Search

openaire: EC/H2020/810377/EU//ConnectToBrain Background: Prefrontal theta oscillations are involved in neuronal information transfer and retention. Phases along the theta cycle represent varied excitability states, whereby high-excitability states correspond to high-frequency neuronal activity and heightened capacity for plasticity induction, as demonstrated in animal studies. Human studies corroborate this model and suggest a core role of prefrontal theta activity in working memory (WM). Objective/Hypothesis: We aimed at modulating prefrontal neuronal excitability and WM performance in healthy humans, using real-time EEG analysis for triggering repetitive transcranial magnetic stimulation (rTMS) theta-phase synchronized to the left dorsomedial prefrontal cortex. Methods: 16 subjects underwent 3 different rTMS interventions on separate days, with pulses triggered according to the individual's real-time EEG activity: 400 rTMS gamma-frequency (100 Hz) triplet bursts applied during either the negative peak of the prefrontal theta oscillation, the positive peak, or at random phase. Changes in cortical excitability were assessed with EEG responses following single-pulse TMS, and behavioral effects by using a WM task. Results: Negative-peak rTMS increased single-pulse TMS-induced prefrontal theta power and theta-gamma phase-amplitude coupling, and decreased WM response time. In contrast, positive-peak rTMS decreased prefrontal theta power, while no changes were observed after random-phase rTMS. Conclusion: Findings point to the feasibility of EEG-TMS technology in a theta–gamma phase–amplitude coupling mode for effectively modifying WM networks in human prefrontal cortex, with potential for therapeutic applications.

Sensorimotor µ-rhythm phase is correlated with corticospinal excitability. Transcranial magnetic stimulation (TMS) of motor cortex results in larger motor evoked potentials (MEPs) during the negative peak of the EEG oscillation as extracted with a surface Laplacian. However, the anatomical source of the relevant oscillation is not clear and demonstration of the relationship is sensitive to the choice of EEG montage.Here, we compared two EEG montages preferentially sensitive to oscillations originating from the crown of precentral gyrus (dorsal premotor cortex) vs. postcentral gyrus (secondary somatosensory cortex). We hypothesized that the EEG signal from precentral gyrus would correlate more strongly with MEP amplitude, given that the corticospinal neurons are located in the anterior wall of the sulcus and the corticospinal tract has input from premotor cortex.Real-time EEG-triggered TMS of motor cortex was applied in 6 different conditions in randomly interleaved order, 3 phase conditions (positive peak, negative peak, random phase of the ongoing µ-oscillation), and each phase condition for 2 different EEG montages corresponding to oscillations preferentially originating in precentral gyrus (premotor cortex) vs. postcentral gyrus (somatosensory cortex), extracted using FCC3h vs. C3 centered EEG montages.The negative vs. positive peak of sensorimotor µ-rhythm as extracted from the C3 montage (postcentral gyrus, somatosensory cortex) correlated with states of high vs. low corticospinal excitability (p 0.001), replicating previous findings. However, no significant correlation was found for sensorimotor µ-rhythm as extracted from the neighboring FCC3 montage (precentral gyrus, premotor cortex). This implies that EEG-signals from the somatosensory cortex are better predictors of corticospinal excitability than EEG-signals from the motor areas.The extraction of a brain oscillation whose phase corresponds to corticospinal excitability is highly sensitive to the selected EEG montage and the location of the EEG sensors on the scalp. Here, the cortical source of EEG oscillations predicting response amplitude does not correspond to the cortical target of the stimulation, indicating that even in this simple case, a specific neuronal pathway from somatosensory cortex to primary motor cortex is involved.

Highlights • Optimized sham TMS-EEG is introduced and tested. • Sham combined auditory and supramaximal electrical somatosensory stimulation. • Subjects reported equal sensory perception during sham and real TMS. • Subtraction revealed evoked EEG potentials and beta-band power specific to real TMS. • The optimized sham procedure is relevant in research and therapeutic settings., Introduction Electroencephalography (EEG) is increasingly used to investigate brain responses to transcranial magnetic stimulation (TMS). A relevant issue is that TMS is associated with considerable auditory and somatosensory stimulation, causing peripherally evoked potentials (PEPs) in the EEG, which contaminate the direct cortical responses to TMS (TEPs). All previous attempts to control for PEPs suffer from significant limitations. Objective/Hypothesis To design an optimized sham procedure to control all sensory input generated by subthreshold real TMS targeting the hand area of the primary motor cortex (M1), enabling reliable separation of TEPs from PEPs. Methods In 23 healthy (16 female) subjects, we recorded EEG activity evoked by an optimized sham TMS condition which masks and matches auditory and somatosensory co-stimulation during the real TMS condition: auditory control was achieved by noise masking and by using a second TMS coil that was placed on top of the real TMS coil and produced a calibrated sound pressure level. Somatosensory control was obtained by electric stimulation (ES) of the scalp with intensities sufficient to saturate somatosensory input. ES was applied in both the sham and real TMS conditions. Perception of auditory and somatosensory inputs in the sham and real TMS conditions were compared by psychophysical testing. Transcranially evoked EEG signal changes were identified by subtraction of EEG activity in the sham condition from EEG activity in the real TMS condition. Results Perception of auditory and somatosensory inputs in the sham vs. real TMS conditions was comparable. Both sham and real TMS evoked a series of similar EEG signal deflections and induced broadband power increase in oscillatory activity. Notably, the present procedure revealed EEG potentials and a transient increase in beta band power at the site of stimulation that were only present in the real TMS condition. Discussion The results validate the effectiveness of our optimized sham approach. Despite the presence of typical responses attributable to sensory input, the procedure provided evidence for direct cortical activation by subthreshold TMS of M1. The findings are relevant for future TMS-EEG experiments that aim at measuring regional brain target engagement controlled by an optimized sham procedure.

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) enables noninvasive probing of excitability and connectivity in human cortex. This method involves the application of a cortical stimulus followed by the analysis of the neuronal response of the stimulated cortical site and beyond by EEG. This has prompted the successful use of TMS-EEG in the understanding of the neurophysiological underpinnings of neuropsychiatric disorders such as schizophrenia, major depressive disorder, and Alzheimer’s disease. In this chapter, we introduce the methodological issues involved in TMS-EEG experiments, including the measures obtained by this tool and their neurophysiological significance. We also review the findings of TMS-EEG studies involving neuropsychiatric disorders, introducing how particular cortical dysfunctions revealed by these studies relate to the current understanding of these diseases, as well as how these and future results can be used to further increase our pathophysiological understanding of these disorders and to design therapeutic interventions.

Background The analysis of cortical responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) has been successfully applied to study human cortical physiology. However, in addition to the (desired) activation of cortical neurons and fibers, TMS also causes (undesired) indirect brain responses through auditory and somatosensory stimulation, which may contribute significantly to the overall EEG signal and mask the effects of intervention on direct cortical responses. Objectives To test differences in EEG responses to real TMS at intensities above and below resting motor threshold (RMT) and a realistic sham stimulation. Methods 12 healthy subjects participated in one session in which single-pulse TMS was applied to the left motor cortex in 3 different blocks, 150 pulses per block: 110%RMT, 90%RMT and realistic sham stimulation. Cortical responses were collected by a 64 electrode EEG system. TMS evoked potentials (TEPs) and TMS induced oscillations were analyzed. Methods 12 healthy subjects participated in one session in which single-pulse TMS was applied to the left motor cortex in 3 different blocks, 150 pulses per block: 110%RMT, 90%RMT and realistic sham stimulation. Cortical responses were collected by a 64-channel EEG system. TMS evoked potentials (TEPs) and TMS induced oscillations were analyzed. Results TEPs from all conditions differed significantly, with TEPs from 110%RMT showing overall highest amplitudes and realistic sham lowest amplitudes. Sham stimulation had only minor effects on induced cortical oscillations compared to pre-stimulus baseline, TMS at 90%RMT resulted in a significant increase (50–200 m s) followed by a decrease (200–500 m s) in power of alpha and beta oscillations; TMS at 110% RMT led to an additional increase in beta power at late latencies (650–800 m s). Conclusions Real TMS of motor cortex results in cortical responses significantly different from realistic sham. These differences very likely reflect to a significant extent direct activation of neurons, rather than sensory evoked activity.

Several medical procedures, especially magnetic resonance imaging (MRI), can be severely distressing for individuals who suffer from enclosed space phobia. The psychotherapeutic approach to minimize the discomfort for these patients can be a safe and effective alternative to increase these patients' acceptance of the exam. A cohort of 30 subjects with MRI aversion was randomly divided into 2 intervention groups: 15 subjects received 1 session of Acceptance and Commitment Therapy (ACT) based psychotherapy, and 15 subjects received 7 sessions ACT based psychotherapy. The primary outcome was considered being able to undergo an MRI simulation after therapy completion. Subjects also filled a set of questionnaires at baseline and after 1 month and 3 months of treatment completion. The self-assessment questionnaires were performed before and after the treatment: Rachmann and Taylor Claustrophobia Inventory (1993), Beck Depression Inventory (1961) and the State-Trait Anxiety Inventory (STAI) (1970). Subjects who received the seven session therapy were more likely to complete the simulation. Subjects from the seven-session therapy also showed improvement in the claustrophobia scale, which lasted for at least three months after treatment completion. The study showed that a one-session therapy was of inferior efficacy compared to the sevensession therapy. The seven-session therapy group showed a high success rate with lasting benefits. A brief psychotherapy course may be a safe and effective alternative for individuals with MRI avoidance.

The effect of a stimulus to the brain depends not only on the parameters of the stimulus but also on the dynamics of brain activity at the time of the stimulation. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time brain state-dependent stimulation system allows the study of relations of dynamics of brain activity, cortical excitability, and plasticity induction. Here, we demonstrate a newly developed method to synchronize the timing of brain stimulation with the phase of ongoing EEG oscillations using a real-time data analysis system. This real-time EEG-triggered TMS of the human motor cortex, when TMS is synchronized with the surface EEG negative peak of the sensorimotor µ-alpha (8-14 Hz) rhythm, has shown differential corticospinal excitability and plasticity effects. The utilization of this method suggests that real-time information about the instantaneous brain state can be used for efficacious plasticity induction. Additionally, this approach enables personalized EEG-synchronized brain stimulation which may lead to the development of more effective therapeutic brain stimulation protocols.

Introduction Schizophrenia is a severe mental disorder. While some antipsychotic medications have demonstrated efficacy in treating positive symptoms, there is no widely recognized treatment for negative symptoms, which can cause significant distress and impairment for patients with schizophrenia. Here we describe the rationale and design of the STARTS study (Schizophrenia TreAtment with electRic Transcranial Stimulation), a clinical trial aimed to test the efficacy of a non-pharmacological treatment known as transcranial direct current stimulation (tDCS) for treating the negative symptoms of schizophrenia Methods The STARTS study is designed as a randomized, sham-controlled, double-blinded trial evaluating tDCS for the treatment of the negative symptoms of schizophrenia. One-hundred patients will be enrolled and submitted to 10 tDCS sessions over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporoparietal junction (cathodal stimulation) over 5 consecutive days. Participants will be assessed using clinical and neuropsychological tests before and after the intervention. The primary outcome is change in the Positive and Negative Syndrome Scale (PANSS) negative subscale score over time and across groups. Biological markers, including blood neurotrophins and interleukins, genetic polymorphisms, and motor cortical excitability, will also be assessed. Results The clinical results will provide insights about tDCS as a treatment for the negative symptoms of schizophrenia, and the biomarker investigation will contribute towards an improved understanding of the tDCS mechanisms of action. Conclusion Our results could introduce a novel therapeutic technique for the negative symptoms of schizophrenia. Clinical trial registration: ClinicalTrials.gov, NCT02535676 . Resumo Introdução A esquizofrenia é um transtorno mental grave. Embora alguns medicamentos antipsicóticos tenham demonstrado eficácia no tratamento de sintomas positivos, não há tratamento amplamente reconhecido para sintomas negativos, o que pode causar sofrimento e prejuízo significativos para pacientes com esquizofrenia. Aqui descrevemos a fundamentação teórica e o design do estudo STARTS (Schizophrenia TreAtment with electRic Transcranial Stimulation), um ensaio clínico destinado a testar a eficácia de um tratamento não farmacológico conhecido como estimulação transcraniana por corrente contínua (ETCC) para tratar os sintomas negativos da esquizofrenia. Métodos O estudo STARTS foi concebido como um ensaio clínico randomizado, controlado por simulação, duplo-cego, avaliando a ETCC para o tratamento dos sintomas negativos da esquizofrenia. Cem pacientes serão incluídos e submetidos a 10 sessões de ETCC sobre o córtex pré-frontal dorsolateral esquerdo (estimulação anódica) e a junção temporoparietal esquerda (estimulação catodal) durante 5 dias consecutivos. Os participantes serão avaliados através de testes clínicos e neuropsicológicos antes e após a intervenção. O desfecho primário é a mudança na pontuação da subescala negativa da Escala da Síndrome Positiva e Negativa (Positive and Negative Syndrome Scale [PANSS]) ao longo do tempo e entre os grupos. Marcadores biológicos, incluindo neurotrofinas e interleucinas do sangue, polimorfismos genéticos e excitabilidade cortical motora, também serão avaliados. Resultados Os resultados clínicos fornecerão informações sobre a ETCC como um tratamento para os sintomas negativos da esquizofrenia, e a investigação dos biomarcadores contribuirá para uma melhor compreensão dos mecanismos de ação da ETCC. Conclusão Nossos resultados podem trazer uma nova técnica terapêutica para o tratamento dos sintomas negativos da esquizofrenia. Registro do ensaio clínico: ClinicalTrials.gov, NCT02535676.

International audience

O desenvolvimento da estimulação magnética transcraniana (EMT) permitiu o estudo de potenciais evocados motores eliciados pela estimulação direta do córtex cerebral de forma não-invasiva. Foi observado que diferentes paradigmas de estimulação cortical por EMT apresentam diferentes padrões de resposta, que posteriormente foram associados ao funcionamento de circuitos corticais GABAérgicos e glutamatérgicos do córtex motor, compondo assim índices de excitabilidade cortical motora (ECM). Ademais, desvios da normalidade de tais índices foram encontrados em diversas condições clínicas, incluindo transtornos mentais como a esquizofrenia. O uso dessas medidas também auxiliou o desenvolvimento da estimulação transcraniana por corrente contínua (ETCC), técnica que se mostrou capaz de produzir efeitos neuromodulatórios no sistema nervoso central de forma segura e com mínimos efeitos adversos. Tal técnica vem apresentando possibilidades terapêuticas promissoras, como por exemplo, tendo sido observado sua eficácia no alívio de alucinações auditivas de indivíduos com esquizofrenia. O uso de ETCC para tratamento de sintomas negativos da esquizofrenia também pode vir a se mostrar uma abordagem eficaz, e a análise da ECM pode auxiliar no entendimento dos seus mecanismos de ação e atuar como possível preditor de resposta terapêutica. O objetivo do presente estudo é avaliar o perfil de ECM em um grupo de indivíduos com esquizofrenia, e as possíveis influências de um protocolo terapêutico utilizando ETCC sobre essas medidas. Com esse objetivo, foi selecionada uma coorte de sujeitos com esquizofrenia que participou em ensaio clínico randomizado e controlado com placebo (estimulação sham), tendo a ETCC como intervenção ativa alvo. A ECM foi mensurada na avaliação inicial dos sujeitos, assim como após a primeira sessão de ETCC, e quando da avaliação de desfecho primário. O protocolo terapêutico de ETCC envolveu a colocação de 2 eletrodos de área 5x7 cm, pólo anódico aplicado sobre região correspondente ao córtex pré-frontal dorsolateral esquerdo e pólo catódico aplicado sobre córtex de transição temporoparietal esquerdo; com intensidade de corrente de 2 mA, aplicada por 20 minutos. Cada sujeito foi submetido a 10 sessões no total. Encontramos que idade se correlacionou com diminuição da inibição intracortical, reproduzindo resultado previamente encontrado em indivíduos saudáveis. Acerca da modulação da ECM após sessão de ETCC, observamos que sujeitos submetidos à intervenção ativa apresentaram aumento da inibição intracortical no hemisfério estimulado, em oposição à ausência de mudança significativa da ECM nos sujeitos que receberam estimulação placebo. Os resultados sugerem que sessão de ETCC, utilizando os parâmetros aplicados neste estudo, levou ao aumento da inibição intracortical. Devido a evidências prévias de déficit de inibição intracortical em pessoas com esquizofrenia, é possível que o fenômeno observado represente mecanismo terapêutico da ETCC. É necessário verificar se tal efeito sobre a ECM acompanha medidas objetivas de resposta clinica. Caso isto se comprove, a ECM pode se tornar um valioso marcador de resposta terapêutica e evolução clinica em pacientes com esquizofrenia The development of transcranial magnetic stimulation allowed the study of motor evoked potentials by applying direct stimuli to the brain cortex in a non-invasive fashion. Different stimulation protocols were observed to yield different response patterns, which were later associated with the functioning of cortical GABAergic and glutamatergic circuits, assembled as motor cortex excitability indices. Also, deviations from normality of such indices were observed in several clinical conditions, including mental disorders such as schizophrenia. The use of these measurements also helped the development of transcranial direct current stimulation (tDCS), a technique which was shown to promote neuromodulatory effects in central nervous system, with potential treatment applications. This technique has been used with success in the treatment of auditory hallucinations in patients with schizophrenia. The use of tDCS might also be effective in the treatment of negative symptoms of schizophrenia, and motor cortex excitability analysis might be used to clarify its physiological effects and act as a possible treatment response predictor. The aim of the present study is to evaluate the motor cortical excitability profile of individuals with schizophrenia, as well as possible influences of tDCS over these measurements. With this aim, we selected a cohort of subjects with schizophrenia who participated in a randomized placebo controlled clinical trial using transcranial direct current stimulation (and sham stimulation for placebo), and measuring motor cortical excitability during baseline evaluation, after the first stimulation session, and at the time of the primary outcome evaluation. The transcranial direct current stimulation protocol used in the present study involved the use of 2 electrodes of area 5x7 cm, anode placed over the region corresponding to the left dorsolateral prefrontal cortex, and cathode over the left cortical temporoparietal juntion. A current of 2 mA intensity was applied for 20 minutes. Each subject underwent a total of 10 sessions. We found that age was correlated to reduced intracortical inhibition, as has been previously found in healthy subjects. Regarding changes of motor cortical excitability following a transcranial direct current stimulation session, we observed that subjects that received the active stimulation displayed an increase in intracortical inhibition, as opposed to those who received sham stimulation, which did not present with any significant change. Results suggest that transcranial direct current stimulation session, using the parameters described in this study, led to an increase in intracortical inhibition. Given previous evidence of intracortical inhibition deficit in individuals with schizophrenia, it is possible that the observed phenomenon corresponds to a treatment mechanism of the electrical stimulation in this population. This need to be confirmed by comparing such changes in cortical excitability to objective measurements of clinical improvement. In case that is confirmed, measurement of motor cortical excitability may have a valuable application as a marker of treatment response and clinical outcome for patients with schizophrenia

Objectives Parkinson disease (PD) psychosis is a condition associated with several negative outcomes. Despite its impact, there is a lack of validated diagnostic tools for this condition. In this study, we aim to verify the validity of the proposed NINDS criteria for PD psychosis and explore its possible applications in clinical practice. Design, Settings, Participants We prospectively selected 104 subjects with idiopathic PD referred to a movement disorder clinic for a cross-sectional evaluation. Measurements A neurological evaluation confirmed idiopathic PD and classified PD psychosis according to the NINDS criteria. A psychiatrist then classified the subject according to DSM-IV-TR criteria for psychosis, considered the reference standard. We used Cohen's kappa (κ) to quantify reliability between methods. Finally, we designed models assigning a weighted score to each characteristic psychotic symptom from the NINDS criteria (criterion A), and plotted receiver operating curves for each model. Results Of the total sample, 52 (50%) met proposed criteria for NINDS PD psychosis and 16 (15.6%) met reference standard criteria. Inter-rater reliability showed only a fair agreement (κ = 0.30). By using a scoring approach for each NINDS criteria item and a cutoff total score for the diagnosis of PD psychosis, we significantly increased the agreement for diagnosis reliability (κ = 0.72), with sensitivity of 94% and specificity of 91%. Conclusions Although the NINDS criteria had limited reliability for diagnosing PD psychosis, a scoring approach for symptoms showed good reliability, with sensitivity and specificity above 90%. This scoring approach may be an accurate tool for identifying patients with PD psychosis.

Background Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an effective treatment for major depressive disorder (MDD), but response rates are low and effect sizes small. Synchronizing TMS pulses with instantaneous brain oscillations can reduce variability and increase efficacy of TMS-induced plasticity. Objective To study whether brain oscillation-synchronized rTMS is feasible, safe and has neuromodulatory effects when targeting the DLPFC of patients with MDD. Methods Using real-time EEG-triggered TMS we conducted a pseudo-randomized controlled single-session crossover trial of brain oscillation-synchronized rTMS of left DLPFC in 17 adult patients with antidepressant-resistant MDD. Stimulation conditions in separate sessions were: (1) rTMS triggered at the negative EEG peak of instantaneous alpha oscillations (alpha-synchronized rTMS), (2) a variation of intermittent theta-burst stimulation (modified iTBS), and (3) a random alpha phase control condition. Results Triggering TMS at the negative peak of instantaneous alpha oscillations by real-time analysis of the electrode F5 EEG signal was successful in 15 subjects. Two subjects reported mild transient discomfort at the site of stimulation during stimulation; no serious adverse events were reported. Alpha-synchronized rTMS, but not modified iTBS or the random alpha phase control condition, reduced resting-state alpha activity in left DLPFC and increased TMS-induced beta oscillations over frontocentral channels. Conclusions Alpha-synchronized rTMS of left DLPFC is feasible, safe and has specific single-session neuromodulatory effects in patients with antidepressant-resistant MDD. Future studies need to further elucidate the mechanisms, optimize the parameters and investigate the therapeutic potential and efficacy of brain oscillation-synchronized rTMS in MDD.

Objective: Noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are increasingly being used to treat mental disorders, particularly major depression. The aim of this comprehensive review is to summarize the main advances, limitations, and perspectives of the field. Methods: We searched PubMed and other databases from inception to July 2017 for articles, particularly systematic reviews and meta-analyses, evaluating the use of NIBS in psychiatric disorders. Results: We reviewed the mechanisms of action, safety, tolerability, efficacy, and relevant clinical parameters of NIBS. Repetitive TMS is already an established technique for the treatment of depression, and there is theoretically room for further methodological development towards a high-end therapeutic intervention. In contrast, tDCS is a technically easier method and therefore potentially suitable for wider clinical use. However the evidence of its antidepressant efficacy is less sound, and a recent study found tDCS to be inferior to antidepressant pharmacotherapy. Clinical trials using rTMS for other mental disorders produced mixed findings, whereas tDCS use has not been sufficiently appraised. Conclusion: The most promising results of NIBS have been obtained for depression. These techniques excel in safety and tolerability, although their efficacy still warrants improvement.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) shows therapeutic potential in pharmaco-resistant patients with major depression. However, clinical efficacy is limited by high inter-individual variability and low response rates. One possible strategy to improve the effect size and consistency may be brain state dependent brain stimulation, i.e. coupling of TMS pulses to the endogenous brain states as reflected by the instantaneous oscillatory brain activity. Here we present findings from a proof-of-principle study of alpha-oscillation synchronized brain stimulation of the frontal cortex in patients with major depression (BOSSFRONT). Repetitive stimulation consistently on the negative peak of ongoing alpha activity in left DLPFC, but not brain state independent intermittent theta-burst stimulation (iTBS), resulted in suppression of resting-state alpha activity in left DLPFC and an increase in TMS-induced beta activity. Findings show that alpha-synchronized rTMS of left DLPFC is both feasible and safe, and suggest that it interferes with frontal brain networks important in the pathophysiology of major depression.

Ongoing brain activity has been implicated in the modulation of cortical excitability. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time triggered setup is a novel method for testing hypotheses about the relationship between spontaneous neuronal oscillations, cortical excitability, and synaptic plasticity. For this method, a reliable real-time extraction of the neuronal signal of interest from scalp EEG with high signal-to-noise ratio (SNR) is of crucial importance. Here we compare individually tailored spatial filters as computed by spatial-spectral decomposition (SSD), which maximizes SNR in a frequency band of interest, against established local C3-centered Laplacian filters for the extraction of the sensorimotor μ-rhythm. Single-pulse TMS over the left primary motor cortex was synchronized with the surface positive or negative peak of the respective extracted signal, and motor evoked potentials (MEP) were recorded with electromyography (EMG) of a contralateral hand muscle. Both extraction methods led to a comparable degree of MEP amplitude modulation by phase of the sensorimotor μ-rhythm at the time of stimulation. This could be relevant for targeting other brain regions with no working benchmark such as the local C3-centered Laplacian filter, as sufficient SNR is an important prerequisite for reliable real-time single-trial detection of EEG features.

Schizophrenia is a disorder associated with cortical inhibition deficits. Transcranial direct current stimulation (tDCS) induces changes in cortical excitability in healthy subjects and individuals with neuropsychiatric disorders depending on the stimulation parameters. Our aim was to investigate whether a previously published tDCS protocol associated with symptomatic improvement in schizophrenia would induce changes in motor cortical excitability, assessed by transcranial magnetic stimulation paradigms, i.e., short-interval intracortical inhibition (SICI) and intra-cortical facilitation (ICF). We assessed cortical excitability measurements in 48 subjects with schizophrenia before and after a single session of active tDCS (20 min, 2 mA, anode over left dorsolateral prefrontal cortex, cathode over left temporoparietal cortex) or sham. Those who received active tDCS had a significant increase of SICI in the left motor cortex compared to those who received sham stimulation (Cohen's d = 0.54, p = .019). No changes were observed for ICF. In addition, lower SICI was associated with higher age (β = -0.448, p .01). Increase in intracortical inhibition may indicate a mechanism of action of tDCS in this population. Future studies should investigate whether this finding is a biomarker of treatment response for schizophrenia.

Background Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with potential for cost-effective therapeutic neuromodulation. Although positive therapeutic effects were found by stimulating the dorsolateral prefrontal cortex (DLPFC), few studies have investigated physiological effects of DLPFC-tDCS. Objectives To investigate effects of tDCS with different parameter settings applied to the left DLPFC on cortical responses, measured by resting-state electroencephalography (rs-EEG) and transcranial magnetic stimulation (TMS)-evoked/induced EEG responses. Methods 22 healthy subjects underwent 5 tDCS sessions with different tDCS parameter settings in a double-blinded randomized crossover design (1: 1.5 mA, anode left-DLPFC, cathode right-DLPFC; 2: 1.5 mA, cathode left-DLPFC, anode right-DLPFC; 3: 0.5 mA, anode left-DLPFC, cathode right-DLPFC; 4: 1.5 mA, anode left-DLPFC, cathode left deltoid muscle; 5: sham stimulation). Rs-EEG and TMS-EEG were recorded before and after tDCS. Results Rs-EEG power spectrum analysis showed no difference comparing baseline with post stimulation in any of the tDCS conditions. TMS-EEG evoked potential amplitude decreased in parietal cortex after 1.5 mA left-DLPFC anodal tDCS, and TMS-induced gamma and theta oscillations decreased after all conditions using left-DLPFC anodal tDCS. Left-DLPFC cathodal tDCS did not lead to significant change. None of the post-intervention changes was different when comparing the effects across conditions, including sham. Conclusions Our study does not provide evidence that a single tDCS session results in significant changes in rs-EEG, using the current stimulation parameters. Significant changes in EEG responses to TMS pulses were observed following the anodal 1.5 mA tDCS interventions, although these changes were not statistically significant in a group comparison.

Purpose To determine whether patients with comorbid epilepsy and psychogenic nonepileptic seizure (PNES) and their caregivers can distinguish between these two events at least one year after initial diagnosis, and to investigate factors associated with correct identification. Methods Adult patients with at least a one year diagnosis of both epilepsy and PNES, confirmed through video-electroencephalography (VEEG), were selected. Patients and a caregiver of their choice were interviewed and shown videos containing the patients' epileptic and PNES events. Variables associated with correct identification of events by patients and their caregivers were evaluated. Results Twenty-four patients participated in the study. Mean time between VEEG diagnosis and enrollment in the study was 26.8 months (±12.4). Six of patients correctly distinguished between the events shown. Factors associated with correct identification were the absence of intellectual disability, unremitted PNES, and a degree of preserved awareness during the PNES event. Twelve caregivers correctly distinguished between the events shown. Factors associated with correct identification among caregivers were the presentation of only one epileptic seizure type in the patient, and the participation of the caregiver during VEEG monitoring and communication of PNES diagnosis to the patient. Conclusion A significant proportion of patients with epilepsy and PNES and their caregivers seem to be unable to discriminate between these events a year after diagnosis. These findings have implications for both clinical follow-up and research involving this population. Future research should further investigate methods that would allow patients and their caregivers to better distinguish between these two events.

A significant proportion of patients who undergo bariatric surgery fail to achieve enduring weight loss. Previous studies suggest that psychosocial variables affect postoperative outcome, although this subject is still considered unclear. The purpose of this study is to further investigate the impact of psychosocial variables on Roux-en-Y gastric bypass (RYGB) outcomes over long-term follow-up. Individuals eligible for bariatric surgery were evaluated using validated psychopathological scales and the Temperament and Character Inventory in a specialized clinic for bariatric treatment. Adult patients who had RYGB were selected for the study. Percent of excess weight loss (%EWL) was measured after surgery at 6 months, 1 year, 2 years, and on the last clinical observation. This study included 333 subjects who had RYGB. Before surgery, mean age was 35.4 years (±9.5) and mean BMI was 43.3 kg/m2 (±4.8). Higher baseline age and BMI were associated with lower %EWL across endpoints, although this association diminished over time. Follow up at 2 years and on the last clinical observation demonstrated that lower scores on the persistence personality variable and lower body dissatisfaction before surgery predicted lower %EWL. Psychosocial variables and personality traits assessed during preoperative evaluation significantly predicted weight loss after bariatric surgery. Greater impact was observed in long-term follow-up at 2 years. These findings provide guidance in identifying patients at risk for worse outcomes and designing interventions to improve long-term weight loss.

Bipolar depression (BD) is a highly prevalent condition with limited therapeutic options. Deep (H1-coil) transcranial magnetic stimulation (dTMS) is a novel TMS modality with established efficacy for unipolar depression. We conducted a randomized sham-controlled trial to evaluate the efficacy and safety of dTMS in treatment-resistant BD patients. Patients received 20 sessions of active or sham dTMS over the left dorsolateral prefrontal cortex (H1-coil, 55 18 Hz 2 s 120% MT trains). The primary outcome was changes in the 17-item Hamilton Depression Rating Scale (HDRS-17) from baseline to endpoint (week 4). Secondary outcomes were changes from baseline to the end of the follow-up phase (week 8), and response and remission rates. Safety was assessed using a dTMS adverse effects questionnaire and the Young Mania Rating Scale to assess treatment-emergent mania switch (TEMS). Out of 50 patients, 43 finished the trial. There were 2 and 5 dropouts in the sham and active groups, respectively. Active dTMS was superior to sham at end point (difference favoring dTMS=4.88; 95% CI 0.43 to 9.32, p=0.03) but not at follow-up. There was also a trend for greater response rates in the active (48%) vs sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. Deep TMS is a potentially effective and well-tolerated add-on therapy in resistant bipolar depressed patients receiving adequate pharmacotherapy.

Background The negative symptoms of schizophrenia cause significant distress and impairment. The treatment of them is a challenge, with medications having none or little effect. So, new treatments are necessary for this condition. The aim of the study was to ascertain the efficacy of tDCS in treating negative symptoms of schizophrenia Methods This study was designed to be a randomized, sham-controlled, double-blinded trial using tDCS for the treatment of negative symptoms of schizophrenia. One-hundred (here we analyzed only 70% of the sample, the remaining will be presented at the meeting) patients will be enrolled and submitted to ten tDCS session over the left dorsolateral prefrontal cortex (anodal stimulation) and left temporo-parietal junction-left (cathodal stimulation), over 5 consecutive days, with 2 mA of current. Participants were assessed with clinical and neuropsychological tests before and after the intervention. The primary outcome was change (over time and across groups) in the scores of the Negative Subscale of Positive and Negative Symptoms Syndrome (PANSS). Our secondary outcomes consist of others scales as SANSS (Scale of Assessment of Negative Symptoms), Calgary and the AHRS (Auditory Hallucinations Rating Scale). Results From 70% of the sample the active tDCS was significantly superior to sham at endpoint at 6 weeks by negative sub scale of PANSS (mean difference, 3,5 points; SD=6.2; P

INTRODUÇÃO: Uma parcela significativa dos indivíduos submetidos à cirurgia bariátrica evolui com complicações de variada natureza no pós-operatório tardio. Dentre estas estão a redução ponderal insuficiente ou reganho de peso, assim como alterações comportamentais graves, como demonstrado pelos relatos de aumento na prevalência de abuso de substâncias e de mortes por causas não naturais. O presente estudo tem como objetivo investigar fatores pré-operatórios clínicoepidemiológicos e psicossociais, com ênfase principal em traços de personalidade, potencialmente implicados no prognóstico em longo prazo de indivíduos submetidos ao tratamento bariátrico. MÉTODOS: Trata-se de estudo prospectivo envolvendo uma coorte de 333 pacientes submetidos à cirurgia bariátrica (bypass gástrico em Y de Roux). A avaliação inicial no pré-operatório contou com a coleta de dados clínicodemográficos e com a aplicação de instrumentos padronizados na obtenção de variáveis relacionadas a sintomas depressivos e ansiosos, comportamento alimentar, imagem corporal e traços de personalidade, estes obtidos pelo Inventário de Temperamento e Caráter. Foram coletados dados relativos à perda ponderal no pós-operatório de 6 meses, 1 ano e 2 anos, assim como da última observação clínica após 2 anos. Também foi realizada busca ativa de sujeitos para aplicação de questionário sobre hábitos de vida, hábitos alimentares e índice de qualidade de vida e prognóstico de cirurgia bariátrica pelo método de BAROS. RESULTADOS: Foram incluídos 333 sujeitos no presente estudo, 282 (84,7%) mulheres e 51 (15,3%) homens, com IMC médio de 43,3 (±4,8) kg/m2. Análise dos dados ao final de 6 meses revelou maiores IMC inicial e idade na avaliação inicial como preditores de menor perda ponderal. Em 1 ano a análise revelou maior IMC inicial e presença de diabetes como preditores de menor perda ponderal. A análise de 2 anos revelou maiores IMC inicial e idade, além de baixos índices do traço \"persistência\" e de insatisfação com imagem corporal, como preditores de menor perda ponderal, associação que se manteve na análise de pós-operatório superior a 2 anos. Do total de 333 sujeitos, 101 (30,3%) participaram da análise final de hábitos e qualidade de vida. Desses sujeitos, 16 (16%) referiram consumo de álcool de forma excessiva. Foram identificados 50 (49,5%) sujeitos que apresentavam períodos de compulsão alimentar subjetiva (SBE) e 41 (44,6%) relataram a presença de \"beliscar compulsivo\", sendo observado que ambos os grupos apresentaram menor percentual de perda de excesso de peso na avaliação de pós-operatório tardio. Acerca da avaliação prognóstica de cirurgia bariátrica pelo método de BAROS, a análise encontrou como variáveis associadas a melhor prognóstico geral maiores níveis do traço \"persistência\", além de menores níveis de insatisfação corporal no pré-operatório, menor tempo de pós-operatório, práticas de atividade física e ausência de beliscar compulsivo no pós-operatório INTRODUCTION: A significant proportion of patients who undergo bariatric surgery presents with complications of varied nature in the late postoperative period. These include insufficient weight loss or weight regain, and also severe behavioral changes, as demonstrated by the increased prevalence of substance abuse and deaths from non-natural causes reported in literature. The present study aims to investigate clinical-epidemiological and psychosocial pre-operative variables, with emphasis on personality traits, potentially involved in the long-term prognosis of patients undergone bariatric treatment. METHODS: This is a prospective study of a cohort of 333 patients undergone bariatric surgery (Roux-Y gastric bypass). Preoperative assessment included clinical and demographic data and the application of standardized instruments for depression and anxiety sumptoms, eating behavior, body image and personality traits, obtained by the Temperament and Character Inventory. Data on postoperative weight loss was collected after 6 months , 1 year and 2 years, as well as in the last clinical observation after 2 years. Active search of subjects was performed for the application of questionnaires involvind lifestyle and eating habits, and the analysis of bariatric outcome through the BAROS method. RESULTS : 333 subjects were included in this study, 282 (84.7%) women and 51 (15.3%) men, with a mean BMI of 43.3 (±4.8) kg/m2 . Analysis of the data at six months showed higher initial BMI and age at initial assessment as predictors of reduced weight loss. At 1-year, analysis revealed higher initial BMI and the presence of diabetes as predictors of reduced weight loss. The analysis of two years revealed greater initial BMI and age, as well as low levels of the trait \"persistence\" and body image dissatisfaction as predictors of reduced weight loss, an association that remained in the analysis of more than 2 years postoperative. Of the total 333 subjects, 101 (30.3%) participated in the final analysis of habits and quality of life. Of these subjects, 16 (16 %) reported excessive alcohol intake. Fifty (49.5%) subjects presented periods of subjective binge eating (SBE) and 41 (44.6%) reported the presence of \"grazing\". Both groups had a significant lower percentage excess weight loss. Concerning prognosis evaluation using the BAROS method, the analysis found as variables associated with a better overall prognosis: higher levels of trait \"persistence\", as well as lower body image dissatisfaction, shorter postoperative period, physical activity and absence of \"grazing\"

The effect of psychotic symptoms in Parkinson’s disease (PD) is variable among patients, and different methods to assess psychosis may yield conflicting results. A sample of 102 patients with a diagnosis of idiopathic PD underwent neurological, psychiatric, and neuropsychological assessment. Participants were divided into three groups: those who met DSM criteria for psychotic disorder, those who had psychotic symptoms but did not meet DSM criteria, and those without any psychotic symptoms. The first group had significantly worse sleep and worse cognitive and psychopathological symptoms compared with the other two groups. Results suggested that patients meeting DSM criteria for psychotic disorder comprise a separate clinical category.

Psychogenic non-epileptic seizures (PNES) is a relevant differential diagnosis in epilepsy clinics because of its high prevalence and impact on patient’s lives and health care services. An approach to the diagnosis and treatment of PNES is important, and many issues make the subject challenging. Video electroencephalography (VEEG) is considered the gold-standard for PNES diagnosis but there is still risk for false positive and false negative results, both with potential dire consequences. VEEG should be planned and analyzed with caution, as well as paired with other clinical variables in order to increase its predictive value. The frequent coexistence of epilepsy among PNES patients makes diagnosis and treatment even more complex. The clinician should always mind that possibility, which has important implications for diagnosis and treatment of the PNES. Patients’ understanding and acceptance of the disorder as well as health care professionals’ attitude towards the patients have impact on prognosis. Proper and coherent communication is important for patients’ acceptance of diagnosis, treatment, and prognosis.

OBJECTIVE: The Prodromal Questionnaire (PQ) is a 92-item self-report screening tool for individuals at ultra-high risk (UHR) to develop psychosis. This study aims to present the translation to Portuguese and preliminary results in UHR and first episode (FE) psychosis in a Portuguese sample. METHODS: The PQ was translated from English to Portuguese by two bilingual researchers from the research program on early psychosis of the Instituto de Psiquiatria HCFMUSP, São Paulo, Brazil (ASAS - "Evaluation and Follow up of Adolescents and Young Adults in São Paulo") and back translated by two other researchers. The study participants (n = 11-) were evaluated through the Portuguese version of the Prodromal Questionnaire (PQ) and SIPS. RESULTS: The individuals at UHR (n = 7) presented a lower score than first episode patients (n = 4). The UHR mean scores and standard deviation on Portuguese version of the PQ were: 13.0 ± 10.0 points on positive symptoms subscale, and FE patients: 33.0 ± 10.0. CONCLUSION: The UHR and FE patients' of this study presented PQ scores similar to the ones found in the literature; what suggests that it is possible to use the PQ in Brazilian help-seeking individuals as a screening tool. OBJETIVO: O Questionário Prodromal (PQ) é um instrumento de triagem e autorrelato com 92 itens para indivíduos com ultra-alto risco (UHR) para desenvolver psicose. Este estudo tem como objetivo apresentar a tradução desse questionário para português e seus resultados preliminares em uma amostra brasileira de UHR e primeiro episódio (FE) psicótico. MÉTODOS: O PQ foi traduzido do inglês para o português por dois pesquisadores bilíngues do programa de pesquisa sobre psicose precoce do Instituto de Psiquiatria HCFMUSP, São Paulo, Brasil (ASAS "Avaliação e Acompanhamento de Adolescentes e Jovens Adultos em São Paulo") e retrotraduzido por dois outros pesquisadores. Os participantes (n = 11) do estudo foram avaliados por meio da versão em português do Questionário de Prodromal (PQ) e SIPS. RESULTADOS: Os indivíduos com UHR (n = 7) apresentaram menor pontuação do que os pacientes de primeiro episódio (n = 4). Os escores médios e desvio-padrão dos indivíduos de UHR na versão em português do PQ foram: 13,0 ± 10,0 pontos na subescala de sintomas positivos, e dos pacientes de primeiro episódio: 33,0 ± 10,0. CONCLUSÃO: Neste estudo os indivíduos de UHR e pacientes de FE apresentaram pontuação do PQ semelhantes às encontradas na literatura, o que sugere a possibilidade de usar a PQ como um instrumento de triagem em indivíduos brasileiros que apresentam comportamento de procura de ajuda.