stimulus elaboration and attention, whereas right (ipsilateral) insula mainly sub-serves active attention to deviance within a sequence of somatosensory stimuli.
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Patients with migraine with aura have increased flow mediated dilation.
BMC Neurol
PUBLISHED: 03-10-2010
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Endothelium-derived nitric oxide (NO) mediates the arterial dilation following a flow increase (i.e. flow-mediated dilation, FMD), easily assessed in the brachial artery. NO is also involved in cerebral hemodynamics and it is supposed to trigger vascular changes occurring during migraine. This study aimed at investigating whether migraine patients present an altered response to NO also in the peripheral artery system.
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Brain-behavior relations: transcranial magnetic stimulation: a review.
IEEE Eng Med Biol Mag
PUBLISHED: 02-24-2010
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In recent years, noninvasive brain stimulation methods have been proposed as the next-generation technology to probe and eventually interfere with brain function. Transcranial magnetic stimulation (TMS) is a 20-year-old technique originally introduced to investigate nervous propagation along the corticospinal tract, spinal roots, and peripheral nerves in humans. TMS is extensively used in clinical neurophysiology, including rehabilitation and intraoperative monitoring.
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Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: an EEG study.
Clin Neurophysiol
PUBLISHED: 02-16-2010
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Locked-in syndrome (LIS) is a state of complete paralysis, except for ocular movements, which results from ventral brainstem lesions. Patients typically are fully conscious. Here we tested the hypothesis that electroencephalographic (EEG) rhythms are abnormal in LIS patients, possibly due to an impaired neural synchronization between brainstem and cerebral cortex.
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Cortical responses to consciousness of schematic emotional facial expressions: a high-resolution EEG study.
Hum Brain Mapp
PUBLISHED: 02-10-2010
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Is conscious perception of emotional face expression related to enhanced cortical responses? Electroencephalographic data (112 channels) were recorded in 15 normal adults during the presentation of cue stimuli with neutral, happy or sad schematic faces (duration: "threshold time" inducing about 50% of correct recognitions), masking stimuli (2 s), and go stimuli with happy or sad schematic faces (0.5 s). The subjects clicked left (right) mouse button in response to go stimuli with happy (sad) faces. After the response, they said "seen" or "not seen" with reference to previous cue stimulus. Electroencephalographic data formed visual event-related potentials (ERPs). Cortical sources of ERPs were estimated by LORETA software. Reaction time to go stimuli was generally shorter during "seen" than "not seen" trials, possibly due to covert attention and awareness. The cue stimuli evoked four ERP components (posterior N100, N170, P200, and P300), which had similar peak latency in the "not seen" and "seen" ERPs. Only N170 amplitude showed differences in amplitude in the "seen" versus "not seen" ERPs. Compared to the "not seen" ERPs, the "seen" ones showed prefrontal, premotor, and posterior parietal sources of N170 higher in amplitude with the sad cue stimuli and lower in amplitude with the neutral and happy cue stimuli. These results suggest that nonconscious and conscious processing of schematic emotional facial expressions shares a similar temporal evolution of cortical activity, and conscious processing induces an early enhancement of bilateral cortical activity for the schematic sad facial expressions (N170).
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Mobile phone emission modulates inter-hemispheric functional coupling of EEG alpha rhythms in elderly compared to young subjects.
Clin Neurophysiol
PUBLISHED: 11-02-2009
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It has been reported that GSM electromagnetic fields (GSM-EMFs) of mobile phones modulate--after a prolonged exposure--inter-hemispheric synchronization of temporal and frontal resting electroencephalographic (EEG) rhythms in normal young subjects [Vecchio et al., 2007]. Here we tested the hypothesis that this effect can vary on physiological aging as a sign of changes in the functional organization of cortical neural synchronization.
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Synchronous with your feelings: sensorimotor {gamma} band and empathy for pain.
J. Neurosci.
PUBLISHED: 10-09-2009
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Neuroscience studies on the social sharing of observed or imagined pain focused on whether empathic pain resonance is linked to affective or sensory nodes of the pain matrix. However, empathy, like other complex cognitive processes, is inherently linked to the activation of functional networks rather than of separate brain areas. Here, we used magnetoencephalography (MEG) to explore the relationship between empathy and functional coupling of neuronal activity in primary somatosensory (SI) and motor (MI) cortices. MEG recording was performed while healthy participants observed movie-clips depicting the static hand of a stranger model, the same hand deeply penetrated by a needle, or gently touched by a Q-tip. Subjects were asked to rate the movie-derived sensations attributed to self or to the model. For each type of clip observation, we analyzed spectral power and coherence values in alpha, beta, and gamma frequency bands. While spectral power indexes separate neural activity in SI and MI, coherence values index functional cross-talk between these two areas. No power changes of SI or MI sources were induced by observation conditions in any of the frequency bands. Crucially, gamma-band coherence values were significantly higher during needle-in-hand than touch and static hand observation and correlated with self-and other-referred pain ratings derived from needle-in-hand movies observation. Thus, observation of others pain increases neuronal synchronization and cross-talk between the onlookers sensory and motor cortices, indicating that empathic resonance relies upon the activity of functional networks more than of single areas.
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Naming facilitation induced by transcranial direct current stimulation.
Behav. Brain Res.
PUBLISHED: 09-07-2009
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Transcranial direct current stimulation (tDCS) is able to generate a long-term increase or decrease in the neuronal excitability that can modulate cognitive tasks, similar to repetitive transcranial magnetic stimulation. The aim of this study was to explore the effects of tDCS on a language task in young healthy subjects. Anodal, cathodal and sham tDCS were applied to the left dorsolateral prefrontal cortex (DLPFC) before two picture naming experiments, a preliminary study (i.e., experiment 1) and a main study (i.e., experiment 2). The results show that anodal tDCS of the left DLPFC improves naming performance, speeding up verbal reaction times after the end of the stimulation, whereas cathodal stimulation had no effect. We hypothesize that the cerebral network dedicated to lexical retrieval processing is facilitated by anodal tDCS to the left DLPFC. Although the mechanisms responsible for facilitation are not yet clear, the results presented herein implicate a facilitation lasting beyond the end of the stimulation that imply cortical plasticity mechanisms. The opportunity to non-invasively interact with the functioning of these plasticity mechanisms will surely open new and promising scenarios in language studies in basic and clinical neuroscience fields.
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Implications of brain plasticity to brain-machine interfaces operation a potential paradox?
Int. Rev. Neurobiol.
PUBLISHED: 07-18-2009
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The adult brain has the remarkable ability to plastically reorganize itself in order to record memories (experiences), to add abilities, and to learn skills, significantly expanding the carnet of resources useful for facing and solving the unpredictability of any daily life activity, that is, artistic and cultural activities. Brain plasticity also plays a crucial role in reorganizing central nervous systems networks after any lesion, being it sudden and localized, or progressive and diffuse, in order to partly or totally restore lost and/or compromised functions. In severely affected neurological patients unable to move and to communicate with the external environment, technologies implementing brain-machine interfaces (BMIs) can be of valuable help and support. Subjects operating within a BMI frame must learn how to produce a meaningful signal for an external reader; how to increase the signal-to-noise ratio at a level which makes it suitable for rapid communication with the machine; and how to improve the speed and specificity (bit rate) of signal production as a new language for governing and controlling a machine. Since it is of absolute importance for the patient to be able to maintain such a skill for a prolonged lapse of time (i.e., until his/her lost abilities are restored by a therapy and/or a different technology), neurophysiological phenomena at the base of plastic changes are obviously of remarkable importance within any BMI and are the content of the present chapter.
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Interfacing insect brain for space applications.
Int. Rev. Neurobiol.
PUBLISHED: 07-18-2009
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Insects exhibit remarkable navigation capabilities that current control architectures are still far from successfully mimic and reproduce. In this chapter, we present the results of a study on conceptualizing insect/machine hybrid controllers for improving autonomy of exploratory vehicles. First, the different principally possible levels of interfacing between insect and machine are examined followed by a review of current approaches towards hybridity and enabling technologies. Based on the insights of this activity, we propose a double hybrid control architecture which hinges around the concept of "insect-in-a-cockpit." It integrates both biological/artificial (insect/robot) modules and deliberative/reactive behavior. The basic assumption is that "low-level" tasks are managed by the robot, while the "insect intelligence" is exploited whenever high-level problem solving and decision making is required. Both neural and natural interfacing have been considered to achieve robustness and redundancy of exchanged information.
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Sensorimotor interaction between somatosensory painful stimuli and motor sequences affects both anticipatory alpha rhythms and behavior as a function of the event side.
Brain Res. Bull.
PUBLISHED: 07-17-2009
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It has been shown that concomitant painful stimulation and simple movement at the same hand is related to decreased anticipatory alpha event-related desynchronization (ERD) and reduced pain intensity, possibly due to the interference between somatosensory and motor information processing (Babiloni et al. [6]). Here, we tested the hypothesis that such interference also affects motor performance during sequential movements. Visual warning stimuli were followed by imperative stimuli associated to electrical painful stimulation at left or right middle finger; imperative stimuli triggered motor sequences with right index finger. Electroencephalographic data (N=10, 128 electrodes) were spatially enhanced by surface Laplacian transformation. Cortical activity as revealed by the alpha event-related desynchronization (ERD) was compared in "Pain+ipsilateral movement" condition (movements and painful stimuli performed at the right hand) vs. "Pain+contralateral movement" condition (painful stimuli at left hand and movements performed at the right hand). Results showed that compared with the "Pain+contralateral movement" condition, the "Pain+ipsilateral movement" condition induced lower anticipatory alpha ERD (about 10-12 Hz) in left sensorimotor area, lower subjective pain rate, and delayed movement initiation at the group level. These findings suggest that anticipatory alpha rhythms may underlie cortical preparatory sensorimotor processes preceding somatosensory painful and the initiation of sequential motor events occurring at unilateral or bilateral hand.
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Heritability of intracortical inhibition and facilitation.
J. Neurosci.
PUBLISHED: 07-17-2009
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The present twin study investigates heritability of motor cortex excitability, measured by the paired pulse transcranial magnetic stimulation technique. Specifically, intracortical facilitation (ICF) and inhibition (ICI) and corticospinal excitability were tested in monozygotic (MZ), dizygotic (DZ), and unrelated pairs (UP). Robust ICF and ICI effects were found, with a higher similarity of MZ than DZ and UP pairs. Heritability estimates (h(2)) were 0.80 for ICI and 0.92 for ICF. However, corticospinal excitability did not show significant differences between MZ and DZ pairs, whereas both significantly differed from UP. Hence, the study provides--for the first time--a clear evidence of heritable individual differences in motor cortex excitability.
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White-matter lesions along the cholinergic tracts are related to cortical sources of EEG rhythms in amnesic mild cognitive impairment.
Hum Brain Mapp
PUBLISHED: 07-03-2009
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Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimers disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white-matter tracts. Eyes-closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white-matter tracts were detected with fluid-attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi-automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch-; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch-, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects.
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A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimers disease.
Aging Clin Exp Res
PUBLISHED: 05-19-2009
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Epidemiological studies have examined the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Alzheimers disease (AD). Recently, a variety of experimental studies indicates that a subset of NSAIDs, such as ibuprofen or flurbiprofen, also have Abeta-lowering properties in both AD transgenic mice and cell cultures of peripheral, glial and neuronal origin. In this trial, we evaluated whether the non-selective NSAID ibuprofen slows disease progression in patients with mild to moderate AD.
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Cortical sources of visual evoked potentials during consciousness of executive processes.
Hum Brain Mapp
PUBLISHED: 05-01-2009
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What is the timing of cortical activation related to consciousness of visuo-spatial executive functions? Electroencephalographic data (128 channels) were recorded in 13 adults. Cue stimulus briefly appeared on right or left (equal probability) monitor side for a period, inducing about 50% of recognitions. It was then masked and followed (2 s) by a central visual go stimulus. Left (right) mouse button had to be clicked after right (left) cue stimulus. This "inverted" response indexed executive processes. Afterward, subjects said "seen" if they had detected the cue stimulus or "not seen" when it was missed. Sources of event-related potentials (ERPs) were estimated by LORETA software. The inverted responses were about 95% in seen trials and about 60% in not seen trials. Cue stimulus evoked frontal-parietooccipital potentials, having the same peak latencies in the seen and not seen data. Maximal difference in amplitude of the seen and not seen ERPs was detected at about +300-ms post-stimulus (P3). P3 sources were higher in amplitude in the seen than not seen trials in dorsolateral prefrontal, premotor and parietooccipital areas. This was true in dorsolateral prefrontal and premotor cortex even when percentage of the inverted responses and reaction time were paired in the seen and not seen trials. These results suggest that, in normal subjects, the primary consciousness enhances the efficacy of visuo-spatial executive processes and is sub-served by a late (100- to 400-ms post-stimulus) enhancement of the neural synchronization in frontal areas.
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Hand somatosensory subcortical and cortical sources assessed by functional source separation: an EEG study.
Hum Brain Mapp
PUBLISHED: 04-10-2009
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We propose a novel electroencephalographic application of a recently developed cerebral source extraction method (Functional Source Separation, FSS), which starts from extracranial signals and adds a functional constraint to the cost function of a basic independent component analysis model without requiring solutions to be independent. Five ad-hoc functional constraints were used to extract the activity reflecting the temporal sequence of sensory information processing along the somatosensory pathway in response to the separate left and right median nerve galvanic stimulation. Constraints required only the maximization of the responsiveness at specific latencies following sensory stimulation, without taking into account that any frequency or spatial information. After source extraction, the reliability of identified FS was assessed based on the position of single dipoles fitted on its retroprojected signals and on a discrepancy measure. The FS positions were consistent with previously reported data (two early subcortical sources localized in the brain stem and thalamus, the three later sources in cortical areas), leaving negligible residual activity at the corresponding latencies. The high-frequency component of the oscillatory activity (HFO) of the extracted component was analyzed. The integrity of the low amplitude HFOs was preserved for each FS. On the basis of our data, we suggest that FSS can be an effective tool to investigate the HFO behavior of the different neuronal pools, recruited at successive times after median nerve galvanic stimulation. As FSs are reconstructed along the entire experimental session, directional and dynamic HFO synchronization phenomena can be studied.
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Choice of multivariate autoregressive model order affecting real network functional connectivity estimate.
Clin Neurophysiol
PUBLISHED: 04-09-2009
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A realistic simulation exploiting real cortical sources identified from non-invasive extra-cranial recordings in healthy subjects has been considered in order to select the most robust procedure for choosing the correct order of multivariate autoregressive (MVAR) models. Different signal-to-noise ratios filter settings and sampling rates were also tested on the estimate of functional connectivity among the network nodes, in simulated and real cases.
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Validation of Alzheimers disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimers Disease Neuroimaging Initiative (E-ADNI).
Exp. Gerontol.
PUBLISHED: 04-06-2009
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Alzheimers Disease Neuroimaging Initiatives ("ADNI") aim to validate neuroimaging and biochemical markers of Alzheimers disease (AD). Data of the pilot European-ADNI (E-ADNI) biological marker programme of cerebrospinal fluid (CSF) and plasma candidate biomarkers are reported.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.