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Linguistic tasks facilitate corticospinal excitability as revealed by increased motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in the dominant hand. This modulation of the primary motor cortex (M1) excitability may reflect the relationship between speech and gestures. It is conceivable that in healthy individuals who use a sign language this cortical excitability modulation could be rearranged. The aim of this study was to evaluate the effect of spoken language tasks on M1 excitability in a group of hearing signers. Ten hearing Italian Sign Language (LIS) signers and 16 non-signer healthy controls participated. Single-pulse TMS was applied to either M1 hand area at the baseline and during different tasks: (i) reading aloud, (ii) silent reading, (iii) oral movements, (iv) syllabic phonation and (v) looking at meaningless non-letter strings. Overall, M1 excitability during the linguistic and non-linguistic tasks was higher in LIS group compared to the control group. In LIS group, MEPs were significantly larger during reading aloud, silent reading and non-verbal oral movements, regardless the hemisphere. These results suggest that in hearing signers there is a different modulation of the functional connectivity between the speech-related brain network and the motor system.
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Córtex Motor , Língua de Sinais , Humanos , Córtex Motor/fisiologia , Idioma , Linguística , Estimulação Magnética Transcraniana , Itália , Potencial Evocado Motor/fisiologiaRESUMO
INTRODUCTION: In patients with Parkinson's disease (PD), impulsivity is still a matter of investigation. It has been hypothesized that impulsive personality traits may favour impulse control disorder (ICD) onset during dopaminergic therapy. In healthy subjects, a relationship between the awareness of motor intention and impulsive personality traits assessed by the Barratt impulsivity scale (BIS-11) has been reported. The aim of this study was to evaluate the relationship between the awareness of voluntary action and impulsivity traits in PD. METHODS: Twenty-eight PD patients (stages I-III on the Hoehn and Yahr scale) underwent an impulsivity trait assessment by the BIS-11 scale and a task based on the Libet's clock. Participants were requested to perform a self-initiated movement and report the time they first feel their intention to move (W-judgement) or the time of the actual movement (M-judgement). RESULTS: In patients with higher BIS-11 scores, the time lag between the W-judgement and the actual movement was significantly lower than in patients with lower BIS-11. No difference emerged in the M-judgement. CONCLUSION: Data suggest that also in PD patients, the impulsive personality trait is related to a "delayed" awareness of motor intention and therefore to a shorter interval to allow a conscious "veto" of the impending action. Characterization of the temporal profile of awareness of motor intention could prove useful in identifying PD patients at risk of developing ICDs during dopaminergic treatment.
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Doença de Parkinson , Humanos , Comportamento Impulsivo , Intenção , Julgamento , Movimento , Doença de Parkinson/tratamento farmacológicoRESUMO
Event-related potentials (ERPs) are obtained from the electroencephalogram (EEG) or the magnetoencephalogram (MEG, event-related fields (ERF)), extracting the activity that is time-locked to an event. Despite the potential utility of ERP/ERF in cognitive domain, the clinical standardization of their use is presently undefined for most of procedures. The aim of the present review is to establish limits and reliability of ERP medical application, summarize main methodological issues, and present evidence of clinical application and future improvement. The present section of the review focuses on well-standardized ERP methods, including P300, Contingent Negative Variation (CNV), Mismatch Negativity (MMN), and N400, with a chapter dedicated to laser-evoked potentials (LEPs). One section is dedicated to proactive preparatory brain activity as the Bereitschaftspotential and the prefrontal negativity (BP and pN). The P300 and the MMN potentials have a limited but recognized role in the diagnosis of cognitive impairment and consciousness disorders. LEPs have a well-documented usefulness in the diagnosis of neuropathic pain, with low application in clinical assessment of psychophysiological basis of pain. The other ERP components mentioned here, though largely applied in normal and pathological cases and well standardized, are still confined to the research field. CNV, BP, and pN deserve to be largely tested in movement disorders, just to explain possible functional changes in motor preparation circuits subtending different clinical pictures and responses to treatments.
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Neurociência Cognitiva , Eletroencefalografia , Encéfalo , Potenciais Evocados , Feminino , Humanos , Itália , Masculino , Psicofisiologia , Reprodutibilidade dos TestesRESUMO
The ability to flexibly regulate our behavior is a fundamental feature of human cognition and requires efficient functioning of cognitive control. During movement preparation, proactive inhibitory control plays a crucial role in regulating the excitatory activity carried out by alertness. The balance between alertness and proactive inhibition could be altered in people with motor impulsivity trait, determining the typical failure in the inhibition of prepotent motor responses. To test this hypothesis, 36 young adults were administered the Barratt Impulsiveness Scale to assess motor impulsivity trait and underwent fMRI acquisition during the execution of an event-related Go/Nogo task. To investigate motor preparation processes, we analyzed the "readiness" period, in which subjects were waiting and preparing for the upcoming stimulus (Go or Nogo). We found a positive significant correlation between motor impulsivity scores and the activation of left sensorimotor cortices. This result indicates that motor impulsivity trait might be associated with a disinhibition of the motor system, characterized by a diminished reactivity threshold and a reduced control over covert urges. Furthermore, we observed a positive significant correlation between motor impulsivity scores and the activation in left inferior and superior parietal lobule, which might be related to a more pronounced proactive control, probably reflecting a compensatory mechanism implemented by participants with a higher degree of motor impulsivity trait to reach a correct inhibition. Current findings provide a rationale for further studies aiming to better understand proactive control functioning in healthy impulsive subjects and under clinical conditions.
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Encéfalo/fisiologia , Inibição Psicológica , Inibição Proativa , Adulto , Cognição/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologiaRESUMO
Second and third generation AEDs have been directly compared to controlled-release carbamazepine (CBZ-CR) as initial monotherapy for new-onset focal epilepsy. Conversely, no head-to-head trials have been performed. The aim of this study was to estimate the comparative efficacy and tolerability of the antiepileptic monotherapies in adults with newly diagnosed focal epilepsy through a network meta-analysis (NMA). Randomized, double-blinded, parallel group, monotherapy studies comparing any AED to CBZ-CR in adults with newly diagnosed untreated epilepsy with focal-onset seizures was identified. The outcome measures were the seizure freedom for 6 and 12 months, the occurrence of treatment-emergent adverse events (TEAEs), and the treatment withdrawal due to TEAEs. Mixed treatment comparisons were conducted by a Bayesian NMA using the Markov chain Monte Carlo methods. Effect sizes were calculated as odds ratios (ORs) with 95% credible intervals (CrIs). Four trials were included involving 2856 participants, 1445 for CBZ-CR and 1411 for the comparative AEDs. Monotherapy AEDs compared to CBR-CR were levetiracetam (LEV), zonisamide (ZNS), lacosamide (LCM), and eslicarbazepine acetate (ESL). There were no statistical differences in the 6- and 12-month seizure freedom and TEAEs occurrence between LEV, ZNS, LCM, ESL, and CBZ-CR In the analysis of drug withdrawal due to TEAEs, LCM treatment was associated with a significantly lower discontinuation rate than CBZ-CR (OR 0.659, 95% CrI 0.428-0.950). LEV, ZNS, LCM, and ESL are effective initial monotherapy treatments in adult patients with newly diagnosed focal epilepsy and represent suitable alternatives to CBZ-CR.
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Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Adulto , Humanos , Masculino , Metanálise em Rede , Resultado do TratamentoRESUMO
AIMS: Experimental studies show that some antiepileptic drugs (AEDs) may modify natural immune defences, thus influencing the risk of developing infectious diseases. The aim of this meta-analysis was to explore whether AEDs as a class of drugs or singularly may increase risk of infectious diseases. METHODS: A meta-analysis of all randomized, double-blind, placebo-controlled trials (RCTs) investigating any AED in any condition was performed. All terms that could be coded in the System Organ Classes (SOCs) of infections and infestations using the Medical Dictionary for Regulatory Activities were recorded. Additional subanalyses were performed also pooling together AEDs sharing similar mechanisms of action. RESULTS: Two hundreds and sixty-nine double-blind, placebo-controlled studies were identified and, among them, 127 RCTs with 16 AEDs (brivaracetam, gabapentin, lacosamide, levetiracetam, lamotrigine, oxcarbazepine, perampanel, pregabalin, phenytoin, remacemide, retigabine, rufinamide, tiagabine, topiramate, valproate, zonisamide) reported at least one of 19 symptoms or diseases that could be included in the Medical Dictionary for Regulatory Activities SOC term infections and infestations. These terms were singularly recorded and then pooled together in the SOC term infection and infestation. Topiramate was significantly associated with an increased risk of infection (risk difference = 0.04; 95% confidence interval = 0.01/0.06), while oxcarbazepine was significantly associated with a lower risk (-0.005; -0.09/-0.01). Risk difference of all studies with all AEDs showed a slight, but significantly increased risk of infection (0.01; 0.00/0.002). Levetiracetam and brivaracetam RCTs, when pooled together, were associated with a significantly increased risk of infection (0.03; 0.01/0.05). CONCLUSIONS: Some AEDs are associated with a mild increased risk of infection.
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Anticonvulsivantes/efeitos adversos , Doenças Transmissíveis/induzido quimicamente , HumanosRESUMO
OBJECTIVE: The objective of this study was to perform a comparative assessment of tolerability of all licensed new antiepileptic drugs (AEDs) through a network meta-analysis (NMA) including all placebo-controlled double-blind clinical trials (RCTs) in all conditions in which these drugs have been tested. METHODS: NMA with a frequentist approach was used to compare proportions of patients withdrawing because of adverse events (AEs). Analyses were conducted for all therapeutic doses pooled and specifically for high therapeutic doses. Patients treated with non-therapeutic doses of each drug were excluded. RESULTS: A total of 195 RCTs were included in the current analysis, comprising a total of 28,013 patients treated with AEDs and 17,908 patients treated with placebo. RCTs included in the analysis were 8 for brivaracetam; 5 for eslicarbazepine; 22 for gabapentin; 7 for lacosamide; 14 for levetiracetam; 14 for lamotrigine; 6 for oxcarbazepine; 9 for perampanel; 50 for pregabalin; 5 for tiagabine; 36 for topiramate; 7 for zonisamide; 4 for gabapentin-extended formulation (ER); 2 each for levetiracetam-ER, lamotrigine-ER, and topiramate-ER; and 1 each for oxcarbazepine-ER and pregabalin-ER. Brivaracetam, gabapentin, gabapentin-ER, and levetiracetam had a significantly lower withdrawal rate compared to several other AEDs, while eslicarbazepine, lacosamide, oxcarbazepine, and topiramate had a higher withdrawal rate. Perampanel, lamotrigine, pregabalin, tiagabine, and zonisamide showed an intermediate pattern of tolerability. Additional analysis has been conducted through selection of highly recommended doses for each drug. This analysis has roughly confirmed results of head to head comparisons of the all-dose analysis, with some exceptions. A further analysis has been conducted after exclusion of RCTs in which patients were allocated to the therapeutic dose of the experimental drug without titration, and it failed to show clinically important differences. SIGNIFICANCE: Relevant differences in short-term tolerability of AEDs have been observed between AEDs. Brivaracetam, gabapentin, and levetiracetam show the best tolerability profile while other AEDs are at higher risk for intolerable adverse effects.
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Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Método Duplo-Cego , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We describe the case of a non-alcoholic patient with chronic myeloid leukemia who developed iatrogenic Wernicke's encephalopathy (WE) following stem cell transplantation. Four years after the WE acute event, the patient's cognitive profile was mainly characterized by moderate memory impairment, and functional and daily-living difficulties. Our report sustains the hypothesis that a iatrogenic form of WE may produce long-term cognitive sequelae even when thiamine therapy is administered in the acute phase until the resolution of the neurological signs.
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Transtornos Cognitivos/etiologia , Transplante de Células-Tronco/efeitos adversos , Encefalopatia de Wernicke/complicações , Encefalopatia de Wernicke/cirurgia , Adulto , Humanos , Leucemia Mieloide/etiologia , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Complicações Pós-Operatórias/fisiopatologia , Transplante HomólogoRESUMO
Placebo response can be defined as any therapeutic change on placebo, while the nocebo response is any ill effect during placebo exposure. Several meta-analytic approaches have investigated the extent of placebo response in randomized, placebo-controlled, clinical trials of focal epilepsies. Placebo response rates (proportion of patients with ≥50% improvement of seizures versus baseline) ranging from 9.9% up to 15.2% have been reported. Interestingly, a sham response of 15.8% has been noted in trials of transcranial magnetic stimulation. Recently, nocebo response rates of 60.3% and 3.9% were noted, which were defined as the proportion of patients with adverse events (AEs) and those withdrawing because of intolerable AEs, respectively. Factors which were found to influence placebo response were as follows: the year of publication (with more recent studies showing higher rates of placebo response), some clinical characteristics of recruited patients (lower placebo response rates with a history of 7 or more prior lifetime AEDs, a high baseline seizure frequency, prior epilepsy surgery, and higher age at diagnosis), trial design and statistical analysis, and whether studies have been conducted in children or adults. Furthermore, placebo and nocebo rates were correlated with respective seizure outcome and adverse events of the experimental AED. Several mechanisms of placebo and nocebo responses are discussed. Specifically, the role of positive or negative expectations of patients and of investigators may influence the placebo and the nocebo response. Finally, recommendations are given on how to address placebo and nocebo responses in clinical practice.
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Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Efeito Nocebo , Efeito Placebo , Anticonvulsivantes/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Projetos de PesquisaRESUMO
Synchronization of body movements to an external beat is a universal human ability, which has also been recently documented in nonhuman species. The neural substrates of this rhythmic motor entrainment are still under investigation. Correlational neuroimaging data suggest an involvement of the dorsal premotor cortex (dPMC) and the supplementary motor area (SMA). In 14 healthy volunteers, we more specifically investigated the neural network underlying this phenomenon using a causal approach by an established 1-Hz repetitive transcranial magnetic stimulation (rTMS) protocol, which produces a focal suppression of cortical excitability outlasting the stimulation period. Synchronization accuracy between rhythmic cues and right index finger tapping, as measured by the mean time lag (asynchrony) between motor and auditory events, was significantly affected when the right dPMC function was transiently perturbed by "off-line" focal rTMS, whereas the reproduction of the rhythmic sequence per se (inter-tap-interval) was spared. This approach affected metrical rhythms of different complexity, but not non-metrical or isochronous sequences. Conversely, no change in auditory-motor synchronization was observed with rTMS of the SMA, of the left dPMC or over a control site (midline occipital area). Our data strongly support the view that the right dPMC is crucial for rhythmic auditory-motor synchronization in humans.
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Potenciais Evocados Auditivos/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Periodicidade , Estimulação Acústica , Adulto , Análise de Variância , Sinais (Psicologia) , Feminino , Lateralidade Funcional , Humanos , Masculino , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Parkinson's disease (PD) is a major worldwide public health problem with a prevalence that is expected to increase dramatically in the coming decades. Because administrative data are useful for epidemiologic and health service studies, we aimed to define procedural algorithms to identify PD patients (on a regional basis) using these data. We built two a priori algorithms, respecting privacy laws, with increasing theoretical specificity for PD including: (1) a hospital discharge diagnosis of PD; (2) PD-specific exemption; (3) a minimum of two separate prescriptions of an antiparkinsonian drug. The two algorithms differed for drugs included. Sensitivities were tested on an opportunistic sample of 319 PD patients from the databases of 5 regional movement disorders clinics. The estimated prevalence of PD in the sample population from Tuscany was 0.49 % for algorithm 1 and 0.28 % for algorithm 2. Algorithm 1 correctly identified 291 PD patients (sensitivity 91.2 %), and algorithm 2 identified 242 PD patients (sensitivity 75.9 %). We developed two reproducible algorithms demonstrating increasing theoretical specificity with good sensitivity in identifying PD patients based on an evaluation of administrative data. This may represent a low-cost strategy to reliably follow up a large number of PD patients as a whole for evaluating the effects of therapies, disease progression and prevalence.
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Bases de Dados Factuais/estatística & dados numéricos , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Antiparkinsonianos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Prevalência , Reprodutibilidade dos Testes , Adulto JovemRESUMO
In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS), we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP), an intracortical, mainly GABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI) and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM). At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the "fatigued" FDI and the "unfatigued" ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation.
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Amantadina/administração & dosagem , Fadiga/fisiopatologia , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Esclerose Múltipla/complicações , Adulto , Amantadina/uso terapêutico , Potencial Evocado Motor/efeitos dos fármacos , Fadiga/complicações , Fadiga/tratamento farmacológico , Feminino , Dedos , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
We aimed at investigating rapid effects of plasma cortisol elevations on the episodic memory phase of encoding or retrieval, and on the strength of the memory trace. Participants were asked either to select a word containing the letter "e" (shallow encoding task) or to judge if a word referred to a living entity (deep encoding task). We intravenously administered a bolus of 20mg of cortisol either 5 min before encoding or 5 min before retrieval, in a between-subjects design. The study included only male participants tested in the late afternoon, and neutral words as stimuli. When cortisol administration occurred prior to retrieval, a main effect of group emerged. Recognition accuracy was higher for individuals who received cortisol compared to placebo. The higher discrimination accuracy for the cortisol group was significant for words encoded during deep but not shallow task. Cortisol administration before encoding did not affect subsequent retrieval performance (either for deep or shallow stimuli) despite a facilitatory trend. Because genomic mechanisms take some time to develop, such a mechanism cannot apply to our findings where the memory task was performed shortly after the enhancement of glucocorticoid levels. Therefore, glucocorticoids, through non-genomic fast effects, determine an enhancement in episodic memory if administered immediately prior to retrieval. This effect is more evident if the memory trace is laid down through deep encoding operations involving the recruitment of specific neural networks.
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Glucocorticoides/administração & dosagem , Hidrocortisona/administração & dosagem , Memória Episódica , Rememoração Mental/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Adulto , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: Network meta-analysis (NMA) is a new technique that allows multiple treatment comparisons and provides estimates of effect sizes for all possible pair-wise comparisons. Several NMAs of antiepileptic drug (AED) efficacy and tolerability in individuals with refractory focal epilepsy, however, came to non-specific and, in some cases, divergent conclusions. We review some clinical factors that may be responsible for these inconsistent findings. RESULTS: A major issue is the small number of individuals included in the meta-analyses with consequent wide confidence intervals and lack of ability to achieve significant results. Further issues are lack of robustness of the measured efficacy outcome-the responder ratio (the percentage of individuals with a >50 % improvement in seizure frequency); the selection of randomized studies (RCTs) included, i.e., the inclusion of studies with heterogeneous populations (children and adults); and inclusion of people treated with different doses of the experimental drug. Some methods of analysing data from RCTs, such as the last observation carried forward (LOCF) analysis, the choice of different phases of the study to compare to baseline, and the year in which the trial was conducted, selectively affect measurement of efficacy outcomes. Titration speed and other methodological aspects selectively affect tolerability. CONCLUSION: Several factors restrict the analysis of clinically useful estimates of the comparative efficacy of AEDs, while analysis of tolerability may be easier to accomplish.
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Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Epilepsias Parciais/epidemiologia , Humanos , Adesão à Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed results, also given the difficulty of applying the fMRI standard approach to tasks usually employed in the cognitive literature. We report an activation likelihood estimation (ALE) meta-analysis to investigate the neural foundation of the dual-process theory of thought. Eligible studies allowed for the identification of cerebral areas associated with dual-process theory-based tasks without differentiating between fast and slow thinking. The ALE algorithm converged on the medial frontal cortex, superior frontal cortex, anterior cingulate cortex, insula, and left inferior frontal gyrus. These structures partially overlap with the cerebral areas recurrently reported in the literature about the neural basis of the dual-process distinction, where the PARCS theory-based interpretation emphasizes the role of the right inferior gyrus. The results confirm the potential (but still almost unexplored) common ground between the dual-process literature and the cognitive control literature.
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A domain-specific perspective to cognitive functioning in stroke patients may predict their cognitive recovery over time and target stroke rehabilitation intervention. However, data about domain-specific cognitive impairment after stroke are still scarce. This study prospectively investigated the domain-specific pattern of cognitive impairments, using the classification proposed by the Montreal Cognitive Assessment (MoCA), in a cohort of 49 stroke patients at admission (T0), discharge (T1), and six-month follow-up (T2) from subacute intensive rehabilitation. The predictive value of T0 cognitive domains cognitive impairment at T1 and T2 was also investigated. Patients' cognitive functioning at T0, T1, and T2 was assessed through the MoCA domains for executive functioning, attention, language, visuospatial, orientation, and memory. Different evolutionary trends of cognitive domain impairments emerged across time-points. Patients' impairments in all domains decreased from T0 to T1. Attention and executive impairments decreased from T0 to T2 (42.9% and 26.5% to 10.2% and 18.4%, respectively). Conversely, altered visuospatial, language, and orientation increased between T1 and T2 (16.3%, 36.7%, and 40.8%, respectively). Additionally, patients' global cognitive functioning at T1 was predicted by the language and executive domains in a subacute phase (p = 0.031 and p = 0.001, respectively), while in the long term, only attention (p = 0.043) and executive (p = 0.019) domains intervened. Overall, these results confirm the importance of a domain-specific approach to target cognitive recovery across time in stroke patients.
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A classic finding of the psychology of memory is the "serial position effect." Immediate free recall of a word list is more efficient for items presented early (primacy effect) or late (recency effect), with respect to those in the middle. In an event-related, randomized block design, we interfered with the encoding of unrelated words lists with brief trains of repetitive TMS (rTMS), applied coincidently with the acoustic presentation of each word to the left dorsolateral pFC, the left intraparietal lobe, and a control site (vertex). Interference of rTMS with encoding produced a clear-cut double dissociation on accuracy during immediate free recall. The primacy effect was selectively worsened by rTMS of the dorsolateral pFC, whereas recency was selectively worsened by rTMS of the intraparietal lobe. These results are in agreement with the double dissociation between short-term and long-term memory observed in neuropsychological patients and provide direct evidence of distinct cortical mechanisms of encoding in the human brain.
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Encéfalo/fisiologia , Rememoração Mental/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Psicolinguística/métodos , Fatores de Tempo , Estimulação Magnética Transcraniana/instrumentação , Adulto JovemRESUMO
PURPOSE: Defining the tolerability and safety profile of recently marketed antiepileptic drugs, such as lacosamide (LCM), is a prerequisite for their optimal utilization in clinical practice. We aimed to identify any adverse event (AE) associated with LCM treatment by conducting a systematic review and meta-analysis of all available randomized controlled trials (RCTs). We also evaluated the association of serious AEs with LCM, the proportion of study withdrawals due to intolerable AEs at different LCM doses, and whether the tolerability profile of LCM differs according to the disorder in which it was investigated. METHODS: We searched MEDLINE and Cochrane CENTRAL to May 2011 for LCM RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs and investigated the therapeutic effects of oral LCM in adults with any condition. AEs were assessed for their association with LCM after identification/exclusion of synonyms, rare AEs, and non-assessable AEs. We used risk differences to evaluate the association of any (99% confidence intervals [CIs]) or serious AEs (95% CIs) with LCM and to investigate dose-response relationships of identified AEs. KEY FINDINGS: Ten RCTs (three in pharmacoresistant epilepsy, four in neuropathic pain, one in migraine, one in fibromyalgia, and one in knee osteoarthritis) were included in our study. Their duration varied from 12-18 weeks. The total number of patients included was 3,148. No serious AE was significantly associated with LCM treatment. Of 21 identified AEs, 11 (52%) were found to be significantly associated with LCM. The number of AEs significantly associated with LCM increased with increasing dose: one at 200 mg/day (dizziness); six at 400 mg/day (dizziness, vertigo, abnormal coordination, abnormal vision, nausea, and vomiting); nine at 600 mg/day (dizziness, vertigo, ataxia, balance disorder, diplopia, fatigue, nausea, vomiting, and tremor). The proportion of AE-related study withdrawals also significantly increased with increasing dose. LCM AEs tended to occur more frequently in patients with drug-resistant epilepsy compared with patients with other disorders. SIGNIFICANCE: A range of AEs suggestive of vestibulocerebellar dysfunction is significantly associated with LCM treatment and their incidence increases with increasing doses.
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Acetamidas/efeitos adversos , Anticonvulsivantes/efeitos adversos , Acetamidas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Relação Dose-Resposta a Droga , Epilepsia/tratamento farmacológico , Humanos , Lacosamida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: In Parkinson's disease (PD), impulsivity as a personality trait may be linked to the risk of developing impulse control disorders (ICDs) during dopaminergic therapy. However, studies evaluating differences in trait impulsivity between patients with PD and healthy controls or between patients with PD with and without ICDs reported partly inconsistent findings. Objectives: We conducted a systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) of studies comparing Barratt Impulsiveness Scale (BIS-11) scores between patients with PD and healthy controls and between patients with PD with and without ICDs. Methods: Eligible studies were identified through a systematic search in 3 databases. Mean differences with 95% confidence intervals (CIs) for BIS-11 total and subscale scores were separately calculated for studies comparing patients with PD and healthy controls and patients with PD with and without ICDs. Meta-regressions were performed to explore sources of heterogeneity (percentage of men, age, disease duration, and levodopa equivalent daily dose). Results: A total of 40 studies were included in the quantitative analyses. BIS-11 total scores were significantly higher in patients with PD compared with healthy controls (mean difference 2.43; 95% CI, 1.03, 3.83), and in patients with PD with active ICDs compared with patients without ICDs (6.62; 95% CI, 5.01, 8.23). No significant moderators emerged by meta-regression analyses. Conclusions: The present meta-analysis supports that impulsivity, as a personality trait, may characterize patients with PD, even in the absence of ICDs. Moreover, these data corroborate findings of clinical studies reporting higher levels of trait impulsivity in PD patients with ICDs compared with patients without ICDs.
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Culture greatly influences our attitudes, beliefs, and behaviors, affecting how we communicate and make decisions. There is an ongoing debate regarding the belief that people from Eastern cultures possess greater self-control abilities when compared to people from Western cultures. In this study, we conducted a meta-analysis using the Activation Likelihood Estimation (ALE) algorithm to compare 30 studies (719 subjects, 373 foci) that used fMRI to investigate the performance in Go-Nogo and Stop Signal Tasks of participants from Western and/or Eastern countries. Our meta-analysis found differences between the networks activated in Eastern and Western culture participants. The right prefrontal cortex showed distinct patterns, with the Inferior Frontal gyrus more active in the Eastern group and the middle and superior frontal gyri more active in the Western group. Our findings suggest that Eastern culture subjects have a higher tendency to activate brain regions involved in proactive inhibitory control, while Western culture subjects rely more on reactive inhibitory brain regions during cognitive control tasks. This implies that proactive inhibition may play a crucial role in promoting the collective and interdependent behavior typical of Eastern cultures, while reactive inhibition may be more important for efficient cognitive control in subjects of Western cultures that prioritize individualism and independence.